# What's That Peptide?: full reference Honest, UK-focused, evidence-graded peptide reference. Educational only, not medical advice. Most peptides here are not licensed medicines in the UK. --- # 5-ALA (5-Aminolevulinic Acid) **Evidence grade: C (Early / limited human data).** Area: Longevity. > A natural building-block your own cells use to make haem and fuel your mitochondria. It's a licensed medicine — but as a glow-in-the-dark dye for brain-tumour surgery, not as the energy-and-metabolism supplement it's sold as. **Also known as:** 5-aminolevulinic acid, 5-ala, aminolevulinic acid, ala (5-ala), 5-ala phosphate, delta-aminolevulinic acid, gliolan, levulan, aminolevulinic acid hydrochloride **Class:** Endogenous non-protein amino acid; first committed precursor of haem biosynthesis (not a peptide) ## Why this grade Confusingly, the molecule splits into two stories. As a hospital drug it is a fully licensed medicine with grade-A evidence — but only as a surgical dye, not as something you take to feel better. For the longevity, metabolic and anti-fatigue uses people actually buy it for, the human data is early and small: a handful of mostly Japanese RCTs on blood-sugar control plus tiny pilot trials, with effects that are modest or not statistically significant. That mix of early, limited human data lands it at C. ## In plain terms **Simple.** Every cell in your body makes energy in tiny power-plants called mitochondria. To do that they need haem, the same iron-rich molecule that makes your blood red. 5-ALA is the very first ingredient your body uses to build haem from scratch. Because your body already makes it (and makes a bit less as you get older), people take it as a supplement hoping for more energy, less tiredness and steadier blood sugar. It has one clever proven trick, though: surgeons give a dose before brain-tumour operations because cancer cells soak it up and turn it into something that glows bright red under a special blue light — so the surgeon can see exactly what to cut out. That use really works. The 'feel younger and more energetic' use is far less proven. **Standard.** 5-ALA is a small molecule your body makes naturally as the first committed step in producing haem — the iron-containing core of haemoglobin and of the cytochromes that drive energy production in mitochondria. The longevity pitch is straightforward: haem synthesis is thought to decline with age, so topping up 5-ALA (usually paired with an iron source, sodium ferrous citrate) might support mitochondrial function, antioxidant defences and metabolism. The strongest human signal is on blood sugar: several randomised trials, mostly in Japan, suggest 5-ALA plus iron can modestly lower fasting and post-meal glucose in people with prediabetes or type 2 diabetes, and it has a clean safety record there. Beyond that, the human evidence thins out fast — small pilot studies on fatigue, exercise capacity and rare mitochondrial diabetes, often with non-significant results. Separately, and importantly, 5-ALA is a genuinely licensed prescription medicine in the UK and EU — but as a photosensitiser that makes tumour tissue fluoresce during surgery, which tells you nothing about whether the supplement does what it claims. **Technical.** 5-ALA (δ-aminolevulinic acid) is the product of the rate-limiting step of haem biosynthesis, condensed from glycine and succinyl-CoA by ALA synthase (ALAS) in the mitochondrial matrix; SLC25A38 transports glycine/ALA across the inner membrane. Exogenous 5-ALA bypasses the ALAS bottleneck, feeding the downstream pathway (ALAD → porphobilinogen → … → protoporphyrin IX → ferrochelatase + Fe²⁺ → haem), which is why oral formulations co-administer iron as sodium ferrous citrate. Proposed effects rest on upregulation of haem-dependent respiratory-chain complexes (notably complex IV / cytochrome c oxidase) and induction of haem oxygenase-1 (HMOX1), yielding antioxidant and anti-inflammatory carbon-monoxide/biliverdin signalling. Human RCT data are most developed in dysglycaemia: placebo-controlled work in mildly hyperglycaemic subjects reduced fasting and post-load glucose, and a randomised dose-escalation safety study in T2DM reported tolerability alongside oral hypoglycaemics. Other human work is pilot-grade: a 24-week single-arm study in maternally inherited diabetes and deafness (MIDD) showed only a non-significant insulin-secretion trend, and a Phase II randomised trial in mild-to-moderate COVID-19 missed its primary endpoints (no effect on viral load or symptom score). The selective tumour accumulation of PpIX — exploited diagnostically in fluorescence-guided resection — reflects altered porphyrin enzyme kinetics in malignant cells rather than any systemic 'longevity' mechanism. ## How it is thought to work 5-ALA is the first committed intermediate of the haem biosynthetic pathway. Normally its production by ALA synthase is the rate-limiting step; supplying 5-ALA orally (typically with an iron source such as sodium ferrous citrate, because the final step needs ferrous iron) is thought to push more flux down the pathway toward protoporphyrin IX and then haem. More haem means more functional cytochromes for the mitochondrial respiratory chain — hence the claimed boost to cellular energy metabolism and glucose handling. 5-ALA is also reported to induce haem oxygenase-1, an antioxidant/anti-inflammatory enzyme. In its licensed surgical use, the mechanism is different and well-established: tumour cells preferentially accumulate the fluorescent intermediate protoporphyrin IX, which glows red under blue light, marking out cancer tissue. ## Studied for Research contexts, not proven uses. - Glucose control / prediabetes and type 2 diabetes (with iron) - Mitochondrial / energy metabolism support - Fatigue and aerobic exercise capacity - Fluorescence-guided tumour surgery (licensed medicinal use) - Actinic keratosis / skin lesions (topical photodynamic therapy) - COVID-19 (investigated, did not meet endpoints) ## What the human evidence shows Two very different bodies of human evidence sit under the same name. The licensed medicinal form (5-ALA hydrochloride) has robust human data for what it's approved to do: as Gliolan it improves the extent of brain-tumour resection by making malignant tissue fluoresce, and topical formulations are established for photodynamic treatment of actinic keratosis. For the supplement uses that put it in the longevity bucket, the evidence is much weaker. The best human signal is on blood sugar: randomised, placebo-controlled trials (largely from Japan) report that 5-ALA phosphate plus sodium ferrous citrate modestly lowers fasting and post-meal glucose in prediabetic and type 2 diabetic adults, with a good safety profile and a randomised dose-escalation safety study in type 2 diabetes. Beyond glycaemia, human studies are small and inconsistent: a 24-week single-arm pilot in maternally inherited diabetes and deafness found only a non-significant trend in insulin secretion, and a Phase II randomised COVID-19 trial failed to improve viral load or symptom scores. Claims about energy, anti-ageing and athletic performance rest mostly on mechanism, animal work and small studies (for example a 14-person crossover on redox balance and aerobic capacity) rather than convincing human trials. ## Concerns and unknowns - Photosensitivity is the standout risk: 5-ALA makes skin and eyes temporarily hypersensitive to light, so light exposure after dosing can cause burns — this is dose-dependent and well documented for the medicinal form (the Gliolan SmPC mandates avoiding strong light and direct sunlight for 24 hours). - Two products, one name: the licensed prescription drug (5-ALA hydrochloride) and the food-grade supplement (5-ALA phosphate) are not interchangeable, and the drug's strong evidence does not transfer to the supplement's marketing claims. - It is pushed for people with diabetes/prediabetes, where it could interact additively with blood-sugar-lowering medicines — a setting that needs medical oversight, not self-experiment. - Most of the supportive RCTs are small, single-region (Japan) and frequently industry-linked, with modest effect sizes; independent replication is limited. - Theoretical concern in anyone with a porphyria or haem-pathway enzyme deficiency, where loading the pathway with its precursor could be harmful. - Supplement-grade products have variable quality and purity outside regulated channels. ## UK status Split status. As a medicine, 5-aminolevulinic acid hydrochloride is licensed in the UK — Gliolan (oral, for fluorescence-guided glioma surgery) holds a marketing authorisation, and topical 5-ALA products are used in dermatology; these are prescription-only and supplied through the NHS/specialists, with side-effects reportable to the MHRA Yellow Card scheme. As a supplement, 5-ALA (usually the phosphate salt with iron) is sold widely in Japan and online as a food/dietary supplement, but it has no UK medicines authorisation for any energy, metabolic or anti-ageing indication. Selling it in the UK with disease or treatment claims would bring it under medicines law (Human Medicines Regulations 2012) and MHRA oversight; marketed purely as a food supplement it falls under food rather than medicines rules. Buying unlicensed 5-ALA online to self-treat conditions like diabetes is outside any regulated, evidence-checked pathway. ## Sport / WADA Not a WADA-prohibited substance. 5-ALA is not named on the WADA Prohibited List and is not a recognised performance-enhancing agent in the doping sense; the human exercise/aerobic-capacity data are too thin to suggest a meaningful ergogenic effect. As with any supplement, athletes face the usual contamination risk from unregulated products, and the photosensitivity effect is a practical consideration for outdoor sport. ## Key trials - **Randomised, placebo-controlled trials of oral 5-ALA phosphate/iron on glucose metabolism in prediabetes and type 2 diabetes** (Phase II, Completed). Part of the prediabetes/dysglycaemia evidence base; mostly Japanese, modest effects. - **Randomised exploratory Phase II trial of 5-ALA phosphate/iron in mild-to-moderate COVID-19 (PMID 37653769)** (Phase II, Completed). Did not meet primary endpoints (no significant effect on viral load or symptom score). - **5-ALA (Gliolan) fluorescence-guided resection in high-grade gliomas** (Interventional, Licensed use). Concerns the licensed surgical/diagnostic use, not the supplement claims. ## Sources 1. Therapeutic potential of 5-aminolevulinic acid in metabolic disorders: Current insights and future directions. Kuryata O et al., iScience, 2024 2. 5-aminolevulinic acid, a precursor of heme, reduces both fasting and postprandial glucose levels in mildly hyperglycemic subjects. Higashikawa F et al., Nutrition, 2013 3. Pilot Trial on the Effect of 5-Aminolevulinic Acid on Glucose Tolerance in Patients with Maternally Inherited Diabetes and Deafness. Nakamura Y, Haraguchi A, Horie I, Kawakami A, Abiru N, Diabetes Therapy, 2023 4. Safety and efficacy of 5-aminolevulinic acid phosphate/iron in mild-to-moderate coronavirus disease 2019: A randomized exploratory phase II trial. Phase II randomized trial, Japan, Medicine (Baltimore), 2023 5. The Safety and Tolerability of 5-Aminolevulinic Acid Phosphate with Sodium Ferrous Citrate in Patients with Type 2 Diabetes Mellitus in Bahrain. Al-Saber A et al., Journal of Diabetes Research, 2016 6. Gliolan 30mg/ml powder for oral solution — Summary of Product Characteristics (SmPC). Photonamic / electronic medicines compendium, emc (medicines.org.uk), 2024 7. The Impact of 5-Aminolevulinic Acid Supplementation on Redox Balance and Aerobic Capacity. Saga N et al., International Journal of Molecular Sciences, 2024 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/5-amino-levulinic-acid . Educational only, not medical advice. --- # 5-Amino-1MQ **Evidence grade: D (Animal data only).** Area: Weight & Metabolic. > A lab-made small molecule that blocks an enzyme (NNMT) to nudge fat tissue toward burning rather than storing energy — convincing in obese mice, completely untested in people. **Also known as:** 5-amino-1-methylquinolinium, 5a1mq, nnmt inhibitor, 5 amino 1mq peptide **Class:** Small-molecule NNMT inhibitor (quaternary quinolinium compound) — not a peptide despite the marketing label ## Why this grade Promising mouse and cell data for fat loss and muscle ageing, but zero published or completed human trials. ## In plain terms **Simple.** 5-Amino-1MQ is a chemical that switches off a tiny cellular machine called NNMT. In overweight bodies that machine runs hot and helps fat cells hang on to fat. Block it and, at least in mice, the fat cells shrink and the animals lose weight without eating less. People sell it online as a 'weight-loss peptide', but two things are worth knowing: it isn't actually a peptide, and nobody has ever run a proper trial of it in humans. So the exciting headlines are all about mice, not you. **Standard.** 5-Amino-1MQ inhibits nicotinamide N-methyltransferase (NNMT), an enzyme that becomes overactive in obese fat tissue and ageing muscle. NNMT burns through nicotinamide and methyl groups; blocking it raises NAD+ and SAM levels inside cells, which is thought to flip fat cells from storage toward fat-burning and to re-energise tired muscle stem cells. In diet-induced obese mice a short course cut body weight by roughly 5%, shrank white fat by about a third and lowered cholesterol — all without changing how much the mice ate. A separate study rejuvenated aged-muscle stem cells. None of this has been replicated in humans: there are no completed clinical trials, no MHRA or FDA approval, and the products sold online are unlicensed research chemicals of unverified purity. It is best understood as an interesting drug candidate, not a proven treatment. **Technical.** 5-Amino-1MQ (5-amino-1-methylquinolinium) is a membrane-permeable, substrate-competitive small-molecule inhibitor of nicotinamide N-methyltransferase (NNMT), the cytosolic SAM-dependent methyltransferase that converts nicotinamide to 1-methylnicotinamide. NNMT is upregulated in obese white adipose tissue and senescent skeletal muscle; its activity depletes the nicotinamide salvage pool feeding NAD+ biosynthesis and consumes S-adenosylmethionine. Inhibition is proposed to raise intracellular NAD+ and SAM, augmenting sirtuin (SIRT1) signalling and epigenetic methylation capacity, thereby increasing adipocyte energy expenditure and restoring myogenic stem-cell (muSC) function. In Neelakantan et al. (Biochem Pharmacol 2018), systemic dosing in diet-induced obese mice reduced body weight (~5%), white adipose mass (~35%), adipocyte diameter and plasma cholesterol without altering caloric intake. A 2019 study reported reversal of muSC senescence and improved post-injury regeneration in aged murine muscle. There are no published human pharmacokinetic, efficacy or safety data; oral bioavailability, human NNMT engagement and long-term consequences of NAD+/SAM perturbation in humans remain uncharacterised. ## How it is thought to work Inhibits nicotinamide N-methyltransferase (NNMT), an enzyme overexpressed in obese fat tissue and ageing muscle. NNMT methylates nicotinamide using SAM as the methyl donor, consuming both nicotinamide and methyl groups. Blocking it is thought to spare nicotinamide for recycling into NAD+ and preserve SAM, raising both. Higher NAD+ supports sirtuin (SIRT1) activity and cellular energy metabolism, which in animals shifts fat cells away from storage and toward energy expenditure and reactivates dormant muscle stem cells. ## Studied for Research contexts, not proven uses. - Fat loss / reversing diet-induced obesity (mice) - Metabolic rate and NAD+ elevation - Ageing muscle: stem-cell rejuvenation and strength (mice) - Longevity / cellular energy signalling (preclinical) ## What the human evidence shows There is essentially none. Every headline figure — 5% weight loss, 35% fat reduction, restored muscle stem cells — comes from mice or cell cultures, not people. As of mid-2026 there are no completed, published human clinical trials of 5-Amino-1MQ, no MHRA- or FDA-approved indication, and no Investigational New Drug data in the public domain; reviews of NNMT as a drug target (e.g. Frontiers in Pharmacology, 2024) still describe it as preclinically validated only. Claims of a 'favourable safety profile in humans' circulating on supplement sites are not supported by any published human study. Whether NNMT inhibition produces the same metabolic effects in humans, and whether chronically raising NAD+ and SAM is safe long-term, is simply unknown. ## Concerns and unknowns - No human trials at all — efficacy and safety in people are unproven; all benefits are extrapolated from rodents. - Marketed misleadingly as a 'peptide'; it is a small synthetic quinolinium molecule, which matters for how it is regulated and what 'research chemical' purity claims mean. - Sold by unlicensed online vendors as a 'research chemical' — no pharmaceutical-grade manufacturing, dose accuracy or contaminant testing guaranteed. - Manipulating NAD+/SAM and sirtuin pathways systemically has unknown long-term consequences, including theoretical effects on cell proliferation and cancer biology that have not been studied in humans. - Often stacked with NAD+ precursors and sold for anti-ageing on the basis of mechanism alone, far ahead of the evidence. ## UK status 5-Amino-1MQ is not a licensed medicine in the UK and holds no MHRA marketing authorisation for any condition. It is not an approved weight-loss treatment. Products sold online are unlicensed and typically labelled 'research chemical, not for human consumption' to sidestep the Human Medicines Regulations 2012; supplying or promoting it for human use as a medicine without authorisation would fall foul of MHRA rules. There is no approved route for a person to obtain or use it lawfully as a treatment in the UK. ## Sport / WADA Not specifically named on the WADA Prohibited List. However, as an unlicensed, untested compound with no current marketing approval for human therapeutic use, it could fall under WADA's catch-all clause S0 (non-approved substances). Using it also carries a real risk of contamination with prohibited substances. Athletes should treat it as high-risk. ## Key trials - **No registered or completed human clinical trials identified** (None). As of mid-2026, no Phase 1+ trials of 5-Amino-1MQ are listed as completed on ClinicalTrials.gov or published in peer-reviewed literature. All evidence is preclinical. ## Sources 1. Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice. Neelakantan H, Vance V, Wetzel MD, et al., Biochemical Pharmacology, 2018 2. Small molecule nicotinamide N-methyltransferase inhibitor activates senescent muscle stem cells and improves regenerative capacity of aged skeletal muscle. Neelakantan H, Brightwell CR, Graber TG, et al., Biochemical Pharmacology, 2019 3. Nicotinamide N-methyltransferase (NNMT): a novel therapeutic target for metabolic syndrome. (review), Frontiers in Pharmacology, 2024 4. 5-Amino-1-methylquinolinium — compound summary. PubChem, NCBI PubChem, 2026 5. Search: 5-amino-1MQ NNMT inhibitor human clinical trials. PubMed, PubMed, 2026 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/5-amino-1mq . Educational only, not medical advice. --- # AHK-Cu **Evidence grade: D (Animal data only).** Area: Skin & Aesthetics. > A synthetic copper-carrying peptide used in hair and skin cosmetics, with promising lab data but no human trials proving it works. **Also known as:** Copper Tripeptide-3, Ala-His-Lys copper complex, Alanyl-Histidyl-Lysine copper peptide, AHK copper peptide, Cu-AHK, ahk, ahk copper, copper peptide, copper tripeptide **Class:** Synthetic copper-binding tripeptide (cosmetic peptide / copper complex) ## Why this grade The primary evidence is a single 2007 ex-vivo/in-vitro study (cultured human dermal papilla cells and isolated human hair-follicle organ culture) plus general copper-peptide cosmetic literature. No published controlled human clinical trials exist for AHK-Cu itself for hair growth or skin ageing. Its cosmetic use rests on read-across from the better-studied GHK-Cu and mechanistic plausibility, not human efficacy data. Grade D: mechanistically interesting, human evidence absent. ## In plain terms **Simple.** AHK-Cu is a synthetic protein fragment that carries copper, a mineral your skin uses to make collagen. In lab dishes it stimulated hair-root cells and skin cells, which is why it appears in hair serums and anti-ageing creams. But the evidence comes only from cells in a dish, not from real people. So it is a plausible ingredient with a logical story, not a proven hair or wrinkle treatment. **Standard.** AHK-Cu (Copper Tripeptide-3) is a three-amino-acid peptide (alanine-histidine-lysine) bound to a copper ion. It is a variant of the better-known GHK-Cu, with the first amino acid changed, claimed to favour hair-follicle activity. The main science is a 2007 laboratory study showing it lengthened human hair follicles cultured outside the body and boosted dermal papilla cell proliferation (the cells at the follicle base that drive growth), with associated higher VEGF (linked to blood supply) and lower TGF-beta1. The stimulation appeared only at very low concentrations and diminished at higher doses. It is a recognised cosmetic ingredient (INCI-listed) used in serums and creams. No published human trials demonstrate it grows hair or reduces wrinkles. Marketing leans heavily on cell-culture data and GHK-Cu's reputation. **Technical.** AHK-Cu is the synthetic tripeptide Ala-His-Lys complexed with Cu(II), designated INCI Copper Tripeptide-3 and structurally analogous to GHK-Cu (Gly-His-Lys-Cu, Copper Tripeptide-1), differing only at the N-terminal residue. The histidine imidazole and amino terminus provide high-affinity Cu(II) chelation analogous to the albumin/GHK copper-transport motif, functioning as a copper-delivery vehicle to copper-dependent enzymes (lysyl oxidase, superoxide dismutase) and matrix remodelling. Principal evidence is Pyo et al. (Arch Pharm Res, 2007): in cultured human dermal papilla cells AHK-Cu increased proliferation with upregulated VEGF and suppressed TGF-beta1; in ex-vivo human hair-follicle organ culture it promoted follicle elongation. Stimulation occurred at picomolar-to-nanomolar concentrations (10^-12 to 10^-9 M). The reported anti-apoptotic shift (reduced apoptotic dermal papilla cells on annexin-V/PI flow cytometry) did not reach statistical significance, so anti-apoptosis remains a hypothesis. Beyond this single paper, evidence comprises general copper-peptide cosmetic literature and read-across from GHK-Cu. No registered RCTs, no human pharmacokinetic data, and no comparative efficacy data versus minoxidil or finasteride exist for AHK-Cu. Mechanistic claims (anagen prolongation, anti-apoptosis, angiogenesis) remain unvalidated in vivo. ## How it is thought to work A small peptide (alanine-histidine-lysine) that chelates copper(II) and acts as a copper carrier, delivering copper to copper-dependent enzymes involved in collagen cross-linking and matrix remodelling. In cell culture it was associated with increased VEGF (pro-angiogenic) and suppressed TGF-beta1, plus increased dermal papilla cell proliferation, proposed to prolong the follicle growth (anagen) phase. Applied topically in cosmetics. Laboratory effects appeared only at very low concentrations. ## Studied for Research contexts, not proven uses. - Hair follicle stimulation / androgenetic alopecia (lab and ex-vivo only) - Dermal papilla cell proliferation (in vitro) - Skin collagen/extracellular-matrix support and anti-ageing (cosmetic context) - General copper-peptide skin repair (read-across from GHK-Cu) ## What the human evidence shows None specific to AHK-Cu. No published controlled clinical trials demonstrate that AHK-Cu grows hair, reduces hair loss, or improves skin ageing in humans. The main evidence is a single 2007 study using cultured human dermal papilla cells and isolated human hair follicles in organ culture. Its presence in cosmetics relies on mechanistic data and borrowing from the broader cosmetic experience with GHK-Cu. Claims of proven human results for AHK-Cu itself overstate the evidence. ## Concerns and unknowns - No human efficacy trials: marketing claims for hair regrowth and anti-ageing lack clinical data specific to AHK-Cu. - Read-across overreach: benefits are often borrowed from GHK-Cu studies, a different molecule. - Concentration-dependent effects: lab data showed stimulation only at very low concentrations, so 'more is better' marketing is mechanistically questionable. - Grey-market quality: many products are sold as unlicensed 'research chemicals' with no verified purity, copper content, sterility, or peptide identity testing. - Copper exposure: copper can be irritating or sensitising to skin in some formulations; injectable/grey-market use carries sterility and contamination risks. - Regulatory ambiguity: legitimate as a topical cosmetic, but products promising therapeutic hair-loss outcomes make unlicensed medicinal claims. ## UK status AHK-Cu (Copper Tripeptide-3) is recognised as a cosmetic ingredient (INCI-listed) and may be used in topical cosmetic products in the UK if they are safety-assessed and make only cosmetic (not medicinal) claims under the UK Cosmetics Regulation, enforced by the Office for Product Safety and Standards (OPSS) and local Trading Standards. It is not a licensed UK medicine and holds no MHRA marketing authorisation for hair loss, skin ageing, or any therapeutic use. Any product marketed as treating, preventing, or curing a condition (such as claiming to regrow hair in androgenetic alopecia) makes a medicinal claim and would require MHRA authorisation under the Human Medicines Regulations 2012, which it does not have. Peptide powders or vials sold for reconstitution and injection with labels such as 'research use only' or 'not for human consumption' are unlicensed and outside any approved medical use. Selling or supplying them for human use is unlawful. ## Sources 1. The effect of tripeptide-copper complex on human hair growth in vitro. Pyo HK, Yoo HG, Won CH, et al., Archives of Pharmacal Research 2007;30(7):834-839, 2007 2. GHK and DNA: Resetting the Human Genome to Health (review of copper-peptide GHK-Cu biology). Pickart L, Margolina A, International Journal of Molecular Sciences, 2018 3. Copper, lysyl oxidase and collagen cross-linking in skin and connective tissue (background literature). Dermatology / trace-element literature, 2015 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/ahk-cu . Educational only, not medical advice. --- # AOD-9604 **Evidence grade: C (Early / limited human data).** Area: Weight & Metabolic. > A synthetic fragment of growth hormone designed to burn fat without the hormone's side effects, but human trials showed it failed to produce meaningful weight loss and development was abandoned. **Also known as:** AOD9604, hGH fragment 176-191, growth hormone fragment 176-191, Tyr-hGH 177-191, anti-obesity drug 9604, aod, frag 176-191, fat burning fragment **Class:** Synthetic peptide; modified C-terminal fragment of human growth hormone (residues 176-191, with an added N-terminal tyrosine) ## Why this grade AOD-9604 was taken through a genuine clinical programme, rare for a grey-market peptide: six human trials in roughly 900 people, run by Metabolic Pharmaceuticals between 2001 and 2006. An early Phase 2a (about 300 obese adults, 12 weeks) showed a small but statistically significant weight loss. The larger, pivotal Phase 2b (about 536 adults, 24 weeks) failed to beat placebo, and drug development was abandoned in 2007. Substantial human evidence exists, but it points to no clinically meaningful weight loss. Graded C (limited human data that did not pan out) because there is no ongoing credible programme and no positive pivotal result; not D because real RCTs exist. ## In plain terms **Simple.** Growth hormone is a large natural hormone. Scientists identified a small tail-end piece thought to be responsible for fat-burning, without the side effects of the full hormone like raised blood sugar. AOD-9604 is a synthetic copy of that piece. It worked in mice. Unlike most peptides sold online, it was tested properly in hundreds of real people, which is unusual. In the decisive trial, however, it did not produce more weight loss than a dummy injection. The company gave up on it in 2007. Today it's sold online as a 'research chemical', not as an approved medicine. **Standard.** AOD-9604 is a synthetic copy of the last 15 amino acids (residues 176-191) of human growth hormone, the region thought to carry its fat-burning (lipolytic) effect, omitting the parts that raise IGF-1 or disturb blood sugar. In obese mice it reduced body fat. Metabolic Pharmaceuticals (Australia) then did something unusual: real human trials, six of them, involving roughly 900 participants. An early study showed a small but statistically significant weight-loss signal, but the larger pivotal Phase 2b trial failed to show a significant difference from placebo. The company stopped developing it as a drug around 2007. It was later self-affirmed as 'GRAS' (a US food-ingredient category), which is not the same as approval as a weight-loss medicine. It is banned in sport by WADA. In the UK it is not a licensed medicine; what's sold online is unlicensed and of uncertain quality. **Technical.** AOD-9604 is a synthetic analogue of the C-terminal lipolytic domain of hGH (residues 176-191), with an N-terminal tyrosine added to the native sequence (Tyr-hGH 177-191). The rationale was to isolate hGH's lipolytic activity from its somatogenic/diabetogenic actions. Preclinical work (Heffernan et al., Endocrinology 2001) showed reduced body weight and fat in obese mice and increased beta-3 adrenoceptor expression. In beta-3-AR knock-out mice the lipolytic effect was abolished, indicating that beta-3-AR signalling is required; the peptide does not appear to act as a direct beta-3-AR agonist. Across the human programme it did not raise serum IGF-1 and did not impair glucose tolerance or insulin sensitivity (Stier et al., J Endocrinol Metab 2013, pooled safety analysis of ~893 subjects). Clinical development by Metabolic Pharmaceuticals progressed through Phase 1 and Phase 2. An earlier multicentre RCT in obese adults (~300 subjects, 12 weeks) reported a statistically significant but modest weight reduction (~2.6 kg vs ~0.8 kg placebo). The larger pivotal Phase 2b (~536 subjects, 24 weeks) did not meet its primary efficacy endpoint; development was terminated around 2007. A subsequent GRAS self-affirmation positioned it as a food ingredient, separate from drug approval. WADA lists it under S0 (non-approved substances). No marketing authorisation exists with the MHRA, EMA or FDA for any indication. ## How it is thought to work Designed as the isolated lipolytic fragment of human growth hormone (C-terminal residues 176-191 plus an added N-terminal tyrosine). In rodent and in-vitro models it stimulated lipolysis, inhibited lipogenesis and increased beta-3 adrenoceptor expression in adipocytes. Its lipolytic effect was lost in beta-3-AR knock-out mice, implying beta-3-AR signalling is required, though the peptide does not appear to be a direct receptor agonist. Across human trials it did not raise IGF-1 and did not impair glucose metabolism. The intended selling point was fat loss without growth hormone's metabolic downsides. However, the mechanism that worked in mice did not translate into clinically meaningful fat loss in the pivotal human trial. ## Studied for Research contexts, not proven uses. - Obesity / body-fat reduction (the original drug indication; failed in the pivotal human trial) - Hypercholesterolaemia and metabolic parameters (exploratory) - Cartilage repair / osteoarthritis (later preclinical interest, not part of the original obesity programme) ## What the human evidence shows Substantial for a peptide of this type, but negative on efficacy. Metabolic Pharmaceuticals ran six human clinical trials (2001-2006) involving roughly 893-900 participants. An earlier Phase 2a multicentre RCT in obese adults (about 300 people over 12 weeks) reported a small but statistically significant weight loss (roughly 2.6 kg at the active dose vs ~0.8 kg for placebo). The safety profile was reassuring: adverse events comparable to placebo, no effect on IGF-1, no adverse effect on glucose or insulin. The larger pivotal Phase 2b trial (about 536 people over 24 weeks) did not show statistically significant weight loss over placebo. The company terminated development as a weight-loss drug around 2007. The human data do not support a clinically meaningful effect on body weight or fat mass. ## Concerns and unknowns - Efficacy is the core problem. The pivotal human trial failed and the drug was abandoned in 2007. The marketing pitch ('GH fat-burning without the downsides') was not borne out in people. - Marketing emphasises mouse and in-vitro data and the favourable safety profile while omitting the negative human efficacy result. - GRAS status is routinely misrepresented online as a weight-loss approval. It is a US food-ingredient self-affirmation category and says nothing about clinical efficacy as a drug. - Sold as an unlicensed 'research chemical' labelled 'not for human consumption'. Purity, concentration, sterility and even peptide identity are unverified in grey-market products. - Banned in sport under WADA S0 (non-approved substances). Athletes face sanctions. - No long-term human safety data beyond the original trial follow-up periods. Injectable use carries sterility and injection-site risks. ## UK status Not a licensed medicine in the UK. AOD-9604 has no Marketing Authorisation from the MHRA, EMA or FDA for any indication. It is an unlicensed, investigational compound whose drug development was discontinued. Selling or supplying it with therapeutic or weight-loss claims without authorisation breaches the Human Medicines Regulations 2012. In practice it is sold online as an unlicensed 'research chemical' labelled 'not for human consumption', a framing used to sidestep medicines law. It is also prohibited in sport under the WADA Prohibited List (category S0, non-approved substances). ## Key trials - **Metabolic Pharmaceuticals AOD-9604 obesity programme: early Phase 2a multicentre RCT in obese adults** (Phase 2a, Completed; small but statistically significant weight-loss signal reported). About 300 obese adults over ~12 weeks; active dose lost ~2.6 kg vs ~0.8 kg placebo; safety comparable to placebo. - **Metabolic Pharmaceuticals AOD-9604 pivotal Phase 2b obesity trial** (Phase 2b, Completed; failed primary efficacy endpoint). About 536 adults over ~24 weeks; failed to show statistically significant weight loss vs placebo; led to termination of drug development around 2007. NCT identifier not confirmed. ## Sources 1. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice. Heffernan MA, Summers RJ, Thorburn AW, et al., Endocrinology, 2001 2. Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans. Stier H, Vos E, Kenley D, Journal of Endocrinology and Metabolism, 2013;3(1-2):7-15 3. The effect of AOD9604 on weight loss in obese adults: results of a randomized, double-blind, placebo-controlled, multicenter study. Stier H, et al., Reported clinical trial (Metabolic Pharmaceuticals Phase 2 programme) 4. WADA statement on substance AOD-9604. World Anti-Doping Agency, 2013 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/aod-9604 . Educational only, not medical advice. --- # ARA-290 (Cibinetide) **Evidence grade: C (Early / limited human data).** Area: Recovery & Repair. > A lab-made 11-amino-acid offcut of the hormone EPO, engineered to keep its tissue-repair and anti-inflammatory effects while losing the red-blood-cell boost — with promising but unfinished human trials in nerve damage. **Also known as:** Cibinetide, ARA290, ara-290, non-erythropoietic EPO peptide, innate repair receptor agonist, EPO helix-B peptide **Class:** Synthetic 11-amino-acid peptide derived from erythropoietin (non-erythropoietic EPO fragment) ## Why this grade Unusually for a grey-market peptide, ARA-290 has completed several small, properly designed, placebo-controlled human Phase 2 trials (sarcoidosis small-fibre neuropathy and type 2 diabetes) with measurable, positive signals on nerve fibres and symptoms. But the trials are small, short and few, there is no completed Phase 3 replication, it is approved nowhere, and the developing company (Araim Pharmaceuticals) has ceased operations. So: real, encouraging early human data, but unfinished — a clear C rather than the D most peptides earn. ## In plain terms **Simple.** EPO is a natural hormone famous for boosting red blood cells (and for being doped in cycling). Scientists noticed EPO also quietly protects and repairs injured tissue, and that this repair job uses a different switch from the blood-boosting one. ARA-290 is a tiny man-made piece designed to flip only the repair switch. In a few small human studies it helped people with damaged small nerves (in sarcoidosis and diabetes) feel less pain and grow some nerve fibres back. That's genuinely interesting, but the studies were small and short, no big follow-up trial was ever finished, and it isn't an approved medicine anywhere. **Standard.** ARA-290, also called cibinetide, is a synthetic 11-amino-acid peptide based on a region of erythropoietin (EPO). EPO does two separate jobs: it tells the body to make red blood cells, and — through a different receptor — it protects and repairs stressed tissue. ARA-290 was engineered to trigger only the second, tissue-protective pathway, so it doesn't raise red-cell count or carry EPO's clotting and cardiovascular risks. The real draw is its human data: small randomised, placebo-controlled Phase 2 trials in sarcoidosis-related small-fibre neuropathy and in type 2 diabetes reported reduced neuropathic pain, regrowth of corneal and skin nerve fibres, and some metabolic improvements, with no notable safety problems. The honest caveats: each trial had only a few dozen people, ran around a month, and no confirmatory Phase 3 was completed. It holds a US FDA orphan-drug (and Fast Track) designation for sarcoidosis but is approved nowhere, and what's sold online as 'ARA-290' is an unlicensed research chemical of unknown quality. **Technical.** ARA-290 (cibinetide; sequence pGlu-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser, CAS 1208243-50-8) is a non-erythropoietic hendecapeptide modelled on the helix-B surface of erythropoietin. The rationale rests on the 'innate repair receptor' (IRR) hypothesis of Brines and Cerami: tissue-protective EPO signalling is proposed to be mediated not by the classical homodimeric EPOR but by a heteroreceptor of EPOR with the beta-common receptor (CD131), upregulated in injured/inflamed tissue, signalling via JAK2/STAT, PI3K-Akt and antiapoptotic cascades. By engaging this complex without the erythropoietic EPOR homodimer, ARA-290 in principle delivers cytoprotection and resolution of inflammation without erythropoiesis, polycythaemia or thrombotic risk. Human evidence: Heij et al. (Mol Med 2012, PMID 23168581) ran a 22-patient randomised, double-blind pilot in sarcoidosis small-fibre neuropathy using intravenous dosing thrice weekly over four weeks; Brines et al. (Mol Med 2015, PMID 25387363) reported a 4-week placebo-controlled Phase 2 in type 2 diabetes (daily subcutaneous) with improvements in HbA1c, lipid ratios, PainDetect score and corneal nerve fibre measures; a later 28-day, 64-subject dose-ranging Phase 2b in sarcoid small-fibre neuropathy (subcutaneous) met its primary endpoint of increased corneal nerve fibre area and reported increased skin intraepidermal GAP-43+ nerve fibre length, with pain benefit in those with worse baseline pain. All are small, short, and single-disease; the IRR/CD131 mechanism remains debated and not fully validated; and development by Araim Pharmaceuticals did not advance to a completed Phase 3 before the company ceased operations. ## How it is thought to work ARA-290 is designed to selectively activate the so-called 'innate repair receptor' — proposed to be a heteromeric complex of the erythropoietin receptor (EPOR) and the beta-common receptor (CD131) that is upregulated in injured and inflamed tissue. Engaging this complex is thought to switch on anti-apoptotic and anti-inflammatory signalling (JAK2/STAT and PI3K-Akt pathways), dampening pro-inflammatory cytokines and supporting survival and regrowth of small nerve fibres. Crucially it does not bind the classical EPOR homodimer that drives red-blood-cell production, so it is non-erythropoietic. The receptor model itself is still scientifically debated and not universally accepted. ## Studied for Research contexts, not proven uses. - Sarcoidosis-associated small-fibre neuropathy - Neuropathic pain - Type 2 diabetes: neuropathic symptoms and metabolic control - Small nerve fibre regeneration - Anti-inflammatory / tissue protection (mostly preclinical) - Other indications such as mood disorders have been proposed but lack robust published human trials ## What the human evidence shows There is real, if limited, human evidence — which sets ARA-290 apart from most peptides sold online. A 22-patient randomised, double-blind, placebo-controlled pilot in sarcoidosis patients with small-fibre neuropathy (Heij 2012, intravenous dosing thrice weekly for four weeks) found it safe and improved a validated neuropathy symptom score and quality-of-life measures. A roughly month-long placebo-controlled Phase 2 trial in type 2 diabetes (Brines 2015, daily subcutaneous) reported improvements in HbA1c, lipid profile, the PainDetect neuropathic-symptom score and corneal nerve fibre density. A later dose-ranging Phase 2b in sarcoid small-fibre neuropathy (64 patients, 28 days, subcutaneous) met its primary endpoint with increased corneal nerve fibre area and increased skin intraepidermal nerve fibre length, plus a meaningful pain reduction in those with worse baseline pain. Across these, tolerability looked good. The big limitations: every trial was small (tens of patients), short (about four weeks of dosing), and in a narrow patient group; no Phase 3 confirmatory trial was completed; and it is not approved as a medicine anywhere. Claims about general 'tissue repair', recovery or anti-ageing in healthy people are not backed by these trials. ## Concerns and unknowns - No completed Phase 3 trial and no marketing approval anywhere; the developer, Araim Pharmaceuticals, has ceased operations and there is no active development programme. - Human data is confined to small, short trials in specific diseases (sarcoidosis, diabetes) — it tells you little about use in otherwise healthy people for 'recovery' or longevity. - The 'innate repair receptor' (EPOR/CD131) mechanism it relies on is still scientifically contested. - Material sold online as ARA-290 is an unlicensed research chemical: no guarantee of identity, purity or sterility, and self-injection carries infection and other risks. - Long-term safety in humans is essentially unknown beyond the roughly one-month trial windows. - Because it derives from EPO, buyers may wrongly assume it boosts performance like EPO — it is specifically engineered not to raise red cells, so online sellers' claims should be treated sceptically. ## UK status ARA-290 / cibinetide is not a licensed medicine in the UK — the MHRA has not authorised it for any indication, and it is not an approved product on the UK market. It would be regarded as an unlicensed, investigational substance; supplying or selling it for human use without the appropriate authorisations would fall foul of the Human Medicines Regulations 2012. In practice it is sold as a 'research chemical not for human consumption', which places it outside any medicines-quality or safety oversight. It holds a US FDA orphan-drug (and Fast Track) designation for sarcoidosis, but those are development incentives, not approvals, and have no bearing on UK legality. ## Sport / WADA ARA-290 is not individually named on the WADA Prohibited List, but athletes should be cautious. Although it is engineered to be non-erythropoietic, it is derived from and acts on the erythropoietin-receptor system, and WADA prohibits erythropoietin-receptor agonists and related agents under section S2 (Peptide Hormones, Growth Factors and Mimetics). Its status as an unapproved substance also means it could be caught by the clause covering substances with no current approval for human therapeutic use. Anyone in tested sport should assume risk and seek guidance rather than treat it as clearly permitted. ## Key trials - **ARA 290 in sarcoidosis patients with small-fibre neuropathy (pilot)** (Phase II (pilot), Completed). 22 patients, randomised double-blind, intravenous dosing thrice weekly for 4 weeks; improved neuropathy symptom score (Heij 2012). - **ARA 290 in type 2 diabetes — metabolic control and neuropathic symptoms** (Phase II, Completed). Placebo-controlled, ~28 days daily subcutaneous; improved HbA1c, lipid ratios, PainDetect and corneal nerve fibre density (Brines 2015). - **Cibinetide dose-ranging Phase 2b in sarcoidosis-associated small-fibre neuropathy** (Phase IIb, Completed). 64 patients, dose-ranging subcutaneous vs placebo over 28 days; met primary endpoint with increased corneal nerve fibre area and skin GAP-43+ nerve fibre length, plus pain benefit in more severe cases. ## Sources 1. Safety and Efficacy of ARA 290 in Sarcoidosis Patients with Symptoms of Small Fiber Neuropathy: A Randomized, Double-Blind Pilot Study. Heij L, Niesters M, Swartjes M, et al., Molecular Medicine, 2012 2. ARA 290, a Nonerythropoietic Peptide Engineered from Erythropoietin, Improves Metabolic Control and Neuropathic Symptoms in Patients with Type 2 Diabetes. Brines M, Dunne AN, van Velzen M, et al., Molecular Medicine, 2015 3. Cibinetide improves corneal nerve fibre abundance in sarcoidosis-associated small nerve fibre loss and neuropathic pain (Phase 2b, dose-ranging) — PubMed search. Brines M, et al., PubMed (search), 2017 4. Cibinetide / ARA-290 clinical and preclinical literature — PubMed search. Various, PubMed (search), 2026 5. Cibinetide. Wikipedia contributors, Wikipedia, 2026 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/ara-290 . Educational only, not medical advice. --- # Adipotide **Evidence grade: D (Animal data only).** Area: Other. > An experimental peptide that kills the blood vessels feeding fat tissue, with striking results in mice and a few monkeys. **Also known as:** FTPP, Prohibitin-Targeting Peptide-1 (Prohibitin-TP01 / PTP-1), CKGGRAKDC-GG-D(KLAKLAK)2, fat-targeted proapoptotic peptide, adipotide, prohibitin-targeting peptide **Class:** Synthetic chimeric pro-apoptotic targeting peptidomimetic (vascular-disrupting / anti-angiogenic) ## Why this grade The compelling data come from rodents and a single obese-rhesus-monkey study (Science Translational Medicine, 2011). First-in-human Phase 1 oncology trials were registered (notably NCT01262664 at MD Anderson, and a later Arrowhead Phase 1 obesity programme). The animal work flagged a dose-dependent kidney injury signal, and the human trials did not advance past Phase 1. Promising biology with a documented safety concern keeps this firmly at D rather than C. ## In plain terms **Simple.** Fat tissue needs blood vessels to survive, just like any other part of your body. Adipotide is a lab-made molecule built from two halves stuck together: one half is a 'homing tag' that sticks to the blood vessels feeding fat, and the other half is a tiny 'self-destruct' message that tells those vessel cells to die. Starve the fat of its blood supply and the fat shrinks away. It worked impressively in obese mice and in some obese monkeys. They lost weight and their blood-sugar control improved. The animal studies also found kidney damage, though. It is not a medicine you can be prescribed. What is sold online is unlicensed 'research chemical' material, not something approved for people to inject. **Standard.** Adipotide (also called FTPP) is a two-part synthetic peptide. One part is a short peptide sequence (CKGGRAKDC) that homes specifically to the lining of blood vessels inside white fat. Those vessels carry an unusually high amount of a protein called prohibitin. The second part is a pro-apoptotic sequence, D(KLAKLAK)2, that wrecks the mitochondria and triggers programmed cell death once it enters the cell. The idea is elegant: selectively destroy the micro-blood-supply of fat tissue so the fat cannot survive and gets reabsorbed by the body. In obese mice this caused dramatic weight loss. In a 2011 study obese rhesus monkeys lost roughly a tenth of their body weight and became markedly more insulin-sensitive. Animal studies showed a dose-related kidney injury, though reversible in monkeys: raised creatinine, plus protein and glucose in the urine. Early-phase human trials in cancer patients were registered but the trials did not yield weight-loss results. The drug never progressed to Phase 2. In the UK it is not a licensed medicine and anything sold to consumers is an unlicensed research chemical with no quality guarantees. **Technical.** Adipotide is a chimeric peptidomimetic identified through in vivo phage-display biopanning (Kolonin et al., Nature Medicine 2004). It couples a cyclic nonapeptide homing motif, CKGGRAKDC, which binds prohibitin on the luminal endothelial surface of white adipose tissue microvasculature, to the pro-apoptotic amphipathic D-enantiomer peptide D(KLAKLAK)2. The KLAKLAK moiety is non-toxic extracellularly but disrupts the mitochondrial membrane once internalised, precipitating caspase-dependent apoptosis of the targeted adipose endothelium. The resulting microvascular ablation produces ischaemic involution and resorption of white-adipose-tissue depots, with downstream reduction in adiposity and improved insulin sensitivity. In diet-induced obese mice this drove substantial weight loss. Subsequent rodent work attributed much of the weight loss to a reduction in food intake rather than energy expenditure alone (Kim, Woods & Seeley, Diabetes 2010). The non-human-primate study (Barnhart et al., Science Translational Medicine 2011) in spontaneously obese rhesus macaques reported approximately 11% body-weight reduction over a 28-day course with improved insulin resistance. The dose-limiting toxicity was renal: dose-dependent, largely reversible elevations in serum creatinine with glucosuria, proteinuria and proximal tubular epithelial changes, consistent with renal handling of cationic peptides. First-in-human Phase 1 oncology studies were registered, including NCT01262664 (single-cycle prohibitin-targeting peptide in metastatic castrate-resistant prostate cancer with obesity, MD Anderson) and a later Arrowhead Pharmaceuticals Phase 1 obesity programme. Neither trial produced published efficacy or safety results, and clinical development did not advance. ## How it is thought to work A chimeric peptide: the CKGGRAKDC homing motif binds prohibitin, which is over-expressed on the endothelium of white adipose tissue blood vessels, delivering the fused D(KLAKLAK)2 pro-apoptotic sequence into those endothelial cells. There it disrupts mitochondrial membranes and triggers apoptosis, ablating the fat depot's microvasculature so the white fat undergoes ischaemic resorption, reducing adiposity and improving insulin sensitivity in animal models. Rodent data also suggest a significant component of the weight loss is driven by reduced food intake. ## Studied for Research contexts, not proven uses. - Obesity / body-fat reduction (animal models) - Improvement of insulin resistance and metabolic parameters (obese monkeys) - Targeted vascular ablation as an anti-cancer / anti-angiogenic strategy (early oncology context, including a prostate-cancer Phase 1) ## What the human evidence shows Effectively none for obesity. The strong data are preclinical: dramatic weight loss in diet-induced obese mice and approximately 11% body-weight loss with improved insulin sensitivity in obese rhesus monkeys (Science Translational Medicine, 2011). First-in-human Phase 1 studies were registered in oncology populations (for example NCT01262664 at MD Anderson; a separate Arrowhead Pharmaceuticals Phase 1 obesity trial began in 2012). No published efficacy or safety results emerged and the programmes did not advance. ## Concerns and unknowns - Nephrotoxicity: dose-dependent renal tubular injury (raised creatinine, proteinuria, glucosuria) was reversible in monkeys but represents a serious dose-limiting toxicity signal. - No completed, published human efficacy or safety trial; any human use is uncontrolled experimentation. - Destroying fat via vascular apoptosis is non-selective in principle. The long-term consequences of ablating adipose microvasculature in humans are unknown. - Sold only as an unlicensed research chemical. No pharmaceutical-grade manufacturing, purity, sterility or dose-accuracy guarantees. - Marketing as a fat-melting peptide grossly overstates an animal-stage compound with a documented kidney risk. ## UK status Not a licensed medicine in the UK. Adipotide has no MHRA marketing authorisation and is not approved anywhere in the world. It cannot lawfully be prescribed or sold as a medicine for human use. It is an investigational early-stage research compound whose clinical development stalled. Material offered to consumers online is an unlicensed substance typically labelled 'for research use only / not for human consumption'. Supplying or marketing it for human use would fall foul of the Human Medicines Regulations 2012. ## Key trials - **A First-in-Man, Phase I Evaluation of a Single Cycle of Prohibitin-Targeting Peptide 1 in Patients With Metastatic Prostate Cancer and Obesity** (NCT01262664, Phase 1, No published weight-loss efficacy/safety read-out; program did not advance). Run at MD Anderson Cancer Center in castrate-resistant prostate cancer with obesity. Included to be transparent that human testing was attempted, not that human efficacy or safety was demonstrated. - **Arrowhead Pharmaceuticals first-in-human Phase 1 study of Adipotide in obesity** (Phase 1, First patient dosed 2012; no published completed efficacy/safety read-out; program discontinued). Separate industry-sponsored Phase 1 obesity programme. No NCT identifier confirmed here; clinical development subsequently stalled. ## Sources 1. Reversal of obesity by targeted ablation of adipose tissue. Kolonin MG, Saha PK, Chan L, Pasqualini R, Arap W, Nature Medicine, 2004 2. A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys. Barnhart KF, Christianson DR, Hanley PW, et al., Science Translational Medicine, 2011 3. Peptide designed to elicit apoptosis in adipose tissue endothelium reduces food intake and body weight. Kim DH, Woods SC, Seeley RJ, Diabetes, 2010 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/adipotide . Educational only, not medical advice. --- # Argireline (Acetyl Hexapeptide-8) **Evidence grade: C (Early / limited human data).** Area: Skin & Aesthetics. > A lab-made six-amino-acid peptide sold in anti-ageing creams as a topical Botox alternative, with a plausible mechanism but thin, mostly cosmetic-grade human evidence and a serious question over whether it can penetrate skin at all. **Also known as:** Acetyl Hexapeptide-8, Acetyl Hexapeptide-3, Argireline, Ac-EEMQRR-NH2, argireline peptide, topical botox alternative, botox in a bottle **Class:** Synthetic acetylated hexapeptide (6 amino acids); SNAP-25 N-terminal fragment mimetic ## Why this grade Some human data exists - including one small double-blind placebo-controlled trial - but the foundational wrinkle study was uncontrolled (n=10), most studies measure cosmetic surrogates rather than muscle activity, the one rigorous RCT was effectively negative for efficacy, and it is unclear the peptide even reaches its target through intact skin. ## In plain terms **Simple.** Argireline is a tiny man-made protein fragment put into wrinkle creams. The idea is that it works a bit like Botox: it tries to stop the tiny muscles in your face from tensing, so the skin above them creases less. The catch is that Botox is injected straight into muscle, while a cream just sits on the surface - and your skin is very good at keeping things out. There's some evidence it slightly smooths fine lines, but the studies are small and shaky, and nobody is sure the peptide even gets deep enough to do what it claims. It's a cosmetic ingredient, not a medicine, and it definitely isn't injectable. **Standard.** Argireline (acetyl hexapeptide-8) is a synthetic peptide marketed as a needle-free Botox alternative in serums and creams. It mimics a fragment of SNAP-25, a protein that nerves use to release the signal telling muscles to contract; in theory it interferes with that release and relaxes the small facial muscles that cause expression lines. The original 2002 study reported up to a 30% reduction in wrinkle depth, but it tested only 10 people and wasn't a proper blinded, placebo-controlled trial. The bigger problem is delivery: lab penetration studies suggest the vast majority of applied peptide never gets past the outer skin layer, so whether it reaches facial nerves and muscle at meaningful levels is genuinely unresolved. A more rigorous double-blind trial in people with eyelid spasm found only a non-significant trend. So it's plausible and probably harmless, but the human evidence is weak and the headline claims outrun the data. **Technical.** Argireline is Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2, an acetylated, C-terminally amidated hexapeptide modelled on the N-terminal domain of SNAP-25. Proposed mechanism: competitive interference with SNARE complex assembly (SNAP-25/syntaxin/VAMP), destabilising the ternary complex required for Ca2+-dependent vesicular exocytosis at the neuromuscular junction, thereby attenuating acetylcholine release and reducing subjective muscle contraction - mechanistically downstream-convergent with botulinum neurotoxin A, but via non-enzymatic competitive inhibition rather than SNARE proteolysis. In vitro it inhibits catecholamine release in chromaffin cells dose-dependently. The dominant pharmacokinetic objection is dermal bioavailability: as a ~889 Da hydrophilic, charged peptide it penetrates the lipophilic stratum corneum poorly (Kraeling et al. 2015 reported ~0.22% recovery confined to human stratum corneum and no peptide in the dermis or receptor compartment over 24h), so achieving neuromuscular-junction concentrations sufficient to inhibit SNARE assembly via passive topical application is biophysically implausible without enhancers (W/O/W emulsions, microneedling, iontophoresis). Most positive in vivo reports measure skin-biomechanical/topography surrogates (elasticity, replica-derived wrinkle depth) rather than EMG-confirmed contraction inhibition; the review literature notes no in vivo study has confirmed muscle-contraction inhibition. Observed cosmetic effects may reflect formulation/occlusion or surface hydration rather than the claimed neuromodulatory action. ## How it is thought to work Argireline is a fragment-mimetic of SNAP-25, one of the SNARE proteins that nerve endings use to dock and fuse the vesicles that release neurotransmitters. By competing with SNAP-25 during SNARE complex assembly, it is proposed to destabilise the complex needed for calcium-dependent exocytosis, dampening acetylcholine release at the neuromuscular junction and so reducing the facial muscle contractions that drive expression lines. This converges on the same endpoint as botulinum toxin but without cleaving any protein - it is a reversible competitive interference, not enzymatic destruction, and far weaker. The whole mechanism is contingent on the peptide actually reaching nerve and muscle through intact skin, which is the central unresolved problem. ## Studied for Research contexts, not proven uses. - Periorbital and forehead expression lines / wrinkle depth - Topical adjunct to botulinum toxin (extending duration) - Blepharospasm (as a topical add-on) ## What the human evidence shows Thin and mostly low-quality. The founding study (Blanes-Mira 2002) reported up to ~30% reduction in periorbital wrinkle depth with a hexapeptide emulsion over 30 days, but it was an uncontrolled proof-of-concept in only 10 women, with the human portion bolted onto in-vitro and animal data. Later in-vivo reports claim larger wrinkle-depth reductions but measure surrogate skin-topography/biomechanical parameters, not actual muscle activity, and review authors note that no in-vivo study has confirmed inhibition of facial muscle contraction. The one genuinely rigorous human trial - a double-blind, placebo-controlled randomised pilot in 24 blepharospasm patients (Lungu 2013, NCT01750346) - found only a non-significant trend toward longer symptom control (3.7 vs 3.0 months) and did not meet its primary endpoint, though it confirmed topical safety. Overlaying all of this is strong in-vitro evidence that the peptide barely penetrates the stratum corneum, casting doubt on whether positive cosmetic findings reflect the claimed neuromuscular mechanism at all. ## Concerns and unknowns - Skin penetration is the core problem: lab studies suggest the vast majority of applied peptide never passes the outer skin layer, so it may never reach the nerves/muscle it is supposed to act on - any visible effect could be down to moisturisation or formulation, not the advertised mechanism. - Marketing far outruns the evidence: 'Botox in a bottle' implies injectable-grade muscle relaxation that topical data simply do not support. - The strongest cosmetic claim rests on a tiny (n=10), uncontrolled 2002 study; the only well-designed RCT was for eyelid spasm and did not show a statistically significant benefit. - Sold as a cosmetic, so concentration, purity and formulation quality vary widely between brands and are not tightly regulated for efficacy. - Safety panels (CIR) have only formally concluded safety at very low concentrations (up to around 0.005%, the highest concentration in the data they reviewed), with data deemed insufficient to judge the higher concentrations actually marketed - though no significant topical toxicity signal has emerged. - If it truly worked by altering muscle function it would arguably be a drug, not a cosmetic - the fact it's sold freely partly reflects that it probably doesn't do that much. ## UK status In the UK, argireline is sold as a cosmetic ingredient, not a licensed medicine. It falls under the UK Cosmetic Products Regulation (retained Regulation (EC) No 1223/2009), enforced via Trading Standards and the OPSS, rather than under the MHRA. That status depends on it being presented and claimed as a cosmetic - improving the appearance of the skin - and not as something that treats disease or modifies a physiological function. A product making genuine medicinal/neuromuscular claims could in principle be pulled into medicines regulation under the Human Medicines Regulations 2012 and MHRA guidance on borderline products, but in practice topical argireline creams are treated as cosmetics. It is not an approved medicine for wrinkles or any other indication in the UK. ## Sport / WADA Not specifically named on the WADA Prohibited List. As a topical cosmetic peptide with negligible systemic absorption and no plausible performance-enhancing effect, it is not a realistic anti-doping concern. Athletes should still rely on the current WADA list and a reputable batch-tested product rather than assume any peptide product is clean. ## Key trials - **Topical Acetyl Hexapeptide-8 in Blepharospasm Patients Receiving Botulinum Toxin (NCT01750346)** (Pilot RCT, Completed). Double-blind, placebo-controlled, n=24. Topically safe; only a non-significant trend toward extended symptom control (3.7 vs 3.0 months) - did not demonstrate efficacy on the primary endpoint. - **Blanes-Mira 2002 human topography proof-of-concept** (Uncontrolled pilot, Completed). n=10, no blinded placebo arm; reported ~30% wrinkle-depth reduction. Methodologically weak; the basis for most marketing claims. ## Sources 1. A synthetic hexapeptide (Argireline) with antiwrinkle activity. Blanes-Mira C, et al., International Journal of Cosmetic Science, 2002 2. Pilot study of topical acetyl hexapeptide-8 in the treatment for blepharospasm in patients receiving botulinum toxin therapy. Lungu C, Considine E, Zahir S, Ponsati B, Arrastia S, Hallett M, European Journal of Neurology, 2013 3. Acetyl Hexapeptide-8 in Cosmeceuticals - A Review of Skin Permeability and Efficacy. Zdrada-Nowak J, Surgiel-Gemza A, Szatkowska M, International Journal of Molecular Sciences, 2025 4. In vitro skin penetration of acetyl hexapeptide-8 from a cosmetic formulation. Kraeling MEK, Zhou W, Wang P, Ogunsola OY, Cutaneous and Ocular Toxicology, 2015 5. Safety Assessment of Acetyl Hexapeptide-8 and Acetyl Hexapeptide-8 Amide as Used in Cosmetics. Cosmetic Ingredient Review (CIR) Expert Panel, Cosmetic Ingredient Review / International Journal of Toxicology, 2025 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/argireline . Educational only, not medical advice. --- # BPC-157 **Evidence grade: D (Animal data only).** Area: Recovery & Repair. > A lab-made peptide based on a fragment of a protein found in stomach fluid, widely studied in animals for tissue repair but essentially untested in humans. **Also known as:** Body Protection Compound 157, PL 14736, Bepecin, PLD-116, bpc, bpc157, wolverine peptide, body protection compound, wolverine stack **Class:** Synthetic pentadecapeptide (15 amino acids) ## Why this grade Extensive animal research but almost no completed human trials. The healing signals seen in rats have not been shown in people. ## In plain terms **Simple.** BPC-157 is a man-made copy of a fragment of a natural stomach protein. In animals, it helps injuries heal faster, including tendons, muscles and the gut lining. Almost all this work is in rats. It is not yet known whether it works the same way in humans, or whether it is safe. **Standard.** BPC-157 is a synthetic 15-amino-acid peptide derived from a sequence within a protein in human gastric juice. In rodent studies it speeds up healing across many tissues, including tendon, ligament, muscle, gut and nerve. It works mainly by promoting angiogenesis, the growth of new blood vessels. The animal data is notably consistent. There are no completed, published human trials of injectable BPC-157. It is not an approved medicine anywhere, and almost all is sold as an unregulated 'research chemical' of uncertain purity. **Technical.** BPC-157 is a stable gastric pentadecapeptide (sequence GEPPPGKPADDAGLV) originally isolated as a fragment of body protection compound from gastric juice. Preclinical work, predominantly from Sikiric's Zagreb group, reports cytoprotective and angiogenic effects across musculoskeletal, gastrointestinal, hepatic and neural models. Proposed mechanisms involve the VEGFR2–Akt–eNOS pathway, nitric-oxide system modulation, upregulation of growth-hormone receptor expression in tendon fibroblasts, and interaction with dopaminergic and serotonergic systems. The oral analogue PL 14736 reached early-phase study for inflammatory bowel disease. The evidence base is heavily concentrated in one research lineage. Human pharmacokinetic and efficacy data are absent for the injectable form, and independent replication outside the originating group is limited. ## How it is thought to work The leading explanation is that BPC-157 promotes angiogenesis, the formation of new blood vessels, by upregulating VEGFR2 signalling. Better blood supply to damaged tissue then supports repair. Animal work also points to modulation of the nitric-oxide system, increased expression of growth-hormone receptors in tendon cells, and effects on dopamine and serotonin pathways that may explain the reported gut-brain and neuroprotective findings. ## Studied for Research contexts, not proven uses. - Tendon & ligament healing - Muscle injury recovery - Gut & GI lining repair - Wound healing - Inflammatory bowel disease (oral analogue) - Neuroprotection (preclinical) ## What the human evidence shows Very limited. The most-cited human work concerns the oral analogue PL 14736 in early inflammatory-bowel-disease studies. For the injectable form that people actually buy, there are no completed peer-reviewed human efficacy trials and no published human pharmacokinetics or safety data. Claims of benefit in people rest on extrapolation from animals and anecdote, not controlled human research. ## Concerns and unknowns - Almost the entire evidence base is animal data from a single research lineage, with limited independent replication. - No published human safety data for injectable use, so long-term risks are genuinely unknown. - Grey-market product purity is unverified, and what is in the vial may not match the label. - There is a theoretical concern that strong pro-angiogenic effects could be unwanted in anyone with cancer or proliferative disease. - It is marketed heavily online with claims that far outrun the actual human evidence. ## UK status BPC-157 is not a licensed medicine in the UK and has no marketing authorisation from the MHRA. It is not a controlled drug, but cannot legally be sold or supplied for human consumption. Online sellers avoid this by labelling it 'for research use only / not for human consumption'. Selling it as a treatment or making medicinal claims breaches the Human Medicines Regulations. ## Sport / WADA Prohibited in sport. BPC-157 was added to the World Anti-Doping Agency Prohibited List in 2022 under S0 (non-approved substances), so it is banned for tested athletes at all times. ## Key trials - **PL 14736 (oral BPC-157 analogue) early-phase studies for inflammatory bowel disease** (Phase I/II (historical), Not progressed to approval). The closest thing to human data, and it is for the oral analogue, not the injectable form sold online. ## Sources 1. Brain–gut axis and pentadecapeptide BPC 157: theoretical and practical implications. Sikiric P et al., Current Neuropharmacology, 2016 2. Stable Gastric Pentadecapeptide BPC 157 in the Treatment of Wound Healing and Tissue Repair (review). Seiwerth S et al., Current Pharmaceutical Design, 2018 3. Multifunctionality and Possible Medical Application of the BPC 157 Peptide — Literature and Patent Review. Józwiak M et al., Pharmaceuticals, 2025 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/bpc-157 . Educational only, not medical advice. --- # CJC-1295 **Evidence grade: C (Early / limited human data).** Area: Muscle & Performance. > A synthetic long-acting trigger for growth hormone release, tested in humans briefly in the early 2000s and then abandoned. Sold now only as an unlicensed research chemical. **Also known as:** CJC-1295 DAC, CJC-1295 with DAC, DAC:GRF, Modified GRF (1-29) (the no-DAC version), Teserelin (proposed INN), cjc, cjc1295, cjc dac, mod grf **Class:** Synthetic growth hormone-releasing hormone (GHRH) analogue / long-acting growth hormone secretagogue ## Why this grade Genuine human data exist, but they are narrow. Two early-2000s placebo-controlled trials in healthy adults (published 2006) established that CJC-1295 raises GH and IGF-1 for days to weeks and characterised its pharmacokinetics. This is more than most grey-market peptides. However, no human trials show it improves any clinical or performance outcome (muscle mass, strength, body composition, fat loss). The development programme was abandoned after a participant death in a 2006 HIV-lipodystrophy study, and there is no modern controlled safety data. Real human PK/PD exists, but no proven benefit and no long-term safety picture. Rated C, not B, because the human trials measured only surrogate hormone endpoints rather than meaningful clinical efficacy. ## In plain terms **Simple.** Your body makes growth hormone in pulses, controlled by a natural signal called GHRH. CJC-1295 is a man-made copy of that signal, redesigned to last far longer in the blood so it keeps nudging the body to release more growth hormone for days. Scientists tested it in healthy people in the mid-2000s and it did raise growth hormone levels. The company developing it stopped after a person died in a trial. Doctors attributed the death to an existing heart problem, not the drug, but they halted development to be safe. It was never approved as a medicine and was never shown to actually build muscle or improve anything in people. Today it is sold online as an unlicensed 'research chemical', not a medicine, and nobody checks what is really in the vial. **Standard.** CJC-1295 is a synthetic analogue of growth hormone-releasing hormone (GHRH), the natural hormone that tells the pituitary gland to release growth hormone (GH). Four amino-acid swaps make it resistant to the enzyme DPP-IV that normally breaks GHRH down within minutes. The most common 'DAC' version carries a chemical hook that binds to albumin (a blood protein), turning it into a slow-release depot with a half-life of roughly a week. In two small trials in healthy adults around 2006, it reliably raised GH and IGF-1 for several days after a single dose, with IGF-1 staying elevated for weeks after repeated dosing, and was reasonably well tolerated in the short term. Those trials measured hormone levels, not real-world results. There is no human evidence it builds muscle, burns fat, or improves performance. Development was discontinued by the original company (ConjuChem) after a participant died of a heart attack in a separate HIV-lipodystrophy study. The death was attributed to pre-existing coronary disease rather than the drug, but the programme never resumed. It has no UK or US marketing authorisation and is banned in sport. **Technical.