At a glance

What it is

A peptide your own mitochondria make

MOTS-c stands for mitochondrial open reading frame of the 12S rRNA-c. It has 16 amino acids. Most proteins are coded in the nucleus of a cell. This one is coded in the small ring of DNA inside mitochondria. A research group at the University of Southern California described it in 2015.

Your body already makes MOTS-c, and it circulates in blood. In mouse and cell experiments it acts mainly on skeletal muscle and switches on AMPK, an enzyme that senses cellular energy. FDA reviewers noted in their 2026 briefing that the exact molecular target is still unknown, so it is hard to predict which organs it affects.

Regulatory status

Where MOTS-c stands with FDA, as of November 10, 2026

MOTS-c is not an FDA-approved drug. It is also not yet on the official list of bulk substances that 503A pharmacies may use, called the 503A bulks list. Here is the sequence of events.

• July 23-24, 2026: FDA’s Pharmacy Compounding Advisory Committee reviewed MOTS-c and five other peptides. The committee voted to recommend adding them to the bulks list. Its votes are advice, not binding. FDA’s own review staff had concluded the balance of criteria weighed against listing MOTS-c, citing the lack of human data.
• October 28-30, 2026: The Department of Health and Human Services, FDA’s parent department, issued a notice titled Enforcement Discretion Policy Regarding 503A Compounding Using Certain Peptide Bulk Drug Substances. It was signed and filed on October 28 and published in the Federal Register on October 30. Under it, federal officials do not intend to take enforcement action against a state-licensed pharmacy that prepares one of six listed peptides, including MOTS-c, for an individual patient while formal rulemaking continues. The Federal Register notice itself gives only that outline. The policy’s conditions include a certificate of analysis from an FDA-registered manufacturer, a single active ingredient, adverse event reporting to FDA’s MedWatch and a compounded-product label, and for MOTS-c the policy covers the acetate form as a subcutaneous or intramuscular injectable only. The National Community Pharmacists Association reported it on October 29 as an FDA action.
• Still pending: Formal rulemaking to decide whether MOTS-c joins the 503A bulks list. No timeframe was given for how long the interim policy lasts. HHS calls it a draft, says it creates no rights, and may revisit it if a safety signal or product quality problem appears.

The evidence

What the research actually shows

Animal and cell studies

• Lee et al., Cell Metabolism, 2015. In mice, MOTS-c treatment prevented insulin resistance that develops with age and with a high-fat diet, and prevented diet-induced obesity.
• Reynolds et al., Nature Communications, 2021. MOTS-c improved physical performance in young, middle-aged and old mice. Treatment started late in life, three times a week, increased physical capacity and healthspan in mice. Two authors disclosed ties to CohBar, a company developing MOTS-c related drugs.

FDA reviewers noted that studies so far are limited to rodents and cells and have not measured dose-response, so the clinical meaning is unknown.

Human studies: the body’s own MOTS-c, not the injected peptide

The human studies below measured natural MOTS-c levels. None gave people MOTS-c as a drug.

• von Walden et al., 2021. Thirty adults were randomized to endurance exercise, resistance exercise or rest, 10 per group. Humanin, a related peptide, rose after endurance exercise. MOTS-c showed only a trend upward. Levels did not track fitness.
• Dieli-Conwright et al., 2021. In 49 breast cancer survivors, 16 weeks of aerobic and resistance exercise raised MOTS-c in non-Hispanic White women but not in Hispanic women. In the group that rose, higher MOTS-c went with less fat mass and lower insulin resistance. This was a secondary analysis, so it cannot show cause.
• Domin et al., 2023. In 20 healthy, physically active volunteers, higher resting MOTS-c matched greater muscle mass and jump power but not peak oxygen uptake. This was a single snapshot.
• Cuyas et al., 2022. Metformin works through a pathway that overlaps with MOTS-c. Yet in breast cancer patients treated for 24 weeks, metformin did not change circulating MOTS-c.

What has not been done

FDA’s reviewers searched for human studies of MOTS-c given to people and found none. They also found no studies of how the body absorbs and clears it after injection, and no outsourcing facility had reported making it between January 2017 and December 2025. A lab study found MOTS-c breaks down quickly in human blood, and whether an injection reaches active levels is unknown. No trial shows that MOTS-c treats insulin resistance, obesity, bone loss or aging in people. Individual results vary, and with no human trials there is no typical result to describe.

