MOTS-c: research

A peptide the body makes; injection benefits and safety remain unproven.

Also called: MOTS-C, Mitochondrial open reading frame of the 12S rRNA-c.

Mitochondrial-derived peptides · 16-amino-acid mitochondrial signaling peptide.

Endogenous biomarker measurements, registrations without results and administration of the CB4211 analogue do not establish direct human MOTS-c results. A direct-administration evidence level is not established here.

Studies

• Kidney failure and stress signals. cohort, n=240, 160 adults with kidney failure and 80 controls. Circulating mitochondrial peptides were lower in kidney failure; MOTS-c was inversely linked to the AGE/sRAGE ratio. (source)
• Exercise in cerebral palsy. cohort, Adults with cerebral palsy, and typically developing adults and adolescents. Natural peptide levels were similar at rest; a 45-minute run caused no or modest changes across groups. (source)
• Hashimoto's thyroiditis. cohort, n=180, 90 people with Hashimoto's thyroiditis and 90 matched controls. MOTS-c was lower in Hashimoto's thyroiditis, p<0.001. Levothyroxine use was not linked to different levels. (source)
• Atrial fibrillation biomarkers. cohort, n=78, 39 people with atrial fibrillation and 39 sinus-rhythm controls. Atrial tissue humanin and MOTS-c were lower in atrial fibrillation; plasma MOTS-c was also lower. (source)
• Kidney transplant biomarkers. cohort, n=150, 118 kidney transplant recipients and 32 controls. Median MOTS-c was 178 vs 142 ng/mL, p=0.014. It was not significantly linked to cardiovascular disease or mortality. (source)
• Dialysis and arterial stiffness. cohort, n=32, 32 people receiving peritoneal dialysis. Urinary MOTS-c correlated with arterial stiffness, r=0.708, p=0.001; dialysate MOTS-c correlated inversely, r=-0.717, p=0.019. (source)
• Heart attack and reperfusion injury. cohort, n=72, 72 people undergoing PCI after heart attack. Postoperative MOTS-c predicted reperfusion injury with AUC 0.648; adjusted OR 0.986, 95% CI 0.976-0.996. (source)
• Adolescent PCOS. cohort, n=246, 121 adolescents with PCOS and 125 controls. MOTS-c did not differ significantly, p=0.059. All participants had the wild-type A/A genotype. (source)
• Adult PCOS and muscle. cohort, n=80, 40 women with PCOS and 40 matched controls. Serum MOTS-c was 220.2±147.6 vs 498.3±224.4 pg/mL, p<0.001. Muscle expression was also lower in PCOS. (source)
• Obesity and bariatric surgery. cohort, n=54, 32 adults with obesity and 22 lean controls; 10 surgical follow-ups. MOTS-c was 273±56 vs 223±50 pg/mL, p<0.01; it did not change 6 months after surgery, p=0.913. (source)
• Multiple myeloma follow-up. cohort, n=29, 29 people with newly diagnosed multiple myeloma. MOTS-c increased after therapy in responders, with little or no change in refractory cases. (source)
• Acute coronary syndrome. cohort, n=400, 400 people with heart attack, unstable angina or normal coronary arteries. MOTS-c was higher in acute coronary syndrome; diagnostic AUC 0.739, 95% CI 0.647-0.832. (source)
• Alzheimer's disease biomarkers. cohort, People with Alzheimer's disease, mild impairment or subjective cognitive decline. Blood/plasma transcripts were lower in Alzheimer's disease; plasma peptide proteins did not distinguish Alzheimer's from mild impairment. (source)
• Prostate disease biomarkers. cohort, n=375, 375 men undergoing evaluation for suspected prostate cancer. MOTS-c was higher in precancerous lesions than benign enlargement; a combined plasma model had 95% cross-validated accuracy. (source)
• Heat during leg immobilization. rct, n=19, 19 active men, randomized to heat or sham during ankle immobilization. Heat increased circulating MOTS-c, p=0.033. Immobilization still reduced muscle thickness and cross-sectional area. (source)
• Sleep apnea severity. cohort, n=77, 53 people with sleep apnea and 24 controls. More severe sleep apnea was linked to lower MOTS-c after adjustment for BMI. (source)
• Acute coronary biomarkers. cohort, n=38, 18 people with acute coronary syndrome and 20 controls. MOTS-c and PGC-1α were lower in acute coronary syndrome; no significant sex effect was found. (source)
• Heart attack follow-up. cohort, People with heart attack and angiography controls. MOTS-c did not differ between groups, but changed across days 0, 3 and 30 after heart attack. (source)
• Aortic valve disease. cohort, n=39, 17 people scheduled for valve replacement and 22 controls. MOTS-c and PGC-1α were lower in aortic valve disease. No peptide was given. (source)
• Heart-lung bypass biomarkers. cohort, n=107, 107 people undergoing cardiopulmonary bypass. MOTS-c was lower in patients who developed acute lung injury. Peptide treatment was tested only in laboratory models. (source)
• Diabetes medicines and MOTS-c. cohort, n=163, 163 adults with type 2 diabetes and high cardiovascular risk. At 12 months, empagliflozin and empagliflozin plus liraglutide increased MOTS-c; liraglutide alone did not. (source)