** CJC-1295 is a GHRH(1-29) analogue carrying four substitutions (D-Ala2, Gln8, Ala15, Leu27) that confer DPP-IV resistance. The DAC ('Drug Affinity Complex') variant appends a maleimidopropionic acid linker that forms a covalent bond with cysteine-34 of circulating albumin, creating a bioconjugate depot and extending the half-life to roughly 6-8 days. The no-DAC 'modified GRF(1-29)' lacks the albumin-binding linker and is short-acting. It is an agonist at the GHRH receptor (GHRHR) on pituitary somatotrophs, driving cAMP/PKA-mediated GH synthesis and secretion. Human pharmacology: Teichman et al. (JCEM 2006) reported dose-dependent 2-10-fold rises in mean GH sustained beyond 6 days and 1.5-3-fold rises in IGF-1 for 9-11 days after single subcutaneous dosing, with IGF-1 elevated up to ~28 days after repeated dosing. Ionescu & Frohman (JCEM 2006) demonstrated pulsatile GH architecture is largely preserved despite continuous GHRHR stimulation, with elevated trough GH. Proof-of-concept animal work includes the GHRH-knockout mouse normalisation study (Alba et al., Am J Physiol Endocrinol Metab 2006). No Phase 3 work or clinical-endpoint efficacy data exist (lean mass, lipolysis, performance). The programme was discontinued following a fatal myocardial infarction in a Phase 2 HIV-lipodystrophy cohort (adjudicated as pre-existing CAD/plaque rupture, deemed unrelated to treatment). The theoretical risk profile mirrors GH/IGF-1 excess: insulin resistance, fluid retention and oedema, arthralgia, and an unquantified neoplastic concern from sustained IGF-1 elevation. ## How it is thought to work CJC-1295 is a synthetic GHRH(1-29) analogue with four stabilising amino-acid substitutions that resist degradation by dipeptidyl peptidase-IV (DPP-IV). The 'DAC' version bears an albumin-binding linker that covalently couples it to circulating serum albumin, forming a long-lived depot with a half-life of roughly 6-8 days. It acts as an agonist at pituitary GHRH receptors on somatotroph cells, stimulating cAMP-dependent synthesis and pulsatile release of endogenous growth hormone, which in turn raises hepatic IGF-1. It works upstream of the pituitary's own machinery rather than supplying GH directly, so GH secretion remains broadly pulsatile. ## Studied for Research contexts, not proven uses. - Sustained elevation of endogenous growth hormone and IGF-1 in healthy adults (pharmacology/PK studies) - GH-axis stimulation as a potential alternative to recombinant GH (proof of concept) - HIV-associated lipodystrophy (Phase 2 programme, halted) - GH deficiency / growth normalisation (animal models, e.g. GHRH-knockout mice) ## What the human evidence shows Real but limited and old. Two early randomised, placebo-controlled trials in healthy adults (published 2006) established the core human evidence: a single subcutaneous dose produced dose-dependent increases in GH (roughly 2-10-fold) for six or more days and in IGF-1 (about 1.5-3-fold) for 9-11 days, with IGF-1 remaining elevated for up to about 28 days after repeated dosing, and a half-life of roughly 6-8 days. GH pulsatility was largely preserved and short-term tolerability in these small studies was acceptable. However, these trials measured hormone levels only. There is no human evidence that CJC-1295 improves muscle mass, strength, body composition, fat loss or any clinical outcome. A separate Phase 2 trial in HIV lipodystrophy was halted in 2006 after a participant died of a myocardial infarction, attributed by investigators to pre-existing coronary artery disease rather than the drug. The developer discontinued the programme. There have been no modern Phase 2/3 trials and no long-term controlled safety data. ## Concerns and unknowns - No marketing authorisation anywhere: never an approved medicine in the UK, US or EU. Development was abandoned after the mid-2000s. - No proven benefit in humans: every human study measured hormone levels only. None demonstrated improved muscle, fat loss or performance. - Participant death in a Phase 2 lipodystrophy trial (cardiac) ended the development programme. Long-term human safety is essentially uncharacterised. - Sustained elevation of GH and IGF-1 carries plausible risks: insulin resistance and raised blood glucose, fluid retention and oedema, joint pain, and a theoretical (unquantified) increase in cancer risk from chronic IGF-1 elevation. - Grey-market quality: products sold 'for research use only / not for human consumption' are unregulated. Documented cases of mislabelled or impure preparations mean you cannot be sure what is in the vial or its purity. - Banned in sport (WADA S2), so use risks sanctions for any tested athlete. - The short-acting 'modified GRF(1-29)' or 'no-DAC' product is frequently sold under the CJC-1295 name, creating confusion about what is actually being supplied. ## UK status Not a licensed medicine in the UK. The MHRA has granted no marketing authorisation for CJC-1295 for any indication. It is an abandoned investigational drug, now sold almost exclusively as an unlicensed 'research chemical' labelled 'not for human consumption'. Supplying or selling it for human use without authorisation is unlawful under the Human Medicines Regulations 2012. It is prohibited at all times in sport under section S2 of the WADA Prohibited List (adopted by UK Anti-Doping). ## Sport / WADA Prohibited at all times (in- and out-of-competition) under section S2 of the WADA Prohibited List, as a growth hormone-releasing factor / GHRH analogue. ## Key trials - **Randomised, placebo-controlled, double-blind ascending-dose trials of CJC-1295 in healthy adults (ConjuChem programme)** (Phase 1/2, Completed (reported 2006); programme subsequently discontinued). Two trials (28- and 49-day) at two sites in healthy adults, single and repeated subcutaneous dosing; basis of the Teichman 2006 JCEM publication. - **Phase 2 trial of CJC-1295 in HIV-associated lipodystrophy** (Phase 2, Halted in 2006 after a participant death (cardiac, adjudicated as unrelated/pre-existing disease); development discontinued). The halt led ConjuChem to abandon CJC-1295 development; no NCT identifier confidently known. ## Sources 1. Prolonged Stimulation of Growth Hormone (GH) and Insulin-Like Growth Factor I Secretion by CJC-1295, a Long-Acting Analog of GH-Releasing Hormone, in Healthy Adults. Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA, Journal of Clinical Endocrinology & Metabolism, 2006 2. Pulsatile Secretion of Growth Hormone (GH) Persists during Continuous Stimulation by CJC-1295, a Long-Acting GH-Releasing Hormone Analog. Ionescu M, Frohman LA, Journal of Clinical Endocrinology & Metabolism, 2006 3. Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse. Alba M, Fintini D, Sagazio A, Lawrence B, Castaigne JP, Frohman LA, Salvatori R, American Journal of Physiology - Endocrinology and Metabolism, 2006 4. Identification of CJC-1295, a growth-hormone-releasing peptide, in an unknown pharmaceutical preparation. Henninge J, Pepaj M, Hullstein I, Hemmersbach P, Drug Testing and Analysis, 2010 5. CJC-1295 - overview, development history and discontinuation. Wikipedia, 2026 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/cjc-1295 . Educational only, not medical advice. --- # CagriSema **Evidence grade: B (Promising human evidence).** Area: Weight & Metabolic. > An investigational once-weekly injection combining semaglutide with cagrilintide (a synthetic amylin analogue) to achieve greater weight loss than either component alone. **Also known as:** Cagrilintide/Semaglutide, cagrilintide + semaglutide, cagrilintide-semaglutide, cagri sema, cagrisema, cagri+sema **Class:** Fixed-dose combination injectable: long-acting amylin analogue (cagrilintide) plus GLP-1 receptor agonist (semaglutide) ## Why this grade Large, well-conducted Phase 3 human RCTs (the REDEFINE programme, thousands of participants) show clinically meaningful weight loss versus placebo and versus each component alone, with REDEFINE 1 published in the New England Journal of Medicine. It is not graded A because as of mid-2026 it is not approved by any regulator (FDA filing began December 2025) and long-term safety and cardiovascular outcome data are incomplete. ## In plain terms **Simple.** CagriSema is a single injection that mixes two medicines that both make you feel full. One of them, semaglutide, is the same ingredient as Wegovy and Ozempic. The other, cagrilintide, copies a different hunger hormone called amylin. Together they suppress appetite more effectively than either drug alone. In large, properly conducted studies, people lost around a fifth of their body weight on average. The evidence is genuine and strong, but as of mid-2026 it is still being assessed by regulators and is not approved anywhere in the world. Products sold online today calling themselves 'CagriSema' are not the tested medicine. **Standard.** CagriSema is Novo Nordisk's investigational follow-up to semaglutide (Wegovy/Ozempic). It combines two appetite-suppressing hormones in one weekly injection. Semaglutide is a GLP-1 receptor agonist. Cagrilintide is a long-acting amylin analogue, mimicking a hormone the pancreas releases with insulin to signal fullness. Targeting two complementary fullness pathways produces greater weight loss than either alone. In the Phase 3 REDEFINE 1 trial (over 3,400 adults with obesity, published in the New England Journal of Medicine), people on CagriSema lost about 22.7% of body weight when they completed treatment, or roughly 20% across all participants regardless of adherence, versus about 3% on placebo. REDEFINE 2 (adults with type 2 diabetes) showed around 16% weight loss. Side effects are mainly gastrointestinal: nausea, vomiting, diarrhoea. The key point: it is still investigational. Novo Nordisk filed with the FDA in December 2025 but as of mid-2026 it is not approved or licensed anywhere, including the UK. **Technical.** CagriSema is a fixed-dose, once-weekly subcutaneous combination of cagrilintide (a long-acting amylin analogue with agonist activity at amylin and calcitonin receptors, AMY1-3 and CTR) and semaglutide (a GLP-1 receptor agonist). The rationale is complementary central appetite suppression. GLP-1R signalling occurs in the hypothalamus and brainstem, complemented by amylinergic signalling (area postrema, nucleus tractus solitarius), with amylin also implicated in restoring leptin sensitivity. The Phase 3 REDEFINE programme provides the pivotal human evidence. REDEFINE 1 (n=3,417; overweight/obesity without diabetes; 68 weeks; randomised against cagrilintide alone, semaglutide alone and placebo; published NEJM 2025) reported ~22.7% mean weight reduction on the trial-product estimand and ~20.4% on the treatment-policy estimand versus ~3.0% with placebo, with monotherapy arms at ~11.5% (cagrilintide) and ~14.9% (semaglutide). Secondary improvements included systolic blood pressure, waist circumference, lipids and glycaemia. REDEFINE 2 (n=1,206; type 2 diabetes; 68 weeks) showed ~15.7% weight loss versus ~3.1% placebo. The REIMAGINE programme extends evidence in type 2 diabetes, with REIMAGINE 2 reporting HbA1c reduction of ~1.91 percentage points alongside ~14% weight loss. REDEFINE 1 fell short of Novo Nordisk's internal target (~25%), partly due to flexible dose escalation in which many participants did not reach the top dose. Regulatory status: US FDA submission December 2025, first review decision expected late 2026; not approved in any jurisdiction as of mid-2026. No MHRA submission has been publicly confirmed. Long-term cardiovascular outcome data are not yet available. ## How it is thought to work Dual GLP-1/amylin appetite suppression. Semaglutide agonises the GLP-1 receptor to enhance satiety, slow gastric emptying and improve glycaemic control. Cagrilintide is a long-acting amylin analogue that agonises amylin and calcitonin receptors to promote satiety and reduce food intake via brainstem (area postrema) and hypothalamic circuits, with a proposed role in restoring leptin sensitivity. The two pathways are complementary, producing greater appetite reduction and weight loss than either alone. Administered by subcutaneous injection once weekly. ## Studied for Research contexts, not proven uses. - Weight management in adults with obesity or overweight (with weight-related comorbidity) - Weight loss and glycaemic control in adults with obesity/overweight and type 2 diabetes - HbA1c reduction in type 2 diabetes (REIMAGINE programme) ## What the human evidence shows Strong and direct for a peptide combination at this stage. The Phase 3 REDEFINE programme enrolled thousands of participants. REDEFINE 1 (n=3,417, without diabetes; published in the New England Journal of Medicine, 2025) showed ~22.7% mean weight loss on the trial-product estimand (~20.4% treatment-policy) versus ~3% placebo over 68 weeks, with both individual drugs as comparator arms. REDEFINE 2 (n=1,206, with type 2 diabetes) showed ~15.7% weight loss versus ~3.1% placebo. This is genuine peer-reviewed human RCT evidence, far beyond animal or in-vitro data backing most grey-market peptides. Long-term and cardiovascular outcome data are still maturing, and no regulator had approved it as of mid-2026. ## Concerns and unknowns - Investigational and unapproved: as of mid-2026 CagriSema is not licensed by the MHRA, FDA or any other regulator and cannot be legally prescribed or sold as a medicine. - Grey-market counterfeits: products sold as 'CagriSema' or 'cagri + sema' by research-chemical vendors are unlicensed, unregulated, and of unknown identity, purity, dose and sterility. They are not the trialled product. - Gastrointestinal side effects (nausea, vomiting, diarrhoea, constipation) are common, consistent with the GLP-1/amylin class. - Headline efficacy fell short of Novo Nordisk's internal expectations in REDEFINE 1, partly due to flexible dose escalation in which many participants did not reach the top dose. - Long-term safety and cardiovascular outcome data are not yet available. - As with other GLP-1 agents, weight regain is expected after stopping, and loss of lean/muscle mass plus class-wide cautions apply. ## UK status Investigational and not licensed in the UK. As of mid-2026 CagriSema holds no MHRA marketing authorisation and is not approved anywhere in the world. Novo Nordisk filed with the FDA in December 2025, with a first decision expected in late 2026. No UK/MHRA submission has been publicly confirmed. It cannot lawfully be prescribed or sold as a medicine in the UK. Any product marketed as 'CagriSema' by research-chemical suppliers is an unlicensed substance, not the trialled medicine, and selling or supplying it for human use would breach the Human Medicines Regulations 2012. A future NHS route would require NICE appraisal after any MHRA licence is granted. ## Sport / WADA Not specifically listed by WADA. GLP-1/amylin agonists are not currently prohibited for weight loss in sport, but athletes should check the current WADA Prohibited List and guidance directly. ## Key trials - **REDEFINE 1 - CagriSema in overweight/obesity without type 2 diabetes** (NCT05567796, Phase 3, Completed / reported (NEJM 2025)). n=3,417; 68 weeks; ~22.7% mean weight reduction (trial-product estimand) vs ~3% placebo; included cagrilintide and semaglutide monotherapy arms. - **REDEFINE 2 - CagriSema in overweight/obesity with type 2 diabetes** (NCT05669755, Phase 3, Completed / reported (2025)). n=1,206; ~15.7% weight loss vs ~3.1% placebo at 68 weeks. ## Sources 1. Cagrilintide-Semaglutide in Adults with Overweight or Obesity (REDEFINE 1). New England Journal of Medicine, 2025 2. Once-weekly cagrilintide for weight management in people with overweight and obesity: a dose-finding phase 2 trial. Lau DCW, Erichsen L, Francisco AM, et al., The Lancet (vol 398, pp 2160-2172), 2021 3. Novo Nordisk files for FDA approval of CagriSema, the first once-weekly combination of GLP-1 and amylin analogues for weight management. Novo Nordisk company announcement / PR Newswire, 2025 4. CagriSema demonstrates superior weight loss in adults with obesity or overweight and type 2 diabetes in the REDEFINE 2 trial. Novo Nordisk company announcement, 2025 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/cagrisema . Educational only, not medical advice. --- # Cagrilintide **Evidence grade: B (Promising human evidence).** Area: Weight & Metabolic. > Cagrilintide is an experimental once-weekly injection mimicking the body's fullness hormone amylin to reduce appetite and body weight. The trial results are impressive, but it is not yet an approved medicine. **Also known as:** AM833, Cagri, long-acting amylin analogue, cagrilintide, amylin analogue **Class:** Long-acting amylin (and calcitonin receptor) analogue; injectable peptide ## Why this grade Substantial, good-quality human evidence for an unapproved drug. Multiple published randomised controlled trials include a Phase 1b combination study, two Phase 2 trials, and a 68-week Phase 3 trial (REDEFINE 1) showing cagrilintide monotherapy at roughly 11.8% mean weight loss versus about 2.3% on placebo. No regulator, including the MHRA, EMA or FDA, has licensed cagrilintide as a standalone agent. The dedicated Phase 3 monotherapy programme is still underway, preventing Grade A. Most efficacy data come from the manufacturer's trial programme, and the headline Phase 3 figure was first reported via conference and company disclosure rather than a peer-reviewed primary publication. ## In plain terms **Simple.** After you eat, your body releases a hormone called amylin that tells your brain you are full. Cagrilintide is a man-made copy, engineered so a single weekly injection keeps working for days. In clinical trials it helped people eat less and lose weight. The important thing: it is still being tested and no medicines regulator has approved it. Any 'cagri' sold online to the public is unlicensed, so you cannot know what is actually in it. **Standard.** Cagrilintide (developed by Novo Nordisk, codename AM833) is a long-acting version of amylin, a hormone the pancreas releases alongside insulin. Amylin promotes fullness and slows stomach emptying. It works through a different appetite pathway from GLP-1 drugs like semaglutide, which is why it is being tested both alone and combined with semaglutide (that combination is CagriSema). The human evidence is strong for an investigational drug. A Phase 2 dose-finding trial showed roughly 10.8% weight loss at 26 weeks at the highest dose, outperforming liraglutide. The 68-week Phase 3 REDEFINE 1 trial reported about 11.8% mean weight loss for cagrilintide alone versus around 2.3% on placebo. The main side effects are gastrointestinal: nausea and vomiting. Cagrilintide is not licensed by the MHRA or any other regulator, and the CagriSema combination is at most under regulatory review. It remains investigational, and grey-market 'cagri' powders sold online are unlicensed research chemicals of unknown quality. **Technical.** Cagrilintide (AM833) is a lipidated, long-acting non-selective amylin/calcitonin receptor agonist engineered for once-weekly subcutaneous administration. Amylin (islet amyloid polypeptide) is co-secreted with insulin and acts on amylin receptors (AMY1-3, the calcitonin receptor dimerised with receptor activity-modifying proteins RAMP1-3) in the area postrema and hypothalamus to suppress food intake, slow gastric emptying and reduce glucagon secretion. This anorexigenic pathway is mechanistically distinct from GLP-1 receptor agonism, explaining why cagrilintide is being developed as monotherapy and in fixed co-administration with semaglutide (CagriSema). Human data: Lau et al. (Lancet 2021; PMID 34798060) reported a Phase 2 dose-finding RCT showing dose-dependent weight loss of approximately 10.8% at 26 weeks at the top dose versus about 3.0% on placebo and 9.0% on liraglutide. Enebo et al. (Lancet 2021) demonstrated favourable PK/PD and tolerability of cagrilintide co-administered with semaglutide in a Phase 1b trial. Frias et al. (Lancet 2023) reported a Phase 2 combination trial in type 2 diabetes. The Phase 3 REDEFINE 1 programme reported cagrilintide monotherapy delivering roughly 11.8% mean weight loss at 68 weeks versus about 2.3% on placebo, prompting advancement into a dedicated Phase 3 monotherapy programme; this headline monotherapy figure was disseminated via conference and company disclosure ahead of a peer-reviewed primary publication. Adverse events are predominantly mild-to-moderate gastrointestinal. No marketing authorisation exists from the MHRA, EMA or FDA for cagrilintide as a standalone agent; the CagriSema combination is at most under regulatory review. ## How it is thought to work A long-acting synthetic analogue of the satiety hormone amylin. It activates amylin/calcitonin (AMY) receptors in the area postrema and hypothalamus, suppressing appetite, slowing gastric emptying and reducing glucagon. This appetite-regulation pathway is distinct from and complementary to GLP-1 receptor agonists, which is why it is combined with semaglutide in CagriSema. Given by once-weekly subcutaneous injection. ## Studied for Research contexts, not proven uses. - Weight management in overweight and obesity (as monotherapy) - Weight loss in combination with semaglutide (the CagriSema programme) - Glycaemic control and weight loss in type 2 diabetes (combination studies) ## What the human evidence shows Unusually strong for a drug not yet on the market, though incomplete. Published randomised controlled trials include a Phase 1b combination study (Lancet 2021), a Phase 2 dose-finding monotherapy trial (Lancet 2021) showing roughly 10.8% weight loss at 26 weeks, outperforming liraglutide, and a Phase 2 combination trial in type 2 diabetes (Lancet 2023). The 68-week Phase 3 REDEFINE 1 trial reported approximately 11.8% mean body-weight reduction with cagrilintide monotherapy versus about 2.3% with placebo. That monotherapy headline was first reported through conference and company disclosure rather than a peer-reviewed primary paper. A dedicated Phase 3 monotherapy programme is underway. Most data sit within Novo Nordisk's CagriSema/REDEFINE programme, with limited independent replication. ## Concerns and unknowns - Not licensed by the MHRA or any other regulator. It is investigational, so its safety/efficacy balance has not been signed off for routine clinical use. - Gastrointestinal side effects (nausea, vomiting, diarrhoea, constipation) are common. - Long-term safety data are still being collected; the dedicated monotherapy Phase 3 programme had not fully reported in a peer-reviewed primary publication at the time of writing. - Grey-market 'cagrilintide' or 'cagri' powders sold online are unlicensed research chemicals of unverified identity, purity and sterility. Buyers cannot confirm what they are injecting. - Most published efficacy data come from the manufacturer's trial programme, with limited independent replication. - The strongest weight-loss results come from combination with semaglutide (CagriSema). Cagrilintide's standalone effect is more modest. ## UK status Investigational drug, not a licensed UK medicine. The MHRA has not granted cagrilintide a marketing authorisation, it is not available on prescription or via the NHS, and the CagriSema combination is at most under regulatory review. Legitimate UK access is only through enrolment in a registered clinical trial. Material sold online as 'cagrilintide' or 'cagri' is an unlicensed research chemical marketed 'not for human consumption'. Supplying it for human use breaches the Human Medicines Regulations 2012. ## Key trials - **REDEFINE 1: 68-week Phase 3 trial of once-weekly CagriSema, cagrilintide monotherapy and semaglutide monotherapy vs placebo in adults with obesity/overweight without type 2 diabetes** (Phase 3, Completed / reported). Cagrilintide monotherapy arm: ~11.8% mean weight loss vs ~2.3% placebo at 68 weeks. Headline monotherapy figure reported via company/conference disclosure. - **Dedicated Phase 3 monotherapy programme evaluating cagrilintide on its own for weight management** (Phase 3, Ongoing). Standalone monotherapy programme triggered by REDEFINE 1 data. ## Sources 1. Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial. Lau DCW, et al., The Lancet, 2021 2. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide for weight management: a randomised, controlled, phase 1b trial. Enebo LB, et al., The Lancet, 2021 3. Efficacy and safety of co-administered once-weekly cagrilintide with once-weekly semaglutide in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. Frias JP, et al., The Lancet, 2023 4. Novo Nordisk presents phase 3 data for next-generation amylin cagrilintide, leading to advancement into a dedicated clinical programme (REDEFINE 1; ~11.8% mean weight loss at 68 weeks with monotherapy). Novo Nordisk, Novo Nordisk company announcement / press release, 2025 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/cagrilintide . Educational only, not medical advice. --- # Cerebrolysin **Evidence grade: C (Early / limited human data).** Area: Cognition & Mood. > An injectable mix of small protein fragments from pig brain, used in some countries for stroke and dementia, but independent reviewers say the evidence of benefit is weak. **Also known as:** Cere, EVER Neuro Pharma Cerebrolysin, FPF-1070, cerebro, cerebrolysin **Class:** Porcine brain-derived neuropeptide and amino acid mixture (neurotrophic/neuropeptide preparation), given by injection ## Why this grade Unusually for a grey-market peptide, there is a genuine body of human RCT evidence (CARS, CASTA, multiple stroke and dementia trials) and several Cochrane reviews. The independent verdict, however, is consistently that the evidence is insufficient or low/very-low quality. The primary endpoint in the largest stroke trial (CASTA, ~1070 patients) was neutral. Most positive results come from manufacturer-sponsored studies. The 2023 Cochrane stroke review found moderate-certainty evidence of more non-fatal serious adverse events. This places it above the typical animal-only peptide but well short of a proven, approved treatment backed by robust independent RCTs. Limited, conflicting human data justifies a C. ## In plain terms **Simple.** Cerebrolysin is a liquid made by breaking down pig brains into tiny protein pieces, then injected into people. The idea is that these fragments act like fertiliser for brain cells, helping them survive and recover after a stroke or in dementia. It is used in quite a few countries. When independent scientists review all the good-quality trials together, they consistently find they cannot be sure it helps. The most recent reviews also found it may cause more side effects (though not fatal ones). It is not approved or sold as a medicine in the UK. **Standard.** Cerebrolysin is a neuropeptide preparation made by enzymatically digesting purified porcine brain protein into a standardised mix of low-molecular-weight peptides and free amino acids. It is given by injection or infusion and is marketed in dozens of countries (much of Europe, the Middle East, Asia, Latin America, Russia and CIS states) for acute ischaemic stroke, traumatic brain injury and dementia. The theory is that the peptide fragments mimic the body's own neurotrophic (nerve-growth) factors. There has been a fair amount of human testing, including large randomised trials like CARS and CASTA. The picture is mixed. CASTA, the largest stroke trial, missed its main goal. Most positive findings come from manufacturer-funded studies. Independent Cochrane reviews across stroke and vascular dementia repeatedly conclude the evidence is too weak or low-quality to recommend it. The 2023 Cochrane stroke review also flagged a probable increase in non-fatal serious adverse events. It is not a licensed medicine in the UK, US or Australia. **Technical.** Cerebrolysin is a peptidergic preparation produced by standardised enzymatic (proteolytic) breakdown of purified porcine brain protein, yielding a mixture of biologically active low-molecular-weight peptides and free amino acids. It is proposed to have pleiotropic neurotrophic and neuroprotective actions, partially mimicking endogenous neurotrophic factors (BDNF, GDNF, CNTF, NGF-like signalling), modulating amyloid processing, attenuating excitotoxicity and apoptosis, and supporting neuroplasticity and neurogenesis in preclinical models. It is administered intravenously or intramuscularly and is marketed in dozens of countries for acute ischaemic stroke, traumatic brain injury and dementia. The human evidence base is substantial in volume but contested. The CARS programme reported a positive motor-recovery endpoint (Action Research Arm Test) post-stroke. CASTA (n approximately 1070) was neutral on its primary endpoint, with positive findings confined to post-hoc severe-stroke subgroups. Independent synthesis is unfavourable. The Ziganshina et al. Cochrane review on acute ischaemic stroke (updated 2023, CD007026.pub7) found probably little or no effect on all-cause death and moderate-certainty evidence of an increase in non-fatal serious adverse events. The Cui et al. Cochrane review on vascular dementia (2019, CD008900.pub3) reported a possible cognitive and global-function signal but rated the evidence as low/very-low quality and not definitive. Pervasive industry sponsorship, heterogeneity and risk of bias undermine confidence. Batch-to-batch compositional variability of a biologically-derived, incompletely-defined peptide mixture is an inherent pharmacological concern. ## How it is thought to work Proposed to act as a pleiotropic neurotrophic/neuroprotective agent. The peptide fragments are thought to partially mimic endogenous neurotrophic factors (BDNF, GDNF, CNTF, NGF-like signalling), supporting neuronal survival, reducing excitotoxic and apoptotic injury, modulating amyloid precursor protein processing, and promoting neuroplasticity, synaptogenesis and neurogenesis. Most mechanistic data are preclinical (cell and animal models); the precise active components and human pharmacodynamics of this incompletely-defined biological mixture are not fully characterised. ## Studied for Research contexts, not proven uses. - Recovery after acute ischaemic stroke (motor and global function) - Vascular dementia and cognitive impairment - Alzheimer's disease - Traumatic brain injury - Other neurorehabilitation contexts ## What the human evidence shows Unusually for a grey-market peptide, real human RCTs exist. The CARS trial reported improved upper-limb motor recovery after stroke, and numerous manufacturer-supported studies report benefit. The largest stroke trial, CASTA (approximately 1070 patients), was neutral on its primary endpoint, with apparent benefit only in post-hoc severe-stroke subgroups. Independent Cochrane reviews provide the key assessment. The acute ischaemic stroke review (Ziganshina et al., updated 2023) found probably little or no effect on all-cause death and moderate-certainty evidence of increased non-fatal serious adverse events. The vascular dementia review (Cui et al., 2019) found a possible cognitive and global-function signal but rated the evidence as low/very-low quality and not definitive. Heavy industry sponsorship and risk of bias weaken confidence throughout. ## Concerns and unknowns - Independent (Cochrane) reviews repeatedly conclude the evidence is insufficient or low/very-low quality to support routine use, despite many positive industry-sponsored trials - The 2023 Cochrane stroke review found moderate-certainty evidence of increased non-fatal serious adverse events - Derived from pig brain tissue: a biologically variable, incompletely-defined mixture with inherent batch-to-batch consistency and theoretical biological-contamination concerns - Not a licensed medicine in the UK, US or Australia; any UK supply would be unlicensed/imported and outside MHRA assurance - Injectable product: grey-market or self-administered injectables carry sterility and contamination risks - Marketing in some countries and on wellness sites overstates efficacy relative to the independent evidence ## UK status Not a licensed medicine in the UK. Cerebrolysin holds no UK marketing authorisation from the MHRA and is not approved for any indication. It is sold in many countries (much of Europe, Asia, the Middle East, Russia and CIS states, Latin America) but is also unapproved in the US and Australia. In the UK it exists only as an unlicensed, imported product or as a research chemical sold not for human consumption. There is no NHS use and no MHRA quality or safety assurance behind grey-market supply. ## Sport / WADA Not specifically listed on the WADA Prohibited List; not a recognised performance-enhancing agent. ## Key trials - **Cerebrolysin and Recovery After Stroke (CARS)** (NCT01070498, Phase 4, Completed). Motor recovery after acute ischaemic stroke; reported positive Action Research Arm Test outcome. - **Cerebrolysin in Acute Stroke Treatment in Asia (CASTA)** (Phase 3/4, Completed). ~1070 patients; neutral on primary endpoint, apparent benefit only in post-hoc severe-stroke subgroup. ## Sources 1. Cerebrolysin for acute ischaemic stroke (Cochrane Database of Systematic Reviews). Ziganshina LE, Abakumova T, Nurkhametova D, Ivanchenko K, Cochrane Database Syst Rev, 2023 2. Cerebrolysin for vascular dementia (Cochrane Database of Systematic Reviews). Cui S, Chen N, Yang M, et al., Cochrane Database Syst Rev, 2019 3. Cerebrolysin and Recovery After Stroke (CARS): A Randomized, Placebo-Controlled, Double-Blind, Multicenter Trial. Muresanu DF, Heiss WD, Hoemberg V, et al., Stroke, 2016 4. Cerebrolysin in patients with acute ischemic stroke in Asia: results of a double-blind, placebo-controlled randomized trial (CASTA). Heiss WD, Brainin M, Bornstein NM, Tuomilehto J, Hong Z (CASTA Investigators), Stroke, 2012 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/cerebrolysin . Educational only, not medical advice. --- # Cortagen **Evidence grade: D (Animal data only).** Area: Cognition & Mood. > A lab-made four-amino-acid peptide, derived from a cow-brain extract, that Russian researchers claim repairs nerves and protects the brain, but the real evidence is almost all from rats and cell dishes produced by one group, with no proper human trials. **Also known as:** AEDP, Ala-Glu-Asp-Pro, cortagen peptide, brain cortex bioregulator, cerebral cortex peptide, cortexin-derived tetrapeptide **Class:** Synthetic ultra-short peptide (tetrapeptide, Ala-Glu-Asp-Pro); brain/nerve-targeted Khavinson-group "bioregulator" ## Why this grade The evidence base is almost entirely in-vitro and rodent work, overwhelmingly from a single research group (Khavinson and affiliates in St Petersburg). The human reports that exist are old, mostly Russian-institute case series and open-label work without blinding, randomisation or independent replication to modern standards. There are no registered, independent randomised controlled efficacy trials. By the site's rubric that is a clear D: animal/in-vitro data with no meaningful, replicated human evidence. ## In plain terms **Simple.** Cortagen is a tiny man-made protein fragment, just four building blocks long. It was copied from a Russian medicine made out of cow brain, and the idea is that it helps damaged nerves heal and keeps brain cells healthy. In experiments on rats and on cells in dishes it does seem to do something, for example helping cut nerves regrow a bit faster. But those are laboratory tests, not proper tests in people. There are no solid human trials proving it actually works or is safe, so the brain-boosting claims you see online are mostly hope, not proof. In the UK it isn't a medicine you can be prescribed; it's sold as a grey-market 'research chemical'. **Standard.** Cortagen is the tetrapeptide Ala-Glu-Asp-Pro, one of the 'bioregulator' peptides from Vladimir Khavinson's group in Russia. It was designed from amino-acid analysis of cortexin, an older cattle-brain-cortex extract used in Russian neurology, as a defined-sequence stand-in for that messy mixture. It's studied mainly for nerve repair and brain protection: in rats, giving Cortagen after a sciatic-nerve injury reportedly speeded up how fast the nerve regrew and how well it conducted signals, and in rodent stroke/low-oxygen models it's reported to reduce brain damage and behavioural deficits. The honest picture is that this is preclinical science, largely from one institution. Older Russian clinical reports describe improvements in nerve injury and cerebrovascular patients, but they lack blinding and modern trial design and haven't been reproduced by independent Western labs. The dramatic 'cognitive enhancement' and 'anti-ageing' claims are extrapolations from rats and cells. In the UK it is not a licensed medicine and is sold unlicensed, usually labelled 'not for human consumption'. **Technical.** Cortagen is the tetrapeptide Ala-Glu-Asp-Pro (AEDP), a member of the Khavinson family of short 'bioregulator' peptides, synthesised on the basis of amino-acid analysis of cortexin (a bovine cerebral-cortex polypeptide preparation). The proposed mechanism mirrors the wider Khavinson hypothesis: that ultra-short peptides penetrate cell and nuclear membranes and interact sequence-preferentially with promoter DNA and chromatin to modulate transcription of tissue-relevant genes, here in neural and (secondarily) cardiac tissue. Supporting data: a 2004 oligonucleotide-microarray study in mouse heart (Anisimov, Khavinson, Anisimov) reported altered expression of ~110 genes including Bmp2, Wnt4 and Hsc70. In peripheral-nerve work (Turchaninova et al., 2000), intramuscular Cortagen after sciatic-nerve transection in Wistar rats increased regenerating-fibre growth rate and conduction velocity by ~27% and ~40% respectively. Rodent chronic-ischaemia and ischaemic-preconditioning models (Zarubina & Shabanov) report reduced neurological deficit and antioxidant action. Critically: the direct intranuclear DNA-binding model remains contested outside the originating group; human pharmacokinetic, bioavailability and dose-response data are absent; trial registration and independent replication are lacking; and the human clinical literature is largely unblinded Russian-institute work, not RCT-grade evidence. ## How it is thought to work Cortagen is the tetrapeptide Ala-Glu-Asp-Pro, designed as a defined-sequence analogue of the active fraction of cortexin (a bovine cerebral-cortex peptide extract). Its proposed mechanism, per the Khavinson group, is the generic short-peptide bioregulator model: the peptide enters cells and the nucleus and interacts sequence-preferentially with promoter DNA and chromatin, modulating transcription of tissue-relevant genes in neural and cardiac tissue. Downstream, this is reported to stimulate nerve regeneration (faster axonal regrowth and conduction velocity after nerve injury), exert neuroprotective and antioxidant effects in ischaemia/hypoxia models, and shift expression of genes involved in development and stress response (e.g. Bmp2, Wnt4, Hsc70 in cardiac microarray work). This direct DNA-interaction model is mechanistically unusual and not independently established; the regenerative and neuroprotective effects are documented mainly in rodents and in vitro. ## Studied for Research contexts, not proven uses. - Peripheral nerve regeneration after injury (rodent models) - Neuroprotection in ischaemia/hypoxia and chronic cerebral ischaemia (rodent models) - Post-stroke and cerebrovascular recovery (older, unblinded Russian clinical reports) - Proposed regulation of gene expression in neural/cardiac tissue (mechanistic, preclinical) ## What the human evidence shows Thin and low-quality. There are no completed, registered, independent randomised controlled trials of Cortagen for nerve repair, cognition or any other outcome. Older Russian-institute reports describe benefit in cerebrovascular and post-stroke patients, but these are largely open-label or unblinded case series that predate and fall short of modern trial-methodology standards, and they have not been reproduced by independent Western laboratories. The robust, reproducible data are in rats and cultured cells (sciatic-nerve regeneration, ischaemia/hypoxia neuroprotection, cardiac gene-expression microarrays), overwhelmingly from the Khavinson group. Claims of human cognitive enhancement, nerve 'healing' or anti-ageing benefit should be treated as unproven in people. ## Concerns and unknowns - No RCT-grade human efficacy or safety data; the human reports are unblinded Russian-institute work and the strong data are rodent/in-vitro only. - Near-total reliance on a single research group with little independent replication, raising publication-bias and reproducibility concerns. - Sold as an unlicensed grey-market 'research chemical', usually labelled 'not for human consumption'; no UK marketing authorisation and not prescribable as a recognised therapy. - Grey-market products have no guarantee of identity, purity, sterility or endotoxin content; injectable peptides carry infection and contamination risks. - The proposed 'peptide enters the nucleus and directly regulates genes' mechanism is contested and not well established outside the originating group. - Some confusion exists in marketing material over the exact sequence (Cortagen is AEDP, but it is sometimes mislabelled as an 'AEDG complex'); buyers cannot verify what they are actually receiving. - Long-term effects of chronically manipulating gene expression in the brain are entirely unstudied in humans. ## UK status Cortagen is not a licensed medicine in the UK and holds no MHRA marketing authorisation. It is not an approved or recognised treatment for nerve injury, stroke, cognition or anything else, and there are no MHRA-authorised UK clinical trials of it. (Cortexin, the related cattle-brain extract it derives from, is a registered drug in Russia but not in the UK.) In practice Cortagen is sold online as an unlicensed 'research chemical', typically labelled 'not for human consumption' to sidestep medicines regulation. Selling or supplying it for human use would engage the Human Medicines Regulations 2012; a UK clinician cannot lawfully prescribe it as a recognised therapy. ## Sport / WADA Cortagen is not specifically named on the WADA Prohibited List. However, peptides marketed for tissue repair and 'neuro-recovery' sit in a heavily scrutinised area of anti-doping, and substances without marketing approval can fall under the catch-all S0 (non-approved substances) clause for any substance not addressed by another section and with no current approval by a governmental health authority for human therapeutic use. Athletes should treat it as high-risk and seek guidance from their anti-doping organisation before use. ## Sources 1. Effect of tetrapeptide cortagen on regeneration of sciatic nerve. Turchaninova LN, Kolosova LI, Malinin VV, Moiseeva AB, Nozdrachev AD, Khavinson VK, Bulletin of Experimental Biology and Medicine, 2000 2. Elucidation of the effect of brain cortex tetrapeptide Cortagen on gene expression in mouse heart by microarray. Anisimov SV, Khavinson VKh, Anisimov VN, Neuroendocrinology Letters, 2004 3. Neuroprotective Effects of Peptides during Ischemic Preconditioning. Zarubina IV, Shabanov PD, Bulletin of Experimental Biology and Medicine, 2016 4. [Cortexin and cortagen as correcting agents in functional and metabolic disorders in the brain in chronic ischemia]. Zarubina IV, Shabanov PD, Eksperimental'naia i Klinicheskaia Farmakologiia (Eksp Klin Farmakol), 2011 5. Search: Cortagen / brain cortex tetrapeptide AEDP (PubMed). PubMed _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/cortagen . Educational only, not medical advice. --- # DSIP (Delta Sleep-Inducing Peptide) **Evidence grade: C (Early / limited human data).** Area: Other. > A brain peptide discovered in sleeping rabbits in the 1970s and tested as a sleep aid in humans, but development stalled and it never became a licensed medicine. **Also known as:** Delta Sleep-Inducing Peptide, Delta sleep inducing peptide, DSIP nonapeptide, Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu, dsip, sleep peptide **Class:** Endogenous nonapeptide (neuropeptide); not a licensed medicine. Sold grey-market as a "research chemical". ## Why this grade Small human studies ran in the late 1970s and 1980s, including a double-blind trial in chronic insomniacs, so there is genuine human data rather than animal-only evidence. However, the studies were tiny (single digits to low tens of subjects), mostly open-label or weakly controlled, decades old, and never replicated at scale. Results were modest and inconsistent. No modern RCTs exist, no regulatory approval has been granted, and DSIP's status as a true endogenous sleep factor remains disputed. This defines early and limited human evidence: grade C. ## In plain terms **Simple.** DSIP is a tiny natural molecule discovered in the blood of sleeping rabbits in the 1970s. Small experiments in people suggested it might help insomnia, but that was decades ago and the results were modest. It was never turned into an approved sleeping pill. Today it is sold online as an unregulated 'research chemical', not a real medicine, and its safety and effectiveness remain unknown. **Standard.** Delta Sleep-Inducing Peptide is a nine-amino-acid neuropeptide isolated in the 1970s from the blood of rabbits during slow-wave sleep. The hope was that it might be a natural sleep signal. Small human studies in the early 1980s, including a double-blind trial in people with chronic insomnia, suggested it could modestly improve sleep quality without daytime sedation. Other work explored it for stress and pain. The trials were tiny and old, findings were inconsistent, and research stalled. It was never licensed as a medicine. What is sold today is unlicensed material marked 'for research only', with no quality guarantees and no modern evidence. **Technical.** DSIP is an endogenous nonapeptide (Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu) characterised by Schoenenberger and Monnier at the University of Basel, isolated from the cerebral venous blood of rabbits during electrically induced thalamic slow-wave sleep and reported in the late 1970s. Despite the name, its physiological role as a true somnogenic factor was never firmly established and remains contested. No specific high-affinity DSIP receptor has been definitively characterised, and proposed actions span sleep modulation, stress/HPA-axis attenuation, thermoregulation, analgesia and antioxidant effects; this multivariate profile undermines a coherent mechanistic story. Human data are limited to small studies from the late 1970s and 1980s, including Schneider-Helmert and Schoenenberger's double-blind study in chronic insomniacs (Experientia, 1981) reporting improved sleep, plus other small or open trials in insomnia, withdrawal states and chronic pain. None constitute a robust contemporary RCT programme and no Phase 2/3 development or marketing authorisation occurred. Pharmacokinetics are poorly defined and the peptide is rapidly degraded. Evidence grade C reflects genuine but thin, dated, unreplicated human data. ## How it is thought to work DSIP is a small endogenous neuropeptide originally proposed to be a humoral sleep factor that promotes slow-wave (delta) EEG activity. Its actual mechanism is poorly defined and disputed. No specific receptor has been definitively identified, and reported effects in animals and in vitro span sleep architecture modulation, stress/HPA-axis attenuation (lowering cortisol and ACTH responses), thermoregulation, antinociception and antioxidant activity. This broad, non-specific range of claimed actions itself argues against a single clear pharmacological pathway. In research settings it has been given by injection, since the peptide would be rapidly degraded if taken orally. ## Studied for Research contexts, not proven uses. - Insomnia and disturbed sleep regulation - Stress and HPA-axis / cortisol modulation - Chronic pain and analgesia - Withdrawal / abstinence syndromes (e.g. alcohol, opioid) - Antioxidant and stress-protective effects (largely preclinical) ## What the human evidence shows Human testing peaked in the late 1970s and 1980s with small studies, the best-known being a double-blind intravenous trial in people with chronic insomnia (Schneider-Helmert and Schoenenberger, Experientia 1981) reporting improved sleep without daytime sedation. Other small open or weakly controlled trials examined insomnia, pain and withdrawal states with mixed results. Sample sizes were tiny, designs were mostly open-label or underpowered, and the work was never replicated in modern large RCTs. There is no Phase 2/3 development programme. DSIP's status as a true natural sleep factor remains scientifically contested. The evidence is suggestive but does not meet modern standards for efficacy or safety. ## Concerns and unknowns - No marketing authorisation anywhere. DSIP is not an approved medicine, so there is no regulator-vetted evidence of efficacy, safety or manufacturing quality. - Evidence is decades old, small-scale and unreplicated. Modern RCTs do not exist. - Its identity as a genuine endogenous sleep factor and its mechanism remain scientifically disputed. - Grey-market 'research chemical' supply has no guarantee of purity, identity, dose accuracy, sterility or endotoxin control. - Injecting unregulated material carries infection, contamination and dosing-error risks. - Long-term human safety is essentially unstudied. - Marketing hype vastly outruns the evidence. The name oversells what has ever been demonstrated. ## UK status DSIP is not a licensed medicine in the UK and holds no MHRA marketing authorisation. It is an experimental peptide sold online as an unlicensed 'research chemical' marked 'for research use only / not for human consumption', a label used to sidestep medicines regulation. Selling or supplying it for human use as a medicine without authorisation contravenes the Human Medicines Regulations 2012, and the material is unregulated for quality and safety. It is not a controlled drug under the Misuse of Drugs Act. There is no legitimate route to obtain DSIP for human use in the UK outside an approved clinical trial. ## Sources 1. The delta EEG (sleep)-inducing peptide (DSIP). XI. Amino-acid analysis, sequence, synthesis and activity of the nonapeptide. Schoenenberger GA, Maier PF, Tobler HJ, Wilson K, Monnier M, Pflugers Archiv (Pflugers Arch), 1978 2. The influence of synthetic DSIP (delta-sleep-inducing peptide) on disturbed human sleep. Schneider-Helmert D, Schoenenberger GA, Experientia, 1981 3. A clinical trial with DSIP. Kaeser HE, European Neurology (Eur Neurol), 1984 4. Characterization, properties and multivariate functions of delta-sleep-inducing peptide (DSIP). Schoenenberger GA, European Neurology (Eur Neurol), 1984 5. PubMed search: delta sleep-inducing peptide (DSIP) literature. PubMed (search across the DSIP literature), 2026 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/dsip . Educational only, not medical advice. --- # Dihexa **Evidence grade: D (Animal data only).** Area: Cognition & Mood. > An experimental memory-drug candidate derived from a blood-pressure hormone fragment that showed dramatic effects in rats but has never been tested in humans, and whose foundational study was retracted for falsified data. **Also known as:** N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, PNB-0408, Ang IV analog, dihexa, dihexapeptide **Class:** Angiotensin IV-derived peptidomimetic; proposed HGF/c-Met potentiator (nootropic/synaptogenic) ## Why this grade All efficacy data come from rodents and cultured neurons. There are no completed or registered human trials, no published human pharmacokinetic data, and no published human safety data, and there is no regulatory approval anywhere. Worse than the usual grey-market peptide, the preclinical base is partly compromised: the headline mechanistic paper underpinning the proposed HGF/c-Met action was formally retracted in 2025 after a Washington State University investigation found falsified/fabricated images, and a related 2013 paper carries a notice of concern. Grade D (animal/in-vitro only, no meaningful human evidence) rather than F, because the issue is absence of human data rather than documented human harm. ## In plain terms **Simple.** Dihexa is a lab-made molecule built from a tiny piece of a hormone your body uses to help control blood pressure. Scientists tweaked it so it could survive in the body and reach the brain, where it seemed to help rats grow new connections between brain cells and remember things better. The early excitement was huge, with some reports claiming it was around ten million times stronger than the brain's own growth signal. It has never been given to a person in a proper study. We do not know if it works in humans, whether it is safe, or what it does over time. The main scientific paper that explained how it supposedly works was officially withdrawn by the journal because investigators found the data had been faked. Today it is sold online as an unapproved 'research chemical', not a medicine. **Standard.** Dihexa is a peptidomimetic (a synthetic drug-like cousin of a peptide) derived from angiotensin IV, a fragment of the angiotensin system best known for blood-pressure regulation. Researchers at Washington State University chemically modified it to be metabolically stable and able to cross the blood-brain barrier. In animals, it appeared to restore memory in rats whose cognition had been impaired (by scopolamine or ageing) and to trigger synapse formation in cultured neurons. The most-quoted claim is that it is around seven orders of magnitude (roughly ten million times) more potent than BDNF at promoting synapse formation in a cell dish. This number should be treated with caution because it comes from a narrow lab assay, not from any clinical outcome. The proposed mechanism is that it binds hepatocyte growth factor (HGF) and amplifies signalling through HGF's receptor, c-Met. None of this has translated to humans. There are no registered clinical trials, no published human safety or pharmacokinetic data, and no approval anywhere. The preclinical record is also undermined by misconduct: the foundational mechanistic paper was retracted in 2025 after an institutional investigation found falsified images, and a related paper carries a notice of concern. Confidence in even the rodent data has been shaken. It is currently sold by grey-market vendors labelled 'not for human consumption'. **Technical.** Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide) is an N- and C-terminally modified angiotensin IV analogue (Ang IV: Val-Tyr-Ile-His-Pro-Phe), engineered by the Harding/Wright group at WSU for metabolic stability, oral bioavailability and CNS penetration. The original mechanistic model held that Ang IV-derived peptides exert their procognitive action not as classical AT4/IRAP ligands but by potentiating the hepatocyte growth factor (HGF)/c-Met receptor tyrosine kinase axis. Dihexa was reported to bind HGF (sub-nanomolar affinity), augment HGF-dependent c-Met autophosphorylation at sub-threshold HGF concentrations, and drive hippocampal dendritic spinogenesis and functional synaptogenesis, with procognitive effects abolished by c-Met blockade or HGF/Met knockdown (Benoist et al., JPET 2014; McCoy et al., JPET 2013). Reported picomolar in-vitro spinogenic potency underlies the widely cited '~10^7 x BDNF' figure. Research misconduct has now undermined this foundation. The 2014 JPET paper carried a 2021 expression of concern and was retracted in April 2025 after a WSU investigation found falsified/fabricated images attributed to first co-author Leen Kawas (later CEO of Athira Pharma). The related 2012/2013 JPET work also attracted retraction and notice-of-concern actions. Athira's fosgonimeton (ATH-1017), which targets the same HGF/Met pathway but is a distinct molecule, failed its primary endpoint in the Phase 2/3 LIFT-AD trial (reported September 2024), a cautionary signal for the broader HGF/Met cognition thesis. For dihexa specifically there are no human PK data, no IND-stage clinical programme, and no published toxicology. ## How it is thought to work Dihexa is a metabolically stabilised, brain-penetrant peptidomimetic derived from angiotensin IV. Its proposed mechanism is to bind hepatocyte growth factor (HGF) and potentiate signalling through the c-Met receptor tyrosine kinase, promoting dendritic spine formation and synaptogenesis in the hippocampus. In rodent and cell models this was associated with augmented c-Met phosphorylation and enhanced cognition. The central paper establishing this mechanism was retracted in 2025 after an institutional investigation found falsified data, so the mechanism should be regarded as proposed and poorly supported rather than established. ## Studied for Research contexts, not proven uses. - Memory and learning restoration in scopolamine-impaired and aged rodents - Synaptogenesis and dendritic spine formation in cultured neurons - Alzheimer's-type cognitive impairment (preclinical models only) - General nootropic / cognitive-enhancement research (grey market, no human data) ## What the human evidence shows None. There are no completed or registered human clinical trials, no published human pharmacokinetic data, and no published human safety or toxicology data. Every efficacy claim derives from rodent studies and in-vitro neuronal assays. Marketing comparisons such as 'ten million times more potent than BDNF' come from a narrow cell-culture spine-formation assay, not from any human outcome. The foundational 2014 mechanistic paper was retracted in 2025 for falsified data, further compromising the preclinical record. ## Concerns and unknowns - Efficacy, safety and tolerability in people are entirely unknown. - The key mechanistic paper (Benoist et al., JPET 2014) was retracted in 2025 following a 2021 expression of concern, after a Washington State University investigation found falsified/fabricated images. A related paper also attracted notice-of-concern and retraction actions. This undermines confidence in the proposed HGF/c-Met mechanism and the underlying rodent claims. - The HGF/c-Met pathway drives cell growth and proliferation. Chronically potentiating a growth-factor signalling system raises theoretical oncological concerns that have never been formally assessed. - Sold by grey-market vendors as an unlicensed 'research chemical' labelled 'not for human consumption', with no pharmaceutical-grade manufacturing and no purity or identity assurance. - Hype far exceeds evidence. The '10 million times stronger than BDNF' figure is routinely stripped of its narrow in-vitro context. - Frequently conflated with Athira Pharma's fosgonimeton (ATH-1017), a different molecule targeting the same pathway that failed its Phase 2/3 LIFT-AD Alzheimer's trial, a cautionary signal for the broader HGF/Met cognition thesis. ## UK status Not a licensed medicine in the UK. It has no MHRA marketing authorisation and is not an approved or prescribable drug. There is no recognised UK clinical-trial programme. In practice, it reaches the UK only via grey-market vendors selling it as an unlicensed 'research chemical' marked 'not for human consumption'. Supplying or selling it for human use without authorisation would breach the Human Medicines Regulations 2012. ## Sources 1. The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system. Benoist CC, Kawas LH, Zhu M, Tyson KA, Stillmaker L, Appleyard SM, Wright JW, Wayman GA, Harding JW, Journal of Pharmacology and Experimental Therapeutics, 2014 2. Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents. McCoy AT, Benoist CC, Wright JW, Kawas LH, Bule-Ghogare JM, Zhu M, Appleyard SM, Wayman GA, Harding JW, Journal of Pharmacology and Experimental Therapeutics, 2013 3. Retraction notice: The Procognitive and Synaptogenic Effects of Angiotensin IV-Derived Peptides Are Dependent on Activation of the Hepatocyte Growth Factor/c-Met System. Journal of Pharmacology and Experimental Therapeutics, 2025 4. Athira's Alzheimer's drug fosgonimeton (ATH-1017) fails to meet endpoints in Phase 2/3 LIFT-AD trial. STAT News / company announcement, 2024 5. Dihexa - Cognitive Vitality review. Alzheimer's Drug Discovery Foundation, AlzDiscovery.org (Cognitive Vitality) _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/dihexa . Educational only, not medical advice. --- # Epitalon **Evidence grade: D (Animal data only).** Area: Longevity. > Epitalon is a lab-made four-amino-acid peptide promoted as an anti-ageing telomere treatment, but the human evidence behind those claims is thin and largely from one research group. **Also known as:** Epithalon, Epithalone, AEDG peptide, Ala-Glu-Asp-Gly, Epitalone, epitalon, epithalamin, epitalon peptide **Class:** Synthetic pineal tetrapeptide (peptide bioregulator) ## Why this grade The evidence base is overwhelmingly cell-culture and animal work, the bulk of it from a single Russian group (Khavinson and colleagues) and rarely independently replicated. The handful of human reports are small, old and methodologically weak. There is no robust human trial showing Epitalon extends lifespan, lengthens telomeres in living people, or treats any disease. This places it firmly at D: an interesting preclinical signal with negligible meaningful human evidence. ## In plain terms **Simple.** Epitalon is a tiny man-made peptide (a chain of just four building blocks) based on a substance from the pineal gland, a small organ in the brain. Sellers claim it can switch your body's cells back into a younger mode by protecting telomeres, the caps on the ends of your DNA that wear down as you age. Almost all the encouraging results come from cells in a dish and from mice and rats, mostly produced by one Russian laboratory. The few studies in actual people were small and old. Nobody has run a proper modern trial showing it makes humans live longer or healthier. The anti-ageing story remains a hopeful idea, not a proven fact. **Standard.** Epitalon (also spelled Epithalon) is a synthetic tetrapeptide, sequence Ala-Glu-Asp-Gly, derived from epithalamin, an extract of the pineal gland first studied in the Soviet Union. It is marketed as a longevity bioregulator said to activate telomerase (the enzyme that rebuilds telomeres), normalise melatonin and circadian rhythm, and slow ageing. In test tubes it can lengthen telomeres in human cell lines. Khavinson's group reported reduced tumour rates and effects on ageing markers in rodents. The problem is the quality and independence of the evidence. The literature is dominated by one research group. Lifespan findings are inconsistent: some rodent studies showed no change in average lifespan. Human data amount to a couple of small, dated studies, not the large randomised trials needed to support the bold claims. In the UK it is not a licensed medicine. It is sold online as an unlicensed research chemical. **Technical.** Epitalon is the synthetic tetrapeptide Ala-Glu-Asp-Gly (AEDG), a short-chain peptide bioregulator derived from the pineal polypeptide preparation epithalamin, developed by V.Kh. Khavinson and colleagues at the St Petersburg Institute of Bioregulation and Gerontology. Proposed mechanisms include induction of telomerase reverse transcriptase (hTERT) expression with telomere elongation in somatic cells (reported to enable human fetal fibroblasts to exceed the Hayflick limit), epigenetic/gene-expression modulation via direct peptide-DNA interaction, restoration of pineal melatonin secretion and circadian rhythm, and antioxidant enzyme upregulation. Preclinically, Anisimov et al. (Biogerontology 2003) reported reduced spontaneous tumour incidence and effects on ageing biomarkers in female SHR mice, notably without an increase in mean lifespan in that cohort. A 2025 in-vitro study (Al-Dulaimi et al., Biogerontology) reported dose-dependent telomere elongation via telomerase/hTERT upregulation in normal cells and ALT activation in cancer cell lines. Human evidence is limited to small, methodologically weak studies (e.g. retinitis pigmentosa cohorts; circadian/melatonin work in elderly subjects) with no contemporary, adequately powered, blinded RCTs and no hard longevity endpoints. The pharmacology is constrained by the very short plasma half-life expected of an unprotected linear tetrapeptide and the absence of robust human PK/PD data. Evidence grade D reflects an extensive preclinical signal but negligible high-quality human data and heavy single-group dependence. ## How it is thought to work A synthetic tetrapeptide (Ala-Glu-Asp-Gly) modelled on a pineal-gland extract. Proposed to upregulate telomerase (hTERT), lengthen telomeres, modulate gene expression via direct peptide-DNA interaction, and restore pineal melatonin/circadian signalling. These mechanisms are demonstrated mostly in vitro; confirmation in living humans remains lacking. ## Studied for Research contexts, not proven uses. - Cellular ageing / telomere length (largely in vitro) - Lifespan and tumour incidence in rodents - Melatonin secretion and circadian rhythm in ageing - Retinitis pigmentosa (small early human reports) - Age-related immune and antioxidant markers ## What the human evidence shows Genuinely thin. Despite decades of publications, human data are limited to a few small, old and methodologically weak studies, including retinitis pigmentosa cohorts and circadian/melatonin observations in elderly subjects. Almost all come from the Khavinson group. There are no modern, adequately powered, independently run randomised controlled trials, and no human study demonstrating telomere lengthening in living people or any extension of human lifespan or healthspan. The dramatic 'anti-ageing' claims rest on cell-culture and rodent work, not on humans. ## Concerns and unknowns - Evidence dominated by a single Russian research group with limited independent replication - No modern, adequately powered human RCTs; longevity and telomere claims unproven in people - Some animal studies show no increase in mean lifespan, undercutting headline claims - Sold in the UK as an unlicensed research chemical / not for human consumption. No regulatory oversight of identity, purity, sterility or dose - Grey-market injectable products carry contamination, mislabelling and sterility risks - Long-term safety in humans is essentially unknown. Theoretical concern attaches to any agent claimed to activate telomerase, given telomerase's role in cancer cells - Marketing routinely overstates the evidence as if it were clinically established ## UK status Not a licensed medicine in the UK and not approved by the MHRA for any use. It is not an authorised medicinal product, so any product making medical claims would contravene the Human Medicines Regulations 2012. In practice it is sold online as an unlicensed research chemical labelled not for human consumption, outside any pharmaceutical quality, safety or efficacy oversight. Supplying it for human use or marketing it with medicinal claims is unlawful. ## Sport / WADA Not specifically listed by name on the WADA Prohibited List. Substances are not 'permitted' simply because they are unnamed; novel peptides can fall under broad catch-all categories, so athletes should treat it as high-risk. ## Sources 1. Overview of Epitalon - Highly Bioactive Pineal Tetrapeptide with Promising Properties. Bryl R, et al., International Journal of Molecular Sciences, 2025 2. Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice. Anisimov VN, Khavinson VKh, et al., Biogerontology, 2003 3. Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity. Al-Dulaimi S, et al., Biogerontology, 2025 4. Epitalon (Epithalon) - peptide bioregulator overview. Wikipedia _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/epitalon . Educational only, not medical advice. --- # Follistatin-344 **Evidence grade: D (Animal data only).** Area: Muscle & Performance. > A natural protein that jams the muscle-growth brake by binding myostatin, but the only real human evidence comes from gene therapy in muscular dystrophy patients, not from the injectable peptide sold online. **Also known as:** FS-344, FST-344, Follistatin 344, FS344, AAV1.CMV.FS344 (gene therapy construct), follistatin-344, fst 344, follistatin **Class:** Myostatin/activin antagonist (TGF-beta superfamily binding protein); naturally occurring glycoprotein isoform ## Why this grade The only human data come from a single tiny, uncontrolled early-phase gene-therapy trial (AAV-delivered follistatin gene injected into muscle, six Becker muscular dystrophy patients plus a small Duchenne cohort) - not from the injectable "Follistatin-344 peptide" sold on the grey market. There are no controlled human trials of injected follistatin protein in healthy people for muscle growth. The grey-market product and the validated gene-therapy approach are biologically and practically different interventions, so the injectable peptide grades D under the rubric: animal/in-vitro only, no meaningful human evidence for the thing actually being sold. ## In plain terms **Simple.** Your body has a built-in brake on muscle growth called myostatin. It stops your muscles getting too big. Follistatin is a natural protein that jams that brake so muscle can grow more. In mice, dogs and cattle this causes huge muscle gains. Almost nobody has tested injecting it into healthy people. The human research that does exist used gene therapy (changing cells so they make their own follistatin) in boys and men with muscle-wasting diseases - a different thing from the powder sold online. The dramatic 'double your muscle' claims come from preclinical models, not from any test in healthy humans. **Standard.** Follistatin-344 (FS-344) refers to one of the two natural human forms of follistatin, a protein that binds and neutralises myostatin and activin. These are signals that normally limit skeletal muscle growth. Block them and you get dramatic muscle growth in models like the 'double-muscled' Belgian Blue cattle, which carry a broken myostatin gene. That underlying biology is real and well established. Whether injecting follistatin protein is useful or safe in healthy humans remains unknown - there are essentially no controlled trials. The only genuine human work used gene therapy (a virus carrying the FS344 gene injected into thigh muscle) in a handful of Becker and Duchenne muscular dystrophy patients, where some (not all) showed improved walking distance. The peptide you can buy online is sold as an unregulated 'research chemical' and borrows credibility from that separate gene-therapy research. **Technical.** Follistatin is an autocrine glycoprotein and high-affinity antagonist of TGF-beta superfamily ligands, principally activin A and myostatin (GDF-8). Two isoforms arise by alternative splicing: the longer FS-315 (from the FS344 transcript, predominantly circulating, weak heparin-binding) and the shorter FS-288 (from the FS317 transcript, tissue/cell-surface-bound via heparan sulphate proteoglycans, higher activin affinity). By sequestering myostatin and activin, follistatin de-represses the ActRIIB-ALK4/5 to SMAD2/3 axis, removing inhibition of muscle protein accretion and satellite-cell activity and driving hypertrophy and hyperplasia in rodent, canine and non-human-primate models. The landmark human data are not from recombinant protein but from AAV1.CMV.FS344 intramuscular gene transfer. Mendell, Al-Zaidy and colleagues at Nationwide Children's Hospital ran an open-label Phase 1/2a trial in Becker MD (NCT01519349, also enrolling sporadic inclusion body myositis patients) with a parallel Duchenne cohort (NCT02354781), reporting variable gains in six-minute walk distance, reduced endomysial fibrosis and central nucleation, with acceptable short-term safety in small numbers. This validates intramuscular follistatin gene expression in dystrophic contexts, not systemic injectable FS-344 peptide for hypertrophy in healthy adults, for which controlled efficacy and safety data are absent. ## How it is thought to work Follistatin binds and sequesters myostatin (GDF-8) and activin A with high affinity, preventing them from engaging the ActRIIB receptor complex. This blocks the downstream SMAD2/3 signalling cascade that normally restrains skeletal-muscle protein synthesis and satellite-cell proliferation, effectively releasing a negative brake on muscle growth. The FS-315 isoform (from the FS344 transcript) is the soluble, circulating form with weak heparin-binding, versus the cell-surface-anchored FS-288. In preclinical models, muscle hypertrophy has been achieved largely through gene transfer or transgenic/knockout manipulation of myostatin signalling rather than through injected follistatin protein. ## Studied for Research contexts, not proven uses. - Muscular dystrophy (Becker and Duchenne) via AAV follistatin gene therapy - Myostatin/activin inhibition and muscle hypertrophy (predominantly animal models) - Muscle-wasting and regeneration contexts (preclinical) - Reduction of muscle fibrosis and improvement of fibre regeneration (gene-therapy trial endpoints) ## What the human evidence shows Genuinely thin and easily overstated. The only meaningful human evidence is a small, open-label, uncontrolled early-phase gene-therapy programme led by Mendell and colleagues at Nationwide Children's Hospital, delivering the follistatin gene (AAV1.CMV.FS344) by direct intramuscular injection into the quadriceps of six Becker muscular dystrophy patients (the trial also enrolled sporadic inclusion body myositis patients), with a parallel Duchenne cohort. Several patients showed improved six-minute walk distance and histological signs of better muscle regeneration and less fibrosis, but responses were variable and some showed no improvement. This was uncontrolled, tiny and disease-specific. There are essentially no controlled human trials of injected follistatin protein for building muscle in healthy people; the popular muscle-growth claims rest on animal data. Some follistatin gene-therapy efficacy claims, particularly in inclusion body myositis, were later publicly disputed. ## Concerns and unknowns - The injectable 'Follistatin-344 peptide' sold online is an unlicensed research chemical with no human efficacy or safety data for muscle building. It is not the validated gene-therapy product. - Marketing routinely conflates a small disease-specific gene-therapy trial with the grey-market peptide. They are biologically and practically different interventions. - Myostatin/activin inhibition is not muscle-selective. Activin and TGF-beta signalling affect reproduction, fibrosis, the ovarian/pituitary axis and tumour biology, so chronic systemic suppression carries theoretical risks that are unstudied in healthy humans. - Some published follistatin gene-therapy efficacy claims were subsequently challenged in the literature, so even the disease-specific human data should be read cautiously. - Grey-market products carry no guarantee of identity, purity, sterility, correct protein folding or biological activity. Injected proteins also carry immunogenicity and infection risks. - Often sold 'for research use only / not for human consumption' to sidestep medicines regulation. - Muscle growth in preclinical models was largely achieved by gene transfer or genetic knockout, which does not translate to a self-administered injectable protein. ## UK status Not a licensed medicine in the UK. There is no MHRA marketing authorisation for follistatin in any form. The AAV follistatin construct exists only as an investigational gene therapy in early-stage trials (conducted in the US) and is not an approved product anywhere. The injectable "Follistatin-344" peptide is an unlicensed substance typically sold as a "research chemical / not for human consumption", a label intended to keep it outside medicines law on paper. In practice, marketing or supplying it for human use would engage the Human Medicines Regulations 2012 and could attract MHRA enforcement. It is not a controlled drug under the Misuse of Drugs Act, but it cannot lawfully be marketed for human use. ## Key trials - **Follistatin Gene Transfer to Patients With Becker Muscular Dystrophy and Sporadic Inclusion Body Myositis** (NCT01519349, Phase 1/2a, Completed). rAAV1.CMV.huFollistatin344 intramuscular delivery (Mendell/Nationwide Children's); six BMD patients, some with improved six-minute walk distance. Open-label, uncontrolled. - **Intramuscular Gene Transfer of rAAV1.CMV.huFollistatin344 in Duchenne Muscular Dystrophy** (NCT02354781, Phase 1/2, Completed). Parallel follistatin gene-therapy cohort in DMD patients. ## Sources 1. A Phase 1/2a Follistatin Gene Therapy Trial for Becker Muscular Dystrophy. Mendell JR, Sahenk Z, Al-Zaidy S, et al., Molecular Therapy, 2015 2. Follistatin Gene Therapy Improves Ambulation in Becker Muscular Dystrophy. Al-Zaidy SA, Sahenk Z, Rodino-Klapac LR, Kaspar B, Mendell JR, Journal of Neuromuscular Diseases, 2015 3. Regulation of myostatin activity and muscle growth. Lee SJ, McPherron AC, PNAS, 2001 4. Clinical Intramuscular Gene Transfer of rAAV1.CMV.huFollistatin344 to Patients With Duchenne Muscular Dystrophy. ClinicalTrials.gov, 2015 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/follistatin-344 . Educational only, not medical advice. --- # GHK-Cu **Evidence grade: C (Early / limited human data).