MOTS-c Benefits: Claims vs What Studies Show
Benefits people claim for MOTS-c, set against what published studies measured, and where no study exists.
Medical review pendingMitochondrial-derived peptideUpdated
- Strongest evidence
- Human RCT
- Human / animal studies
- 7 / 7
- in our evidence file (PubMed search, 11 Oct 2026)
- FDA status
- Not approved
- Off Category 2, 15 Apr 2026
Claimed benefits and what studies show
Each row is an area where people claim a benefit, with the strongest study we summarise behind it. Animal and cell results are labelled and are not human results. User reports are not counted as evidence here.
| Claim | Best evidence | Studies (human / animal) | What was measured | Page |
|---|---|---|---|---|
| Diabetes | Human RCT evidence, 4 of 4 | 2 / 3 | Circulating MOTS-c with metformin; MOTS-c response to lipid and insulin; Hyperglycemia and islet inflammation | Evidence for diabetes |
| Muscle growth | Human RCT evidence, 4 of 4 | 2 / 2 | Circulating MOTS-c with heat; MOTS-c and body composition (association); Immobilization-induced muscle loss | Evidence for muscle growth |
| Athletes | Human RCT evidence, 4 of 4 | 2 / 1 | Circulating MOTS-c after exercise; Circulating MOTS-c after acute exercise; Physical performance in mice | Evidence for athletes |
| Energy | Human RCT evidence, 4 of 4 | 1 / 2 | Circulating MOTS-c after exercise; Physical performance in mice; Endogenous MOTS-c with exercise in humans | Evidence for energy |
| Weight loss | Human RCT evidence, 4 of 4 | 2 / 2 | MOTS-c and body composition (association); Serum MOTS-c in obesity; Ovariectomy-induced obesity | Evidence for weight loss |
| Strength | Animal evidence, 2 of 4 | 0 / 3 | Immobilization-induced muscle loss; Physical performance in mice; Myostatin and muscle atrophy signalling | Evidence for strength |
| Menopause | Animal evidence, 2 of 4 | 0 / 2 | Ovariectomy-induced obesity; Bone loss | Evidence for menopause |
| Osteoporosis | Animal evidence, 2 of 4 | 0 / 2 | Bone loss; Type I collagen synthesis | Evidence for osteoporosis |
Strongest study per claim: Diabetes, Aging 2022, PMID 36490309; Muscle growth, Medicine and science in sports and exercise 2025, PMID 40674654; Athletes, Scientific reports 2021, PMID 34413391.
What the studies measured
| Outcome | Result | Study type | Source |
|---|---|---|---|
| Circulating MOTS-c with heat | Repeated heat treatment increased circulating MOTS-c (P = 0.033) and lowered muscle FGF21 (P = 0.027). | Human RCTn = 19 | Medicine and science in sports and exercise 2025, PMID 40674654 |
| Circulating MOTS-c with metformin | No significant change in circulating MOTS-c after 24 weeks of chemotherapy with or without metformin. | Human RCT | Aging 2022, PMID 36490309 |
| Circulating MOTS-c after exercise | Exercise raised plasma MOTS-c in non-Hispanic White survivors, but not in Hispanic survivors. | Human RCTn = 49 | Scientific reports 2021, PMID 34413391 |
| MOTS-c and body composition (association) | Post-exercise MOTS-c levels were associated with lower fat mass, body weight, HOMA-IR and CRP and higher lean mass in non-Hispanic White survivors (association, not a treatment effect). | Human RCTn = 49 | Scientific reports 2021, PMID 34413391 |
| Circulating MOTS-c after acute exercise | MOTS-c showed only a trend to increase after endurance exercise. | Human RCTn = 30 | Journal of applied physiology 2021, PMID 34351816 |
| Serum MOTS-c in obesity | Serum MOTS-c was 14.33 pg/mL with obesity versus 13.67 pg/mL at normal BMI, not significantly different. | Human observationaln = 85 | Archives of endocrinology and metabolism 2025, PMID 41004666 |
| MOTS-c response to lipid and insulin | Intralipid raised plasma MOTS-c in controls and PCOS subjects; insulin blunted the response. | Human observational | Clinical endocrinology 2019, PMID 31066084 |
| Circulating MOTS-c and endothelial function | Plasma MOTS-c was lower in patients with coronary endothelial dysfunction (p=0.007). | Human observationaln = 40 | International journal of cardiology 2018, PMID 29242099 |
| Immobilization-induced muscle loss | Immobilization reduced muscle mass by about 15%; MOTS-c attenuated this to a 5% reduction in mice. | Animal · mouse (not a human result) | American journal of physiology. Endocrinology and metabolism 2024, PMID 38170165 |
| Physical performance in mice | MOTS-c enhanced physical performance in young (2 mo.), middle-age (12 mo.) and old (22 mo.) mice. | Animal · mouse (plus human exercise samples) (not a human result) | Nature communications 2021, PMID 33473109 |
