MOTS-c: The Mitochondrial Peptide - Evidence, Dosage Chart & What to Expect

Key takeaways

• MOTS-c is a 16-amino-acid peptide encoded inside mitochondrial DNA, discovered in 2015. In mice it activates the energy sensor AMPK, improves insulin sensitivity, prevents diet-induced obesity and lets old animals run about twice as long. Exercise raises it about 12-fold in human muscle, which is why it is sold as an "exercise in a vial".
• Every efficacy result is a mouse result. In humans, only the body's own MOTS-c has been measured. No trial has ever given MOTS-c to a person, and FDA's reviewers said so in July 2026.
• The one human trial in this family tested CB4211, a modified analog, for four weeks in 20 adults with obesity and fatty liver: it was safe, lowered liver enzymes and glucose, showed only a trend on weight, and did not beat placebo on liver fat. The company merged into a cancer biotech in 2023 and the program went nowhere.
• The dosage charts online (5 to 10 mg two or three times a week) were written by sellers. The studied doses are mouse doses of 0.5 to 15 mg per kilogram a day by intraperitoneal injection; nobody knows the human dose, half-life or immune response.
• Legal status: MOTS-c was on FDA's Category 2 list from September 2023, came off it on April 15, 2026, and was recommended for the 503A list by FDA's advisory committee on July 23, 2026 (7 to 5, 2 abstaining) against FDA staff advice. No rule has issued, so no US pharmacy may compound it, and research vials sold for injection are unapproved drugs. We give no purchase guidance for it.

MOTS-c at a glance

Also called

mitochondrial open reading frame of the 12S rRNA-c, MOTS-c peptide, CB4211 (a modified analog, development stopped)

Class

Mitochondrial-derived peptide: a 16-amino-acid peptide encoded inside the mitochondrial 12S ribosomal RNA gene; activates AMPK and regulates nuclear genes in preclinical studies

Route

Intraperitoneal injection in every published mouse study; subcutaneous injection in vendor protocols; no human pharmacokinetic data

FDA status

Not FDA-approved and never tested in a human trial. FDA placed it in Category 2 (significant safety risk) in September 2023 and removed it on April 15, 2026 after the nomination was withdrawn; its advisory committee voted 7 to 5 with 2 abstentions on July 23, 2026 to recommend it for the 503A list against FDA reviewers' advice. No rule has been issued, so it cannot be legally compounded.

FDA Category 2 (compounding restricted)

No

Available by prescription (US)

Not as a prescription product

Best-studied use

Mouse studies of insulin sensitivity, diet-induced obesity and exercise capacity; human studies of blood and muscle levels only; one 4-week phase 1b of a modified analog (CB4211) in 20 adults with obesity and fatty liver

Typical monthly cost (telehealth, 2026)

No legal product exists to price; research vials are unapproved drugs and we do not list their prices

What MOTS-c is and how it works

Mitochondria carry their own small genome, 16,569 base pairs in humans, which was long thought to encode only 13 proteins of the respiratory chain plus the RNAs needed to make them. In 2001 researchers found a short open reading frame hidden inside one of those RNA genes that encodes a 24-amino-acid peptide, humanin. In 2015 a group at the University of Southern California reported a second one: a 16-amino-acid peptide encoded within the 12S ribosomal RNA gene, which they named MOTS-c, for mitochondrial open reading frame of the 12S rRNA-c (Lee 2015).

The biology they described is the reason it sells. In cells, MOTS-c inhibits the folate cycle and the purine synthesis tethered to it, which raises AICAR, an intermediate that switches on AMPK, the master energy sensor that exercise and metformin also activate. Its main target organ in mice appeared to be skeletal muscle, where it increased glucose uptake. Under metabolic stress the peptide also moves into the nucleus and regulates nuclear genes, including stress-response and antioxidant programs, which makes it one of the few known signals running from the mitochondrial genome to the nuclear one (Reynolds 2021). In the same mice, MOTS-c levels in muscle and serum fell with age, in step with the development of insulin resistance.

That package, an AMPK activator that muscle makes more of during exercise and less of with age, is what the longevity market heard. The gap between the package and a human drug is the subject of the rest of this page.

