MOTS-c — a year of dosing, metabolic labs, and what I actually think is happening
32 posts
Year of MOTS-c in the books. Posting because the writeups on this compound are mostly 'felt great' with no numbers, and the skeptic takes are mostly 'no human data' without engaging with what the human data that exists actually says.
Me: 45F, T2D family hx but personally pre-metabolic-syndrome-y (HbA1c 5.6, fasting glucose 98, HOMA-IR 2.1 at baseline), BMI 27, lifting 3x/week + Zone 2 3x/week. Nothing else changed during the trial year.
Dose: 10 mg SubQ once weekly, Monday AM. Ran 8 weeks on / 4 weeks off cycles, four cycles total. Picked the weekly dose based on the Lee 2015 paper and the subsequent pharmacokinetic work.
Labs, cycle-by-cycle (baseline -> end):
- HbA1c: 5.6 -> 5.3 -> 5.3 -> 5.2 -> 5.2
- Fasting glucose: 98 -> 92 -> 90 -> 88 -> 89
- Fasting insulin: 7.4 -> 6.1 -> 5.8 -> 5.5 -> 5.7
- HOMA-IR: 2.1 -> 1.4 -> 1.3 -> 1.2 -> 1.3
- ApoB: 88 -> 85 -> 86 -> 84 -> 82
- hs-CRP: 1.8 -> 1.2 -> 1.0 -> 1.1 -> 1.0
- Body fat (DEXA): 31% -> 29% -> 28% -> 28% -> 27%
Caveats (obligatory):
- Training and diet were stable but not measured to the gram. A 5-10% improvement in diet adherence over a year on its own could move many of these markers.
- I also lost ~8 lb over the year. Weight loss alone moves HOMA-IR and insulin sensitivity.
- MOTS-c has been a darling of the longevity community for about 3 years without a lot of human RCT support. My data is consistent with 'it's working' and consistent with 'I got healthier and it took credit.'
Mechanism, as I understand it: MOTS-c is a mitochondrial-derived peptide encoded within the 12S rRNA mitochondrial gene. It upregulates AMPK, improves insulin sensitivity in muscle, and seems to have anti-inflammatory effects. Read the Lee lab papers if you're curious.
What I'll keep: yes. The ratio of injection burden (1/wk) to plausible benefit (real, even if I can't isolate it) is the best in the longevity class IMO.
Happy to answer questions, will not discuss sources.
15 Replies
33 posts
These are exactly the labs I'd want to see. HOMA-IR from 2.1 to 1.3 in a year is real regardless of what drove it. Fasting insulin dropping ~25% is meaningful.
50 posts
Good writeup. Question: did you time bloodwork to a consistent point in the dosing cycle? (e.g., always week 6 of an 8-week on block, always 5 days post-dose, etc.) Because AMPK activation is transient and the exact timing matters for interpreting fasting insulin.
34 posts
Published human MOTS-c data is thin. The in vitro and rodent work is cleaner. Your ApoB drop (88 -> 82) is consistent with modest weight loss plus improved insulin sensitivity; it's not MOTS-c-specific signature. The HOMA-IR trajectory is the most interesting piece.
31 posts
ApoB move is in the noise, I wouldn't hang anything on it. HOMA-IR is the real signal. That's a substantial improvement that would be clinically meaningful if repeatable.
115 posts
MOTS-c as a signaling peptide is one of the more interesting stories in mitochondrial biology. The therapeutic translation is unproven. Your data doesn't prove it either, but it's a useful data point. Stack of similar writeups is how the pattern becomes real.
45 posts
3% body fat off via DEXA across a year at stable weight (or ~8 lb loss with presumably some lean mass retention) is a legit body recomposition. That alone explains most of the metabolic markers.
36 posts
Running MOTS-c alongside Epithalon. MOTS-c feels like the clearer metabolic lever, Epi feels like the clearer sleep lever. If I could keep only one, MOTS-c.
16 posts
The honest uncertainty in this post ('consistent with MOTS-c working and consistent with me getting healthier and it took credit') is what I want from longevity writeups. Not certainty — calibrated uncertainty.
22 posts
HOMA-IR 2.1 to 1.3 is the number I'm going to think about all week. That's a real metabolic shift.
31 posts
Curious if you'd have gotten the same markers from Zone 2 + lifting + 8 lb loss without MOTS-c. Genuine question not a jab.
71 posts
Writeup is good but the correct reference paper to cite for MOTS-c mechanism is Lee et al 2015 Cell Metabolism. Everyone on here handwaves 'AMPK.' Cite the paper.