| Endogenous MOTS-c with exercise in humans | In people, exercise raises the body's own MOTS-c in skeletal muscle and blood. | Animal · mouse (plus human exercise samples) (not a human result) | Nature communications 2021, PMID 33473109 |
| Hyperglycemia and islet inflammation | MOTS-c ameliorated hyperglycemia and reduced islet-infiltrating immune cells in NOD mice. | Animal · mouse (plus human serum) (not a human result) | Cell reports 2021, PMID 34320351 |
| Serum MOTS-c in type 1 diabetes | Patients with type 1 diabetes had lower serum MOTS-c than healthy controls. | Animal · mouse (plus human serum) (not a human result) | Cell reports 2021, PMID 34320351 |
| Myostatin and muscle atrophy signalling | MOTS-c prevented palmitic acid-induced atrophy in C2C12 myotubes and decreased plasma myostatin in diet-induced obese mice. | Animal · mouse (plus C2C12 myotubes and human plasma) (not a human result) | American journal of physiology. Endocrinology and metabolism 2021, PMID 33554779 |
| Ovariectomy-induced obesity | MOTS-c prevented ovariectomy-induced obesity and insulin resistance in mice. | Animal · mouse (not a human result) | Journal of molecular medicine 2019, PMID 30725119 |
| Bone loss | MOTS-c treatment significantly alleviated bone loss on micro-CT in ovariectomized mice. | Animal · mouse (not a human result) | Biochemical and biophysical research communications 2016, PMID 27237975 |
| Obesity and insulin resistance | MOTS-c treatment prevented age-dependent and high-fat-diet-induced insulin resistance and diet-induced obesity in mice. | Animal · mouse (not a human result) | Cell metabolism 2015, PMID 25738459 |
| Type I collagen synthesis | MOTS-c increased type I collagen synthesis in cultured human osteoblasts. | In vitro (not a human result) | European review for medical and pharmacological sciences 2019, PMID 31081069 |
Not shown in any study we cite. Searches behind this page: PubMed search on 2 Oct 2026 for “("MOTS-c"[tiab] OR MOTSc[tiab])”: 262 results. PubMed search on 2 Oct 2026 for “("MOTS-c"[tiab] OR MOTSc[tiab]) AND (humans[mh] OR human[tiab] OR participants[tiab] OR patients[tiab] OR volunteers[tiab])”: 179 results. PubMed search on 2 Oct 2026 for “("MOTS-c"[tiab] OR MOTSc[tiab]) AND (randomized controlled trial[pt] OR "clinical trial"[pt] OR "meta-analysis"[pt] OR "systematic review"[pt])”: 5 results. PubMed search on 2 Oct 2026 for “("MOTS-c"[tiab] OR MOTSc[tiab]) AND (mice[tiab] OR mouse[tiab] OR rat[tiab] OR rats[tiab]) AND (injection[tiab] OR treatment[tiab] OR administration[tiab] OR treated[tiab])”: 72 results.
Weight, insulin and diabetes claims
The weight-loss and insulin claims trace to mouse work in which MOTS-c prevented diet-induced obesity and insulin resistance.[14]
In mice with autoimmune diabetes, MOTS-c reduced the development of hyperglycaemia and the number of immune cells infiltrating the islets.[10]
Muscle, energy and athletic-performance claims
In young, middle-aged and old mice, MOTS-c enhanced physical performance, and late-life intermittent treatment increased physical capacity and healthspan; this is mouse data.[9]
The same paper reports that, in people, exercise raises the body's own MOTS-c, which is not the same as treatment improving performance.[9]
In a randomised study of acute endurance and resistance exercise, circulating MOTS-c showed only a trend to rise after endurance exercise, and plasma levels of these peptides were not related to fitness status.[4]
In a trial of breast cancer survivors, plasma MOTS-c rose after 16 weeks of exercise in non-Hispanic White participants but not Hispanic participants.[3]
Menopause and bone claims (ovariectomised mice)
In ovariectomised mice, MOTS-c prevented obesity and insulin resistance.[12]
In ovariectomised mice, MOTS-c at 5 mg/kg once a day for 12 weeks alleviated bone loss.[13]
What has no trial
The trial-and-review PubMed query run on 2026-10-02 for ("MOTS-c"[tiab] OR MOTSc[tiab]) AND (randomized controlled trial[pt] OR "clinical trial"[pt] OR "meta-analysis"[pt] OR "systematic review"[pt]) found 5 results.
Calculated from query ("MOTS-c"[tiab] OR MOTSc[tiab]) AND (randomized controlled trial[pt] OR "clinical trial"[pt] OR "meta-analysis"[pt] OR "systematic review"[pt]); date 2026-10-02; result count 5. Formula: count reported by the search record in the evidence file
More on MOTS-c
Common questions
Is MOTS-c proven to work?
The strongest study we summarise for MOTS-c is human rct evidence, among 15 studies. A trial result is not an approval; see the legal status.
What does MOTS-c do?
MOTS-c is a mitochondria-encoded signalling peptide that regulates insulin sensitivity and metabolic homeostasis in the cited mouse and cell work.[14]
What does MOTS-c peptide do for muscle?
