Peptides

The mental rule: three tiers of evidence

Tier 1 — Extensively studied in humans. This is where Tesamorelin (FDA-approved for HIV lipodystrophy) and Thymosin Alpha-1 (approved in more than 35 countries for hepatitis B/C, sepsis, and oncology) belong. Clear indication, known safety profile, standardized doses.

Tier 2 — Good animal data and solid human trials. Cerebrolysin, with decades of trials in stroke and dementia; Epitalon, with Russian observational studies. Reasonable evidence, but not always reproduced outside the centers that developed it.

Tier 3 — Preclinical or anecdotal. BPC-157, MOTS-c, Humanin. The animal models are spectacular, Reddit forums are buzzing with testimonials, and published human trials are zero or close to zero. Use is in a legal gray area.

The hype-evidence disconnect

Cross internet popularity with the volume of clinical trials and a clear pattern appears: the most famous peptides are not the best studied. BPC-157 is the most searched on Google and has zero published human trials. Thymosin Alpha-1, almost unknown on social media, has been approved in hospitals for decades. When a peptide generates a lot of noise but has barely any human data, the reasonable assumption is that what we know comes from rats.

The tissue repairers

BPC-157. A pentadecapeptide derived from a protective gastric protein. In rodents, it restores a severed quadriceps, regenerates Achilles tendons, and heals gastric ulcers. In humans: zero published clinical trials. Efficacy and safety are strictly anecdotal, purity in the gray market is variable, and it is banned by WADA. Useful as a concept, premature as a protocol.

TB-500 (Thymosin Beta-4). A 43-amino-acid peptide that sequesters actin and promotes cell migration, angiogenesis, and inflammatory modulation. The only indication with solid human evidence is ophthalmic: phase 2 trials in the cornea (RGN-259) show better epithelialization and relief of severe dry eye. For systemic use in muscle injuries or tendinopathies, there are no valid human data.

The immunomodulators

Thymosin Alpha-1. The best-established immunomodulatory peptide. It stimulates T-cell maturation and reverses signs of immunosenescence. Approved in more than 35 countries (not in the US) for hepatitis B/C, severe sepsis, and oncology. Typical regimen: 1.6 mg subcutaneously twice a week. Use caution in active autoimmunity.

The brain protectors

Cerebrolysin. A mixture of peptides and amino acids derived from porcine brain with neurotrophic action. 30 years of clinical use in Eastern Europe and Asia. Randomized trials show better neurological and functional recovery at 90 days after stroke when administered within the first 24-72 hours. In mild-to-moderate Alzheimer's it improves cognition for up to 6 months, but it does not prevent progression or reduce mortality. Typical dose: 10-30 ml/day intravenously in cycles of 10-21 days.

Semax. A synthetic heptapeptide derived from ACTH(4-10), used intranasally, developed in Russia. It raises brain BDNF, dopamine, and serotonin. Approved in Russia for stroke, neuropathy, and cognitive disorders. Russian trials show benefit, but the methodological quality is below the Western standard and independent replication is scarce.

Epitalon. A synthetic tetrapeptide derived from the pineal extract Epithalamin. In Russian observational trials: 0.5 mg/day for 20 days improves melatonin production in older women; 64.8% of patients with retinitis pigmentosa widened their visual field by 90-120°; prospective studies associate 2-4× lower 15-year mortality in institutionalized older adults. But all the trials are observational, not randomized, and conducted by the patent holder. It urgently needs independent reproduction.

The mitochondrial peptides

MOTS-c. A 16-amino-acid peptide derived from mitochondrial DNA; it activates AMPK under metabolic stress. Its plasma levels rise with HIIT (×1.6 in plasma, ×11.9 in muscle) and fall with age and type 2 diabetes. Zero human trials with direct injection. The idea of "exercise in an injection" is premature marketing.

Humanin. A 24-amino-acid mitochondrial peptide described as neuroprotective against oxidative stress. Lower levels in patients with Alzheimer's. Zero human trials. Association, not causation.

The growth hormone secretagogues

Tesamorelin. A synthetic GHRH analog. FDA-approved to reduce visceral fat in HIV-associated lipodystrophy: a 52-week trial showed a 15-17.5% reduction in visceral fat. It raises IGF-1 to the physiological range via pulsatile endogenous GH release.

MK-677 (Ibutamoren). An oral secretagogue that mimics ghrelin. 25 mg/day for 12 months provides +1.1 kg of lean mass in older adults and increases deep/REM sleep by up to 50%. Limiting side effects: extreme hunger, fluid retention, edema, paresthesias, hyperglycemia. Banned by WADA.

CJC-1295. A synthetic GHRH analog with a prolonged half-life (28 days) through albumin binding. It raises GH 2-10× and IGF-1 1.5-3×. A phase 2 trial was halted after a death (inconclusive regarding causality). Limited clinical data.

The reasonable conclusion

Therapeutic peptides are not a single promise: they are an enormous catalog with very uneven quality of evidence. Tesamorelin and Thymosin Alpha-1 have a defined clinical place; Cerebrolysin has been used for decades in hospitals outside the US; MK-677 works, but its side effects limit chronic use. BPC-157, MOTS-c, Humanin, and company are fascinating in the lab but clinically speculative. Any serious protocol starts by asking how many human trials there are and of what quality; the rest is internet content.