** Area: Skin & Aesthetics. > A tiny copper-carrying skin peptide with modest and mixed human evidence as a topical anti-ageing cosmetic, and almost none for the injectable 'whole-body regeneration' claims sold online. **Also known as:** Copper tripeptide-1, Glycyl-L-histidyl-L-lysine copper(II), Copper peptide, GHK copper complex, Cu-GHK, Lamin (historical trade name), ghk-cu, ghk cu, copper tripeptide, ghk **Class:** Copper-binding tripeptide (matrikine / cosmetic active); endogenous human plasma peptide ## Why this grade For topical cosmetic use on facial skin, there is some genuine human evidence, though modest, dated and not uniformly positive. Small controlled trials, most notably Leyden's 2002 facial-cream and eye-cream photoaging studies, reported improvements in skin density, thickness and fine lines. A controlled trial on CO2-laser-resurfaced skin found no significant objective benefit, only higher subjective patient satisfaction. This mixed topical record justifies a C. The headline mechanistic and 'regenerative' claims (multi-thousand-gene 'resets', systemic wound healing, neural and whole-body anti-ageing) rest entirely on in-vitro and animal work. Injectable and systemic grey-market use has no controlled human efficacy or safety data. Trials are few, small, mostly industry-associated, of modest or mixed effect, and confined to topical aesthetics. ## In plain terms **Simple.** GHK-Cu is a tiny natural molecule found in your blood. It is three protein building blocks attached to a copper atom. Your body has more when you're young, less as you age. In skincare it's used in creams to firm skin and reduce fine lines. A few small studies show modest benefit, but one on skin healing after laser treatment found no real difference. The bigger claims you'll see online are that injecting it 'resets' your genes, regrows tissue and rolls back ageing. Those claims come from experiments in cells and lab models, not from proper human trials. A believable, gentle face-cream ingredient, but the miracle-injection story isn't proven. **Standard.** GHK-Cu (copper tripeptide-1) is a three-amino-acid peptide that naturally binds copper and circulates in human plasma, declining with age. It has been studied for decades, largely by its discoverer Loren Pickart. As a topical cosmetic, it has one of the stronger peptide track records. Small controlled studies including Leyden's 2002 facial-cream and eye-cream trials reported improvements in skin firmness, thickness and fine lines, which is why 'copper peptides' became mainstream serum ingredients. A controlled study of GHK-Cu on CO2-laser-resurfaced skin found no significant objective improvement in wrinkles, redness or skin quality; patients just reported liking it more. The trials are small, several industry-linked, and effects are modest. Lab and animal work shows GHK-Cu influences many genes and stimulates collagen and blood-vessel growth. That is impressive biology, but different from proven benefit in living humans. Injected products marketed for tissue repair and 'anti-ageing' have no real human trials. In the UK it is a regulated cosmetic ingredient, not a medicine. **Technical.** GHK (glycyl-L-histidyl-L-lysine) is an endogenous matrikine first isolated from human plasma by Pickart in the early 1970s. Reported plasma levels fall with age (roughly 200 ng/mL in young adults to roughly 80 ng/mL by the sixth decade). It forms a high-affinity Cu(II) complex (GHK-Cu) acting as a copper shuttle and signalling molecule. Proposed mechanisms include modulation of TGF-beta, VEGF and bFGF; stimulation of collagen, elastin, decorin and glycosaminoglycan synthesis by dermal fibroblasts; regulation of MMPs and their inhibitors; antioxidant and anti-inflammatory actions; angiogenesis. Transcriptomic reanalysis (Pickart & Margolina) reported GHK altering expression of large gene cohorts (roughly 4,000 genes or 31% of assayed genes), shifting profiles toward repair and away from inflammation and fibrosis. This is striking but hypothesis-generating in-vitro and computational data. Human clinical evidence is confined largely to topical aesthetics and is mixed. Leyden 2002 (n approximately 71 facial cream, n approximately 41 eye cream) photoaging trials reported increased dermal density/thickness and reduced wrinkling. Miller et al. 2006 (Arch Facial Plast Surg; n=13 completers) found GHK-Cu on CO2-laser-resurfaced skin produced no statistically significant objective improvement in erythema resolution, wrinkles or skin quality versus control; only patient-reported satisfaction was higher. Effect sizes are modest, several trials are industry-associated and pre-date modern reporting standards. There are no robust RCTs for systemic or injectable administration. Regulatory status: copper tripeptide-1 is an accepted cosmetic ingredient; injectable formulations are unlicensed. ## How it is thought to work GHK is a copper-binding tripeptide that complexes Cu(II). It is thought to act as a signalling matrikine and copper carrier. Proposed actions include stimulating dermal fibroblast synthesis of collagen, elastin, glycosaminoglycans and proteoglycans (e.g. decorin), modulating matrix metalloproteinases and their inhibitors to remodel the extracellular matrix, and upregulating growth factors (TGF-beta, VEGF, bFGF) implicated in angiogenesis and tissue repair. Copper appears required for most effects; chelating it abolishes activity in vitro. Gene-expression profiling suggests broad transcriptional modulation toward repair and away from inflammation, though this is predominantly in-vitro, computational and animal data. Topically it is delivered in creams and serums (copper tripeptide-1). Grey-market products are also offered for injection, a route with no controlled human evidence. ## Studied for Research contexts, not proven uses. - Topical reduction of facial photoaging signs (fine lines, skin density and thickness) - Periorbital/eye-area skin appearance - Post-procedure skin recovery after CO2 laser resurfacing (controlled study found no significant objective benefit) - Wound healing and tissue repair (predominantly animal/in-vitro) - Hair growth (limited/early, mostly preclinical) - Antioxidant and anti-inflammatory skin effects (mechanistic) - Broad gene-expression modulation and 'regenerative/anti-ageing' biology (in-vitro/animal/computational) ## What the human evidence shows Genuine but limited, modest and mixed, and almost entirely topical. The best-known supportive data are Leyden's 2002 controlled cosmetic trials of a GHK-Cu facial cream (approximately 71 women) and eye cream (approximately 41 women) in photoaging, reporting improved skin density and thickness and reduced fine lines and wrinkling versus comparators. A controlled study of topical copper tripeptide on CO2-laser-resurfaced skin (Miller et al. 2006, 13 completers) found no statistically significant objective improvement in erythema, wrinkles or overall skin quality; only patient-reported satisfaction was higher. These trials were small, of modest effect size and several industry-associated, but they are real human data. The dramatic mechanistic claims (collagen super-stimulation, multi-thousand-gene resets, systemic wound healing, neural and whole-body anti-ageing) come overwhelmingly from laboratory and preclinical studies. There are no controlled human efficacy or safety trials for injected or systemic GHK-Cu. ## Concerns and unknowns - Topical evidence is modest, dated and partly industry-linked; effect sizes are small, results are mixed (at least one controlled trial was objectively negative), and few modern independent RCTs exist - Injectable and systemic GHK-Cu sold online has no controlled human efficacy or safety data. Claims of 'whole-body regeneration' and gene 'resetting' extrapolate from cell, animal and computational work - Grey-market injectable 'research chemical' products carry the usual risks: unverified identity and purity, sterility and endotoxin contamination, and unknown copper exposure - Excess systemic copper is toxic. Injecting a copper-loaded peptide raises a theoretical risk of copper overload not present with low-level topical cosmetics - Marketing routinely conflates impressive lab biology with proven human benefit, a key honesty gap - Sensitisation and irritation possible with some topical formulations ## UK status In the UK, copper tripeptide-1 (GHK-Cu) is widely used and accepted as a cosmetic ingredient, regulated under the GB Cosmetic Products Regulation (retained EU Regulation 1223/2009). Each finished cosmetic requires a Cosmetic Product Safety Report. It is not a licensed medicine. There is no MHRA marketing authorisation and no NHS or NICE endorsement for treating skin ageing, hair loss or any medical condition. Cosmetics may only make appearance-related claims. A product making medicinal claims, or any injectable GHK-Cu preparation, falls outside cosmetic rules and would be treated by the MHRA as an unlicensed medicine. Injectable GHK-Cu is typically sold as an unlicensed 'research chemical' labelled 'not for human consumption' and is not approved for human use. ## Sources 1. Leyden et al. clinical trials of a topical GHK-Cu facial cream and eye cream in photoaging (presented at the American Academy of Dermatology, 2002). Leyden J, et al., American Academy of Dermatology meeting / cosmetic trial reports, 2002 2. Effects of Topical Copper Tripeptide Complex on CO2 Laser-Resurfaced Skin. Miller TR, Wagner JD, Baack BR, Eisbach KJ, Archives of Facial Plastic Surgery 8(4):252-259, 2006 3. Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data. Pickart L, Margolina A, International Journal of Molecular Sciences 19(7):1987, 2018 4. Skin Regenerative and Anti-Cancer Actions of Copper Peptides. Pickart L, Vasquez-Soltero JM, Margolina A, Cosmetics (MDPI) 5(2):29, 2018 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/ghk-cu . Educational only, not medical advice. --- # GHRP-2 **Evidence grade: C (Early / limited human data).** Area: Growth Hormone. > A lab-made peptide that prompts the pituitary to release a burst of growth hormone. It is a licensed single-dose diagnostic test in Japan but is sold elsewhere as an unlicensed research chemical for bodybuilding and anti-ageing, where long-term evidence barely exists. **Also known as:** Pralmorelin, Growth Hormone Releasing Peptide-2, KP-102, GPA-748, pralmorelin hydrochloride, ghrp-2, ghrp 2, ghrp2 **Class:** Synthetic hexapeptide growth hormone secretagogue; ghrelin receptor (GHS-R1a) agonist ## Why this grade GHRP-2 reliably triggers a growth-hormone pulse in humans and is licensed in Japan for single-dose diagnostic testing of GH deficiency, so its acute pharmacology is well characterised. But that approval is for one-off diagnostic use only. There are no robust long-term RCTs supporting the chronic uses it is actually sold for: muscle gain, fat loss, anti-ageing, recovery. The evidence for real-world marketed uses is therefore early and limited, not approved-medicine grade. Graded C, not B, because no ongoing late-stage trials target these chronic-use claims. ## In plain terms **Simple.** Your body makes growth hormone in spurts from a gland in your brain. GHRP-2 copies a natural hunger-and-growth signal that taps that gland and tells it to release a burst of growth hormone. Doctors in Japan use a single dose as a test. They give the injection, then measure how much growth hormone comes out, which shows whether someone's pituitary is working. Online it is sold for muscle-building, fat loss and anti-ageing, but those uses have barely been tested in people over time. It also flips on the hunger switch, so it tends to make you eat more. In the UK it is not a medicine you can buy in a pharmacy. What's sold online is an unapproved chemical labelled 'not for human consumption'. **Standard.** GHRP-2 (pralmorelin) is a synthetic six-amino-acid peptide that behaves like ghrelin, the hunger hormone, switching on the same pituitary receptor to trigger a sharp pulse of growth hormone. It is one of the more potent classic growth-hormone-releasing peptides. Its only validated, approved use is as a diagnostic agent. Japan licensed it in 2004 as a single-injection provocation test for growth hormone deficiency because the size of the GH response separates healthy people from those with pituitary failure. Beyond that test, the picture is thin. It is marketed online for muscle gain, recovery, fat loss and anti-ageing, but there are no solid long-term human trials backing those claims. Because it works through the ghrelin receptor it also increases appetite and can raise cortisol and prolactin. In the UK it is not a licensed medicine. The versions sold online are unlicensed research chemicals. **Technical.** GHRP-2 (pralmorelin; D-Ala-D-2Nal-Ala-Trp-D-Phe-Lys-NH2) is a synthetic hexapeptide GH secretagogue and agonist at the growth hormone secretagogue receptor 1a (GHS-R1a), the endogenous receptor for ghrelin. It derives from Bowers' enkephalin-based GHRP work of the 1980s. At the somatotroph it couples via Gq/11 to phospholipase C, generating IP3/DAG and mobilising intracellular Ca2+ to drive GH granule exocytosis. It also acts at the hypothalamus to blunt somatostatinergic tone and amplify GHRH signalling, producing synergistic GH release when co-administered with a GHRH analogue. It is among the more potent classic GHRPs by peak GH amplitude. Japan approved it (PMDA; Kaken Pharmaceutical) in 2004 as a single-dose provocation test for GH deficiency in adults and children, with a GH cut-off to distinguish deficient subjects; diagnostic discrimination is good. As a GHS-R1a agonist it is orexigenic (controlled infusion studies show increased ad libitum food intake in lean healthy men) and can stimulate ACTH/cortisol and prolactin. No adequately powered long-term RCTs support the chronic anabolic, lipolytic, recovery or geroprotective uses for which it is marketed. Chronic GH-axis stimulation raises theoretical concerns around insulin resistance, fluid retention and IGF-1-mediated growth signalling. ## How it is thought to work GHRP-2 is an agonist at the ghrelin receptor (GHS-R1a) on pituitary somatotrophs and in the hypothalamus. Activation couples through Gq/11 to phospholipase C, raising intracellular calcium and triggering growth hormone release while reducing inhibitory somatostatin tone. Because it acts on the ghrelin receptor it shares ghrelin's appetite-stimulating effect and can modestly raise cortisol and prolactin. It is administered by injection. ## Studied for Research contexts, not proven uses. - Diagnostic provocation testing for growth hormone deficiency in adults and children (its licensed Japanese use) - Stimulation of endogenous growth hormone secretion - Appetite/food-intake stimulation (orexigenic effect via the ghrelin receptor) - Marketed but poorly evidenced contexts: muscle gain, fat loss, recovery, anti-ageing ## What the human evidence shows GHRP-2 reproducibly evokes a sharp GH pulse in humans, the basis of its only regulatory approval: Japan licensed pralmorelin in 2004 as a single-dose provocation test for GH deficiency. Controlled studies confirm its ghrelin-like effect. A subcutaneous infusion study in lean healthy men found it increased ad libitum food intake by roughly a third versus saline, a finding later extended to obese subjects. For the chronic uses it is actually sold for online (muscle gain, fat loss, recovery, anti-ageing), human evidence is essentially absent. ## Concerns and unknowns - Not a licensed medicine in the UK. Grey-market product is sold as an unlicensed research chemical labelled 'not for human consumption', with no guarantee of identity, purity, sterility or correct content - Stimulates appetite via the ghrelin receptor, which works against the fat-loss goals it is often marketed for - Can raise cortisol and prolactin. Chronic GH-axis stimulation carries theoretical risks of insulin resistance, fluid retention, joint pain and IGF-1-driven growth signalling - The approved human use is a single diagnostic dose only. Repeated or long-term self-administration is unstudied and unlicensed - Banned by WADA at all times in sport as a growth hormone secretagogue - No long-term human safety data for the chronic anabolic or anti-ageing use that drives most grey-market demand ## UK status Not a licensed medicine in the UK and not approved by the MHRA for any indication. Its only known marketing authorisation is in Japan (2004, PMDA), as a single-dose diagnostic agent for growth hormone deficiency. It is not licensed in the UK even for diagnostic use. Any clinical use would be unlicensed. Material sold online to UK buyers is an unlicensed research chemical, typically labelled 'not for human consumption' to sidestep medicines law. Supplying it for human use would fall foul of the Human Medicines Regulations 2012. It is also prohibited in sport by WADA at all times. ## Sources 1. Growth hormone releasing peptide-2 (GHRP-2), like ghrelin, increases food intake in healthy men. Laferrère B, Abraham C, Russell CD, Bowers CY, Journal of Clinical Endocrinology & Metabolism, 2005 2. Pralmorelin: GHRP 2, GPA 748, growth hormone-releasing peptide 2, KP-102 D, KP-102 LN, KP-102D, KP-102LN. Adis profile (Drugs in R&D), Drugs in R&D, 2004 3. Synthetic Growth Hormone-Releasing Peptides (GHRPs): A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects. Berlanga-Acosta J, et al., Clinical Medicine Insights: Cardiology, 2017 4. Obese subjects respond to the stimulatory effect of the ghrelin agonist growth hormone-releasing peptide-2 on food intake. Laferrère B, et al., Obesity (Silver Spring), 2006 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/ghrp-2 . Educational only, not medical advice. --- # GHRP-6 **Evidence grade: C (Early / limited human data).** Area: Growth Hormone. > An old experimental peptide that genuinely makes your body release a burst of its own growth hormone, but which was never turned into an approved medicine and is sold today only as an unlicensed research chemical. **Also known as:** Growth Hormone Releasing Peptide-6, GHRP6, Growth Hormone Releasing Hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2, SKF-110679, ghrp-6, ghrp 6 **Class:** Synthetic hexapeptide growth hormone secretagogue (ghrelin/GHS-R1a agonist) ## Why this grade GHRP-6 reliably and reproducibly raises growth hormone in humans. That pharmacodynamic effect is genuinely well established from research and diagnostic-style studies dating to the late 1980s. But it has never been licensed as a medicine anywhere, was abandoned by its original developers in favour of orally active successors, and the more interesting modern claims (cardioprotection, tissue protection, body-composition benefit) rest almost entirely on animal and in-vitro work. Solid human data exist for the narrow pharmacological action; human outcome data for anything people actually buy it for are thin to absent. That mix sits at the optimistic end of C, not B. ## In plain terms **Simple.** GHRP-6 is a tiny lab-made protein, just six building blocks long. It tickles the same switch in your brain that the hunger hormone normally flips, and that switch tells your pituitary gland to squirt out a pulse of your own growth hormone. It does work, and that part has been shown in people. Scientists figured this out back in the 1980s, never managed to turn it into an actual approved medicine, and moved on to other drugs. What you can buy now is unregulated 'research' powder, not a tested treatment, and most of the exciting claims about protecting your heart or building muscle come from rats, not humans. **Standard.** GHRP-6 is a synthetic six-amino-acid peptide, one of the first 'growth hormone secretagogues' ever made. Instead of being growth hormone itself, it triggers your own pituitary to release a pulse of growth hormone by acting on the ghrelin receptor, the same receptor the appetite hormone ghrelin uses, which is why it tends to make people hungry. The growth-hormone-releasing effect is real and was demonstrated in human volunteers decades ago. GHRP-6 was overtaken by orally active, more selective successors and never became a marketed drug. The headline modern claims (heart protection, healing, anti-ageing) are mostly based on animal studies. In the UK it is not a licensed medicine; it is sold grey-market as a 'research chemical' not for human use, with no quality guarantees. **Technical.** GHRP-6 (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) is the prototype peptidyl growth hormone secretagogue, derived by Bowers and Momany from met-enkephalin analogues in the early-to-mid 1980s. It is a potent agonist at the growth hormone secretagogue receptor GHS-R1a (the ghrelin receptor), a Gq/11-coupled GPCR expressed on anterior pituitary somatotrophs and hypothalamic arcuate neurons. Receptor activation drives PLC-mediated IP3/DAG signalling, intracellular Ca2+ mobilisation and GH exocytosis, acting synergistically with GHRH and partly by functional antagonism of somatostatin. GHRP-6 reproducibly elevates pulsatile GH in humans (Bowers et al., normal men, JCEM 1990), establishing proof-of-mechanism, but unlike its successors (MK-677/ibutamoren, hexarelin) it was not advanced as a therapeutic. A distinct strand of work attributes cardioprotective and broader cytoprotective effects to a separate CD36-mediated pathway, attenuating ischaemia/reperfusion and doxorubicin-induced injury. These data are overwhelmingly rodent and in-vitro. Note the GHS-R1a activation also drives orexigenic signalling and modest prolactin/ACTH/cortisol elevation, reducing its selectivity relative to ipamorelin. ## How it is thought to work Agonist at the growth hormone secretagogue receptor (GHS-R1a, the ghrelin receptor) on pituitary somatotrophs and hypothalamic neurons. Activation of this Gq-coupled receptor triggers phospholipase C signalling, intracellular calcium release and exocytosis of stored growth hormone, amplified by synergy with GHRH and reduced somatostatin tone. A separate proposed pathway involves the CD36 scavenger receptor in non-pituitary tissues, implicated in its preclinical cytoprotective effects. Because it hits the ghrelin receptor it also stimulates appetite and can transiently nudge prolactin and cortisol. ## Studied for Research contexts, not proven uses. - Stimulating endogenous growth hormone release (proof-of-mechanism and as a research/diagnostic probe of pituitary function) - Investigational diagnosis and characterisation of growth hormone deficiency - Preclinical cardioprotection against ischaemia/reperfusion and doxorubicin (anthracycline) cardiotoxicity - Preclinical cytoprotection of liver, kidney, lung and gut tissue - Appetite/ghrelin-receptor pharmacology research ## What the human evidence shows The one thing that is genuinely well established in humans is the core pharmacology: GHRP-6 reliably triggers a pulse of growth hormone release in healthy people, shown by Bowers and colleagues from the late 1980s onward, and it acts synergistically with GHRH. It has a short circulating half-life (on the order of tens of minutes). Beyond that, human evidence is thin. It was studied diagnostically and as a candidate to stimulate the GH axis, but it was never developed into a licensed product and was superseded by orally active secretagogues. The much-promoted cardioprotective and tissue-protective benefits come almost entirely from rodent and in-vitro studies (e.g. doxorubicin-cardiotoxicity models), not human outcome trials. There is no robust human evidence that it improves body composition, performance, recovery or longevity. ## Concerns and unknowns - Not a licensed medicine: sold as an unlicensed 'research chemical' labelled 'not for human consumption', with no pharmaceutical quality control on identity, purity, sterility or endotoxin content. - Grey-market products may be underdosed, contaminated, mislabelled or non-sterile; injection of unsterile material carries infection risk. - Stimulates the ghrelin receptor, so it characteristically increases appetite; it can also transiently raise prolactin and cortisol, reducing selectivity versus newer secretagogues. - Sustained, non-pulsatile GH/IGF-1 elevation in general carries theoretical risks (insulin resistance, fluid retention, joint pain, carpal-tunnel-type symptoms) and unknown long-term effects from chronic unsupervised use. - Banned in competitive sport under the WADA Prohibited List (growth hormone secretagogues, class S2). - Modern marketing extrapolates animal cardioprotection/anti-ageing data to humans without supporting human trials. This is a major overclaim. ## UK status Not a licensed medicine in the UK. The MHRA has not authorised GHRP-6 for any indication, and it is not an approved or routinely available prescription product. It is an investigational/research substance. As a synthetic peptide intended to have a physiological effect it falls within the scope of the Human Medicines Regulations 2012, so supplying or selling it for human use without authorisation is unlawful; vendors sidestep this by labelling it a 'research chemical' or reagent 'not for human consumption'. There is no quality, safety or efficacy oversight of material sold on that basis. It is also prohibited in sport under UK Anti-Doping/WADA rules. ## Sport / WADA Prohibited at all times under the WADA Prohibited List, class S2 (peptide hormones, growth factors and related substances), covering growth hormone secretagogues / ghrelin receptor agonists. ## Sources 1. On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone. Bowers CY, Momany FA, Reynolds GA, Hong A, Endocrinology, 1984 2. Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone. Bowers CY, Reynolds GA, Durham D, Barrera CM, Pezzoli SS, Thorner MO, Journal of Clinical Endocrinology & Metabolism, 1990 3. A receptor in pituitary and hypothalamus that functions in growth hormone release. Howard AD, Feighner SD, Cully DF, et al., Science, 1996 4. Growth hormone releasing peptide-6 (GHRP-6) prevents doxorubicin-induced myocardial and extra-myocardial damages by activating prosurvival mechanisms. Berlanga-Acosta J, et al., Frontiers in Pharmacology, 2024 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/ghrp-6 . Educational only, not medical advice. --- # Glutathione **Evidence grade: C (Early / limited human data).** Area: Longevity. > Glutathione is the body's main built-in antioxidant. The biology is real, but swallowing or injecting it as an anti-ageing or skin-lightening treatment rests on thin human evidence and, for IV use, real safety warnings. **Also known as:** GSH, L-glutathione, reduced glutathione, gamma-glutamylcysteinylglycine, the master antioxidant, glutathione, master antioxidant **Class:** Endogenous tripeptide antioxidant (gamma-glutamyl-cysteinyl-glycine); thiol-based redox buffer / cofactor ## Why this grade Glutathione is unquestionably real biology. It is the body's principal intracellular antioxidant, and the licensed medicine N-acetylcysteine works largely by replenishing it. But for glutathione TAKEN AS A SUPPLEMENT OR INJECTION to slow ageing, lighten skin or boost health, the human evidence is early and limited. A small number of short human RCTs show oral glutathione can raise the body's measured glutathione stores, but they are modestly sized, short, and report surrogate markers, not longevity or hard clinical outcomes. The precursor-combination (GlyNAC) work that drives much of the longevity excitement is dominated by very small, mostly open-label studies from a single research group and needs independent large-scale replication. The skin-lightening and "anti-ageing IV drip" uses have essentially no controlled efficacy evidence and a documented safety signal. Grade C reflects genuine but thin and outcome-poor human data; the popular longevity and aesthetic claims taken on their own would be D. ## In plain terms **Simple.** Your cells make a little molecule called glutathione that acts like a tiny clean-up crew, mopping up the chemical 'rust' (oxidation) that builds up as you live and age. Because it's so important, people sell it as a pill or an injection promising younger skin, more energy and a longer life. Your body already makes its own, levels naturally drift down with age, and there's surprisingly little solid proof that topping it up from outside does much for healthy people. The injectable 'skin-whitening' drips sold in some salons are a different and more worrying story. UK regulators have warned they are unlicensed and can be dangerous. **Standard.** Glutathione (GSH) is a small protein-like molecule (a tripeptide) found in nearly every cell, where it is the workhorse antioxidant and a key part of how cells handle toxins and oxidative stress. Levels tend to fall with age, illness and oxidative load, which is why it is marketed for longevity, immunity, liver health, fatigue and, especially, skin lightening. The biology is rock-solid: the standard paracetamol-overdose antidote, N-acetylcysteine, works precisely by restoring glutathione. The case for taking glutathione itself is far weaker. A small six-month trial showed oral glutathione can raise the body's glutathione stores, and a precursor combination of glycine plus N-acetylcysteine ('GlyNAC') has shown encouraging effects on ageing markers. Those GlyNAC findings come almost entirely from very small studies by one group, several without a placebo arm, and none of this proves you will live longer or look younger. Skin-lightening, the biggest commercial driver, has almost no controlled evidence, and intravenous 'glutathione drips' have triggered formal UK safety warnings. **Technical.** Glutathione is the gamma-glutamyl-cysteinyl-glycine tripeptide that constitutes the dominant non-protein thiol and principal intracellular redox buffer, cycling between reduced (GSH) and oxidised (GSSG) forms. It is the cofactor for glutathione peroxidases (neutralising H2O2 and lipid peroxides), glutathione-S-transferases (phase II xenobiotic conjugation) and the glutaredoxin system, and regenerates other antioxidants (vitamins C/E). It is synthesised de novo via the ATP-dependent enzymes glutamate-cysteine ligase (GCL; rate-limiting, cysteine-limited) and glutathione synthetase, with the gamma-glutamyl cycle governing turnover. The GSH:GSSG ratio is a canonical marker of cellular redox state, and age-associated GSH decline is a recurring observation in the geroscience literature. Clinically, GSH biology is exploited by N-acetylcysteine, the licensed antidote in paracetamol/acetaminophen hepatotoxicity, where toxicity is driven by NAPQI-mediated GSH depletion. For exogenous GSH itself, oral bioavailability of the intact tripeptide is poor owing to gut gamma-glutamyltransferase and peptidase hydrolysis, though Richie et al. (Eur J Nutr 2015; n=54, six months) reported that sustained oral dosing raised erythrocyte, plasma, lymphocyte and buccal-cell GSH. Precursor strategies (GlyNAC = glycine + N-acetylcysteine), studied chiefly by Sekhar's group at Baylor, report improvements in glutathione status, mitochondrial function, oxidative stress, insulin resistance, strength and cognition. The flagship 2021 data are from a small open-label trial (n=8), with only limited small randomised follow-up; the programme requires independent, adequately powered replication with hard clinical endpoints. The dermatological/aesthetic rationale (tyrosinase inhibition and a shift from eumelanin toward phaeomelanin) underpins IV 'skin-whitening' use, for which controlled efficacy data are essentially absent and a clear adverse-event and infection-risk profile exists. ## How it is thought to work A tripeptide thiol antioxidant. Reduced glutathione (GSH) directly scavenges reactive oxygen species and serves as the cofactor for glutathione peroxidases (detoxifying peroxides) and glutathione-S-transferases (conjugating and clearing xenobiotics/toxins), cycling to oxidised GSSG and back. It also recycles other antioxidants such as vitamins C and E. It is synthesised intracellularly from glutamate, cysteine (rate-limiting) and glycine via glutamate-cysteine ligase and glutathione synthetase. In skin, it inhibits tyrosinase and shifts melanin synthesis toward lighter phaeomelanin, which forms the basis for cosmetic 'whitening' claims. ## Studied for Research contexts, not proven uses. - Age-associated decline in cellular antioxidant capacity and redox balance (geroscience context) - Skin lightening / hyperpigmentation (the dominant commercial, largely unproven use) - Oxidative stress and mitochondrial dysfunction in older adults (mostly via GlyNAC precursor studies) - Glutathione depletion states (e.g. the underlying rationale for NAC in paracetamol overdose) - Liver health and metabolic markers (e.g. HbA1c in small diabetes studies) - Fatigue, immunity and general 'wellness' marketing claims ## What the human evidence shows Mixed and outcome-poor. The underlying biology is established and indirectly validated in the clinic. N-acetylcysteine, which replenishes glutathione, is the standard licensed antidote for paracetamol overdose. For glutathione taken as a supplement, a six-month double-blind RCT (Richie et al., Eur J Nutr 2015, n=54) showed oral GSH raised body glutathione stores, but measured surrogate markers, not longevity or disease outcomes. The glutathione-precursor combination GlyNAC (glycine + N-acetylcysteine, Sekhar's group) has reported improvements in several ageing-related markers plus physical and cognitive measures in older adults. The headline 2021 study was open-label in just eight participants, with only small randomised follow-up since, so these findings need large, independent confirmatory trials. Skin-lightening, the biggest real-world use, has essentially no robust controlled trials, and intravenous use for cosmetic skin whitening has no published RCTs supporting it. No high-quality human evidence shows glutathione supplementation extends lifespan or healthspan. ## Concerns and unknowns - Intravenous 'skin-whitening' glutathione drips are a major UK safety concern: in 2025 the Chartered Trading Standards Institute issued a public warning (alongside a Channel 4 News investigation), and the MHRA regards such products as unlicensed with no legitimate cosmetic 'special need'. Reported risks include kidney strain, liver and nervous-system toxicity, severe skin reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis), anaphylaxis requiring hospitalisation, and infection transmission (HIV, hepatitis B/C) from non-medical administration. - Over 300 UK salons have been found offering IV glutathione without medical supervision. This is an unregulated, high-risk grey market. - Oral glutathione has poor intact bioavailability (largely broken down in the gut), so much marketing overstates what a pill actually delivers. - Efficacy for the headline claims (anti-ageing, skin lightening, energy) is largely unproven; surrogate-marker changes are not clinical benefits. - Cosmetic-grade or 'research chemical' injectable products carry no guarantee of purity, sterility or correct labelling. - GlyNAC longevity findings come from very small studies (the flagship trial was open-label, n=8) by a single research group and await independent large-scale replication. ## UK status Glutathione itself is a naturally occurring endogenous molecule and is sold legally in the UK as an oral food supplement, regulated as a food rather than a medicine, so no anti-ageing or disease claims are permitted. Its precursor N-acetylcysteine is a licensed MHRA medicine (e.g. as the IV/oral antidote in paracetamol overdose and as a mucolytic). INJECTABLE glutathione for cosmetic 'skin whitening' is treated as an unlicensed medicine. Such products hold no UK Marketing Authorisation, and in 2025 the Chartered Trading Standards Institute issued a public warning about dangerous IV glutathione skin-lightening drips offered in beauty salons. Importing and supplying these unlicensed injectables for cosmetic use breaches the Human Medicines Regulations 2012. There is no licensed glutathione product for anti-ageing or skin-lightening in the UK. ## Key trials - **Randomized controlled trial of oral glutathione supplementation on body stores of glutathione (Richie et al.)** (Investigator-initiated RCT, Completed (2015)). Six months, n=54 non-smoking adults; measured glutathione in blood compartments and buccal cells (surrogate markers, no clinical endpoints). - **GlyNAC (glycine + N-acetylcysteine) supplementation in older adults (Sekhar group, Baylor)** (Open-label pilot / small RCT, Completed small studies; larger powered trials advocated). Flagship 2021 study was open-label (n=8); reported improvements in glutathione status, oxidative stress, mitochondrial function, strength and cognition. Awaits independent, adequately powered replication with clinical endpoints. ## Sources 1. Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Richie JP Jr, Nichenametla S, Neidig W, et al., European Journal of Nutrition, 2015 2. Glycine and N-acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: results of a pilot clinical trial. Kumar P, Liu C, Suliburk J, et al. (Sekhar RV group), Clinical and Translational Medicine, 2021 3. Public warning issued about dangerous glutathione skin whitening IV drips. Chartered Trading Standards Institute (CTSI), CTSI / Trading Standards UK press release, 2025 4. Exploring the Safety and Efficacy of Glutathione Supplementation for Skin Lightening: A Narrative Review. Cureus, 2025 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/glutathione . Educational only, not medical advice. --- # Gonadorelin **Evidence grade: A (Approved / strong human evidence).** Area: Libido & Hormonal. > Gonadorelin is a lab-made copy of the brain's own fertility hormone (GnRH) that tells the pituitary gland to release the hormones driving the testes and ovaries. It only works properly when delivered in tiny, regular pulses, the way the body does it naturally. **Also known as:** GnRH, Gonadotropin-releasing hormone, LHRH, Luteinising hormone-releasing hormone, Factrel, Lutrelef, Lutrepulse, gonadorelin **Class:** Synthetic gonadotropin-releasing hormone (GnRH) decapeptide ## Why this grade Gonadorelin is the synthetic copy of the body's own GnRH and is a long-established, approved medicine with decades of human data in its licensed uses: as a diagnostic test of pituitary function, and, when given in pulses via a pump, as a treatment for hypogonadotropic hypogonadism and the associated infertility/anovulation. Grade A reflects that licensed, properly studied use of the molecule itself. The grade does NOT endorse the grey-market self-injected "TRT add-on / libido booster" use, for which there are essentially no dedicated controlled trials; judged on its own, that use would be a D at best. ## In plain terms **Simple.** Deep in your brain there is a hormone called GnRH that works like a metronome. Every so often it gives the pituitary gland a tap, and that tap tells the body to make sex hormones like testosterone and to support fertility. Gonadorelin is an exact man-made copy of that hormone. Doctors use it in two ways. As a quick test, they give a single dose and measure how the pituitary responds, which tells them whether a problem is in the brain or in the gland. As a treatment for certain people whose brains don't make enough GnRH, it is dripped in through a small pump in regular little pulses to switch fertility back on. The rhythm matters. Given in steady little taps it turns the system on. Given constantly, the body tunes out the signal and switches off instead. That is why it can't be injected casually and treated like a magic testosterone or libido booster. **Standard.** Gonadorelin is identical to natural gonadotropin-releasing hormone (GnRH), the hypothalamic hormone that controls the whole reproductive axis. The hypothalamus normally releases GnRH in pulses; this drives the pituitary to release luteinising hormone (LH) and follicle-stimulating hormone (FSH), which in turn stimulate the testes (testosterone, sperm) or ovaries (oestrogen, ovulation). Medically it has two well-established roles. A single injection serves as a diagnostic test: clinicians measure the LH/FSH rise to see whether a hormone or fertility problem sits in the pituitary or higher up. Delivered in regular pulses by a small infusion pump, it can restore fertility in people with hypogonadotropic hypogonadism (a brain-level deficiency) and trigger ovulation in hypothalamic amenorrhoea, where the human evidence is genuinely good. The crucial pharmacological point is that pulsatile delivery stimulates the axis, whereas continuous exposure desensitises and suppresses it. That is the same principle exploited by long-acting GnRH analogues like leuprorelin to shut hormones down. Because its half-life is only minutes, it does not behave like a stable injectable hormone. The fashionable grey-market use of self-injecting gonadorelin as an hCG substitute on testosterone therapy to keep the testes active is plausible on paper but is NOT how the drug was studied, and has no dedicated trial support. **Technical.** Gonadorelin is synthetic GnRH/LHRH, the native hypothalamic decapeptide (pyroGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2). It binds the GnRHR, a Gq/11-coupled GPCR on pituitary gonadotropes, triggering PLC/IP3/DAG signalling, calcium flux and secretion of LH and FSH. The defining feature is frequency-dependent receptor regulation: physiological pulsatile stimulation maintains gonadotrope responsiveness and gonadotropin output, whereas continuous or high-dose exposure causes receptor downregulation and desensitisation. This is the mechanism exploited therapeutically by superagonist depot analogues (leuprorelin, triptorelin, goserelin) to achieve medical castration. Plasma half-life is very short (minutes), reflecting rapid peptidase cleavage. Approved/established uses: (1) the diagnostic GnRH stimulation test of pituitary gonadotroph reserve (e.g. Factrel; UK emc-listed 'Gonadorelin 100 micrograms powder for solution for injection'); (2) pulsatile administration via portable infusion pump (Lutrelef/Lutrepulse, Ferring) for induction of ovulation in hypothalamic amenorrhoea and for hypogonadotropic hypogonadism/infertility, with efficacy broadly comparable to exogenous gonadotropin therapy and lower multiple-pregnancy and OHSS risk in suitable patients. A functioning pituitary is a prerequisite; it is ineffective in primary pituitary failure. The grey-market application is intermittent subcutaneous self-injection as an LH-mimetic/hCG analogue to preserve testicular steroidogenesis during exogenous androgen therapy. This conflates GnRH (a pituitary secretagogue) with hCG (a direct LH-receptor agonist on Leydig cells), is pharmacokinetically questionable given the minutes-long half-life, and has no dedicated controlled-trial evidence for this indication or for 'libido' as a standalone endpoint. ## How it is thought to work Gonadorelin is identical to natural GnRH. It binds the GnRH receptor on pituitary gonadotrope cells (a Gq-coupled GPCR), driving release of LH and FSH, which then stimulate the gonads to produce testosterone/oestrogen and support gametogenesis. Critically, the effect is frequency-dependent: pulsatile delivery stimulates the axis, while continuous exposure desensitises and suppresses it. It requires a functioning pituitary to work and has a half-life of only a few minutes. ## Studied for Research contexts, not proven uses. - Diagnostic testing of anterior pituitary gonadotroph function (LH/FSH response) - Induction of ovulation in hypothalamic amenorrhoea (pulsatile, pump-delivered) - Hypogonadotropic hypogonadism and associated infertility in men and women (pulsatile) - Grey-market use as an hCG-style adjunct on testosterone replacement therapy to preserve testicular function (not trial-supported) - Libido/hormonal optimisation claims in the wellness market (no dedicated human evidence) ## What the human evidence shows Strong for its licensed roles. As a diagnostic GnRH stimulation test it has decades of clinical use. As pulsatile pump therapy for hypogonadotropic hypogonadism and hypothalamic anovulation it has good controlled human evidence, with ovulation and fertility outcomes broadly comparable to injectable gonadotropins and lower rates of ovarian hyperstimulation and multiple pregnancy in appropriate patients. The use of self-injected gonadorelin as an hCG alternative on TRT, or as a standalone libido enhancer, has essentially no dedicated controlled trial evidence. It is an off-label extrapolation from mechanism, complicated by the very short half-life and the real risk that the wrong delivery rhythm suppresses rather than stimulates the axis. ## Concerns and unknowns - Frequency-dependent paradox: get the rhythm wrong (too frequent or continuous) and it downregulates the receptor and SUPPRESSES the hormone axis. This is the same mechanism used to chemically castrate prostate cancer patients. - Very short half-life (minutes) makes naive intermittent self-injection pharmacologically dubious as steady hormone support. - Ineffective if the pituitary itself is damaged. It is a pituitary secretagogue, not a direct gonadal stimulator like hCG. - Conflated in the wellness market with hCG; the two act at different points in the axis and are not interchangeable. - Anaphylaxis and hypersensitivity reactions have been reported with GnRH/gonadorelin administration. - Grey-market 'research chemical' vials sold for self-injection carry the usual unlicensed-product risks: no quality control, uncertain purity/sterility, no clinical or pharmacist oversight. - No dedicated human trials exist for the libido or TRT-adjunct uses it is most often marketed for. ## UK status Gonadorelin is a licensed prescription-only medicine (POM) in the UK. There is an MHRA-authorised product listed on the electronic medicines compendium ('Gonadorelin 100 micrograms powder for solution for injection') used for the diagnostic GnRH stimulation test of pituitary gonadotroph function. Pulsatile pump formulations (e.g. Lutrelef/Lutrepulse, Ferring) have been used for hypogonadotropic infertility, although the availability of specific brands has varied over time and some have been discontinued for commercial reasons. As a regulated medicine it is intended to be prescribed and supervised by a clinician. Separately, gonadorelin is widely sold online by 'research chemical' suppliers labelled 'not for human consumption'; supplying or self-administering such unlicensed product outside the regulated medicines framework sits outside MHRA authorisation and carries the legal and safety risks of any unlicensed injectable. ## Sport / WADA Gonadorelin itself is not listed by name as a prohibited substance for general athletes. However, agents that act on the hypothalamic-pituitary-gonadal axis to alter endogenous hormone levels attract anti-doping scrutiny, and in male athletes manipulation of gonadotropins/testosterone is the kind of intervention monitored under the WADA framework. Any hormone-axis drug should be treated as potentially relevant and checked against the current WADA Prohibited List. ## Key trials - **Pulsatile subcutaneous GnRH (gonadorelin) via pump for ovulation induction in women with hypogonadotropic hypogonadism / primary amenorrhoea (Ferring programme)** (NCT01976728, Phase 3). Randomised, placebo-controlled study of pulsatile gonadorelin (FE 999037/FE 999903) delivered by wearable pump for ovulation induction. ## Sources 1. FACTREL (gonadorelin hydrochloride) for injection — US prescribing information / FDA label. DailyMed / FDA (NDA 017866) 2. Gonadorelin 100 micrograms powder for solution for injection — Summary of Product Characteristics (SmPC). electronic medicines compendium (emc), UK 3. Belchetz PE et al. Hypophysial responses to continuous and intermittent delivery of hypothalamic gonadotropin-releasing hormone. Science, 1978 4. Pulsatile gonadotrophin-releasing hormone for ovulation induction in subfertility (Cochrane systematic reviews). Cochrane Database of Systematic Reviews _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/gonadorelin . Educational only, not medical advice. --- # HGH Fragment 176-191 **Evidence grade: D (Animal data only).** Area: Weight & Metabolic. > The tail-end snippet of growth hormone that's marketed as a "fat-burning" peptide, based mostly on mouse studies - the human version of this idea (AOD-9604) was tested properly and didn't work. **Also known as:** hgh frag 176-191, growth hormone fragment 176-191, gh frag 176-191, frag 176-191, lipolytic fragment, fat-burning hgh fragment **Class:** Synthetic C-terminal fragment of human growth hormone (amino acids 176-191) ## Why this grade The fragment itself has essentially no completed human trials. The only relevant human data comes from a closely related modified analogue (AOD-9604), which was safe but failed to beat placebo for weight loss in its pivotal trial. ## In plain terms **Simple.** Growth hormone is a long chain of building blocks. Scientists noticed that just the last little piece of that chain - the bit numbered 176 to 191 - seemed to do most of the fat-burning in animals, without the muscle-and-bone-growing effects of the whole hormone. So people sell that little piece on its own and call it a fat-loss peptide. The catch: almost all the encouraging results are from mice and lab dishes. When a slightly tweaked, more stable version of the exact same idea was given to real people in proper trials, it didn't actually melt fat any better than a dummy injection. So the hype runs way ahead of the human proof. **Standard.** HGH Fragment 176-191 is a synthetic copy of the last 16 amino acids of human growth hormone. In the 1990s, Australian researchers found this C-terminal region appeared to carry most of growth hormone's fat-mobilising activity in rodents, while leaving out the parts that raise IGF-1 and disturb blood sugar. The pitch is therefore "fat loss without the side effects of real HGH." In practice, the raw fragment is chemically unstable, so the cleaner research story belongs to its tyrosine-modified cousin AOD-9604. AOD-9604 went through roughly six human trials and about 900 participants in the early 2000s: it was consistently safe, an early study hinted at modest weight loss, but the larger pivotal Phase IIb trial failed to beat placebo, and the programme was scrapped in 2007. The bare 176-191 fragment sold today has never had that level of human testing at all - its reputation is borrowed almost entirely from animal work and from a related compound that ultimately flopped. **Technical.** HGH Fragment 176-191 corresponds to the C-terminal residues 176-191 of the 191-amino-acid hGH molecule, the region implicated in the hormone's lipolytic and anti-lipogenic actions independent of its somatogenic, IGF-1-mediated and diabetogenic effects. Mechanistic work (Heffernan et al., Endocrinology 2001) using diet-induced obese mice and beta3-adrenoceptor knockouts showed that chronic hGH/AOD9604 treatment failed to produce its usual reductions in body weight and increases in lipolysis in beta3-AR-null animals, and that treatment restored suppressed beta3-AR mRNA. Notably, however, AOD9604 still increased energy expenditure and fat oxidation acutely in the knockouts, leading the authors to conclude the lipolytic actions are not mediated directly via the beta3-AR - rather, the compounds raise beta3-AR expression, which may secondarily enhance lipolytic sensitivity. The clinically developed entity was AOD-9604 (Tyr-hGH177-191), an N-terminally tyrosine-extended, more stable analogue from Metabolic Pharmaceuticals. Its clinical dossier (~6 trials, ~900 subjects) demonstrated favourable tolerability but the 24-week Phase IIb study (~500+ subjects) failed its primary weight-loss endpoint versus placebo, terminating development in 2007. Crucially, the unmodified 176-191 peptide marketed in grey channels lacks this clinical evidence base; its human efficacy claims rest on extrapolation from rodent data and from a structurally related analogue that did not meet endpoints. ## How it is thought to work Proposed to reproduce the lipolytic (fat-mobilising) action that resides in growth hormone's C-terminal tail while omitting the regions responsible for raising IGF-1 and impairing insulin sensitivity. Animal studies link its effects to the breakdown of stored triglycerides into free fatty acids and glycerol via hormone-sensitive lipase, alongside inhibition of new fat formation (lipogenesis). In beta3-adrenoceptor knockout mice the chronic fat-loss effect largely disappears and the compound restores suppressed beta3-AR expression; but acute energy-expenditure effects persist in those knockouts, so the original researchers concluded the lipolysis is not directly mediated by the beta3-adrenoceptor and the full mechanism remains unsettled. Typically administered by subcutaneous injection. ## Studied for Research contexts, not proven uses. - Fat loss / weight reduction (chiefly in animals) - Lipolysis without growth-hormone-like metabolic side effects - Cartilage/joint repair (for the analogue AOD-9604, early research) ## What the human evidence shows The bare 176-191 fragment has no meaningful completed human efficacy trials - its reputation is built on rodent and in-vitro work. The nearest human evidence is for its modified analogue AOD-9604: roughly six trials and around 900 participants in the early 2000s established a clean safety profile, and an earlier study suggested a small weight-loss signal (about 2.6 kg vs 0.8 kg on placebo). But the pivotal 24-week Phase IIb trial (over 500 subjects) failed to show statistically significant weight loss over placebo, and clinical development was abandoned in 2007. So even the best-studied form of this idea did not work in a proper trial, and the marketed fragment is one step removed from that. ## Concerns and unknowns - Sold as a "research chemical" with no UK marketing authorisation; purity, dose accuracy and sterility of grey-market vials are unverified. - Human efficacy is essentially unproven for the fragment itself, and the closely related analogue AOD-9604 failed its pivotal weight-loss trial. - The raw 176-191 peptide is chemically unstable, so what's in a vial may not match the label. - Marketing claims (e.g. "more potent than HGH for fat burning", large fat-loss figures) trace back to animal data and are not supported by human outcomes. - Long-term human safety data are absent; the FDA placed the related analogue AOD-9604 in Category 2 of its interim compounding bulks list, citing limited safety data, peptide impurities and immunogenicity concerns. - Injectable use carries the usual infection, contamination and unverified-product risks of self-injecting an unregulated substance. ## UK status Not a licensed medicine in the UK - the MHRA has not authorised HGH Fragment 176-191 (or AOD-9604) for any indication. It has no marketing authorisation, so it cannot legally be sold or supplied for human consumption; vials are typically traded online labelled "for research use only / not for human use" to sidestep the Human Medicines Regulations 2012. Buying it does not make it tested, safe or legal to inject. There is no NHS or NICE route to it. ## Sport / WADA Prohibited in sport at all times. WADA lists growth hormone fragments - naming both hGH fragment 176-191 and AOD-9604 - under section S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics). They are banned regardless of whether they actually enhance performance. ## Key trials - **AOD-9604 Phase IIb obesity trial (24 weeks)** (Phase IIb, Completed - failed primary endpoint). ~500+ subjects; no statistically significant weight loss vs placebo. Development of the analogue terminated in 2007. The bare 176-191 fragment itself has no comparable trial. ## Sources 1. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice. Heffernan M, Summers RJ, Thorburn A, Ogru E, Gianello R, Jiang WJ, Ng FM, Endocrinology 142(12):5182-5189, 2001 2. AOD9604 in obese humans - clinical (Phase II) literature on the GH fragment analogue (search). Metabolic Pharmaceuticals / various, PubMed search, 2007 3. WADA Prohibited List - S2 Peptide Hormones, Growth Factors, Related Substances and Mimetics (growth hormone fragments incl. AOD-9604 and hGH 176-191). World Anti-Doping Agency, 2024 4. FDA Pharmacy Compounding Advisory Committee briefing - AOD-9604 placed in Category 2 of the interim 503A bulks list. U.S. Food and Drug Administration (PCAC), 2024 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/hgh-fragment-176-191 . Educational only, not medical advice. --- # Hexarelin **Evidence grade: C (Early / limited human data).** Area: Muscle & Performance. > An old experimental peptide that triggers a growth hormone burst, but the body quickly adapts and it was never approved as a medicine. **Also known as:** Examorelin, EP-23905, Hexarelin acetate, hexarelin, hexa **Class:** Synthetic hexapeptide growth hormone secretagogue (GHRP-6 analogue); GHS-R1a and CD36 agonist ## Why this grade Real human pharmacology data exist: multiple short-term studies confirm hexarelin triggers a dose-dependent growth-hormone spike in healthy volunteers, the elderly, and GH-deficient adults and children. Development reached Phase 2 but was never licensed anywhere. The GH effect desensitises with repeated dosing, and there are no long-term outcome trials showing it builds muscle, improves cardiac endpoints, or delivers any clinically meaningful benefit. Early, short and incomplete: a C, not a B. ## In plain terms **Simple.** Hexarelin is a lab-made peptide that tells the pituitary gland to release growth hormone, the body's natural building-and-repair signal. In the 1990s scientists hoped it could help children with severe short stature or adults who don't make enough of their own. After a few weeks of regular use the body stops responding as strongly, so the effect fades. It was tested in people but never became an approved medicine. Today it's sold online as an unlicensed 'research chemical', not as something proven safe or effective for building muscle. **Standard.** Hexarelin is a synthetic six-amino-acid peptide, closely related to GHRP-6, that acts as a growth hormone secretagogue by binding the ghrelin receptor (GHS-R1a) in the pituitary and triggering a strong pulse of growth hormone (GH). A single dose in humans reliably produces a marked GH spike, well documented in studies from the 1990s. With repeated dosing the GH response blunts through desensitisation, though it recovers after a break. This undermines its use as a sustained tool for muscle-building or recovery. Hexarelin also binds CD36, a receptor in heart tissue, which drove interest in possible cardioprotection. Some of those effects appear independent of growth hormone. Despite reaching Phase 2 trials for GH-deficiency diagnosis and cardiac indications, it was never licensed anywhere and development stalled. There are no robust trials showing it increases lean mass or athletic performance in healthy people. It appears on the muscle-performance shelf because of how it is marketed, not because the evidence supports that use. **Technical.** Hexarelin (His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2) is a synthetic hexapeptide GH secretagogue of the GHRP family, differing from GHRP-6 by a 2-methyl-Trp substitution that confers metabolic stability. It is a potent agonist of the GH secretagogue receptor GHS-R1a (the ghrelin receptor), stimulating GH release via a mechanism synergistic with GHRH and partly opposed by somatostatin. Human dose-response and route-of-administration studies in the 1990s (Ghigo, Arvat and colleagues) established robust, dose-dependent GH release after intravenous and other routes. It also acutely raises ACTH, cortisol and prolactin, so it is not a selective GH stimulus. Tachyphylaxis is documented: partial attenuation of the GH response develops with repeated administration but is reversible after a washout (Rahim & Shalet, Growth Horm IGF Res 1998). Hexarelin binds CD36, a class B scavenger receptor on cardiomyocytes and vascular tissue. Bodart et al. (Circ Res 2002) demonstrated CD36-mediated cardiovascular actions independent of GHS-R1a/GH, accounting for GH-independent cardioprotective effects observed largely in rodent ischaemia-reperfusion and post-MI models. Clinical development reached Phase 2 (GH-deficiency diagnostic provocation; cardiac indications) but never achieved marketing authorisation anywhere. No controlled trials demonstrate ergogenic, body-composition or hard clinical-outcome benefit in healthy adults. The human evidence base is short-term pharmacodynamic and mechanistic. ## How it is thought to work Hexarelin is an agonist at the growth hormone secretagogue receptor (GHS-R1a, the ghrelin receptor) in the anterior pituitary and hypothalamus, evoking pulsatile release of endogenous growth hormone. Acutely, it also raises ACTH, cortisol and prolactin. It binds CD36, a scavenger receptor in cardiac and vascular tissue, producing cardiovascular effects that appear independent of GH release. Repeated administration causes partial, reversible desensitisation of the GH response. ## Studied for Research contexts, not proven uses. - Provocative testing/diagnosis of growth hormone deficiency - Growth hormone deficiency in adults and children - Cardioprotection in ischaemic heart disease and heart failure (mechanistic/early, mostly preclinical) - Age-related decline in GH/IGF-1 secretion - Anabolic/body-composition effects (largely unproven in humans) ## What the human evidence shows Real but early and incomplete. Single-dose human studies from the 1990s clearly show hexarelin produces a strong, dose-dependent growth-hormone spike in healthy volunteers, the elderly, and GH-deficient adults and children, and it was studied as a diagnostic provocation agent. The GH effect desensitises (tachyphylaxis) with repeated dosing and recovers after a washout, a significant limitation for any sustained use. A small number of cardiac studies explored CD36-mediated, GH-independent cardioprotection, though the cardiac case rests mostly on animal data. Development reached Phase 2 but the compound was never licensed anywhere. There are no robust controlled trials demonstrating that hexarelin increases muscle mass, strength or athletic performance in healthy people. ## Concerns and unknowns - Never approved as a medicine in any country; development stalled at Phase 2 - GH response desensitises with repeated use, undermining any sustained benefit - Acutely raises ACTH, cortisol and prolactin. Not a selective GH stimulus - No long-term human safety data. Unknown effects of chronic GH/IGF-1 elevation and theoretical risks of abnormal tissue growth - Sold as an unregulated 'research chemical' with no guarantee of identity, purity, sterility or dose - Marketed for muscle-building despite no human evidence supporting that use - Prohibited in sport at all times by WADA as a growth hormone secretagogue ## UK status Not a licensed medicine in the UK. Hexarelin holds no MHRA marketing authorisation and is not an approved or prescribed drug. It is an investigational compound whose development was abandoned. It is sold online as an unlicensed 'research chemical' labelled 'not for human consumption'. Selling or supplying it for human medicinal use, or marketing it with health or muscle-building claims, engages the Human Medicines Regulations 2012, and the MHRA enforces action against such sales. It is not a controlled drug under the Misuse of Drugs Act 1971. ## Sport / WADA Prohibited at all times under WADA Section S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics). Hexarelin (examorelin) is explicitly named as a GH-releasing peptide/growth hormone secretagogue. ## Sources 1. Growth hormone-releasing activity of hexarelin in humans: a dose-response study. Ghigo E, Arvat E, et al., European Journal of Clinical Pharmacology, 1994 2. CD36 mediates the cardiovascular action of growth hormone-releasing peptides in the heart. Bodart V, Febbraio M, et al., Circulation Research, 2002 3. Does desensitization to hexarelin occur?. Rahim A, Shalet SM, Growth Hormone & IGF Research, 1998 4. Hexarelin growth hormone secretagogue / GHRP literature (PubMed search). PubMed, 1998 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/hexarelin . Educational only, not medical advice. --- # Humanin **Evidence grade: D (Animal data only).** Area: Longevity. > A tiny protective peptide your own mitochondria make, which looks fascinating in lab animals and correlates with healthy ageing in people, but has never been properly tested as a drug in humans. **Also known as:** HN, HNG (S14G-Humanin, a more potent analogue), Mitochondrial-derived peptide (MDP), MTRNR2, humanin, humanin peptide **Class:** Mitochondrial-derived peptide (MDP); endogenous 24-amino-acid cytoprotective peptide ## Why this grade Humanin is a real, well-characterised endogenous peptide with a large preclinical literature (cell and rodent studies) and intriguing human OBSERVATIONAL data: higher circulating levels track with longevity and better cognitive ageing. But there are no completed interventional human trials of administered humanin (or its analogues) demonstrating clinical benefit, and its human pharmacology is essentially uncharacterised. As a therapeutic given to people, the human efficacy evidence is negligible, which puts it firmly at D rather than C. The observational human correlations are interesting biology, not proof that injecting it helps. ## In plain terms **Simple.** Inside every cell are little power plants called mitochondria. Scientists found that they also make a tiny protein called humanin that seems to protect cells from dying when they're under stress. In lab dishes and in mice it can shield brain cells, calm down damage and even help mice live a bit longer and stay sharper. People who naturally have more of it in their blood tend to live longer and age better. That sounds exciting, but here's the honest catch: nobody has ever run a proper trial of giving humanin to humans to see whether it actually makes them healthier. So right now it's a promising lab story, not a proven treatment. **Standard.** Humanin is a 24-amino-acid peptide encoded within the mitochondrial genome, one of the first 'mitochondrial-derived peptides' (MDPs) discovered. It was identified around 2001 in brain tissue from an Alzheimer's patient as a factor that protected neurons from dying. In cells and animals it's broadly cytoprotective: it guards against oxidative stress, programmed cell death (apoptosis), low oxygen and metabolic injury, and it interacts with insulin/IGF signalling. In mice, the more potent analogue S14G-humanin (HNG) can improve cognition in old age, and circulating humanin levels track with lifespan across species. In humans, observational studies link higher natural humanin levels to longevity and better cognitive ageing. What's missing is the bit that matters most: no completed randomised human trials show that giving humanin as a drug does anything beneficial. So the human evidence is correlational, not interventional. It is not a licensed medicine anywhere; grey-market 'humanin' or analogues are sold only as unlicensed research chemicals. **Technical.** Humanin (HN) is a 24-residue peptide translated from a short open reading frame (MTRNR2) within the mitochondrial 16S rRNA gene, with nuclear-encoded paralogues (MTRNR2L1-13). It was discovered by Hashimoto et al. (PNAS 2001) via functional screening of an Alzheimer's-disease occipital cortex cDNA library, identified as a factor abolishing neuronal death induced by FAD mutants (APP, PS1/PS2) and Abeta. Mechanistically it is pleiotropic: it binds and sequesters the pro-apoptotic BH3 protein BAX to inhibit mitochondrial apoptosis; it signals extracellularly through a trimeric receptor complex (CNTFR/WSX-1/gp130) activating STAT3, and through the formyl peptide receptor FPRL1/FPR2; and it modulates insulin/IGF axis biology, including binding IGFBP3. The MDP family it founded includes MOTS-c and the small humanin-like peptides (SHLPs). Preclinical data span neuroprotection (S14G-HN, 'HNG', is markedly more potent), cardioprotection (ischaemia-reperfusion models), improved insulin sensitivity, and lifespan/healthspan effects in invertebrate and rodent models, with circulating HN declining with age and correlating with longevity across taxa. Human data are observational: cross-sectional and cohort associations between higher plasma humanin and longevity, offspring of centenarians, and cognitive-age phenotypes (Yen et al., Sci Rep 2018; Aging 2020). Critically, there are no completed registered interventional RCTs of exogenous humanin or analogues demonstrating clinical endpoints; human pharmacology (PK, route, immunogenicity, dosing) is essentially uncharacterised. The evidence base is therefore preclinical-plus-observational. ## How it is thought to work Humanin is an endogenous peptide produced from a small gene inside the mitochondrial genome. It acts as a broad cytoprotective signal. Intracellularly it blocks apoptosis by binding the pro-death protein BAX, preventing mitochondrial-mediated cell death. Extracellularly it acts as a secreted signalling peptide via a trimeric receptor complex (CNTFR/WSX-1/gp130, driving STAT3 signalling) and via the formyl peptide receptor FPR2/FPRL1, and it modulates insulin/IGF-1 signalling (including interaction with IGFBP3). Net effect in models: protection against oxidative stress, apoptosis, hypoxia and metabolic injury. ## Studied for Research contexts, not proven uses. - Neuroprotection in Alzheimer's disease / amyloid-beta toxicity models - Cognitive ageing and lifespan/healthspan (invertebrate and rodent models; human observational correlations) - Cardioprotection (ischaemia-reperfusion injury models) - Insulin sensitivity and metabolic stress resistance - Cellular protection against oxidative stress and apoptosis ## What the human evidence shows Human evidence is observational, not interventional. Cohort and cross-sectional studies report that higher levels of naturally circulating humanin are associated with longevity, with offspring of long-lived/centenarian families, and with better cognitive-age phenotypes, and that endogenous humanin tends to fall with age. These are correlations in people, not tests of humanin as a treatment. Crucially, there are no completed published randomised controlled trials of administered humanin (or analogues such as S14G-humanin) showing clinical benefit, and its pharmacokinetics, optimal route, immunogenicity and safety in humans are essentially uncharacterised. Almost all efficacy data come from cell culture and rodent (and some invertebrate) models. ## Concerns and unknowns - No completed human interventional trials: efficacy as an administered drug in people is unproven. - Human pharmacology unknown: PK, bioavailability, route, half-life, immunogenicity and long-term safety of exogenous humanin/analogues have not been established. - Not a licensed medicine anywhere; products sold online are unlicensed 'research chemicals' labelled not for human consumption, with no quality, purity or sterility guarantees. - Pleiotropic signalling (STAT3, IGF/insulin axis, anti-apoptosis) cuts both ways: anti-apoptotic and growth-modulating effects raise theoretical concerns (e.g. around cancer cell survival) that are unresolved in humans. - Marketing hype: observational longevity correlations are routinely overstated as proof that injecting humanin extends human lifespan, which the data do not support. ## UK status Not a licensed medicine in the UK: the MHRA has not authorised humanin or any humanin analogue for any indication, and there is no UK marketing authorisation. It is not an approved drug and is not available on prescription. Any humanin sold to UK consumers is an unlicensed substance, typically marketed as a 'research chemical' or 'not for human consumption' to sidestep the Human Medicines Regulations 2012; selling or supplying it for human medicinal use without authorisation would breach those regulations. The quality and identity of such grey-market material are unverified. ## Sources 1. