What is MOTS-c? Research, benefits claims and Philippines status
Not yet medically reviewed. Fact-checked against the sources listed below on October 7, 2026.How we write and review
Last updated October 7, 2026
MOTS-c is a 16 amino acid peptide made naturally from mitochondrial DNA. In mice it reduced diet-induced obesity and insulin resistance, but the US FDA found no studies giving MOTS-c to people. A related analog had only a small company trial. WADA bans MOTS-c in sport, and no FDA Philippines record was found.
Key takeaways
- MOTS-c is a 16 amino acid peptide encoded by mitochondrial DNA, first described in 2015 by researchers at the University of Southern California and UCLA. The version the US FDA reviewed is synthetic.
- Evidence that it reduces obesity or insulin resistance comes from mouse, rat and cell studies. The US FDA's 2026 review found no clinical studies giving MOTS-c to people.
- CB4211, a modified analog, completed a small phase 1a/1b trial in 2021. Its results come from the sponsor's filings with the US Securities and Exchange Commission and were not peer reviewed. CB4211 is a different molecule.
- A phase 2a trial of MOTS-c in people with prediabetes was registered in March 2026 and is recruiting in China. It has no results yet.
- WADA has named MOTS-c in class S4.4.1 (AMPK activators) since its 2025 list. It is prohibited at all times.
- No record of MOTS-c was found in an FDA Philippines Verification Portal search on October 7, 2026, and no FDA Philippines advisory naming it was found.
What is MOTS-c?
MOTS-c is a peptide of 16 amino acids that the body makes from its mitochondrial DNA. Its full name is "mitochondrial open reading frame of the 12S rRNA-c". It is one of a group called mitochondrial-derived peptides.
It was described in 2015 by researchers at the University of Southern California and UCLA. Their paper reported "a sORF within the mitochondrial 12S rRNA encoding a 16-amino-acid peptide named MOTS-c". A sORF is a short open reading frame: here, a stretch of 51 base pairs.
According to those researchers, MOTS-c appears highly conserved across species, is found in tissues including skeletal muscle, heart and brain, and circulates in the blood of humans and rodents.
The US FDA describes the product it reviewed as "a synthetic version" of this peptide, with the sequence Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg. The FDA treats MOTS-c (free base) and MOTS-c acetate as different substances. MOTS-c is not a component of any FDA-approved drug, and the European Medicines Agency lists no authorised product containing it.
How is MOTS-c thought to work?
No one knows exactly. The US FDA says that although its effects "appear to depend, at least in part, on AMPK signaling, the molecular target(s) through which MOTS-c acts remains unknown."
What cell and mouse studies propose:
- Energy sensing: MOTS-c inhibits the folate cycle and the building of purines inside cells, which switches on AMPK, an enzyme that senses cell energy.
- Muscle: its main target organ appeared to be skeletal muscle in the 2015 discovery paper.
- Gene control under stress: in cell studies, MOTS-c moved into the cell nucleus under metabolic stress and regulated many genes, including antioxidant response genes, in an AMPK-dependent way.
Because the target is unknown, the FDA says "it is difficult to predict which organs might be targeted and affected by MOTS-c."
The body's own MOTS-c. In people, studies so far measure natural levels rather than giving MOTS-c. In 10 sedentary healthy young men, a cycling session raised MOTS-c in skeletal muscle (about 11.9-fold on a western blot) and in the blood. A 2015 paper also suggests that a MOTS-c gene variant found in Northeast Asian populations "may be among the putative biological mechanisms explaining the high longevity of Japanese people". That is a hypothesis, not a treatment study.
What do animal and lab studies show?
