What does the research show about mots-c?

MOTS-c

Grey marketNot approved for human use in the US, and sold anyway.

MOTS-c is not FDA-approved and is banned in sport. Its claimed benefits for weight, blood sugar, endurance, aging and bone rest on mouse and lab studies. FDA's 2026 compounding review found no human exposure data for MOTS-c by any route, stated its risks in humans are unknown, and found its identity and purity data lacking.

Add to Bio HackChecked 2026-11-13

Status: Not FDA-approved for any use in the US. FDA removed MOTS-c from compounding category 2 on April 22, 2026, after its nomination was withdrawn, and did not place it in category 1. Under a draft, interim HHS policy announced October 30, 2026, HHS does not intend to take enforcement action against state-licensed pharmacies, federal facilities or licensed physicians compounding with MOTS-c while the 503A bulks list is developed through rulemaking. Prohibited at all times by WADA (S4.4, metabolic modulators).
Also called: MOTSc, MOTS c, MOTS-c acetate, mitochondrial open reading frame of the 12S rRNA-c, mitochondrial-derived peptide
Taken for: fat loss, weight loss, insulin sensitivity, blood sugar, endurance, metabolism, longevity, bone health

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help0

No benefit shown in research yet.

Reported risks4

LimitedFDA states it has no human exposure data and lacks important safety information on MOTS-c. It removed MOTS-c from category 2 in April 2026 after the nomination was withdrawn.How often is not known
LimitedFDA states potential safety risks in humans are unknown, with no human or toxicity studies, and concluded the criteria weigh against allowing it for compounding.How often is not known
LimitedHHS states it does not intend to take enforcement action against licensed compounding with MOTS-c for now, and that compounded drugs are not FDA-approved.How often is not known
LimitedWADA lists MOTS-c as a metabolic modulator, prohibited at all times in sport.How often is not known

What people take it for, and what was found

Claimed, not studied in people5

Untested

Weight, fat loss and metabolism

Not studied in people. In mice, MOTS-c treatment prevented the obesity a high-fat diet otherwise caused.

No study in people. This rests on animal studies, lab studies.

The numbers and sources

Effect: MOTS-c treatment in mice prevented diet-induced obesity. Its primary target organ appeared to be skeletal muscle, where it inhibited the folate cycle and the purine synthesis tied to it, leading to activation of AMPK, an energy-sensing enzyme [9].
Population: Mice, and cells in the lab [9].
Sources: [9], [10]
Caveats: Studies in people have measured the MOTS-c the body makes, not MOTS-c given as a treatment. In one, circulating levels were higher in 32 adults with obesity than in 22 lean adults, and did not change 6 months after bariatric surgery in 10 patients despite lower BMI [10]. FDA found no human exposure data for MOTS-c by any route [3].

Untested

Insulin sensitivity and blood sugar

Not studied in people. In mice, MOTS-c treatment prevented insulin resistance brought on by aging and by a high-fat diet.

No study in people. This rests on animal studies, how it acts in the body.

The numbers and sources

Effect: MOTS-c treatment in mice prevented age-dependent and high-fat-diet-induced insulin resistance [9]. A 2023 review describes MOTS-c as acting mainly through the AICAR-AMPK pathway, with effects on the expression of genes such as GLUT4, a glucose transporter [11].
Population: Mice [9]. Mechanisms reviewed in [11].
Sources: [9], [11], [10]
Caveats: In people, only the MOTS-c the body makes has been measured. In one study, body mass index and HOMA-IR, a measure of insulin resistance, each predicted higher circulating MOTS-c [10]. That is an association, not a test of taking it. FDA found no human exposure data for MOTS-c by any route [3].

Untested

Endurance and physical capacity

Not studied in people. MOTS-c raised physical performance in young, middle-aged and old mice, and a single dose lengthened running in untrained mice.

No study in people. This rests on animal studies.

The numbers and sources

Effect: MOTS-c treatment enhanced physical performance in young (2 months), middle-aged (12 months) and old (22 months) mice [12]. In untrained mice, a single dose raised total running time by 12% and distance by 15% in an exercise test [13]. In people, exercise raised the MOTS-c the body makes, in skeletal muscle and in the blood [12].
Population: Mice [12][13].
Sources: [12], [13]
Caveats: A rise in the body's own MOTS-c with exercise is not a test of taking it. No study giving MOTS-c to people was located, and FDA found no human exposure data by any route [3].