What the evidence actually shows

MOTS-c claims, graded by the evidence behind them

Claim	Grade	What the evidence shows	Sources
Improves insulin sensitivity and prevents obesity	D	Mouse data only. MOTS-c 5 mg/kg a day intraperitoneally for 7 days improved glucose clearance in young mice, raised the glucose infusion rate on a clamp by about 30% in high-fat-fed mice, and restored muscle insulin sensitivity in 12-month-old mice to the level of 3-month-old ones. At 0.5 mg/kg a day for 8 weeks it prevented obesity on a 60% fat diet without reducing food intake.	Lee 2015
Improves endurance and physical function in old age	D	Mouse data only. At 15 mg/kg a day for 2 weeks, 22-month-old mice ran about 2-fold longer and 2.16-fold farther on a treadmill; 17% reached the final sprint stage versus none untreated. Late-life treatment three times a week from about 23.5 months improved grip strength, stride length, a walking test and blood glucose, and reduced fat mass.	Reynolds 2021
Extends lifespan	D	In the late-life mouse experiment, median and maximum lifespan rose by about 6.4% and 7.0%, but the survival curve was not statistically different (P = 0.23); the authors wrote that larger cohorts are needed. No lifespan data exist in any other species.	Reynolds 2021
Works as an exercise mimetic in people	C	Only endogenous levels have been measured. In 10 sedentary young men, ten 60-second cycling sprints raised MOTS-c about 11.9-fold in muscle biopsies and about 1.5-fold in plasma, returning toward baseline within 4 hours. Nobody has injected MOTS-c into a human to see whether it reproduces any effect of exercise.	Reynolds 2021
Low MOTS-c marks obesity and insulin resistance in people	C	Mixed observational data. In 40 obese children and 57 controls, circulating MOTS-c was lower in obese boys (465 versus 584 ng/mL) and correlated with insulin resistance, but not in girls. In 10 lean and 10 obese adults, levels were the same in both groups. A lipid infusion raised plasma MOTS-c two- to three-fold and insulin blunted it; eight weeks of exercise training did not change resting levels.	Du 2018; Cataldo 2018; Ramanjaneya 2019
Linked to exceptional longevity	D	A 2015 commentary suggested that an East Asian mitochondrial DNA variant inside the MOTS-c sequence (m.1382A>C) might help explain Japanese longevity. A 2021 analysis of 27,527 people found the same variant associated with a higher prevalence of type 2 diabetes in men, and showed that the variant peptide (K14Q) has less metabolic activity. The longevity link remains a hypothesis.	Fuku 2015; Zempo 2021
Produces weight loss or metabolic benefit in humans	C	Analog only. CB4211, a modified MOTS-c analog, was given at 25 mg subcutaneously once daily for 4 weeks to 11 obese adults with fatty liver, versus 9 on placebo. ALT fell 21% versus a 4% rise, AST fell 28% versus 11%, glucose fell 6% versus 0% (all significant); body weight showed a non-significant trend; liver fat fell about 5 percentage points in both groups. The company did not run a phase 2.	CohBar 2021; Medthority 2023
Safe for human use	D	No human trial of MOTS-c itself exists. CB4211 produced no serious adverse events over 4 weeks; the only adverse events in more than 10% of subjects were injection-site reactions. In July 2026 FDA's reviewers recommended against compounding MOTS-c, citing nonexistent human clinical data, uncertain product identity and immunogenicity risk.	CohBar 2021; Kelley Drye 2026; Orrick 2026

Three things stand out from that table.

First, the species. The entire efficacy case for MOTS-c is two mouse papers from one laboratory, both excellent, both with authors who disclosed consulting for and holding shares in CohBar, the company founded to commercialize mitochondrial peptides. That is not a reason to disbelieve the mouse results. It is a reason to notice that nobody independent has tried to reproduce the lifespan or insulin findings, and that the human evidence consists of measuring a hormone the body already makes.

