MOTS-c: FDA Searched the Literature and Found No Documented Human Administration

FDA searched the published literature for humans given MOTS-c and reported finding none. At the time it wrote that, Peptigrity was tracking 494 independent lab tests of MOTS-c across 72 shops holding stock. That gap is what this article measures.

MOTS-c is a mitochondrial-derived peptide encoded inside mitochondrial DNA, marketed as an "exercise mimetic" on the strength of mouse data, banned by WADA under a named mechanistic category, and sold at a median of $4.50 a milligram. Everything in that sentence is true simultaneously, which is why the compound sits awkwardly in the immune support and longevity peptides category and in our overview of peptides for energy and mitochondrial function.

What is MOTS-c, and what encodes it?

MOTS-c is a 16-residue mitochondrial-derived peptide, sequence MRWQEMGYIFYPRKLR, CAS 1627580-64-6, encoded not in the nuclear genome but inside MT-RNR1 — the mitochondrial 12S ribosomal RNA gene. It is supplied at three molecular weights: 2,174.6 free base, 2,234.64 acetate and 2,288.6 TFA salt, a spread of 114 daltons. The discovery came from Pinchas Cohen's group at the University of Southern California and is established science, not a marketing construct.

The biology is genuinely interesting and genuinely established. MOTS-c belongs to a small family of peptides transcribed from mitochondrial DNA rather than the nuclear genome, and that discovery changed how the field thinks about mitochondrial signalling.

Preclinically, MOTS-c activates AMP-activated protein kinase, promotes glucose uptake, and improves metabolic parameters in mice — including in aged mice, where it improved physical capacity. That aged-mouse result is where the "exercise mimetic" label comes from. Vendor listings and the MOTS-c compound page are where it goes next.

Why does the MOTS-c salt form change your dose?

MOTS-c ships as a free base, an acetate salt or a TFA salt, and those three forms differ by up to 114 Da — more than 5% of the mass you are weighing. A vial labelled 10 mg of TFA salt contains roughly 9.5 mg of peptide. That is chemistry, not a defect. It becomes a defect only if the certificate of analysis fails to state which form was weighed, because your dose calculation then uses a different quantity than the scale did.

This is one of the few practical checks available on a compound with no clinical literature, and it is cheap to run: read the salt form off the certificate before you read the purity percentage. See TFA versus acetate versus amidate salt forms and why 10 mg isn't 10 mg.

Has MOTS-c ever been given to a human?

No published record of one exists. In its briefing document for the July 2026 advisory committee meeting, FDA stated that it "did not identify clinical studies evaluating administration of MOTS-c-related BDSs in human subjects" — BDS being the agency's own abbreviation for bulk drug substances. That is not a finding that the evidence is weak, or that the trials were small. It is a regulator reporting that its literature search returned no documented instance of a human receiving this compound.

The distinction matters because it changes what kind of caution applies. A compound with weak human evidence has a risk profile you can argue about. A compound with no documented human administration has no risk profile at all — nothing has been observed, so nothing has been characterised, and the absence of reported adverse events carries no information.

One honest caveat belongs here, and it is FDA's caveat as much as ours: a literature search that finds nothing is not proof that nothing exists. Unpublished, unregistered or non-English administration would not necessarily surface. What can be said is that the agency looked, in the course of a formal regulatory review, and reported finding none.

What is the complete human clinical record for MOTS-c?

One trial, and it is still recruiting. NCT07505745, sponsored by Hudson Biotech in Shenzhen, opened in February 2026 with a target enrolment of 120 participants. No participants have been reported and no data has been published. That is the whole record. Every mechanism claim, dose recommendation and forum protocol attached to MOTS-c traces instead to mouse work, cell culture, or observational associations between naturally circulating MOTS-c levels and health outcomes.

Six months of recruitment is not a criticism of the sponsor. It is simply where the evidence base stands: one industry-sponsored trial, opened this year, with nothing yet to read.

Do endogenous MOTS-c levels tell you anything about injecting it?

No. Observational work associating higher naturally circulating MOTS-c with better metabolic markers tells you something about mitochondrial function as a biomarker. It tells you nothing about what happens when synthetic MOTS-c is injected subcutaneously, at doses nobody has established, for durations nobody has studied. Correlation with an endogenous peptide level is not evidence for exogenous administration, and treating it as though it were is how a compound with zero human trials acquires a dosing protocol.