All evidence that MOTS-c reduces obesity or insulin resistance comes from animals and cells. The results below are animal and lab studies, not human trials.
| Study | Type | What was reported |
|---|---|---|
| Lee et al. 2015, discovery paper | Mouse and cell study | MOTS-c "prevented age-dependent and high-fat-diet-induced insulin resistance, as well as diet-induced obesity" in mice. In the US FDA's summary, male mice on a high-fat diet given MOTS-c injections for 8 weeks weighed about 20% less than mice given an inactive control (vehicle), with higher energy expenditure, less liver fat and suppressed high insulin levels. In older mice, muscle insulin sensitivity returned to levels like younger mice |
| Kim et al. 2018 | Cell study | MOTS-c moved into the nucleus under metabolic stress and regulated nuclear genes, including antioxidant response genes |
| Reynolds et al. 2021 | Mouse study | MOTS-c improved physical performance in young, middle-aged and old mice. Treatment started late in life increased physical capacity and healthspan. The US FDA's summary adds median lifespan of 970 days with MOTS-c versus 912 days with an inactive control (vehicle) |
| Other studies summarised by the US FDA (2026) | Mouse and rat studies, rat stem cells | According to their authors, MOTS-c suppressed diet-induced obesity and insulin resistance in mice, prevented obesity and insulin resistance in mice after ovary removal, promoted bone cell formation from rat stem cells, inhibited bone loss, and reduced blood vessel calcification in a rat model |
Limits the US FDA points out. These studies "have been limited to in-vivo and in-vitro rodent models", did not test dose-response, and the clinical relevance of the findings "is currently unknown".
Who did the research. The senior author of the 2018 paper declared he is a consultant for and shareholder of CohBar, Inc., the company that developed the analog CB4211. Two authors of the 2021 paper are CohBar consultants and shareholders; its funding included the US National Institute on Aging.
What human evidence exists?
There are no completed human trials of MOTS-c itself. The US FDA's 2026 review "did not identify clinical studies evaluating administration of MOTS-c-related BDSs in human subjects".
CB4211, an analog. CohBar, Inc. tested CB4211, which it describes as an analog of MOTS-c. CB4211 is a different molecule, so its results do not show that MOTS-c itself works or what its risks are.
| CB4211 trial | What was reported |
|---|---|
| Design (ClinicalTrials.gov, NCT03998514) | Randomized, double-blind, placebo-controlled phase 1a/1b trial of CB4211 injected under the skin. Ran July 2018 to April 2021 at US sites, 88 participants: healthy non-obese adults, and adults with nonalcoholic fatty liver disease treated for 28 days. Completed, with no results posted on ClinicalTrials.gov |
| Phase 1a, as reported in CohBar's 2021 SEC annual report | "Mild, but persistent injection site reactions", described as painless bumps under the skin. The trial was temporarily suspended in 2019 to address these, and the formulation was changed |
| Phase 1b, as reported in CohBar's 2021 SEC annual report | 11 obese adults with fatty liver disease on CB4211 and 9 on placebo, for four weeks. No serious adverse events. Statistically significant falls versus placebo in the liver enzymes ALT and AST and in glucose, and "a trend towards lower body weight". Liver fat fell by a similar amount on CB4211 and placebo |
These are exploratory results reported by the company in filings with the US Securities and Exchange Commission. They were not peer reviewed, and no journal publication of the trial was found. CohBar's 2022 annual report, filed in March 2023, says the company was exploring "strategic alternatives", including a merger or asset sale. No later CB4211 trial was found on ClinicalTrials.gov.
A MOTS-c trial now recruiting.
| Trial | Details |
|---|---|
| NCT07505745, phase 2a | Registered March 2026. Randomized, quadruple-blind, placebo-controlled trial of MOTS-c injected under the skin for 12 weeks, plus lifestyle counselling, in adults with prediabetes and overweight or obesity. Estimated 120 participants at a site in Shenzhen, China, with a commercial lead sponsor. Main outcomes: insulin sensitivity (Matsuda index) and adverse events. Recruiting, estimated completion May 2028 |
Other registered studies. A ClinicalTrials.gov search for "MOTS-c" on October 7, 2026 returned 9 studies. Apart from NCT07505745, they measure the body's own MOTS-c levels, for example in diabetes, exercise, fasting, kidney transplant or dialysis studies, and do not give MOTS-c as a treatment.
A caution on blood tests. An anti-doping laboratory in Cologne could not confirm MOTS-c levels in 20 healthy people that a commercial ELISA kit had reported, and noted "considerable differences" between the methods. Published human blood levels measured by ELISA should be read with caution.