Untested

Aging and longevity

Not studied in people. MOTS-c treatment started late in life raised physical capacity and healthspan in old mice.

No study in people. This rests on animal studies.

The numbers and sources

Effect: In mice, MOTS-c treatment begun at 23.5 months of age increased physical capacity and healthspan [12]. A 2022 review reports that MOTS-c levels in plasma decline with age, and reviews reported effects on diabetes, cardiovascular disease, osteoporosis, postmenopausal obesity and Alzheimer's disease [14].
Population: Old mice [12]. Studies reviewed in [14].
Sources: [12], [14]
Caveats: The study abstract reports physical capacity and healthspan, not lifespan [12]. Lower MOTS-c levels with age in people do not show that taking it changes how people age.

Untested

Bone health

Not studied in people. In mice with their ovaries removed, MOTS-c reduced bone loss, and in the lab it slowed the formation of bone-resorbing cells.

No study in people. This rests on animal studies, lab studies.

The numbers and sources

Effect: In mice with ovariectomy-induced osteoporosis, MOTS-c treatment reduced bone loss measured by micro-CT. In the lab, it inhibited the formation of osteoclasts, the cells that break down bone, partly through AMPK [15]. A 2023 review reports that MOTS-c promotes the growth, maturation and mineralization of osteoblasts, the cells that build bone, and inhibits osteoclast production [16].
Population: Mice, and bone cells in the lab [15][16].
Sources: [15], [16]
Caveats: Bone loss after ovary removal in mice does not show what happens in people. FDA found no human exposure data for MOTS-c by any route [3].

Risks

Reported risks4

LimitedHow often is not known

FDA compounding category 2 listing

FDA states it has no human exposure data and lacks important safety information on MOTS-c. It removed MOTS-c from category 2 in April 2026 after the nomination was withdrawn.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: FDA states that it has not identified any human exposure data on drug products containing MOTS-c and that it lacks important information regarding any safety issues raised by MOTS-c. MOTS-c appears on FDA's list of substances previously in category 2 whose nominations were withdrawn by the nominators [1]. FDA removed MOTS-c from category 2 on April 22, 2026, because the nomination was withdrawn, and MOTS-c does not appear in category 1 of that update [2].
Population: Compounded drug products in the US [1][2].
Sources: [1], [2]
Caveats: A regulatory assessment of compounded products, not a study of harm.

LimitedHow often is not known

FDA's 2026 safety review

FDA states potential safety risks in humans are unknown, with no human or toxicity studies, and concluded the criteria weigh against allowing it for compounding.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: FDA's briefing document for its Pharmacy Compounding Advisory Committee found no clinical studies or human exposure data for MOTS-c by any route, no human pharmacokinetic studies and no nonclinical toxicity studies, and concluded that potential safety risks in humans are unknown. FDA described MOTS-c as not well characterized: tests for impurities, aggregates and endotoxins were not found in the published literature, and the nomination included no certificate of analysis. Because MOTS-c is a 16 amino acid peptide, FDA stated concern about immune reactions when it is injected, from possible aggregation and peptide-related impurities. FDA concluded that the balance of criteria weighs against placing MOTS-c on the list of substances allowed for pharmacy compounding [3].
Population: FDA review of published literature, adverse event databases and the nomination [3].
Sources: [3]
Caveats: The nomination was withdrawn, and FDA evaluated MOTS-c anyway [3]. The advisory committee met on July 23, 2026, and its votes are advice to FDA, which makes the final determination [3]. Trade press reported that the committee voted 7 to 5, with 2 abstentions, to recommend adding MOTS-c to the 503A bulks list [4][5]. No FDA-published tally was located for this page.

LimitedHow often is not known

HHS interim compounding policy

HHS states it does not intend to take enforcement action against licensed compounding with MOTS-c for now, and that compounded drugs are not FDA-approved.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: In a notice of a draft, interim policy, HHS states that it does not intend to take enforcement action against a State-licensed pharmacy, Federal facility or licensed physician compounding with a peptide listed in the policy's Appendix A while the 503A bulks list is developed through rulemaking [6]. MOTS-c is on that list [7]. The notice states: "Compounded drugs are not FDA-approved, which means FDA does not review their safety, effectiveness, or quality before they are marketed." HHS may revisit the policy "if, among other things, a safety signal or product quality issue arises" with a compounded product it covers, and the policy is "not binding on HHS or the public" [6].
Population: Compounded drug products in the US [6][7].
Sources: [6], [7]
Caveats: A statement of enforcement intent, not an FDA approval and not a study of harm. FDA's future rulemaking may or may not add MOTS-c to the 503A bulks list [6].