Second, the direction of the human data. The exercise study is often quoted as if it showed that MOTS-c improves fitness. It showed the reverse causation: fitness activity raises MOTS-c. Whether raising MOTS-c from outside does anything that exercise does is exactly the untested question. The observational studies do not settle it either; low MOTS-c tracked insulin resistance in obese boys but not in obese adults, and a fat infusion raised it, which suggests the body releases it in response to metabolic load rather than as a simple marker of health (Ramanjaneya 2019).

Third, the lifespan number. The late-life mouse study is the one most quoted by sellers, and its survival result was a trend that did not reach significance. The authors were careful; the marketing is not.

The only human trial was of a different molecule

CohBar, founded by the discoverers of MOTS-c, built an analog called CB4211 with modifications to make it more drug-like, and it is the only MOTS-c-family compound ever given to people under a trial protocol. Everything known about it comes from a company press release of August 10, 2021, filed with the SEC, not from a peer-reviewed paper (CohBar 2021).

The phase 1a stage gave single and multiple ascending doses to 65 healthy adults over one week to pick a dose. The phase 1b stage randomized 20 obese adults with at least 10% liver fat to CB4211 25 mg or placebo, injected subcutaneously once daily for four weeks while they lived in a clinical unit. The primary endpoint was safety, which it met: no serious adverse events, and injection-site reactions as the only adverse events affecting more than 10% of treated subjects. The exploratory endpoints are the numbers sellers quote: ALT fell 21% on CB4211 against a 4% rise on placebo, AST fell 28% against 11%, and glucose fell 6% against 0%, each significant at the 5% level by t-test in a group of 20. Body weight showed "a trend towards lower body weight". Liver fat by MRI fell 5.03 percentage points on CB4211 and 4.88 on placebo, from different baselines (21.1% versus 15.9%), and the proportion of responders was 36% versus 33%. In other words, the one endpoint that would have mattered for a liver-disease drug did not separate from placebo in four weeks, which is also not surprising in four weeks.

What happened next is the part the dosing guides omit. No phase 2 was announced. In May 2023 CohBar agreed to a reverse merger with Morphogenesis, a cancer-immunotherapy company, forming TuHURA Biosciences, with the combined company's stated focus on Morphogenesis's technologies (Medthority 2023). As of October 2026 we could find no further clinical development of CB4211 or of any MOTS-c analog by any company. A molecule that produces a trend on weight and no separation on liver fat in a 20-person study is not a failure; it is an early signal. But it is the whole of the human record, and it was not MOTS-c.

What you are promised versus what is documented

Seller pages list fat loss, better insulin sensitivity, endurance, "mitochondrial optimization", longevity, bone density and recovery. The evidence sorts those into three bins.

• Documented in humans: that MOTS-c exists, circulates, rises with exercise and with lipid load, and is lower in some obese boys. That the analog CB4211 lowered liver enzymes and glucose over four weeks without serious adverse events.
• Plausible from mice, untested in humans: fat loss, insulin sensitization, exercise capacity, protection against age-related physical decline.
• Not supported anywhere: lifespan extension (a non-significant mouse trend), bone density (no study we could find in any species that tests injected MOTS-c for osteoporosis, despite it being a nominated use), cognitive or "energy" benefits, and any claim about what a given milligram dose does in a person.

MOTS-c vs exercise, GLP-1 drugs, NAD+ precursors and elamipretide

The realistic alternatives are the things that do what MOTS-c is sold for, with human evidence and a legal product.

Read the GLP-1 guide and the NAD+ profile for the detail on those two; the legal tracker has the status of the rest.

Dosage: the charts that circulate versus what was studied

The arithmetic matters. The standard conversion from mouse to human dosing divides the mouse milligram-per-kilogram dose by about 12.3 to account for body surface area. By that formula, 0.5 mg/kg in a mouse corresponds to about 0.04 mg/kg in a person, or roughly 3 mg a day for a 70 kg adult; 5 mg/kg corresponds to about 28 mg a day; 15 mg/kg to about 85 mg a day. The vendor charts, 10 to 30 mg a week, sit near the bottom of that range and are given by a different route (under the skin, not into the abdominal cavity) on a different schedule. The conversion is also only a starting guess: it says nothing about how long MOTS-c lasts in human blood, whether it reaches muscle, or whether the immune system reacts to repeated injections, because none of that has been measured. A chart that assigns a milligram dose to a human effect is describing an experiment nobody has run.

