Which is better, MOTS-c or humanin?
Neither has evidence to support clinical use and neither can currently be lawfully compounded; MOTS-c has a pending PCAC recommendation, which is advisory. Both sit at the animal only evidence grade, and the human data for each are association studies of natural blood levels or genetics rather than treatment trials. Humanin also carries a theoretical tumor survival concern from its anti-apoptotic action that has not been studied in people. [1] [2] [4] [7] [8] [9]
How do MOTS-c and humanin compare?
| Dimension | MOTS-c | Humanin |
|---|---|---|
| Origin [1] [4] | 16 amino acids, encoded in the mitochondrial 12S rRNA gene. | 24 amino acids, encoded in the mitochondrial 16S rRNA gene (MT-RNR2). |
| Mechanism [1] [4] [5] | Inhibits the folate cycle and purine synthesis, raising AICAR and activating AMPK, which increases muscle glucose uptake and fat oxidation; moves to the nucleus under metabolic stress. | Binds Bax and IGFBP-3 inside cells to block apoptosis and signals through a CNTFR, WSX-1, and gp130 receptor complex that activates STAT3. |
| Strongest animal findings [1] [2] [4] [5] [7] | Prevented diet induced obesity and insulin resistance in mice (0.5 mg/kg daily) and improved running capacity in young and old mice (15 mg/kg). | Rescued neurons from Alzheimer's related death in culture, improved hepatic insulin sensitivity in rats, and the analog HNG improved metabolic healthspan and memory in middle aged mice without extending mean life span. |
| Human data [2] [3] [6] [7] | Blood and muscle levels rise acutely with exercise in 10 young men; a MOTS-c sequence variant is associated with type 2 diabetes in Japanese men. No treatment trial. | Higher plasma levels associated with preserved coronary endothelial function in 40 patients; levels decline with age and are higher in centenarian offspring. No treatment trial. |
| Theoretical safety concerns [1] [4] [5] | Possible added glucose lowering with diabetes drugs, extrapolated from mouse AMPK data. | Possible support of tumor cell survival from its anti-apoptotic, STAT3 activating action; possible added glucose lowering. |
| Note: Neither concern has been tested in people because no human safety data exist for either peptide. | ||
| FDA and compounding status [8] [9] | Removed from the 503A Category 2 list on April 15, 2026; PCAC recommended adding it to the 503A bulks list on July 23 to 24, 2026; no final FDA rule at verification. | Not identified on any 503A nomination list or PCAC agenda, so a 503A pharmacy cannot lawfully compound it as a bulk substance. |
| Access and cost [8] [9] | No lawful compounded channel today: PCAC recommended it for the 503A bulks list in July 2026, but the recommendation is advisory and FDA has not published a final rule. | No lawful channel. Only research chemical listings, which are not lawful for human use or verified for purity. |
| Animal study dose ranges [1] [2] [5] [7] | 0.5 mg/kg per day intraperitoneally (metabolic) up to 15 mg/kg (exercise) in mice. | 0.1 to 4 mg/kg intraperitoneally in rodents; 2 to 4 mg/kg HNG twice weekly in the mouse healthspan study. |
| Note: No human dose has been established for either peptide. | ||
Evidence grade and regulatory status
Pulled from each peptide’s own record, so it stays in step with the peptide pages.
| Attribute | MOTS-c | Humanin |
|---|---|---|
| Class | Mitochondrial derived peptide (16 amino acids) encoded in the 12S rRNA region of mitochondrial DNA | Mitochondrial derived peptide (24 amino acids) encoded in the 16S rRNA region of mitochondrial DNA |
| What it is | A 16 amino acid peptide coded by mitochondrial DNA that improves metabolism and exercise capacity in mice; human data limited to blood levels and genetics. | A 24 amino acid peptide coded by mitochondrial DNA, protective in cells and rodents and tied to blood levels in people; no human treatment trials. |
| Evidence | Evidence: Animal-only evidence | Evidence: Animal-only evidence |
| FDA status | Regulatory: Under FDA review | Regulatory: Unscheduled |
| Compounding | MOTS-c was placed on the FDA 503A Category 2 list (substances with significant safety risks) in 2023 and removed from it on April 15, 2026. On July 23 to 24, 2026 the Pharmacy Compounding Advisory Committee recommended adding MOTS-c to the 503A bulks list. As of the last verification date FDA has not published a final rule, so compounding pharmacies and state boards vary in whether they will fill it. It is not an FDA approved drug and is not eligible for 503B outsourcing. | Humanin is not an FDA approved drug and PeptideAgent has not identified it on the FDA 503A bulks nomination lists or in any Pharmacy Compounding Advisory Committee review. Without a listing, a 503A pharmacy cannot lawfully compound it as a bulk substance. It is not eligible for 503B outsourcing. Products sold under this name are not lawful for human use. |
| WADA | WADA: WADA prohibited | WADA: WADA prohibited |
| Routes | Subcutaneous injection (as sold), Intraperitoneal injection (animal studies) | Subcutaneous injection (as sold), Intraperitoneal and intracerebroventricular injection (animal studies) |
| Typical cost | No lawful compounded price: MOTS-c is not on the 503A bulks list, and PCAC's July 2026 recommendation is advisory until FDA publishes a final rule. Advertised clinic prices are not a comparable price. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity. | Not available through licensed channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity. |
| Last verified |
Has MOTS-c been tested directly against humanin?