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta. Hashimoto Y, Niikura T, Tajima H, et al., PNAS, 2001 2. The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan. Yen K, Mehta HH, Kim SJ, et al., Aging (Albany NY), 2020 3. Humanin Prevents Age-Related Cognitive Decline in Mice and is Associated with Improved Cognitive Age in Humans. Yen K, Wan J, Mehta HH, et al., Scientific Reports, 2018 4. Humanin and Its Pathophysiological Roles in Aging: A Systematic Review. Coradduzza D, Congiargiu A, Chen Z, et al., Biology (MDPI), 2023 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/humanin . Educational only, not medical advice. --- # IGF-1 LR3 **Evidence grade: D (Animal data only).** Area: Muscle & Performance. > A lab-engineered, longer-lasting version of the body's growth factor IGF-1, sold as a "research chemical" for muscle building, though it has never been tested in humans for that purpose. **Also known as:** Long R3 IGF-1, Long Arg3-IGF-1, LR3-IGF-1, IGF-1 Long R3, LONG R3 IGF-I, lr3, igf lr3, igf-1 lr3, igf1 lr3 **Class:** Engineered long-acting analogue of insulin-like growth factor 1 (IGF-1); recombinant protein / IGF-1 receptor agonist ## Why this grade IGF-1 LR3 itself has never been tested in humans for any therapeutic or performance use. It is a laboratory cell-culture reagent that has migrated into the grey market. The parent molecule (native human IGF-1, sold as the licensed medicine mecasermin) does have robust human data, but only for a narrow childhood growth-disorder indication. That evidence does not transfer to this modified, longer-acting, binding-protein-evading analogue. For muscle and performance use there are no human RCTs, no clinical safety data and no regulatory evaluation, only cell-culture work and theoretical reasoning. The grade is D rather than F because the mechanism is well characterised and a related drug is approved, but for the way people actually use it, this sits firmly in territory where the only data are animal and in-vitro studies. ## In plain terms **Simple.** Your body makes a hormone called IGF-1 that tells muscle and other cells to grow and repair. IGF-1 LR3 is a man-made, tweaked copy designed to dodge the proteins that normally switch IGF-1 off quickly, so it stays active far longer and pushes harder. It was originally invented to grow cells in laboratory dishes. Bodybuilders buy it hoping it will build muscle, but no one has ever run a proper human study to show it does that, or that it is safe. Because it forces a powerful growth signal to stay switched on, the obvious worries are dangerous drops in blood sugar and the long-term question of whether constantly telling cells to grow is a good idea. **Standard.** IGF-1 is a hormone, made mainly in the liver under the control of growth hormone, that drives cell growth and tissue repair, including in muscle. Normally most IGF-1 in the blood is bound up by carrier proteins (IGF binding proteins) that limit how much is active and how long it lasts. IGF-1 LR3 is a deliberately engineered version: scientists added a short tail to one end and swapped one of its building blocks. Those changes make it bind the carrier proteins much more weakly, so it stays free and active for far longer than natural IGF-1, and it is somewhat more potent. It was created as a reagent for growing cells in industrial cell culture, not as a medicine. There is a licensed IGF-1 medicine, mecasermin, but that is plain native IGF-1 used only for rare childhood growth disorders, and its main known risk is hypoglycaemia (low blood sugar). IGF-1 LR3 has never been through human trials for muscle growth or anything else, and is sold online as an unlicensed 'research chemical, not for human consumption'. The picture is a strong, well-understood growth signal, an attractive theory, and essentially zero human evidence that it is safe or effective for what people buy it for. **Technical.** IGF-1 LR3 is an 83-residue recombinant analogue of human IGF-1 (native mature IGF-1 is 70 residues). It carries an N-terminal 13-residue extension and an Arg-for-Glu substitution at position 3. The position-3 substitution markedly reduces affinity for the IGF binding proteins (notably IGFBP-3), preventing sequestration into the ternary IGFBP-3/ALS complex. The net effect is a greater free fraction, higher potency than rhIGF-1 in cell systems, and a substantially extended circulating half-life. It remains a full agonist at the IGF-1 receptor (a receptor tyrosine kinase signalling through IRS-1/PI3K/Akt and Ras/MAPK), and like IGF-1 has weak cross-reactivity at the insulin receptor, the basis for its hypoglycaemic potential. It was developed and is marketed (e.g. as LONG R3 IGF-I) as a serum-free cell-culture supplement for biomanufacturing, not as a therapeutic. No clinical pharmacology, efficacy or safety data exist for IGF-1 LR3 in humans, for muscle hypertrophy, performance or any other indication. The clinically validated comparator is mecasermin (native rhIGF-1, Increlex), FDA-approved in 2005 for severe primary IGF-1 deficiency, whose pharmacovigilance signal (dose-related hypoglycaemia, lymphoid hyperplasia, intracranial hypertension, slipped capital femoral epiphysis, and a theoretical neoplasia concern from chronic mitogenic IGF-1R signalling) is the best available proxy for the hazards of supraphysiological IGF-1R agonism. Extrapolating that proxy to a more potent, longer-acting, IGFBP-evading analogue used without medical supervision is a reasonable basis for caution, but remains extrapolation, not evidence. WADA prohibits IGF-1 and its analogues at all times (class S2). ## How it is thought to work Full agonist at the IGF-1 receptor (a receptor tyrosine kinase), activating IRS-1/PI3K/Akt and Ras/MAPK signalling to drive cell proliferation, protein synthesis and survival. The engineered N-terminal extension and the Arg3 substitution sharply reduce binding to the IGF binding proteins (especially IGFBP-3), so the molecule escapes the normal carrier-protein 'sink', circulates as a higher free fraction, is more potent and lasts considerably longer than native IGF-1. Like native IGF-1 it has weak insulin-receptor cross-reactivity, which underlies its hypoglycaemic potential. Administered parenterally (by injection). ## Studied for Research contexts, not proven uses. - Serum-free supplement for industrial and research cell culture / biomanufacturing (its actual developed purpose) - Promoting expansion and differentiation of stem cells and primary cells in vitro (including muscle-lineage cells) - Speculative, clinically untested contexts for muscle hypertrophy, recovery and body recomposition, extrapolated from native IGF-1 biology ## What the human evidence shows None for IGF-1 LR3 specifically. The molecule was engineered as a cell-culture reagent and has no published human pharmacokinetic, efficacy or safety studies for muscle growth, performance, recovery or any therapeutic use. Every claim of human benefit is extrapolated from native IGF-1 biology and laboratory work. The only solid human IGF-1 data come from mecasermin (native recombinant IGF-1), approved narrowly for severe primary IGF-1 deficiency in children, and from small investigational studies such as a controlled trial in Rett syndrome. These involve a different molecule used for different purposes, and hypoglycaemia was the dominant adverse effect. There is no basis to assume those efficacy results, or that safety profile, apply to a more potent, longer-acting, binding-protein-evading analogue self-administered for bodybuilding. ## Concerns and unknowns - No human trials of IGF-1 LR3 itself for any purpose (efficacy and safety in people are simply unknown). - Hypoglycaemia: IGF-1 cross-reacts with the insulin receptor and suppresses hepatic glucose output; a more potent, longer-acting analogue raises a real risk of prolonged low blood sugar. - Theoretical cancer/neoplasia concern: chronic supraphysiological IGF-1R (mitogenic, pro-survival) signalling is biologically the wrong direction for anyone with, or at risk of, malignancy; long-term consequences in healthy users are unstudied. - Other adverse signals seen with mecasermin include lymphoid tissue hyperplasia, intracranial hypertension, slipped capital femoral epiphysis and tissue overgrowth. - Quality/identity risk: grey-market 'research chemical' vials are unregulated and may be underdosed, mislabelled, degraded, non-sterile or not actually contain LR3-IGF-1. - Sold explicitly as 'not for human consumption': no pharmaceutical-grade manufacturing, no medical oversight, no informed-consent framework. - Banned in sport by WADA at all times; use carries doping sanctions. ## UK status IGF-1 LR3 is not a licensed medicine in the UK (the MHRA has authorised no IGF-1 LR3 product). The only licensed IGF-1 medicine is mecasermin (native rhIGF-1, brand Increlex), a prescription-only medicine for severe primary IGF-1 deficiency in children; it is designated an orphan medicine and is a different molecule for a different purpose. IGF-1 LR3 is sold online as an unlicensed 'research chemical' labelled 'not for human consumption', a label that sidesteps but does not satisfy medicines law: marketing or supplying it for human use would engage the Human Medicines Regulations 2012 as an unlicensed medicinal product. As an IGF-1 analogue it is also a WADA-prohibited substance (class S2) at all times in sport. There is no legitimate, regulated route to obtain it for human use in the UK. ## Sport / WADA Prohibited at all times (WADA class S2, peptide hormones / growth factors and mimetics). IGF-1 and its analogues, including IGF-1 LR3, are banned both in and out of competition. ## Sources 1. IGF-1 LR3 (Long R3 IGF-1) — structure, IGFBP affinity, potency and half-life. Wikipedia, 2024 2. Mecasermin (recombinant human insulin-like growth factor I). Keating GM, Drugs, 2008 3. INCRELEX (mecasermin) US Prescribing Information — indication (severe primary IGF-1 deficiency), hypoglycaemia, lymphoid hyperplasia and intracranial hypertension warnings. FDA Drugs@FDA label, BLA 021839, 2019 4. Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome. Khwaja OS et al., PNAS, 2014 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/igf-1-lr3 . Educational only, not medical advice. --- # Ipamorelin **Evidence grade: C (Early / limited human data).** Area: Muscle & Performance. > A lab-made peptide that nudges your own pituitary gland to release a pulse of growth hormone. Proven to do that in humans, but never proven to actually make anyone healthier, stronger or leaner. **Also known as:** NNC 26-0161, Aib-His-D-2-Nal-D-Phe-Lys-NH2, ipa, ipamorelin, cjc ipamorelin, cjc/ipa **Class:** Synthetic pentapeptide growth hormone secretagogue (ghrelin/GHS-R1a receptor agonist) ## Why this grade Human pharmacology is genuinely established. Early-phase human studies confirm it does what it says biochemically: it reliably triggers a growth-hormone pulse in people and is well tolerated. But it has never been shown to deliver a clinical benefit in humans. Its single efficacy trial, a proof-of-concept study in postoperative ileus, was negative. There is no human evidence for the muscle, body-composition, recovery, sleep or anti-ageing uses it is marketed for. Real human safety and pharmacokinetic data exist (better than most grey-market peptides), but no proven human outcome. That places it at C, not B (which would need ongoing or supportive efficacy trials that do not exist) and not D (it is far better characterised in humans than animal-only peptides). ## In plain terms **Simple.** Ipamorelin is a small man-made protein that tickles a switch in your brain's pituitary gland, telling it to squirt out a short burst of your own growth hormone. It is billed as 'clean': older peptides that do the same job also made people hungry or raised stress hormones, but ipamorelin mostly just does the growth-hormone thing. Scientists have shown it raises growth hormone in people, but no proper study has shown that this leads to anything you'd actually care about: more muscle, faster healing, better skin or weight loss. The one time it was tested for a real medical problem (a sluggish gut after surgery) it didn't work. It is not an approved medicine anywhere. In the UK it's sold to the grey market labelled 'for research, not for human use', which is a legal dodge, not a sign it's safe to inject. **Standard.** Ipamorelin is a synthetic pentapeptide (five amino acids) that acts as a ghrelin-receptor agonist - it mimics the 'hunger hormone' ghrelin at the growth-hormone secretagogue receptor (GHS-R1a) in the pituitary, prompting a pulse of natural growth hormone (GH). It was designed by Novo Nordisk in the 1990s to be highly selective: unlike earlier GH-releasing peptides such as GHRP-6, it raises GH without meaningfully bumping cortisol, prolactin or appetite. That selectivity is real and well documented. What is NOT documented is benefit: human studies confirmed it elevates GH and is well tolerated, but the one controlled efficacy trial - a proof-of-concept study using it to restart the gut after bowel surgery (postoperative ileus) - was negative on its primary endpoint, and that line of development did not progress. None of the things it's sold for in fitness and 'anti-ageing' circles (muscle gain, fat loss, recovery, better sleep, skin) have been demonstrated in humans. It is unlicensed in the UK and not approved as a medicine anywhere. Most product sold online is unregulated 'research chemical' material of unknown purity. **Technical.** Ipamorelin (Aib-His-D-2-Nal-D-Phe-Lys-NH2) is a synthetic pentapeptide growth hormone secretagogue and selective agonist of the growth hormone secretagogue receptor type 1a (GHS-R1a), the endogenous receptor for ghrelin. Binding GHS-R1a on pituitary somatotrophs activates Gq/phospholipase-C signalling, raising intracellular calcium and driving GH exocytosis; it acts in concert with, but distinct from, GHRH signalling. Its defining property, characterised by Raun et al. (1998), is GH-release selectivity comparable to GHRH itself - in contrast to GHRP-6/GHRP-2, ipamorelin produces minimal ACTH/cortisol and prolactin elevation and limited orexigenic effect, reflecting cleaner receptor pharmacology. Human data: early-phase work confirmed GH secretion and good tolerability. The principal clinical efficacy test was a proof-of-concept Phase 2 study for acceleration of GI recovery after bowel resection (postoperative ileus), sponsored by Helsinn (NCT00672074; published Beck et al., Int J Colorectal Dis 2014); it was negative on its primary endpoint (time to tolerance of a solid meal; ~117 patients, p approximately 0.15) and that indication did not advance. Crucially, there are no controlled human trials supporting hypertrophy, lipolysis, body-composition, dermatological, sleep or geroprotective claims; downstream GH/IGF-1-mediated outcomes in healthy or athletic populations are unstudied. Regulatory: no marketing authorisation in any jurisdiction. US compounding status has fluctuated - ipamorelin acetate was added to the FDA's interim 503A category-2 bulk drug substances list (significant safety concerns) in 2023, then removed in September 2024 after the nomination was withdrawn; at the October 2024 PCAC review the FDA recommended against its inclusion on the 503A bulks list, so it remains outside any legitimate compounding pathway. ## How it is thought to work Ipamorelin is a selective agonist of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R1a) on pituitary somatotrophs. Activating this Gq-coupled receptor triggers phospholipase-C signalling and calcium-dependent release of stored growth hormone, producing a GH pulse that subsequently raises IGF-1. Unlike non-selective GH-releasing peptides, it does so with minimal effect on cortisol, prolactin and appetite. It is administered parenterally because as a peptide it is not orally bioavailable. ## Studied for Research contexts, not proven uses. - Acceleration of gastrointestinal recovery after bowel surgery (postoperative ileus) - negative on its primary efficacy endpoint - Stimulation of endogenous growth hormone secretion as a pharmacological probe - Characterisation of GHS-R1a (ghrelin receptor) selectivity versus older GH-releasing peptides ## What the human evidence shows Genuine but limited. Early-phase human studies confirm ipamorelin raises endogenous growth hormone and is generally well tolerated, so its core biochemical action is real in humans. This puts it ahead of most grey-market peptides. The only controlled test of clinical benefit, a proof-of-concept Phase 2 study for postoperative ileus (NCT00672074, Helsinn; published 2014, approximately 117 patients), was negative on its primary endpoint and that indication did not advance. There are no controlled human trials demonstrating the muscle-building, fat-loss, recovery, sleep, skin or anti-ageing outcomes for which it is marketed. Proven to release GH in people. Not proven to do anything useful with it. ## Concerns and unknowns - No proven clinical benefit in humans: its single controlled efficacy trial (postoperative ileus) was negative, and the popular fitness/anti-ageing uses are completely unstudied in humans. - Not an approved medicine anywhere; no marketing authorisation. In the UK it is an unlicensed substance sold as a 'research chemical' labelled 'not for human consumption' - a legal workaround, not a safety endorsement. - Grey-market product is unregulated: purity, sterility, peptide identity and dosing accuracy are not guaranteed, and contamination/endotoxin from non-pharmaceutical sources is a real injection risk. - Raising GH/IGF-1 is not consequence-free: theoretical and class-level concerns include fluid retention, joint pain, insulin resistance/raised blood glucose, and the general caution that chronically elevated IGF-1 may have implications for tumour growth - none of which has been characterised for long-term ipamorelin use in healthy people. - US compounding status has been unstable: ipamorelin acetate was placed on the FDA's interim 503A category-2 bulk drug substances list (significant safety concerns) in 2023, then removed in 2024 after the nomination was withdrawn, with the FDA subsequently recommending against its inclusion on the 503A bulks list - it has no settled legitimate route in the US either. - Marketing routinely overstates a clean GH boost as if it equals real-world physique or longevity benefits; that inferential leap is unsupported. ## UK status Not a licensed UK medicine and holds no MHRA marketing authorisation. It is an investigational compound whose only controlled clinical trial (in postoperative ileus) was negative and was not pursued further. It is not a controlled drug under the Misuse of Drugs Act, but selling or supplying it for human use without authorisation would breach the Human Medicines Regulations 2012. It is sold online as an unlicensed 'research chemical' labelled 'not for human consumption'. There is no legitimate UK prescription route for it. ## Sport / WADA Prohibited at all times under WADA category S2 (peptide hormones, growth factors, related substances) as a growth hormone secretagogue / GHS-R agonist. ## Key trials - **Safety and Efficacy of Ipamorelin for Management of Post-Operative Ileus** (NCT00672074, Phase 2 (proof-of-concept), Completed - negative; primary efficacy endpoint not met). Sponsor Helsinn Therapeutics; randomised, double-blind, placebo-controlled in bowel-resection patients (~117 enrolled). Primary endpoint (time to tolerance of a solid meal) showed no significant difference versus placebo; published Int J Colorectal Dis 2014. ## Sources 1. Ipamorelin, the first selective growth hormone secretagogue. Raun K, Hansen BS, Johansen NL, Thogersen H, Madsen K, Ankersen M, Andersen PH, European Journal of Endocrinology, 1998 2. Prospective, randomized, controlled, proof-of-concept study of the ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. Beck DE, et al., International Journal of Colorectal Disease, 2014 3. Growth hormone secretagogues: history, mechanism of action, and clinical development. Ishida J, et al., JCSM Rapid Communications, 2020 4. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (interim 503A category-2 list). US Food and Drug Administration, FDA, 2024 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/ipamorelin . Educational only, not medical advice. --- # KPV **Evidence grade: D (Animal data only).** Area: Recovery & Repair. > A three-amino-acid fragment of alpha-MSH that suppresses inflammation in cell and animal studies but has never been tested in humans. **Also known as:** Lys-Pro-Val, Lysine-Proline-Valine, alpha-MSH (11-13), alpha-MSH C-terminal tripeptide, kpv, kpv peptide **Class:** Tripeptide; C-terminal fragment of alpha-melanocyte-stimulating hormone (alpha-MSH) ## Why this grade All meaningful efficacy data come from cell-culture and rodent models (DSS/TNBS colitis, peritonitis, corneal wounds). There are no completed or registered human clinical trials for KPV in any indication, so human efficacy and safety are essentially unknown. A reasonably reproducible preclinical anti-inflammatory signal keeps it out of grade F, but the complete absence of human data caps it firmly at D. ## In plain terms **Simple.** KPV is three amino acids snipped from the end of a natural hormone called alpha-MSH. In cell cultures and mice it appears to dampen inflammation. People are interested in it for gut problems, skin irritation and recovery. However, no human trials have ever been done, so we do not know whether it works or is safe in people. Currently it is sold as an unlicensed 'research chemical', not as a medicine. **Standard.** KPV stands for lysine-proline-valine, the three amino acids that make it up. It is the C-terminal fragment (the tail end) of alpha-MSH, a hormone with anti-inflammatory properties. This small fragment appears to retain the anti-inflammatory action of the full hormone whilst avoiding its skin-darkening effects. In laboratory cells and mouse models of colitis, KPV dampens inflammatory signalling and reduces inflammatory molecules like TNF-alpha and IL-6. This has generated interest in inflammatory bowel disease, eczema, wound healing and general recovery. However, evidence is limited to the laboratory and animal studies. No human clinical trials have been completed or registered. In the UK it is not a licensed medicine and is sold only as a 'not for human consumption' research compound, with no guarantee of purity, sterility or dose accuracy. **Technical.** KPV (Lys-Pro-Val) is the C-terminal tripeptide (residues 11-13) of alpha-MSH. Unlike the core melanocortin message, KPV exerts anti-inflammatory activity largely through a melanocortin-receptor-independent, intracellular route. Intestinal epithelial and immune cells take it up via the di/tripeptide transporter PepT1 (hPepT1/SLC15A1), which is upregulated in inflamed colonic mucosa. At nanomolar concentrations, KPV inhibits NF-kB activation by preserving IkBalpha and blocking IKK-driven p65 nuclear translocation, and attenuates MAP kinase signalling, reducing TNF-alpha, IL-6 and other pro-inflammatory cytokines (Dalmasso et al., Gastroenterology 2008). Alpha-MSH-derived peptides have been reported to show direct antimicrobial activity against Candida albicans and Staphylococcus aureus in vitro, though findings have not been uniformly reproduced. All efficacy data come from in vitro assays and rodent models (DSS- and TNBS-induced colitis, peritonitis, corneal wound healing). No Phase 1-3 human trials are registered; pharmacokinetics, immunogenicity and long-term safety in humans remain uncharacterised. ## How it is thought to work KPV is the C-terminal tripeptide of alpha-MSH. Its anti-inflammatory action, as characterised preclinically, appears largely independent of melanocortin receptors. It crosses intestinal epithelial and immune cells via the peptide transporter PepT1, which is upregulated in inflamed colonic mucosa. Once inside cells, KPV inhibits NF-kB activation by preserving IkBalpha and blocking p65 nuclear translocation, and dampens MAP kinase signalling. This reduces production of pro-inflammatory cytokines such as TNF-alpha and IL-6. Alpha-MSH-derived peptides including KPV have also been reported to show direct antimicrobial activity against Candida albicans and Staphylococcus aureus in vitro, though these findings are contested. Routes studied preclinically include oral, topical and parenteral. ## Studied for Research contexts, not proven uses. - Intestinal inflammation / inflammatory bowel disease (mouse colitis models) - Skin inflammation and dermatitis (preclinical) - Wound and corneal healing (animal models) - Antimicrobial / antifungal activity (in vitro, contested) - General anti-inflammatory and recovery contexts (extrapolated from alpha-MSH biology) ## What the human evidence shows None. Despite widespread marketing claims for gut health, eczema and recovery, there are no completed or registered human clinical trials of KPV in any indication. The entire efficacy case rests on in-vitro cell work and animal studies. Human pharmacokinetics, dosing, absorption, immunogenicity, drug interactions and long-term safety are completely uncharacterised. Any clinical claim is unsupported by human data. ## Concerns and unknowns - No human clinical trial data; efficacy and safety in people are unknown. - Sold in the UK as an unlicensed 'research chemical' / 'not for human consumption', with no regulatory oversight of purity, sterility, dose accuracy or contaminants. - Marketing routinely claims human benefits based solely on laboratory findings. - Some preclinical claims (e.g. antimicrobial activity) have not been consistently reproduced. - Long-term effects and immunogenicity in humans are uncharacterised. - Injectable grey-market use carries sterility, dosing and contamination risks inherent in unlicensed self-administered products. - A strong preclinical mechanism does not guarantee clinical benefit. Many anti-inflammatory peptides have failed to translate to humans. ## UK status Not a licensed medicine in the UK. KPV has no MHRA marketing authorisation and is not an approved prescription drug. It also has no approval from the FDA or EMA. It is sold almost exclusively as an unlicensed research chemical labelled 'not for human consumption'. Selling or supplying it for human medicinal use without authorisation would breach the Human Medicines Regulations 2012. There is no recognised UK medical indication. ## Sources 1. PepT1-Mediated Tripeptide KPV Uptake Reduces Intestinal Inflammation. Dalmasso G, Charrier-Hisamuddin L, Nguyen HTT, Yan Y, Sitaraman S, Merlin D, Gastroenterology, 2008 2. Antimicrobial effects of alpha-MSH peptides. Cutuli M, Cristiani S, Lipton JM, Catania A, Journal of Leukocyte Biology, 2000 3. Alpha-Melanocyte Stimulating Hormone: An Emerging Anti-Inflammatory Antimicrobial Peptide. Singh M, Mukhopadhyay K, BioMed Research International, 2014 4. Critical Role of PepT1 in Promoting Colitis-Associated Cancer and Therapeutic Benefits of the Anti-inflammatory PepT1-Mediated Tripeptide KPV in a Murine Model. Wu D, Wang X, et al., Cellular and Molecular Gastroenterology and Hepatology, 2016 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/kpv . Educational only, not medical advice. --- # Kisspeptin-10 **Evidence grade: C (Early / limited human data).** Area: Libido & Hormonal. > A short lab-made copy of a brain hormone that controls reproduction. Small human studies hint at effects on sexual arousal, but the data is early and the evidence grade reflects that. **Also known as:** KP-10, Kisspeptin-112-121, Metastin 45-54, KISS1 (112-121), kp10, kisspeptin, metastin **Class:** Reproductive neuropeptide / KISS1R (GPR54) agonist; decapeptide fragment of kisspeptin ## Why this grade The kisspeptin system is well-studied in humans and is a validated upstream control point for reproduction. Multiple academic clinical studies (largely from Imperial College London) show real effects on gonadotrophin release and on sexual and emotional brain processing. However, much of that programme used the longer kisspeptin-54, or gave short intravenous kisspeptin-10 infusions in tightly controlled research settings. KP-10's own human dataset is comparatively small and acute. There is no approved kisspeptin-10 medicine, no large efficacy trials proving durable benefit for low libido, and the grey-market subcutaneous product has never been studied in real-world use. Solid but early and limited human data for KP-10 specifically, hence C rather than B. ## In plain terms **Simple.** Your body has a master 'on switch' that controls puberty, fertility and sex hormones. Kisspeptin is the natural signal that presses that switch in your brain. Kisspeptin-10 is a short lab-made copy of part of that signal. Scientists have given it to volunteers in carefully controlled hospital studies, and it tells the brain to start the hormone chain that leads the body to make testosterone or oestrogen. In some small studies it also seemed to boost the brain's response to romantic and sexual cues, even in people with low desire. The studies were small and short, though, much of the work used a longer related version rather than kisspeptin-10 itself, and almost everything sold online is an unlicensed research chemical, not a tested medicine. **Standard.** Kisspeptin is a neuropeptide that sits at the very top of the hormonal cascade controlling reproduction. It acts on neurons in the hypothalamus to trigger GnRH release, which in turn drives the pituitary to release LH and FSH, the hormones that tell the testes or ovaries to make testosterone, oestrogen and gametes. Without kisspeptin signalling, puberty doesn't happen. Kisspeptin-10 is the minimal active 10-amino-acid fragment. It works the same way as the longer natural forms but is cleared from the blood much faster. UK academic groups, notably Imperial College London, have run a substantial body of human research showing kisspeptin reliably stimulates the reproductive axis and can be used to trigger egg maturation in IVF. In small randomised studies it increased activity in sexual brain regions and improved some measures of arousal in men and women with low sexual desire. These were short, controlled, mostly intravenous studies, and much of the HSDD and IVF work used the longer kisspeptin-54 rather than KP-10. There is no licensed kisspeptin-10 product, no proof of lasting real-world benefit, and continuous dosing can desensitise the system rather than help it. **Technical.** Kisspeptin-10 (KP-10) is the C-terminal decapeptide of the KISS1 gene product and a high-affinity agonist at KISS1R (GPR54), a Gq/11-coupled receptor expressed on hypothalamic GnRH neurons and within limbic structures (inferior frontal/cingulate cortex, hippocampus, amygdala). KISS1R activation depolarises GnRH neurons, driving pulsatile GnRH secretion into the hypophyseal portal system and downstream pituitary gonadotrophin (LH/FSH) release. Loss-of-function KISS1R mutations cause normosmic idiopathic hypogonadotropic hypogonadism, establishing the system as indispensable for puberty and reproduction. KP-10 and KP-54 differ pharmacokinetically, with KP-10 having a shorter circulating half-life. In a direct intravenous comparison in healthy men (Narayanaswamy et al., Hum Reprod 2015), KP-10 and KP-54 produced broadly similar gonadotrophin responses, though GnRH was more potent than either. Beyond the HPG axis, Comninos and colleagues (J Clin Invest 2017) demonstrated that kisspeptin modulates limbic sexual and emotional brain processing on fMRI. Subsequent randomised crossover trials from the same programme (JAMA Network Open 2022 in women, 2023 in men with HSDD) reported enhanced sexual brain activity and behavioural and penile-tumescence signals. Chronic continuous administration produces KISS1R desensitisation and tachyphylaxis. Much of the clinical efficacy programme (IVF triggering, HSDD) used KP-54. KP-10's own human dataset is comparatively limited, acute and largely mechanistic. ## How it is thought to work Kisspeptin-10 binds and activates KISS1R (GPR54) on hypothalamic GnRH neurons, stimulating pulsatile GnRH secretion, which drives pituitary LH and FSH release and thus gonadal sex-steroid production. KISS1R is also expressed in limbic brain regions, where kisspeptin appears to directly modulate sexual and emotional processing partly independent of its downstream hormone effects. ## Studied for Research contexts, not proven uses. - Stimulation of the hypothalamic-pituitary-gonadal axis (LH/FSH/sex-steroid release) - Triggering oocyte maturation in IVF as an alternative to hCG (largely with kisspeptin-54) - Idiopathic hypogonadotropic hypogonadism and disorders of puberty - Hypothalamic amenorrhoea - Hypoactive sexual desire disorder in men and women (brain processing and arousal) - Probing reproductive neuroendocrine physiology in research settings ## What the human evidence shows Substantial mechanistic human research exists, mostly from a single UK academic programme (Imperial College London). Controlled studies show kisspeptin reliably stimulates LH/FSH, can trigger oocyte maturation in IVF, and on fMRI modulates limbic sexual brain regions. Small randomised crossover trials in hypoactive sexual desire disorder reported increased sexual brain activity and some behavioural and physiological arousal signals. Most data are acute, intravenous and conducted in tightly controlled clinical settings. Much of the IVF and HSDD work used the longer kisspeptin-54 rather than KP-10 itself, whose specific human dataset is smaller. There are no large efficacy trials proving durable real-world benefit for libido or any condition, no licensed product, and continuous administration can desensitise the receptor. ## Concerns and unknowns - No licensed kisspeptin-10 medicine anywhere. Products sold to consumers are unlicensed research chemicals marketed 'not for human consumption' with no guarantee of identity, purity or sterility. - Real human trial data used pharmaceutical-grade peptide in monitored settings, often the kisspeptin-54 form rather than KP-10. This does not validate self-administered grey-market product. - Continuous or repeated dosing can cause KISS1R desensitisation (tachyphylaxis), potentially blunting rather than boosting the reproductive axis. - Manipulating the master switch of the reproductive axis has predictable downstream hormonal consequences that are unmonitored outside a clinic. - Marketing hype around the 'libido peptide' far outstrips the short, small, early-stage and largely mechanistic nature of the actual human arousal evidence. - Injectable peptide carries the usual risks of contamination, dosing error and adverse reactions when used without medical supervision. ## UK status Not a licensed medicine in the UK. The MHRA has approved no kisspeptin-10 product. It remains an investigational compound studied under clinical trial authorisations and is an unlicensed substance otherwise. It is typically sold online as a research chemical labelled 'not for human consumption', which sidesteps medicines law. Supplying or marketing it for human medicinal use without authorisation would breach the Human Medicines Regulations 2012. There is no routine route to obtain it as a prescribed treatment in the UK outside a clinical trial or specialist research setting. ## Key trials - **Kisspeptin in men with hypoactive sexual desire disorder (Imperial College London programme)** (Early-phase randomised crossover (academic), Completed/published 2023). Showed enhanced sexual brain processing and penile-tumescence signals; mechanistic rather than registrational. - **Kisspeptin in women with hypoactive sexual desire disorder (Imperial College London programme)** (Early-phase randomised crossover (academic), Completed/published 2022). Increased BOLD activity in sexual brain networks vs placebo. ## Sources 1. Kisspeptin modulates sexual and emotional brain processing in humans. Comninos AN, Wall MB, Demetriou L, et al., Journal of Clinical Investigation, 2017 2. Direct comparison of the effects of intravenous kisspeptin-10, kisspeptin-54 and GnRH on gonadotrophin secretion in healthy men. Narayanaswamy S, Jayasena CN, Ng N, et al., Human Reproduction, 2015 3. Effects of Kisspeptin on Sexual Brain Processing and Penile Tumescence in Men With Hypoactive Sexual Desire Disorder: A Randomized Clinical Trial. Mills EG, Ertl N, Wall MB, et al., JAMA Network Open, 2023 4. Effects of Kisspeptin Administration in Women With Hypoactive Sexual Desire Disorder: A Randomized Clinical Trial. Thurston L, Hunjan T, Ertl N, et al., JAMA Network Open, 2022 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/kisspeptin-10 . Educational only, not medical advice. --- # LL-37 **Evidence grade: B (Promising human evidence).** Area: Recovery & Repair. > A natural germ-killing peptide your own body makes to fight infection and help heal skin, tested in real wound-healing trials that have so far been promising but inconclusive. **Also known as:** Cathelicidin, Human cathelicidin, hCAP18 (precursor), CAMP, LL37, Ropocamptide (synthetic drug development name), ll-37, cap-18 **Class:** Endogenous human host-defence (cathelicidin) peptide; antimicrobial and immunomodulatory peptide ## Why this grade Unusually for a grey-market peptide, a synthetic version of LL-37 (development name ropocamptide) has been through genuine placebo-controlled human RCTs for chronic wounds. A small dose-ranging Phase I/II study (Gronberg 2014) was safe and positive on healing predictors, but the larger, pivotal Phase IIb HEAL LL-37 trial (Mahlapuu 2021) MISSED its primary efficacy endpoint, showing significance only in a post-hoc subgroup of the largest ulcers. So real human trials exist, but the pivotal one was negative overall and the programme has not advanced to a successful Phase III; the evidence is genuinely more than early/limited yet far from conclusive. There is no approved LL-37 medicine anywhere. B sits at the lower boundary: it reflects the existence of completed RCTs, not a positive result. Note that almost all consumer claims of "recovery"/anti-ageing benefit have essentially no human evidence at all. ## In plain terms **Simple.** LL-37 is a tiny protein your own body already makes as part of your immune system. It pokes holes in bacteria, viruses and fungi to kill them, and it also helps damaged skin repair itself and tells immune cells where to go. Because of that, scientists made a lab version and tested it as a treatment for stubborn leg ulcers that won't heal. An early test looked encouraging and it seemed safe, but the bigger, more careful test did not clearly work overall; it only hinted at helping the very largest wounds. So it is a real and interesting molecule, not just hype, but it is still unproven as a treatment and is not an approved medicine. There is also a catch: in some people LL-37 switches the immune system on the wrong way and is part of what drives diseases like psoriasis and lupus, so 'natural' does not mean 'harmless'. **Standard.** LL-37 is the only cathelicidin made by humans. It is the active, 37-amino-acid business end of a precursor protein (hCAP18) found in white blood cells, skin, and the linings of the gut and lungs. It does two main jobs: it directly kills a broad range of bacteria, fungi and some viruses by disrupting their membranes, and it acts as an immune signal, recruiting immune cells, neutralising bacterial toxins, and promoting wound repair and new blood-vessel growth. That wound-healing angle is why a synthetic version (development name ropocamptide) was trialled as a topical drug for hard-to-heal venous leg ulcers. A first small randomised trial looked safe and positive, but the larger Phase IIb trial failed to beat placebo across all patients, with only a hint of benefit in a subgroup of the largest ulcers found after the fact. The honest summary: more clinical evidence than almost any other 'research peptide', but not a clear win, and no licensed product. Crucially, LL-37 also has a dark side; it is a recognised self-antigen that helps drive inflammation in psoriasis and lupus, so it is genuinely double-edged. **Technical.** LL-37 is the sole human cathelicidin, encoded by the CAMP gene (chromosome 3p21) as the ~18 kDa precursor hCAP18. The cationic, amphipathic 37-residue C-terminal peptide is liberated extracellularly by serine proteases, notably proteinase 3 in neutrophils and kallikreins in skin. Direct microbicidal action proceeds via electrostatic binding to anionic microbial membranes and permeabilisation (carpet/toroidal-pore models), with broad-spectrum, anti-biofilm activity against Gram-positives, Gram-negatives, fungi and enveloped viruses, plus LPS/endotoxin neutralisation. Immunomodulatory effects are receptor-mediated: chemotaxis via FPR2 (FPRL1), with signalling through P2X7, EGFR transactivation and GPCRs driving keratinocyte/fibroblast migration, angiogenesis and re-epithelialisation. Therapeutically, synthetic LL-37 (ropocamptide) reached randomised clinical testing for hard-to-heal venous leg ulcers: a dose-ranging Phase I/II (Gronberg, Wound Repair Regen 2014, n=34) was safe with favourable healing kinetics, but the pivotal Phase IIb HEAL LL-37 study (Mahlapuu, Wound Repair Regen 2021, n=148 treated) did not meet its primary efficacy endpoint (sustained complete closure), with significance only in a post-hoc large-ulcer subgroup; the programme has not since advanced to a successful pivotal Phase III. The major caveat is its pathophysiological dual role: LL-37 complexes with self-DNA/RNA to break tolerance and trigger pDC type-I interferon (Lande, Nature 2007), and is a bona fide CD4+/CD8+ T-cell autoantigen in psoriasis (Lande, Nat Commun 2014), with native/citrullinated forms implicated in SLE. It is additionally explored mechanistically in oncology and antimicrobial-resistance contexts, largely preclinically. ## How it is thought to work LL-37 is a cationic, amphipathic peptide cleaved from the hCAP18 precursor (CAMP gene product) by serine proteases such as proteinase 3. It kills microbes directly by electrostatically binding and permeabilising negatively charged microbial membranes (broad-spectrum, anti-biofilm) and by neutralising bacterial endotoxin (LPS). Beyond killing microbes it is a host-defence/immunomodulatory peptide: it recruits immune cells via the formyl-peptide receptor FPR2, transactivates EGFR, and promotes keratinocyte and fibroblast migration, angiogenesis and re-epithelialisation, which is the basis of its wound-healing rationale. The same properties cut both ways: complexed with self-DNA/RNA it activates plasmacytoid dendritic cells to produce type-I interferon and acts as a T-cell autoantigen, contributing to psoriasis and lupus. ## Studied for Research contexts, not proven uses. - Hard-to-heal chronic wounds (venous leg ulcers, diabetic foot ulcers), topical - Broad-spectrum and anti-biofilm antimicrobial / antibiotic-resistant infection research - Innate immune modulation and endotoxin (LPS) neutralisation - Skin barrier and re-epithelialisation / tissue repair - Mechanistic study as an autoantigen in psoriasis and systemic lupus erythematosus - Exploratory anticancer and antiviral activity (preclinical) ## What the human evidence shows Genuinely more advanced than most grey-market peptides, but still inconclusive. A dose-ranging Phase I/II randomised, placebo-controlled trial in venous leg ulcers (Gronberg et al., 2014, 34 patients) reported good safety and tolerability and faster healing predictors. However, the larger pivotal Phase IIb HEAL LL-37 trial (Mahlapuu et al., 2021, 148 treated patients) FAILED its primary efficacy endpoint (sustained complete wound closure) across the full population, with a statistically significant benefit only in a post-hoc subgroup of large refractory ulcers. Smaller randomised data also exist for diabetic foot ulcers. There is no approved LL-37 product anywhere, and the development programme has not advanced to a successful Phase III. Separately, robust human immunology data establish LL-37 as a driver and self-antigen in psoriasis and lupus, which is relevant human evidence, but of harm, not benefit. Consumer claims of systemic 'recovery', anti-ageing or performance benefit have essentially no supporting human evidence. ## Concerns and unknowns - No LL-37 medicine is approved or licensed anywhere; topical wound products remain investigational and the pivotal Phase IIb trial missed its primary endpoint. - Double-edged biology: LL-37 is a recognised autoantigen that drives inflammation in psoriasis and lupus (via self-DNA/RNA complexes and type-I interferon), so 'made by the body' does not equal 'safe'. Potential to aggravate autoimmune or inflammatory skin disease. - Cationic peptides can be cytotoxic and pro-inflammatory to host cells, particularly at high local concentrations. - Grey-market LL-37 sold as a 'research chemical' has no guarantee of identity, purity, sterility or endotoxin content; injecting unsterile peptide carries infection and immune-reaction risk. - Almost all touted 'recovery', anti-ageing or systemic benefits in consumers rest on in-vitro or animal data, not human trials. - Implicated mechanistically in tumour biology in a context-dependent way (can be pro- or anti-tumour), so systemic use is not benign by default. ## UK status Not a licensed medicine in the UK. There is no LL-37 (ropocamptide) product authorised by the MHRA and no marketing authorisation for any indication. It is an investigational drug (industry-run clinical wound-healing trials) and, in the consumer/grey market, an unlicensed peptide typically sold as a 'research chemical' labelled 'not for human consumption' to sidestep medicines law. Supplying or selling an unlicensed product for human use as a medicine breaches the Human Medicines Regulations 2012. There is no legitimate UK route to obtain LL-37 for self-administration, and it is not a prescribable medicine. ## Key trials - **HEAL LL-37: Phase IIb double-blind, randomised, placebo-controlled trial of topical LL-37 (ropocamptide) with compression in hard-to-heal venous leg ulcers** (Phase 2b, Completed; primary endpoint not met overall (148 patients treated)). Sponsored by Promore Pharma; reported in Mahlapuu et al. 2021. - **Dose-ranging Phase I/II randomised, placebo-controlled first-in-man trial of topical LL-37 in venous leg ulcers** (Phase 1/2, Completed; positive on healing predictors (34 patients)). Reported in Gronberg et al. 2014. ## Sources 1. Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial. Gronberg A, Mahlapuu M, Stahle M, Whately-Smith C, Rollman O, Wound Repair and Regeneration, 2014 2. Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: a multicentric prospective randomized placebo-controlled clinical trial (HEAL LL-37). Mahlapuu M, et al., Wound Repair and Regeneration, 2021 3. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Lande R, et al., Nature, 2007 4. The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis. Lande R, et al., Nature Communications, 2014 5. In vitro and in vivo wound healing-promoting activities of human cathelicidin LL-37. Carretero M, et al., Journal of Investigative Dermatology, 2008 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/ll-37 . Educational only, not medical advice. --- # Larazotide **Evidence grade: B (Promising human evidence).** Area: Recovery & Repair. > An experimental gut-barrier peptide that aimed to be the first drug for coeliac disease, but failed its large Phase 3 trial and is approved nowhere. **Also known as:** Larazotide acetate, AT-1001, INN-202, Zonulin antagonist, larazotide, at1001 **Class:** Synthetic octapeptide; tight-junction regulator (gut barrier / "leaky gut" modulator) ## Why this grade Unusually well-studied for a peptide: multiple human randomised controlled trials, including a Phase 2b study (Leffler 2015) that met its symptom endpoint, and a large Phase 3 programme (CeDLara, NCT03569007). Graded B rather than A because the pivotal Phase 3 trial was discontinued in June 2022 for futility after a pre-specified interim analysis, the Phase 2b benefit was confined to a single dose arm with a flat/inverse dose-response, an earlier gluten-challenge study missed its primary permeability endpoint, and the drug is not approved anywhere. Real human data exist, but the headline efficacy claim in its lead indication (coeliac disease) was not confirmed. ## In plain terms **Simple.** Your gut wall is like a brick wall, and the 'mortar' between the bricks can loosen and let things leak through that shouldn't. Larazotide is a small peptide designed to tighten that mortar. The big hope was that it would help people with coeliac disease who still feel ill even when they avoid gluten. It looked promising in some mid-stage tests, but the largest, most important trial showed it didn't reliably beat a dummy treatment, so it was stopped. It is not a medicine you can be prescribed. **Standard.** Larazotide (larazotide acetate) is a synthetic 8-amino-acid peptide that acts on the 'tight junctions' between the cells lining your gut, the seals that control what passes between cells into the bloodstream. By tightening these seals it was meant to reduce the leakiness that lets gluten fragments through in coeliac disease. It got further than almost any other peptide of its kind: a mid-stage (Phase 2b) trial reported that one dose eased symptoms in coeliac patients who still had problems despite a strict gluten-free diet, though oddly the higher doses did not work. On the strength of that signal it entered a large Phase 3 trial (CeDLara). In June 2022 that trial was halted early because an interim look at the data showed larazotide was not separating meaningfully from placebo. So despite genuine human evidence, it never proved itself and is not an approved or licensed medicine. **Technical.** Larazotide acetate (AT-1001 / INN-202) is a synthetic octapeptide (Gly-Gly-Val-Leu-Val-Gln-Pro-Gly) and a tight-junction regulator that antagonises the zonulin pathway. Zonulin (pre-haptoglobin-2) reversibly disassembles epithelial tight junctions; in coeliac disease, gliadin triggers zonulin release, increasing paracellular permeability and antigen translocation. Larazotide promotes tight-junction reassembly and actin cytoskeleton rearrangement, reducing paracellular flux of immunogenic gliadin peptides. It is minimally absorbed and acts locally in the gut lumen. Clinically: Kelly 2013 (Aliment Pharmacol Ther; exploratory gluten-challenge RCT, n=184) reduced gluten-induced symptoms and immune reactivity but did NOT meet its primary permeability endpoint (LAMA urinary ratio). The Leffler 2015 Phase 2b RCT (Gastroenterology; n=342, persistent symptoms despite a gluten-free diet) met its primary symptom endpoint (CeD-GSRS) only at the lowest dose arm, with a non-monotonic dose-response (higher doses no better than placebo) - a result that weakens the signal. The Phase 3 CeDLara trial (NCT03569007, 9 Meters Biopharma, target ~525 patients, multiple dose arms vs placebo, CeD-PRO abdominal domain primary endpoint over a 12-week double-blind period) was terminated in June 2022 following a pre-specified interim analysis: the estimated sample size needed to detect a significant effect was judged too large to support continuation. The compound has also been explored on a barrier-restoration rationale in NASH and in paediatric multisystem inflammatory syndrome (MIS-C). ## How it is thought to work Acts locally in the gut lumen as a tight-junction regulator, antagonising the zonulin pathway. Zonulin signalling normally opens the tight junctions between intestinal epithelial cells; in coeliac disease gliadin drives this opening, increasing paracellular ("leaky") permeability and letting immunogenic gluten peptides cross the gut barrier. Larazotide promotes reassembly of tight junctions and stabilises the epithelial actin cytoskeleton, reducing that leak. It is minimally systemically absorbed, so its effect is intended to be confined to the gut. ## Studied for Research contexts, not proven uses. - Coeliac disease (persistent symptoms despite a gluten-free diet) - the lead indication - Coeliac disease in a deliberate gluten-challenge model - Intestinal barrier / 'leaky gut' permeability more generally - Non-alcoholic steatohepatitis (NASH) - exploratory - Paediatric multisystem inflammatory syndrome (MIS-C) associated with COVID-19 - exploratory ## What the human evidence shows Substantial for a peptide, but ultimately negative where it mattered. Multiple randomised, placebo-controlled human studies were run. An exploratory gluten-challenge RCT (Kelly et al., 2013, n=184) suggested reductions in gluten-induced symptoms but did not meet its primary intestinal-permeability endpoint. A Phase 2b RCT in 342 adults with coeliac disease who still had symptoms despite a gluten-free diet (Leffler et al., 2015) met its primary symptom endpoint, but only at the lowest dose tested, with higher doses showing no benefit - a non-monotonic pattern that should temper confidence. That signal nonetheless drove CeDLara, a large Phase 3 trial (NCT03569007, target ~525 patients) - reportedly the first Phase 3 trial of any coeliac disease drug. In June 2022 it was stopped early after a pre-specified interim analysis indicated the trial was unlikely to demonstrate a meaningful effect over placebo (futility). So while real human efficacy signals existed at Phase 2, the definitive trial did not confirm benefit, and larazotide is approved nowhere. ## Concerns and unknowns - Failed its pivotal Phase 3 trial (CeDLara) - discontinued for futility in June 2022; the Phase 2 benefit did not replicate at scale. - The Phase 2b signal was confined to a single dose with a flat/inverse dose-response, and the earlier gluten-challenge study missed its primary permeability endpoint - the human evidence base is weaker than a headline 'positive trial' suggests. - Not an approved or licensed medicine in the UK, EU or US for any condition. - Coeliac disease has an effective management strategy (a strict gluten-free diet); any unproven peptide is no substitute and could give a false sense of security around gluten exposure. - Grey-market 'larazotide' sold as a 'research chemical' or 'gut peptide' is unregulated: identity, purity, sterility and actual content are unverified, and it is sold 'not for human consumption'. - Marketing it for 'leaky gut' in healthy people extrapolates well beyond the evidence - the human data are in coeliac disease, and even there the drug did not succeed. - Long-term safety in non-coeliac or self-dosing populations is essentially uncharacterised. ## UK status Not a licensed medicine in the UK. Larazotide has no MHRA marketing authorisation and is not approved by the EMA or FDA for any indication. It is an investigational drug whose lead development programme (coeliac disease) was discontinued in 2022. Any product sold to UK consumers as "larazotide" is an unlicensed research chemical, typically labelled "not for human consumption"; supplying or selling it for human use would fall foul of the Human Medicines Regulations 2012. It is not available on NHS or private prescription. ## Key trials - **CeDLara: Phase 3 study of larazotide acetate in coeliac disease patients with persistent symptoms on a gluten-free diet** (NCT03569007, Phase 3, Discontinued (terminated June 2022 after a pre-specified interim futility analysis)). Sponsor 9 Meters Biopharma; target ~525 patients; primary endpoint CeD-PRO abdominal domain over a 12-week double-blind period. Reportedly the first Phase 3 trial of any coeliac disease drug. - **Phase 2b randomised controlled trial of larazotide acetate for persistent coeliac symptoms (Leffler 2015)** (Phase 2b, Completed - met primary endpoint at the lowest dose only). n=342; the trial that drove the move into Phase 3, though the benefit was dose-discordant. ## Sources 1. Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial. Leffler DA, Kelly CP, Green PHR, et al., Gastroenterology, 2015 2. Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study. Kelly CP, Green PHR, Murray JA, et al., Alimentary Pharmacology & Therapeutics, 2013 3. 9 Meters Biopharma Announces Interim Analysis of Phase 3 Study of Larazotide for Celiac Disease Does Not Support Trial Continuation. 9 Meters Biopharma (company announcement), BioSpace / company press release, 2022 4. Larazotide acetate, zonulin and tight-junction regulation in coeliac disease (PubMed search). PubMed, 2021 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/larazotide . Educational only, not medical advice. --- # Lipo-C (Lipotropic / MIC Injection) **Evidence grade: D (Animal data only).** Area: Weight & Metabolic. > A clinic-mixed injection of everyday nutrients (methionine, inositol, choline, often with carnitine and B-vitamins) marketed as a fat-burner, with no controlled human evidence that the shot itself burns fat. **Also known as:** mic injection, lipotropic injection, fat burner shot, lipo shot, lipo-mic, skinny shot, mic plus, lipo-b **Class:** Compounded injectable cocktail of nutrients (not a peptide) — typically Methionine, Inositol, Choline (MIC), often with L-carnitine and B-vitamins ## Why this grade No randomised controlled trials show that injecting these nutrients causes meaningful fat loss in well-nourished people. The components have real biology, but the product as a fat-loss treatment is essentially unevidenced in humans. ## In plain terms **Simple.** Lipo-C isn't really a peptide at all — it's a mixed jab of nutrients your body already gets from food, like a few B-vitamins, an amino acid called methionine, and choline (found in eggs). Clinics inject it and call it a 'fat-burner' or 'skinny shot'. The catch: there's basically no proper proof that injecting these things melts fat. The nutrients each do useful jobs in the body, but that's not the same as the injection making you slimmer. People who lose weight on these programmes are usually also dieting and exercising — and that's what's actually doing the work. **Standard.** Lipo-C (a 'lipotropic' or MIC injection) is a compounded blend rather than a single drug. The core is MIC — methionine (an amino acid), inositol (a sugar alcohol involved in cell signalling) and choline (an essential nutrient for liver fat handling) — usually bulked out with L-carnitine and B-vitamins like B12. The marketing claim is that these 'lipotropic' agents mobilise fat from the liver and help you burn it. The biology of each ingredient is genuine, but it relates to correcting a deficiency, not to producing weight loss in someone who already eats normally. No randomised trial shows the injection itself causes clinically meaningful fat loss; reported results come from programmes that also include calorie restriction and exercise. It's increasingly sold alongside GLP-1 drugs as an 'add-on', which muddies any apparent benefit further. **Technical.** Lipotropic/MIC formulations are compounded parenteral preparations combining methionine, myo-inositol and choline, frequently with levocarnitine, cyanocobalamin (B12) and other B-complex vitamins. The rationale rests on each component's role in hepatic lipid metabolism: choline and methionine (via SAM and the PEMT pathway) are required for phosphatidylcholine synthesis and hence VLDL assembly and triglyceride export from hepatocytes; carnitine mediates mitochondrial long-chain fatty-acyl import for beta-oxidation; inositol contributes to insulin signalling. Choline deficiency demonstrably causes hepatic steatosis in depletion-repletion studies, and inositol has RCT support in PCOS-associated insulin resistance — but these are deficiency-correction and metabolic-modulation findings, not demonstrations that supraphysiological injected doses drive lipolysis or net adipose loss in replete individuals. There are no adequately powered RCTs isolating the injection's contribution to weight loss; the construct conflates substrate availability with rate-limiting flux. Bioavailability arguments ('bypassing the gut') are largely irrelevant given that oral choline and carnitine are well absorbed in healthy people. ## How it is thought to work The proposed mechanism is that 'lipotropic' nutrients help the liver mobilise and export fat. Choline and methionine are needed to make phosphatidylcholine, which the liver uses to package and ship out triglyceride as VLDL; without enough, fat accumulates in the liver (steatosis). L-carnitine shuttles long-chain fatty acids into mitochondria where they are burned for energy. Inositol participates in insulin signalling, and B-vitamins are cofactors in energy metabolism. The leap the marketing makes is from 'these nutrients are involved in handling fat' to 'injecting more of them makes you lose body fat' — a step that does not follow, because in a well-nourished person these pathways are not limited by a shortage of these substrates. ## Studied for Research contexts, not proven uses. - Weight / fat loss (claimed, not demonstrated) - Liver fat handling (component-level) - Energy and metabolism support (marketing claim) - Add-on to GLP-1 weight-loss programmes ## What the human evidence shows There are no randomised controlled trials showing that a lipotropic/MIC injection produces clinically meaningful weight or fat loss independent of diet and exercise. The injection is not a licensed medicine for weight loss. Evidence cited by clinics is almost entirely about the individual nutrients — for example, choline depletion causing fatty liver, or inositol improving insulin sensitivity in PCOS — which addresses deficiency or specific metabolic conditions, not fat-burning in an otherwise replete person. Where people on MIC programmes lose weight, the programmes also impose calorie restriction and exercise, and increasingly the injection is bundled with GLP-1 drugs, so any weight change cannot be attributed to the shot. In short: the components are real and studied; the product as a fat-loss treatment is essentially untested in proper human trials. ## Concerns and unknowns - Marketed as a 'fat-burner' with no controlled evidence it burns fat — the claim outruns the data. - Compounded/unlicensed: contents, concentration and sterility vary between clinics and aren't held to licensed-medicine standards. - Injection-site pain, bruising, redness and rare infection or abscess; intramuscular injections carry the usual risks. - Often sold as an add-on to GLP-1 drugs or alongside B12, making it impossible to know what (if anything) it's contributing while you pay for it. - Methionine loading can transiently raise homocysteine; the relevance of repeated injections is poorly characterised. - Opportunity cost: money and faith placed in an unproven shot instead of interventions that actually work. ## UK status In the UK an injectable product is a medicinal product, so a lipotropic/MIC injection used clinically falls under the Human Medicines Regulations 2012 and the MHRA. These blends are not licensed medicines — they are unlicensed compounded 'specials' or imported products. GMC guidance says unlicensed medicines should only be used where a licensed option can't meet clinical need, with documented rationale, informed consent and monitoring; using an unproven nutrient injection purely for cosmetic weight loss sits awkwardly against that. The MHRA has repeatedly warned about unlicensed injectable 'weight-loss' products bought online or given in non-clinical settings, citing contamination, dosing and quality concerns. There is no NHS endorsement of lipotropic injections for any indication. ## Sport / WADA The individual nutrients (methionine, inositol, choline, carnitine, B-vitamins) are not themselves on the WADA Prohibited List. However, under M2.2 WADA prohibits intravenous infusions and/or injections of more than 100 mL per 12-hour period unless legitimately received during hospital treatment, surgery or clinical diagnostic investigation — so a large-volume IV 'drip' version could breach the rules on volume grounds even though the ingredients are permitted. Intramuscular shots are typically well under that volume. Athletes should treat any compounded injectable with caution given contamination and mislabelling risk. ## Key trials - **No registered RCT isolating lipotropic/MIC injection for weight loss** (None identified). Searches of trial registries and PubMed return no adequately controlled trial testing the injection's independent effect on body weight or fat mass. ## Sources 1. Choline: an essential nutrient for public health. Zeisel SH, da Costa KA, Nutrition Reviews, 2009 2. Effects of Inositol(s) in Women with PCOS: A Systematic Review of Randomized Controlled Trials. Unfer V, Nestler JE, Kamenov ZA, Prapas N, Facchinetti F, International Journal of Endocrinology, 2016 3. Lipotropic (MIC) injections for weight loss — search of published human trials. PubMed 4. WADA Prohibited List — M2 Chemical and Physical Manipulation (intravenous infusions and injections, >100 mL/12 h threshold). World Anti-Doping Agency 5. MHRA warnings on unlicensed injectable weight-loss products. MHRA / GOV.UK _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/lipo-c . Educational only, not medical advice. --- # Liraglutide **Evidence grade: A (Approved / strong human evidence).** Area: Weight & Metabolic. > A daily injectable prescription medicine that mimics a natural gut hormone to reduce appetite and aid weight loss, sold as Saxenda for weight management and Victoza for type 2 diabetes. **Also known as:** Saxenda, Victoza, Nevolat, NN2211, lira, liraglutide **Class:** GLP-1 receptor agonist (incretin mimetic) ## Why this grade Grade A is justified: this is a fully licensed medicine supported by robust large-scale human RCTs. It is approved by the MHRA, EMA and FDA for type 2 diabetes (Victoza) and chronic weight management (Saxenda). The SCALE Obesity and Prediabetes RCT (NEJM 2015, ~3,700 participants) demonstrated clinically meaningful weight loss. The LEADER trial (NEJM 2016, ~9,300 patients) showed reduced major cardiovascular events in type 2 diabetes with high cardiovascular risk. ## In plain terms **Simple.** Liraglutide mimics a hormone your gut naturally releases when you eat. It tells your brain you're full and slows stomach emptying, so you feel satisfied with less food. It's a licensed medicine you get on prescription (as Saxenda for weight loss or Victoza for diabetes), given as a daily injection under the skin. It works in proper studies but produces less weight loss than newer weekly drugs like semaglutide. Common side effects are nausea and stomach upset. **Standard.** Liraglutide is a GLP-1 receptor agonist: a lab-made copy of the hormone GLP-1 (glucagon-like peptide-1) your gut releases in response to food. It activates GLP-1 receptors to increase insulin release when blood sugar is high, slow stomach emptying, and reduce hunger via appetite centres in the brain. It is a fully approved prescription-only medicine in the UK, sold as Victoza (lower-dose version for type 2 diabetes) and Saxenda (higher-dose version for weight management). In the SCALE obesity trial, people on the weight-management version lost around 8 percent of body weight versus 2–3 percent on placebo over roughly a year. It is given as a daily injection, so newer weekly drugs (semaglutide, tirzepatide) have become more popular for weight loss. Common side effects are gastrointestinal: nausea, vomiting, diarrhoea, constipation. Following UK patent expiry in late 2024, lower-cost generic versions have entered the market. **Technical.** Liraglutide is an acylated, long-acting GLP-1 receptor agonist with approximately 97 percent sequence homology to native human GLP-1. A C16 palmitic fatty-acid chain attached via a glutamic acid spacer promotes reversible albumin binding and self-association, extending the half-life to approximately 13 hours and enabling once-daily subcutaneous administration. GLP-1 receptor agonism drives glucose-dependent insulinotropic action, suppression of inappropriate glucagon secretion, delayed gastric emptying, and anorexigenic signalling via hypothalamic POMC/CART and arcuate-nucleus pathways. It is approved for type 2 diabetes (Victoza, lower maintenance dose) and chronic weight management (Saxenda, higher maintenance dose), with an additional adolescent (12+) obesity indication. The SCALE Obesity and Prediabetes RCT (Pi-Sunyer et al., NEJM 2015; NCT01272219) showed placebo-subtracted weight loss of approximately 5.6 kg at 56 weeks. The LEADER trial (Marso et al., NEJM 2016; NCT01179048) demonstrated statistically significant reduction in 3-point MACE in type 2 diabetes with high cardiovascular risk. In the head-to-head STEP 8 RCT (JAMA 2022), daily liraglutide (approximately 6.4 percent weight loss at 68 weeks) produced less weight loss than once-weekly semaglutide (approximately 15.8 percent). Class warnings include a rodent C-cell thyroid tumour signal (medullary thyroid carcinoma/MEN2 contraindication), pancreatitis risk, and gallbladder events. ## How it is thought to work Liraglutide is a GLP-1 receptor agonist that binds the GLP-1 receptor and reproduces the actions of the native incretin hormone GLP-1: glucose-dependent enhancement of insulin secretion, suppression of glucagon, delayed gastric emptying, and central appetite suppression via hypothalamic pathways. A palmitoyl fatty-acid modification promotes albumin binding and slows degradation, extending the half-life sufficiently for once-daily subcutaneous injection. ## Studied for Research contexts, not proven uses. - Chronic weight management in obesity and in overweight with weight-related comorbidities - Glycaemic control in type 2 diabetes mellitus - Cardiovascular risk reduction in type 2 diabetes with established or high cardiovascular risk - Paediatric and adolescent obesity (age 12+) - Prediabetes and progression to type 2 diabetes ## What the human evidence shows Extensive. Multiple large, randomised, placebo-controlled human trials underpin its approvals. The SCALE Obesity and Prediabetes RCT (~3,700 adults, NEJM 2015) established weight-management efficacy with placebo-subtracted weight loss of approximately 5–6 percent of body weight over 56 weeks. The LEADER trial (~9,300 patients, NEJM 2016) demonstrated reduced major adverse cardiovascular events in type 2 diabetes with high cardiovascular risk. Head-to-head data (STEP 8, JAMA 2022) show liraglutide produces clearly less weight loss than once-weekly semaglutide. This is genuine, high-quality human evidence, not extrapolation from animal data. ## Concerns and unknowns - Common gastrointestinal side effects: nausea, vomiting, diarrhoea, constipation, especially during dose escalation - Risk of acute pancreatitis and increased gallbladder events including cholelithiasis - Class warning for rodent thyroid C-cell tumours; contraindicated in personal or family history of medullary thyroid carcinoma or MEN2 - Less effective for weight loss than newer agents (semaglutide, tirzepatide) and requires daily rather than weekly injection - Risk of hypoglycaemia when combined with insulin or sulfonylureas - Grey-market and unlicensed 'research chemical' versions exist; only pharmacy-supplied, prescribed product has assured identity, purity and dose ## UK status A licensed, prescription-only medicine (POM) in the UK, regulated by the MHRA. It is marketed as Victoza for type 2 diabetes and as Saxenda for weight management in adults with obesity (or overweight with a weight-related comorbidity) and in adolescents aged 12 and over. Following UK patent expiry in late 2024, lower-cost generic versions such as Nevolat have entered the market. It must be obtained on prescription. Products sold online as unlicensed 'research chemicals' are illegitimate and unregulated. ## Key trials - **SCALE Obesity and Prediabetes** (NCT01272219, Phase 3, Completed). Pivotal weight-management efficacy trial; published NEJM 2015. - **LEADER - Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results** (NCT01179048, Phase 3b, Completed). Demonstrated cardiovascular benefit in type 2 diabetes with high cardiovascular risk; NEJM 2016. - **STEP 8 - once-weekly semaglutide vs once-daily liraglutide for weight loss** (NCT04074161, Phase 3b, Completed). Showed greater weight loss with once-weekly semaglutide than daily liraglutide; JAMA 2022. ## Sources 1. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management (SCALE Obesity and Prediabetes). Pi-Sunyer X, Astrup A, Fujioka K, et al., New England Journal of Medicine, 2015 2. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes (LEADER). Marso SP, Daniels GH, Brown-Frandsen K, et al., New England Journal of Medicine, 2016 3. A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity. Kelly AS, Auerbach P, Barrientos-Perez M, et al., New England Journal of Medicine, 2020 4. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes (STEP 8). Rubino DM, Greenway FL, Khalid U, et al., JAMA, 2022 5. MHRA / EMA Saxenda and Victoza (liraglutide) summaries of product characteristics. Medicines and Healthcare products Regulatory Agency, 2024 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/liraglutide . Educational only, not medical advice. --- # MK-677 (Ibutamoren) **Evidence grade: B (Promising human evidence).** Area: Growth Hormone. > A growth-hormone-boosting pill that genuinely raises IGF-1 and adds a little lean mass, but in every completed trial it failed to make people stronger, healthier or better-functioning. Its maker abandoned it. **Also known as:** Ibutamoren, Ibutamoren mesylate, MK-0677, L-163,191, mk677, nutrobal, oratrope **Class:** Orally active non-peptide growth hormone secretagogue (ghrelin receptor / GHSR-1a agonist). NOT a peptide and NOT a SARM, despite frequent mislabelling ## Why this grade Unusually well-studied for a grey-market compound: multiple completed randomised controlled trials in humans, including a 2-year aging RCT in older adults, a Phase 2 Alzheimer's trial, and a Phase 2b hip-fracture trial. It reliably raises IGF-1 and modestly increases fat-free mass. It earns a B rather than an A because that target engagement did not translate into clinical benefit in any completed trial. No gain in strength, physical function, quality of life or cognition. The programmes surfaced safety signals: reduced insulin sensitivity, fluid retention, and a congestive-heart-failure signal in the hip-fracture study. Merck abandoned development. ## In plain terms **Simple.** MK-677 is a pill that nudges your body into releasing more of its own growth hormone. It works by copying ghrelin, the 'hunger hormone'. At the chemistry level it works: growth hormone and a blood marker called IGF-1 go up, and people add a little lean weight. But none of that turned into people actually being stronger, fitter or healthier in the trials. It tends to make people hungrier, causes water retention, and pushes blood sugar upward. The company that invented it ran several big trials and then abandoned it. Today it is sold online as a research chemical, not as an approved medicine. **Standard.