In immobilised mice it limited muscle loss, an animal result.[8]
More on MOTS-c
DosageDoses used in published studies, with the source for each.CalculatorVial, water and dose to syringe units.Side effectsWhat labels and studies report, and what is unknown.ResultsStudy outcomes and when they were measured.PricePrice per mg and per week from dated listings. No vendor links.How it worksTarget, mechanism and how long it acts, from the label or studies.
Sources
- 1Repeated Heat Stress Modulates the Levels of the Mitokines MOTS-C and FGF21 in Active Men during Calf Muscle Immobilization.Medicine and science in sports and exercise · 2025PMID 40674654Accessed 2 Oct 2026
- 2Circulating levels of MOTS-c in patients with breast cancer treated with metformin.Aging · 2022PMID 36490309Accessed 2 Oct 2026
- 3Effect of aerobic and resistance exercise on the mitochondrial peptide MOTS-c in Hispanic and Non-Hispanic White breast cancer survivors.Scientific reports · 2021PMID 34413391Accessed 2 Oct 2026
- 4Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans.Journal of applied physiology (Bethesda, Md. : 1985) · 2021PMID 34351816Accessed 2 Oct 2026
- 5MOTS-C levels ın ındividuals with and without obesity and ıts association with ınflammation, insulin resistance and endothelial dysfunction.Archives of endocrinology and metabolism · 2025PMID 41004666Accessed 2 Oct 2026
- 6Lipids and insulin regulate mitochondrial-derived peptide (MOTS-c) in PCOS and healthy subjects.Clinical endocrinology · 2019PMID 31066084Accessed 2 Oct 2026
- 7Downregulation of circulating MOTS-c levels in patients with coronary endothelial dysfunction.International journal of cardiology · 2018PMID 29242099Accessed 2 Oct 2026
- 8Mitochondrial-derived microprotein MOTS-c attenuates immobilization-induced skeletal muscle atrophy by suppressing lipid infiltration.American journal of physiology. Endocrinology and metabolism · 2024PMID 38170165Accessed 2 Oct 2026
- 9MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis.Nature communications · 2021PMID 33473109Accessed 2 Oct 2026
- 10Mitochondrial-encoded MOTS-c prevents pancreatic islet destruction in autoimmune diabetes.Cell reports · 2021PMID 34320351Accessed 2 Oct 2026
- 11MOTS-c reduces myostatin and muscle atrophy signaling.American journal of physiology. Endocrinology and metabolism · 2021PMID 33554779Accessed 2 Oct 2026
- 12MOTS-c peptide regulates adipose homeostasis to prevent ovariectomy-induced metabolic dysfunction.Journal of molecular medicine (Berlin, Germany) · 2019PMID 30725119Accessed 2 Oct 2026
- 13Mitochondria related peptide MOTS-c suppresses ovariectomy-induced bone loss via AMPK activation.Biochemical and biophysical research communications · 2016PMID 27237975Accessed 2 Oct 2026
- 14The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance.Cell metabolism · 2015PMID 25738459Accessed 2 Oct 2026
- 15MOTS-c improves osteoporosis by promoting the synthesis of type I collagen in osteoblasts via TGF-β/SMAD signaling pathway.European review for medical and pharmacological sciences · 2019PMID 31081069Accessed 2 Oct 2026
- 16PubMed search: ("MOTS-c"[tiab] OR MOTSc[tiab]) (262 results)PubMed · 2026pubmed.ncbi.nlm.nih.govAccessed 2 Oct 2026
- 17PubMed search: ("MOTS-c"[tiab] OR MOTSc[tiab]) AND (humans[mh] OR human[tiab] OR participants[tiab] OR patients[tiab] OR volunteers[tiab]) (179 results)PubMed · 2026pubmed.ncbi.nlm.nih.govAccessed 2 Oct 2026
- 18PubMed search: ("MOTS-c"[tiab] OR MOTSc[tiab]) AND (randomized controlled trial[pt] OR "clinical trial"[pt] OR "meta-analysis"[pt] OR "systematic review"[pt]) (5 results)PubMed · 2026pubmed.ncbi.nlm.nih.govAccessed 2 Oct 2026
- 19PubMed search: ("MOTS-c"[tiab] OR MOTSc[tiab]) AND (mice[tiab] OR mouse[tiab] OR rat[tiab] OR rats[tiab]) AND (injection[tiab] OR treatment[tiab] OR administration[tiab] OR treated[tiab]) (72 results)PubMed · 2026pubmed.ncbi.nlm.nih.govAccessed 2 Oct 2026
- 20PubMed search: ("MOTS-c"[tiab] OR MOTSc[tiab]) AND (half-life[tiab] OR pharmacokinetic*[tiab]) (3 results)PubMed · 2026pubmed.ncbi.nlm.nih.govAccessed 2 Oct 2026
- 21PubMed search: ("MOTS-c"[tiab] OR MOTSc[tiab] OR CB4211[tiab]) AND (adverse[tiab] OR "side effect*"[tiab] OR safety[tiab] OR tolerab*[tiab] OR toxicity[tiab] OR "case report"[pt]) (20 results)PubMed · 2026pubmed.ncbi.nlm.nih.govAccessed 11 Oct 2026
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