No published trial has compared MOTS-c and humanin directly. The dimensions above come from separate studies and labels, and cross-trial comparisons are less reliable than a direct trial.
What do MOTS-c and humanin cost?
| Dimension | MOTS-c | Humanin |
|---|---|---|
| Typical cost | No lawful compounded price: MOTS-c is not on the 503A bulks list, and PCAC's July 2026 recommendation is advisory until FDA publishes a final rule. Advertised clinic prices are not a comparable price. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity. | Not available through licensed channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity. |
| Price detail | MOTS-c price by channel | Price index in progress |
Where a price index exists, the range is the cash price per month across branded, compounded, and telehealth channels, without insurance. The cost pages give each channel separately with its sources. Otherwise the typical cost from the peptide record is shown. Legal access depends on your state: see peptide legality by state.
Frequently asked questions
Which is better for longevity, MOTS-c or humanin?
Neither has been shown to extend life or healthspan in people. In mice, MOTS-c improved physical capacity in old animals and the humanin analog HNG improved metabolic healthspan and memory without extending mean life span. Human data for both are limited to blood level associations. [2] [7]
Are MOTS-c and humanin the same kind of peptide?
Yes, both are mitochondrial derived peptides translated from short reading frames inside mitochondrial ribosomal RNA genes, but from different genes (12S for MOTS-c, 16S for humanin) and with different mechanisms: MOTS-c works through AMPK and metabolism, humanin through anti-apoptotic and STAT3 signaling. [1] [4] [5]
Can I get a prescription for either one?
Not today. FDA removed MOTS-c from Category 2 and PCAC recommended it for the 503A bulks list in 2026, but the recommendation is advisory and FDA had not issued a final rule at verification, so a 503A pharmacy has no federal basis to compound it from bulk. Humanin has never been nominated and has no lawful US route. [8] [9]
Are they allowed in sport?
No. Both are prohibited at all times: MOTS-c is named under WADA section S4.4 as a metabolic modulator, and humanin falls under section S0 as a non-approved substance. [10]
Does humanin protect against Alzheimer's disease?
Humanin was discovered because it protected cultured neurons from damage caused by Alzheimer's related genes and amyloid beta, but that work was in cells. No human trial has tested humanin or an analog for Alzheimer's disease or cognition. [4] [7]
Conditions studied
Sources
Numbered citations above point to these primary sources. PubMed entries link to the indexed abstract.
- [1]Lee C et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab 2015PubMed 25738459, 2015
- [2]Reynolds JC et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun 2021PubMed 33473109, 2021
- [3]Zempo H et al. A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c. Aging (Albany NY) 2021PubMed 33468709, 2021
- [4]Hashimoto Y et al. 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 2001PubMed 11371646, 2001
- [5]Muzumdar RH et al. Humanin: a novel central regulator of peripheral insulin action. PLoS One 2009PubMed 19623253, 2009
- [6]Widmer RJ et al. Circulating humanin levels are associated with preserved coronary endothelial function. Am J Physiol Heart Circ Physiol 2013PubMed 23220334, 2013
- [7]Yen K et al. The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan. Aging (Albany NY) 2020PubMed 32575074, 2020
- [8]FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)FDA
- [9]FDA Pharmacy Compounding Advisory Committee meetings (July 2026 meeting on peptide nominations)FDA
- [10]WADA Prohibited List (section S0 non-approved substances and section S4.4 metabolic modulators)WADA
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PeptideAgent. (2026, September 27). MOTS-c vs humanin: evidence, cost, and legality. https://peptideagent.ai/compare/mots-c-vs-humanin- HTML link
<a href="https://peptideagent.ai/compare/mots-c-vs-humanin">MOTS-c vs humanin: evidence, cost, and legality</a>, PeptideAgent, updated September 27, 2026.