** MK-677 (ibutamoren) is an orally active growth hormone secretagogue, a small molecule that mimics ghrelin and switches on the growth-hormone-release machinery in the pituitary gland. It is not a peptide and not a SARM, despite being sold that way. It reliably raises growth hormone and IGF-1 (roughly 60-70% in trials) and increases fat-free mass by a kilogram or two. The problem is the gap between biomarkers and real benefit. In a 2-year trial in healthy older adults it added lean mass but did not improve strength, physical function or quality of life, and worsened insulin sensitivity. In Alzheimer's disease it produced a clear IGF-1 rise but did nothing to slow decline. In hip-fracture recovery the functional benefits were marginal and a congestive-heart-failure safety signal led to early termination. Merck discontinued it. Common effects include increased appetite, water retention, joint aches and raised blood sugar. **Technical.** MK-677 (ibutamoren mesylate; MK-0677; L-163,191) is a spiropiperidine non-peptidic agonist of the growth hormone secretagogue receptor (GHSR-1a), the endogenous ghrelin receptor. By mimicking ghrelin it amplifies GH release through dual action: augmenting GHRH signalling and attenuating somatostatin tone at the somatotrophs, producing increased pulsatile GH secretion and downstream rise in hepatic IGF-1. Its pharmacological distinction from injectable secretagogues (GHRPs, sermorelin, CJC-1295) is high oral bioavailability and prolonged half-life permitting oral administration. Human pharmacology is well characterised: trials consistently show roughly 60-73% increases in IGF-1 with preserved GH pulsatility. The clinical narrative is robust target engagement without clinical efficacy. Nass et al. (Ann Intern Med 2008; NCT00474279), a 2-year RCT in healthy adults aged 60-81, restored GH/IGF-1 toward young-adult levels and increased fat-free mass (~1.6 kg) but showed no improvement in muscle strength, function or quality of life and reduced insulin sensitivity. Sevigny et al. (Neurology 2008) randomised 563 mild-to-moderate Alzheimer's patients; despite a ~73% IGF-1 rise at 12 months there was no effect on ADAS-Cog, CIBIC-plus, ADCS-ADL or CDR-SB. The hip-fracture Phase 2b study (Adunsky et al. 2011) yielded marginal or inconsistent functional gains and a congestive-heart-failure safety signal that prompted early termination, contributing to Merck's discontinuation. Recognised adverse effects: increased appetite, fluid retention or oedema, arthralgia, transient elevations in fasting glucose and HbA1c, and reduced insulin sensitivity. These are biologically expected from sustained, non-physiologically-patterned GH/IGF-1 elevation and chronic GHSR agonism. ## How it is thought to work Non-peptide agonist of the growth hormone secretagogue receptor (GHSR-1a), the ghrelin receptor. By mimicking ghrelin at the hypothalamus and pituitary it increases pulsatile GH secretion through enhanced GHRH signalling and suppressed somatostatin tone, driving downstream rise in hepatic IGF-1. It is orally bioavailable with prolonged half-life, distinguishing it from injectable peptide secretagogues. ## Studied for Research contexts, not proven uses. - Body composition / fat-free mass in healthy older adults (aging research) - Sarcopenia and muscle wasting - Functional recovery after hip fracture - Cognitive decline in Alzheimer's disease (trial was negative) - Growth hormone secretion / diagnostic GH stimulation - Catabolic states and frailty ## What the human evidence shows Several completed human RCTs exist. The landmark 2-year trial in healthy older adults (Nass et al. 2008) confirmed it raises GH/IGF-1 and adds roughly 1.6 kg of fat-free mass, but found no gain in strength, physical function or quality of life and worsened insulin sensitivity. A 563-patient Alzheimer's RCT (Sevigny et al. 2008) showed clear biomarker engagement (about 73% IGF-1 rise) yet zero clinical benefit on any cognitive or functional endpoint. A Phase 2b hip-fracture trial (Adunsky et al. 2011) showed marginal or inconsistent functional effects and was terminated early after a congestive-heart-failure safety signal. Merck ran these programmes and then discontinued development. ## Concerns and unknowns - Not an approved medicine anywhere. Merck abandoned development after its trials failed to show clinical benefit. - Worsens insulin sensitivity and raises fasting glucose/HbA1c. A real diabetes-risk concern with sustained use. - Fluid retention and oedema. A congestive-heart-failure signal appeared in the hip-fracture trial and prompted early termination. - Sustained, non-physiological GH/IGF-1 elevation carries theoretical long-term risks (e.g. promoting growth of existing tumours). Long-term safety in healthy users is unknown. - Marked appetite stimulation and reports of lethargy or sleepiness are common. - Sold as an unlicensed research chemical with 'not for human consumption' labels to sidestep medicines law. No pharmaceutical-grade quality control over identity, purity or content. - WADA-prohibited at all times. Banned in sport. - Routinely marketed as a SARM or a peptide. It is neither. ## UK status Not a licensed medicine in the UK. It has no MHRA marketing authorisation and is not approved as a medicine anywhere in the world. It is an abandoned investigational drug now sold online as an unlicensed research chemical, typically labelled 'not for human consumption' to sidestep medicines law. Selling or supplying it for human use would fall foul of the Human Medicines Regulations 2012, which prohibit placing an unlicensed medicinal product on the market. It is not a controlled drug under the Misuse of Drugs Act, but it is neither legitimately obtainable nor prescribable. It is on the WADA Prohibited List as a growth hormone secretagogue. ## Sport / WADA Prohibited at all times (in and out of competition) as a growth hormone secretagogue under WADA Prohibited List section S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics). ## Key trials - **Effects of an Oral GH Secretagogue (MK-677) on Body Composition and Functional Ability of Older Adults** (NCT00474279, Phase 2, Completed (published Nass et al. 2008)). The 2-year aging RCT in adults aged 60-81: positive on lean mass, null on function, negative on insulin sensitivity. - **MK-677 in mild-to-moderate Alzheimer's disease** (Phase 2, Completed, negative (Sevigny et al., Neurology 2008)). 563 patients; target engagement (IGF-1 rise) without any clinical benefit. - **MK-0677 for recovery after hip fracture** (Phase 2b, Completed, terminated early (Adunsky et al. 2011)). Marginal functional effect; a CHF safety signal prompted early termination and contributed to programme discontinuation. ## Sources 1. Effects of an Oral Ghrelin Mimetic on Body Composition and Clinical Outcomes in Healthy Older Adults: A Randomized Trial. Nass R, Pezzoli SS, Oliveri MC, et al., Annals of Internal Medicine, 2008 2. Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial. Sevigny JJ, Ryan JM, van Dyck CH, et al., Neurology, 2008 3. MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study. Adunsky A, Chandler J, Heyden N, et al., Archives of Gerontology and Geriatrics, 2011 4. Ibutamoren (MK-677) — overview, pharmacology and clinical development. PubMed search (background) _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/mk-677 . Educational only, not medical advice. --- # MOTS-c **Evidence grade: D (Animal data only).** Area: Longevity. > A tiny peptide your own mitochondria produce during exercise, promising for metabolism in mice, but in humans only measured as a biomarker rather than proven to work as an injected drug. **Also known as:** Mitochondrial ORF of the 12S rRNA type-c, Mitochondrial-derived peptide (MDP), MOTSc, MOTS-C, mots c, exercise mimetic, mitochondrial peptide **Class:** Mitochondrial-derived peptide (MDP); endogenous mitochondrial-encoded signalling peptide ## Why this grade The therapeutic story rests almost entirely on rodent and cell studies. In mice, administered MOTS-c improves insulin sensitivity, resists diet-induced obesity and extends physical capacity into old age. The genuine human data is observational, not interventional. Circulating and muscle MOTS-c rises with exercise and falls in metabolic disease, but that tells us it is a biomarker, not that injecting it works. A first interventional human study (Phase 2a, NCT07505745) only registered in 2025 and has reported no efficacy results. As a treatment in humans, the evidence is effectively preclinical. Not an F because the mechanism is real and a registered controlled trial now exists. Firmly D until that trial reads out with positive data. ## In plain terms **Simple.** Your cells contain mitochondria, the little batteries that turn food into energy. Those batteries also make a tiny messenger called MOTS-c that tells the body to burn fuel more efficiently, a bit like the signals you get from exercising. In mice, giving extra MOTS-c kept them leaner, steadied their blood sugar and let them stay physically stronger into old age. That is why people got excited about it for ageing and metabolism. Almost all of that evidence is in animals. In humans we mostly know that MOTS-c naturally goes up when you exercise and tends to be low in people with diabetes. That is a useful clue, but very different from proving that buying and injecting it makes a healthy person healthier. A proper human trial has only just started, so right now this is a hopeful science story, not a proven treatment. **Standard.** MOTS-c is a 16-amino-acid peptide encoded not by your normal nuclear DNA but by your mitochondrial DNA, the separate little genome inside your cellular powerhouses. It acts like a stress-and-exercise signal. When energy demand rises, MOTS-c is produced and helps shift the body toward burning fuel and maintaining insulin sensitivity, partly by activating AMPK, the same low-fuel master switch that exercise and the diabetes drug metformin engage. In mice the results are striking. It blunts diet-induced obesity and insulin resistance, and late-in-life dosing improved physical capacity. In humans, the solid findings are correlational. MOTS-c rises in muscle and blood after exercise, and lower levels track with insulin resistance, diabetes and other metabolic problems. That makes it an interesting biomarker and a plausible drug target, but until recently nobody had run a controlled trial of giving it to people. A Phase 2a study in prediabetes and overweight/obesity is now registered and getting underway. The gap is large: exciting mechanism and animal data, essentially no human efficacy data yet, and everything currently sold to the public is unlicensed grey-market material. **Technical.** MOTS-c (mitochondrial ORF of the 12S rRNA type-c) is a 16-residue peptide translated from a short open reading frame within the mitochondrial 12S rRNA gene (MT-RNR1), one of the founding members of the mitochondrial-derived peptide (MDP) family alongside humanin and the SHLP series. Mechanistically (Lee et al., Cell Metabolism 2015) it modulates the folate–methionine one-carbon cycle and de novo purine biosynthesis. The resulting AICAR accumulation and altered AMP/ATP dynamics activate AMPK, driving GLUT4-mediated glucose uptake and a metabolic phenotype resembling exercise or caloric restriction, with skeletal muscle as a principal target. Under metabolic stress MOTS-c translocates to the nucleus and acts as a transcriptional regulator, associating with stress-response elements such as antioxidant response elements and influencing NRF2- and AMPK-dependent gene programmes (Kim et al., Cell Metabolism 2018). Reynolds et al. (Nature Communications 2021) showed exercise induces endogenous skeletal-muscle and circulating MOTS-c in humans and that intermittent administration improved healthspan and physical capacity in aged mice. Clinical translation is nascent. Human data remain observational (exercise induction; inverse association with HOMA-IR, HbA1c, T2D), with the first registered interventional efficacy study (Phase 2a, NCT07505745) in prediabetes with overweight/obesity using an OGTT-derived Matsuda index as primary endpoint. No pharmacokinetic or immunogenicity profile is established in a regulatory sense, and no efficacy endpoint has yet been met in humans. ## How it is thought to work Encoded within the mitochondrial 12S rRNA, MOTS-c is a 16-amino-acid mitochondrial-derived peptide that interferes with the folate one-carbon cycle and de novo purine synthesis, causing AICAR accumulation and activating the cellular energy sensor AMPK. This promotes glucose uptake via GLUT4 and a metabolic state resembling exercise. Under metabolic stress it translocates to the nucleus, where it regulates stress-response and antioxidant gene programmes including NRF2-linked pathways. Skeletal muscle is the principal target tissue. ## Studied for Research contexts, not proven uses. - Insulin sensitivity and prevention of insulin resistance (mostly rodent; one Phase 2a human trial registered/ongoing) - Diet-induced obesity and metabolic homeostasis (rodent) - Age-related physical decline and 'healthspan' (rodent) - Exercise physiology and skeletal-muscle adaptation (human observational biomarker) - Type 2 diabetes and metabolic disease as a circulating biomarker (human observational) ## What the human evidence shows Genuine human evidence is observational, not interventional. Studies show MOTS-c is induced in skeletal muscle and rises in the circulation after acute exercise, and that lower circulating levels correlate with insulin-resistance markers (HOMA-IR, HbA1c) and with type 2 diabetes, PCOS and other metabolic conditions. These establish MOTS-c as a biomarker and plausible target but do not show that administering it benefits people. As of mid-2026 the first registered controlled interventional efficacy trial (Phase 2a, NCT07505745, prediabetes with overweight/obesity) is registered and getting underway but has not reported results. No efficacy endpoint has yet been met in any human trial. ## Concerns and unknowns - Human efficacy is unproven. To date the only human data are observational or biomarker studies; no completed controlled trial shows benefit from administering it. - Everything sold to the public is unlicensed research chemical material labelled 'not for human consumption'. It is not a medicine and has no MHRA marketing authorisation. - Grey-market purity, sterility, dose accuracy and endotoxin contamination are real risks with injectable research peptides. Injection itself carries infection and abscess risk. - Long-term safety in humans is essentially unknown. Immunogenicity and the effects of chronic supraphysiological dosing are unstudied. - Marketing routinely extrapolates striking mouse longevity and metabolic data directly to humans, a classic overclaim the actual evidence does not support. - Circulating MOTS-c measurement by antibody has been debated within the science, complicating the biomarker literature. ## UK status Not a licensed medicine in the UK. MOTS-c has no MHRA marketing authorisation and is not approved for any indication. It is an investigational or preclinical agent. It is not a controlled drug, but selling or supplying it for human use would breach the Human Medicines Regulations 2012; vendors therefore market it as a research chemical or reference standard labelled not for human consumption. There is no legitimate UK prescription route. As an endogenous metabolic or exercise-mimetic peptide it also attracts anti-doping interest; anyone subject to sport testing should check current WADA guidance. For the general public the key fact is that it is an unlicensed, unregulated product. ## Sport / WADA Not specifically named on the WADA Prohibited List, but as an exercise-mimetic peptide affecting metabolism it sits in a category of interest; athletes subject to testing should seek explicit guidance rather than assume it is permitted. ## Key trials - **MOTS-c (MDP) subcutaneous injection in insulin resistance, prediabetes and overweight/obesity** (NCT07505745, Phase 2a, Registered 2025; getting underway as of 2026, with no efficacy results reported). Randomised, double-blind, placebo-controlled; primary endpoint OGTT-derived insulin sensitivity (Matsuda index); secondary endpoints include HbA1c, fasting/2-hour glucose and safety/immunogenicity. ## Sources 1. The Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis and Reduces Obesity and Insulin Resistance. Lee C, Zeng J, Drew BG, et al., Cell Metabolism, 2015 2. The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress. Kim KH, Son JM, Benayoun BA, Lee C, Cell Metabolism, 2018 3. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Reynolds JC, Lai RW, Woodhead JST, et al., Nature Communications, 2021 4. MOTS-c: review of mechanism and the preclinical-versus-human evidence gap for the mitochondrial-derived peptide. PubMed (review literature), 2022 5. MOTS-c (MDP), subcutaneous, in insulin resistance / prediabetes with overweight/obesity (Phase 2a). 2025 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/mots-c . Educational only, not medical advice. --- # Matrixyl (Palmitoyl Pentapeptide) **Evidence grade: C (Early / limited human data).** Area: Skin & Aesthetics. > A lab-made fragment of collagen, attached to a fatty acid so it can sink into skin, used in face creams to nudge skin cells into making a bit more collagen. **Also known as:** Palmitoyl Pentapeptide-4, Palmitoyl Pentapeptide-3 (pre-2006 INCI name), Pal-KTTKS, Matrixyl, Palmitoyl-Lys-Thr-Thr-Lys-Ser, matrixyl 3000, kttks **Class:** Topical cosmetic matrikine (lipidated collagen-fragment signal peptide) ## Why this grade Matrixyl has some genuine human data, including a published double-blind, vehicle-controlled, split-face randomised trial (Robinson 2005) plus smaller cosmetic studies showing modest reductions in fine lines versus the cream base. However, the evidence base is small and largely manufacturer-affiliated, built on cosmetic surrogate endpoints such as image analysis and profilometry rather than histological or clinically meaningful outcomes. This is real but limited human evidence (C), not the robust independent RCT base required for B or A grades. It remains a cosmetic ingredient, not a licensed medicine. ## In plain terms **Simple.** Matrixyl is a tiny piece of collagen (the protein that keeps skin firm) made in a lab and stuck onto a fatty molecule so it can sink into the skin. The idea is that when your skin spots this little fragment, it thinks some collagen has been damaged and makes fresh collagen to repair it. It is a cosmetic ingredient in anti-ageing creams, not a medicine and not an injection. The real-world effect on wrinkles is genuine but small and gradual, and the headline numbers you see in adverts are far more impressive than what most people would actually notice in the mirror. **Standard.** Matrixyl is the trade name (from Sederma) for a short peptide called pal-KTTKS, also listed as palmitoyl pentapeptide-4. KTTKS is a five-amino-acid fragment naturally released from type I procollagen during collagen synthesis. It acts as a feedback signal, or 'matrikine', instructing fibroblasts to produce more collagen and extracellular-matrix proteins. On its own, KTTKS cannot penetrate skin, so it is attached to palmitic acid (the 'palmitoyl' part) to help it cross the outer barrier. It is used at very low concentrations in topical anti-ageing products. A double-blind, vehicle-controlled, split-face trial (Robinson 2005) found measurable but modest improvements in fine lines compared to the base cream alone, with good tolerability. It remains a cosmetic ingredient with cosmetic-grade evidence, not a drug with proven clinical anti-ageing effects. **Technical.** Pal-KTTKS (palmitoyl pentapeptide-4; formerly INCI palmitoyl pentapeptide-3) is a synthetic matrikine: the pentapeptide Lys-Thr-Thr-Lys-Ser derived from the type I procollagen alpha-1 chain propeptide region, N-acylated with palmitic acid to confer lipophilicity and improve stratum corneum penetration. In cultured human dermal fibroblasts KTTKS upregulates synthesis of collagen I, III and fibronectin. The matrikine concept is mechanistically linked to TGF-beta-like feedback signalling, though the precise receptor and intracellular pathway in vivo remain incompletely defined. The pivotal human evidence is Robinson et al. (Int J Cosmet Sci 2005), a 12-week double-blind, vehicle-controlled, split-face RCT (n=93 women aged 35-55) of a low-concentration pal-KTTKS moisturiser reporting statistically significant reductions in wrinkle and fine-line parameters by quantitative image analysis and expert grading versus vehicle, with good tolerability. Foundational fibroblast and matrikine work is associated with Lintner & Peschard (Int J Cosmet Sci 2000). Limitations include small, mostly manufacturer-affiliated studies; surrogate cosmetic endpoints (profilometry, image analysis) rather than histological or clinically meaningful outcomes; modest effect sizes; and limited percutaneous delivery of even a lipidated pentapeptide, which is highly formulation-dependent. Commercial 'Matrixyl 3000' combines pal-KTTKS with palmitoyl tripeptide-1; published independent evidence for that combination is sparse and largely proprietary. ## How it is thought to work KTTKS is a fragment of type I procollagen that acts as a matrikine, a matrix-derived signal telling skin fibroblasts to increase production of collagen, fibronectin and other extracellular-matrix proteins. It mimics the feedback the skin receives during normal collagen turnover and repair. The peptide is conjugated to palmitic acid (palmitoylation) to make it lipophilic enough to cross the stratum corneum when applied topically. In vitro it upregulates collagen I and III and fibronectin synthesis. Mechanistically it is linked to TGF-beta-type feedback signalling, though the exact receptor and pathway in human skin in vivo are not fully characterised. ## Studied for Research contexts, not proven uses. - Reduction of fine lines and wrinkle depth in photoaged facial skin (topical cosmetic studies) - Improvement of skin texture, roughness and firmness - Stimulation of collagen and extracellular-matrix synthesis in cultured fibroblasts (in vitro) - Comparative cosmetic efficacy versus other anti-wrinkle peptides ## What the human evidence shows Genuine but limited. The anchor is Robinson et al. 2005 (International Journal of Cosmetic Science), a 12-week double-blind, vehicle-controlled, split-face randomised trial in 93 women showing statistically significant but modest reductions in fine lines and wrinkles by image analysis and expert grading versus the cream base alone, with good tolerability. A handful of further small cosmetic studies and head-to-head comparisons with other peptides exist, generally reporting modest improvements. The endpoints are cosmetic surrogates (profilometry, photographic image analysis), effect sizes are small, sample sizes are limited, and several studies are industry-affiliated. There are no large independent RCTs and no clinical outcomes such as histological or functional anti-ageing measures. Marketing claims such as 'wrinkle depth reduced 68 percent' or 'collagen up 117 percent' derive from in-vitro assays or selected cosmetic measures and substantially overstate what a typical user would perceive. ## Concerns and unknowns - Marketing hype vastly outstrips the data. Dramatic percentage claims come from in-vitro assays or cherry-picked cosmetic metrics, not from clinical outcomes. Real-world wrinkle improvement is modest. - Most efficacy studies are small and conducted or funded by the ingredient manufacturer or product makers. Independent confirmation is scarce. - Topical penetration of even a palmitoylated pentapeptide is limited. How much active peptide actually reaches the living dermis from a finished cream is uncertain and depends on formulation. - Endpoints are cosmetic surrogates (image analysis, profilometry) rather than clinically meaningful measures. - As a cosmetic ingredient there is no medicines-grade regulatory assessment of efficacy claims. Product quality, actual peptide content and stability vary between brands. - It is a topical cosmetic. Claims that it can be injected or used systemically are unsupported and fall outside how the ingredient was studied and how it is legally classified. ## UK status Matrixyl (palmitoyl pentapeptide-4) is sold legally in the UK as a cosmetic ingredient in topical skincare products. It is not a licensed medicine and is not regulated by the MHRA as a drug. Cosmetics are regulated under the UK Cosmetics Regulation (the retained EU Cosmetic Products Regulation), with enforcement led by the Office for Product Safety and Standards (OPSS) and Trading Standards. This framework governs product safety and labelling but does not assess therapeutic efficacy. No prescription is required, and there is no UK marketing authorisation for any medicinal anti-ageing claim. If a product were marketed for systemic or injectable use, or made medicinal claims, it would fall outside cosmetics law and into medicines regulation under the Human Medicines Regulations 2012. ## Sport / WADA Not relevant / not prohibited. Matrixyl is a topical cosmetic ingredient and does not appear on the WADA Prohibited List. ## Key trials - **Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin (Robinson 2005)** (Cosmetic RCT (not a regulated clinical-trial phase), Completed/published). 12-week, double-blind, vehicle-controlled, split-face randomised study, n=93 women aged 35-55; the single most-cited human efficacy study for Matrixyl. No NCT identifier (a cosmetic study, outside clinical-trial registration). ## Sources 1. Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin. Robinson LR, Fitzgerald NC, Doughty DG, Dawes NC, Berge CA, Bissett DL, International Journal of Cosmetic Science 27(3):155-160, 2005 2. Biologically active peptides: from a laboratory bench curiosity to a functional skin care product. Lintner K, Peschard O, International Journal of Cosmetic Science 22(3):207-218, 2000 3. Topical Peptide Treatments with Effective Anti-Aging Results. Schagen SK, Cosmetics (MDPI) 4(2):16, 2017 4. Palmitoyl pentapeptide-4 (overview, INCI history and trade-name origin). Wikipedia contributors, Wikipedia, 2024 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/matrixyl . Educational only, not medical advice. --- # Mazdutide **Evidence grade: B (Promising human evidence).** Area: Weight & Metabolic. > An injectable obesity drug, approved in China but not the UK, that mimics two gut hormones to suppress appetite and increase energy expenditure. **Also known as:** IBI362, LY3305677, OXM-3, mazdutide injection, maz, glp-1/glucagon **Class:** GLP-1 receptor / glucagon receptor dual agonist (oxyntomodulin analogue) ## Why this grade Genuinely strong human evidence by peptide standards. Multiple completed Phase 2 and Phase 3 randomised, placebo-controlled trials in Chinese adults (obesity and type 2 diabetes), including the GLORY-1 obesity trial published in the New England Journal of Medicine (2025). Marketing approval from China's NMPA for chronic weight management (June 2025) and for glycaemic control in type 2 diabetes (September 2025). The grade stops at B because the trial dataset is almost entirely Chinese, there is no UK/EU/US marketing authorisation, and no completed long-term cardiovascular outcome trial. Grade A is reserved for medicines with robust human RCTs also approved in major Western markets and with mature outcome data. ## In plain terms **Simple.** Mazdutide is a weekly injection that helps people lose weight. It mimics two natural hormones your gut makes after eating. One (GLP-1) tells your brain you're full, so you eat less, similar to Wegovy and Mounjaro. The second (glucagon) increases how much energy your body burns and helps clear fat from the liver. Chinese trials showed significant weight loss, and the medicine was approved there in 2025 for obesity and type 2 diabetes. It is not approved in the UK. Almost all testing was done in Chinese people, so how well the results apply to other populations remains unclear. In the UK it is only sold by grey-market vendors, usually labelled 'not for human consumption' with no guarantee of what is in the vial. **Standard.** Mazdutide (also IBI362) is a 'dual agonist' obesity drug. It activates two hormone receptors: the GLP-1 receptor (same target as semaglutide/Wegovy, which curbs appetite and slows the stomach) and the glucagon receptor (which raises energy expenditure and reduces liver fat). The glucagon component adds energy burning on top of reduced eating. It is based on oxyntomodulin, a natural gut hormone that activates both receptors. The human evidence is strong by the standards of most peptides on this site. The pivotal GLORY-1 obesity trial (New England Journal of Medicine 2025) reported roughly 14% mean weight loss over 48 weeks at its higher tested dose. A separate higher-dose Phase 3 trial (GLORY-2) reported around 20% loss. Side effects were mainly nausea, diarrhoea and vomiting, typically mild-to-moderate, similar to other GLP-1 drugs. China's NMPA approved it for chronic weight management in June 2025 and for type 2 diabetes in September 2025. It is not approved in the UK, and almost all trial participants were Chinese, so how well results generalise to other populations is unclear. There is no completed long-term cardiovascular outcome trial. **Technical.** Mazdutide (IBI362; originally Eli Lilly's LY3305677, an oxyntomodulin/OXM-3 analogue, licensed to Innovent Biologics for Greater China) is a unimolecular dual agonist of GLP-1R and GCGR. The GLP-1R component drives glucose-dependent insulinotropic action, delayed gastric emptying and central anorexigenic signalling. The GCGR component increases energy expenditure, promotes hepatic lipid oxidation and reduces hepatic steatosis; its potential to raise glucose is counterbalanced by GLP-1R-mediated insulin secretion. The molecule carries a fatty-acid chain conferring albumin binding and a once-weekly pharmacokinetic profile. Human evidence is substantial: a dose-escalation Phase 1b multiple-ascending-dose RCT (eClinicalMedicine 2022), a two-part Phase 2 RCT in overweight/obesity (Nature Communications 2023), and Phase 3 programmes including GLORY-1 in overweight/obesity (NEJM 2025; ~14% mean weight reduction over 48 weeks at the higher of two tested levels), the higher-dose GLORY-2 trial (top-line ~20% reduction reported), and back-to-back Phase 3 type 2 diabetes trials published in Nature (2025). Reported safety comprises predominantly gastrointestinal treatment-emergent adverse events (nausea, diarrhoea, vomiting), low discontinuation, modest mean heart-rate increase, and reductions in hepatic fat fraction attributed to GCGR engagement. NMPA approval for chronic weight management was granted in June 2025 and for glycaemic control in type 2 diabetes in September 2025; a higher-dose supplementary application for moderate-to-severe obesity is under review. No MHRA/EMA/FDA marketing authorisation exists. Principal evidentiary gaps include the near-exclusively Chinese trial populations, absence of a completed cardiovascular outcome trial, and limited long-term safety data on chronic GCGR agonism. ## How it is thought to work A synthetic analogue of the gut hormone oxyntomodulin that activates the GLP-1 receptor (reducing appetite, slowing gastric emptying, enhancing glucose-dependent insulin release) and the glucagon receptor (increasing energy expenditure and promoting hepatic fat breakdown). It is given as a once-weekly subcutaneous injection. Fatty-acid acylation extends its half-life via albumin binding. ## Studied for Research contexts, not proven uses. - Chronic weight management in adults with overweight or obesity - Glycaemic control in type 2 diabetes - Reduction of hepatic fat / metabolic-associated fatty liver - Cardiometabolic risk factor improvement ## What the human evidence shows Strong by the standards of most peptides on this site. Mazdutide has completed multiple randomised, placebo-controlled human trials. An early Phase 1b dose-escalation study and a two-part Phase 2 trial in Chinese adults were published in eClinicalMedicine (2022) and Nature Communications (2023) respectively. The pivotal Phase 3 GLORY-1 obesity trial (610 Chinese adults) was published in the New England Journal of Medicine in 2025, reporting around 14% mean weight loss over 48 weeks at its higher tested level, with a low discontinuation rate. A separate higher-dose Phase 3 trial (GLORY-2) reported top-line mean weight loss of roughly 20%. Two Phase 3 type 2 diabetes trials were published back-to-back in Nature in 2025. China's NMPA approved mazdutide for chronic weight management in June 2025 and for glycaemic control in type 2 diabetes in September 2025. Trial populations were almost entirely Chinese, so efficacy and safety in other ethnic groups are not yet established. There is no completed long-term cardiovascular outcome trial. ## Concerns and unknowns - Not licensed by the MHRA, EMA or FDA. Approval to date is China-only (NMPA, 2025); any UK supply is unlicensed. - Material sold to UK consumers as 'mazdutide' from research-chemical vendors is unregulated, of unverified identity, purity and sterility, and typically labelled 'not for human consumption'. - Almost all clinical evidence comes from Chinese populations; how well it generalises to other groups is unproven. - No completed long-term cardiovascular outcome data. Chronic glucagon-receptor agonism is a relatively new mechanism with limited very-long-term safety follow-up. - Gastrointestinal adverse events (nausea, vomiting, diarrhoea) are common, as with all GLP-1 class drugs. A small mean heart-rate increase has been observed. - Glucagon agonism can theoretically raise blood glucose and affect hepatic metabolism. Trials used careful medical monitoring that unsupervised self-administration bypasses. - Class-wide GLP-1 cautions apply: pancreatitis signal, gallbladder events, and the thyroid C-cell tumour signal seen in rodents for the class. ## UK status Not a licensed medicine in the UK. Mazdutide holds marketing approval only from China's NMPA (chronic weight management, June 2025; type 2 diabetes, September 2025). It has no MHRA, EMA or FDA authorisation. In UK terms it is an unlicensed/investigational drug. It is not available on the NHS or by private prescription, and any material sold online to UK buyers is an unlicensed 'research chemical', typically labelled 'not for human consumption' and entirely outside MHRA quality oversight. ## Key trials - **GLORY-1: efficacy and safety of mazdutide in Chinese participants with overweight or obesity** (Phase 3, Completed / published (NEJM 2025); supported NMPA approval). 610 Chinese adults; mazdutide at two dose levels vs placebo over 48 weeks; primary weight-loss endpoints met. - **GLORY-2: higher-dose mazdutide in Chinese adults with moderate-to-severe obesity** (Phase 3, Top-line results reported (~20% mean weight loss); primary and key secondary endpoints met). Higher-dose programme supporting a supplementary NMPA application. - **Mazdutide Phase 3 programme in Chinese adults with type 2 diabetes** (Phase 3, Completed; two trials published back-to-back in Nature (2025); supported NMPA diabetes approval). Glycaemic control and weight outcomes in type 2 diabetes. ## Sources 1. Mazdutide for Chinese adults with overweight or obesity (GLORY-1): a randomised, double-blind, placebo-controlled phase 3 trial. New England Journal of Medicine, 2025 2. A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity. Nature Communications, 2023 3. Safety and efficacy of a GLP-1 and glucagon receptor dual agonist mazdutide (IBI362) 9 mg and 10 mg in Chinese adults with overweight or obesity: a randomised, placebo-controlled, multiple-ascending-dose phase 1b trial. eClinicalMedicine (Lancet Discovery Science), 2022 4. Innovent Announces Mazdutide, First Dual GCG/GLP-1 Receptor Agonist, Received Approval from China's NMPA for Chronic Weight Management. Innovent Biologics / PR Newswire, 2025 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/mazdutide . Educational only, not medical advice. --- # Melanotan I (Afamelanotide) **Evidence grade: A (Approved / strong human evidence).** Area: Skin & Aesthetics. > A synthetic copy of a natural hormone that activates skin pigmentation. The same molecule is an approved medicine for a rare phototoxic disease and, separately, an unlicensed grey-market tanning product. **Also known as:** Afamelanotide, Scenesse, Melanotan-1, MT-I, MT-1, [Nle4-D-Phe7]-alpha-MSH, NDP-MSH, CUV1647, mt1, melanotan i **Class:** Synthetic alpha-melanocyte-stimulating hormone (alpha-MSH) analogue; melanocortin-1 receptor (MC1R) agonist (tridecapeptide) ## Why this grade As the licensed medicine afamelanotide (Scenesse), it is supported by randomised, double-blind, placebo-controlled Phase 3 trials and holds EMA (2014) and FDA (2019) approval for erythropoietic protoporphyria (EPP). This grade A applies only to the approved, controlled-release subcutaneous implant for EPP. It does not validate grey-market self-injected Melanotan I powder used for cosmetic tanning, which has no approval, no quality control, and no robust human safety or efficacy data. If graded independently, the grey-market product would be a D. ## In plain terms **Simple.** Your body makes a hormone that tells skin cells to produce brown pigment (melanin), which protects you from the sun. Melanotan I is a man-made, longer-lasting version of that hormone. It exists in two forms. In one form, packed into a tiny implant placed under the skin by a doctor, it is an approved medicine called Scenesse. It is given to people with a rare condition where sunlight causes severe pain. More pigment shields them from this reaction. The exact same molecule is also sold online as a tanning injection powder you mix and inject yourself. That version is not approved, not quality-checked, and UK regulators have warned against it. The science behind the medicine is solid. The unregulated tanning version is not. **Standard.** Melanotan I is afamelanotide, a synthetic version of alpha-melanocyte-stimulating hormone (alpha-MSH). It switches on the MC1R receptor on pigment cells, driving production of eumelanin (the protective brown pigment). It exists in two completely different worlds. As a licensed medicine (brand name Scenesse, made by Clinuvel) it is a slow-release implant inserted by a clinician, approved by the EMA in 2014 and the FDA in 2019 to reduce painful sunlight reactions in erythropoietic protoporphyria (EPP), a rare inherited disorder. This approval rests on randomised controlled trials. Separately, the same peptide is sold as grey-market injectable powder for cosmetic tanning. That version is unlicensed, unregulated, and warned against by the UK MHRA. People often confuse Melanotan I with Melanotan II; they are different molecules. MT-II acts on more melanocortin receptors and is more associated with the cosmetic-injection and libido market. The evidence grade A here belongs to the regulated implant for a specific disease, not to a tan-in-a-vial bought online. **Technical.** Afamelanotide ([Nle4-D-Phe7]-alpha-MSH, NDP-MSH) is a synthetic tridecapeptide analogue of alpha-MSH. Substitutions of norleucine at position 4 and D-phenylalanine at position 7 confer metabolic stability and prolonged, potent agonism at the melanocortin-1 receptor (MC1R). MC1R activation on epidermal melanocytes raises intracellular cAMP, upregulating MITF and the eumelanogenic enzymes (tyrosinase, TYRP1, DCT) and shifting melanogenesis toward photoprotective eumelanin. Proposed ancillary effects include enhanced nucleotide-excision DNA repair, antioxidant induction and immunomodulation. Clinuvel developed the molecule as a bioresorbable, controlled-release subcutaneous implant. Pivotal evidence comes from randomised, double-blind, placebo-/vehicle-controlled US (CUV039) and European (CUV029) Phase 3 trials reported by Langendonk et al. (NEJM 2015), which showed increased pain-free direct-sunlight exposure in EPP. Supportive long-term observational data exist. Regulatory: EMA approval 2014 (Scenesse, EPP), FDA approval 2019. In the UK, NICE (HST27) did not recommend it for routine NHS use in England on cost-effectiveness grounds, whereas the SMC accepted it for NHS Scotland via the ultra-orphan pathway. Distinct from Melanotan II, a cyclic heptapeptide with broader melanocortin agonism (MC1R/MC3R/MC4R) tied to the cosmetic/libido grey market. Self-administered illicit lyophilised MT-I of unverified identity and purity used for tanning has effectively no controlled human data. ## How it is thought to work Afamelanotide is a stable, potent agonist of the melanocortin-1 receptor (MC1R) on melanocytes. Binding raises intracellular cAMP, activating the MITF transcription pathway and melanin-synthesis enzymes (notably tyrosinase). This increases production of photoprotective eumelanin. The resulting skin darkening, together with proposed antioxidant, DNA-repair and anti-inflammatory effects, reduces phototoxic reactions in EPP. The same pigment-driving mechanism is why it is misused cosmetically as a tanning agent. Clinically it is delivered as a slow-release subcutaneous implant. Grey-market cosmetic use involves self-injection. ## Studied for Research contexts, not proven uses. - Prevention of phototoxicity in erythropoietic protoporphyria (EPP) - the approved indication - Vitiligo, in combination with phototherapy (investigational) - Other photodermatoses and UV-related skin conditions (investigational) - Cosmetic skin tanning - the grey-market, non-medical use, which is not a validated indication ## What the human evidence shows Strong for the approved use, weak-to-absent for cosmetic use. For EPP, two randomised, double-blind, placebo-/vehicle-controlled Phase 3 trials (US CUV039 and European CUV029, reported in NEJM 2015) showed the implant increased pain-free direct-sunlight exposure. This underpins EMA (2014) and FDA (2019) approval. Long-term observational data support sustained benefit and tolerability. Vitiligo and other photodermatoses have been explored in investigational studies. There is essentially no robust human trial evidence for the safety or efficacy of self-injected grey-market Melanotan I powder for cosmetic tanning. That practice has never been through controlled trials and uses an unregulated product of unknown identity, content and purity. ## Concerns and unknowns - Two products, one name: the rigorous evidence belongs to the regulated Scenesse implant for EPP, not to injectable grey-market tanning powder. Do not let the approval launder the illicit product. - Grey-market Melanotan I is unlicensed in the UK. The MHRA has warned that its safety is unknown and that supplying or advertising it is illegal. - Unregulated injectable peptide powders carry risks of contamination, variable content, non-sterile reconstitution and injection-site infection. - Frequent confusion with Melanotan II (a different, broader-acting molecule more linked to cosmetic injection and reports of darkening or changing moles, nausea and priapism). - Stimulating melanocytes raises a theoretical concern about existing moles and melanoma surveillance. New or changing pigmented lesions warrant dermatological review. - Common labelled adverse effects of the approved implant include headache, nausea, fatigue and implant-site reactions. - NHS access to the approved drug is restricted. NICE did not recommend Scenesse for routine NHS use in England, while the SMC accepted it for NHS Scotland via the ultra-orphan pathway. Even legitimate patients can face access hurdles depending on where they live. ## UK status Split status. As afamelanotide (Scenesse), it is a licensed, prescription-only medicine in the UK/EU (EMA approval 2014) for preventing phototoxicity in adults with EPP. It is supplied as a clinician-administered subcutaneous implant. NICE (guidance HST27) did not recommend it for routine NHS use in England on cost-effectiveness grounds. The Scottish Medicines Consortium accepted it for NHS Scotland under the ultra-orphan medicines pathway. Access differs by nation. The same molecule sold as injectable Melanotan I powder for cosmetic tanning is an unlicensed medicinal product. The MHRA has warned that its safety is unknown and that advertising or supplying it in the UK is illegal. It is not a legal cosmetic. When marketed for tanning it is an unauthorised medicinal product. ## Sport / WADA Not specifically prohibited as such; afamelanotide is not a recognised performance-enhancing agent. (Verify current WADA Prohibited List for definitive status.) ## Key trials - **Phase 3 study of afamelanotide implant in EPP (United States, CUV039)** (NCT01605136, Phase 3, Completed). One of the pivotal vehicle-controlled EPP trials reported in NEJM 2015. ## Sources 1. Afamelanotide for Erythropoietic Protoporphyria. Langendonk JG, Balwani M, Anderson KE, et al., New England Journal of Medicine, 2015 2. Afamelanotide: A Review in Erythropoietic Protoporphyria. Kim ES, Garnock-Jones KP, American Journal of Clinical Dermatology, 2016 3. SCENESSE (afamelanotide) implant, for subcutaneous use - FDA prescribing information. US FDA, 2019 4. Afamelanotide for treating erythropoietic protoporphyria (HST27). NICE (National Institute for Health and Care Excellence), 2023 5. MHRA / public-health warnings on unlicensed Melanotan tanning products. UK MHRA and contemporaneous reporting _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/melanotan-1 . Educational only, not medical advice. --- # Melanotan II **Evidence grade: C (Early / limited human data).** Area: Skin & Aesthetics. > An unlicensed injectable peptide that darkens skin without sun exposure, sold illegally in the UK and linked to nausea, prolonged erections and worrying changes in moles. **Also known as:** MT-II, MT2, Melanotan 2, MTII, the 'Barbie drug', tanning jab, mt-2, barbie drug, tanning peptide, tanning injection, melanotan ii **Class:** Synthetic cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone (alpha-MSH); non-selective melanocortin receptor agonist ## Why this grade Melanotan II reliably produces skin tanning in humans and genuine early human data exists (small studies in the 1990s-2000s and an extensive case-report literature), so it clears the bar for D. However, it was never approved, no completed late-phase efficacy and safety programme exists for tanning, and the human dataset is small and old. Most current knowledge comes from adverse-event case reports of unregulated grey-market use rather than controlled trials. This combination of real but early and limited human data, no approval, and a growing harm signal places it at C, not B. ## In plain terms **Simple.** Melanotan II is a lab-made copy of a natural body signal that tells your skin to make more brown pigment. People inject it to go darker without the sun. It does work, but it is not a medicine you can legally buy in the UK. Nobody checks what is actually in the vials sold online. It comes with real downsides: feeling sick, your face flushing, moles darkening or new ones appearing. In men, erections can become painfully prolonged. Doctors have reported skin cancers in some people who used it. The idea that it gives you a safer tan is misleading. **Standard.** Melanotan II is a synthetic version of alpha-MSH, the hormone that signals skin cells (melanocytes) to produce melanin, the pigment that darkens skin. Injecting it triggers tanning even with minimal sun exposure. It earned the nickname the 'Barbie drug' for this reason. It is not a licensed product and it is illegal to sell for human use in the UK. What people buy online is an unregulated 'research chemical' of unknown purity and sterility. Because the drug also activates receptors involved in appetite and sexual function, reported effects include nausea, facial flushing, darkening of moles and freckles, and in men spontaneous erections that can become dangerously prolonged (priapism). Published reports describe new atypical moles and melanoma (skin cancer) appearing in users. Any claim that it offers a protective tan is not supported by evidence. **Technical.** Melanotan II is a cyclic alpha-MSH-derived heptapeptide and non-selective agonist at melanocortin receptors MC1R, MC3R, MC4R and MC5R. MC1R activation on epidermal melanocytes drives eumelanogenesis via the cAMP–PKA–MITF pathway, producing facultative pigmentation largely independent of UV. MC4R agonism in the CNS underlies pro-erectile and anorectic effects. This pharmacology is shared with bremelanotide/PT-141, an MC4R-preferring analogue later licensed for premenopausal women with acquired generalised hypoactive sexual desire disorder. Melanotan II was originally investigated at the University of Arizona as a sunless tanning agent and potential photoprotection strategy but was never approved for any indication. Contemporary clinical knowledge comes from case reports and small series of unregulated use: hyperpigmentation and rapid darkening, eruptive and dysplastic melanocytic naevi, melanoma (cutaneous and mucosal), ischaemic priapism, nausea and vomiting, and acute systemic toxicity including hypertension and rhabdomyolysis. Theoretical oncological concern centres on melanocyte proliferation in a population that self-selects for high UV exposure; causation versus surveillance bias for naevus findings remains unresolved. Purity, sterility and content of grey-market product are uncontrolled, adding injection-related and blood-borne infection risk. ## How it is thought to work Non-selective agonism at melanocortin receptors. MC1R activation on melanocytes upregulates melanin synthesis (eumelanogenesis) via the cAMP–PKA–MITF pathway, producing UV-independent skin darkening. MC4R agonism in the central nervous system drives appetite suppression and erectile responses. MC3R and MC4R activity contribute to cardiovascular and sympathetic effects. Typically administered by subcutaneous injection; unregulated use also occurs as nasal spray. ## Studied for Research contexts, not proven uses. - Sunless / UV-independent skin tanning - Photoprotection against UV damage (early academic rationale) - Erectile response (early studies of the MC4R activity that led to the related licensed drug bremelanotide/PT-141) - Appetite and energy-balance effects via MC4R (mechanistic interest only) ## What the human evidence shows Real but limited and old. Small human studies in the 1990s and 2000s confirmed that Melanotan II produces measurable skin darkening and explored its erectile effects. The same melanocortin pharmacology produced a licensed cousin, bremelanotide/PT-141, for premenopausal women with acquired generalised hypoactive sexual desire disorder. Melanotan II itself was never taken through completed late-stage efficacy and safety trials and was never approved. Most current knowledge comes from case reports describing harms in people using unregulated product: nausea and vomiting, facial flushing, mole darkening, eruptive and atypical naevi, cutaneous and mucosal melanoma, ischaemic priapism, and acute systemic toxicity including hypertension and rhabdomyolysis. There is no controlled evidence that it is safe for cosmetic use. ## Concerns and unknowns - Unlicensed and illegal to sell or supply for human use in the UK; grey-market vials have unknown purity, content and sterility - Multiple published case reports of melanoma (cutaneous and mucosal) and eruptive/atypical moles in users; any 'protective tan' claim is not supported - Ischaemic priapism in men, which can require emergency intervention and may cause lasting erectile dysfunction - Acute systemic toxicity reported: hypertension, tachycardia, severe nausea/vomiting, rhabdomyolysis - Non-sterile injecting and shared equipment carry blood-borne infection risk - Users tend to self-select for high UV/sunbed exposure, compounding melanocyte stimulation in an already higher-risk group - Nasal-spray formulations sold online add mucosal exposure, with at least one reported case of oral mucosal melanoma ## UK status Not a licensed medicine in the UK. Melanotan II is an unlicensed product and it is illegal to sell or supply it for human use. The MHRA has repeatedly warned the public not to use unlicensed tanning injections or nasal sprays containing melanotan and has acted to shut down supplying websites. It is sold online as a 'research chemical' labelled 'not for human consumption', a tactic to sidestep medicines regulation but one that does not make human use safe or legal. There is no legitimate prescription route for cosmetic tanning. ## Sources 1. Melanotropic peptides: more than just 'Barbie drugs' and 'sun-tan jabs'?. Langan EA, Nie Z, Rhodes LE, British Journal of Dermatology, 2010 2. Melanotan-associated melanoma. Paurobally D, Jason F, Dezfoulian B, et al., British Journal of Dermatology, 2011 3. alpha-Melanocyte-stimulating hormone-induced eruptive nevi. Cardones AR, Grichnik JM, Archives of Dermatology, 2009 4. Melanotan Tanning Injection: A Rare Cause of Priapism. Mallory CW, Lopategui DM, Cordon BH, Sexual Medicine, 2021 5. Melanotan II nasal spray: a possible risk factor for oral mucosal malignant melanoma?. International Journal of Oral and Maxillofacial Surgery, 2025 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/melanotan-2 . Educational only, not medical advice. --- # N-Acetyl Semax Amidate **Evidence grade: D (Animal data only).** Area: Cognition & Mood. > A chemically tweaked, longer-lasting version of the Russian nootropic peptide Semax, sold online for focus and brain health but never tested in a human trial in its own right. **Also known as:** NASA, NA-Semax Amidate, N-Acetyl Semax, na semax amidate, acetyl semax, semax amidate **Class:** Modified synthetic heptapeptide (N-terminally acetylated, C-terminally amidated analogue of Semax, itself an ACTH(4-10) derivative) ## Why this grade No human trials exist on NASA itself; the chemical modifications are an unstudied tweak. Even the parent compound Semax has only limited, mostly Russian-language human data of modest quality. ## In plain terms **Simple.** NASA is a souped-up version of a Russian brain peptide called Semax. Scientists took Semax and added two tiny chemical 'caps' to its ends so the body breaks it down more slowly, the idea being it lasts longer and works harder. People online spray it up their nose hoping it sharpens focus and protects the brain. The honest catch: while the original Semax was actually given to patients in Russia, this modified NASA version has never been properly tested in people at all. So you'd be trusting a lab idea, not a proven result. **Standard.** N-Acetyl Semax Amidate (NASA) is a modified form of Semax, a heptapeptide derived from a fragment of the hormone ACTH that Russia has used since the 1990s for stroke and cognitive problems. The 'N-acetyl' and 'amidate' refer to chemical caps added to the two ends of the molecule, which slow enzymatic breakdown and are claimed to extend how long it lasts and improve how well it crosses into the brain. In the nootropic community it is taken (usually as a nasal spray) for focus, mood and neuroprotection. Crucially, those longer-lasting claims are inferred from chemistry and animal-style reasoning, not from trials: NASA itself has no published human studies, and even Semax's human evidence is thin, mostly Russian-language, and often methodologically weak. **Technical.** NASA is a doubly-modified Semax analogue. Semax is Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP), a synthetic ACTH(4-10) fragment retaining neurotrophic/nootropic activity while shedding corticotropic (steroidogenic) action. N-terminal acetylation and C-terminal amidation are conventional strategies to blunt aminopeptidase and carboxypeptidase cleavage and increase metabolic half-life and lipophilicity/BBB partitioning. Proposed pharmacodynamics (extrapolated from Semax): rapid upregulation of hippocampal BDNF and TrkB phosphorylation and NGF; inhibition of enkephalin-degrading enzymes (Semax IC50 ~10 microM) prolonging endogenous opioid peptide signalling; modulation of serotonergic/dopaminergic tone; and possible melanocortin (MC4/MC5) interactions. No published pharmacokinetic, receptor-occupancy, or clinical efficacy data exist for the acetylated/amidated analogue specifically; the assumption that the modifications translate to superior clinical effect is untested. ## How it is thought to work Semax derives from the ACTH(4-10) fragment but lacks the hormone's steroid-stimulating activity. In animal and in-vitro work it rapidly raises brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the hippocampus, increases nerve growth factor (NGF), and inhibits the enzymes that break down enkephalins, which may prolong endogenous opioid and regulatory-peptide signalling. It also appears to modulate dopamine and serotonin systems. The N-acetyl and amidate modifications in NASA are intended to protect the peptide from being chopped up by the body's peptidases, lengthening its half-life and improving brain penetration. This proposed mechanism is inferred from the parent compound and from chemistry; it has not been confirmed for NASA itself. ## Studied for Research contexts, not proven uses. - Cognitive enhancement / focus and attention - Neuroprotection after ischaemic stroke (parent Semax) - Mild cognitive impairment (parent Semax) - Mood and stress resilience ## What the human evidence shows There are no published human trials of N-Acetyl Semax Amidate itself — every claim made for it borrows from the parent compound Semax. Semax's own human evidence is limited and comes almost entirely from Russia, where it has been a registered drug since the 1990s. Reported studies include small randomised work suggesting improved attention and short-term memory in healthy volunteers, and trials in acute ischaemic stroke reporting faster neurological recovery when given intranasally early after onset. A 2018 resting-state fMRI study in healthy volunteers (PMID 30225715) did show measurable changes in default-mode-network activity after intranasal Semax versus placebo, confirming it does something to the brain — but that is a mechanistic readout, not proof of clinical benefit. Most of this literature is Russian-language, small, and not replicated to Western regulatory standards. The bottom line: the modified NASA molecule is essentially untested in people. ## Concerns and unknowns - No human safety or efficacy data on the acetylated/amidated analogue specifically — you are first-in-line. - Sold as an unlicensed 'research chemical'; purity, dose and even correct identity are unverified and unregulated in the UK. - Most supporting human data is for a different (parent) molecule, is Russian-language, small, and methodologically weak. - Long-term effects of chronically raising BDNF and manipulating neurotrophin and opioid-peptide systems in healthy people are unknown. - Intranasal self-administration of grey-market peptides carries contamination and dosing-error risks. - Marketed online with confident nootropic claims that outrun the actual evidence. ## UK status N-Acetyl Semax Amidate is not a licensed medicine in the UK and has not been authorised or assessed by the MHRA. Neither it nor Semax holds a UK marketing authorisation. Sold as an unlicensed "research chemical," it cannot lawfully be marketed or supplied for human use as a medicine under the Human Medicines Regulations 2012; products are typically labelled "not for human consumption" to sidestep this. It is not a controlled drug, but buying it does not make self-administration safe or legal in any medicinal sense — there is no regulated product, no quality assurance and no clinical oversight. ## Sport / WADA Not listed by name on the WADA Prohibited List. However, as an unapproved peptide with no marketing authorisation by any government health authority, it could fall foul of section S0 ("non-approved substances"), which prohibits any pharmacological substance not currently approved for human therapeutic use. Athletes in tested sport should treat it as off-limits. ## Key trials - **No registered or completed clinical trials of N-Acetyl Semax Amidate (NASA) could be identified** (None found). Human trial activity, where it exists, concerns the parent compound Semax, largely conducted in Russia and reported in Russian-language literature. ## Sources 1. Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Dolotov OV, Karpenko EA, Inozemtseva LS, et al., Brain Research, 2006 2. Semax and selank inhibit the enkephalin-degrading enzymes from human serum. Kost NV, Sokolov OIu, Gabaeva MV, et al., Bioorganicheskaia Khimiia, 2001 3. Effects of Semax on the Default Mode Network of the Brain. Lebedeva IS, Panikratova YaR, Sokolov OYu, et al., Bulletin of Experimental Biology and Medicine, 2018 4. Semax (Wikipedia overview: structure, mechanism, Russian regulatory status) 5. PubMed search: N-acetyl Semax amidate human evidence _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/n-acetyl-semax-amidate . Educational only, not medical advice. --- # NAD+ **Evidence grade: C (Early / limited human data).** Area: Longevity. > A coenzyme your cells already make and use for energy and DNA repair; levels fall with age, so people take it (or its precursors) hoping to turn back the clock, but the human anti-ageing evidence is thin. **Also known as:** nad, nad plus, nicotinamide adenine dinucleotide, nad iv, nad+ infusion, nad therapy **Class:** Endogenous coenzyme (nicotinamide adenine dinucleotide); not a peptide. Administered directly by IV/injection, or raised indirectly via precursor vitamins (NR, NMN, niacin) ## Why this grade Human trials confirm NAD+ levels can be raised and that precursors are safe, but robust evidence for anti-ageing or clinical benefit in humans is largely absent; most efficacy claims rest on animal data. ## In plain terms **Simple.** NAD+ is a tiny helper molecule that every cell in your body already makes. It's a bit like a battery pack the cell plugs into to turn food into energy and to fix damaged DNA. As you get older, your levels of it drop, and scientists noticed that older, tired cells tend to have less of it. So a whole industry sprang up selling NAD+ drips, injections and pills that claim to top you back up and make you feel young again. Here's the honest bit: scientists can prove the levels go up, and in mice it does some impressive-looking things. But in actual humans, nobody has properly shown it makes you live longer, look younger or fixes much at all. It's promising, but it's nowhere near proven. **Standard.** NAD+ (nicotinamide adenine dinucleotide) is a coenzyme central to cellular metabolism: it shuttles electrons in the reactions that turn food into ATP, and it's the fuel for repair and signalling enzymes like the sirtuins and PARPs. Tissue NAD+ declines with age, which led to the popular theory that 'topping it up' could slow ageing. You can't easily get whole NAD+ into cells by mouth, so it's sold two ways: directly as IV infusions or injections (popular in private wellness clinics), or indirectly via precursor vitamins like nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), which cells convert into NAD+. The genuinely solid human findings are narrow: precursor supplements reliably raise blood NAD+ and are well tolerated over months. What's missing is proof that this raised level translates into the headline benefits — more energy, longevity, reversed ageing, better brains. Most of those claims come from rodents, not people. IV NAD+ is barely studied beyond tiny safety/pharmacokinetic pilots. Treat the marketing as far ahead of the science. **Technical.** NAD+ is the obligate redox cofactor for hundreds of oxidoreductases (glycolysis, the TCA cycle, oxidative phosphorylation, fatty-acid oxidation) and the consumed substrate for NAD+-dependent signalling enzymes — the sirtuins (SIRT1-7), PARPs, and the NADases CD38/CD157/SARM1. Intracellular NAD+ is synthesised de novo from tryptophan and, dominantly, salvaged from nicotinamide via the NAMPT-catalysed rate-limiting step, plus the Preiss-Handler pathway from nicotinic acid and the NRK route from NR. Age-related NAD+ decline is attributed to rising NADase activity (notably CD38 upregulation, which depletes NAD+ and impairs SIRT3-dependent mitochondrial function) alongside reduced salvage capacity. The therapeutic rationale is that restoring NAD+ reactivates sirtuin/PARP-mediated mitochondrial biogenesis, genome maintenance and stress resistance. Human pharmacology is the crux: oral NR/NMN dose-dependently elevate whole-blood NAD+ and the NAD+ metabolome and are well tolerated, but RCTs to date show, at best, modest exploratory signals (e.g. blood pressure, arterial stiffness) and no robust functional or longevity endpoints. IV NAD+ pharmacokinetics show near-complete first-pass extraction with delayed appearance of intact plasma NAD+, raising mechanistic questions about how much intact dinucleotide reaches tissues versus being catabolised to nicotinamide and salvaged. Compartmentalisation (cytosolic vs mitochondrial vs nuclear pools, transporter SLC25A51) and the precursor-versus-direct-delivery debate remain unresolved. ## How it is thought to work NAD+ works in two distinct modes. As a redox coenzyme it cycles between NAD+ and NADH to carry electrons through the metabolic pathways (glycolysis, TCA cycle, oxidative phosphorylation) that generate cellular ATP. As a signalling substrate it is consumed by enzymes — the sirtuins (which deacetylate proteins controlling mitochondrial biogenesis, stress resistance and gene expression), the PARPs (DNA repair), and NADases such as CD38. With age, tissue NAD+ falls, partly through increased CD38-driven consumption and reduced salvage synthesis, and this decline is linked in animal models to mitochondrial dysfunction. The intended therapeutic effect is to restore NAD+ — directly by infusion/injection, or indirectly by feeding cells precursors (NR, NMN, niacin) that are enzymatically converted to NAD+ — thereby reactivating sirtuin- and PARP-dependent repair and metabolic programmes. ## Studied for Research contexts, not proven uses. - Ageing and 'cellular rejuvenation' - Metabolic health (insulin sensitivity, fatty liver) - Cardiovascular markers (blood pressure, arterial stiffness) - Neurodegeneration (Parkinson's, Alzheimer's — ongoing trials) - Fatigue and 'wellness' (clinic IV drips) - Addiction/withdrawal recovery (claimed, largely unevidenced) ## What the human evidence shows More than a dozen human trials of NAD+ precursors (mainly nicotinamide riboside and NMN), some up to 6 months, consistently show two things: they are safe and well tolerated, and they reliably raise blood NAD+ levels. The much-cited Martens et al. (2018, Nature Communications) placebo-controlled crossover in 24 middle-aged/older adults confirmed NR roughly doubled NAD+ and hinted at reduced blood pressure and arterial stiffness — but only as exploratory signals that did not survive statistical correction. Beyond raising the biomarker, robust clinical benefit is largely missing: human studies have shown only limited efficacy for metabolic endpoints, and the overall evidence for mitigating age-related disease is weak. Direct IV NAD+ — the version sold in wellness clinics — is barely studied: the main human data are tiny pharmacokinetic/tolerability pilots (e.g. Grant et al. 2019, n=11), which found infused NAD+ is rapidly cleared from plasma and largely catabolised, with no efficacy outcomes. Most trials testing genuine anti-ageing or neuroprotective benefit are ongoing or not yet reported. In short: the biology is real, the biomarker moves, the human payoff is unproven. ## Concerns and unknowns - The biomarker (raised NAD+) is not the same as a clinical benefit — moving the number proves very little about ageing, energy or longevity in humans. - Direct IV NAD+, the form most heavily marketed by clinics, has the least evidence and is largely catabolised before reaching tissues intact. - IV infusions commonly cause unpleasant dose-rate effects: chest pressure, flushing, nausea, abdominal cramping, anxiety — usually managed by slowing the drip, but it reflects how fast it's pushed. - Marketing massively outruns the science; 'reverses ageing' and addiction-cure claims are not supported by controlled human data. - Theoretical concern that boosting NAD+ could also fuel processes you don't want amplified (e.g. supporting some tumour metabolism) — unresolved, not a proven harm, but a reason for caution. - Private clinic quality varies: unlicensed 'specials', variable sourcing, and practitioners of varying qualification. ## UK status NAD+ itself is not licensed as a medicine by the MHRA for any therapeutic indication, and no NAD+ IV or injectable product holds a UK or EU marketing authorisation. When given for a medical purpose it can only be supplied legally as an unlicensed 'special' medicinal product, made or imported by an MHRA-registered specials manufacturer, against a prescription from a doctor or other authorised prescriber for a specific patient's needs. Unlicensed medicines cannot be advertised to the public. IV NAD+ is delivered through private wellness clinics rather than the NHS; clinics carrying out such regulated activity should be CQC-registered with appropriately registered prescribers (GMC/NMC). The precursor vitamins are treated differently and are sold as foods rather than medicines: nicotinamide riboside (NR) is marketed as a food supplement, while nicotinamide mononucleotide (NMN) is currently a novel food 'under assessment' by the Food Standards Agency in Great Britain (not yet authorised, but available transitionally). Neither precursor is MHRA-licensed to treat any disease, and medicinal claims for them would bring them under MHRA control. ## Sport / WADA NAD+ and its precursors (nicotinamide riboside, NMN, niacin) are not on the WADA Prohibited List and are not banned in or out of competition. As ever, the practical risk for tested athletes is contamination of unregulated supplement products rather than the molecule itself. ## Key trials - **Nicotinamide riboside in healthy middle-aged and older adults (Martens et al.)** (Phase I/II, Completed). Established safety and NAD+ elevation; cardiovascular signals exploratory only. - **Nicotinamide riboside in Parkinson's disease (NADPARK / NO-PARK programme)** (Phase I (NADPARK) / Phase III (NO-PARK), NADPARK completed; NO-PARK ongoing). NADPARK was a 30-patient phase I pilot showing raised brain NAD+; NO-PARK (~400 participants) tests whether boosting NAD+ alters Parkinson's progression — among the most rigorous clinical tests of the hypothesis. - **IV NAD+ metabolome pilot (Grant et al.)** (Pilot, Completed). Pharmacokinetics/tolerability of direct IV NAD+; no efficacy endpoints. ## Sources 1. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Martens CR, et al., Nature Communications, 2018 2. A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD+. Grant R, et al., Frontiers in Aging Neuroscience, 2019 3. NAD+ and sirtuins in aging and disease. Imai S, Guarente L, Trends in Cell Biology, 2014 4. CD38 dictates age-related NAD decline and mitochondrial dysfunction through an SIRT3-dependent mechanism. Camacho-Pereira J, et al., Cell Metabolism, 2016 5. NAD+ precursor supplementation in human ageing: clinical evidence and challenges. Vinten KT, Houtkooper RH, et al., Nature Metabolism, 2025 6. PubMed search: NAD+ precursor supplementation human clinical trial aging. Various, PubMed, 2026 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/nad-plus . Educational only, not medical advice. --- # NMN (Nicotinamide Mononucleotide) **Evidence grade: C (Early / limited human data).** Area: Longevity. > A NAD+ building-block sold as an anti-ageing supplement; it genuinely raises NAD+ levels in human blood, but whether that does anything meaningful for ageing or healthspan is still unproven. **Also known as:** nicotinamide mononucleotide, beta-nicotinamide mononucleotide, β-NMN, nmn, nad+ booster, mib-626 **Class:** Nucleotide; NAD+ precursor (a vitamin-B3-derived molecule, not actually a peptide) ## Why this grade Several small, short human RCTs exist and reliably show NMN raises blood NAD+, but downstream benefits (walking, sleep, insulin sensitivity) are modest, inconsistent, surrogate-based and measured over weeks rather than years. No human trial demonstrates it extends healthspan or lifespan, so this is early/limited human data (C), not incomplete-but-meaningful clinical-outcome data (B). ## In plain terms **Simple.** Your cells run on a helper molecule called NAD+, a bit like a rechargeable battery that powers the chemistry that keeps cells working. As you get older, NAD+ levels drop. NMN is one of the raw materials your body uses to make NAD+, so the idea is: swallow NMN, top the battery back up, and maybe slow down some of the wear-and-tear of ageing. Studies in people do show that taking NMN raises NAD+ in the blood. The catch is that 'higher NAD+ on a blood test' isn't the same as 'living longer or feeling younger', and so far the proof that NMN actually does the second thing in humans is thin. It's been tested in mice a lot, in people only a little, and mostly for a few weeks at a time. **Standard.** NMN (nicotinamide mononucleotide) is a precursor your body converts into NAD+, a coenzyme central to energy metabolism, DNA repair and the activity of sirtuins (enzymes linked to ageing). NAD+ falls with age, and the longevity hypothesis is that restoring it with precursors like NMN could counteract age-related decline. Mouse studies have been striking — improvements in metabolism, blood vessels, muscle and more. Human data is where it gets honest: a handful of small randomised controlled trials (typically a few dozen people over a couple of months) consistently show NMN raises blood NAD+ and is well tolerated, with scattered hints of benefit — slightly better walking ability in older adults, improved muscle insulin sensitivity in prediabetic women, modest sleep and fatigue changes. But effects are small, the endpoints are surrogate markers rather than hard health outcomes, follow-up is short, and several findings haven't been replicated. No human trial has shown it slows ageing or extends life. It's also worth knowing the related pharmaceutical-grade version (MIB-626) is being run through proper drug trials. **Technical.