MOTS-c Compounding Legal Status: What the FDA Has and Has Not Approved

Is MOTS-c an FDA-approved drug?

No. MOTS-c is not approved for any indication, and it is not a component of any approved drug. FDA's July 2026 evaluation found no USP or National Formulary monograph for it, no entry in the European or Japanese pharmacopeias, and no product authorized by the European Medicines Agency [1].

MOTS-c (mitochondrial open reading frame of the 12S rRNA-c) is a 16-amino-acid peptide, molecular weight about 2174.6 g/mol, encoded in mitochondrial DNA and first reported in 2015 by Lee and colleagues in Cell Metabolism [1][9]. MOTS-c is a common name rather than an official drug name, and FDA treats the free base and the acetate salt as separate bulk substances [1].

What FDA found when it reviewed MOTS-c

FDA staff reviewed MOTS-c as a nominated bulk drug substance and proposed in a July 2026 briefing document that neither the free base nor the acetate be added to the pharmacy bulks list. The stated reasons: the substance is not well characterized, with inconsistent naming and no impurity, aggregate or endotoxin data; its actual use in compounding is unknown; there are no human safety or effectiveness data and no animal toxicity studies; and FDA-approved treatments exist for obesity and osteoporosis, two of the nominated uses [1].

The nominated uses were insulin resistance, obesity, osteoporosis, vascular calcification, muscle and fat metabolism, and longevity, formulated as 5 mg and 10 mg subcutaneous injections [1]. FDA's search of PubMed, Embase, the Cochrane library and other sources found no published study in which MOTS-c was given to a person, and the 12 papers the nominator cited were not clinical studies [1]. No outsourcing facility reported compounding MOTS-c between January 2017 and December 2025 [1]. It is sold on websites and in combinations, including an IV cocktail offered by a wellness clinic [1].

Where MOTS-c sits on FDA's compounding lists

FDA's page on bulk substances that may present significant safety risks, with content dated 04/22/2026, lists MOTS-c in the nominated-but-withdrawn table. That table holds substances previously placed in category 2 whose nominators later withdrew them. FDA's stated concerns were that it had not identified any human exposure data for MOTS-c by any route, that important safety information is missing, and that injectable peptides may pose immunogenicity risk from aggregation and peptide-related impurities. Removal from category 2 was not a finding that MOTS-c is safe [7].

MOTS-c appears in none of the three categories on FDA's list for state-licensed pharmacies and physicians (updated May 14, 2026) and is absent from FDA's list for outsourcing facilities (updated March 21, 2025) [2][3][10]. The category 1 interim policy, under which FDA generally does not intend to act against compounders who meet its conditions, does not extend to MOTS-c [10].

FDA's page says a state-licensed pharmacy may compound with a bulk drug substance only if it complies with a USP or National Formulary monograph, is a component of an FDA-approved drug product, or appears on FDA's bulks list [10]. MOTS-c meets none of those three conditions [1][10]. Compounded drugs are not FDA-approved, and FDA does not review their safety, effectiveness or quality before they reach patients [11].

What the July 2026 advisory committee vote did and did not do

FDA's Pharmacy Compounding Advisory Committee took up MOTS-c free base and MOTS-c acetate at its July 23, 2026 meeting, with obesity and osteoporosis as the uses FDA reviewed [5]. The committee voted in favor of adding MOTS-c to the pharmacy bulks list, against FDA staff's recommendation [5][4].

That vote is advice only. It did not place MOTS-c on the list, and adding a substance takes formal rulemaking [5][4].

The HHS draft enforcement policy

HHS filed a draft enforcement-discretion policy for compounding with certain peptides on October 28, 2026 (Federal Register document 2026-22192, publication scheduled for October 30, 2026, with comments due two weeks after publication). MOTS-c is one of the peptides named, alongside BPC-157, epitalon, KPV, Semax and TB-500. The policy covers MOTS-c acetate given by subcutaneous or intramuscular injection [4][6].

HHS says it does not intend to take enforcement action against a state-licensed pharmacy, a federal facility or a licensed physician compounding with MOTS-c if the policy's conditions are met. Those conditions include a single active ingredient, a patient-specific prescription, an FDA-registered manufacturer with a certificate of analysis, and a label reading 'This is a compounded drug product. Not for resale.' [4][6].

The draft does not put MOTS-c on any list. Its notice states that it does not establish any rights for any person and is not binding on HHS or the public, and HHS may revisit the policy, for example if a safety signal or product quality issue arises [4].

Does MOTS-c have an FDA-approved label?

No. There is no FDA-approved prescribing information for MOTS-c because no MOTS-c product is FDA-approved [1]. The label wording in the HHS draft policy ('This is a compounded drug product. Not for resale.') is a condition of that policy, not prescribing information [4][6].

What human evidence exists

The pharmacology of MOTS-c comes from cells and rodents. In mice on a high-fat diet, injected MOTS-c at 0.5 mg/kg/day (intraperitoneal) was associated with about 20% lower body weight after 8 weeks, along with improved insulin sensitivity and exercise performance [1][9]. A late-life schedule of 15 mg/kg three times weekly from 23.5 months of age lengthened median lifespan from 912 to 970 days in one study [1]. Effects appear to involve AMPK signalling and reduced one-carbon (folate) metabolism, but FDA says the molecular targets are unknown and no dose-response relationships were assessed [1][9].

Reynolds and colleagues, writing in Nature Communications in 2021, reported that MOTS-c improved physical performance in young (2-month), middle-aged (12-month) and old (22-month) mice, and that intermittent treatment started at 23.5 months of age increased physical capacity and healthspan. In humans that study measured only that exercise raises the body's own MOTS-c in skeletal muscle and in circulation; participants were not given the peptide [12].

A randomized trial by von Walden and colleagues, published in the Journal of Applied Physiology in 2021, assigned 30 healthy adults to endurance exercise (n=10), resistance exercise (n=10) or control (n=10). Circulating humanin rose significantly after endurance exercise; MOTS-c showed only a trend to increase, and plasma peptide levels were not related to fitness [13].

FDA's adverse-event database searches through March 9, 2025 retrieved no MOTS-c reports [1]. For injection, FDA's stated concern is immunogenicity (an immune reaction) from aggregation and peptide-related impurities, and no immunogenicity data exist for this 16-amino-acid peptide [1]. An in-vitro study found MOTS-c is quickly broken down in human blood, which raises the question whether injecting it can produce active levels in people [1].

Is there a dose of MOTS-c?

MOTS-c has no approved dose and no human dosing study [1]. The nominated products were 5 mg and 10 mg subcutaneous injections [1]. The rodent doses used in research, from 0.5 to 15 mg/kg, cannot be converted into human doses [1]. No pharmacokinetic data exist in humans or in live animals [1].

Anti-doping status

WADA's Prohibited List names MOTS-c in section S4.4.1 among metabolic modulators, specifically activators of AMP-activated protein kinase. It is prohibited at all times, in and out of competition, and S4.4 substances are non-Specified Substances. It appears on the 2026 List, in force since January 1, 2026, and remains on the 2027 List in the tracked-changes version dated 26 August 2026; FDA notes it was already on the 2024 List [8][14][1].