"MOTS-c before and after" is searched as if there were a set of results to look at. There is not. No published study has given MOTS-c to people and measured what happened to their weight, body fat, blood sugar or fitness. What exists is a body of mouse research, a set of human studies that measured the body's own MOTS-c, and one short trial of a modified version of the molecule. This page lays out each, says which is which, and sets the claims that circulate online beside them.
What MOTS-c is — a 16-amino-acid peptide encoded in mitochondrial DNA, described in 2015 — is on Peptide Lexicon's MOTS-c entry. Reported side effects are on our MOTS-c side effects page and figures quoted for it on our MOTS-c dosage page. Nothing here is a recommendation; any decision about an unapproved substance belongs with a clinician.
The short answer, by question
| Question | Human evidence | Where the claim comes from |
|---|---|---|
| Weight loss | None for MOTS-c. A "trend" in one 4-week analogue trial, figure not published | Mice on a high-fat diet (Lee 2015) |
| Belly or liver fat | None for MOTS-c. Analogue trial: liver fat fell equally on placebo | Mice; clinic pages |
| Insulin sensitivity | None published. A 12-week phase 2a trial is recruiting | Mice (Lee 2015) |
| Endurance or performance | None for MOTS-c given as a drug | Mice (Reynolds 2021) |
| Does the body make more with exercise? | Yes, in small studies | Reynolds 2021; von Walden 2021; Dieli-Conwright 2021 |
What was seen in mice
The 2015 paper that named MOTS-c (Lee et al., Cell Metabolism, PMID 25738459) reported that MOTS-c acts mainly on skeletal muscle, switches on the energy sensor AMPK, and that treating mice "prevented age-dependent and high-fat-diet-induced insulin resistance, as well as diet-induced obesity." Every weight-loss claim for MOTS-c traces back to this paper or its successors. It is a mouse result.
The 2021 follow-up (Reynolds et al., Nature Communications, PMID 33473109) gave mice 15 mg/kg a day by injection into the abdomen for two weeks, then put them on a treadmill. Old mice ran twice as long and 2.16 times as far as untreated old mice, and 17% of the treated old mice reached the fastest running stage against none of the untreated group. Mice that began treatment late in life, three times a week, also kept more physical capacity. The paper's own conflict-of-interest statement records that two of its senior authors were consultants and shareholders of CohBar, the company developing MOTS-c analogues.
Mouse doses do not convert to human doses by body weight, and a two-week treadmill test is not a human outcome. These studies show what the molecule can do in an animal model. They do not show what it does in a person.
What has been measured in people: the body's own MOTS-c
The human studies on PubMed measure MOTS-c as a hormone the body makes, not as a drug it is given. A PubMed search for "MOTS-c" on 14 October 2026 returned 258 records; restricted to clinical-trial publication types, it returned five, and none of the five gave MOTS-c to anyone:
| Study | Who | What was measured | Finding |
|---|---|---|---|
| Reynolds 2021 (Nat Commun) | 10 sedentary young men | MOTS-c in muscle and plasma around a cycling session | Muscle 11.9-fold after exercise; plasma 1.6-fold during, 1.5-fold after, back to baseline at 4 h |
| von Walden 2021 (J Appl Physiol, PMID 34351816) | 30 adults: endurance, resistance or no exercise | Plasma and muscle MOTS-c at 30 min and 3 h | Only a trend to rise after 45 min of cycling; plasma levels not correlated with VO2max or strength |
| Dieli-Conwright 2021 (Sci Rep, PMID 34413391) | 49 breast cancer survivors, 16-week exercise programme | Fasting plasma MOTS-c | Rose in non-Hispanic white women, not in Hispanic women |
| Cuyàs 2022 (Aging, PMID 36490309) | Breast cancer patients randomised to metformin or not | Circulating MOTS-c | No change with 24 weeks of metformin |
| Elhusseiny 2025 (Med Sci Sports Exerc, PMID 40674654) | 19 active men, ankle immobilisation | Circulating and muscle mitokines | Repeated heat treatment raised circulating MOTS-c |
One detail is often lost when these numbers are repeated: the 11.9-fold figure is muscle tissue measured by biopsy, not blood. The blood rise in the same men was about one and a half times, and it was gone four hours later. A Swedish study of 30 adults (von Walden 2021) found only a trend for plasma MOTS-c to rise after 45 minutes of cycling, and no link between resting levels and fitness — so even the exercise signal is small and inconsistent in blood. The 16-week exercise study also found that its participants' MOTS-c levels tracked with falls in fat mass and insulin resistance — an association within an exercise programme, which shows MOTS-c moving with fitness, not MOTS-c causing it.