• Peritoneal dialysis and muscle. cohort, n=32, 32 people receiving peritoneal dialysis. Higher sarcopenia risk was linked to lower serum and higher dialysate MOTS-c. (source)
• Type 1 diabetes in children. cohort, n=143, 82 children with type 1 diabetes and 61 controls. MOTS-c was lower in diabetes, p<0.001, but did not predict early diabetic kidney disease. (source)
• Marathon runners. cohort, Marathon runners and sedentary controls. Natural MOTS-c levels were associated with aerobic exercise capacity. Peptide dosing experiments were in mice. (source)
• Untreated preeclampsia. cohort, Pregnant women with preeclampsia and controls. MOTS-c was lower, p<0.05; humanin did not differ significantly between groups. (source)
• K14Q variant in older adults. cohort, n=683, 683 Korean adults aged 65 or older. Men carrying the C allele had more appendicular muscle, 21.6±3.0 vs 19.5±2.2 kg, p=0.018; the pattern was absent in women. (source)
• SGLT2 medicines in heart failure. cohort, n=111, 74 adults with diabetes and reduced-ejection-fraction heart failure; 37 controls. SGLT2 inhibitor use for at least 2 months was linked to higher MOTS-c, but not humanin. (source)
• Hemodialysis prognosis. cohort, n=94, 94 people receiving hemodialysis. 53 reached death or a nonfatal cardiovascular event over median 26.5 months; adding MOTS-c increased model AUC from 0.727 to 0.743. (source)
• Sleep apnea and cognition. cohort, n=268, 268 people, including sleep-apnea and cognitive-impairment groups. Exosome MOTS-c predicted cognitive impairment in sleep apnea, OR 5.453, 95% CI 3.112-9.556; levels fell after CPAP. (source)
• Radiotherapy biomarkers. cohort, 35 lung cancer patients, 34 breast cancer patients, and healthy controls. Lung cancer was linked to higher MOTS-c, further increased by radiotherapy; no such effect was found in breast cancer. (source)
• COPD exacerbation. cohort, n=211, 51 people with a COPD flare and 160 with stable COPD. MOTS-c was lower during a flare, p<0.001; high levels predicted readmission, HR 3.441, 95% CI 1.252-9.297. (source)
• Strength and endurance. cohort, n=20, 20 active volunteers: 17 men and 3 women. MOTS-c correlated with jump strength and power, but not maximum oxygen uptake. (source)
• Hepatitis B. cohort, n=489, 404 people with hepatitis B and 85 healthy controls. The study linked MOTS-c with hepatitis B biology; administered-peptide experiments were in cells and mice. (source)
• Fatty liver and fibrosis scores. cohort, n=234, 150 people with fatty liver and 84 controls. MOTS-c was lower in fatty liver, p=0.009, and in metabolic syndrome, p=0.01. (source)
• Heart surgery and lung injury. cohort, People undergoing off-pump coronary bypass surgery. Human MOTS-c and oxidative-stress levels were measured; protective dosing experiments used cells and animals. (source)
• Childhood obesity and blood vessels. cohort, n=443, 225 children with obesity and 218 healthy children. Children with obesity had lower MOTS-c; associations with vascular function did not test peptide injections. (source)
• COVID and long-COVID exosomes. cohort, n=64, 16 acute COVID, 30 long-COVID, 8 recovered and 10 uninfected participants. Exosomal mitochondrial-protein patterns during acute infection were linked to later long COVID. (source)
• Stable COPD. cohort, n=189, 142 people with stable COPD and 47 smokers with normal lung function. MOTS-c was lower in COPD, p=0.02; low levels were linked to oxygen desaturation, OR 3.25, 95% CI 1.456-8.522. (source)
• COVID blood biomarkers. cohort, n=62, 30 adults with COVID and 32 healthy volunteers. COVID was linked to lower humanin and higher MOTS-c. These were measurements, not dosing outcomes. (source)
• Heart attack and coronary flow. cohort, n=94, 52 people with STEMI and 42 angiography controls. MOTS-c was 91.9±8.9 vs 171.8±12.5 pg/mL, p<0.001; reported no-reflow prediction AUC was 0.95. (source)
• Preeclampsia comparison. cohort, n=90, 30 uncomplicated pregnancies, 30 mild and 30 severe preeclampsia cases. MOTS-c was 159.1±28.7, 129.6±54.7 and 146.4±48.3 ng/mL, respectively; p=0.166. (source)
• Metformin in breast cancer. cohort, Women in the METTEN randomized breast-cancer study. After 24 weeks, adding daily metformin to chemotherapy/trastuzumab did not significantly change circulating MOTS-c. (source)
• Neurological disease biomarkers. cohort, Alzheimer's, Parkinson's, stroke and MS groups, 32 patients per subgroup. MOTS-c was lower in Alzheimer's disease and acute ischemic stroke; the MS group did not differ from controls. (source)
• Multiple sclerosis. cohort, n=84, 43 people with relapsing-remitting MS and 41 controls. Serum MOTS-c differed between MS and control groups; no peptide treatment was tested. (source)
• Prostate cancer and ancestry. cohort, Men undergoing prostate biopsy, analyzed by race. Circulating mitochondrial peptides were associated with prostate-cancer risk in a race-dependent analysis. (source)