We do not publish a reconstitution example for MOTS-c. The reconstitution calculator exists for medications a pharmacy has dispensed with a labeled concentration; a research vial has neither.

Side effects and theoretical risks

What is known: almost nothing. The only human safety data come from four weeks of the analog CB4211, where injection-site reactions were the only common adverse event and there were no serious ones (CohBar 2021). Four weeks in 11 people cannot detect anything rarer than about one in four.

What FDA's reviewers raised in July 2026, for the seven peptides as a group: insufficient or nonexistent human clinical trial data, gaps in safety and effectiveness evidence, uncertainty about product quality and identity, and potential safety concerns including immunogenicity (Kelley Drye 2026). For MOTS-c specifically, the briefing summarized by Orrick found no human data at all and noted that MOTS-c is on the World Anti-Doping Agency's prohibited list (Orrick 2026).

What is theoretical but worth naming:

• Immunogenicity. MOTS-c is a native human peptide, but a synthetic copy injected repeatedly, with whatever impurities a research vial carries, can provoke antibodies; nobody has looked.
• Metabolic effects. An AMPK activator that increases muscle glucose uptake could, in principle, lower blood sugar in someone on insulin or sulfonylureas. Untested.
• Cancer biology. MOTS-c regulates nuclear gene expression and cell stress programs; its effect on existing tumors, in either direction, is unknown.
• Product quality. Research vials have no sterility, potency or identity testing, and FDA told the committee that peptide products of this kind lack settled identity.

Do not use MOTS-c if you are pregnant or breastfeeding, have an active cancer, use insulin or other glucose-lowering drugs, or compete in tested sport. For everyone else, the practical answer in October 2026 is the same: there is no legal, labeled product to use.

Legal status in the United States

MOTS-c is the clearest example of the gap between "a committee recommended it" and "you can get it". The sequence, consistent with our legal tracker:

• September 2023. FDA placed MOTS-c in Category 2 of its interim 503A list, substances that may present significant safety risks, alongside BPC-157, CJC-1295, ipamorelin, epitalon and others, which ended any routine compounding (FDA Category 2).
• April 15, 2026. FDA announced that twelve of those peptides, MOTS-c among them, would come off Category 2 because their nominators had withdrawn the original nominations. As the compounding lawyers at Frier Levitt wrote at the time, removal does not make a substance eligible for compounding under section 503A; it only ends the safety flag (Frier Levitt 2026).
• July 23, 2026. FDA's Pharmacy Compounding Advisory Committee reviewed MOTS-c, nominated for obesity and osteoporosis, and voted 7 in favor, 5 against, with 2 abstentions, to recommend adding its free base and acetate forms to the 503A bulks list, the closest vote of the meeting (FDA PCAC 2026) (Hyman Phelps 2026). FDA's review team had recommended against every substance on the agenda; opponents at the meeting called MOTS-c a poorly characterized experimental drug and argued that listing it would amount to an uncontrolled human trial without adverse-event reporting.
• After the vote. The vote is advisory. FDA must publish a proposed rule, take comments and finalize it before any pharmacy may compound MOTS-c, a process the law firms following it expect to take a year or more, and FDA is not bound by the recommendation. Whether FDA will place MOTS-c in Category 1 in the meantime, or exercise enforcement discretion if pharmacies start compounding, were open questions at the meeting (Hyman Phelps 2026). As of October 9, 2026, no proposed rule has appeared.

So: not approved anywhere, not compoundable by any 503A pharmacy or 503B outsourcing facility, and not a component of any approved drug. The only MOTS-c for sale is research-use vials, which FDA treats as unapproved drugs when websites supply dosing guides, injection instructions or bacteriostatic water, the evidence it cited in its August 24, 2026 warning letters to five vendors. MOTS-c was not named in those letters as far as we can tell; the reasoning applies to it exactly.

