MOTS-c vs Semax
Sold as a way to get the benefits of exercise without training. Mice given it stayed lean and ran longer, but it has not been tested in people. A nasal spray sold to sharpen memory and protect the brain after stroke. Studies from Russia look promising, but none was a proper blinded trial.
Semax has the stronger evidence, grade B (some human evidence) against grade C for MOTS-c. Neither is FDA approved.
Evidence
CAnimal and cell studies
BSome human evidence
Human studies cited
Animal or cell studies cited
Why the grade
The efficacy data are in mice: the 2015 discovery paper showing protection from diet-induced obesity and insulin resistance, and a 2021 paper showing better physical performance in young and old mice. The only human data measure the body's own MOTS-c rising in muscle and blood after exercise. No human has received MOTS-c in a published trial, so C.
Five Russian clinical studies cover stroke (30 patients versus 80 controls in 1997; 110 patients in 2018), chronic cerebrovascular insufficiency (187 patients), optic nerve disease and a 24-person imaging study in healthy volunteers. Several had control groups but none describes randomization and blinding in the way a modern trial would, and none has been replicated outside Russia. Controlled human studies exist, so B, but at the weak end.
FDA
Not approved
Not approved by the FDA for any use and sold as a research chemical. MOTS-c was placed in Category 2 (significant safety risk) in 2023; the nomination was withdrawn, the FDA removed it from that category in April 2026, and the Pharmacy Compounding Advisory Committee voted in July 2026 to recommend it for the compounding list. On 28 October 2026 HHS issued an enforcement discretion policy covering injectable MOTS-c acetate compounded by licensed pharmacies and physicians for named patients under sourcing, testing, labeling and reporting conditions. That is not an approval. It is also on the 2026 WADA Prohibited List.
Not approved
Semax is not approved by the FDA for any use and is sold in the United States as a research chemical. It is registered as a prescription drug in Russia. In July 2026 the FDA's Pharmacy Compounding Advisory Committee voted to recommend adding semax to the list of substances pharmacies may compound, against the advice of FDA staff. On 28 October 2026 HHS issued an enforcement discretion policy covering semax as a nasal product only, compounded by licensed pharmacies and physicians for named patients under sourcing, testing, labeling and reporting conditions. That is not an approval.
Sold for
MOTS-c is sold as an 'exercise mimetic', a mitochondrial peptide said to burn fat, improve insulin sensitivity, and boost endurance the way training does.
Semax is sold as a nasal nootropic that sharpens memory and attention and protects the brain after stroke.
Studies say
Mice given MOTS-c resisted obesity and ran longer, and humans make more of it after exercise, but no trial has given it to people, so the evidence is grade C.
Russian clinical studies report faster recovery after stroke and fewer vascular events in chronic cerebrovascular disease, and a small imaging study shows it changes brain network activity in healthy people, but no blinded placebo-controlled trial has been published, so the cognitive claims are unproven.
Class
Mitochondrial-derived peptide
Nootropic peptide (ACTH(4-10) analog)
Route
Injection
Nasal