Safety

What we do not know about the risks

There is no label, no boxed warning and no list of known side effects, because no one has studied it in people well enough to write them. FDA’s briefing said the potential safety risks of MOTS-c in humans are unknown. That is different from saying it is risky or harmless.

Who should not use it

People for whom MOTS-c is a poor fit

With so little human data, the list of people who should avoid it is long. Dr. Miranda is unlikely to consider it for any of these.

• Anyone who is pregnant, trying to conceive or breastfeeding.
• Children and teenagers.
• Anyone with an active cancer or a recent cancer history, since the effects on cell growth are unstudied.
• Anyone with a history of serious allergic reactions to injectable medicines or peptides.
• Anyone looking for a substitute for approved treatments for obesity, diabetes or osteoporosis. Those drugs have trial data behind them.
• Anyone who expects a certain result. No one can promise one.

Summit’s role

What Summit does with MOTS-c

Dr. Miranda decides whether this fits you after your history and labs. If he prescribes it, a state-licensed pharmacy prepares it for you as a named patient. Summit does not dispense or sell it and keeps no stock.

Nothing on this page promises a prescription. If MOTS-c does not fit, you will hear why, and he will tell you plainly when a goal is better served by an approved treatment or by lifestyle changes. Labs may show insulin resistance or other issues worth treating first. See pricing for what the program includes, and apply to start with a physician review.

Keep reading

Related medications

Sources

Where this comes from

All retrieved November 10, 2026.

1. HHS. Enforcement Discretion Policy Regarding 503A Compounding Using Certain Peptide Bulk Drug Substances, with Appendix A and B. Federal Register FR Doc 2026-22192, October 30, 2026. https://www.hhs.gov/sites/default/files/hhs-503a-peptide-enforcement-discretion-policy-appendix-b.pdf
2. HHS. Enforcement Discretion Policy Regarding 503A Compounding Using Certain Peptide Bulk Drug Substances. Federal Register, October 30, 2026 (91 FR 68526). https://www.federalregister.gov/documents/2026/10/30/2026-22192/enforcement-discretion-policy-regarding-503a-compounding-using-certain-peptide-bulk-drug-substances
3. FDA. Briefing Document for MOTS-c-Related Bulk Drug Substances, Pharmacy Compounding Advisory Committee, July 23-24, 2026. https://www.fda.gov/media/193347/download
4. FDA. July 23-24, 2026 Meeting of the Pharmacy Compounding Advisory Committee: meeting page and materials. https://www.fda.gov/advisory-committees/advisory-committee-calendar/july-23-24-2026-meeting-pharmacy-compounding-advisory-committee-07232026
5. NCPA. FDA grants enforcement discretion to compounding six peptides. October 29, 2026. https://ncpa.org/newsroom/qam/2026/10/29/fda-grants-enforcement-discretion-compounding-six-peptides
6. Holland & Knight. HHS Issues Interim Enforcement Discretion Policy for Compounding of 6 Peptides. November 4, 2026 (secondary summary of the policy’s conditions). https://www.hklaw.com/en/insights/publications/2026/11/hhs-issues-interim-enforcement-discretion-policy-for-compounding
7. Lee C et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab 2015. https://pubmed.ncbi.nlm.nih.gov/25738459/
8. Reynolds JC et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun 2021. https://pubmed.ncbi.nlm.nih.gov/33473109/
9. von Walden F et al. Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans. J Appl Physiol 2021. https://pubmed.ncbi.nlm.nih.gov/34351816/
10. Dieli-Conwright CM et al. Effect of aerobic and resistance exercise on the mitochondrial peptide MOTS-c in Hispanic and Non-Hispanic White breast cancer survivors. Sci Rep 2021. https://pubmed.ncbi.nlm.nih.gov/34413391/
11. Domin R et al. MOTS-c serum concentration positively correlates with lower-body muscle strength and is not related to maximal oxygen uptake. Int J Mol Sci 2023. https://pubmed.ncbi.nlm.nih.gov/37834399/
12. Cuyas E et al. Circulating levels of MOTS-c in patients with breast cancer treated with metformin. Aging 2022. https://pubmed.ncbi.nlm.nih.gov/36490309/
13. Knoop A et al. Development of a mass spectrometry based detection method for MOTS-c in plasma samples for doping control purposes. Rapid Commun Mass Spectrom 2019. https://pubmed.ncbi.nlm.nih.gov/30394592/