MOTS-c

Mitochondrial-derived peptide · D-tier (Dr. Alex Tatem) · Preclinical evidence

Nicknamed “exercise in a vial” because it activates the same energy sensor (AMPK) as exercise. That’s exciting in mice, but it’s unproven in people.

Dr. Tatem’s take

D-tier in Pt. 2 (no placebo-controlled human data). On Diary of a CEO he called it “exercise in a vial”, and his deep dive calls it “one of the most genuinely exciting molecules”, while stressing that human data hasn’t delivered yet.

In Dr. Tatem’s tier list

• Unique on his list: it’s derived from the mitochondria.
• His framework: you lose fat by eating less (how GLP-1s mainly work) or by raising energy expenditure. MOTS-c is meant to rev up mitochondria and raise basal metabolism.
• Users say they feel more energetic, but so do people given sugar water they’re told is caffeine — that’s why placebo-controlled trials exist, and MOTS-c hasn’t had good ones.
• Verdict: D tier — less data than the secretagogues (C), but not “complete trash” like AOD-9604. (In a later deep-dive video he’s more enthusiastic about the science.)

History & background

MOTS-c was discovered in 2015 by Changhan David Lee and Pinchas Cohen at the University of Southern California — a 16-amino-acid peptide encoded inside mitochondrial DNA, which was itself a surprise. In mice it activated AMPK, improved insulin sensitivity and prevented diet-induced obesity.

CohBar tested an analog (CB4211) in a small human trial around 2021 with modest results. FDA advisers voted 7–5–2 in July 2026 to recommend MOTS-c for compounding; it is banned in sport.

Benefits

• Improved insulin sensitivity and prevented diet-induced obesity in mice.

Risks

• No human safety data beyond 28 days.
• Injection-site reactions (analog trial).

Dosing protocols (informational, labeled by evidence)

• Community (bro science): Circulating protocol (per Tatem) — 5–15 mg, SubQ, 3x/week, 8–12 wk
• Community (bro science): Low daily variant — 1–3 mg, SubQ, Daily, Varies

Status: Not approved. FDA advisers voted 7–5–2 in July 2026 to allow compounding (obesity, osteoporosis). Rulemaking is pending.

Grade and commentary: Dr. Alex Tatem. Watch: MOTS-c: The Peptide That Makes Your Cells Think You’re Exercising, Truth About More Popular Peptides (What Works, What’s Overhyped) | Peptide Tier List pt.2, Peptide Expert: What Do Peptides Actually Do? (EXPLAINED) - Dr Alex Tatem. Subscribe: @DrAlexTatem.