** NMN is an intermediate in the NAD+ salvage pathway: NAMPT converts nicotinamide to NMN, which NMNAT1/2/3 adenylylate to NAD+. Exogenous NMN is hypothesised to replenish the age-associated decline in tissue NAD+, thereby supporting sirtuin (SIRT1–7) and PARP activity, mitochondrial function and redox balance. A contested point is cellular uptake: Slc12a8 was proposed as a direct NMN transporter (Grozio et al., Nat Metab 2019), but a rebuttal argued the data do not support NMN transport by Slc12a8 and that NMN is largely dephosphorylated extracellularly to nicotinamide riboside, taken up via equilibrative nucleoside transporters and rephosphorylated by NRK1/2 — so the precursor actually entering cells is debated. Human RCTs (e.g. Yoshino et al., Science 2021, n=25 prediabetic postmenopausal women; Yi et al., GeroScience 2023, dose-ranging, n=80; arterial-stiffness and sleep trials) robustly demonstrate dose-dependent elevation of circulating NAD+ and its metabolome with good short-term tolerability, but report only modest, often non-significant or unreplicated functional endpoints. Notably the Yoshino trial improved skeletal-muscle insulin sensitivity without a detectable rise in muscle NAD+ content, and its randomisation was later questioned. Critically, no trial powers for or demonstrates effects on incident age-related disease, validated biological-ageing endpoints tied to hard outcomes, or mortality. MIB-626, a microcrystalline NMN polymorph (Metro International Biotech), is in formal clinical drug development, which is part of why NMN's regulatory status became contentious. ## How it is thought to work NMN feeds the NAD+ salvage pathway. Inside cells, the enzymes NMNAT1/2/3 convert NMN into NAD+, a coenzyme required for mitochondrial energy production, DNA-repair (PARP) enzymes, and sirtuins — a family of enzymes implicated in cellular ageing and stress resistance. NAD+ declines with age, and the rationale is that supplying NMN restores it. How NMN actually gets into cells is debated: a proposed dedicated transporter (Slc12a8) was challenged by work suggesting NMN is first broken down to nicotinamide riboside outside the cell, imported, then rebuilt. Either way, the net measurable effect in humans is a rise in circulating NAD+. ## Studied for Research contexts, not proven uses. - Raising NAD+ levels - Healthy ageing / longevity (hypothesis) - Muscle insulin sensitivity / metabolic health - Physical performance and walking ability in older adults - Sleep quality and fatigue - Arterial stiffness / vascular ageing ## What the human evidence shows Unusually for a 'longevity' compound, NMN does have completed human RCTs — and they tell a consistent, sobering story. Across roughly a dozen small trials (typically a few dozen participants over a couple of months, taken orally), NMN reliably and dose-dependently raises blood NAD+ and is well tolerated, with no serious adverse events reported. Beyond that, benefits are modest and patchy. Yoshino et al. (Science, 2021) found improved muscle insulin sensitivity in 25 prediabetic, overweight/obese postmenopausal women — but the effect appeared without a detectable rise in muscle NAD+ content, several other metabolic markers didn't move, the trial's randomisation was later questioned, and the result hasn't been broadly replicated. Yi et al. (GeroScience, 2023), an 80-person dose-ranging trial, reported longer six-minute walking distance and better SF-36 quality-of-life scores. Other trials hint at small improvements in sleep, fatigue and arterial stiffness, though the arterial-stiffness change only trended and was not statistically significant. The honest summary: NMN does what it says on the tin biochemically (NAD+ goes up), but no human trial has shown it slows ageing, prevents age-related disease, or extends life, and the functional benefits seen so far are small, short-term and surrogate-based. The pharma-grade version, MIB-626, is being taken through formal drug trials, which is the more rigorous route. ## Concerns and unknowns - The headline claim — that NMN slows ageing or extends healthy life in humans — is unproven. Raising a blood NAD+ number is not the same as living longer or better. - Trials are small and short (weeks, not years), so long-term safety of sustained use is genuinely unknown. - Supplement-grade NMN is poorly regulated; independent testing has found products that under-deliver or contain impurities, so what's in the bottle may not match the label. - There is a theoretical concern that boosting NAD+ could fuel existing cancers (NAD+ supports cell proliferation), though this isn't established in humans either way — it's a reason for caution, not proven harm. - Marketing massively outruns the evidence: dramatic mouse results are routinely presented as if they apply to people, which they have not been shown to. ## UK status NMN is not a licensed medicine in the UK. Its supplement status hinges on novel food rules: NMN was not widely eaten before 15 May 1997, so it is treated as a 'novel food' requiring Food Standards Agency authorisation before legal sale as a food supplement. As of 2026 NMN is not authorised in Great Britain — it sits 'under assessment' in the FSA novel foods process, meaning it cannot lawfully be marketed as a food supplement here, even though it is sold online from overseas. (For contrast, the related precursor nicotinamide riboside chloride is FSA-authorised as a novel food.) Anything making medicinal claims would fall under MHRA medicines law. Note the regulatory turbulence: the US FDA initially excluded NMN from supplements in late 2022 because it had been authorised for investigation as a drug (MIB-626), then reversed that position in 2025 — UK and US frameworks differ, so US status doesn't make it legal to sell as a supplement here. ## Sport / WADA NMN is not specifically named on the WADA Prohibited List as of 2026. However, because it is not an approved medicine, anti-doping bodies note it could fall within WADA's catch-all S0 category (non-approved substances), and the strict-liability principle means athletes use unregulated supplements at their own risk, including the risk of contamination. Not a banned substance by name, but not a free pass either. ## Key trials - **NMN in prediabetic postmenopausal women (Yoshino/Klein, Washington University)** (Phase II (investigator-led RCT), Completed). Improved muscle insulin sensitivity; n=25; surrogate endpoints only; no muscle NAD+ rise detected. - **Dose-ranging NMN in healthy middle-aged adults (Yi et al.)** (Phase II, Completed). Low/mid/high oral dose arms over ~2 months; NAD+ rose dose-dependently, walking distance and quality-of-life scores improved. - **MIB-626 (microcrystalline NMN, Metro International Biotech) programme** (Phase II, Ongoing). Formal drug-development trials across indications incl. metabolic/muscle and kidney; the rigorous regulatory route. ## Sources 1. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Yoshino M, Yoshino J, Kayser BD, et al., Science, 2021 2. The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. Yi L, Maier AB, Tao R, et al., GeroScience, 2023 3. MIB-626, an Oral Formulation of a Microcrystalline Unique Polymorph of β-Nicotinamide Mononucleotide, Increases Circulating Nicotinamide Adenine Dinucleotide and its Metabolome in Middle-Aged and Older Adults. Pencina KM, Lavu S, Dos Santos M, et al., Journals of Gerontology: Series A, 2023 4. Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial. Katayoshi T, Nakajo T, Tsuji-Naito K, et al., Scientific Reports, 2023 5. Slc12a8 is a nicotinamide mononucleotide transporter (and the published rebuttal questioning it). Grozio A, et al.; rebuttal Schmidt MS & Brenner C, Nature Metabolism, 2019 6. NMN regulatory status: US FDA supplement-vs-drug reversal and UK FSA novel-food assessment. Regulatory/news coverage (FDA/NPA; UK FSA novel foods catalogue), Regulatory news and FSA novel foods catalogue, 2025 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/nmn . Educational only, not medical advice. --- # Nicotinamide Riboside (NR) **Evidence grade: C (Early / limited human data).** Area: Longevity. > A form of vitamin B3 that genuinely raises the cellular fuel-handling molecule NAD+ in people, sold as an anti-ageing supplement, but human trials have mostly failed to show it makes you meaningfully healthier. **Also known as:** nr, niagen, nicotinamide riboside chloride, nrc, tru niagen, nad+ booster, vitamin b3 derivative **Class:** Vitamin B3 derivative / NAD+ precursor (a small molecule, not a peptide) ## Why this grade A substantial body of completed human RCTs shows NR reliably and safely raises NAD+, but clinical benefit is inconsistent: most efficacy outcomes are null, with a few positive signals (notably the NICE peripheral artery disease trial). No approved indication and no robustly reproduced clinical benefit, so efficacy is not established. ## In plain terms **Simple.** Every cell in your body runs on a helper molecule called NAD+, a bit like a rechargeable battery that helps turn food into energy. As you age, your NAD+ levels drop, and some scientists think that's part of why old cells slow down. Nicotinamide riboside (NR) is a type of vitamin B3 you can swallow as a pill, and it really does top up your NAD+ levels. The catch: in proper human studies, topping up the battery hasn't reliably made people fitter, stronger, sharper or longer-lived. One trial in people with poor leg circulation did find they could walk a bit further, but most studies show no clear payoff. So NR does the thing it claims on the tin (more NAD+), but that mostly hasn't translated into the anti-ageing benefit people are paying for. It's sold legally as a supplement, looks safe at the doses tested, and is not a magic youth pill. **Standard.** NR is one of several NAD+ precursors (alongside nicotinamide mononucleotide, NMN, and plain niacin) marketed for 'cellular ageing'. NAD+ is a coenzyme central to energy metabolism and to enzymes like sirtuins and PARPs, and its levels decline with age and in some diseases. NR is well absorbed orally and consistently boosts blood NAD+ by meaningful amounts, which is more than can be said for many supplements. The honest problem is the gap between biomarker and benefit. Across dozens of randomised controlled trials in healthy older adults, people with metabolic disease, athletes and patients, NR repeatedly raises NAD+ but largely fails to improve insulin sensitivity, muscle function, blood pressure, mitochondrial function or cognition. The clearest positive is the NICE trial, where NR modestly improved walking distance in peripheral artery disease. A 2023 critical review of 25 human studies concluded the field tends to overstate weak findings. NR is legal in the UK as an authorised novel food (sold as Tru Niagen and similar), appears safe and well tolerated, but the case that it does anything you'd notice remains, on balance, unproven. **Technical.** NR (and its chloride salt, NRC) is salvaged to NAD+ via a route distinct from the de novo and Preiss-Handler pathways: nicotinamide riboside kinases NRK1 (NMRK1, ubiquitous) and NRK2 (NMRK2, muscle/cardiac) phosphorylate NR to NMN, which NMNAT then adenylylates to NAD+, bypassing NAMPT, the rate-limiting salvage enzyme. This NAMPT-independence is the theoretical pharmacological advantage. Pharmacokinetics are well characterised: Trammell et al. (2016) showed dose-dependent rises in the blood NAD+ metabolome, with NAAD emerging as a sensitive biomarker of effective NAD+ repletion. Subsequent RCTs (e.g. Martens 2018) confirmed chronic dosing elevates whole-blood NAD+ substantially and is well tolerated. However, target engagement has largely not delivered phenotypic efficacy: trials in overweight/obese and metabolically impaired cohorts found no effect on hepatic/intramyocellular lipid, insulin sensitivity, mitochondrial respiration or cardiometabolic indices, and a meta-analysis (Prokopidis 2025) found NR/NMN did not preserve skeletal muscle mass or function in older adults. There are exceptions: the NICE RCT in peripheral artery disease met its primary endpoint, with a statistically significant improvement in 6-minute walk distance, the strongest clinical signal to date. The NR-SAFE high-dose trial in Parkinson's disease was a safety study (tolerable, no methyl-donor depletion) rather than an efficacy demonstration, and an RCT in long-COVID raised NAD+ but did not improve cognition, fatigue, sleep or mood. A preclinical concern (Goun lab, 2022) reported NR uptake promoting triple-negative breast cancer and brain metastasis in murine models, mechanistically plausible given proliferating tumour cells' NAD+ demand, though unconfirmed in humans. Net: robust biomarker modulation, mostly thin but not uniformly negative clinical evidence, plausible-but-unproven oncological caveat. ## How it is thought to work NR is a precursor that the body converts into NAD+, a coenzyme essential for converting nutrients into cellular energy and for powering enzymes such as sirtuins and PARPs involved in DNA repair and metabolic regulation. Taken orally, NR enters cells and is phosphorylated by nicotinamide riboside kinases (NRK1/NRK2) to nicotinamide mononucleotide (NMN), which is then converted to NAD+. Crucially this route bypasses NAMPT, the normally rate-limiting enzyme of the NAD+ salvage pathway, which is the proposed reason NR can raise NAD+ efficiently. The therapeutic hypothesis is that restoring the age-related decline in NAD+ will improve mitochondrial and metabolic function; in humans the NAD+ increase is real but the downstream functional benefit has, in most trials, not materialised. ## Studied for Research contexts, not proven uses. - Age-related NAD+ decline / 'healthy ageing' - Metabolic health and insulin sensitivity - Skeletal muscle function and mitochondrial biogenesis - Blood pressure and arterial stiffness - Peripheral artery disease (walking performance) - Cognition and neurodegeneration (incl. Parkinson's, long-COVID) ## What the human evidence shows Unusually for a supplement, there is a substantial body of completed human RCTs, and that's exactly why the honest verdict is sobering. NR is reliably absorbed and consistently raises blood NAD+ (Trammell 2016 established the pharmacokinetics; Martens 2018 showed a marked, well-tolerated chronic elevation in healthy middle-aged and older adults). But the trials measuring actual health outcomes are mostly null or marginal: studies in overweight/obese and metabolically impaired people found no improvement in insulin sensitivity, body composition, mitochondrial function or hepatic fat, and a 2025 systematic review/meta-analysis (Prokopidis et al.) found NR/NMN did not preserve muscle mass or function in older adults. The notable exception is the NICE randomised trial in peripheral artery disease (2024), which met its primary endpoint with a modest but statistically significant gain in 6-minute walk distance. Safety-focused trials in Parkinson's disease (NR-SAFE, high-dose) confirmed tolerability without proving benefit, and a long-COVID RCT raised NAD+ but did not improve cognition, fatigue, sleep or mood. A 2023 critical review in Science Advances assessed 25 human studies and concluded NR has displayed few clinically relevant effects, with a tendency in the literature to exaggerate weak results. In short: the biomarker reliably moves, and apart from a walking benefit in PAD the patient generally doesn't. ## Concerns and unknowns - Efficacy gap: NR reliably raises NAD+ but most human trials have failed to show clinical benefit, so broad anti-ageing claims are unproven; the clearest positive signal is limited to walking distance in peripheral artery disease. - Marketing outpaces evidence: supplements are sold with strong longevity/energy claims that the human data do not support. - A 2022 animal study reported NR may promote triple-negative breast cancer growth and metastasis to the brain; unconfirmed in humans but a genuine flag given proliferating cells' high NAD+ demand. - Long-term safety in humans is established mainly over weeks-to-months at the doses tested; effects of years of continuous use are unknown. - Supplement quality is not regulated as a medicine, so actual NR content and purity can vary between products. - Authorised novel-food conditions are for healthy adults and exclude infants and children; pregnant and breastfeeding women are subject to a lower permitted intake. ## UK status Not a licensed medicine. Nicotinamide riboside chloride is an authorised novel food in Great Britain (following the EFSA 2019 assessment under Regulation (EU) 2015/2283, retained in UK law), permitted in food supplements for healthy adults, with a lower permitted intake for pregnant and breastfeeding women. It is therefore sold legally as a food supplement (e.g. Tru Niagen) rather than regulated by the MHRA as a medicine, which means it has not undergone the efficacy and safety scrutiny required of a licensed drug and cannot legally be marketed with claims to treat or prevent disease (such claims would fall foul of the Human Medicines Regulations 2012). ## Sport / WADA Not on the WADA Prohibited List. As a vitamin B3 derivative and NAD+ precursor it is not a banned substance; athletes are nonetheless responsible for supplement contamination risk. ## Key trials - **Chronic NR supplementation in healthy middle-aged and older adults (Martens 2018)** (Phase I/II, Completed). Raised NAD+ and was well tolerated; only suggestive effects on blood pressure/arterial stiffness. - **NR-SAFE high-dose NR in Parkinson's disease** (Phase I (safety), Completed). High doses tolerable with no methyl-donor depletion; designed to assess safety, not prove benefit. - **Nicotinamide riboside for peripheral artery disease (NICE)** (Phase II, Completed). RCT that met its primary endpoint: NR modestly but significantly improved 6-minute walk distance; the strongest positive clinical signal for NR so far. - **NR for cognition and symptom recovery in long-COVID** (Phase II, Completed). Double-blind RCT over 24 weeks; NR raised NAD+ several-fold but did not improve cognition, fatigue, sleep or mood versus placebo. ## Sources 1. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Trammell SAJ et al., Nature Communications, 2016 2. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Martens CR et al., Nature Communications, 2018 3. What is really known about the effects of nicotinamide riboside supplementation in humans. Damgaard MV, Treebak JT, Science Advances, 2023 4. The effect of nicotinamide mononucleotide and riboside on skeletal muscle mass and function: a systematic review and meta-analysis. Prokopidis K et al., Journal of Cachexia, Sarcopenia and Muscle, 2025 5. NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson's disease. Brakedal B et al., Nature Communications, 2023 6. Nicotinamide riboside for peripheral artery disease: the NICE randomized clinical trial. McDermott MM et al., Nature Communications, 2024 7. Safety of nicotinamide riboside chloride as a novel food (EFSA opinion). EFSA Panel on Nutrition, Novel Foods and Food Allergens, EFSA Journal, 2019 8. A bioluminescent-based probe for in vivo non-invasive monitoring of nicotinamide riboside uptake reveals a link between metastasis and NAD+ metabolism. Goun lab (Sazonova EV et al.), Biosensors and Bioelectronics, 2022 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/nicotinamide-riboside . Educational only, not medical advice. --- # Oxytocin **Evidence grade: B (Promising human evidence).** Area: Libido & Hormonal. > Oxytocin is a natural hormone and a genuine, decades-old hospital medicine for childbirth that has been heavily marketed as a "love and bonding" nasal spray, but that bonding use mostly fails to hold up in good trials. **Also known as:** Syntocinon, Pitocin, the "love hormone", the "cuddle chemical", OXT, love hormone, cuddle hormone, hug hormone, bonding hormone, love drug **Class:** Endogenous nonapeptide hormone / neuropeptide; the synthetic form is a licensed obstetric medicine (a uterotonic) ## Why this grade This is a split verdict, graded honestly rather than letting the strongest use flatten the weakest. As an intravenous drug in obstetrics (inducing or augmenting labour, controlling postpartum bleeding), oxytocin is a long-established MHRA-licensed medicine with decades of robust clinical evidence; that specific use is genuinely Grade A. Almost nobody buys oxytocin on the grey market for childbirth. They buy intranasal sprays for social bonding, libido, autism, anxiety or "connection", and that evidence is weak: the largest, best-conducted trial (SOARS-B, 277 autistic children and adolescents, NEJM 2021) was flatly negative, and meta-analyses of intranasal oxytocin show small, inconsistent, poorly-replicated effects. The entry is graded B overall. Real and substantial human trial evidence exists across both stories, but the popular psychoactive and libido claims that drive most interest are unproven and on their own would rate a C. A single "A" badge would mislead anyone scanning grades into thinking the bonding spray works. It does not. The molecule's reputation and its actual evidence point in opposite directions depending on the use. ## In plain terms **Simple.** Oxytocin is a chemical your own body makes. It does real jobs in childbirth and breastfeeding. A man-made version is given through a drip in hospitals to help labour along and stop bleeding after birth. That part is solid, proven medicine. It also became famous as the "love hormone" or "cuddle chemical", and people sell nasal sprays claiming it makes you bond, trust, feel close or boost your sex life. When scientists tested those bonding claims properly, the sprays mostly did not work. The biggest, best study in autistic children found it did nothing more than a dummy spray. So: trusted medicine for one job, mostly hype for the other. **Standard.** Oxytocin is a hormone made in the hypothalamus and released by the pituitary gland. It triggers womb contractions during labour and the "let-down" of milk during breastfeeding. It is involved in social behaviours like bonding and trust, which earned it the nickname "love hormone". The synthetic version (brand name Syntocinon in the UK) is a properly licensed medicine, given by drip to start or speed up labour and to control bleeding after birth. That use is well evidenced and routine in maternity units. The controversial part is the nasal-spray market: companies and biohackers sell oxytocin sprays claiming they boost intimacy, trust, libido, social ease, or treat autism and anxiety. The reality is far less impressive. Only a little of a sniffed dose reaches the brain. The single biggest, best-run trial of 277 autistic children and teenagers over 24 weeks (NEJM 2021) found oxytocin was no better than placebo on any measure. Results across studies are small and contradictory. The popular "bonding spray" promise is largely unproven, even though the obstetric drug is genuinely effective. **Technical.** Oxytocin is a nine-amino-acid cyclic neuropeptide synthesised in the magnocellular and parvocellular neurons of the paraventricular and supraoptic nuclei of the hypothalamus, transported axonally to the posterior pituitary and released into the systemic circulation; parvocellular projections also release it centrally. It acts on the G-protein-coupled oxytocin receptor (OXTR; Gq/11-coupled, PLC/IP3/Ca2+ signalling), driving myometrial contraction (uterotonic action) and myoepithelial contraction in mammary alveoli (milk ejection). Synthetic oxytocin (Syntocinon) is an MHRA-licensed parenteral uterotonic for induction/augmentation of labour and prevention/treatment of postpartum haemorrhage; this indication rests on a deep, gold-standard evidence base. OXTR is expressed across limbic and reward circuitry (amygdala, nucleus accumbens, hypothalamus), underpinning a large translational literature on affiliative behaviour, pair-bonding, trust, fear extinction and social salience. Much of this work is rodent-based plus small human intranasal crossover studies with well-documented replication and reverse-inference problems and uncertain CNS bioavailability after intranasal dosing. The pivotal clinical trial is SOARS-B (Sikich et al., NEJM 2021; NCT01944046): a 277-participant, 24-week, placebo-controlled trial of intranasal oxytocin in ASD that showed no significant benefit on the Aberrant Behavior Checklist modified Social Withdrawal subscale (ABC-mSW) or any secondary endpoint. Systematic reviews and meta-analyses of intranasal oxytocin for autism and social cognition broadly report small, heterogeneous, non-robust effects, with proposed OXTR-genotype moderation unconfirmed. A validated peripheral uterotonic with a largely unvalidated central/psychoactive reputation. ## How it is thought to work A nine-amino-acid peptide hormone made in the hypothalamus and released from the posterior pituitary. It acts on the oxytocin receptor (OXTR), a Gq-coupled GPCR. Peripherally it contracts uterine smooth muscle (labour) and mammary myoepithelial cells (milk let-down). Centrally, OXTR is expressed in limbic and reward regions (amygdala, nucleus accumbens, hypothalamus) and modulates social salience, bonding, trust and fear processing, the basis for the "love hormone" reputation. Given as a drip in obstetrics it works reliably on the uterus. Given as a nasal spray for brain and behaviour effects, how much actually reaches the central nervous system is uncertain and the behavioural effects are inconsistent. ## Studied for Research contexts, not proven uses. - Induction and augmentation of labour (licensed obstetric use) - Prevention and treatment of postpartum haemorrhage (licensed use) - Autism spectrum disorder / social functioning (large RCT was negative) - Social cognition, trust and bonding (small, inconsistent human studies) - Anxiety and social anxiety - Libido, intimacy and pair-bonding - Mood and depression (exploratory) - Appetite and feeding regulation (early research) ## What the human evidence shows Two distinct stories. As an intravenous obstetric drug, oxytocin has decades of strong human evidence and is standard NHS care for inducing or augmenting labour and managing postpartum bleeding; this is gold-standard. As the "bonding/love/libido" nasal spray that drives grey-market interest, the human evidence is weak and disappointing. Early small crossover studies suggested effects on trust, social gaze and bonding, but these have well-known replication problems. The definitive trial is SOARS-B (Sikich et al., NEJM 2021): 277 autistic children and adolescents over 24 weeks. Intranasal oxytocin was no better than placebo on any primary or secondary outcome. Meta-analyses of intranasal oxytocin for social and autism endpoints report small, heterogeneous, non-robust effects. There is no solid trial evidence supporting nasal oxytocin for libido or general "connection". ## Concerns and unknowns - The popular use (intranasal for bonding, libido or social effects) is largely unproven. The biggest, best-run trial was flatly negative. - Intranasal delivery to the brain is uncertain: it is unclear how much sniffed oxytocin actually reaches the central nervous system, undermining many positive claims. - The licensed obstetric drug is potent and potentially dangerous: misused intravenous oxytocin can cause excessive or tetanic uterine contractions and fetal distress, and is a recurring theme in obstetric litigation. It is hospital-only for good reason. - Water intoxication / hyponatraemia is a recognised risk because oxytocin has antidiuretic activity, especially when given with large fluid volumes. - Grey-market "research chemical" nasal sprays and reconstituted vials carry the usual concerns: unknown purity, sterility, dose accuracy and contamination, with no medical oversight. - Cardiovascular effects (transient changes in blood pressure and heart rate) are documented with the injectable form. - Selling or supplying it for human use outside its licence in the UK is a regulatory offence; "not for human consumption" labelling is a legal dodge, not a safety statement. ## UK status Oxytocin is a licensed prescription-only medicine (POM) in the UK, regulated by the MHRA, marketed as Syntocinon and as generic "Oxytocin" solution for infusion. Its licensed indications are obstetric: induction and augmentation of labour and the prevention and treatment of postpartum haemorrhage, given by drip or injection under medical supervision. It is not licensed for any psychiatric, social, "bonding", anti-anxiety or libido use, and there is no licensed intranasal oxytocin product for those purposes in the UK. Intranasal oxytocin sold online as a nootropic or bonding spray, or as a "research chemical not for human consumption", is unlicensed. Supplying it for human consumption breaches the Human Medicines Regulations 2012. Any legitimate human use is on prescription within its obstetric licence. ## Key trials - **Study of Oxytocin in Autism to Improve Reciprocal Social Behaviors (SOARS-B)** (NCT01944046, Phase 2, Completed (results published, NEJM 2021)). 277 children/adolescents with ASD; 24 weeks intranasal oxytocin vs placebo; negative on all primary and secondary endpoints. ## Sources 1. Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder (SOARS-B). Sikich L, et al., New England Journal of Medicine, 385(16):1462-1473, 2021 2. The effects of oxytocin administration on social and routinized behaviors in autism: a preregistered systematic review and meta-analysis. Psychoneuroendocrinology, vol. 167, article 107067, 2024 3. Oxytocin 10 IU/ml Solution for infusion — Summary of Product Characteristics (SmPC). electronic medicines compendium (emc), UK 4. Maternal and newborn plasma oxytocin levels in response to maternal synthetic oxytocin administration during labour, birth and postpartum — a systematic review. Buckley S, Uvnas-Moberg K, et al., BMC Pregnancy and Childbirth, 2023 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/oxytocin . Educational only, not medical advice. --- # P21 (P021) **Evidence grade: D (Animal data only).** Area: Cognition & Mood. > An experimental brain peptide designed from a natural nerve-growth factor that improves memory and reduces Alzheimer's-like pathology in mice, but has never been tested in humans. **Also known as:** P021, P-021, CNTF-derived peptide, Ac-DGGL-amide (adamantylated), CNTF small-molecule peptidergic mimetic, cntf peptide **Class:** CNTF-derived neurotrophic/neurogenic tetrapeptide mimetic (small-molecule peptidergic) ## Why this grade All published evidence is preclinical: rodent models (notably 3xTg-AD mice) and in-vitro work, largely from a single principal research group, spanning roughly 2010-2022. There are no published or registered human trials of any phase, no MHRA/EMA/FDA approval, and no peer-reviewed human safety or pharmacokinetic data. This sits firmly at D. ## In plain terms **Simple.** P21 is a tiny lab-made peptide based on a natural substance the body uses to help nerve cells grow and survive. In mice bred to develop an Alzheimer's-like illness, it helped the animals make new brain cells, protected the connections between cells, and improved memory in maze tests. Every single study so far has been in mice or in cells in a dish. Nobody has ever tested P21 in people, so we do not know whether it works in humans, what would be safe, or what side effects it might cause. Anything sold online as 'P21' is an unlicensed research chemical, not a medicine. **Standard.** P21 (also written P021) is a modified four-amino-acid peptide engineered from the most active fragment of ciliary neurotrophic factor (CNTF), a natural protein that supports nerve cells. Chemists attached an adamantane group to help it survive in the body and cross into the brain. In Alzheimer's mouse models it boosts the birth of new neurons in the hippocampus, increases BDNF (a key brain growth factor), and reduces the abnormal tau and amyloid changes that damage brain cells. Treated mice perform better on memory tasks. This is all animal and cell data, largely from one research group. There have been no human clinical trials, no regulatory approval anywhere, and no human safety data. It is an investigational compound at the preclinical stage, and any material sold to consumers is an unlicensed 'research chemical'. **Technical.** P021 (Ac-DGGL-amide, C-terminally adamantylated) is a peptidergic small-molecule mimetic derived by epitope mapping of the biologically active region of ciliary neurotrophic factor (CNTF), developed primarily in the laboratory of Khalid Iqbal at the New York State Institute for Basic Research in Developmental Disabilities. The adamantane moiety improves exopeptidase resistance, blood-brain-barrier penetrance and oral bioavailability. P021 enhances dentate gyrus neurogenesis and synaptic plasticity by antagonising leukaemia inhibitory factor (LIF)/CNTF-family signalling that otherwise suppresses neurogenesis, whilst upregulating BDNF. Downstream, BDNF-mediated inhibition of GSK-3-beta (a principal tau kinase) reduces tau hyperphosphorylation. In 3xTg-AD and related models, chronic dietary P021 has rescued dentate neurogenesis, dendritic/synaptic deficits and spatial memory, and attenuated tau and, more modestly, A-beta pathology, including in therapeutic (post-onset) paradigms (e.g. Kazim et al., 2014). Evidence is confined to rodent and in-vitro studies; there are no registered or published human Phase 1-3 trials and no human PK or safety data. The ADDF Cognitive Vitality review classifies it as a preclinical candidate. ## How it is thought to work Engineered from the biologically active region of ciliary neurotrophic factor (CNTF), with an adamantane modification for stability and brain penetration. It enhances hippocampal (dentate gyrus) neurogenesis and synaptic plasticity by antagonising inhibitory LIF/CNTF-family signalling and increasing BDNF expression. Elevated BDNF reduces GSK-3-beta activity, lowering abnormal tau hyperphosphorylation. In animal models this combination is associated with reduced tau and amyloid pathology and improved learning and memory. ## Studied for Research contexts, not proven uses. - Alzheimer's disease pathology (tau hyperphosphorylation, amyloid-beta) in transgenic mouse models - Hippocampal neurogenesis and synaptic/dendritic plasticity - Learning and spatial memory in rodents - Tauopathies more broadly (preclinical) - Neurodevelopmental models (e.g. Down syndrome / Ts65Dn mice) in some reports ## What the human evidence shows None. There are no published or registered human clinical trials of P21/P021 at any phase, no human pharmacokinetic or safety data, and no regulatory approval in the UK, EU or US. The entire evidence base is preclinical and dominated by a single research group. Any claim of cognitive benefit in humans is unsupported. ## Concerns and unknowns - No human data: efficacy, safety, tolerability and side-effect profile in people are entirely unknown. - Evidence is concentrated in one research group. Many neurotrophic Alzheimer's candidates have failed when moved from mice to humans. - Sold as an unlicensed 'research chemical' marked 'not for human consumption', with no pharmaceutical-grade manufacturing and no purity, sterility or content guarantees. - Modulating neurotrophic and neurogenic pathways (BDNF, CNTF-family signalling) is biologically powerful and unproven in humans. Unknown risks surround aberrant cell proliferation or off-target neural effects. - Marketing materials frequently overstate the rodent findings as if they applied to human cognition or Alzheimer's treatment. ## UK status Not a licensed medicine in the UK. The MHRA has approved no P21/P021 product, and there is no known authorised UK clinical trial. It is an unlicensed substance sold by research-chemical vendors labelled 'for research use only / not for human consumption'. Supplying or selling it for human use would engage the Human Medicines Regulations 2012 as an unlicensed medicinal product. There is no legitimate prescription route; any human use is unapproved and unregulated. ## Sources 1. Disease modifying effect of chronic oral treatment with a neurotrophic peptidergic compound in a triple transgenic mouse model of Alzheimer's disease. Kazim SF, Blanchard J, Dai C-L, Tung Y-C, LaFerla FM, Iqbal I-G, Iqbal K, Neurobiology of Disease, 2014 2. Prevention of dendritic and synaptic deficits and cognitive impairment with a neurotrophic compound. Baazaoui N, Iqbal K, Alzheimer's Research & Therapy, 2017 3. Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer's disease. Kazim SF, Iqbal K, Molecular Neurodegeneration, 2016 4. Alzheimer's Disease: Challenges and a Therapeutic Opportunity to Treat It with a Neurotrophic Compound. Baazaoui N, Iqbal K, Biomolecules, 2022 5. P021 - Cognitive Vitality Report. Alzheimer's Drug Discovery Foundation (ADDF), AlzDiscovery.org (Cognitive Vitality), 2025 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/p21 . Educational only, not medical advice. --- # PE-22-28 **Evidence grade: D (Animal data only).** Area: Cognition & Mood. > An experimental brain peptide that blocks the TREK-1 potassium channel to act like a fast antidepressant in mice, with zero human testing to date. **Also known as:** pe 22-28, pe22-28, mini-spadin, spadin analog, trek-1 inhibitor peptide **Class:** Synthetic heptapeptide (7 amino acids), a shortened analogue of spadin ## Why this grade Antidepressant and pro-neurogenic effects have been shown only in mice and in vitro; no registered or completed human trials exist, so there is no human evidence at all. ## In plain terms **Simple.** PE-22-28 is a tiny lab-made protein fragment designed to behave like a quick-acting antidepressant. Your brain cells have lots of little gates that control how excitable they are, and one of these gates is called TREK-1. When TREK-1 is open, certain mood-related signals get dampened. PE-22-28 jams that gate shut, which in mice seems to lift their mood faster than ordinary antidepressants and even helps the brain grow new cells. The catch: every bit of this evidence comes from mice and cells in dishes. No human has ever been tested with it in a proper trial, so nobody actually knows if it works in people or whether it is safe. It is sold online as a 'research chemical', not a medicine. **Standard.** PE-22-28 is a synthetic 7-amino-acid peptide derived from spadin, a natural fragment cut from the sortilin protein. Spadin was discovered as the body's own blocker of TREK-1, a potassium channel that helps set how easily neurons fire. Because mice genetically lacking TREK-1 are unusually resistant to depression, blocking the channel has been pitched as a new, fast-onset antidepressant strategy distinct from SSRIs. Spadin itself broke down too quickly to be useful, so researchers engineered shorter, more stable versions; PE-22-28 came out far more potent at TREK-1 and lasted much longer in the body. In mice, a few days of treatment reduced depression-like behaviour and boosted new neuron growth in the hippocampus. None of this has progressed to humans. There are no completed or registered clinical trials, no regulatory approval anywhere, and the safety profile in people is entirely unknown. **Technical.** PE-22-28 (Gly-Val-Ser-Trp-Gly-Leu-Arg) is a truncated analogue of spadin, a peptide cleaved from the propeptide of NTSR3/sortilin during Golgi maturation; the name reflects residues 22-28 of the spadin sequence. It is a selective inhibitor of TREK-1 (KCNK2), a member of the two-pore-domain (K2P) background potassium channel family. TREK-1 helps set neuronal resting membrane potential and excitability; Trek1 knockout mice exhibit a depression-resistant phenotype with enhanced 5-HT neurotransmission, providing the rationale for TREK-1 antagonism as a rapid-onset antidepressant mechanism distinct from monoaminergic reuptake inhibition. In hTREK-1 electrophysiology, PE-22-28 reportedly achieved an IC50 around 0.12 nM versus 40-60 nM for spadin, with action duration extended to roughly 23 h. In murine models (forced swim test, novelty-suppressed feeding) sub-chronic dosing reduced immobility and feeding latency, increased hippocampal neurogenesis and CREB phosphorylation, and raised synaptic markers. All data are preclinical (rodent/in vitro); there are no human pharmacokinetic, efficacy or safety data. ## How it is thought to work PE-22-28 selectively inhibits TREK-1 (KCNK2), a two-pore-domain background potassium channel that helps set neuronal resting potential and excitability. By blocking TREK-1, it is thought to increase serotonergic signalling and neuronal excitability in mood-relevant circuits, mimicking the depression-resistant state seen in TREK-1 knockout mice. In rodents this is associated with enhanced hippocampal neurogenesis, CREB phosphorylation and synaptic markers, suggesting a rapid-onset antidepressant mechanism distinct from SSRIs. It is derived from spadin, the body's natural TREK-1-blocking fragment of the sortilin propeptide, but engineered to be more potent and longer-lasting. ## Studied for Research contexts, not proven uses. - Depression (antidepressant-like effects in mice) - Hippocampal neurogenesis and synaptogenesis (preclinical) - Neuroprotection (proposed, preclinical) ## What the human evidence shows There is none. Every published finding on PE-22-28 comes from mouse behavioural models and in-vitro electrophysiology. No human pharmacokinetic, efficacy or safety study has been completed, and no clinical trial of PE-22-28 (or its parent spadin) appears to be registered. Claims that it is a fast-acting antidepressant or memory aid in people are extrapolations from rodent data, not human results. ## Concerns and unknowns - No human safety data whatsoever — unknown dosing, toxicity, immunogenicity or long-term effects in people. - Sold as an unlicensed 'research chemical'; grey-market products have no guarantee of identity, purity or sterility. - TREK-1 is expressed widely (brain, heart, smooth muscle, pain pathways), so off-target effects on cardiovascular function and pain are plausible but uncharacterised in humans. - Marketing routinely overstates the evidence, presenting mouse antidepressant findings as if proven in people. - Self-experimentation with an injectable, untested CNS-active peptide for a serious condition like depression carries real risk and may delay evidence-based treatment. ## UK status PE-22-28 is not a licensed medicine in the UK and has no MHRA marketing authorisation. It exists only as an unlicensed, investigational peptide typically sold 'for research use only'. Marketing or supplying it for human use would bring it within the Human Medicines Regulations 2012 as an unlicensed medicinal product, and any human therapeutic claims would be unlawful. There is no approved route for a person to obtain or use it legitimately as a treatment. ## Sport / WADA Not specifically named on the WADA Prohibited List. It is not an established performance-enhancing agent and there is no human evidence in a sport context; as a novel, non-approved CNS peptide its status would be uncertain, and athletes should treat any such compound with caution. ## Key trials - **No registered or completed human clinical trials of PE-22-28** (None). As of this review, no PE-22-28 (or spadin) trial appears registered on ClinicalTrials.gov or other registries. All evidence is preclinical. ## Sources 1. Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity. Djillani A, Pietri M, Moreno S, Heurteaux C, Mazella J, Borsotto M, Frontiers in Pharmacology, 2017 2. Spadin, a Sortilin-Derived Peptide, Targeting Rodent TREK-1 Channels: A New Concept in the Antidepressant Drug Design. Mazella J, Petrault O, Lucas G, et al., PLoS Biology, 2010 3. PE-22-28 and spadin TREK-1 antidepressant peptide research (PubMed search). PubMed, 2026 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/pe-22-28 . Educational only, not medical advice. --- # PT-141 (Bremelanotide) **Evidence grade: A (Approved / strong human evidence).** Area: Libido & Hormonal. > A brain-acting peptide that affects sexual desire through melanocortin receptors. It is the only such drug actually approved (in the US, as Vyleesi) for low sexual desire in premenopausal women. **Also known as:** Bremelanotide, Vyleesi, PT-141, PT141, libido peptide, the horny peptide **Class:** Melanocortin receptor agonist (cyclic heptapeptide; MC4R/MC3R agonist) ## Why this grade The grade applies narrowly. For its specific licensed indication (acquired, generalised HSDD in premenopausal women), bremelanotide is a genuinely approved medicine backed by two large, identical Phase 3 randomised, placebo-controlled trials (RECONNECT) plus a 52-week open-label extension and a pooled safety programme. That earns an A for that population. The popular grey-market uses (male erectile dysfunction, general "libido boosting" in men or postmenopausal women) are not the approved indication and rest on much weaker, mostly older or exploratory human data. Judged alone those uses would grade no better than C-D. The approval is US (FDA) only, and the absolute benefit even in the approved group is modest. ## In plain terms **Simple.** PT-141, sold in the US under the name Vyleesi, is a medicine that works on the brain to increase sexual desire. Unlike Viagra, which boosts blood flow, this one acts on brain chemistry. It is properly approved in America for one specific group: women before the menopause who have a distressing loss of sexual desire. The benefit is real but fairly small. Common side effects include nausea (around 4 in 10 users), flushing and headaches, and it can briefly raise blood pressure. In the UK it is not an approved medicine, and versions sold online as 'research chemicals' are unregulated and unchecked. **Standard.** PT-141 (bremelanotide) is a peptide that activates melanocortin receptors in the brain, engaging the neural circuitry involved in sexual desire and arousal. This differs fundamentally from PDE5 inhibitors like sildenafil (Viagra), which act on blood vessels. It is FDA-approved in the US as Vyleesi for acquired, generalised hypoactive sexual desire disorder (HSDD) in premenopausal women, based on two large Phase 3 trials. The improvement was statistically real but modest, and dropout was high, largely from nausea (around 40% of users), plus flushing and headache. It also transiently raises blood pressure, so caution is needed in people with cardiovascular risk. It is used on an as-needed basis rather than daily. In the UK there is no MHRA licence for it. Material sold online is unlicensed and labelled 'not for human consumption'. The widely promoted uses in men, or for general libido in either sex, are extrapolation beyond the approved indication without equivalent trial support. **Technical.** Bremelanotide (development code PT-141) is a cyclic heptapeptide analogue of alpha-MSH and a non-selective melanocortin receptor agonist, with relevant activity at MC4R and MC3R in CNS pathways modulating sexual desire and arousal. It was derived from the earlier melanocortin agonist melanotan-II. Mechanistically it is upstream and central, contrasting with peripheral PDE5 inhibition. FDA approval (Vyleesi, June 2019) was for acquired, generalised HSDD in premenopausal women, supported by two identical Phase 3 RECONNECT trials (NCT02333071, NCT02338960; integrated double-blind N approx. 1,247), which met co-primary endpoints on the Female Sexual Function Index-desire domain and the Female Sexual Distress Scale-DAO Item 13 (both P<0.001 versus placebo), with modest absolute effect sizes and substantial discontinuation. A 52-week open-label extension supported durability. Safety (pooled programme): nausea (~40%), flushing (~20%), headache (~11-12%), injection-site reactions, and transient increases in systolic/diastolic blood pressure with compensatory heart-rate reduction. Focal hyperpigmentation has been reported with repeated dosing (a melanocortin class effect via MC1R). Earlier intranasal development for erectile dysfunction was discontinued partly over blood-pressure concerns, with no comparable Phase 3 efficacy package in men. UK regulatory status: no MHRA marketing authorisation or EU approval; grey-market supply is unlicensed. ## How it is thought to work A cyclic peptide analogue of alpha-melanocyte-stimulating hormone that agonises central melanocortin receptors (notably MC4R and MC3R). This activates brain pathways governing sexual desire and arousal, acting centrally rather than on genital blood flow. It is given by subcutaneous injection on an as-needed basis. Off-target MC1R activity underlies flushing and skin pigmentation. Melanocortin signalling also drives the transient blood-pressure rise seen with the drug. ## Studied for Research contexts, not proven uses. - Acquired, generalised hypoactive sexual desire disorder (HSDD) in premenopausal women (approved indication) - Female sexual arousal/desire dysfunction more broadly (beyond the approved population) - Erectile dysfunction in men (earlier, now-discontinued intranasal programme) - Sexual dysfunction secondary to antidepressants (exploratory) ## What the human evidence shows Strong for its narrow approved use. Two identical Phase 3 randomised, double-blind, placebo-controlled trials (RECONNECT, integrated N approximately 1,247 premenopausal women with HSDD) showed statistically significant improvements in sexual desire and reductions in associated distress versus placebo, leading to FDA approval (Vyleesi, 2019). A 52-week open-label extension supported longer-term tolerability and durability. Effect sizes were modest, not transformative, and discontinuation was common, mainly due to nausea. Evidence for uses in men or for general libido enhancement is far thinner. The earlier intranasal erectile-dysfunction programme was discontinued partly over blood-pressure concerns, with no comparable Phase 3 efficacy package for those populations. ## Concerns and unknowns - Nausea is very common (~40% of users) and the leading reason people stop. Flushing (~20%) and headache (~11-12%) are also frequent. - Transiently raises blood pressure and lowers heart rate. Caution is needed in people with uncontrolled hypertension or established cardiovascular disease. - Repeated use can cause focal skin hyperpigmentation (a melanocortin class effect), including on the face and gums. - Approved only for one specific population (premenopausal women with HSDD). Use in men or for general 'libido boosting' is extrapolation beyond the indication without equivalent trial support. - Not licensed by the MHRA in the UK or approved in the EU. Material sold online is unlicensed 'research chemical' of unverified identity, purity and sterility, with no pharmacy oversight. - Efficacy even in the approved group is modest, not transformative. ## UK status Not a licensed medicine in the UK. Bremelanotide has no MHRA marketing authorisation, and Vyleesi is a US (FDA) approval only with no EU approval. It is not available on prescription here. Product sold by UK suppliers is unlicensed material marketed as a "research chemical" or "not for human consumption", outside the Human Medicines Regulations 2012 framework for approved medicines. Supplying or advertising it for human use would breach UK medicines law. ## Sport / WADA Not listed by name on the WADA Prohibited List and not a recognised performance-enhancing agent. Confirm against the current WADA list before relying on this. ## Key trials - **Study to Evaluate the Efficacy/Safety of Bremelanotide in Premenopausal Women With HSDD (RECONNECT, Study 301)** (NCT02333071, Phase 3, Completed). One of the two pivotal identical RECONNECT trials supporting Vyleesi approval. - **Bremelanotide in Premenopausal Women With HSDD (RECONNECT, Study 302)** (NCT02338960, Phase 3, Completed). Second identical pivotal RECONNECT trial. ## Sources 1. Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials. Kingsberg SA, Clayton AH, Portman D, et al., Obstetrics & Gynecology, 2019 2. Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder. Simon JA, Kingsberg SA, Portman D, et al., Obstetrics & Gynecology, 2019 3. Safety Profile of Bremelanotide Across the Clinical Development Program. Clayton AH, Kingsberg SA, Portman D, et al., Journal of Women's Health, 2022 4. VYLEESI (bremelanotide injection) US Prescribing Information / FDA approval. US FDA / accessdata.fda.gov, 2019 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/pt-141 . Educational only, not medical advice. --- # Pinealon **Evidence grade: D (Animal data only).** Area: Other. > A lab-made three-amino-acid peptide claimed to protect brain cells. The evidence is almost entirely from cell dishes and rodents, produced by one research group, with no proper human trials. **Also known as:** EDR, Glu-Asp-Arg, EDR peptide, Cortagen-related tripeptide, khavinson peptide, brain bioregulator **Class:** Synthetic ultra-short peptide (tripeptide) "bioregulator"; neuro-targeted Khavinson-group peptide ## Why this grade Essentially all evidence is in-vitro and rodent work from a single research group (Khavinson and affiliates in St Petersburg). There are no completed, registered, independent randomised controlled human efficacy trials. By the site's rubric that is a clear D: animal/in-vitro data with no meaningful, replicated human evidence. ## In plain terms **Simple.** Pinealon is a tiny man-made protein fragment, just three building blocks long. Russian researchers believe it shields brain cells from stress and ageing. In experiments on cells in dishes and in rats it does seem to help cells survive. But those are animal and lab tests, not tests in people. There are no real trials showing it works or is safe in humans, so claims about 'brain benefits' remain unproven. In the UK it isn't a medicine you can be prescribed. It's sold as a grey-market 'research chemical'. **Standard.** Pinealon (also called EDR, the peptide Glu-Asp-Arg) is one of the 'bioregulator' peptides developed by the Khavinson group in Russia, who claim very short peptides fine-tune gene activity in specific tissues. The brain-targeted version is studied for neuroprotection. In cultured neurons and in rodents it has been reported to reduce markers of cell death after oxidative stress or oxygen deprivation, boost antioxidant enzymes, and preserve neuronal connections in Alzheimer's-type models. This is preclinical science, largely from one institution, and has not been confirmed in independent human trials. Most claims about memory, longevity and 'anti-ageing' are extrapolations from rodents and cells. In the UK it is not a licensed medicine and is sold unlicensed, typically labelled 'not for human consumption'. **Technical.** Pinealon is the tripeptide Glu-Asp-Arg (EDR), a member of the Khavinson family of 'bioregulator' peptides hypothesised to act as epigenetic modulators. The proposed mechanism is that ultra-short peptides penetrate cell and nuclear membranes and bind sequence-specifically to CG-rich promoter regions and histone proteins, modulating DNA methylation, chromatin accessibility and transcription of target genes. In rat cortical neuron cultures under H2O2-induced oxidative stress, EDR has been reported to reduce caspase-3 activation and reactive oxygen species, preserve mitochondrial membrane potential and upregulate antioxidant genes (SOD2, CAT, GPx1). In rodent hypoxia models it reportedly normalised antioxidant enzyme activity and rescued latent-learning deficits. EDR and the related tripeptide KED have been reported to prevent dendritic spine loss in transgenic and in-vitro Alzheimer's-disease models. The mechanistic literature (e.g. the 2021 Molecules EDR paper and the 2022 IJMS neuroepigenetics review) is hypothesis-generating. Trial registration and independent replication are absent, dose-response and pharmacokinetic/bioavailability data in humans are lacking, and the direct-DNA-binding model remains contested outside the originating group. ## How it is thought to work Pinealon is the tripeptide Glu-Asp-Arg (EDR). Its proposed mechanism, per the Khavinson group, is that very short peptides enter cells and the nucleus and bind directly to specific DNA sequences (CG-rich promoter sites) and histones, acting as epigenetic regulators that switch target genes on or off. In neuronal models this is reported to upregulate antioxidant-enzyme genes (e.g. SOD2, catalase), reduce apoptosis markers (caspase-3), lower reactive oxygen species and preserve mitochondrial function and synaptic structure. This direct DNA-interaction model is mechanistically unusual and not independently established. The antioxidant and anti-apoptotic effects are documented mainly in vitro and in rodents. ## Studied for Research contexts, not proven uses. - Neuroprotection against oxidative stress in cultured neurons (in vitro) - Rodent hypoxia/ischaemia models and recovery of learning behaviour - Preservation of dendritic spines in transgenic Alzheimer's-type mouse models - Proposed epigenetic regulation of gene expression / cellular ageing (mechanistic, preclinical) ## What the human evidence shows Very thin to non-existent. There are no completed, registered, independent randomised controlled trials of Pinealon/EDR for any neurological or cognitive outcome. The published literature is dominated by in-vitro neuronal cultures, rodent hypoxia and Alzheimer's-type models, and mechanistic/epigenetic hypothesis papers, with almost all originating from the Khavinson group and affiliated Russian institutions. Claims of human cognitive, memory or longevity benefit should not be treated as demonstrated in people. ## Concerns and unknowns - No meaningful human efficacy or safety data. Benefits are inferred from cells and rodents only. - Near-total reliance on a single research group with little independent replication. Publication-bias and reproducibility concerns are significant. - Sold as an unlicensed grey-market 'research chemical', usually labelled 'not for human consumption'; no UK marketing authorisation. - Grey-market products have no guarantee of identity, purity, sterility or endotoxin content. Injectable peptides carry infection and contamination risks. - The proposed 'peptide binds DNA directly to regulate genes' mechanism is contested and not well established outside the originating group. - Long-term effects of chronic gene expression manipulation in the brain are entirely unstudied in humans. ## UK status Pinealon is not a licensed medicine in the UK and holds no MHRA marketing authorisation. It is not an approved or recognised treatment for any condition, and there are no MHRA-authorised clinical trials of it. In practice it is sold online as an unlicensed "research chemical", typically labelled "not for human consumption" to sidestep medicines regulation. Selling or supplying it for human use would engage the Human Medicines Regulations 2012. It is not something a UK clinician can lawfully prescribe as a recognised therapy. ## Sources 1. EDR Peptide: Possible Mechanism of Gene Expression and Protein Synthesis Regulation Involved in the Pathogenesis of Alzheimer's Disease. Khavinson V, Linkova N, Kozhevnikova E, Trofimova S, Molecules, 2021 2. Neuroepigenetic Mechanisms of Action of Ultrashort Peptides in Alzheimer's Disease. Ilina A, Khavinson V, Linkova N, Petukhov M, International Journal of Molecular Sciences, 2022 3. Peptide Regulation of Gene Expression: A Systematic Review. Khavinson V, Popovich I, Linkova N, Mironova E, Ilina A, Molecules, 2021 4. Search: Pinealon / EDR peptide neuroprotection (PubMed). PubMed _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/pinealon . Educational only, not medical advice. --- # Prostamax **Evidence grade: D (Animal data only).** Area: Libido & Hormonal. > A Russian "bioregulator" sold for prostate health that is really two different products under one banner — a lab-made four-amino-acid peptide with only cell and animal data, and a cow-prostate extract backed by weak Russian studies. **Also known as:** Libidon, KEDP, Lys-Glu-Asp-Pro, prostate peptide bioregulator, prostate cytomax, A-16, khavinson prostate peptide **Class:** Two different things sold under similar names: a synthetic tetrapeptide (Lys-Glu-Asp-Pro, KEDP) and an animal-tissue peptide extract from bovine prostate (a "Cytomax") ## Why this grade The synthetic KEDP peptide has only animal and in-vitro (cell-culture chromatin) data. The related bovine-extract products have Russian clinical reports of low methodological quality that don't meet international RCT standards, and none isolate a defined "Prostamax" molecule. ## In plain terms **Simple.** Prostamax is sold to men as something that keeps the prostate (a gland that sits below the bladder) healthy. The confusing part is that the name is stuck on two completely different things. One is a tiny man-made peptide — a chain of just four building blocks. The other, often called Libidon, is a powder squeezed out of cow prostate glands. Neither has been properly tested in big, fair human trials. The bigger studies behind it come from one group in Russia and weren't run to the strict standards that proper medicines have to pass. So the honest answer is: nobody really knows if it does anything for a human prostate. **Standard.** Prostamax belongs to the Russian "peptide bioregulator" family developed by Vladimir Khavinson's St. Petersburg institute. There are really two products hiding under the name. The grey-market injectable "Prostamax" is a synthetic tetrapeptide, Lys-Glu-Asp-Pro (KEDP), claimed to switch on genes in prostate cells. The oral supplement version (branded Libidon or A-16) is a "Cytomax": a low-molecular-weight peptide fraction extracted from cattle prostate, closely related to the registered Russian urology drug Prostatilen. The evidence is lopsided: the synthetic peptide has only laboratory and animal work (chromatin changes in cultured cells, reduced inflammation in rat prostatitis models), while the human data attached to the extract come almost entirely from older Russian studies on prostatitis and benign prostatic enlargement that were small, often uncontrolled, and never independently replicated. Marketing freely mixes the two, implying the rat and cell findings apply to the pills men actually buy. **Technical.** Prostamax denotes a synthetic tetrapeptide Lys-Glu-Asp-Pro (KEDP; C20H33N5O9, ~487 Da) from the Khavinson short-peptide programme, marketed alongside the tissue-derived "Cytomax" Libidon/A-16 — an ultrafiltered acid-extracted polypeptide complex from bovine prostate that is functionally the precursor chemistry of the registered Russian drug Prostatilen (prostatilen). The proposed mechanism for the synthetic peptide is epigenetic: KEDP and sister peptides (Epitalon, Livagen, Vilon, Cortagen) are reported to bind DNA in a sequence/groove-dependent manner and induce deheterochromatinisation — decondensation of pericentromeric/facultative heterochromatin and de-repression of rRNA genes in senescent lymphocytes (Khavinson, Lezhava, Malinin, Bull Exp Biol Med 2004). Tissue-specific tropism for prostate stroma/epithelium is asserted but the molecular target is undefined. Preclinical rat prostatitis models report reduced oedema, leukocyte infiltration and fibrosis. Human evidence is confined to the tissue-extract lineage (Prostatilen): Russian clinical reports across ~30 years in chronic abacterial prostatitis, BPH and prostatitis-associated fertility/sexual dysfunction describe anti-inflammatory, immunomodulatory and microcirculatory effects, but these are predominantly small, open-label, single-centre, non-blinded studies indexed mainly in Russian-language journals, with no high-quality international RCT and no PK/PD characterisation of orally administered peptide fractions (oral bioavailability of intact peptides is implausible). The synthetic KEDP entity itself has no completed human trial. ## How it is thought to work Two distinct proposed mechanisms map onto the two products. The synthetic KEDP tetrapeptide is claimed to act epigenetically: small DNA-binding peptides in the Khavinson family are reported to unwind tightly packed (hetero)chromatin in ageing cells and reactivate previously silenced genes, including ribosomal RNA genes, supposedly nudging prostate tissue toward a more youthful regulatory state. The bovine-prostate extract (Libidon/Prostatilen lineage) is instead a mixture of small peptides claimed to have tissue tropism for the prostate, exerting anti-inflammatory, antioxidant, antiplatelet/microcirculatory and immunomodulatory effects on prostate stroma and epithelium. Neither mechanism has a defined receptor or validated human target; the chromatin work is in cultured cells and the tissue-specificity claims rest largely on animal and Russian clinical observation. ## Studied for Research contexts, not proven uses. - Chronic prostatitis / chronic pelvic pain syndrome - Benign prostatic hyperplasia (enlarged prostate) - Prostatitis-associated male fertility and sexual dysfunction - Anti-ageing / "cellular rejuvenation" claims (synthetic KEDP) ## What the human evidence shows There is essentially no acceptable human evidence for the synthetic KEDP peptide that grey-market vendors sell as injectable "Prostamax" — its data are cell-culture (chromatin decondensation in aged lymphocytes) and rat prostatitis models. The human studies that marketing leans on belong to the related bovine-prostate extract lineage (Prostatilen, and Cytomax products like Libidon). Russian clinical literature spanning roughly three decades reports benefit in chronic prostatitis, BPH and associated fertility/sexual complaints — for example, anti-inflammatory and immunomodulating effects with improved urination in complicated prostatitis. But these reports are overwhelmingly small, single-centre, frequently uncontrolled or open-label, published mainly in Russian-language journals, and have not been independently replicated or confirmed in a high-quality international randomised controlled trial. For an oral supplement, the further problem is plausibility: intact peptides are largely digested, so oral "Cytomax" capsules delivering an active peptide to the prostate is biologically dubious and untested. Bottom line: thin, low-quality human data on a tissue extract, and none on the defined synthetic molecule. ## Concerns and unknowns - The name covers two different substances (a synthetic tetrapeptide vs a cow-prostate extract); marketing applies cell/animal findings from one to the pills people actually buy. - Almost all human data come from one Russian research lineage, are small/uncontrolled, and have never been independently replicated to international standards. - Oral 'bioregulator' capsules are biologically implausible — peptides are mostly broken down in digestion before reaching the prostate. - Grey-market injectable 'Prostamax' is an unlicensed research chemical with no quality control, sterility guarantee, or proven contents. - Self-treating prostate symptoms (urinary trouble, pelvic pain) with an unproven peptide can delay diagnosis of treatable conditions, including prostate cancer. - Animal-tissue extracts carry theoretical contamination/immunogenicity concerns and inconsistent batch composition. ## UK status Neither the synthetic KEDP peptide nor the bovine-prostate Cytomax extract is a licensed medicine in the UK; the MHRA has authorised no such product. Prostatilen and the Khavinson Cytomaxes are Russian products with no UK marketing authorisation. Injectable "Prostamax" vials are sold as "research chemicals" / "not for human consumption", which places them outside the regulated medicines system — supplying an unlicensed product as a treatment for prostate disease would breach the Human Medicines Regulations 2012. Oral "Libidon" capsules imported as supplements have no recognised UK food-supplement or medicinal status and make health claims that would not be permitted under UK rules. In short: unlicensed, unregulated, and not something a UK clinician can prescribe or recommend. ## Sport / WADA Not on the WADA Prohibited List and not known to be performance-enhancing in sport; it has no established hormonal or anabolic action. As with any unlicensed peptide bought from grey-market sources, an athlete risks contamination with prohibited substances, so use cannot be considered safe from an anti-doping standpoint. ## Key trials - **No registered international randomised controlled trial of synthetic Prostamax (KEDP)** (N/A, None identified). No completed or registered Western/international RCT for the synthetic peptide; evidence is preclinical only. - **Russian-tradition clinical reports of the prostate peptide extract (Prostatilen lineage) in chronic prostatitis and BPH** (Not standardised, Reported (low quality)). Mostly small, open-label, single-centre, Russian-language; not independently replicated. ## Sources 1. Effects of Short Peptides on Lymphocyte Chromatin in Senile Subjects. Khavinson V.Kh., Lezhava T.A., Malinin V.V., Bulletin of Experimental Biology and Medicine, 2004 2. Polypeptide prostatilen in the treatment of patients with complicated prostatitis. Boiko N.I., Likars'ka Sprava (Lik Sprava), 2004 3. Prostatic bioregulatory polypeptide prostatilen: pharmacological properties and 30-year experience of clinical application in urology. Kuzmin I.V., Borovets S.Yu., Gorbachev A.G., Al-Shukri S.Kh., Urology Reports (St. Petersburg) / Urologicheskie vedomosti, 2020 4. Possibilities of using bioregulatory peptide in prostate diseases (Prostatex) — review. Gadzhieva Z.K., Urologiia, 2024 5. Prostamax / KEDP / Libidon — PubMed search. Various, PubMed, 2026 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/prostamax . Educational only, not medical advice. --- # Retatrutide **Evidence grade: B (Promising human evidence).** Area: Weight & Metabolic. > An experimental once-weekly injectable that hits three metabolic hormone receptors at once and has produced the largest trial weight-loss results seen so far. It is not yet an approved medicine. **Also known as:** LY3437943, 'triple-G' agonist, reta, retta, triple g, triple agonist, glp-3 **Class:** Synthetic triple receptor agonist peptide (GLP-1 / GIP / glucagon) ## Why this grade A genuine investigational medicine with large, published, randomised human trials showing some of the biggest weight-loss figures recorded. It scores B rather than A only because it is still in Phase 3 and not yet approved. The human evidence is strong and growing, but not yet final. ## In plain terms **Simple.** Retatrutide is a new weight-loss injection being tested by a big drug company. It copies three of the body's own 'I'm full / handle sugar / burn fuel' signals at the same time, instead of just one like the current injections. In studies, people lost more weight than with any existing medicine. It works in proper human trials, but it hasn't finished testing yet, so you can't get it prescribed. **Standard.** Retatrutide (LY3437943) is an investigational once-weekly peptide from Eli Lilly that activates three receptors. GLP-1, GIP and glucagon together drive appetite reduction and increased energy expenditure. In its Phase 2 obesity trial, participants on the highest dose lost about 24% of body weight at 48 weeks, the largest figure reported for any obesity drug to that point. Phase 3 (the TRIUMPH programme) is underway. This is a real pharmaceutical candidate with robust, peer-reviewed human data. It simply hasn't completed the approval process yet. **Technical.** Retatrutide is a single-molecule triple agonist of the GLP-1, GIP and glucagon receptors. The dual incretin component (GLP-1/GIP) drives satiety and glycaemic control, while glucagon-receptor agonism is hypothesised to raise energy expenditure and promote hepatic lipid mobilisation. This mechanism is also of interest in MASLD/NAFLD. The Phase 2 obesity RCT (Jastreboff et al., NEJM 2023) reported placebo-adjusted weight reduction of roughly 22–24% at the 12 mg dose by week 48, with no apparent plateau, alongside dose-dependent improvements in glycaemia and hepatic fat. Adverse events are dominated by dose-related gastrointestinal effects (nausea, vomiting, diarrhoea) consistent with the incretin class. Transient increases in heart rate have been observed. Phase 3 outcomes (TRIUMPH) will determine durability, cardiovascular and metabolic endpoints, and ultimately licensing. ## How it is thought to work Retatrutide is a unified peptide that switches on three receptors at once. GLP-1 and GIP agonism reduce appetite and improve blood-sugar handling. Glucagon-receptor agonism is thought to increase energy expenditure and mobilise fat from the liver. The combination drives weight loss beyond what single- or dual-agonists achieve. ## Studied for Research contexts, not proven uses. - Obesity / weight management - Type 2 diabetes - Metabolic-associated fatty liver disease (MASLD) ## What the human evidence shows Strong and published. The Phase 2 obesity trial in the New England Journal of Medicine reported up to ~24% body-weight reduction at 48 weeks (the highest seen for an anti-obesity agent at the time), with parallel diabetes and fatty-liver data. The Phase 3 TRIUMPH programme is in progress and will decide durability, cardiovascular safety and approval. This is real clinical-grade evidence, not extrapolation. ## Concerns and unknowns - Not yet approved or licensed anywhere. It remains investigational, so safety conclusions are provisional until Phase 3 completes. - Dose-related gastrointestinal side effects (nausea, vomiting, diarrhoea) are common, as with the whole incretin class. - Transient increases in heart rate have been reported and are still being characterised. - Because it is unapproved, any 'retatrutide' sold online is grey-market, unregulated and of unverified identity and purity. This is a very different and much riskier proposition than a future licensed product. - Long-term outcomes, muscle-mass effects and weight regain after stopping are not yet established. ## UK status Retatrutide is an investigational medicine with no MHRA marketing authorisation. It is not available on prescription or legally for sale in the UK. It can only be received as a participant in an approved clinical trial. Any product marketed to UK consumers as 'retatrutide' is unlicensed and unlawful to supply for human use. For contrast, related GLP-1 medicines such as semaglutide and tirzepatide are MHRA-approved and prescription-only. ## Sport / WADA Not a specific WADA-listed substance, but metabolic modulators and unapproved agents are scrutinised in sport; athletes should treat any unapproved peptide with caution. ## Key trials - **Phase 2 dose-finding study in obesity (Jastreboff 2023)** (NCT04881760, Phase 2, Completed / published). Basis for the headline ~24% weight-loss figure. - **Phase 3 obesity & related outcome trials** (TRIUMPH programme, Phase 3, Ongoing). Will determine durability, safety and whether retatrutide is approved. ## Sources 1. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. Jastreboff AM et al., New England Journal of Medicine, 2023 2. Retatrutide for type 2 diabetes: a randomised, double-blind, Phase 2 trial. Rosenstock J et al., The Lancet, 2023 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/retatrutide . Educational only, not medical advice. --- # SNAP-8 (Acetyl Octapeptide-3) **Evidence grade: C (Early / limited human data).** Area: Skin & Aesthetics. > A face-cream peptide marketed as a needle-free, milder cousin of Botox. The mechanism is plausible, but the evidence is thin and mostly from the manufacturer. **Also known as:** Acetyl Octapeptide-3, SNAP-8, Acetyl Glutamyl Heptapeptide-1, Octapeptide-3 acetate, snap8, argireline alternative **Class:** Topical synthetic neuropeptide (cosmetic anti-wrinkle active); SNAP-25 N-terminal mimetic ## Why this grade Borderline C/D. The mechanism is plausible and SNAP-8 is a real, long-established, widely-sold cosmetic ingredient, but the human evidence is almost entirely manufacturer-sponsored, small, and largely unpublished in independent peer-reviewed journals. The available data consist mostly of in-house consumer-perception and profilometry testing rather than independent randomised, vehicle-controlled, blinded trials. The frequently quoted wrinkle-reduction percentages are supplier marketing data, not independent RCTs. The fundamental unresolved question of whether a large, charged 8-amino-acid peptide actually penetrates intact skin to reach the neuromuscular junction at cosmetic concentrations has never been convincingly answered. It scrapes a C rather than a D only because it is a real cosmetic ingredient with some human cosmetic testing behind it; it falls well short of the robust independent human data needed for a B. ## In plain terms **Simple.** SNAP-8 is an ingredient added to anti-wrinkle creams and serums. The idea is that it gently calms the tiny muscle signals that scrunch your face when you frown or smile, so over time the lines those movements leave behind look softer. People sometimes call it a 'Botox in a jar', but that's misleading. Botox is an injection that strongly switches muscles off. SNAP-8 is a cream that, at best, nudges things a little. The impressive numbers you see advertised come mostly from the company that sells the ingredient, not from independent scientists. Nobody has clearly shown that a fairly big molecule like this actually sinks deep enough into the skin to reach the muscles it's meant to affect. It's generally considered safe to put on your skin, but 'safe' and 'proven to work well' are not the same thing. **Standard.** SNAP-8 (INCI name Acetyl Octapeptide-3) is a synthetic eight-amino-acid peptide used as a topical anti-wrinkle active, developed by the Spanish company Lipotec (now part of Lubrizol Life Science). It was designed as an extended version of Argireline (Acetyl Hexapeptide-8/-3), marketed as being more active. Both are 'neuropeptides' that copy a fragment of SNAP-25, a protein nerves use to release the signal (acetylcholine) that tells facial muscles to contract. The theory is that SNAP-8 competes with the real protein, slightly dampening those micro-contractions so expression lines (crow's feet, forehead lines) form and deepen more slowly. The mechanism is plausible in a test tube. Real-world human proof is weak, and the headline figures trace back to the ingredient supplier's own testing rather than independent, peer-reviewed clinical trials. Peptides this size also struggle to cross the skin's outer barrier, so how much ever reaches the muscle is uncertain. It is a cosmetic, not a medicine: no needles, no prescription, and any effects are subtle and reversible, nothing like botulinum toxin. **Technical.** SNAP-8 is Acetyl Octapeptide-3, a synthetic acetylated octapeptide marketed as a topical 'neurocosmetic' anti-wrinkle active, originated by Lipotec (now Lubrizol Life Science). It is positioned as an elongated analogue of acetyl hexapeptide-8/-3 (Argireline), both modelled on the N-terminal domain of SNAP-25 (synaptosomal-associated protein, 25 kDa). SNAP-25 is one of the three core SNARE proteins (with syntaxin-1 and VAMP/synaptobrevin) that assemble into the ternary SNARE complex driving Ca2+-triggered vesicle fusion and acetylcholine exocytosis at the neuromuscular junction. The proposed mechanism is competitive interference: the peptide mimics the SNAP-25 N-terminus, destabilising or slowing productive SNARE assembly and thereby attenuating ACh release and the strength of repetitive facial muscle micro-contractions. This is conceptually a soft, presynaptic, reversible analogue of botulinum neurotoxin A, which instead enzymatically cleaves SNAP-25. Two pharmacological gaps exist. First, percutaneous delivery: a hydrophilic, charged ~1 kDa peptide faces a steep barrier crossing the stratum corneum and reaching dermal/muscular motor endplates at cosmetically permitted concentrations, and convincing penetration/biodistribution data to the target are lacking. Second, evidence quality: efficacy claims derive predominantly from manufacturer in-vitro assays and small in-house consumer-perception and profilometry studies, not independent randomised, vehicle-controlled, blinded trials with histological or electrophysiological endpoints. There are no registered medicinal (drug) trials because it is regulated as a cosmetic ingredient, not a medicinal product. ## How it is thought to work A synthetic 8-amino-acid peptide that mimics the N-terminal fragment of SNAP-25, a core SNARE-complex protein controlling acetylcholine release at the neuromuscular junction. By competing with native SNAP-25, it is proposed to slow or destabilise SNARE complex assembly, reducing the intensity of facial muscle micro-contractions that drive dynamic expression lines. Applied topically, it is conceptually a much milder, reversible, presynaptic analogue of botulinum toxin, which enzymatically cleaves SNAP-25 rather than competing with it. Whether enough peptide penetrates intact skin to reach motor endplates at cosmetic concentrations is unresolved. ## Studied for Research contexts, not proven uses. - Reduction in the appearance of dynamic expression wrinkles (crow's feet, forehead and glabellar lines) - As a topical, non-injectable alternative concept to botulinum toxin in cosmetics - Comparative cosmetic activity versus Argireline (acetyl hexapeptide-8/-3) ## What the human evidence shows Thin and low-quality by clinical standards. SNAP-8 is a widely-sold cosmetic ingredient with a long market history, but the human data supporting its wrinkle claims are predominantly manufacturer (Lipotec/Lubrizol) in-house testing: small consumer-perception and instrumental (profilometry) studies rather than independent, randomised, vehicle-controlled, blinded clinical trials published in peer-reviewed journals. The commonly cited percentage reductions in wrinkle depth originate from supplier promotional material. There are no registered medicinal trials (NCT programmes) because it is regulated as a cosmetic, not a drug. The related predecessor peptide Argireline has somewhat more published cosmetic literature (including the foundational Blanes-Mira work), but even that is modest and small-scale. SNAP-8 specifically has less independent evidence than its predecessor. The mechanism is plausible, but the human evidence is limited and mostly self-interested. ## Concerns and unknowns - Headline efficacy figures (e.g. large percentage wrinkle reductions, or claims of being more active than Argireline) come from the ingredient manufacturer's own testing, not independent peer-reviewed RCTs. - Skin penetration is the core unanswered question: a large, charged peptide may not cross the stratum corneum in meaningful amounts to reach the neuromuscular junction at cosmetic concentrations. - Effects, if real, are subtle, gradual and reversible, not comparable to botulinum toxin, despite 'Botox in a jar' marketing. - Grey-market 'research chemical' vials sold as powders or solutions 'not for human consumption' have no quality assurance for identity, purity or sterility, unlike a regulated finished cosmetic. - Marketing frequently overstates the strength and certainty of the evidence. ## UK status Not a medicine. In the UK, Acetyl Octapeptide-3 is regulated as a cosmetic ingredient under the UK (Great Britain) Cosmetics Regulation, the assimilated Regulation (EC) No 1223/2009, enforced via the Cosmetic Products Enforcement Regulations 2013 by the Office for Product Safety and Standards (OPSS) and Trading Standards, not by the MHRA. It is legal to sell in finished cosmetic products that carry a valid safety assessment and the required product notification. It is not an MHRA-licensed medicine, has no marketing authorisation, and there is no prescription involved. Raw SNAP-8 sold by peptide vendors as a powder or solution labelled 'for research use only / not for human consumption' sits in an unregulated grey market. Such products are not assessed as either cosmetics or medicines, and attaching medicinal claims to them could bring them within MHRA medicines law. ## Sources 1. A synthetic hexapeptide (Argireline) with antiwrinkle activity. Blanes-Mira C, Clemente J, Jodas G, et al., International Journal of Cosmetic Science, 2002 2. Acetyl Octapeptide-3 — CosIng cosmetic ingredient entry (COSING Ref No. 54131). European Commission CosIng cosmetic ingredient database 3. Cosmeceutical peptides in the framework of sustainable wellness economy (review of neurotransmitter-inhibiting / SNAP-25-mimetic cosmetic peptides). Frontiers in Chemistry, 2020 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/snap-8 . Educational only, not medical advice. --- # SS-31 (Elamipretide) **Evidence grade: B (Promising human evidence).** Area: Longevity. > A peptide that homes in on the power plants of your cells to help them work better. It is now a genuine, if narrowly approved, medicine for one rare disease, but unproven for the anti-ageing uses it is hyped for. **Also known as:** Elamipretide, SS-31, MTP-131, Bendavia, Forzinity, elamipretide hydrochloride, ss31 **Class:** Mitochondria-targeting (cardiolipin-binding) cell-penetrating tetrapeptide ## Why this grade This is the rare peptide that genuinely earns more than a D. It has extensive human trial data and, in September 2025, received an FDA accelerated approval (as Forzinity, from Stealth BioTherapeutics) for the ultra-rare Barth syndrome, to improve muscle strength. That secures a real human-evidence floor in ONE narrow indication. The grade is B rather than A because: (1) it is an *accelerated* approval based on an intermediate surrogate endpoint (knee-extensor muscle strength), with confirmatory clinical-benefit trials still required and approval potentially revocable; (2) it covers a tiny rare-disease population, not the longevity/anti-ageing use it is sold for online; and (3) in the larger, common-disease indications it was actually developed for, it failed. The Phase 3 MMPOWER-3 trial in primary mitochondrial myopathy missed its co-primary endpoints, and programmes in heart failure (HFpEF) and dry AMD/geographic atrophy did not deliver. There is essentially NO human evidence for the healthy-ageing, anti-fatigue or general "mitochondrial rejuvenation" claims made by grey-market sellers; that part of the story is animal/in-vitro only. The grade applies to the molecule's evidence base overall, not to the unlicensed "research chemical" version, which has none of its own. ## In plain terms **Simple.** Every cell has tiny batteries called mitochondria that make its energy. In some rare diseases these batteries are damaged and people get very weak and tired. SS-31 is a small lab-made protein that sticks to a specific fatty part of the battery and helps it hold its shape and run more cleanly. After many years of testing, a medical version (brand name Forzinity) was approved in the US in 2025 for one rare inherited disease called Barth syndrome, where it improved muscle strength. When it was tried in bigger, more common problems like a different muscle disease and heart failure, it did not really work. There is no good human proof it slows ageing or boosts energy in healthy people, even though that is how it is sold online. **Standard.** SS-31 (elamipretide) is a mitochondria-targeting tetrapeptide that binds cardiolipin, a fat unique to the inner membrane of mitochondria. By stabilising that membrane and the energy-producing machinery embedded in it, it aims to restore efficient ATP production and cut the leakage of damaging free radicals. It has a long clinical history under several names (Bendavia, MTP-131) and a lot of human trial data. In September 2025 the US FDA gave accelerated approval to the branded form, Forzinity, to improve muscle strength in Barth syndrome. This is a genuine regulatory milestone that makes it one of very few 'peptides' to become an approved drug. Its larger trials were disappointing: it missed the primary endpoints of a Phase 3 trial in primary mitochondrial myopathy and did not succeed in heart failure or age-related macular degeneration. The picture overall is a real medicine for a rare disease, repeated failures in common diseases, and zero solid human evidence for the general 'longevity / anti-fatigue' use that drives its grey-market sales. **Technical.** Elamipretide (D-Arg-2',6'-dimethyltyrosine-Lys-Phe-NH2; formerly SS-31, MTP-131, Bendavia) is an aromatic-cationic cell-permeable tetrapeptide that concentrates in the inner mitochondrial membrane and binds cardiolipin without entering the matrix. Cardiolipin scaffolds the electron-transport-chain supercomplexes and cristae architecture. By binding cardiolipin and protecting it from peroxidation, elamipretide is proposed to preserve cristae morphology, improve OXPHOS coupling efficiency and ATP synthesis, and reduce mitochondrial ROS emission. Clinical programme: TAZPOWER (NCT03098797; Barth syndrome, TAFAZZIN variants). The randomised crossover phase missed its primary endpoints (6MWT, BTHS-SA), but the open-label extension reported durable gains in muscle strength and cardiac measures, supporting FDA accelerated approval of Forzinity (Sept 2025) on the surrogate endpoint of knee-extensor strength, with confirmatory trials required. MMPOWER-3 (NCT03323749, Phase 3, n=218, primary mitochondrial myopathy) failed its co-primary endpoints (change in 6MWT and PMMSA total fatigue), though a post-hoc nuclear-DNA-variant subgroup signalled possible benefit. Programmes in HFpEF and in dry AMD/geographic atrophy (ReCLAIM/ReCLAIM-2) likewise did not meet primary efficacy endpoints. No registered human trial supports a healthy-ageing/geroprotective indication; that rationale rests on rodent and in-vitro work (e.g. restoration of ATPmax in aged muscle). Tolerability across trials has been reasonable, with injection-site reactions the most frequent adverse event. ## How it is thought to work A synthetic tetrapeptide that penetrates cells and accumulates in the inner mitochondrial membrane, where it binds the phospholipid cardiolipin. Cardiolipin organises the respiratory-chain complexes and the folded cristae structure; by binding cardiolipin and shielding it from oxidative damage, elamipretide is thought to preserve cristae architecture, improve the coupling efficiency of ATP production, and reduce the leakage of reactive oxygen species from damaged mitochondria. In clinical trials it has been given by subcutaneous injection. ## Studied for Research contexts, not proven uses. - Barth syndrome (rare X-linked TAFAZZIN/cardiolipin disorder), now a US-approved indication - Primary mitochondrial myopathy (Phase 3, failed primary endpoints) - Heart failure, including HFpEF, and post-MI cardioprotection - Dry age-related macular degeneration / geographic atrophy - Other genetic mitochondrial diseases (investigator-initiated work) - Preclinical age-related mitochondrial dysfunction (animal/in-vitro only) ## What the human evidence shows Substantial by the standards of peptides sold online, but decidedly mixed. Multiple Phase 2/3 randomised controlled trials exist, and the branded form (Forzinity) received FDA accelerated approval in September 2025 to improve muscle strength in Barth syndrome, based largely on the TAZPOWER programme and its open-label extension. The results across the wider programme are uneven: the Phase 3 MMPOWER-3 trial in primary mitochondrial myopathy missed its co-primary endpoints (6-minute walk distance and fatigue scores), and programmes in heart failure (HFpEF) and dry AMD/geographic atrophy did not succeed. There is NO controlled human evidence for the general anti-ageing, anti-fatigue, exercise-recovery, or 'mitochondrial rejuvenation in healthy people' claims under which it is marketed in the grey market. That case rests entirely on rodent and cell-culture data. The drug has generally been well tolerated in trials, with injection-site reactions the most common issue, but safety data come from sick patient populations over limited durations. ## Concerns and unknowns - Marketing mismatch: it is approved only for an ultra-rare disease (Barth syndrome), and only in the US, yet sold online for vague 'longevity', 'anti-ageing' and 'energy' purposes for which there is no human evidence. - Accelerated approval means the Barth-syndrome benefit rests on a surrogate endpoint (muscle strength); confirmatory clinical-outcome evidence is still required and the approval could be withdrawn if it is not delivered. - Repeated late-stage failures in larger indications (primary mitochondrial myopathy, heart failure, dry AMD) show the mechanism does not reliably translate into clinical benefit in common conditions. - Grey-market 'research chemical' SS-31 is unlicensed and unregulated, sold 'not for human consumption'. There is no guarantee of identity, purity, sterility or correct peptide sequence. - Injectable use carries infection and injection-site risks when self-administered outside medical supervision. - Long-term safety data in healthy people are absent; trial safety data come from sick patients over limited durations. ## UK status As of mid-2026, elamipretide is NOT a licensed medicine in the UK. The September 2025 Forzinity approval is a US FDA accelerated approval only, with no MHRA marketing authorisation. In the UK it is an investigational/unlicensed drug, and any legitimate clinical use would be through a clinical trial or a 'specials'/named-patient route under specialist supervision. The 'SS-31' sold by online peptide vendors is an unlicensed research chemical, marketed 'not for human consumption' to sidestep medicines law. Supplying or selling it for human use without authorisation would breach the Human Medicines Regulations 2012 and fall foul of the MHRA. It is not an approved over-the-counter or prescription product for ageing, fatigue or performance in the UK. ## Sport / WADA Not specifically named on the WADA Prohibited List. As a metabolic/mitochondrial-function modifier it does not fall under the classic peptide-hormone or hormone-axis categories; athletes should nonetheless treat any unlicensed peptide with caution and seek anti-doping guidance, as status can change and S0 (non-approved substances) considerations may apply. ## Key trials - **TAZPOWER: Elamipretide in Barth syndrome (Phase 2/3 randomised crossover plus open-label extension)** (NCT03098797, Phase 2/3, Completed; basis for FDA accelerated approval (Forzinity, 2025)). Missed primary endpoints in the crossover phase; the open-label extension reported sustained muscle-strength and cardiac improvements. - **MMPOWER-3: Elamipretide in Primary Mitochondrial Myopathy (Phase 3)** (NCT03323749, Phase 3, Completed, failed primary endpoints). No significant benefit on 6-minute walk distance or fatigue; post-hoc nuclear-DNA-variant subgroup signal only. ## Sources 1. A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome, a genetic disorder of mitochondrial cardiolipin metabolism (TAZPOWER). Reid Thompson W, et al., Genetics in Medicine, 2021 2. Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial. Karaa A, et al., Neurology, 2023 3. FDA Grants Accelerated Approval to First Treatment for Barth Syndrome (FORZINITY / elamipretide). U.S. Food and Drug Administration press announcement, 2025 4. Elamipretide: A Review of Its Structure, Mechanism of Action, and Therapeutic Potential. International Journal of Molecular Sciences, 2025 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/ss-31 . Educational only, not medical advice. --- # Selank **Evidence grade: C (Early / limited human data).** Area: Cognition & Mood. > A nasal-spray anxiety peptide developed and prescribed in Russia, with promising but mostly Russian small-scale human evidence and no licence in the UK. **Also known as:** TP-7, Thr-Lys-Pro-Arg-Pro-Gly-Pro, TKPRPGP, tuftsin analogue heptapeptide, selank nasal **Class:** Synthetic heptapeptide; tuftsin (immunopeptide) analogue; investigational anxiolytic/nootropic ## Why this grade Human data exist and are more substantial than for most grey-market peptides. Selank is a registered intranasal medicine in Russia, and several Russian clinical studies report anxiolytic effects in generalised anxiety disorder and neurasthenia, including a small randomised comparison against the benzodiazepine medazepam. These trials are small, single-country, and largely from the originating groups; they have not been replicated in independent Western RCTs. It is not licensed anywhere in the West. That places it at early/limited human data rather than robust RCT evidence. Grade C: kept above D by the genuine human data, and below B by the absence of large, well-controlled, independently reproduced trials. ## In plain terms **Simple.** Selank is a tiny man-made protein, sprayed up the nose, that Russian scientists designed to calm anxiety without making you drowsy or dependent. In Russia doctors can prescribe it, and small studies there suggest it eases anxiety about as well as some traditional anti-anxiety pills. Nearly all the evidence comes from one country, the studies are small, and nobody outside Russia has properly confirmed it works. In the UK it is not a prescribable medicine, and anything sold online is an unlicensed research chemical. **Standard.** Selank is a synthetic seven-amino-acid peptide based on tuftsin, a natural immune-signalling molecule. Russian researchers added a few extra building blocks so it survives longer in the body and reaches the brain. It is sold in Russia as a nasal spray, officially registered there for generalised anxiety disorder (GAD) and 'neurasthenia' (an old term for nervous exhaustion). Russian trials report it reduces anxiety roughly comparably to benzodiazepines like medazepam, without the sedation, memory fog or dependence those drugs cause, and possibly with a mild mood- and focus-lifting effect. The human studies are small, largely from the original developers, and have not been independently repeated to Western regulatory standards. In the UK and elsewhere in the West it has never been licensed; what you find online is an unapproved 'research chemical', often labelled 'not for human consumption'. **Technical.** Selank (TP-7, Thr-Lys-Pro-Arg-Pro-Gly-Pro) is a synthetic heptapeptide developed at the Institute of Molecular Genetics, Russian Academy of Sciences (Myasoedov and colleagues). The N-terminal Thr-Lys-Pro-Arg is the immunomodulatory tetrapeptide tuftsin; a C-terminal Pro-Gly-Pro extension confers enzymatic stability and neurotropic activity. Proposed mechanisms are multimodal and incompletely defined: inhibition of enkephalin-degrading enzymes (prolonging endogenous enkephalin tone), modulation of GABAergic signalling (variously described as positive allosteric modulation of GABA binding and as altered expression of GABA-A receptor subunit and related genes, rather than direct receptor agonism), effects on monoamine (serotonin/dopamine) turnover, BDNF upregulation, and immunomodulation (IL-6 and Th1/Th2 cytokine balance). Much of this is characterised in rodent rather than human tissue. It is registered by the Russian Ministry of Health as an intranasal anxiolytic for GAD and neurasthenia. Clinical evidence comprises small Russian studies, including a randomised comparison with medazepam (Zozulia, Neznamov et al., 2008; ~62 patients on Hamilton/Zung/CGI scales) reporting comparable anxiolysis with additional antiasthenic effects, less sedation and no withdrawal on discontinuation. These studies are limited in size, largely from the originating groups, and lack independent Western Phase 2/3 replication. No marketing authorisation exists in the UK, EU or US. ## How it is thought to work A tuftsin-derived heptapeptide given intranasally. Rather than binding a single receptor, it appears to act broadly: inhibiting breakdown of endogenous enkephalins, modulating GABAergic neurotransmission (described both as positive allosteric modulation of GABA binding and as changes in GABA-A receptor subunit gene expression, not direct agonism), normalising serotonin and dopamine turnover, raising BDNF, and exerting immunomodulatory effects on cytokines such as IL-6. Much of this characterisation is from animal work. The net reported clinical effect is anxiolysis without the sedation or dependence typical of benzodiazepines. ## Studied for Research contexts, not proven uses. - Generalised anxiety disorder (GAD) - Neurasthenia / stress-related asthenic states - Anxiety with depressive or asthenic features - Cognitive and attention complaints (nootropic context) - Immunomodulation (cytokine balance) ## What the human evidence shows Genuine human evidence exists, which is unusual for a grey-market peptide. Selank is a registered intranasal medicine in Russia for GAD and neurasthenia, and several Russian clinical studies report meaningful anxiolytic effects, including a small randomised head-to-head comparison against the benzodiazepine medazepam (around 62 patients) using standard psychometric scales (Hamilton, Zung, CGI). Anxiolytic efficacy was characterised as broadly comparable to medazepam, with added antiasthenic effects and without sedation or dependence. These trials are small, mostly conducted by or close to the originating Russian institutions, and have not been independently replicated in large, blinded Western RCTs. There are no UK/EU/US-regulated efficacy trials. It is more evidenced than most peptides in its market niche, but the evidence base remains early, limited and geographically narrow. ## Concerns and unknowns - Not a licensed medicine in the UK, EU or US. It is registered only in Russia. Western product sold online is an unlicensed 'research chemical', often labelled 'not for human consumption'. - Most efficacy data come from small Russian studies, largely from the developers, without independent Western replication. - Grey-market material has no guarantee of identity, purity or sterility; intranasal or injectable use of unregulated product carries contamination and mislabelling risk. - Long-term safety data in humans are sparse; immunomodulatory effects (cytokine changes) are not well characterised over time. - Marketing frequently overstates benefits ('benzo-equivalent, no downsides') beyond what the limited evidence supports. ## UK status Not licensed by the MHRA. Selank has no UK marketing authorisation and is not an approved or prescribable medicine in the UK. It is registered only in Russia. Material sold to UK buyers is an unlicensed, unapproved substance typically marketed as a 'research chemical' and labelled 'not for human consumption'. Supplying or selling it for human use would fall foul of the Human Medicines Regulations 2012. It is not a controlled drug under the Misuse of Drugs Act. ## Sport / WADA Not listed on the WADA Prohibited List as a named substance and not a recognised performance-enhancing agent. Athletes should still exercise caution given its unlicensed status. ## Sources 1. Peptide-based Anxiolytics: The Molecular Aspects of Heptapeptide Selank Biological Activity. Protein and Peptide Letters, 2018 2. Selank Administration Affects the Expression of Some Genes Involved in GABAergic Neurotransmission. Frontiers in Pharmacology, 2016 3. Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia (Zozulia, Neznamov et al.). Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova (Russian), 2008 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/selank . Educational only, not medical advice. --- # Semaglutide **Evidence grade: A (Approved / strong human evidence).** Area: Weight & Metabolic. > A licensed prescription medicine that mimics a gut hormone to suppress appetite, improve blood sugar, and reliably produce weight loss. **Also known as:** Ozempic, Wegovy, Rybelsus, NN9535, sema, semi **Class:** GLP-1 receptor agonist (incretin mimetic) ## Why this grade Semaglutide is a fully licensed UK medicine backed by a large, consistent body of high-quality human trials. The SUSTAIN and PIONEER programmes established efficacy in type 2 diabetes, the STEP programme in obesity (STEP 1 showed roughly 15% mean weight loss over 68 weeks), and the 17,604-patient SELECT trial demonstrated a 20% relative reduction in major adverse cardiovascular events. Efficacy, safety and dose-response are well characterised in humans. The grade applies strictly to the licensed, quality-controlled product, not to grey-market unbranded vials of unverified identity and purity. ## In plain terms **Simple.** Semaglutide mimics a natural hormone your gut releases after eating. It tells your brain you are full and slows your stomach's emptying, so you feel satisfied on less food. It was first made to treat type 2 diabetes (sold as Ozempic), but at higher strengths it produces reliable weight loss (sold as Wegovy). A large study showed it also lowers the risk of heart attacks and strokes in people with heart disease. Unlike most peptides bought online, this is a real, approved medicine with strong evidence. It is a proper drug with genuine side effects and should only be used under a doctor's supervision. **Standard.** Semaglutide is a GLP-1 receptor agonist: a long-acting, engineered form of glucagon-like peptide-1, a hormone released by the gut after meals. It boosts insulin when blood sugar is high, slows stomach emptying, and reduces hunger via appetite centres in the brain. It is licensed in the UK in three forms: Ozempic (a weekly injection for type 2 diabetes), Wegovy (a higher-strength weekly injection for chronic weight management), and Rybelsus (a daily tablet for diabetes). In the STEP obesity trials, semaglutide produced roughly 15% average body-weight loss over about 68 weeks, far beyond placebo. The SELECT trial in people with obesity and established heart disease showed a 20% relative reduction in heart attacks, strokes and cardiovascular deaths. The most common side effects are gastrointestinal: nausea, vomiting, diarrhoea, constipation. It is effective and it is a medicine. The legitimate product is prescription-only. The danger lies in the grey-market 'research chemical' supply, where contents are unverified. **Technical.** Semaglutide is an acylated, structurally stabilised GLP-1 analogue with ~94% homology to native human GLP-1. An Aib substitution at position 8 confers DPP-4 resistance and a C18 fatty-diacid linker drives albumin binding, giving a terminal half-life of approximately one week and enabling once-weekly subcutaneous administration. The oral formulation (Rybelsus) is co-formulated with the absorption enhancer SNAC. It is a selective agonist at the GLP-1 receptor (class B GPCR), producing glucose-dependent insulinotropic and glucagonostatic effects, delayed gastric emptying, and central anorexigenic signalling via hypothalamic and area postrema GLP-1 receptors. The clinical dossier is extensive: the SUSTAIN programme (NCT01720446; glycaemic efficacy and cardiovascular safety), PIONEER (oral), and STEP obesity programme. STEP 1 (NCT03548935; Wilding et al., NEJM 2021) showed ~14.9% placebo-adjusted weight reduction at 68 weeks. SELECT (NCT03574597; Lincoff et al., NEJM 2023) demonstrated 20% relative risk reduction in 3-point MACE in non-diabetic patients with obesity and established ASCVD. Class risks include dose-dependent GI adverse events, gallbladder events, an acute pancreatitis signal, and a rodent C-cell/medullary thyroid carcinoma signal (contraindication in personal or familial MTC or MEN2). Head-to-head data (tirzepatide, SURMOUNT/SURPASS programmes) show greater weight loss with dual GIP/GLP-1 agonism. ## How it is thought to work Selective agonist at the GLP-1 receptor (class B G-protein-coupled receptor). It enhances glucose-dependent insulin secretion, suppresses inappropriate glucagon release, slows gastric emptying, and activates appetite-regulating neurons in the hypothalamus and area postrema, reducing hunger and energy intake. Structural modifications (an Aib substitution at position 8 for DPP-4 resistance and a fatty-acid linker for albumin binding) extend its half-life to roughly one week. Administered subcutaneously (Ozempic/Wegovy) or orally with an absorption enhancer (Rybelsus). ## Studied for Research contexts, not proven uses. - Type 2 diabetes glycaemic control - Chronic weight management in obesity/overweight - Reduction of major adverse cardiovascular events in established cardiovascular disease - Weight loss in adolescents with obesity - Heart failure with preserved ejection fraction in obesity - Chronic kidney disease in type 2 diabetes - Metabolic dysfunction-associated steatohepatitis (MASH) ## What the human evidence shows Extensive and high quality. Multiple large, double-blind, placebo- and active-controlled RCTs across diabetes (SUSTAIN, PIONEER) and obesity (STEP). STEP 1 (n=1,961) showed mean weight loss of about 14.9% versus 2.4% on placebo over 68 weeks. The SELECT trial (n=17,604) showed a 20% relative reduction in major adverse cardiovascular events in people with obesity and prior cardiovascular disease without diabetes. This is among the best-evidenced agents in metabolic medicine. The evidence applies to the licensed, quality-controlled product, not to unbranded grey-market vials of unverified contents, dose accuracy and purity. ## Concerns and unknowns - Very common gastrointestinal side effects: nausea, vomiting, diarrhoea, constipation, especially during dose escalation - Risk of gallbladder disease and a recognised (though uncommon) acute pancreatitis signal - Rodent thyroid C-cell tumour signal; contraindicated in personal or family history of medullary thyroid carcinoma or MEN2 - Loss of lean muscle and bone mass can accompany rapid weight loss. Weight regain is common after discontinuation - Reports of aspiration risk under anaesthesia due to delayed gastric emptying - GREY MARKET: large volumes of unlicensed 'research' semaglutide are sold online 'not for human consumption' with no guarantee of identity, dose accuracy, sterility or purity; counterfeit pens and mislabelled vials are a documented problem - Not for use in pregnancy; should be stopped before planned conception - Prescription-only: self-sourcing bypasses the gradual dose titration and medical screening that mitigate the real risks ## UK status A fully licensed UK medicine, prescription-only (POM), regulated by the MHRA. Marketed as Ozempic and Rybelsus (type 2 diabetes) and Wegovy (chronic weight management). In 2026 the MHRA became the first regulator to approve the highest-strength single-dose Wegovy pen for adults with obesity, and Wegovy is also approved to reduce cardiovascular risk in eligible adults. NICE recommends Wegovy on the NHS within specialist weight-management services for defined BMI thresholds. Ozempic is restricted to diabetes to protect supply and should not be prescribed solely for weight loss. Legitimate access is via prescription. Unbranded semaglutide sold online as a 'research chemical' is unlicensed, of unverified quality, and falls entirely outside regulatory oversight. ## Sport / WADA Not prohibited by WADA; semaglutide and GLP-1 receptor agonists are not on the WADA Prohibited List. ## Key trials - **STEP 1: Semaglutide in adults with overweight or obesity** (NCT03548935, Phase 3, Completed). Pivotal obesity efficacy trial underpinning Wegovy. - **SELECT: Semaglutide effects on cardiovascular outcomes in obesity without diabetes** (NCT03574597, Phase 3, Completed). Demonstrated 20% MACE reduction; basis for CV risk-reduction indication. - **SUSTAIN-6: Cardiovascular and long-term outcomes with semaglutide in type 2 diabetes** (NCT01720446, Phase 3, Completed). Cardiovascular safety/outcomes in type 2 diabetes. ## Sources 1. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). Wilding JPH, et al., New England Journal of Medicine, 2021 2. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). Lincoff AM, et al., New England Journal of Medicine, 2023 3. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SUSTAIN-6). Marso SP, et al., New England Journal of Medicine, 2016 4. Single-dose 7.2 mg semaglutide (Wegovy) pen approved to treat adult patients with obesity. MHRA / GOV.UK, 2026 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/semaglutide . Educational only, not medical advice. --- # Semax **Evidence grade: C (Early / limited human data).** Area: Cognition & Mood. > A Russian brain peptide, prescribed there for strokes and concentration problems, that raises brain growth factors in animals but has almost no independent Western trial evidence. **Also known as:** Semaks, ACTH(4-10) Pro-Gly-Pro, Met-Glu-His-Phe-Pro-Gly-Pro, n-acetyl semax, semax nasal **Class:** Synthetic neuropeptide; ACTH(4-10) analogue (melanocortin-derived heptapeptide) ## Why this grade Genuine human use and human trial data exist. Semax is an approved medicine in Russia and has been studied there in stroke and cognitive patients for decades. But almost all of that evidence is Russian-language, typically small, single-centre, open-label or otherwise methodologically limited, and has never been replicated in large, independent, blinded Western randomised controlled trials. That places it above pure animal-only peptides (D) but well short of the robust, reproducible human RCTs needed for an A or B. Strong mechanistic story, weak independent confirmation; this is a deliberately cautious C, not a generous one. ## In plain terms **Simple.** Semax is a small protein-like molecule that Russian scientists made in the 1980s by copying a piece of a natural body hormone. In Russia it is a real prescription medicine, usually sprayed into the nose, given to people recovering from strokes or with attention and memory problems. In animals it raises the levels of chemicals that help brain cells grow and survive, which is why some people hope it sharpens thinking. Almost all the research is Russian, the studies are often small or not done to strict modern standards, and no big independent trial outside Russia has confirmed it works in people. Outside Russia it is not an approved medicine at all. It is sold online as an unlicensed 'research chemical'. **Standard.** Semax is a synthetic heptapeptide (a chain of seven amino acids) based on the ACTH(4-10) fragment of the hormone ACTH, with an added Pro-Gly-Pro tail that helps it survive longer in the body. It was developed at the Russian Academy of Sciences and has been an approved medicine in Russia since the 1990s, sitting on Russia's list of Vital and Essential Drugs, where it is used (typically as a nasal spray) for ischaemic stroke, transient ischaemic attacks, cognitive disorders and optic nerve disease. Its appeal as a 'nootropic' comes mainly from animal work showing it rapidly raises BDNF (a key brain-growth protein) and nerve growth factor, and influences dopamine and serotonin systems. The human evidence is mostly Russian-language, frequently small, open-label or otherwise limited, and has not been reproduced in large, blinded Western trials. The mechanism is interesting and the Russian clinical tradition is real, but proof of meaningful benefit in healthy people or by modern trial standards is thin. In the UK it is not a licensed medicine and is sold only as an unlicensed substance. **Technical.** Semax is a synthetic heptapeptide, Met-Glu-His-Phe-Pro-Gly-Pro, comprising the ACTH(4-7) core of the ACTH(4-10) melanocortin sequence with a C-terminal Pro-Gly-Pro extension that confers resistance to enzymatic degradation and prolongs half-life. Developed at the Institute of Molecular Genetics, Russian Academy of Sciences, it is registered in the Russian Federation (on the Vital and Essential Drugs list) for ischaemic stroke, TIA, cognitive disorders and optic neuropathy, administered intranasally or parenterally given negligible oral bioavailability. Preclinical pharmacology: Dolotov et al. (Brain Research, 2006) reported that intranasal Semax upregulates hippocampal BDNF (exon-specific mRNA and protein) and increases TrkB receptor phosphorylation, implicating engagement of the BDNF–TrkB neurotrophic axis; further work reports concurrent NGF upregulation, modulation of dopaminergic and serotonergic transmission, and antioxidant/anti-inflammatory and anti-excitotoxic effects relevant to ischaemia. The receptor-level mechanism is incompletely defined. Proposed actions include melanocortin receptor activity and inhibition of enkephalin-degrading enzymes. Human data centre on ischaemic stroke (e.g. Gusev, Martynov et al., Zh Nevrol Psikhiatr Im S S Korsakova, 2018, an open-label study reporting improved functional/motor recovery and raised plasma BDNF), but trials are predominantly single-centre, Russian-language, with heterogeneous design and limited blinding or independent replication. There has been no Western regulatory evaluation. Mechanistic plausibility substantially outstrips the quality of reproducible human efficacy evidence. ## How it is thought to work Semax is an analogue of the ACTH(4-10) fragment of adrenocorticotropic hormone, stabilised against breakdown by a C-terminal Pro-Gly-Pro tail. In animal models it rapidly upregulates brain-derived neurotrophic factor (BDNF) and increases phosphorylation of its TrkB receptor in the hippocampus, engaging the BDNF–TrkB neurotrophic signalling pathway, and also increases nerve growth factor (NGF). It additionally modulates dopaminergic and serotonergic systems and shows antioxidant, anti-inflammatory and anti-excitotoxic effects relevant to ischaemia. The precise receptor-level target in humans is not firmly established. Proposed routes include melanocortin receptor activity and inhibition of enkephalin-degrading enzymes. As a peptide it is given intranasally or by injection rather than orally. ## Studied for Research contexts, not proven uses. - Recovery and neuroprotection after ischaemic stroke and transient ischaemic attack - Cognitive and attention disorders - Optic nerve disease (optic neuropathy) - General cognitive enhancement / nootropic use (largely unproven in humans) - Animal models of Alzheimer's disease and chronic stress ## What the human evidence shows Real human use exists. Semax is an approved prescription medicine in Russia (and used across the CIS) and has been administered to stroke and cognitive-disorder patients for decades, with studies such as Gusev/Martynov et al. (2018) reporting improved neurological and functional recovery alongside raised plasma BDNF. However, the human evidence base is weak by modern standards: it is overwhelmingly Russian-language, often single-centre, small, open-label or otherwise methodologically limited, and has not been independently replicated in large, well-controlled, blinded Western randomised trials. Evidence for benefit in healthy people seeking cognitive enhancement is essentially absent. A genuine clinical tradition and a plausible mechanism exist, but thin reproducible proof of efficacy. ## Concerns and unknowns - Not a licensed medicine in the UK, US or EU. Sold online as an unlicensed 'research chemical' / 'not for human consumption', outside any pharmaceutical quality control. - Almost all efficacy evidence is Russian-language and has not been independently replicated in large blinded Western RCTs; meaningful risk of publication and methodological bias. - Grey-market products carry purity, sterility, dosing-accuracy and contamination risks, especially for injectable or intranasal use. - Long-term safety data, particularly in healthy users taking it for cognitive enhancement, are limited. - Mechanism in humans is incompletely characterised, so off-target or chronic-use effects are poorly mapped. - Marketing routinely overstates 'BDNF-boosting' nootropic benefits by extrapolating from animal data to healthy humans. ## UK status Not a licensed medicine in the UK. Semax has never been evaluated or authorised by the MHRA and holds no UK marketing authorisation. It is not an approved treatment for stroke, cognition or any other indication here. Under the Human Medicines Regulations 2012, a product making medicinal claims would require authorisation, so Semax is sold only as an unlicensed substance, typically labelled a 'research chemical' or 'not for human consumption'. It is not a controlled drug under the Misuse of Drugs Act, but supplying it for human medicinal use without authorisation would breach medicines law. Anyone obtaining it does so outside regulated pharmaceutical supply and quality control. ## Sources 1. Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Dolotov OV, Karpenko EA, Inozemtseva LS, et al., Brain Research, 2006 2. The efficacy of semax in the treatment of patients at different stages of ischemic stroke. Gusev EI, Martynov MYu, Kostenko EV, Petrova LV, Bobyreva SN, Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova, 2018 3. Semax (overview of structure, Russian regulatory status and indications). Wikipedia, 2024 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/semax . Educational only, not medical advice. --- # Sermorelin **Evidence grade: B (Promising human evidence).** Area: Growth Hormone. > A synthetic fragment of the body's own growth-hormone-releasing hormone that nudges the pituitary to make its own growth hormone. Once an approved medicine, now sold grey-market for largely unproven anti-ageing claims. **Also known as:** GHRH (1-29), GRF 1-29, Sermorelin acetate, Geref, Geref Diagnostic, GHRF(1-29)-NH2, ghrh, sermo **Class:** Growth-hormone-releasing hormone (GHRH) analogue / growth hormone secretagogue ## Why this grade Unlike most grey-market peptides, sermorelin has genuine human evidence. It was a fully FDA-approved medicine (Geref), used as a diagnostic test of pituitary growth-hormone reserve and to treat growth hormone deficiency in children, backed by controlled paediatric studies. That regulator-grade paediatric evidence lifts it above the C/D grade typical of research peptides and justifies a B. It falls short of A because the licensed product was discontinued in 2008 and FDA approval withdrawn in 2009 for commercial, not safety reasons. It has never held current UK or US marketing authorisation since. The modern wellness uses it is now sold for (adult vitality, body composition, sleep, longevity) are not what the strong evidence covers. Those claims rest on small, old or extrapolated data, with no robust modern RCTs in healthy adults. The B reflects strong evidence for its historical licensed indications, not weak evidence for what people actually buy it for today. ## In plain terms **Simple.** Your brain has a natural messenger that tells a gland (the pituitary) to release growth hormone. Sermorelin is a lab-made copy of the business end of that messenger. Instead of injecting growth hormone directly, it tells your body to make its own. It used to be a proper, doctor-prescribed medicine, mainly used to test whether children's growth glands were working and to help kids who weren't growing properly. The company stopped selling it because it wasn't making money, not because it was dangerous. Today it is mostly sold online to adults who want it for energy, muscle, sleep or anti-ageing. The strong evidence is about those old medical uses in children, not about making healthy adults feel younger. **Standard.** Sermorelin is the first 29 amino acids of growth-hormone-releasing hormone (GHRH), the shortest piece that still does the full job. GHRH is the natural signal from the hypothalamus (a control centre in the brain) that tells the pituitary gland to release pulses of growth hormone (GH). Because sermorelin stimulates your own pituitary rather than replacing GH directly, the GH release still passes through the body's normal feedback brakes, which makes runaway overshoot harder than with injected GH. It was approved in the US as Geref in 1997 as a diagnostic agent to test pituitary GH response and to treat growth failure in GH-deficient children. The manufacturer discontinued it in 2008 and the FDA formally withdrew the approval effective 2009, not for safety or effectiveness reasons. It was never a mainstream licensed product in the modern UK. It has since reappeared as a grey-market research chemical and, in the US, a compounding-pharmacy product, marketed to adults for body composition, recovery, sleep and longevity uses for which the human evidence is thin and dated. **Technical.** Sermorelin (GHRH(1-29)-NH2, GRF 1-29) is the synthetic amino-terminal 29-residue fragment of endogenous human GHRH (a 44-residue hypothalamic peptide). Residues 1-29 retain essentially full biological potency. It is a GHRH-receptor (GHRHR) agonist acting on somatotrophs of the anterior pituitary, signalling via Gs/adenylate cyclase/cAMP to stimulate synthesis and pulsatile release of growth hormone, with downstream hepatic IGF-1 production. Because it acts upstream and preserves negative feedback (via IGF-1 and somatostatin tone), GH secretion remains broadly physiological and self-limiting compared with exogenous somatropin. It was approved in the US as Geref/Geref Diagnostic (1997) for assessing pituitary somatotroph reserve (note it cannot distinguish hypothalamic GHD, since a blunted response could reflect either the pituitary or absent endogenous GHRH drive) and for paediatric idiopathic GHD, where subcutaneous administration increased GH secretion and height velocity in controlled studies. Plasma half-life is short (on the order of minutes), reflecting rapid proteolytic cleavage. This short duration is one reason longer-acting GHRH analogues (e.g. tesamorelin) and GH-secretagogue-receptor agonists (ghrelin mimetics) were subsequently pursued. EMD Serono discontinued the product in 2008. The FDA withdrew approval effective 2009 and in a 2013 Federal Register notice formally determined the withdrawal was not for reasons of safety or efficacy. There is no current MHRA marketing authorisation. Contemporary adult anti-ageing/recomposition use is unlicensed and not supported by robust modern RCTs in healthy adults. ## How it is thought to work Sermorelin is a GHRH-receptor agonist. It mimics endogenous growth-hormone-releasing hormone at somatotroph cells in the anterior pituitary, activating Gs-coupled cAMP signalling to stimulate synthesis and pulsatile secretion of growth hormone, which in turn raises hepatic IGF-1. Because it acts upstream of the pituitary and leaves the body's somatostatin/IGF-1 negative feedback intact, the resulting GH release is comparatively physiological and self-limiting, rather than the fixed feedback-bypassing exposure delivered by injecting GH directly. It has a very short circulating half-life (on the order of minutes) due to rapid enzymatic degradation. The general route of administration is subcutaneous injection. ## Studied for Research contexts, not proven uses. - Diagnostic testing of anterior-pituitary growth hormone reserve (its original licensed use) - Treatment of idiopathic growth hormone deficiency / growth failure in children (its licensed therapeutic use) - Adult growth hormone insufficiency and age-related decline in GH secretion (older, limited research) - Body composition, recovery and sleep in adults (grey-market / marketing claims, weak evidence) - Anti-ageing and longevity (marketing context, not an established or proven use) ## What the human evidence shows Substantial for its historical licensed indications, weak for what it is sold for today. Sermorelin was a fully approved US medicine (Geref, approved 1997) as a diagnostic test of pituitary GH reserve and for treating growth hormone deficiency in children, where controlled paediatric studies showed increased GH secretion and improved height velocity. That is real, regulator-grade human evidence and is why this scores higher than a typical research peptide. The modern use case driving grey-market demand boosting GH/IGF-1 in healthy or ageing adults for vitality, muscle, fat loss, sleep and longevity rests on small, old or extrapolated data and lacks robust modern randomised trials demonstrating meaningful clinical benefit or long-term safety. The product was discontinued in 2008 and FDA approval was withdrawn effective 2009. The FDA confirmed in a 2013 Federal Register notice that this was not for reasons of safety or effectiveness. ## Concerns and unknowns - No current UK (MHRA) marketing authorisation and no current FDA approval. The licensed product was discontinued in 2008 and approval withdrawn in 2009. Anything sold now is unlicensed. - Grey-market vials sold as research chemicals or not for human consumption carry no guarantee of identity, purity, dose accuracy or sterility. Injecting unregulated product carries infection and contamination risk. - Raising GH/IGF-1 is not consequence-free. Recognised risks of GH-axis stimulation include fluid retention, joint pain, carpal tunnel symptoms, impaired glucose tolerance and insulin resistance. There is a theoretical concern about promoting growth of existing malignancies, warranting caution with any cancer history or active disease. - Evidence for the popular adult anti-ageing and body-composition claims is thin and dated. Marketing routinely overstates benefit by borrowing from the paediatric-deficiency and diagnostic literature. - Even in its legitimate diagnostic role it cannot distinguish GH deficiency of hypothalamic origin. - Use without endocrine supervision means no monitoring of glucose, IGF-1 or adverse effects. - Potential for misuse in sport: stimulating endogenous GH falls under anti-doping prohibitions. WADA prohibits GH secretagogues and GHRH analogues at all times. ## UK status Not a licensed UK medicine. Sermorelin has no current MHRA marketing authorisation and does not appear in the BNF. The historical Geref/Geref Diagnostic products are no longer marketed. The US approval was withdrawn in 2009 following discontinuation in 2008, for commercial rather than safety reasons. In the UK it is encountered only as an unlicensed substance sold through research chemical suppliers, typically labelled not for human consumption to sidestep medicines regulation. Supplying it for human medicinal use without authorisation would breach the Human Medicines Regulations 2012. It is not a controlled drug under the Misuse of Drugs Act, but it is also not legally available as an off-the-shelf treatment outside an authorised or properly governed unlicensed-medicine (specials) route under prescriber responsibility. ## Sources 1. Determination That GEREF (Sermorelin Acetate) Injection Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness. US FDA, Federal Register (2013-04827), 2013 2. Growth hormone secretagogues: history, mechanism of action, and clinical development. Ishida J, et al., JCSM Rapid Communications (Wiley), vol 3, 25-37, 2020 3. Sermorelin: a better approach to management of adult-onset growth hormone insufficiency? (review of GHRH(1-29) pharmacology and clinical rationale). Review literature indexed on PubMed, 2010 4. Sermorelin (overview of structure, GHRH(1-29) pharmacology and Geref approval/withdrawal history). Wikipedia / DrugBank summary, 2024 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/sermorelin . Educational only, not medical advice. --- # Survodutide **Evidence grade: B (Promising human evidence).** Area: Weight & Metabolic. > An experimental once-weekly weight-loss and liver-disease injection that works on two metabolic hormone targets at once. Strong trial results so far, but not yet approved anywhere. **Also known as:** BI 456906, BI456906, glucagon/GLP-1 receptor dual agonist, survo, bi-456906 **Class:** Glucagon receptor (GCGR) / GLP-1 receptor (GLP-1R) dual agonist peptide (incretin-based, once-weekly subcutaneous injectable) ## Why this grade Substantial human evidence for an unapproved peptide. A completed Phase 2 dose-finding obesity trial (Lancet Diabetes Endocrinol 2024) and a completed Phase 2 MASH/fibrosis trial (NEJM 2024) both met their primary endpoints. The first large Phase 3 obesity trial (SYNCHRONIZE-1, 76 weeks) has reported positive results. However, it remains investigational with no regulatory approval, and the wider pivotal programme (further SYNCHRONIZE obesity trials, a cardiovascular outcomes trial, and the LIVERAGE Phase 3 MASH outcome trials) is still ongoing with several trials not yet fully published. This is squarely "human trials exist but incomplete" - Grade B, not A. ## In plain terms **Simple.** Survodutide is an experimental weekly injection being developed as a weight-loss and liver-disease drug. It works like Wegovy and Mounjaro but presses two buttons in the body instead of one. It copies a gut hormone that curbs appetite and also nudges a second hormone called glucagon, which helps the body handle fat and burn energy. In studies, people lost roughly one-sixth of their body weight in one mid-stage trial. It looks promising but is still being tested. No regulator anywhere has approved it yet, so you cannot get it on prescription. Anything sold online claiming to be survodutide is unapproved, unregulated and of unknown contents. **Standard.** Survodutide (codename BI 456906) is an investigational injectable peptide developed by Boehringer Ingelheim and licensed from Zealand Pharma. It is a dual agonist that switches on the GLP-1 receptor (the same target as semaglutide/Wegovy, which curbs appetite and slows stomach emptying) and the glucagon receptor (which can raise energy expenditure and reduce liver fat). Adding glucagon action aims to deliver extra fat-burning and liver benefit on top of GLP-1 appetite suppression. In a mid-stage Phase 2 obesity trial, people lost up to roughly 18-19% of their body weight over about a year. The larger Phase 3 SYNCHRONIZE-1 trial reported up to about 16.6% loss over 76 weeks versus 3.2% on placebo. It also showed positive results in a Phase 2 trial for fatty liver disease (MASH), earning it a US FDA Breakthrough Therapy designation for that use. It is not approved or licensed anywhere yet. The large confirmatory trials are still running. Side effects so far are mainly gastrointestinal (nausea, vomiting), as with other incretin drugs. **Technical.** Survodutide (BI 456906) is a synthetic, acylated, once-weekly GCGR/GLP-1R dual agonist developed by Boehringer Ingelheim under licence from Zealand Pharma. Preclinical work (Zimmermann et al., Mol Metab 2022) characterised it as delivering near-full GLP-1R agonism with partial GCGR agonism at therapeutic exposures, combining GLP-1-mediated anorexia, delayed gastric emptying and glucose-dependent insulinotropism with glucagon-mediated increases in energy expenditure and hepatic lipid handling. The Phase 2 dose-finding obesity trial (le Roux et al., Lancet Diabetes Endocrinol 2024; ~386 adults, BMI >=27, without T2D, 46 weeks) reported up to roughly 18-19% mean weight loss in a per-protocol treatment-completer analysis with no clear plateau. The Phase 2 MASH/fibrosis trial (Sanyal et al., NEJM 2024;391(4):311-319; DOI 10.1056/NEJMoa2401755; biopsy-confirmed MASH with F1-F3 fibrosis, 48 weeks) met its primary endpoint of MASH improvement without worsening of fibrosis (up to approximately 62% on the highest dose versus approximately 14% placebo), with fibrosis improvement of at least one stage without MASH worsening reported in up to approximately 64.5% of F2/F3 patients versus approximately 25.9% placebo. This supported FDA Breakthrough Therapy designation (2024) for non-cirrhotic MASH with moderate-to-advanced fibrosis and the Phase 3 LIVERAGE and LIVERAGE-Cirrhosis programmes. The Phase 3 obesity programme is SYNCHRONIZE (SYNCHRONIZE-1, NCT06066515, obesity without T2D: up to approximately 16.6% weight loss at 76 weeks on the efficacy estimand versus 3.2% placebo; MRI substudy showed preferential visceral and hepatic fat reduction; SYNCHRONIZE-2 in T2D, a SYNCHRONIZE cardiovascular outcomes trial, and SYNCHRONIZE-MASLD are ongoing). GI adverse events (nausea, vomiting, diarrhoea) are titration-dependent and the main tolerability limiter, typical of the class. Glucagon agonism warrants attention to heart rate and glycaemia. No regulatory approval anywhere to date. ## How it is thought to work Dual agonist of the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR), given by subcutaneous injection. GLP-1R activation suppresses appetite, slows gastric emptying and enhances glucose-dependent insulin secretion. GCGR activation is thought to add increased energy expenditure and reduced hepatic fat. The combination aims to amplify weight loss and improve metabolic and liver disease beyond GLP-1 agonism alone. In preclinical characterisation it delivers near-full GLP-1R activation but only partial GCGR activation at therapeutic exposures. ## Studied for Research contexts, not proven uses. - Obesity / overweight (weight management) - Metabolic dysfunction-associated steatohepatitis (MASH/NASH) and liver fibrosis - Type 2 diabetes (glycaemic control, in obesity) - Cardiovascular outcomes in obesity (ongoing outcomes trial) - Reduction of visceral and hepatic fat (imaging substudies) ## What the human evidence shows Genuinely substantial for an unapproved peptide, but still incomplete. Two completed Phase 2 trials met their primary endpoints: a dose-finding obesity trial (le Roux et al., Lancet Diabetes & Endocrinology 2024) showing up to roughly 18-19% mean weight loss over 46 weeks in completers, and a MASH/fibrosis trial (Sanyal et al., NEJM 2024) showing MASH improvement without worsening of fibrosis in up to about 62% of patients on the highest dose versus around 14% on placebo at 48 weeks. The first large Phase 3 obesity trial (SYNCHRONIZE-1, 76 weeks) reported positive results (up to about 16.6% weight loss versus 3.2% placebo on the efficacy estimand). However, the rest of the Phase 3 obesity programme (including a type 2 diabetes trial and a cardiovascular outcomes trial) and the Phase 3 MASH outcome programme (LIVERAGE, LIVERAGE-Cirrhosis) are still ongoing with several trials not yet fully published or completed. Strong mid-stage and emerging late-stage human data exists, but the confirmatory long-term safety and outcomes picture is incomplete and no regulator has reviewed it. ## Concerns and unknowns - Not approved or licensed by the MHRA, FDA, EMA or any other regulator. It remains investigational, so efficacy and long-term safety have not been confirmed by a regulatory review. - Gastrointestinal side effects (nausea, vomiting, diarrhoea) are common and titration-dependent, consistent with the incretin drug class. - Glucagon receptor agonism can raise heart rate and affect glucose and blood pressure. Long-term cardiovascular and metabolic safety is still being established in dedicated trials. - Pivotal Phase 3 obesity and MASH outcome trials are still ongoing. Current weight-loss and liver figures may not fully reflect the eventual licensed picture, and durability after stopping is not yet established. - Anything sold online as survodutide is by definition unlicensed and unregulated material of unverified identity, purity, sterility and content. This is a real quality and safety hazard. - As with other potent weight-loss agents, loss of lean mass and use without medical supervision are genuine concerns. ## UK status Not a licensed UK medicine. Survodutide is investigational with no MHRA marketing authorisation, so it cannot be lawfully sold or prescribed as an approved medicine in the UK. Legitimate access is only through authorised clinical trials. It is not a controlled drug, but supplying or selling an unlicensed medicinal product for human use is restricted under the Human Medicines Regulations 2012. Material marketed online as a research chemical or not for human consumption is unlicensed, unregulated and sits entirely outside any quality or safety oversight. ## Sport / WADA Not specifically listed by name on the WADA Prohibited List. GLP-1/glucagon dual agonists are not established performance-enhancing agents and are not recognised doping agents; any status would follow general WADA rules rather than a named prohibition. ## Key trials - **A Study to Test Safety and Efficacy of Survodutide (BI 456906) in Adults With NASH/MASH and Fibrosis (F1-F3)** (NCT04771273, Phase 2, Completed). MASH/fibrosis trial published in NEJM 2024. - **SYNCHRONIZE-1: Phase 3 trial of survodutide for obesity/overweight without type 2 diabetes** (NCT06066515, Phase 3, Reported topline (76 weeks); full publication pending). Up to ~16.6% weight loss vs 3.2% placebo on the efficacy estimand. - **LIVERAGE: Phase 3 trial of survodutide in MASH with moderate-to-advanced fibrosis (F2-F3)** (NCT06632444, Phase 3, Ongoing). Pivotal MASH outcome trial. NCT identifier should be re-verified before publication. ## Sources 1. A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis. Sanyal AJ, et al., New England Journal of Medicine 2024;391(4):311-319, 2024 2. Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial. le Roux CW, et al., The Lancet Diabetes & Endocrinology 2024;12(3):162-173, 2024 3. BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist. Zimmermann T, et al., Molecular Metabolism, 2022 4. Survodutide Phase III SYNCHRONIZE-1 obesity trial results (company announcement). Boehringer Ingelheim, Boehringer Ingelheim press release, 2026 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/survodutide . Educational only, not medical advice. --- # TB-500 **Evidence grade: D (Animal data only).** Area: Recovery & Repair. > A lab-made fragment of a natural repair protein, sold as a research chemical for healing and recovery on the strength of animal studies, with no proven human benefit. **Also known as:** TB500, TB4 fragment, Thymosin beta-4 (17-23) fragment, Ac-LKKTETQ, Tβ4 fragment, tb4, thymosin beta-4, wolverine stack **Class:** Synthetic peptide fragment (actin-binding 17-23 domain of thymosin beta-4) ## Why this grade TB-500 is the synthetic, N-terminally acetylated actin-binding heptapeptide fragment (Ac-LKKTETQ, residues 17-23) of thymosin beta-4. Claimed regenerative and anti-inflammatory effects rest almost entirely on animal and in-vitro work. Human clinical trials in wound healing, dry eye, neurotrophic keratopathy, and cardiac repair all used full-length thymosin beta-4 (RegeneRx's RGN-259/RGN-352), not the TB-500 fragment, and none produced a licensed medicine anywhere. An early-phase trial of the fragment itself in stable cardiovascular disease (NCT07487363) was registered in 2025 and is only now recruiting, with no efficacy results. For the substance actually sold as TB-500, meaningful human efficacy evidence is essentially absent. Grade D. ## In plain terms **Simple.** Your body makes a protein called thymosin beta-4 that helps cells move and repair damage after injury. TB-500 is a small man-made piece of that protein. In mice and other animals it speeds up healing of wounds, muscle and heart tissue, which is why athletes and gym-goers buy it to recover faster. Almost all the good news comes from animals. The fragment people actually inject as TB-500 has barely been tested in humans, it is not a licensed medicine, and it is banned in sport. It is sold as a chemical 'not for human consumption', so purity and content are unverified. **Standard.** TB-500 is a synthetic copy of one active region (amino acids 17-23) of thymosin beta-4, a small natural protein that binds actin and is involved in cell migration, blood-vessel growth, inflammation control and tissue repair. Animal and cell studies show encouraging results across skin wounds, muscle, tendon and heart injury. However, the real human clinical trials used full-length thymosin beta-4 (programmes like RGN-259 for eye-surface disease), not the TB-500 fragment sold to consumers. That human data therefore does not transfer to what is in the vial. The first early-phase human study of the fragment itself only began recruiting in 2025 and has no results. In the UK, TB-500 is not an approved or prescribable medicine; it is an unlicensed research chemical. It is banned at all times by WADA. Buying it means trusting an unregulated supplier on purity and content. **Technical.** TB-500 is the N-terminally acetylated thymosin beta-4 (17-23) heptapeptide, Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln (Ac-LKKTETQ), corresponding to the actin-binding motif of the 43-residue G-actin-sequestering protein Tβ4. Tβ4 modulates actin dynamics and cytoskeletal remodelling and exerts pleiotropic effects on cell migration, angiogenesis, anti-apoptosis, anti-fibrosis and inflammation, partly via downregulation of pro-inflammatory cytokines and modulation of cardiac remodelling pathways. Preclinical models show accelerated dermal and corneal re-epithelialisation, cardioprotection post-MI, and tendon/skeletal-muscle repair. The substantive human evidence base is for intact Tβ4, not the 17-23 fragment. RegeneRx's RGN-259 (topical Tβ4, timbetasin) reported a positive epithelial-healing signal in a small randomised, placebo-controlled Phase III neurotrophic keratopathy study (IJMS 2023). Earlier Phase 2 dermal trials (pressure/stasis ulcers, epidermolysis bullosa; NCT00311766) used the full-length peptide. No Tβ4 product holds marketing authorisation. For the TB-500 fragment specifically, human-relevant data derive predominantly from anti-doping metabolism and detection work (WADA-funded; Esposito et al., Drug Test Anal 2012). An early-phase ASCVD biomarker study of the 17-23 fragment (NCT07487363, Phase 1/2, recruiting from 2025) is nascent. Pharmacology is plausible; clinical proof for the fragment is absent. ## How it is thought to work Thymosin beta-4 is the body's main actin-sequestering peptide and orchestrates cytoskeletal remodelling, cell migration, angiogenesis, anti-apoptotic signalling and dampening of inflammation and fibrosis in injured tissue. TB-500 is the short acetylated 17-23 fragment containing the actin-binding motif (Ac-LKKTETQ), proposed to reproduce some of these regenerative actions. It is typically delivered by injection in grey-market use. Most mechanistic evidence is preclinical; effects demonstrated for the full-length protein cannot be assumed to hold for the fragment. ## Studied for Research contexts, not proven uses. - Skin and dermal wound healing (animal models; human trials used full-length Tβ4) - Muscle, tendon and ligament repair (preclinical) - Cardiac repair and remodelling after myocardial infarction (preclinical; early human study of full-length Tβ4) - Corneal and ocular surface healing – neurotrophic keratopathy, dry eye (human trials with full-length Tβ4 / RGN-259) - Anti-inflammatory and anti-fibrotic effects (preclinical) - Anti-doping detection and metabolism (the main human-relevant research on the fragment itself) ## What the human evidence shows Thin and often misrepresented. The credible human trials, including Phase 2 dermal ulcer/epidermolysis bullosa studies and the Phase III RGN-259 ophthalmic study in neurotrophic keratopathy, all used full-length thymosin beta-4, not the TB-500 fragment sold to consumers. Those results are at best preliminary and have not produced any approved medicine anywhere. Essentially the only human-relevant data on the TB-500 (17-23) fragment come from anti-doping metabolism and detection studies. The first early-phase human trial of the fragment, a cardiovascular biomarker study, was registered in 2025 and only began recruiting. No robust human efficacy evidence supports the recovery claims made for TB-500. ## Concerns and unknowns - Human efficacy unproven: marketing leans on animal data and on trials of a different (full-length) molecule. - Unlicensed in the UK – not an approved or prescribable medicine; sold as a 'research chemical, not for human consumption', so purity, identity and sterility are unverified. - Theoretical cancer/angiogenesis concern: a peptide that promotes cell migration and new blood-vessel growth could in principle aid tumour growth or metastasis; this has not been adequately characterised in humans. - No established human safety profile, long-term data or quality control for the fragment. - Banned at all times by WADA (class S2) – a positive test can end a sporting career; also relevant to drug-tested professions. - Grey-market supply means real risk of contamination, mislabelling and incorrect content. ## UK status Not a licensed medicine and not approved by the MHRA for any use. There is no marketing authorisation for thymosin beta-4 or the TB-500 fragment. It is not prescribable. In practice it is sold as an unlicensed research chemical labelled 'not for human consumption'. Supplying or marketing it for human use would breach the Human Medicines Regulations 2012. ## Sport / WADA Prohibited at all times (in and out of competition) under WADA class S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics). ## Key trials - **0.1% RGN-259 (Thymosin β4) Ophthalmic Solution in Neurotrophic Keratopathy (SEER-1)** (Phase 3, Completed / reported (2023)). Used FULL-LENGTH thymosin beta-4, not the TB-500 fragment. Positive epithelial-healing signal in a small cohort; no resulting approval. - **Thymosin Beta 4 on Wound Healing in Patients With Epidermolysis Bullosa** (NCT00311766, Phase 2, Completed). Full-length Tβ4 dermal wound-healing study. - **TB-500 (Thymosin Beta 4 17-23 Fragment) for Cardiovascular Biomarkers in Stable ASCVD** (NCT07487363, Phase 1/2, Recruiting (registered 2025)). First trial of the TB-500 fragment itself in humans; biomarker/safety endpoints, no efficacy results yet. ## Sources 1. 