The one controlled human trial in the class: CB4211
CB4211 is a modified MOTS-c that CohBar developed and described as "a novel and improved analog of MOTS-c." It is not the peptide sold as MOTS-c, and its results cannot be transferred to that peptide. It is still the only placebo-controlled human efficacy data anywhere in the MOTS-c family, so it is the closest thing to a "before and after" the record holds.
The trial (NCT03998514) had two parts: a one-week dose-finding stage in 65 healthy adults, then four weeks of 25 mg daily or placebo by injection in 20 adults with obesity and at least 10% liver fat. Participants lived in the clinical unit for the whole four weeks. CohBar's topline release (10 August 2021, filed with the SEC) reported:
| Measure after 4 weeks | CB4211 25 mg (n=11) | Placebo (n=9) | Difference |
|---|---|---|---|
| ALT, a liver enzyme (% change) | −21% | +4% | −25 points (significant) |
| AST, a liver enzyme (% change) | −28% | −11% | −17 points (significant) |
| Fasting glucose (% change) | −6% | 0% | −6 points (significant) |
| Liver fat at start (MRI) | 21.1% | 15.9% | — |
| Liver fat change (percentage points) | −5.03 | −4.88 | −0.15 (our subtraction) |
| Reached ≥30% relative fall in liver fat | 36% | 33% | 3 points |
| Body weight | "trend towards lower body weight" | — | no figure published |
The release itself states that "both the CB4211 and placebo groups had substantial reductions in liver fat content compared to baseline." A month of supervised residence — controlled meals, no alcohol — lowers liver fat in its own right, which is the most likely reason the placebo group matched the drug. The enzyme and glucose changes were statistically significant against placebo; the fat change, which is what "before and after" searches are asking about, was not different. The significance tests were unpaired t-tests on 11 and 9 people, reported in a press release rather than a peer-reviewed paper; the registry entry had no posted results when we checked.
What the online timelines rest on
Timelines that circulate for this search describe more energy in the first weeks and body-composition change after six to twelve. The census above found no human study of MOTS-c given as a drug, so no point on such a timeline can rest on one. A timeline with no trial behind it is a marketing claim, and it is labelled as one here. Before-and-after photographs carry the further problems set out on our peptides before and after page: lighting, posture, diet and training change between the two pictures, and the photographs shown are chosen.
What would change this page
One registered trial gives MOTS-c itself to people. NCT07505745, sponsored by Hudson Biotech and run in China, is a phase 2a, double-blind, placebo-controlled study of 120 adults with prediabetes and overweight or obesity; both arms also receive lifestyle counselling. Its primary measures are insulin sensitivity from a glucose-tolerance test at 12 weeks and adverse events to 16 weeks. The registry lists it as recruiting since February 2026, with primary completion estimated for 14 February 2027. When it posts results, this page will report them — including if they are null.
Until then, the honest summary is short: MOTS-c has a strong mouse record, an interesting role as an exercise-responsive hormone, and no human efficacy result. How it compares with another mitochondria-targeted peptide that does have approved human data is set out in our SS-31 vs MOTS-c comparison. MuscleLedger's MOTS-c page covers the compound from the gym side.