LimitedHow often is not known

Prohibited in sport

WADA lists MOTS-c as a metabolic modulator, prohibited at all times in sport.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: WADA names MOTS-c under S4.4, metabolic modulators, which are prohibited at all times [8].
Population: Athletes subject to the World Anti-Doping Code [8].
Sources: [8]
Caveats: A sport rule, not a health finding.

Checked, no increase found1

Limited

Reported adverse events

FDA found no adverse event reports for MOTS-c through March 2025. Reporting is voluntary, and no reports does not mean no harm.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Two searches of FDA's adverse event database, through February 28, 2024 and from February 26, 2024 through March 9, 2025, found no reports for MOTS-c [3].
Population: Voluntary reports to FDA [3].
Sources: [3]
Caveats: Reporting is voluntary and incomplete, and FDA notes that pharmacies compounding under section 503A generally do not report adverse events to it [3]. No reports does not mean no harm.

Sources

U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. 2026. https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks
U.S. Food and Drug Administration. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act. Updated April 22, 2026. 2026. https://web.archive.org/web/20260422215502/https://www.fda.gov/media/94155/download
U.S. Food and Drug Administration. FDA Briefing Document: MOTS-c-Related Bulk Drug Substances (MOTS-c (free base) and MOTS-c acetate). Pharmacy Compounding Advisory Committee, July 23-24, 2026. 2026. https://www.fda.gov/media/193347/download
Jacobus N. FDA Panel Votes to Loosen Restrictions for Four Peptides. Pharmaceutical Executive. 2026. https://www.pharmexec.com/view/fda-votes-loosen-restrictions-four-peptides
Steinzor P. FDA Panel Backs 6 Peptides for Compounding. AJMC. 2026. https://ajmc.com/view/fda-panel-backs-6-peptides-for-compounding
U.S. Department of Health and Human Services. Enforcement Discretion Policy Regarding 503A Compounding Using Certain Peptide Bulk Drug Substances. Federal Register 91:68526. 2026. https://www.federalregister.gov/documents/2026/10/30/2026-22192/enforcement-discretion-policy-regarding-503a-compounding-using-certain-peptide-bulk-drug-substances
U.S. Department of Health and Human Services. HHS Enforcement Discretion Policy Regarding 503A Compounding Using Certain Peptide Bulk Drug Substances, with Appendices A and B. 2026. https://www.hhs.gov/sites/default/files/hhs-503a-peptide-enforcement-discretion-policy-appendix-b.pdf
World Anti-Doping Agency. The Prohibited List. 2026. https://www.wada-ama.org/en/prohibited-list
Lee C, Zeng J, Drew BG, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism. 2015. https://doi.org/10.1016/j.cmet.2015.02.009
Yoon SH, Yuan F, Zhu X, et al. Systemic MOTS-c levels are increased in adults with obesity in association with metabolic dysregulation and remain unchanged after weight loss. Journal of Clinical and Translational Endocrinology. 2026. https://doi.org/10.1016/j.jcte.2025.100429
Gao Y, Wei X, Wei P, et al. MOTS-c Functionally Prevents Metabolic Disorders. Metabolites. 2023. https://doi.org/10.3390/metabo13010125
Reynolds JC, Lai RW, Woodhead JST, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nature Communications. 2021. https://doi.org/10.1038/s41467-020-20790-0
Hyatt JK. MOTS-c increases in skeletal muscle following long-term physical activity and improves acute exercise performance after a single dose. Physiological Reports. 2022. https://doi.org/10.14814/phy2.15377
Mohtashami Z, Singh MK, Salimiaghdam N, Ozgul M, Kenney MC. MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases. International Journal of Molecular Sciences. 2022. https://doi.org/10.3390/ijms231911991
Ming W, Lu G, Xin S, et al. Mitochondria related peptide MOTS-c suppresses ovariectomy-induced bone loss via AMPK activation. Biochemical and Biophysical Research Communications. 2016. https://doi.org/10.1016/j.bbrc.2016.05.135
Yi X, Hu G, Yang Y, Li J, Jin J, Chang B. Role of MOTS-c in the regulation of bone metabolism. Frontiers in Physiology. 2023. https://doi.org/10.3389/fphys.2023.1149120

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