0.1% RGN-259 (Thymosin β4) Ophthalmic Solution Promotes Healing and Improves Comfort in Neurotrophic Keratopathy Patients in a Randomized, Placebo-Controlled, Double-Masked Phase III Clinical Trial. International Journal of Molecular Sciences, 2023 2. Synthesis and characterization of the N-terminal acetylated 17-23 fragment of thymosin beta 4 identified in TB-500, a product suspected to possess doping potential. Esposito S et al., Drug Testing and Analysis, 2012 3. Investigation of in vitro/ex vivo TB-500 metabolism, synthesis of relevant metabolites and detection limits in urine and plasma. World Anti-Doping Agency (WADA) funded research, 2018 4. Thymosin Beta 4 on Wound Healing in Patients With Epidermolysis Bullosa. ClinicalTrials.gov, 2006 5. TB-500 (Thymosin Beta 4 17-23 Fragment) for Cardiovascular Biomarkers in Stable ASCVD. ClinicalTrials.gov, 2025 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/tb-500 . Educational only, not medical advice. --- # Tesamorelin **Evidence grade: A (Approved / strong human evidence).** Area: Growth Hormone. > A lab-made copy of the body's own growth-hormone trigger that is an approved prescription medicine in the US for shrinking deep belly fat in people with HIV, but is not licensed in the UK. **Also known as:** Egrifta, Egrifta SV, Egrifta WR, TH9507, tesamorelin acetate, tesa, ghrh **Class:** Synthetic growth hormone-releasing hormone (GHRH) analogue (GHRH receptor agonist / GH secretagogue) ## Why this grade Grade A applies specifically to reducing excess visceral abdominal fat in HIV-associated lipodystrophy. It is a licensed medicine (FDA-approved as Egrifta in 2010, with reformulations since) backed by large randomised, double-blind, placebo-controlled Phase 3 trials plus a smaller RCT in HIV-associated liver fat. This Grade A does not transfer to general fat loss, bodybuilding or anti-ageing use in healthy adults, where there is no comparable RCT evidence. ## In plain terms **Simple.** Your body makes a natural signal that tells a gland in your head (the pituitary) to release growth hormone in little bursts. Tesamorelin is a man-made version of that signal, tweaked to last longer in the blood. Some people with HIV develop a build-up of deep fat around their organs as a side effect of older HIV medicines. In those people, tesamorelin nudges the gland to release more growth hormone, which helps shrink that deep belly fat. It is a genuine, properly tested prescription drug for that one specific problem in the US. It is not approved in the UK, and the evidence does not back using it for ordinary weight loss or anti-ageing. **Standard.** Tesamorelin is a synthetic analogue of growth hormone-releasing hormone (GHRH), the brain peptide that tells the pituitary gland to secrete growth hormone (GH). Because it acts on the body's own GH machinery rather than supplying GH directly, it produces natural pulsatile GH release. It is well-evidenced for one thing: reducing excess visceral (deep abdominal) fat in people with HIV-associated lipodystrophy, where it was FDA-approved as Egrifta in 2010 on the back of large Phase 3 trials. A smaller trial also examined fatty liver disease in people with HIV. Outside that approved HIV context, claims about body recomposition, general fat loss and anti-ageing rest on extrapolation rather than direct proof. It is not licensed by the MHRA in the UK, so anything sold to UK buyers online is unlicensed. **Technical.** Tesamorelin (TH9507) is a synthetic GHRH(1-44) analogue bearing a trans-3-hexenoyl group on the N-terminal tyrosine, a modification conferring resistance to dipeptidyl peptidase-4 (DPP-4) cleavage and prolonging plasma stability while retaining agonism at the pituitary GHRH receptor (GHRHR), a class B GPCR. It augments endogenous pulsatile GH secretion and raises IGF-1 while preserving physiological somatostatin feedback, rather than bypassing it as exogenous rhGH does. FDA approval (Egrifta, 2010; reformulations Egrifta SV 2019 and the F8 'weekly reconstitution' Egrifta WR in March 2025) rests on pivotal randomised placebo-controlled Phase 3 trials in HIV-associated lipodystrophy demonstrating clinically meaningful CT-measured reductions in visceral adipose tissue versus placebo, with triglyceride improvement and partial regain on discontinuation. Stanley et al. (Lancet HIV 2019; NCT02196831; n=61) showed reduced hepatic fat fraction, with a secondary signal of attenuated fibrosis progression, in HIV-associated NAFLD. Key pharmacovigilance signals: dose-related IGF-1 elevation, glucose intolerance/insulin resistance, fluid retention and arthralgia; contraindicated in active malignancy and in disruption of the hypothalamic-pituitary axis. Efficacy in non-HIV populations is not established by adequate RCTs. ## How it is thought to work Tesamorelin is a stabilised analogue of growth hormone-releasing hormone that binds the GHRH receptor on pituitary somatotrophs, stimulating endogenous pulsatile release of growth hormone and raising IGF-1. Because it acts on the body's own GH axis rather than supplying external GH, normal somatostatin negative feedback is preserved. An N-terminal hexenoyl modification resists DPP-4 degradation, prolonging its activity. The resulting increase in GH/IGF-1 signalling promotes lipolysis, preferentially reducing visceral adipose tissue. ## Studied for Research contexts, not proven uses. - Reduction of excess visceral abdominal fat in HIV-associated lipodystrophy (approved indication) - Non-alcoholic fatty liver disease (hepatic steatosis) in people with HIV - Liver fibrosis progression in HIV-associated NAFLD (secondary endpoint in a small trial) - Effects on lipid profile and metabolic markers - Exploratory interest in cognition and general body composition (limited / poor-quality evidence) ## What the human evidence shows Strong within its approved niche, weak everywhere else. Large randomised, double-blind, placebo-controlled Phase 3 trials showed clinically meaningful reductions in visceral adipose tissue (roughly 15-18% versus placebo) in people with HIV-associated lipodystrophy, supporting FDA approval as Egrifta in 2010 (later reformulated as Egrifta SV in 2019 and Egrifta WR in 2025). A separate, smaller randomised trial (Stanley et al., Lancet HIV 2019; NCT02196831; n=61) showed reduced liver fat with a secondary signal of less fibrosis progression in HIV-associated NAFLD. The benefit on visceral fat reverses after stopping treatment. This robust evidence is almost entirely confined to people with HIV. There is no comparable RCT base supporting tesamorelin for general fat loss, bodybuilding or anti-ageing in otherwise healthy adults. ## Concerns and unknowns - Not licensed by the MHRA in the UK for any indication; any UK online supply is unlicensed and often sold as a 'research chemical' not for human use, with no quality assurance of identity, purity or sterility - Raises IGF-1 and GH, which can cause or worsen insulin resistance and glucose intolerance - Fluid retention, peripheral oedema, arthralgia and injection-site reactions reported in trials - Theoretical and label-cautioned concern about stimulating growth of occult malignancy; contraindicated in active cancer - Benefits on visceral fat are not durable and regress after the drug is stopped - Evidence outside the HIV-lipodystrophy population is weak; marketing for cosmetic fat loss or anti-ageing outruns the data - Grey-market product may not be genuine tesamorelin, or may be incorrectly formulated or non-sterile ## UK status Not licensed by the MHRA in the UK. It is approved as a prescription medicine in the US (Egrifta, Egrifta SV, Egrifta WR) for excess visceral abdominal fat in HIV-associated lipodystrophy. In the UK it would only be obtainable as an unlicensed medicinal product (such as a named-patient import under a prescriber's responsibility) or, illegitimately, via grey-market vendors selling it as a research chemical labelled "not for human consumption". Such unlicensed supply carries no guarantee of identity, purity or sterility. ## Key trials - **Tesamorelin Effects on Liver Fat and Histology in HIV** (NCT02196831, Phase 2/3, Completed). Stanley et al., Lancet HIV 2019; reduced liver fat with a secondary signal of attenuated fibrosis progression in HIV-associated NAFLD (n=61). - **Pivotal Phase 3 HIV-lipodystrophy programme (Falutz et al.)** (Phase 3, Completed). Randomised, double-blind, placebo-controlled trials demonstrating ~15-18% visceral fat reduction; basis for FDA approval of Egrifta in 2010. ## Sources 1. Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation (pivotal Phase 3 trial). Falutz J, et al., New England Journal of Medicine, 2007 2. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. Stanley TL, et al., The Lancet HIV, 2019 3. Egrifta (tesamorelin) US Prescribing Information / FDA approval. Theratechnologies / US FDA, Drugs@FDA (Theratechnologies; original approval 2010, Egrifta WR/F8 approved March 2025), 2010 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/tesamorelin . Educational only, not medical advice. --- # Tesofensine **Evidence grade: B (Promising human evidence).** Area: Weight & Metabolic. > A failed Parkinson's/Alzheimer's brain drug, repurposed as a potent appetite suppressant — it produced striking weight loss in a Phase II trial but has never made it through to a licensed obesity medicine. **Also known as:** ns2330, tesofensine peptide (misnomer), the tesomet ingredient **Class:** Small-molecule triple monoamine (serotonin–noradrenaline–dopamine) reuptake inhibitor of the phenyltropane family — not a peptide ## Why this grade A genuine, well-run Phase IIb RCT in obese patients (Astrup, Lancet 2008) showed large weight loss, and a completed Phase III obesity programme in Mexico met its endpoints — but it is not an approved medicine anywhere with a confirmed marketing authorisation (Mexico's regulator gave only a non-binding favourable opinion, not market approval), and development has repeatedly stalled. Real human trials exist but the package is incomplete. ## In plain terms **Simple.** Tesofensine is not actually a peptide, even though it gets sold alongside them. It's a brain chemical drug that was first tested for Parkinson's and Alzheimer's disease — it flopped for those. But researchers noticed people on it lost a lot of weight, so they tested it for that instead. It works by turning up three of the brain's 'mood and reward' chemicals at once, which dampens hunger and makes food less tempting. In one proper trial it produced big weight loss — but it also pushed up people's heart rate and blood pressure, and it has never been approved as a real medicine. Today it mostly floats around grey-market 'peptide' shops, which is not where a powerful brain drug should be coming from. **Standard.** Tesofensine (NS2330) is a small-molecule triple monoamine reuptake inhibitor — it blocks the brain's recycling of serotonin, noradrenaline and dopamine simultaneously, so all three build up. NeuroSearch originally developed it for Parkinson's and Alzheimer's; it failed those trials, but an unexpected appetite-suppressant effect redirected it toward obesity. The headline data is the 2008 Phase II TIPO-1 trial in The Lancet: over 24 weeks, obese patients on the mid and top doses lost roughly 9–11% more than placebo — about double what the obesity drugs available at the time achieved. That's real, robust human evidence, which is rare among the 'peptides' sold online. The catch is that it raises heart rate and blood pressure and can affect mood and sleep, which is exactly why it has never crossed the finish line to approval despite a completed Phase III programme in Mexico. It is unlicensed in the UK. **Technical.** Tesofensine (NS2330) is a phenyltropane-derived triple reuptake inhibitor with high-affinity blockade of the dopamine, noradrenaline and serotonin transporters (DAT/NET/SERT). It has an extremely long human half-life (~9 days for the parent, ~16 days for the desalkyl metabolite NS2360), giving substantial accumulation and a slow approach to steady state — though NS2360 contributes only a small fraction of pharmacological activity. Anorectic action is attributed to enhanced central monoaminergic tone — increased satiety and reduced reward-driven intake — with preclinical work implicating modulation of lateral hypothalamic GABAergic neurons; a thermogenic component (increased resting energy expenditure) is proposed but less firmly established. The pivotal human dataset is the Phase IIb TIPO-1 RCT (Astrup et al., Lancet 2008; n=203): placebo-subtracted mean weight loss of 4.5%, 9.2% and 10.6% at 0.25, 0.5 and 1.0 mg over 24 weeks. The dose-limiting liability is sympathomimetic: dose-dependent rises in heart rate and blood pressure plus mood/sleep disturbance, mirroring the historical regulatory problem with centrally acting anorectics. Later development pursued Tesomet (tesofensine + the beta-1 blocker metoprolol) to blunt the cardiovascular signal, targeting rare hypothalamic obesity and Prader-Willi syndrome; that programme reached Phase 2b and has been paused for funding reasons. ## How it is thought to work It inhibits the presynaptic reuptake transporters for serotonin, noradrenaline and dopamine, raising the synaptic concentration of all three monoamines in the brain. The net effect is appetite suppression — greater satiety and reduced reward-driven, emotional and snack eating — with a proposed secondary increase in resting energy expenditure. Preclinical data suggest it acts in part by silencing GABAergic neurons in the lateral hypothalamus, a feeding-control hub. The same broad monoaminergic activation also drives its main downside: sympathetic stimulation raising heart rate and blood pressure. ## Studied for Research contexts, not proven uses. - Obesity / weight loss - Hypothalamic obesity (as Tesomet) - Prader-Willi syndrome (as Tesomet) - Parkinson's disease (failed) - Alzheimer's disease (failed) ## What the human evidence shows Unusually for something sold in the grey 'peptide' market, tesofensine has real human RCT data. The Phase IIb TIPO-1 trial (Astrup et al., Lancet 2008; 203 obese adults, 24 weeks) showed placebo-subtracted weight loss of 4.5%, 9.2% and 10.6% at the 0.25, 0.5 and 1.0 mg doses respectively — about double the obesity drugs licensed at the time. A Phase III obesity programme was later run in Mexico via the partner Medix (372 patients), and was reported to meet its primary and secondary endpoints with roughly 10% mean weight loss over 24 weeks. Mexico's regulator (Cofepris) issued a favourable but non-binding technical opinion in 2023, which is explicitly not a market authorisation, and as of late-2024 reporting full approval had still not been granted. Trials also consistently flagged dose-dependent increases in heart rate and blood pressure and some mood/sleep effects. So: genuine, sizeable efficacy signal in humans, but no confirmed marketing authorisation anywhere and a development history that has repeatedly stalled. ## Concerns and unknowns - It is a centrally acting brain drug, not a benign peptide — it raises heart rate and blood pressure in a dose-dependent way, the classic liability that has sunk previous appetite suppressants over cardiovascular safety. - Because it boosts dopamine, noradrenaline and serotonin, it can disturb mood and sleep and raises the prospect of psychiatric side effects; combining it with antidepressants or other serotonergic drugs risks serotonin toxicity. - Its half-life is exceptionally long (the parent ~9 days, the metabolite ~16 days), so the drug accumulates for weeks and any adverse effect clears very slowly — a poor fit for casual, unsupervised use. - It has no UK or US marketing authorisation; material sold online is unlicensed and of unknown identity, purity and dose, with no manufacturing oversight. - Being labelled and sold as a 'peptide' is itself a red flag — it is a synthetic small molecule, and the mislabelling signals an unregulated supply chain. ## UK status Tesofensine has no marketing authorisation from the MHRA and is not a licensed medicine in the UK. It is an investigational small-molecule drug; any product offered for sale (including as a 'research chemical' or 'peptide') is unlicensed and may not lawfully be supplied or promoted for human consumption under the Human Medicines Regulations 2012. As a centrally acting agent affecting blood pressure, heart rate and mood, it is the kind of substance the MHRA would expect to be prescription-only were it ever licensed. ## Sport / WADA Not listed on the WADA Prohibited List by name. However, as a stimulant that inhibits dopamine and noradrenaline reuptake and raises sympathetic tone, it is plausibly caught by the catch-all 'other substances with a similar chemical structure or similar biological effect(s)' language under the S6 Stimulants class (prohibited in-competition). Athletes should treat it as high-risk and seek formal guidance rather than assume it is permitted. ## Key trials - **TIPO-1: Effect of Tesofensine on Weight Reduction in Patients With Obesity (NCT00394667)** (Phase II, Completed). 203 obese adults, 24 weeks; large dose-dependent weight loss vs placebo. Published in The Lancet, 2008. - **TIPO-4 open-label extension** (Phase II, Completed). Open-label extension reporting maintained weight loss in continuing patients. - **Phase III obesity programme in Mexico (Medix/Saniona)** (Phase III, Completed; regulatory review (no approval granted)). 372 patients; reported to meet primary and secondary endpoints with ~10% mean weight loss over 24 weeks. Cofepris issued a non-binding favourable opinion (2023) but full market approval was not granted as of late-2024 reporting. - **Tesomet (tesofensine + metoprolol) in hypothalamic obesity and Prader-Willi syndrome** (Phase II, Paused). Combination designed to offset cardiovascular effects; reached Phase 2b but paused due to funding rather than safety/efficacy. ## Sources 1. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Astrup A, Madsbad S, Breum L, Jensen TJ, Kroustrup JP, Larsen TM, The Lancet, 2008 2. Tesofensine — a novel potent weight loss medicine (evaluation of Astrup et al., Lancet 2008). Doggrell SA, Expert Opinion on Investigational Drugs, 2009 3. Tesofensine — Wikipedia (pharmacology, development history, half-life and regulatory status). Wikipedia, 2026 4. Effect of Tesofensine on Weight Reduction in Patients With Obesity (TIPO-1 registry record). ClinicalTrials.gov, 2008 5. Tesofensine and Tesomet development status (hypothalamic obesity, Prader-Willi, Mexico Phase III). Saniona pipeline and PubMed search, 2024 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/tesofensine . Educational only, not medical advice. --- # Thymalin **Evidence grade: C (Early / limited human data).** Area: Longevity. > A Soviet-era extract of calf thymus glands, claimed to "reset" an ageing immune system — backed by decades of striking-looking Russian longevity data that almost nobody outside Russia has been able to check or repeat. **Also known as:** thymalin, thymus polypeptide complex, calf thymus extract, thymulin (NB: different peptide — often confused), khavinson thymic bioregulator **Class:** Polypeptide complex (mixture of short peptides) extracted from calf thymus ## Why this grade There is genuine human data — including one small randomised single-blind controlled trial — which lifts it above animal/in-vitro-only (D). But it sits at the bottom of C: essentially the entire evidence base traces to one Russian research lineage (Khavinson and colleagues), the older studies predate modern RCT standards, and there is no independent or Western replication. Limited, single-lineage human evidence, not the robust trials that would justify B. ## In plain terms **Simple.** Your thymus is a little gland behind your breastbone that trains your immune cells. It shrinks as you get older, which is part of why older people catch more bugs. Thymalin is made by mashing up the thymus glands of young calves and purifying a mixture of tiny protein fragments out of them. Russian scientists have injected it into older people for decades and reported that it perks the immune system back up — and in some long-running studies, that the people who got it lived noticeably longer. The catch is that almost all of this research comes from one Russian team, and the way the studies were run wouldn't pass the strict tests we'd expect today. So it's a genuinely interesting idea with a real story behind it, but not something that's been properly proven. **Standard.** Thymalin isn't a single peptide — it's a complex mixture of short peptides pulled out of calf thymus tissue, developed in the USSR in the 1970s by Vladimir Khavinson's group and still licensed as a medicine in Russia for immune-deficiency states. The thymus is where T-cells mature, and it withers with age (immunosenescence), so the pitch is that thymalin acts as a 'bioregulator' to restore age-related immune decline. Russian studies report it raises T-lymphocyte counts, improves CD4/CD8 ratios and NK-cell activity, and — most eye-catchingly — that elderly people given repeated courses had mortality cut several-fold over 6–8 years. Those longevity numbers are extraordinary, but the trials were largely non-blinded, non-randomised and from a single group, which is exactly the setup that tends to produce results too good to be true. The strongest modern study is a small randomised single-blind COVID-19 trial (80 patients) that did report lower inflammation and roughly halved in-hospital mortality. Promising signal, thin and unverified evidence base. **Technical.** Thymalin is a poorly chemically-defined acid-extracted polypeptide fraction of bovine thymus, the prototype of Khavinson's 'peptide bioregulator' class. Its proposed active principles are ultrashort peptides — notably the di/tripeptides KE (Vilon), EW and EDP — hypothesised to bind double-stranded DNA and histones and epigenetically modulate transcription of immune and 'gerontogene' loci, driving thymocyte/T-cell differentiation and rebalancing Th1/Th2 cytokine output. Reported pharmacodynamics in immunosenescent and stressed subjects include restoration of total T-lymphocyte counts, normalised CD4/CD8 ratio, enhanced NK cytotoxicity and neutrophil/macrophage phagocytosis. The flagship clinical claim derives from Khavinson & Morozov's 6–8 year open-label geroprotection programme (N=266), reporting ~2-fold mortality reduction with thymalin and up to 4.1-fold with combined thymalin+epithalamin — uncontrolled by modern standards (no blinding, no randomisation, single-centre, single investigator group). The Kuznik et al. 2021 prospective, randomised single-blind controlled trial in 80 severe COVID-19 elders (36 thymalin / 44 control, single-centre, Chita) is the most rigorous dataset — reduced IL-6/CRP and in-hospital mortality 19.4% vs 40.9% — but is single-centre, underpowered for mortality and unreplicated, and shares the same investigator lineage. The fundamental limitations are the undefined composition of the extract, the absence of independent confirmation, and publication concentrated in one bibliographic lineage. ## How it is thought to work Thymalin is thought to work as an immune 'bioregulator' rather than a hormone replacement. The thymus normally educates T-lymphocytes; as it involutes with age, T-cell output and immune competence fall. Thymalin's purported active components are very short peptides (e.g. KE, EW, EDP) proposed to enter cells, bind DNA/histones and modulate gene expression, nudging stem cells and thymocytes toward T-cell differentiation and rebalancing cytokine signalling (Th1/Th2). In practice it is a crude tissue extract, so 'mechanism' here is partly inferred from its constituent peptides studied separately, not from a single well-characterised molecule. ## Studied for Research contexts, not proven uses. - Age-related immune decline (immunosenescence) - Immunodeficiency states and recovery after infection - Adjunct during chemotherapy/radiotherapy (Russian indications) - Geroprotection / extending lifespan in the elderly - Severe COVID-19 in older patients ## What the human evidence shows There is human data, which is unusual for a grey-market peptide — but it is heavily caveated. The bulk comes from Vladimir Khavinson's group in St Petersburg over several decades, including a frequently-cited 6–8 year programme in 266 elderly people reporting roughly a 2-fold drop in mortality with thymalin (and up to 4.1-fold combined with epithalamin). These were open-label, non-randomised, single-group studies that would not meet modern trial standards, and no independent Western team has reproduced them. The most methodologically credible study is Kuznik et al. (2021), a prospective randomised single-blind controlled trial of 80 older patients with severe COVID-19 (36 given added thymalin, 44 controls) where the thymalin arm had lower IL-6, lower CRP and roughly halved in-hospital mortality (19.4% vs 40.9%) — but it was single-centre, small, underpowered for mortality and not replicated, and came from the same research lineage. Net: a real but narrow, unverified human evidence base dominated by one research group. ## Concerns and unknowns - Almost all efficacy data comes from a single research group over decades, with little independent or Western replication. - Older studies were largely non-blinded and non-randomised; effect sizes (e.g. multi-fold mortality reductions) are large enough to invite scepticism. - It is a crude animal-tissue extract of undefined composition, not a single defined molecule — batch-to-batch consistency and exactly what is being injected are unclear. - Biological-origin extracts carry theoretical contamination/immunogenicity concerns; grey-market 'research' material has no quality control. - Not a licensed medicine in the UK; anything sold here is an unlicensed product with no MHRA oversight. - Easily confused with thymulin (a different, zinc-dependent thymic nonapeptide) and with thymosin alpha-1. ## UK status Thymalin is not a licensed medicine in the UK. It holds regulatory approval in Russia (and some former-Soviet states) for immune-deficiency indications, but the MHRA has not authorised it and neither has the EMA or FDA. In the UK it would be an unlicensed substance: selling it for human use would engage the Human Medicines Regulations 2012, so it circulates only as a grey-market 'research chemical' with no quality, safety or efficacy guarantees. ## Sport / WADA Not specifically named on the WADA Prohibited List. As an immune-modulating tissue extract it is not a classic doping agent (not a hormone, anabolic or growth-factor secretagogue), so it is not generally a focus for anti-doping. Athletes should still treat any undefined unlicensed extract with caution and check the current list, since contamination and adulteration of grey-market products are real risks. ## Key trials - **6–8 year geroprotection programme in 266 elderly subjects (thymalin ± epithalamin)** (Observational / open-label, Completed (2003)). Reported ~2-fold (thymalin) up to 4.1-fold (combined) mortality reduction. Non-randomised, non-blinded, single group — hypothesis-generating at best. - **Thymalin in severe COVID-19 in older patients (Kuznik et al.)** (Randomised controlled trial (single-blind), Completed (2021)). 80 patients (36 thymalin / 44 control); lower inflammation markers and in-hospital mortality 19.4% vs 40.9%. Single-centre, underpowered for mortality, unreplicated. ## Sources 1. Peptides of pineal gland and thymus prolong human life. Khavinson VKh, Morozov VG, Neuro Endocrinol Lett, 2003 2. Peptide Drug Thymalin Regulates Immune Status in Severe COVID-19 Older Patients. Kuznik BI, Khavinson VKh, Shapovalov KG, et al., Advances in Gerontology, 2021 3. The Use of Thymalin for Immunocorrection and Molecular Aspects of Biological Activity (review). Khavinson VKh, Linkova NS, Chalisova NI, Ivko OM, PubMed Central (review), 2021 4. Thymalin: clinical and mechanistic studies (PubMed search). Various, PubMed search, 2024 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/thymalin . Educational only, not medical advice. --- # Thymosin Alpha-1 **Evidence grade: B (Promising human evidence).** Area: Other. > A lab-made copy of a natural thymus-gland peptide that fine-tunes the immune system. It is a licensed prescription medicine in many countries (as Zadaxin) but not in the UK, where it is sold only as an unlicensed research chemical. **Also known as:** Tα1, Thymalfasin, Zadaxin, TA1, Thymosin α1, ta-1, ta1 peptide **Class:** Immunomodulatory peptide (28-amino-acid N-terminal fragment of prothymosin alpha); thymic peptide ## Why this grade Unusually for a grey-market peptide, this one has a substantial human evidence base. It is a genuinely licensed medicine (thymalfasin/Zadaxin) in 35+ countries for chronic hepatitis B and as an immune adjuvant, tested in many randomised controlled trials across hepatitis, sepsis, and cancer immunotherapy. That far exceeds the grade-D bar most research-chemical peptides sit at. It falls short of A because it is not approved by the MHRA or FDA, much of the favourable trial base comes from concentrated, often Chinese centres using methodologically modest, single-blind designs, the landmark sepsis RCT (ETASS) missed statistical significance on its primary endpoint (28-day mortality), and the uses people actually buy it for online (general immune boosting, longevity) are not licensed indications and are essentially unproven. B reflects real but uneven, indication-specific human evidence. ## In plain terms **Simple.** Your thymus is a small gland that helps train your immune system. Thymosin alpha-1 is a tiny natural protein from that gland, and scientists can now make a copy in the lab. Unlike most things sold online, this one really has been used as a proper prescription medicine in many countries. It is sold under the name Zadaxin, mostly to treat long-term hepatitis infections and to help very sick patients. The problem is it is not approved in the UK or the United States. So even though the science is genuine, anything you buy online here is an unlicensed 'research chemical', not a checked, regulated medicine. There is no good evidence it helps with the vague 'immune boosting' or anti-ageing claims it is often marketed for. **Standard.** Thymosin alpha-1 (Tα1, marketed as thymalfasin/Zadaxin) is a 28-amino-acid peptide originally isolated from the thymus, the gland that educates immune cells. Rather than blindly revving the immune system up, it acts as a modulator. It helps immature dendritic cells and T-cells mature properly and steers the response toward a more effective anti-viral, anti-tumour Th1 pattern. It is a genuinely licensed prescription medicine in 35+ countries (including China, Italy and parts of Asia and the Middle East), chiefly for chronic hepatitis B and as an immune adjuvant with vaccines or in immunocompromised patients. It has been studied in many human trials covering hepatitis B and C, certain cancers, severe sepsis and COVID-19. It has never been approved by the UK's MHRA or the US FDA. In Britain it sits in the same unregulated grey market as most peptides, sold 'for research use only, not for human consumption'. The human evidence is real but uneven. It is reasonable in a few specific niches and marginal or merely suggestive in others. **Technical.** Thymosin alpha-1 is the N-terminally acetylated 28-residue cleavage product of prothymosin alpha, functioning as an endogenous immunomodulator. It engages innate immune sensing by signalling via Toll-like receptors (notably TLR2 and TLR9) through the MyD88 pathway to promote dendritic-cell maturation, enhance MHC class I expression, augment NK-cell cytotoxicity, and drive naive T-cell differentiation with a Th1-skewing effect (increased IFN-γ and IL-2, restoration of CD4/CD8 balance and reduced lymphocyte apoptosis in lymphopenic states). It is best characterised as a context-dependent restorer of immune homeostasis rather than a simple stimulant. Regulatory: licensed as thymalfasin (Zadaxin) in 35+ jurisdictions for chronic hepatitis B and as a vaccine or immune adjuvant; not FDA- or MHRA-approved. The human evidence base comprises Phase 3 chronic hepatitis B trials reporting improved sustained virologic and serologic response versus control; the ETASS multicentre single-blind RCT in severe sepsis (n=361; 181 vs 180), in which the primary endpoint of 28-day all-cause mortality (26.0% vs 35.0%; RR 0.74, 95% CI 0.54-1.02) did not reach significance in the prespecified nonstratified analysis (P=0.062), with secondary in-hospital mortality favouring treatment (28.7% vs 39.4%, P=0.032); and subsequent systematic reviews and meta-analyses of sepsis RCTs reporting pooled mortality reductions (e.g. RR ~0.59), albeit from small, heterogeneous, mostly single-centre Chinese trials. COVID-19 data remain largely observational. UK supply is exclusively unlicensed research-chemical material of unverified identity and purity. ## How it is thought to work Tα1 is an N-terminal fragment of prothymosin alpha that acts as an immune modulator rather than a blanket stimulant. It signals through Toll-like receptors (especially TLR2 and TLR9) via the MyD88 pathway to promote maturation of dendritic cells, enhance MHC class I expression and NK-cell activity, and push T-cell differentiation toward a Th1 (anti-viral, anti-tumour) profile while reducing lymphocyte apoptosis. The net effect is restoration of dysregulated immune response toward balance. Administered by injection. ## Studied for Research contexts, not proven uses. - Chronic hepatitis B (a licensed indication in some countries) - Chronic hepatitis C (often as an adjunct) - Severe sepsis and sepsis-associated immunoparalysis - Cancer immunotherapy adjunct (e.g. melanoma, non-small-cell lung cancer, hepatocellular carcinoma) - Vaccine response enhancement / immune adjuvant in immunocompromised patients - COVID-19 (limited, mostly observational human data) - Primary immunodeficiency (early/exploratory research) ## What the human evidence shows Substantial and unusually real for a peptide of this type. Thymosin alpha-1 is an approved prescription medicine (thymalfasin/Zadaxin) in 35+ countries and has been evaluated in many human trials. Phase 3 chronic hepatitis B trials reported improved sustained virologic and serologic response versus control. In severe sepsis, the multicentre single-blind ETASS RCT (n=361) found lower 28-day all-cause mortality with treatment (26.0% vs 35.0%) but this primary endpoint did not reach statistical significance in the prespecified analysis (P=0.062); a secondary in-hospital mortality endpoint favoured treatment (28.7% vs 39.4%, P=0.032). Later meta-analyses of sepsis RCTs reported a pooled mortality benefit, though they pooled small, heterogeneous, mostly single-centre Chinese trials. COVID-19 data are largely observational. The evidence quality varies sharply by indication, and the popular non-medical uses (longevity, generic immune boosting) are not supported by this trial base. ## Concerns and unknowns - Not licensed by the MHRA (UK) or FDA (US). UK supply is unlicensed 'research chemical' material sold 'not for human consumption', with no guarantee of identity, sterility or purity - Much of the favourable trial base comes from a concentrated set of (often Chinese) centres and includes single-blind designs; the landmark sepsis RCT (ETASS) actually missed significance on its primary 28-day mortality endpoint - As an immunomodulator it carries a theoretical risk of inappropriate immune activation; long-term safety outside studied indications is poorly characterised - Reported adverse effects in trials are generally mild (e.g. injection-site reactions), but real-world grey-market use bypasses the medical supervision and product quality the trial evidence relied on - Self-administering an injectable peptide for unproven indications (longevity, general 'immune boosting') is not supported by the licensed evidence base ## UK status Not a licensed medicine in the UK. Thymosin alpha-1 (thymalfasin) holds no MHRA marketing authorisation, despite being an approved prescription drug (Zadaxin) in 35+ other countries. It is not a controlled drug under the Misuse of Drugs Act, but as an injectable peptide it falls within the scope of the Human Medicines Regulations 2012. Selling or supplying it for human use without authorisation is unlawful, so in practice it is sold domestically only as a 'research chemical, not for human consumption'. There is no legitimate route to obtain it as a prescribed UK medicine, even for the indications it is approved for elsewhere. ## Key trials - **Thymalfasin (Thymosin Alpha 1) to Treat COVID-19 Infection** (NCT04487444, Phase 2, Registered). Registered trial of thymalfasin in COVID-19; illustrative of investigational interest. Human COVID-19 evidence overall remains limited/observational. - **ETASS: Efficacy of Thymosin Alpha 1 for Severe Sepsis** (RCT (multicentre, single-blind), Completed). n=361 across six Chinese tertiary hospitals, 2008-2010. Primary endpoint (28-day all-cause mortality) did not reach statistical significance. ## Sources 1. Thymosin alpha 1: A comprehensive review of the literature. Costantini E, et al., World Journal of Virology, 2020 2. The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Wu J, et al., Critical Care, 2013 3. The efficacy of thymosin α1 as immunomodulatory treatment for sepsis: a systematic review of randomized controlled trials. Liu F, et al., BMC Infectious Diseases, 2016 4. Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act (regulatory status; thymosin alpha-1 not FDA-approved). U.S. Food and Drug Administration _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/thymosin-alpha-1 . Educational only, not medical advice. --- # Thymulin **Evidence grade: D (Animal data only).** Area: Other. > A natural zinc-dependent thymus hormone that helps immune cells mature, sold as a research peptide despite almost no convincing human trial evidence as a treatment. **Also known as:** FTS-Zn, Zinc-FTS, Serum thymic factor, Facteur thymique sérique, FTS, zinc-thymulin, znfts **Class:** Zinc-dependent thymic peptide hormone (nonapeptide) ## Why this grade Thymulin is a genuine, well-characterised natural human hormone with decades of biochemistry behind it, but as an administered drug it has essentially no robust human efficacy evidence. The human treatment record is limited to small, old studies from the 1980s, mostly in rheumatoid arthritis. These were a mix of uncontrolled open trials and a few small placebo-controlled trials of a synthetic analogue (nonathymulin), none of which established convincing clinical benefit. Nothing is approved anywhere. Almost everything claimed for it today (anti-inflammatory, analgesic, anti-asthma, neuroprotective, anti-ageing) rests on preclinical work. That is the textbook definition of grade D: real science, but not real human proof of benefit. ## In plain terms **Simple.** Your thymus is a small gland behind your breastbone that trains your immune cells, like a school for the body's defenders. Thymulin is one of the signals that gland sends out, and it only works when paired with a tiny bit of zinc, like a key that needs its keyring to turn. Scientists discovered it in the 1970s, and they know your levels fall as you get older. Here is the problem: knowing the body makes something is not the same as proving that injecting extra of it helps anyone. Almost all the promising results (anti-inflammation, pain relief, immune boosting) come from experiments in mice and in dishes. There is barely any good human evidence that taking it as a treatment does anything, so anything sold online as thymulin is an unlicensed research chemical, not a tested medicine. **Standard.** Thymulin is a real hormone, a nine-amino-acid peptide made by the epithelial cells of the thymus gland. It was discovered in Paris in 1977 (originally called 'facteur thymique sérique', or serum thymic factor) and is unusual in that it only becomes biologically active when bound to a zinc ion, one zinc per molecule. Its natural job appears to be helping immature T-cells mature and tuning the activity of T-cells and natural killer cells. Blood levels are high in childhood and fall steeply with age, mirroring the shrinking of the thymus, which is why it features in discussions of immune ageing. As a thing the body makes, thymulin is well-studied. As a drug you take, it is not. There were a handful of small human studies in the 1980s, mostly in rheumatoid arthritis. Some were uncontrolled; a couple were small placebo-controlled trials of a synthetic version. None clearly showed it works. The bulk of the encouraging anti-inflammatory and pain-reducing data comes from modern animal experiments, and nothing is approved anywhere. Today it is sold as a grey-market 'research chemical', not as a licensed medicine. **Technical.** Thymulin is a nonapeptide hormone (pGlu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn) secreted by thymic epithelial cells, originally isolated from porcine serum and characterised by Bach, Dardenne and colleagues (Institut Necker, 1977) as 'facteur thymique sérique' (FTS). Biological activity is strictly zinc-dependent: an equimolar Zn2+ ion induces the active conformation, hence the designation FTS-Zn or zinc-thymulin; the apo (zinc-free) peptide is structurally present but inactive. Functionally it participates in thymocyte/T-cell differentiation and modulates peripheral T-cell and NK-cell function, and shows neuroendocrine bidirectionality with the HPA axis (correlations with ACTH, circadian patterning). Serum thymulin declines with thymic involution and is reduced in zinc deficiency and protein-energy malnutrition, restorable by zinc repletion. Preclinical work is extensive: thymulin and a caerulein-coupled analogue (PAT, peptide analogue of thymulin) attenuate inflammatory and neuropathic pain in rodent CFA models, reduce spinal microglial activation, p38 MAPK phosphorylation and TNF-alpha/IL-6, and modulate endotoxin-induced NF-kB nuclear translocation and proinflammatory cytokine release in alveolar epithelium in vitro. Human therapeutic data are sparse, dated and unconvincing: small open-label studies and a few small double-blind placebo-controlled trials (the latter using the synthetic analogue nonathymulin) in rheumatoid arthritis in the 1980s, plus observational associations such as reduced thymulin activity in anorexia nervosa and malnourished children. There are no contemporary registered RCTs demonstrating efficacy and no marketing authorisation. Mechanistically interesting and biologically real, but without demonstrated efficacy as an exogenous therapeutic. ## How it is thought to work Thymulin is a nonapeptide secreted by thymic epithelial cells that requires equimolar zinc (Zn2+) to fold into its biologically active conformation. The zinc-free form is inactive. The active hormone modulates T-cell differentiation and the function of peripheral T-cells and NK cells, and shows anti-inflammatory signalling in preclinical models, including modulation of NF-kB activation, reduced p38 MAPK phosphorylation and lower pro-inflammatory cytokine output (TNF-alpha, IL-6, IL-1beta). It interacts bidirectionally with the hypothalamic-pituitary axis. Endogenous levels fall with age (thymic involution) and with zinc deficiency. ## Studied for Research contexts, not proven uses. - T-cell maturation and immune regulation (basic immunology) - Immunosenescence and age-related thymic decline (observational) - Zinc deficiency and protein-energy malnutrition (as a biomarker) - Inflammatory and neuropathic pain (rodent models) - Rheumatoid arthritis (small historical human studies, mostly uncontrolled) - Allergic airway inflammation / asthma (animal models) - Neuroinflammation and neuroprotection (preclinical) ## What the human evidence shows Thin, dated and unconvincing. Thymulin is a genuine endogenous human hormone, so its biology and age-related decline are well documented. As an administered treatment, the human record is limited to small studies from the 1980s, mostly in rheumatoid arthritis. These were a mix of uncontrolled open trials of thymulin and a few small double-blind placebo-controlled trials of a synthetic analogue (nonathymulin), none of which established clear clinical benefit. There are observational associations such as reduced thymulin activity in anorexia nervosa and malnourished children. No large, modern, properly powered randomised trials demonstrate clinical benefit, and no health authority has approved it for any indication. ## Concerns and unknowns - No convincing controlled human trials of efficacy for any indication. The small historical human studies did not establish benefit. - Sold as an unlicensed 'research chemical' or 'not for human consumption' product with no UK marketing authorisation, no medical oversight and no guaranteed safety data in humans. - Grey-market peptide quality is a real risk: purity, correct sequence, sterility, endotoxin levels and accurate labelling are not assured for products bought online. - Activity is zinc-dependent, so claims around a fixed 'thymulin' product ignore that the relevant biology depends on zinc status, which complicates interpretation of marketed material. - Immunomodulatory agents carry theoretical risks (altering immune balance) that have not been characterised for exogenous thymulin in humans. - Marketing frequently extrapolates rodent anti-ageing and anti-inflammatory findings directly to human benefit, which the evidence does not support. ## UK status Not a licensed medicine in the UK. Thymulin has no MHRA marketing authorisation and is not an approved or routinely prescribed treatment. It is not a recognised investigational medicinal product in active UK clinical use. In practice it is sold online as an unlicensed 'research chemical', typically labelled 'for research use only / not for human consumption'. Supplying or selling it for human medicinal use without authorisation breaches the Human Medicines Regulations 2012. Importing injectable unlicensed peptides for self-administration carries clear legal and safety risks. There is no legitimate UK route to obtain it as a treatment. ## Sources 1. Thymulin, a zinc-dependent hormone. Dardenne M, Bach JF, Medical Oncology and Tumor Pharmacotherapy, 1989 2. Biochemical characterisation of a serum thymic factor. Bach JF, Dardenne M, Pleau JM, Rosa J, Nature, 266:55-56, 1977 3. An open trial of thymulin (FTS-Zn) in rheumatoid arthritis patients: sequential clinical and immunological follow-up. Faure GC, Bene MC, Thomas P, Tamisier JN, Clinical and Experimental Rheumatology, 1987 4. Thymulin treatment attenuates inflammatory pain by modulating spinal cellular and molecular signaling pathways. Nasseri B, Zaringhalam J, Daniali S, et al., International Immunopharmacology, 70:225-234, 2019 5. Thymulin and zinc (Zn2+)-mediated inhibition of endotoxin-induced proinflammatory cytokines and NF-kappaB nuclear translocation in the alveolar epithelium in vitro. International Immunopharmacology, 2009 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/thymulin . Educational only, not medical advice. --- # Tirzepatide **Evidence grade: A (Approved / strong human evidence).** Area: Weight & Metabolic. > A prescription injection that mimics two gut hormones at once to reduce appetite, lower blood sugar and drive substantial weight loss. **Also known as:** Mounjaro, Zepbound, LY3298176, GIP/GLP-1 dual agonist, twincretin, tirz **Class:** Dual GIP and GLP-1 receptor agonist (incretin mimetic), 39-amino-acid synthetic peptide ## Why this grade Licensed UK and US medicine for both type 2 diabetes and chronic weight management, backed by large multi-arm Phase 3 RCT programmes (SURPASS for diabetes, SURMOUNT for obesity) with tens of thousands of participants, plus a head-to-head trial showing superiority over semaglutide. ## In plain terms **Simple.** Tirzepatide, sold as Mounjaro, is a weekly injection that copies two natural gut hormones your body releases after eating. They tell your brain you are full and slow how fast your stomach empties, so you eat less without feeling starved. In big trials people lost around a fifth of their body weight on average. Unlike most things in this directory, it is a real, approved medicine in the UK. It is prescription-only and has genuine side effects, mainly nausea and other gut upsets. **Standard.** Tirzepatide is a once-weekly injectable that switches on two gut-hormone systems at once: GLP-1 (the same target as Ozempic and Wegovy) and GIP. By hitting both, it suppresses appetite, slows stomach emptying and improves how the body handles blood sugar. It is sold as Mounjaro and is MHRA-approved in the UK both for type 2 diabetes and for weight management. In the landmark SURMOUNT-1 obesity trial, average weight loss reached roughly 21 to 22 percent at the highest dose over 72 weeks, more than any previous obesity drug, and in a head-to-head diabetes trial (SURPASS-2) it beat semaglutide on both blood sugar and weight. Side effects are mostly gastrointestinal: nausea, vomiting, diarrhoea and constipation. Weight tends to return once you stop, so it is a long-term treatment rather than a quick fix. On the NHS it is tightly rationed, so many people access it privately, which has fuelled a dangerous online market in counterfeit and unlicensed copies. **Technical.** Tirzepatide (LY3298176) is a 39-residue synthetic peptide engineered as a dual agonist of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, with a C20 fatty-diacid moiety conferring albumin binding and an approximately 5-day half-life suitable for weekly subcutaneous administration. It behaves as an imbalanced agonist, with greater potency at GIPR than at GLP-1R and biased signalling at the GLP-1 receptor. Mechanistically it enhances glucose-dependent insulin secretion, suppresses glucagon, delays gastric emptying and acts on hypothalamic and hindbrain circuits to reduce energy intake. The GIP component is hypothesised to add weight-loss efficacy and potentially modulate GLP-1-mediated nausea, though whether GIPR agonism (versus functional antagonism) drives the benefit remains debated. The SURPASS programme established glycaemic efficacy in T2DM, with SURPASS-2 (NEJM 2021) showing superiority over semaglutide 1 mg on HbA1c and weight. The SURMOUNT obesity programme followed: SURMOUNT-1 (NEJM 2022) reported mean weight reductions of roughly 15, 19.5 and 20.9 percent (5/10/15 mg, treatment-regimen estimand) versus about 3 percent for placebo over 72 weeks, and SURMOUNT-2 confirmed efficacy in the T2DM population. SURMOUNT-5 reported superiority over semaglutide for weight loss in obesity. Beyond metabolic endpoints, dedicated trials have studied HFpEF with obesity (SUMMIT), obstructive sleep apnoea (SURMOUNT-OSA) and MASH/MASLD (SYNERGY-NASH, Phase 2). Common adverse effects are gastrointestinal. Pancreatitis and gallbladder disease occur, and a boxed thyroid C-cell tumour warning (based on a rodent medullary thyroid carcinoma signal) applies as a class effect. ## How it is thought to work Synthetic peptide that simultaneously activates the GLP-1 and GIP incretin receptors to enhance glucose-dependent insulin release, suppress glucagon, slow gastric emptying and reduce energy intake via appetite-regulating centres in the brain. A fatty-acid modification allows albumin binding and a long half-life suited to weekly subcutaneous injection. ## Studied for Research contexts, not proven uses. - Chronic weight management in obesity/overweight - Type 2 diabetes glycaemic control - Obstructive sleep apnoea in obesity (SURMOUNT-OSA) - Heart failure with preserved ejection fraction and obesity (SUMMIT) - Metabolic dysfunction-associated steatohepatitis (MASH/MASLD) - Cardiovascular outcomes ## What the human evidence shows Extensive and high-quality. Multiple large Phase 3 RCTs: the SURPASS programme for type 2 diabetes (including SURPASS-2, which showed superiority over semaglutide on HbA1c and weight) and the SURMOUNT programme for obesity. SURMOUNT-1 showed mean weight loss of roughly 21 to 22 percent at the top dose over 72 weeks, the largest seen for any obesity drug at the time, and SURMOUNT-5 reported head-to-head superiority over semaglutide for weight loss. Further trials cover sleep apnoea, heart failure with preserved ejection fraction, and liver disease (the latter still at Phase 2). ## Concerns and unknowns - Common gastrointestinal side effects: nausea, vomiting, diarrhoea, constipation, the main reason people stop - Weight regain is typical after discontinuation; effectively a long-term treatment - Risk of acute pancreatitis and gallbladder disease (class effect) - Boxed warning for thyroid C-cell tumours (medullary thyroid carcinoma) based on rodent data; contraindicated with a personal or family history of MTC or MEN2 - Loss of lean muscle mass alongside fat, as with all incretin weight-loss drugs - Huge demand has driven a grey market in counterfeit and unlicensed/compounded 'tirzepatide' sold online, carrying serious dosing and contamination risks; only the licensed product (Mounjaro) under prescription is quality-assured - Caution/avoidance in pregnancy; may reduce oral contraceptive absorption around dose changes - NHS access is rationed and rollout is staged, pushing some people toward private and unregulated online supply ## UK status Licensed UK medicine. Tirzepatide (brand Mounjaro, Eli Lilly) holds MHRA marketing authorisation for both type 2 diabetes and chronic weight management (broadly, a BMI of 30 or above, or 27 or above with a weight-related comorbidity). It is a prescription-only medicine (POM). NICE recommends it for weight management (Technology Appraisal TA1026, published December 2024), with a phased NHS rollout that began in primary care in 2025 under tight eligibility criteria. Many patients obtain it privately. Unlicensed or compounded tirzepatide sold online falls outside the regulated supply chain. ## Sport / WADA Not specifically named on the WADA Prohibited List and not a recognised performance-enhancing agent in sport. ## Key trials - **SURMOUNT-1: Tirzepatide in adults with obesity or overweight** (NCT04184622, Phase 3, Completed). Pivotal obesity trial; roughly 21 to 22 percent mean weight loss at top dose over 72 weeks. - **SURPASS-2: Tirzepatide versus semaglutide added to metformin in type 2 diabetes** (NCT03987919, Phase 3, Completed). Demonstrated superiority over semaglutide on HbA1c and weight. - **SURMOUNT-OSA: Tirzepatide in obstructive sleep apnoea and obesity** (Phase 3, Completed). Reduced apnoea-hypopnoea index; supported an OSA indication. - **SUMMIT: Tirzepatide in heart failure with preserved ejection fraction and obesity** (Phase 3, Completed). Outcomes in HFpEF with obesity. ## Sources 1. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). Jastreboff AM, et al., New England Journal of Medicine, 2022 2. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2). Frias JP, et al., New England Journal of Medicine, 2021 3. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Garvey WT, et al., The Lancet, 2023 4. Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis (SYNERGY-NASH). Loomba R, et al., New England Journal of Medicine, 2024 5. NICE Technology Appraisal TA1026: Tirzepatide for managing overweight and obesity. National Institute for Health and Care Excellence, 2024 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/tirzepatide . Educational only, not medical advice. --- # VIP (Vasoactive Intestinal Peptide) **Evidence grade: B (Promising human evidence).** Area: Recovery & Repair. > A natural body hormone that relaxes blood vessels and airways and dampens inflammation. Its lab-made version was tested in serious lung disease but failed to prove it works. **Also known as:** VIP, Vasoactive Intestinal Polypeptide, Aviptadil (synthetic form), RLF-100, ZYESAMI, vasoactive intestinal peptide, vip nasal spray **Class:** Endogenous neuropeptide / secretin-glucagon peptide superfamily; VPAC1/VPAC2 receptor agonist ## Why this grade VIP is a genuine human hormone whose synthetic form (aviptadil) has been through large, independent randomised controlled trials. The definitive NIH-funded TESICO trial (471 patients in the aviptadil comparison, Lancet Respir Med 2023) found no benefit in COVID-19 hypoxaemic respiratory failure and was stopped for futility. Earlier company-sponsored signals were not confirmed, and the FDA had already declined an emergency use authorisation. Substantial, high-quality human trial data exists, but the best trial was negative and there is no approved indication. That is a textbook B (real human RCTs, but incomplete or unconvincing efficacy), not an A. This grade reflects the respiratory-failure programme; for the 'recovery', anti-inflammatory, and CIRS uses under which it is actually sold, human evidence is effectively D. ## In plain terms **Simple.** VIP is a chemical messenger your body makes naturally, found in large amounts in the gut, brain and lungs. It widens blood vessels, opens airways and calms inflammation. Scientists wondered whether extra VIP could help people with severely inflamed lungs. A man-made version (aviptadil) was tested in large, carefully run hospital trials on very ill COVID patients on ventilators. It did not help them survive or recover any better than a placebo. Online it is sold as a peptide for 'recovery', immune support and a condition some call CIRS, but these uses are not proven and the products available are not approved medicines. **Standard.** Vasoactive Intestinal Peptide (VIP) is a 28-amino-acid neuropeptide made naturally in the nervous system, gut and lungs. It relaxes blood vessels, opens airways and produces broad anti-inflammatory and immune-modulating effects, shifting the immune system toward a more regulatory state. These properties made it an attractive drug candidate for inflammatory lung conditions. A synthetic version, aviptadil (branded RLF-100 / ZYESAMI), was promoted heavily during the COVID-19 pandemic after early uncontrolled reports seemed promising. The definitive, large, NIH-funded randomised trial (TESICO, published 2023) found no significant benefit over placebo in COVID respiratory failure and was stopped for futility. The FDA had previously declined an emergency use authorisation. It has also been explored in sarcoidosis and pulmonary hypertension with orphan-drug designations, but it is not an approved medicine anywhere. The grey market sells VIP, typically as a nasal spray, for chronic inflammatory response syndrome (CIRS), immune and recovery support. These products are unlicensed and lack approved-medicine evidence. **Technical.** VIP is a 28-residue neuropeptide of the secretin/glucagon/PACAP superfamily, signalling through class B GPCRs VPAC1 (VIPR1) and VPAC2 (VIPR2), with additional affinity at PAC1. Receptor activation couples to Gs/adenylyl cyclase, raising intracellular cAMP and driving smooth-muscle relaxation (systemic and pulmonary vasodilation, bronchodilation) and immunomodulation: suppression of pro-inflammatory cytokines (TNF-alpha, IL-6), promotion of a Th2/Treg-skewed, tolerogenic phenotype, and reported protection of alveolar type II pneumocytes. VPAC1 predominates in lung parenchyma and T lymphocytes; VPAC2 is found on airway smooth muscle and mast cells. Synthetic aviptadil reached late-phase clinical development with company-sponsored expanded-access and a Phase 2b/3 programme (RLF-100/ZYESAMI) initially reporting survival and recovery signals in critical COVID-19. These were not confirmed by the rigorously designed NIH ACTIV-3b/TESICO randomised, placebo-controlled trial (471 patients in the aviptadil comparison with remdesivir co-randomisation), which found no significant improvement in day-90 ordinal clinical outcome and was halted for futility (Lancet Respir Med 2023). The FDA declined an emergency use authorisation in 2021. VIP/aviptadil has also been investigated in pulmonary arterial hypertension and pulmonary sarcoidosis (including inhaled formulations with FDA orphan designations) on early-phase exploratory data. Native VIP has a very short plasma half-life, limiting systemic use and motivating inhaled formulations and analogue development. This half-life undermines claims of sustained systemic effects from unregulated products. ## How it is thought to work Binds class B G-protein-coupled receptors VPAC1 and VPAC2 (with additional affinity at PAC1), activating Gs/adenylyl cyclase and raising intracellular cAMP. This produces vasodilation, bronchodilation and broad anti-inflammatory and immunomodulatory effects: suppression of TNF-alpha and IL-6, a shift toward regulatory and tolerogenic immune responses, and reported protection of alveolar type II cells. Endogenous VIP is concentrated in the lungs, gut and CNS and has a very short half-life. ## Studied for Research contexts, not proven uses. - COVID-19-associated acute hypoxaemic respiratory failure / ARDS (as synthetic aviptadil) - Pulmonary arterial hypertension (orphan-designated investigational use) - Pulmonary sarcoidosis (inhaled, exploratory) - Acute respiratory distress syndrome more broadly - Anti-inflammatory / immune modulation (preclinical, plus unproven grey-market 'recovery'/CIRS claims) ## What the human evidence shows Substantial in volume but ultimately unconvincing. VIP is a well-characterised endogenous human hormone and synthetic aviptadil has been through genuine clinical trials. Early, largely uncontrolled COVID-19 data (expanded access and company-sponsored Phase 2b/3) suggested benefit. However, the FDA declined an emergency use authorisation in 2021, and the definitive, independent, NIH-funded randomised placebo-controlled trial (TESICO, 471 patients in the aviptadil comparison, Lancet Respir Med 2023) found no significant benefit and was stopped for futility. Earlier-phase work exists in sarcoidosis and pulmonary hypertension with orphan-drug designations but no full regulatory approval. For the 'recovery', immune-boosting and CIRS uses promoted on the grey market, there is no robust human efficacy evidence. ## Concerns and unknowns - The best-quality human trial (TESICO) was negative and the FDA declined an emergency use authorisation. High-profile COVID recovery claims did not hold up under rigorous testing. - Not a licensed medicine in the UK or anywhere else. Aviptadil remains investigational despite orphan-drug designations. - Intravenous administration causes vasodilation-related side effects such as hypotension, flushing and diarrhoea. It is not benign. - Grey-market VIP (often nasal sprays) is sold as an unlicensed 'research chemical' with no guarantee of identity, purity, sterility or correct peptide sequence. - Marketing for CIRS, mould illness and immune support has no approved-medicine-grade evidence. - Native VIP has a very short half-life, so claimed sustained systemic effects from unregulated products are biologically questionable. ## UK status Not a licensed medicine in the UK. VIP/aviptadil has no MHRA marketing authorisation and is an investigational drug. It has held FDA orphan-drug designations for ARDS and sarcoidosis, but designation is not approval. The FDA declined an emergency use authorisation in 2021. Material sold online as 'VIP peptide' is an unlicensed product typically labelled 'research chemical / not for human consumption' and has not been assessed by the MHRA for safety, quality or efficacy. Supplying or selling it for human medicinal use without authorisation breaches the Human Medicines Regulations 2012. ## Key trials - **ACTIV-3b / TESICO: Aviptadil and Remdesivir for Severely Ill Inpatients With COVID-19** (NCT04843761, Phase 3, Completed (aviptadil arm stopped for futility; published 2023)). NIH-funded randomised, placebo-controlled trial; 471 patients in the aviptadil comparison (473 enrolled overall); no significant clinical benefit of IV aviptadil to day 90. - **ZYESAMI (RLF-100/aviptadil) Phase 2b/3 programme in critical COVID-19** (Phase 2b/3, Completed). Company-sponsored programme that reported early positive signals later not confirmed by the independent TESICO trial; FDA declined an emergency use authorisation in 2021. ## Sources 1. Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial. The Lancet Respiratory Medicine, 2023 2. A negative trial for vasoactive intestinal peptide in COVID-19-associated acute hypoxaemic respiratory failure. The Lancet Respiratory Medicine (linked commentary), 2023 3. Vasoactive intestinal peptide (VIP) and its receptors VPAC1/VPAC2 - physiology, receptor distribution and anti-inflammatory pharmacology (review). PubMed search _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/vip . Educational only, not medical advice. --- # Vilon **Evidence grade: D (Animal data only).** Area: Longevity. > Vilon is a lab-made two-amino-acid peptide (Lys-Glu) from the Russian 'bioregulator' family, promoted for immune ageing and longevity, but the human evidence is essentially limited to cells in a dish. **Also known as:** Vilon peptide, Lys-Glu, Lys-Glu dipeptide, L-Lys-L-Glu, KE peptide, ke peptide, vilon ke **Class:** Synthetic dipeptide bioregulator (Lys-Glu / KE) ## Why this grade The evidence is overwhelmingly cell-culture and rodent work, almost all of it from one Russian research group (Khavinson and colleagues) with little independent replication. The only Vilon-specific 'human' data are small in-vitro chromatin studies on cultured lymphocytes taken from elderly donors - not in-vivo trials. The widely-cited 266-person longevity study used Thymalin and Epithalamin, not Vilon. There are no modern, adequately powered, independently run randomised controlled trials of Vilon in living people and no human study showing it treats any disease or extends lifespan. That is a strict D: a preclinical signal with negligible meaningful human evidence. ## In plain terms **Simple.** Vilon is one of the tiniest peptides anyone has tried to use as a medicine - just two of the building blocks that make up proteins (lysine and glutamic acid) joined together. It came out of a Russian programme that designed short peptides meant to 'tune up' specific organs, in Vilon's case the immune system and the thymus, a gland that trains your immune cells and shrinks as you get older. Sellers claim it switches tired old cells back into a younger, more active mode. The honest catch: almost all the encouraging results are from mice, rats, or human cells grown in a lab dish - mostly from one research group. Nobody has run a proper modern trial putting Vilon into real people and showing it helps them live longer or get fewer illnesses. **Standard.** Vilon is a synthetic dipeptide - the sequence lysine-glutamic acid (Lys-Glu, sometimes written KE) - and one of the shortest peptides claimed to have biological activity. It belongs to the 'peptide bioregulator' family developed by Vladimir Khavinson's group at the St Petersburg Institute of Bioregulation and Gerontology, derived conceptually from thymus extracts. It is marketed as an immune and anti-ageing agent said to reactivate silenced genes in old cells, support T-cell function and reduce age-related decline. In the lab there are real findings: Vilon reduced spontaneous tumours and modestly increased lifespan in mice, inhibited chemically-induced tumours in rodents, and 'unrolled' condensed chromatin to reactivate genes in cultured lymphocytes from very elderly donors. The problem is what's missing: the literature is dominated by one group, replication by others is sparse, and the human work is in-vitro (cells in a dish) rather than trials in living people. The often-quoted 266-patient longevity study actually tested Thymalin and Epithalamin, not Vilon. In the UK it is not a licensed medicine; it is sold online as an unlicensed 'research chemical'. **Technical.** Vilon is the synthetic dipeptide L-Lys-L-Glu (KE), a short-chain peptide bioregulator developed by V.Kh. Khavinson and colleagues and conceptually derived from thymic peptide preparations (e.g. Thymalin). The proposed mechanism is epigenetic: direct peptide-DNA/peptide-chromatin interaction driving deheterochromatinisation - relaxation of condensed facultative heterochromatin toward transcriptionally active euchromatin - with reactivation of silenced genes (including ribosomal genes via nucleolus organiser regions) in senescent cells, plus tissue-specific modulation of gene expression in thymocytes and lymphocytes. Notably, in the same cytogenetic work Vilon did not decondense pericentromeric structural heterochromatin, unlike some sister peptides, so the proposed effect is selective rather than global. Preclinical support is reasonably broad for such a small molecule: Khavinson & Anisimov (Dokl Biol Sci 2000) reported reduced spontaneous lung adenoma incidence and increased lifespan in female CBA mice; rodent work reported inhibition of carcinogen-induced tumours and restored age-related intestinal absorption. The principal Vilon-specific 'human' evidence is the Lezhava group's cytogenetic work (Biogerontology 2004; Georgian Med News 2006, 2023) showing Vilon-induced chromatin reactivation in cultured peripheral lymphocytes from donors aged ~75-88 - an ex-vivo/in-vitro signal, not an in-vivo clinical endpoint. There are no contemporary, adequately powered, blinded RCTs; no human PK/PD (an unprotected linear dipeptide would be expected to have a very short plasma half-life and rapid peptidase degradation); and no hard human efficacy or longevity outcomes. Evidence grade D reflects a coherent but single-group-dominated preclinical signal with negligible high-quality human data. ## How it is thought to work A synthetic dipeptide (Lys-Glu) proposed to act epigenetically: binding DNA/chromatin to drive deheterochromatinisation - loosening condensed chromatin back toward an active state - and thereby reactivating genes silenced in ageing cells, including in thymocytes and lymphocytes, with downstream effects on immune-cell proliferation and differentiation. These mechanisms are demonstrated mainly in vitro and in animals, not confirmed in living humans. Typically administered by injection in the grey market. ## Studied for Research contexts, not proven uses. - Immune ageing / thymic function (immunosenescence) - Chromatin reactivation and gene expression in ageing cells (in vitro) - Spontaneous and carcinogen-induced tumours in rodents - Lifespan in mice - Age-related intestinal absorption in rats ## What the human evidence shows Genuinely thin and easy to overstate. The only Vilon-specific human-derived data are in-vitro/ex-vivo cytogenetic studies in which peripheral blood lymphocytes taken from very elderly donors were exposed to Vilon in culture and showed reactivation of condensed chromatin and silenced genes (Lezhava and colleagues). These are cells in a dish, not treatment of living patients with measured clinical outcomes. There are no modern, adequately powered, independently run randomised controlled trials of Vilon in people, and no human study showing it prevents disease, improves immune function clinically, or extends lifespan. The frequently-cited '266 elderly patients over 6-8 years' longevity study used the peptide preparations Thymalin and Epithalamin - not Vilon - so attributing its mortality findings to Vilon is incorrect. ## Concerns and unknowns - Human evidence is essentially in-vitro only; benefits in living people are unproven - Evidence base dominated by a single Russian research group with limited independent replication - Marketing routinely misattributes the Thymalin/Epithalamin longevity trial and other bioregulator data to Vilon - Sold in the UK as an unlicensed 'research chemical' / 'not for human consumption' - no MHRA oversight of identity, purity, sterility or dose - Grey-market injectable products carry contamination, mislabelling and sterility risks - Long-term human safety is essentially unknown; no proper clinical pharmacology or toxicology in people - An agent claimed to broadly reactivate silenced genes warrants caution given the role of dysregulated gene expression in cancer ## UK status Not a licensed medicine in the UK and not approved by the MHRA for any indication. It is not an authorised medicinal product, so any product sold or promoted with medicinal claims would fall foul of the Human Medicines Regulations 2012. In practice it is sold online as an unlicensed 'research chemical' labelled 'not for human consumption', outside any pharmaceutical quality, safety or efficacy control. Supplying it for human use, or marketing it with medical claims, is unlawful. ## Sport / WADA Not specifically named on the WADA Prohibited List. As a peptide marketed for immune and 'anti-ageing' effects rather than direct performance enhancement, it has no established sport-doping use, but athletes should treat any unlicensed grey-market peptide with caution given contamination risk and the catch-all nature of some Prohibited List categories. ## Key trials - **No registered modern interventional RCTs of Vilon in humans identified** (N/A, None found). Searches did not surface contemporary registered clinical trials of Vilon (Lys-Glu) with clinical endpoints. Human-derived data are in-vitro cytogenetic studies, not trials. ## Sources 1. A synthetic dipeptide vilon (L-Lys-L-Glu) inhibits growth of spontaneous tumors and increases life span of mice. Khavinson VKh, Anisimov VN, Doklady Biological Sciences, 2000 2. Bioregulator Vilon-induced reactivation of chromatin in cultured lymphocytes from old people. Lezhava T, Khavinson V, Monaselidze J, et al., Biogerontology, 2004 3. Anti-aging peptide bioregulators induce reactivation of chromatin. Lezhava T, Monaselidze J, Kadotani T, et al., Georgian Medical News, 2006 4. Epigenetic modification under the influence of peptide bioregulators on the 'old' chromatin. Lezhava T, Jokhadze T, Monaselidze J, et al., Georgian Medical News, 2023 5. Peptides of pineal gland and thymus prolong human life (Thymalin/Epithalamin, 266 elderly subjects). Khavinson VKh, Morozov VG, Neuroendocrinology Letters, 2003 6. Vilon and Lys-Glu peptide - PubMed search. Various, PubMed, 2026 _Last reviewed: 2026-06._ Source: https://whatsthatpeptide.co.uk/peptides/vilon . Educational only, not medical advice.