This is the most common error in MOTS-c content, and it is a substitution rather than an exaggeration. The observational literature is about people whose mitochondria are producing more MOTS-c. The product is about putting a synthetic copy into someone whose mitochondria are not. Those are different interventions on different populations measuring different things, and one does not license the other.

Did FDA approve MOTS-c for compounding?

No. MOTS-c was nominated for FDA's 503A bulk substances list, and the agency's own reviewers evaluated it and recommended against listing, citing the absence of human administration studies alongside immunogenicity risk from aggregates and peptide-related impurities. At the meeting held 23–24 July 2026, the Pharmacy Compounding Advisory Committee voted 7–5, with 2 abstentions, to recommend listing it anyway. That vote is advisory only. FDA has issued no decision, and MOTS-c remains an unapproved new drug.

The committee voting against its own agency's reviewers is the live regulatory node on this compound, and it is routinely reported as though FDA were on the verge of approving something. It is not. On the FDA page current 22 April 2026, MOTS-c sits in the table of bulk drug substances nominated but withdrawn — off the active Category 2 list because the nominator withdrew the nomination, not because FDA cleared it. Our FDA peptide regulation timeline tracks what happens next.

WADA is unambiguous, and this one is not a judgement call. MOTS-c is prohibited under S4.4.1 — AMPK activators — on the 2026 Prohibited List. Unlike compounds whose status depends on the S0 catch-all, MOTS-c's mechanism places it inside a named category. Prohibited at all times, in and out of competition. Any tested athlete using MOTS-c is committing an anti-doping rule violation.

There is a quiet irony in that pairing. WADA bans MOTS-c on the strength of a mechanism established in mice, while FDA declines to endorse it for the absence of evidence in humans. Both are reading the same literature and asking different questions of it.

Which MOTS-c claims survive contact with the evidence?

Two of ten. Of the ten claims routinely made for MOTS-c, only its mitochondrial-DNA origin and its WADA ban are straightforwardly true, and both are facts about what the molecule is and where it is banned rather than about what it does. Two rows resolve to no human data, two to preclinical evidence only, one to safety that is simply unknown, one to extrapolation, one to a misapplied correlation, and one — that FDA approved it for compounding — is false.

Read the verdict column downward and the shape is unusual. Nothing in it is refuted, because refuting a claim requires a trial that returned a negative result, and no trial has returned anything.

What dose of MOTS-c is supported by evidence?

None. No published human dose-ranging study exists, no human pharmacokinetic study exists — no measured half-life, no bioavailability, no distribution data — and there is no established therapeutic window, because establishing one requires giving the compound to people and measuring what happens. Every milligram-per-week protocol in circulation is derived from mouse studies dosed for mice, then scaled allometrically. Allometric scaling is a rough estimate under good conditions and is not a substitute for a phase 1 trial.

This is different from a compound whose dose is merely uncertain. Uncertainty implies a range that studies have narrowed. Here there is no range, because nobody has published what happens across one in humans.

The MOTS-c calculator and the reconstitution calculator solve the arithmetic of turning a vial into an injection volume. They cannot tell you what number to put in, and no tool can, because that number does not exist in the literature.

How can 494 lab tests coexist with zero human trials?

Because supply-chain quality and clinical evidence are independent variables. The Purity Index records MOTS-c at 99.43 across 494 recency-weighted tests from 23 laboratories (verified August 2026), against a platform composite of 99.50 — one of the deepest datasets on this platform. That means the material being sold is, by HPLC, consistently what it claims to be. Purity answers whether this is the molecule. It does not answer whether the molecule does anything in people.

MOTS-c price data shows 72 shops in stock at a median of $4.50/mg (verified August 2026). Those figures exclude shipping, taxes and customs, coupon codes, bulk tiers, multi-vial kits and account-gated pricing. Peptigrity tracks 530 shops and 11,852 independent lab tests across 118 peptides, with 1,283 community reviews (verified August 2026), and weights community reviews and independently verified purity equally, at 50% each, in every trust score.

The methionine line is specific to this sequence. MOTS-c carries methionine at positions 1 and 6, and methionine oxidises readily — each oxidation adds 16 Da. Oxidised MOTS-c can still show high HPLC purity while being a different molecule from the one in the mouse studies, which makes storage matter more here than for most peptides. See how to store peptides and where to buy MOTS-c: 7 purity and identity checks.