What to do instead

If what you want is what MOTS-c is sold for, the evidence points somewhere else. Exercise raises your own MOTS-c more than any vial could claim to, and it is the only intervention on this page with human outcome data for aging. For weight and metabolic disease, semaglutide and tirzepatide have the trials and a legal prescription path. For "mitochondrial health", the honest position is that no injectable has earned the phrase; the NAD+ profile explains why the most popular one has not either. Our longevity ranking puts all of them side by side.

Bottom line

MOTS-c is a genuine discovery: a peptide encoded in mitochondrial DNA that, in mice, improves insulin sensitivity, prevents diet-induced obesity and keeps old animals running. It is also, in October 2026, a molecule that has never been given to a human being in a trial, whose only clinical cousin was dropped after a four-week study, whose dosing charts were written by the people selling it, and which no pharmacy in the United States may legally prepare. The July 2026 committee vote moved it one step closer to the permitted list over the objection of FDA's own reviewers, and that step is not a product.

A reasonable position is to watch the Federal Register. An unreasonable one is to inject a research vial on the strength of a mouse treadmill.

Frequently asked questions

+−What is MOTS-c?

MOTS-c is a short peptide, 16 amino acids long, that is encoded not in the cell nucleus but inside the mitochondrial genome, within the gene for the 12S ribosomal RNA. It was described in 2015 by a group at the University of Southern California, who showed that in mice it acts on skeletal muscle, activates the energy sensor AMPK and improves insulin sensitivity. Its levels rise sharply in human muscle during intense exercise, which is why it is called an exercise mimetic. It is a real molecule with real biology; what it is not is a tested human drug.

+−What does MOTS-c do?

In mice, injected MOTS-c prevented the insulin resistance that comes with age and with a high-fat diet, prevented diet-induced obesity without reducing food intake, and let 22-month-old mice run about twice as long on a treadmill. In humans, the only thing that has been measured is the body's own MOTS-c: it rises about 12-fold in muscle and about 1.5-fold in blood during hard exercise, it is lower in obese boys with insulin resistance, and it is raised by a fat infusion and suppressed by insulin. Nobody has given MOTS-c to a person in a trial, so nobody knows what it does when injected.

+−Is MOTS-c good to take?

There is no evidence either way in humans, and in October 2026 there is no legal way to obtain it in the United States: no pharmacy may compound it, and the vials sold online are unapproved drugs. The only human trial in this family tested CB4211, a modified analog, for four weeks in 20 people; it was safe over that period, lowered liver enzymes and glucose, and did not separate from placebo on liver fat or significantly on weight. The company then stopped developing it. If you want the things MOTS-c is sold for, exercise raises your own MOTS-c, and GLP-1 drugs have the weight-loss and cardiovascular trials.

+−What is MOTS-c peptide used for?

In research, as a tool to study how mitochondria signal to the rest of the cell and as a candidate for metabolic disease. In the online market, it is sold for fat loss, insulin sensitivity, endurance, longevity and sometimes bone density, all extrapolated from mouse experiments. Its nomination to FDA's compounding list proposed obesity and osteoporosis as the uses, and FDA's reviewers found no human data supporting either.

+−Is there a MOTS-c dosage chart?

Not from any human study, because none exists. The charts that circulate, usually 5 to 10 mg injected under the skin two or three times a week in cycles of four to eight weeks, were written by sellers. The published doses are mouse doses: 0.5 to 15 mg per kilogram a day by intraperitoneal injection, which, converted by the standard body-surface formula, would correspond to roughly 3 to 85 mg a day in a 70 kg adult. The analog CB4211 was given at 25 mg once a day. None of that is a recommendation; it shows how far the vendor charts are from anything tested.

+−Does MOTS-c work for weight loss?

In mice on a high-fat diet, yes: 0.5 mg per kilogram a day for eight weeks prevented obesity without reducing how much they ate. In people, the only data come from the analog CB4211, which produced a trend toward lower body weight after four weeks that was not statistically significant. For weight loss with human evidence, semaglutide and tirzepatide have trials with tens of thousands of participants; see our GLP-1 guide.

+−What is the strongest peptide for losing weight?

