Mitochondrial-derived cytoprotective peptide

Humanin

aka HN

Evidence grade
Grade D: Preclinical only
for longevity, metabolic and neuroprotective use
User score too few reports (7) needs ≥ 10 reports
US FDA Not approved checked 2026-11-13
WADA 2026 Likely prohibited (S0) by class rule · checked 2026-11-13
EU No data · checked 2026-11-13

Goals: Sleep · Cognition & mood · Longevity Compare with another peptide →

User reports

approximate — combined from two independent Reddit reads

Men 45–60

0 men aged 45–60

No reports in this group yet.

All men

0 men

No reports in this group yet.

Everyone

7 people

small sample · n = 7

Outcome unclear 3 of 7 · positive 2 of 7 · no effect 1 of 7

Benefits mood / anxiety 2 of 7 · sleep 2 of 7 · other 1 of 7

Side effects none reported

Stopped 0 of 7 Used with other compounds 3 of 7

User reports are anecdata, not evidence: self-selected, unverified, often combined with other compounds.

In their words

  • “No perceptible effects in the short or medium term.”

  • “For me MOTs-C vs humanin, humanin was better for me personally”

  • “It's VERY anxiolytic. It's effects for me I'd call it the best feeling drug I've ever taken possibly behind ghk-cu.”

  • “After the second dose I started sleeping a solid 8 hours without waking up. I'm taking 2mgs every other day.”

  • “Yes, I've done last couple doses of 5mg mots-c with 5mg humanin but didn't notice any difference.”

Read summaries and method notes

Read 1. No man aged 45–60 and no explicitly male reporter. One user noticed nothing short or medium term; another found Humanin worked better for them than MOTS-c. No verified side effects, doses or discontinuations. One of the lowest-confidence peptides in the batch.

Read 2. No man aged 45–60 and no sex-specific reports. Six users: 2 positive, 1 no effect, 3 unclear — one HNG user called it strongly anxiolytic, another slept a solid 8 hours from the second dose at 2 mg every other day; two others felt only weak (possibly placebo) anxiety relief or no difference with MOTS-c. No side effects; warnings about very poor stability after reconstitution (about $100 per vial).

Note 1. Only two verified firsthand Humanin outcomes. Other opened threads were prospective questions or literature discussion.

Note 2. Very small sample without age/sex data. Order-intent and question threads had no use reports; one SS-31 thread was excluded. Several seed threads were not available.

Each read counted people independently. Overlap between the two reads is estimated from shared threads and removed; counts are approximate. How we count.

Summary

24-amino-acid peptide encoded in the mitochondrial 16S rRNA gene. Discovered in 2001 by Hashimoto et al. in a cDNA library screen for Alzheimer's-protective factors. First identified mitochondrial-derived peptide (MDP) — opened the entire MDP field that later produced MOTS-c. Cytoprotective and anti-apoptotic. Endogenous concentrations have been studied observationally, including in children of centenarians. No human administration trial was found.

Proposed mechanism

  • Mitochondrial origin: Encoded within the 16S rRNA gene of mtDNA (not nuclear genome). One of ~8 known MDPs. Expression regulated by mitochondrial stress.
  • STAT3 activation: Binds tripartite receptor (CNTFR/WSX-1/gp130) → JAK/STAT3 phosphorylation → anti-apoptotic gene expression. This is the primary signaling pathway.
  • Bax/Bak inhibition: Directly binds pro-apoptotic Bax and tBid, preventing mitochondrial outer membrane permeabilization. Blocks cytochrome c release → blocks caspase cascade.
  • IGFBP-3 binding: Humanin binds IGFBP-3 without competing with IGF-I binding in the original experiment; elevated free IGF-1 in users is unestablished.
  • FPRL1/FPRL2 receptors: Binds formyl peptide receptor-like 1 and 2 (now FPR2/FPR3). Anti-inflammatory signaling, phagocytosis modulation, neuroprotection. The exact receptor-affinity hierarchy is not established by the verified sources.
  • AMPK activation: Downstream metabolic effects overlap with MOTS-c, though via different upstream triggers.

Safety

  • Human dosing, pharmacokinetics, adverse-event rates and long-term safety not found
  • Tumor progression and chemotherapy-resistance signals in experimental models
  • HNG and other analogues cannot be assumed equivalent to native humanin

From labels, regulators and trials. No signal in small studies ≠ safe.

Evidence D longevity, metabolic and neuroprotective use

D stands. Human data are measurements of the body's own humanin, not treatment; no administration trial found.

Human trials · 1

  1. NCT034318442019Prospective observational cohort, not a humanin treatment trial 106 people

    Adults undergoing coronary bypass surgery

    Completed biomarker study of endogenous humanin; no registry results posted and no peptide administered. Source

Bar length = trial size on a log scale.

Dose ranges

Reported ranges from labels and studies, with context. Not a recommendation.

No data.

Editorial ratings EDITORIAL

Editors’ judgement, 0–5. Opinion, not data; separate from grade and user score.

  • Safety 3 out of 5
  • Sleep not rated —
  • Recovery 2 out of 5
  • Cognitive 3 out of 5

Sources

  1. clinicaltrials.gov/study/NCT03431844?rank=3&term=humanin&viewType=Table
  2. precision.fda.gov/uniisearch/srs/unii/H975EUX36G
  3. wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf
  4. pubmed.ncbi.nlm.nih.gov/32575074/
  5. pubmed.ncbi.nlm.nih.gov/14561895/
  6. pubmed.ncbi.nlm.nih.gov/26216267/
  7. fda.gov/media/94155/download
  8. pubmed.ncbi.nlm.nih.gov/32444831/
  9. pubmed.ncbi.nlm.nih.gov/37627089/
  10. pubmed.ncbi.nlm.nih.gov/26384090/
  11. pubmed.ncbi.nlm.nih.gov/11854325/
  12. pubmed.ncbi.nlm.nih.gov/30071007/
  13. pubmed.ncbi.nlm.nih.gov/27146946/
  14. pubmed.ncbi.nlm.nih.gov/33531575/
  15. pubmed.ncbi.nlm.nih.gov/11371646/
  16. fda.gov/advisory-committees/advisory-committee-calendar/july-23-24-2026-meeting-pharmacy-c

Reddit threads read · 8

Research checked 2026-11-13.