How does MOTS-c compare with the other mitochondrial compounds?

MOTS-c is one of two compounds in this group with no human results at all. SS-31 ran multiple phase 2 and phase 3 trials, missed most of its primary endpoints, and was FDA-approved in September 2025 for Barth syndrome alone. NAD+ boosters ran many randomised trials in which the biomarker rose and nothing downstream moved. FOXO4-DRI has never been tested in a human, ever. MOTS-c has one trial, recruiting, with nothing reported.

The instructive comparison is SS-31. It holds an FDA approval and a far worse trial record than its marketing implies, because it actually ran trials, and trials produce failures. MOTS-c has no failures on its record for the same reason it has no successes. For the metabolic claims specifically, see peptides for appetite control.

What trial would settle the MOTS-c question?

The trial that would settle the MOTS-c question is the phase 1 human dose-ranging and pharmacokinetic study nobody has run. Nothing about MOTS-c in humans can be resolved before that exists, because every current protocol is extrapolated from rodents. Beyond it, the design that would actually test the exercise-mimetic claim is a randomised, double-blind, placebo-controlled trial in adults with a defined metabolic phenotype, running at least 12 weeks, with exercise itself as the comparator arm.

NCT07505745 may begin to answer some of this. Until it reports, the honest description of MOTS-c's human evidence base is that it is empty.

Frequently Asked Questions

Has MOTS-c ever been tested in humans?

FDA's July 2026 briefing document states the agency "did not identify clinical studies evaluating administration of MOTS-c-related BDSs in human subjects". One trial, NCT07505745, began recruiting in February 2026 with a target of 120 participants and has not reported results.

Did FDA approve MOTS-c for compounding?

No. FDA's own reviewers recommended against listing it. The Pharmacy Compounding Advisory Committee voted 7–5 with 2 abstentions to recommend listing it anyway, at the July 2026 meeting. That vote is advisory and non-binding; FDA has not acted, and MOTS-c remains an unapproved new drug.

Is MOTS-c banned in sport?

Yes, unambiguously. It falls under WADA section S4.4.1, AMPK activators, prohibited at all times. Unlike compounds whose status depends on the S0 catch-all, MOTS-c is captured by a named mechanistic category.

What dose should I use?

There is no evidence-based answer. No human dose-ranging study and no human pharmacokinetic study has been published. Every protocol in circulation is scaled from mouse experiments, which is an estimate, not a dose.

Doesn't research show higher MOTS-c levels are good for you?

Some observational work associates higher endogenous circulating MOTS-c with better metabolic markers. That is a statement about mitochondrial function as a biomarker. It is not evidence that injecting synthetic MOTS-c produces the same state, and treating it as such is the central logical error in MOTS-c marketing.

If the purity data is so good, why the caution?

Because purity and efficacy are separate questions. 494 tests across 23 labs establish that vendors are selling the correct molecule at high homogeneity. Nothing in that dataset speaks to what the molecule does in a human body, because that has not been studied.

MOTS-c is the cleanest example on this platform of a compound with excellent supply-chain data and no clinical evidence whatsoever. The underlying science is real: peptides encoded in mitochondrial DNA are a legitimate discovery, AMPK activation is well documented in cells and mice, and the aged-mouse results are interesting enough to justify the trial now recruiting in Shenzhen.

What does not exist is any published record of a human being given this compound and observed. FDA looked for one and reported finding none. Meanwhile the substance is sold by seventy-plus shops at a median of $4.50 a milligram, with dosing protocols derived from rodents and an anti-doping ban derived from a mechanism nobody has confirmed operates the same way in people.

The trial has started. In a couple of years there may be something to report. Right now, the most accurate thing anyone can say about what MOTS-c does in humans is that nobody has published the observation.

Browse the immune support and longevity peptides category, or our complete peptide guide with 118 compounds (verified August 2026). For per-injection volume, use the MOTS-c calculator alongside the reconstitution calculator. Compare shops through independent lab tests and community-verified shop reviews.

This article is for educational and informational purposes only and does not constitute medical advice. Peptides discussed may be investigational compounds not approved by the FDA (or equivalent regulators in your jurisdiction) for human use. Always consult a qualified healthcare provider before using any peptide or research compound. Peptigrity is an independent review platform and does not sell, endorse, or recommend specific products or vendors.