• Professional athletes. cohort, n=105, 75 athletes and 30 non-athletes. Athletes had lower MOTS-c and higher humanin than sedentary controls; high-endurance athletes had lower humanin than other athletes. (source)
• K14Q and muscle performance. cohort, 211 Japanese adults; an additional athlete comparison. K14Q variant status was associated with muscle-fiber composition and sprint/power performance. (source)
• Pregnancy and metabolic disorders. cohort, Pregnant women with obesity or thyroid disorders and healthy controls. Circulating MOTS-c varied by metabolic state; the study did not administer MOTS-c during pregnancy. (source)
• Depression and exosomes. cohort, People with major depression and matched controls. Neuron-derived vesicle mitochondrial proteins differed in depression and changed with SSRI response. (source)
• Body-fat distribution. cohort, n=125, 125 Chinese adults without diabetes. MOTS-c and SHLP2 were positively associated with abdominal and liver fat. (source)
• Exercise after breast cancer. rct, n=49, 25 Hispanic and 24 non-Hispanic White breast cancer survivors. After 16 weeks, MOTS-c rose in non-Hispanic White survivors, p<0.01, but not Hispanic survivors, p>0.01. (source)
• One exercise session. rct, n=30, 30 adults randomized to cycling, resistance exercise or rest. Humanin rose after endurance exercise; MOTS-c showed only a trend. Resting levels did not correlate with fitness. (source)
• Type 1 diabetes biomarkers. cohort, People with type 1 diabetes and healthy controls. Serum MOTS-c was lower in type 1 diabetes. T-cell and prevention experiments used cells and mice, not patient injections. (source)
• Myostatin and muscle biology. cohort, Human blood samples, with mouse and muscle-cell experiments. Human plasma MOTS-c was inversely correlated with myostatin; muscle-treatment effects were tested in laboratory models. (source)
• Exercise-induced MOTS-c. cohort, Healthy young men undergoing exercise testing. Exercise increased natural muscle and blood MOTS-c. The performance benefits from injected peptide were demonstrated in mice. (source)
• K14Q and diabetes risk. meta-analysis, n=27527, J-MICC, MEC and TMM cohorts. Across 3 cohorts, the C allele was associated with higher diabetes prevalence in men, particularly sedentary men, but not women. (source)
• First-episode psychosis. cohort, n=20, 10 people with first-episode psychosis and 10 matched controls. Neuron-derived exosome mitochondrial proteins were abnormal in psychosis; no peptide was given. (source)
• Sleep apnea and insulin resistance. cohort, n=90, 70 people with sleep apnea and 20 controls. Circulating MOTS-c was studied in relation to sleep-apnea severity and insulin resistance, without peptide administration. (source)
• Healthy aging and muscle. cohort, Young, middle-aged and older healthy men. Older and middle-aged men had about 1.5-fold higher muscle MOTS-c, although circulating levels fell with age. (source)
• Diabetes after revascularization. cohort, n=121, 121 patients with diabetes and coronary disease; external validation in 90 more. MOTS-c <167 ng/mL predicted major cardiac events over 2 years, relative risk 3.8, p<0.05; 22 of 121 had an event. (source)
• Advanced kidney disease. cohort, People with stage 5 kidney disease and matched controls. Muscle humanin and MOTS-c were lower. Serum humanin was higher while serum MOTS-c was lower in kidney disease. (source)
• Diabetes and natural peptides. cohort, n=225, 68 normal, 33 prediabetes, 31 well-controlled and 93 poorly controlled diabetes cases. Humanin and MOTS-c were lower across diabetes groups; this cross-sectional study did not test replacement injections. (source)
• Chronic fatigue and Q fever. cohort, n=40, 10 each with Q-fever fatigue, chronic fatigue, prior Q fever or healthy status. Monocyte peptide-gene expression was examined across groups; no injected peptide or clinical benefit was tested. (source)
• Insulin, lipids and exercise. cohort, Women with PCOS and healthy controls. Lipid infusion raised MOTS-c to 349±206% of baseline in PCOS; insulin reduced it to 183±177%, p<0.05. (source)
• Blood-test method comparison. cohort, n=20, 20 healthy reference participants. ELISA reported 45.9-218.5 ng/mL MOTS-c, but LC/MS did not confirm those levels; LC/MS detection limit was 100 pg/mL. (source)
• Childhood obesity. cohort, n=97, 40 children/adolescents with obesity and 57 controls. MOTS-c was lower in boys with obesity and correlated with insulin resistance and obesity measures. (source)
• Lean versus obese adults. cohort, n=20, 10 lean and 10 adults with obesity. MOTS-c was 0.48±0.16 vs 0.52±0.15 ng/mL, p=0.60. Associations with insulin sensitivity persisted only in lean adults. (source)
• Coronary vessel function. cohort, n=40, 40 people undergoing coronary function testing. Coronary endothelial dysfunction was associated with lower circulating MOTS-c; no peptide was injected. (source)
• Diabetes risk-model biomarkers. cohort, Adults grouped by HbA1c-defined glucose status. Humanin and MOTS-c ranked differently across glucose-status groups in models of the plasma atherogenic index. (source)