Risks and unknowns
The risks of MOTS-c in people are unknown. The US FDA's 2026 review says: "There is a lack of clinical and nonclinical safety information on the use of MOTS-c."
What the US FDA found missing:
- No repeat-dose toxicity, genotoxicity, developmental and reproductive toxicity or cancer-risk (carcinogenicity) studies.
- No clinical pharmacokinetic data, so how the body absorbs and clears it is not known.
- No human exposure data on drug products containing MOTS-c by any route, according to the FDA's compounding safety page.
"Therefore, potential safety risks associated with the use of MOTS-c in humans are unknown," the FDA concludes.
Immune reactions. The FDA is concerned about immune reactions when MOTS-c is injected under the skin, because peptides can clump together (aggregate) and may contain peptide-related impurities. It notes immune responses can range from harmless antibodies to "life-threatening and catastrophic reactions", and that antibodies could neutralize the body's own MOTS-c.
Adverse event reports. FDA searches of its adverse event reporting system (FAERS) through March 9, 2025 found no reports for MOTS-c. The FDA notes that 503A compounding pharmacies generally do not report adverse events to it.
What users report. USADA says people who report buying MOTS-c online describe side effects including increased heart rate or palpitations, injection site irritation, insomnia, local or whole-body immune reactions and fever. These are anecdotal reports, not trial findings, and USADA says there is no data on long-term use. USADA also says it is unknown under what conditions, if any, MOTS-c can be used without harm, because there are no completed human clinical trials.
Products sold online. USADA says MOTS-c "can be found on many websites with the label 'for research purposes only' or in compounded medications". A 2026 Cureus review groups MOTS-c with "experimental or wellness peptides promoted online despite limited, inconsistent, or nongeneralizable human evidence", and describes the main concern as "consumer experimentation with products of uncertain identity, purity, potency, sterility, and safety." A 2026 Sports Medicine review says "rigorous human safety data are scarce, and there is potential for serious harm to patients" for unapproved peptides including MOTS-c.
What is the US FDA's position on MOTS-c?
The US FDA has not approved MOTS-c, and its 2026 review found that the evidence weighs against adding it to the list of substances US pharmacies may use for compounding.
| Date | What happened |
|---|---|
| Earlier (date not confirmed) | MOTS-c was nominated for the 503A bulks list for insulin resistance, obesity, osteoporosis, vascular calcification, muscle and fat metabolism, and longevity. It was in category 2 of the FDA's interim policies, then the nomination was withdrawn |
| April 22, 2026 | The FDA's safety risks page lists MOTs-C under "Bulk drug substances nominated but withdrawn" |
| May 14, 2026 | The FDA's 503A nominations list does not include MOTS-c in categories 1, 2 or 3 |
| 2026 | The FDA evaluated MOTS-c (free base) and MOTS-c acetate on its own initiative |
| July 23, 2026 | The FDA's Pharmacy Compounding Advisory Committee was asked to vote on whether each form should be placed on the list. AJMC and DLA Piper (both July 31, 2026) reported that MOTS-c passed, with the committee recommending it be added. The two reports give different vote counts |
| As of October 7, 2026 | The FDA had posted no minutes and no decision on its meeting page, and MOTS-c was not on the 503A bulks list |
The FDA's briefing concludes that "the physicochemical characterization, information on historical use, lack of any safety and effectiveness information in humans for both MOTS-c (free base) and MOTS-c acetate weigh against their being added to the 503A Bulks List." The committee's reported vote went the other way. DLA Piper notes that "committee votes are non-binding recommendations, formal rulemaking is required before any substance is added to the list, and FDA is not obligated to follow the AdComm's recommendations."
Other findings from the review:
- MOTS-c has no USP or NF monograph and no monograph in the European or Japanese pharmacopoeias.
- US outsourcing facilities reported no compounded products containing MOTS-c from January 2017 to December 2025.
- Internet searches showed clinics marketing injectable MOTS-c, alone and in combinations, for weight loss, glucose regulation, physical performance and slowing cellular aging.
USADA says MOTS-c "is not approved by the Food and Drug Administration (FDA) for use in humans or in compounded medications."
