Completed experiment · August 2026

MOTS-C

The first two injections changed my breathing and heart rate. The response disappeared, and the full month produced no repeatable training benefit I could detect. Personal experiment record, not medical advice, prescribing, sourcing guidance, or an instruction to copy.

Outcome: One month at 9 mg per week, alongside 30 mg of NAD+ daily, produced an acute response after the first two injections but no repeatable change in workout energy, power, or training feel. Filed as no signal.

Research Summary

What it is

MOTS-C is a 16-amino-acid mitochondrial-derived peptide encoded by a short open reading frame within mitochondrial DNA. The research interest centers on metabolic homeostasis, skeletal-muscle signaling, adaptation to metabolic stress, and AMPK-related pathways.

What the evidence actually shows

A frequently cited study found that exercise increased endogenous MOTS-C in a small group of healthy young men. The injected-treatment performance results in that paper came from mice, not humans. Those findings support a biological role and a research hypothesis; they do not establish that injected MOTS-C improves performance, recovery, or body composition in people.

Why breathing was not an efficacy measure

Heavier breathing and a higher heart rate were real observations, but they do not identify which fuel was being used or prove that mitochondrial performance improved. Substrate oxidation is estimated from measured oxygen consumption and carbon-dioxide production under controlled conditions. During hard or non-steady-state exercise, hyperventilation and carbon dioxide from acid buffering make even those calculations harder to interpret. Perceived breathing alone cannot answer the mechanism question.

NAD+ was a second variable

I used daily NAD+ throughout the MOTS-C run. That means this was not a clean single-variable test. NAD+ was part of the context, not evidence that MOTS-C requires supplementation or that either intervention caused the early breathing and heart-rate response.

Regulatory and exposure context

MOTS-C is not an FDA-approved treatment. FDA says it has not identified human exposure data for drug products containing MOTS-C. MOTS-C is also prohibited at all times for tested athletes under the WADA metabolic-modulator category.

Sources

Reynolds et al., Nature Communications 2021 — endogenous response to exercise in ten men and injected MOTS-C performance experiments in mice.
Indirect calorimetry review, Indian Journal of Endocrinology and Metabolism 2017 — respiratory exchange ratio, substrate estimation, and limits during hyperventilation and non-steady-state exercise.
FDA compounding-risk notice — FDA regulatory assessment and the absence of identified human drug-exposure data for MOTS-C.
USADA MOTS-C advisory — approval status, evidence limits, and anti-doping status.

The Experiment

Context and protocol

I started this one-month run immediately after completing an SS-31 cycle. I used 9 mg of MOTS-C per week, divided into three 3 mg subcutaneous injections across the week. Throughout the run I also used 30 mg of NAD+ daily, or 210 mg per week. These are historical details of what I did, not a suggested protocol.

The first two injections

About 20 minutes after the first injection, my breathing and heart rate rose sharply. The same general response appeared with the second injection. During training, the slower return of my heart rate between sets made it harder to sustain the session and extended my rests. This was an acute response, not a positive performance signal.

Timing change

I moved the injections to after weight training so the acute response would not interfere with the workout. After roughly one to two weeks, I was no longer noticing the breathing or heart-rate change. I then moved MOTS-C back to pre-workout and used it alongside the daily NAD+ injection.

Result

Across the full month, I could not identify a repeatable improvement in workout energy, power, or training feel. The only clear subjective signal was the short-lived breathing and heart-rate response at the beginning, and that disappeared after the first two injections.

Interpretation

I do not know why the acute response disappeared. Adaptation is one possibility, but I did not measure the mechanism. The practical result is clear: nothing repeatable emerged in my training.

Decision

I am closing this run as no signal and removing MOTS-C from the active stack. I may repeat it in six to nine months, potentially after another SS-31 cycle. The useful observation next time will be whether the early breathing and heart-rate response returns after a long washout or remains absent.