• Diabetes and comorbidities. cohort, Patients stratified by diabetes, hypertension and cardiovascular disease. Mitochondrial, inflammatory and oxidative markers differed across metabolic groups; no peptide intervention was given. (source)
• Early pregnancy follow-up. cohort, n=73, 28 women with gestational diabetes and 45 matched pregnant controls. Humanin and MOTS-c fell from first to second trimester; MOTS-c change was linked to insulin resistance, OR 3.73, 95% CI 1.03-13.50. (source)
• Original metabolic experiments. animal, High-fat-fed and aging mice, with cell experiments. MOTS-c reduced diet-related obesity and insulin resistance in mice; cellular effects involved folate/purine metabolism and AMPK. (source)
• Stress response in cells. in-vitro, Cultured cells under metabolic stress. MOTS-c moved to the nucleus under metabolic stress and altered stress-response gene expression. (source)
• Physical performance in mice. animal, Young, middle-aged and old mice. MOTS-c improved physical capacity in mice, including treatment begun at 23.5 months of age. (source)
• Human stem cells in the lab. in-vitro, Cultured fat-derived stromal cells from 6 lean donors and 6 donors with obesity. MOTS-c activated metabolic pathways but impaired some repair functions; metabolic signaling did not ensure better cell repair. (source)
• MOTS-c biomarker meta-analysis. meta-analysis, Secondary synthesis of biomarker or exercise research; not a peptide treatment trial. 7 observational studies, 602 participants: diabetes SMD -0.89, 95% CI -1.12 to -0.65; obesity SMD 0.51, 95% CI 0.21-0.81. (source)
• Exercise evidence review. systematic-review, Secondary synthesis of biomarker or exercise research; not a peptide treatment trial. 9 studies were included; most suggested exercise-related increases. Mixed designs and limited human data prevent dosing conclusions. (source)
• Native MOTS-c, recruiting. rct, n=120, Planned 120 adults with prediabetes and overweight/obesity; registry lists recruiting. Registered native MOTS-c dosing trial; no results or numerical dose are posted. (source)
• Exercise after breast cancer, registry. cohort, n=62, Breast Cancer; actual enrollment. A study record, not evidence that injected MOTS-c works. (source)
• Anesthesia and peptide markers. cohort, n=68, Kidney Disease, End-Stage; planned enrollment. A study record, not evidence that injected MOTS-c works. (source)
• Kidney disease exercise, registry. rct, n=50, Chronic Kidney Disease; planned enrollment. A study record, not evidence that injected MOTS-c works. (source)
• Fasting and peptide markers. cohort, n=120, Mitochondrial Degradation; planned enrollment. A study record, not evidence that injected MOTS-c works. (source)
• CB4211 analog, phase 1a/1b. rct, n=88, 65 healthy adults plus 23 adults with obesity and fatty liver; 20 completed the 4-week portion. The analog showed short-term biomarker changes; its doses cannot be used as native MOTS-c doses. (source)
• Stable coronary artery disease. cohort, n=184, 92 people with coronary disease and 92 angiography controls. MOTS-c was lower in coronary disease, 111±13 vs 161±23, p<0.001. The abstract omits the units for these means. (source)
• Male fertility biomarkers. cohort, Men with low sperm count/motility and healthy controls. Serum MOTS-c was lower in patients and correlated with semen quality. Treatment experiments used mice and cells. (source)
• High-altitude heart disease. cohort, People with high-altitude heart disease or acute coronary syndrome. Circulating MOTS-c was lower in these patient groups; peptide intervention was tested in mice. (source)
• Type 2 diabetes and islet aging. cohort, People with type 2 diabetes and healthy controls. Blood MOTS-c was lower in diabetes; administered-peptide effects on pancreatic aging were tested in mice. (source)
• Allergic asthma biomarkers. cohort, People with asthma and healthy volunteers. Serum MOTS-c was lower in asthma. Peptide administration experiments were in mice and airway cells. (source)
• Lung transplantation biomarkers. cohort, Lung-transplant recipients with or without remote ischemic preconditioning. MOTS-c fell after reperfusion injury but increased with preconditioning. This was not native peptide dosing. (source)
• Liver cancer biomarkers. cohort, People with liver cancer and healthy controls. Blood MOTS-c was lower in liver cancer. Its effects on cancer-cell death were tested in laboratory cells. (source)
• Ovarian cancer biomarkers. cohort, Ovarian cancer tissue, serum samples and survival analyses. MOTS-c was lower in serum and tumor tissue and linked to prognosis; treatment experiments used cells and animals. (source)
• Muscle membrane repair. cohort, Human participants assessed for muscle mitochondrial and membrane markers. MOTS-c correlated with mitochondria and TRIM72; mechanistic repair experiments used cells and mice. (source)

