Humanin vs MOTS-c
The two founding mitochondrial-derived peptides, graded the same way. Humanin's preclinical work is cytoprotective and neuronal; MOTS-c's is metabolic and muscular. Neither has human outcome trials.
Short answer
Both rest mostly on animal and lab work, so the evidence cannot separate humanin from MOTS-c. Humanin is the one sold for longevity and metabolic health, while MOTS-c targets metabolism, endurance and longevity. Both are sold gray-market as research chemicals.
Humanin
A genuine cytoprotective mitochondrial-derived peptide whose levels fall with age — but no randomized human trial shows that taking it does anything for people.
Full Humanin evidence reviewMOTS-c
A genuine mitochondrial-derived peptide with interesting rodent data on metabolism and exercise — but no human outcome trials.
Full MOTS-c evidence reviewHumanin vs MOTS-c: head to head
- FDA status / approved use
Humanin
Not approved for any use; sold as an unregulated research injectableMOTS-c
Not FDA-approved for any use; sold as a research-use-only injectable- Marketed for
Humanin
Longevity, metabolic healthMOTS-c
Metabolism, endurance, longevity- Outcome areas
Humanin
Longevity / lifespan; Mitochondrial / cellular energyMOTS-c
Mitochondrial / cellular energy; Exercise performance / endurance; Longevity / lifespan- Evidence grade
Humanin
Preclinical / minimalMOTS-c
Preclinical / minimal- How it works
Humanin
Mitochondrial-derived peptide that blocks cell death in lab and animal studiesMOTS-c
Mitochondrial peptide targeting the folate-AICAR-AMPK energy-sensing pathway- Route and dosing
Humanin
InjectionMOTS-c
Injection- Headline human result
Humanin
Not establishedMOTS-c
Not established- Strongest evidence
Humanin
Hashimoto, PNAS 2001. Little or no controlled human outcome data for the marketed useHumanin evidence reviewPubMed 11371646MOTS-c
Lee, Cell Metab 2015. Little or no controlled human outcome data for the marketed useMOTS-c evidence reviewPubMed 25738459- Key safety signal
Humanin
Identity, dose, purity and sterility unverified; no long-term human safety dataMOTS-c
No long-term human safety data; research vials of unverified identity, dose, purity and sterility- How it is obtained
Humanin
Sold gray-market as a research chemical; no approved or legitimately compounded human productMOTS-c
Sold gray-market as a research chemical; no approved or legitimately compounded human product
| Humanin | MOTS-c | |
|---|---|---|
| FDA status / approved use | Not approved for any use; sold as an unregulated research injectable | Not FDA-approved for any use; sold as a research-use-only injectable |
| Marketed for | Longevity, metabolic health | Metabolism, endurance, longevity |
| Outcome areas | Longevity / lifespan; Mitochondrial / cellular energy | Mitochondrial / cellular energy; Exercise performance / endurance; Longevity / lifespan |
| Evidence grade | Preclinical / minimal | Preclinical / minimal |
| How it works | Mitochondrial-derived peptide that blocks cell death in lab and animal studies | Mitochondrial peptide targeting the folate-AICAR-AMPK energy-sensing pathway |
| Route and dosing | Injection | Injection |
| Headline human result | Not established | Not established |
| Strongest evidence | Hashimoto, PNAS 2001. Little or no controlled human outcome data for the marketed useHumanin evidence reviewPubMed 11371646 | Lee, Cell Metab 2015. Little or no controlled human outcome data for the marketed useMOTS-c evidence reviewPubMed 25738459 |
| Key safety signal | Identity, dose, purity and sterility unverified; no long-term human safety data | No long-term human safety data; research vials of unverified identity, dose, purity and sterility |
| How it is obtained | Sold gray-market as a research chemical; no approved or legitimately compounded human product | Sold gray-market as a research chemical; no approved or legitimately compounded human product |
marks a row where the two differ. “Not established” marks a cell the available evidence does not answer. Evidence grades come from our evidence matrix, which grades each molecule on the human data for the use it is marketed for.
- Preclinical / minimal:
- Evidence is largely animal, in-vitro, or anecdotal. Little or no controlled human outcome data for the marketed use.
Our verdict
Both sit in the same preclinical tier, and neither has an adequately powered randomized, placebo-controlled human trial for anything it is marketed for. Humanin was the first mitochondrial-derived peptide ever described, though much of its supportive literature uses the more potent engineered analog HNG rather than the native peptide; MOTS-c has the more developed metabolic and exercise story, again in rodents. The human data on both are observational, mainly that circulating levels fall with age, which is a reason to keep studying them and not evidence that injecting them helps. There is no winner to declare here, and both reach buyers as research-only injectables of unverified identity, dose, and purity.
Humanin fits if
Humanin is the better read if your interest is cytoprotection and the neuronal discovery story, provided you note how much of the literature is really about the HNG analog.
MOTS-c fits if
MOTS-c is the closer fit if your interest is metabolic and exercise biology, where the rodent AMPK-pathway work is the most developed part of the field.
Humanin vs MOTS-c: common questions
- Is either humanin or MOTS-c FDA-approved?
- No. Humanin is not approved for any use; sold as an unregulated research injectable. MOTS-c is not FDA-approved for any use; sold as a research-use-only injectable.
- Which has stronger human evidence, humanin or MOTS-c?
- Neither. Both are graded preclinical / minimal, with little or no controlled human outcome data for the marketed use. The key source for humanin is Hashimoto, PNAS 2001; for MOTS-c, it is Lee, Cell Metab 2015.
- What are the main safety concerns with humanin and MOTS-c?
- For humanin, watch for unverified identity, dose, purity and sterility; no long-term human safety data. MOTS-c has no long-term human safety data; research vials of unverified identity, dose, purity and sterility.
Key studies behind each
Humanin
- Hashimoto Y, Niikura T, Tajima H, et al. (2001). A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta. Proc Natl Acad Sci U S A. PubMed 11371646
- Muzumdar RH, Huffman DM, Atzmon G, et al. (2009). Humanin: a novel central regulator of peripheral insulin action. PLoS One. PubMed 19623253
- Yen K, Mehta HH, Kim SJ, et al. (2020). The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan. Aging (Albany NY). PubMed 32575074
- Lee C, Yen K, Cohen P. (2013). Humanin: a harbinger of mitochondrial-derived peptides? Trends Endocrinol Metab. PubMed 23402768
MOTS-c
- Lee C, Zeng J, Drew BG, et al. (2015). The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. PubMed 25738459
- Kim SJ, Miller B, Mehta HH, et al. (2019). The mitochondrial-derived peptide MOTS-c is a regulator of plasma metabolites and enhances insulin sensitivity. Physiol Rep. PubMed 31293078
- Reynolds JC, Lai RW, Woodhead JST, et al. (2021). MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. PubMed 33473109
- Kim SJ, Miller B, Kumagai H, et al. (2021). Mitochondrial-derived peptides in aging and age-related diseases. GeroScience. PubMed 32910336
The full evidence reviews
- Humanin: the first mitochondrial-derived peptide — real biology, no human trials
Discovered in 2001 in a surviving neuron, humanin is a genuine cytoprotective mitochondrial-derived peptide whose levels fall with age — but no randomized human trial shows that taking it does anything for people.
Updated August 2026
- MOTS-c peptide: benefits, side effects and what the evidence shows
Real mitochondrial biology, absent human evidence: a genuine mitochondrial-derived peptide with interesting rodent data on metabolism and exercise, but no human outcome trials. Promising biology, not a proven therapeutic.
Updated October 2026