Tirzepatide. In the SURMOUNT-1 trial, the 15 mg dose produced about 21% weight loss at 72 weeks, more than any other approved medication, and semaglutide 2.4 mg produced about 15% at 68 weeks in STEP 1. Both are FDA-approved peptides with a legal prescription path. MOTS-c has no human weight-loss data; our weight-loss ranking covers the field.

+−What should your C-peptide level be?

C-peptide has nothing to do with MOTS-c; the search engines pair them because of the letter. C-peptide is a fragment released when your pancreas makes insulin, and doctors measure it to see how much insulin you still produce, for example to distinguish type 1 from type 2 diabetes. Reference ranges depend on the laboratory and on whether you were fasting, so interpret your result with the clinician who ordered it.

+−Is MOTS-c expensive?

There is no legal product to price. Because no US pharmacy may compound MOTS-c, everything on sale is a research-use vial, which is an unapproved drug when it is sold for injection, and we do not list prices for those. Whatever the price, it buys no label, no verified content and no clinician.

+−Is MOTS-c legal or FDA approved?

It is not approved for anything, anywhere. In the United States it cannot be compounded: it was on FDA's Category 2 safety-risk list from September 2023, came off that list on April 15, 2026 when its nomination was withdrawn, and was recommended for the permitted list by FDA's advisory committee on July 23, 2026 by 7 votes to 5 with 2 abstentions, over the objection of FDA's own reviewers. Until FDA finishes rulemaking, which the lawyers who follow the committee expect to take a year or more, the recommendation changes nothing. Possessing it is not a crime; selling it for human use is.

Sources

1. StudyLee C et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab 2015;21:443-54. (2015)
2. StudyReynolds JC et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun 2021;12:470. (2021)
3. StudyFuku N et al. The mitochondrial-derived peptide MOTS-c: a player in exceptional longevity? Aging Cell 2015;14:921-3. (2015)
4. StudyZempo H et al. A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c. Aging (Albany NY) 2021;13:1692-717. (2021)
5. StudyDu C et al. Circulating MOTS-c levels are decreased in obese male children and adolescents and associated with insulin resistance. Pediatr Diabetes 2018 (online April 25, 2018). (2018)
6. StudyCataldo LR et al. Plasma MOTS-c levels are associated with insulin sensitivity in lean but not in obese individuals. J Investig Med 2018;66:1019-22. (2018)
7. StudyRamanjaneya M et al. Lipids and insulin regulate mitochondrial-derived peptide (MOTS-c) in PCOS and healthy subjects. Clin Endocrinol (Oxf) 2019;91:278-87. (2019)
8. SourceCohBar Inc. CohBar announces positive topline results from the phase 1a/1b study of CB4211 under development for NASH and obesity. Press release of August 10, 2021, filed with the SEC as exhibit 99.2. (2021)
9. NewsMedthority. CohBar Inc. and Morphogenesis Inc. to merge (combined company to be named TuHURA Biosciences and to focus on Morphogenesis technologies). May 24, 2023. (2023)
10. RegulatoryFDA. Certain bulk drug substances for use in compounding may present significant safety risks (Category 2 list; MOTS-c added September 2023).
11. NewsFrier Levitt. FDA to remove 12 popular peptides from the Category 2 'do not compound' list. April 16, 2026. (2026)
12. RegulatoryFDA. July 23-24, 2026 meeting of the Pharmacy Compounding Advisory Committee (BPC-157, KPV, TB-500, MOTS-c, emideltide, epitalon, semax). (2026)
13. NewsPalmer KL, Snow CD, Bass M. PCAC approves four bulk drug substances for the 503A list (BPC-157, KPV, TB-500, MOTS-c). FDA Law Blog, Hyman Phelps & McNamara, July 24, 2026. (2026)
14. NewsKelley Drye. FDA advisory committee recommends several peptides for compounding despite staff opposition: what stakeholders need to know. July 30, 2026. (2026)
15. NewsOrrick. FDA peptide compounding vote: what to watch at the July PCAC meeting (summary of FDA's briefing documents). July 21, 2026. (2026)