Is MOTS-c banned in sport?
Yes. The World Anti-Doping Agency (WADA) names MOTS-c as an example of an AMPK activator in class S4.4.1, and it is prohibited at all times.
| WADA Prohibited List | MOTS-c status |
|---|---|
| 2024 | The S4.4.1 entry does not name MOTS-c |
| 2025 (in force from January 1, 2025) | Named in S4.4.1: "Activators of the AMP-activated protein kinase (AMPK), e.g. AICAR, mitochondrial open reading frame of the 12S rRNA-c (MOTS-c)" |
| 2026 | Still named in S4.4.1, under S4.4 Metabolic Modulators. S4 substances are "PROHIBITED AT ALL TIMES (IN- AND OUT-OF-COMPETITION)", and those in S4.4 "are non-Specified Substances" |
| 2027 (in force from January 1, 2027) | Still named in S4.4.1 as an AMPK activator |
USADA says MOTS-c "is prohibited at all times under Section 4.4 Metabolic Modulators", and that "It is highly unlikely an athlete would get a TUE approved for MOTS-c because there is no approved therapeutic use for this experimental drug." A TUE is a Therapeutic Use Exemption.
Anti-doping scientists in Cologne validated a mass spectrometry test for MOTS-c in blood plasma in 2019.
Legal status in the Philippines
The FDA Philippines status of MOTS-c is unverified. No record was found in an FDA Philippines Verification Portal search on October 7, 2026.
What was checked on October 7, 2026:
- Verification Portal: a search for "MOTS-c" returned no record in any category. A broader search for "MOTS" returned one unrelated food product and no drug record.
- FDA Philippines website: searches for "MOTS-c", "MOTS", "mitochondrial", "humanin" and "CB4211" each returned no results.
- Prescription status: no Philippine source was found on whether MOTS-c needs a prescription, or on any legal way to obtain it.
A search with no record is not an official FDA Philippines statement about a compound. To check a product yourself, search the portal at verification.fda.gov.ph. For how Philippine rules treat peptides in general, see are peptides legal in the Philippines.
FDA advisory history
No FDA Philippines advisory naming MOTS-c was found in the October 7, 2026 searches listed above.
A missing advisory does not mean a product is registered or approved. For comparison, FDA Philippines has issued advisories on specific unregistered tirzepatide vial products.
What to ask a doctor
If you are considering MOTS-c, or have already used it, a licensed doctor can help. Questions you could bring:
- What approved treatments exist for my weight, blood sugar or energy concerns, and what does the evidence show for them?
- What should I watch for if I have already injected an unapproved peptide?
- If I compete in sport, how does the WADA Prohibited List affect me?
- How can I check whether a product is registered with FDA Philippines?
Frequently asked questions
What is MOTS-c?
MOTS-c is a peptide of 16 amino acids encoded by a short stretch of the mitochondrial 12S rRNA gene. The body makes it naturally, and it circulates in the blood of humans and rodents. The US FDA describes the substance it reviewed as a synthetic version.
What are the claimed benefits of MOTS-c?
The US FDA found clinics marketing injectable MOTS-c for weight loss, glucose regulation, physical performance and slowing cellular aging. These claims rest on mouse, rat and cell studies. The US FDA found no clinical studies giving MOTS-c to people.
Has MOTS-c been tested in humans?
Not as a finished trial. A phase 2a trial of MOTS-c in adults with prediabetes and overweight or obesity was registered in March 2026 and is recruiting, with completion estimated for May 2028. Other registered human studies only measure the body's own MOTS-c levels.
Is CB4211 the same as MOTS-c?
No. CohBar describes CB4211 as an analog of MOTS-c, which means a modified molecule. Its small phase 1a/1b trial results come from the company's SEC filings, were not peer reviewed, and do not show that MOTS-c itself works or is free of harm.
Does MOTS-c help with weight loss?
This has not been shown in people. In male mice on a high-fat diet, 8 weeks of MOTS-c injections led to about 20% lower body weight than mice given an inactive control (vehicle), according to the US FDA's summary. In CB4211's company-reported phase 1b results, there was only "a trend towards lower body weight".