Gaps: Native MOTS-c has no published human dose-response, efficacy or injection-safety results. The new native trial does not disclose its dose and has no posted results. Long-term immune, cancer, reproductive and organ-safety effects are unknown. No validated shelf life or independent survey of retail-vial potency and sterility was found. Many serum studies conflict; assay differences and overlapping cohorts limit interpretation. No verifiable non-selling clinician-published dosing protocol was found. Some reported schedules omit the route; those doses remain in community reports rather than complete protocols.

Related to MOTS-c

• Humanin: A peptide the body makes; injection benefits and safety remain unproven.
• Retatrutide: An experimental weekly injection with phase 3 weight-loss results.
• Ipamorelin: An experimental peptide that triggers growth hormone release.
• NAD+ and precursors: NAD+ helps cells use energy; wellness injection benefits remain unproven.
• Tesamorelin: A peptide approved for deep abdominal fat in adults with HIV lipodystrophy.
• SS-31 (elamipretide): A peptide approved for Barth syndrome muscle strength; benefit needs confirmation and broader energy benefits remain unproven.

MOTS-c: the short version

Sources

• 503B Bulk Drug Substances List, FDA · FDA · 2026
• Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act, FDA · FDA · 2026
• Cellulitis, NHS · NHS · 2026
• Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks, FDA · FDA · 2026
• FDA Briefing Document: MOTS-c-Related Bulk Drug Substances (MOTS-c (free base) and MOTS-c acetate), FDA · 2026
• Federal Register: nonbinding draft HHS interim policy, October 30 2026, 2026
• Find product information about medicines, Medicines and Healthcare products Regulatory Agency · MHRA · 2026
• HHS 503A peptide interim enforcement policy and conditions, October 30 2026, 2026
• July 23-24, 2026: Meeting of the Pharmacy Compounding Advisory Committee - 07/23/2026, FDA · FDA · 2026
• Medicines, European Medicines Agency · European Medicines Agency · 2026
• Peptide products, Therapeutic Goods Administration · TGA · 2026
• Risks of buying peptide products online, Therapeutic Goods Administration · 2026
• The 2026 Prohibited List, World Anti-Doping Agency · WADA · 2026
• Think twice before injecting peptides bought online: unauthorized products can seriously harm you, Health Canada · Health Canada · 2026
• Anaphylaxis, NHS · NHS · 2023

Sources checked: 2026-10-18.

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