Is MOTS-c banned in sport?
Yes. WADA names MOTS-c in class S4.4.1, activators of AMP-activated protein kinase (AMPK), on its 2025, 2026 and 2027 lists. It is prohibited at all times. USADA says a Therapeutic Use Exemption for it is highly unlikely because it has no approved therapeutic use.
Is MOTS-c legal in the Philippines?
Its status is unverified. No record was found in an FDA Philippines Verification Portal search on October 7, 2026, and no Philippine source on a prescription route or any legal way to obtain it was found. A search result with no record is not an official FDA Philippines statement.
Is MOTS-c approved by the US FDA?
No. The US FDA says MOTS-c is not a component of an FDA-approved drug. In 2026 it found that the physicochemical characterization, historical use and "lack of any safety and effectiveness information in humans" weigh against adding MOTS-c to the list of substances US pharmacies may use in compounding. AJMC and DLA Piper reported in July 2026 that its advisory committee voted to recommend adding MOTS-c. That vote is non-binding, and no final FDA decision was found as of October 7, 2026.
What are the side effects of MOTS-c?
They are not known from trials. The US FDA says potential safety risks in humans are unknown. USADA says people who report buying it online describe increased heart rate or palpitations, injection site irritation, insomnia, immune reactions and fever, but these are anecdotal reports.
Does exercise raise MOTS-c?
In one study of 10 sedentary healthy young men, a cycling session raised MOTS-c in muscle (about 11.9-fold on one lab measure) and in the blood. No MOTS-c was given in that study.
Can MOTS-c be detected in a drug test?
An anti-doping laboratory in Cologne validated a mass spectrometry test for MOTS-c in blood plasma in 2019. The same study could not confirm levels reported by a commercial ELISA kit, so blood levels measured that way should be read with caution.
Sources
- US FDA, briefing document on MOTS-c, Pharmacy Compounding Advisory Committee, July 2026
- US FDA, Pharmacy Compounding Advisory Committee questions, July 23, 2026
- US FDA, July 23 to 24, 2026 meeting of the Pharmacy Compounding Advisory Committee
- AJMC, FDA panel backs 6 peptides for compounding, July 31, 2026
- DLA Piper, FDA AdComm recommends adding six peptides to bulk list, July 31, 2026
- US FDA, bulk drug substances that may present significant safety risks (page current as of April 22, 2026)
- US FDA, bulk drug substances nominated for use in compounding under section 503A (updated May 14, 2026)
- Lee et al., discovery of MOTS-c, Cell Metabolism, 2015 (PMID 25738459)
- Kim et al., MOTS-c and the cell nucleus, Cell Metabolism, 2018 (PMID 29983246)
- Reynolds et al., MOTS-c and physical capacity, Nature Communications, 2021 (PMC7817689)
- Fuku et al., MOTS-c gene variant and longevity, Aging Cell, 2015 (PMID 26289118)
- Knoop et al., mass spectrometry test for MOTS-c in plasma, 2019 (PMID 30394592)
- ClinicalTrials.gov, NCT03998514 (CB4211 phase 1a/1b)
- CohBar, Inc., annual report for 2021 (Form 10-K), US SEC
- CohBar, Inc., annual report for 2022 (Form 10-K), US SEC
- ClinicalTrials.gov, NCT07505745 (MOTS-c phase 2a in prediabetes)
- ClinicalTrials.gov search for MOTS-c
- USADA, what is MOTS-c peptide
- Mendias and Awan, review of approved and unapproved peptides, Sports Medicine, 2026 (PMID 41966639)
- Hailu et al., unregulated peptide use, Cureus, 2026, full text via Europe PMC (PMC13355462)
- WADA, 2025 Prohibited List
- WADA, 2026 Prohibited List
- WADA, 2027 Prohibited List
- FDA Philippines Verification Portal, search for MOTS-c, October 7, 2026
- FDA Philippines, site search for MOTS-c (opened October 7, 2026)
Related reading
This content is for education only and is not medical advice. Talk to a licensed doctor before starting any treatment.