MOTS-c for Health & Longevity - Quick Reference Sheet

MOTS-c for Health & Longevity

Created on 08/07/2026 – Quick Reference based on Evidence Review created using AI4L / Opus 5 Audit

A very short protein made inside the cell's energy compartments, acting on its main low-energy sensor. Animal work is consistent and in places striking; no completed study has given it to people. Dose, duration, long-term consequences and effects in women are unmeasured, and material bought outside research settings carries purity and sterility uncertainty. (Full Review)

Protocol

The only human-tested regimen
25 mg analogue CB4211, once daily for 4 weeks
Subcutaneous, in adults with obesity and at least 10% liver fat. A modified molecule, not MOTS-c; equivalence not public.
The regimen now under test
Fixed daily dose of MOTS-c for 12 weeks
Subcutaneous, in adults 18–65 with prediabetes and a body mass index of 27–40 kg/m². The dose is not disclosed in the registry record.
Regimens circulating in practice
Single-digit milligram range, subcutaneously
Daily for a short block, or two to three times weekly for several weeks. Convention rather than evidence; no published dose-finding study.
Time to effect
Liver enzymes
4 weeks
The only human data point, from the analogue trial. No earlier timepoint was reported.
Glucose
4 weeks
Nothing measurable is expected inside two weeks; four to twelve weeks is the window for biomarker change, if any.
Physical performance, in mice
Weeks of dosing
After weeks of intermittent treatment, not single doses. No human equivalent has been measured.

Benefits

Contraindications
  • Pregnancy, breastfeeding or planning pregnancy
  • Under 18 years of age
  • eGFR below 60 mL/min/1.73 m² (or creatinine clearance below 90 mL/min)
  • ALT or AST above 2.5× upper limit of normal, or significant liver disease
  • Active malignancy requiring treatment (except treated non-melanoma skin cancer)
  • Type 1 diabetes, or type 2 on insulin or a sulfonylurea, unsupervised
  • Established diabetes (HbA1c ≥6.5%, fasting glucose ≥126 mg/dL, or two-hour glucose ≥200 mg/dL)
  • Cardiovascular disease within six months (myocardial infarction, stroke, unstable angina), or uncontrolled hypertension
  • Known hypersensitivity to peptide therapeutics or formulation components
  • Competitive athletes subject to anti-doping rules
Key Interactions
  • Insulin and insulin secretagogues (insulin glargine, insulin aspart, glipizide, glimepiride, glyburide, repaglinide)
  • Other glucose-lowering agents (metformin, GLP-1 receptor agonists such as semaglutide and tirzepatide, SGLT2 inhibitors such as empagliflozin and dapagliflozin)
  • Antifolate drugs (methotrexate, pemetrexed, trimethoprim, sulfasalazine, pyrimethamine)
  • Corticosteroids (prednisone, dexamethasone)
  • Glucose-lowering supplements with additive effects (berberine, alpha-lipoic acid, chromium picolinate, gymnema, bitter melon, cinnamon extract)
  • Folate and B-vitamin supplements (folic acid, 5-methyltetrahydrofolate, vitamin B12)
  • Other peptide and small-molecule interventions
  • Over-the-counter medications: no interaction has been documented (NSAIDs, paracetamol, antihistamines, proton pump inhibitors)
  • Exercise, heat exposure and fasting: potentiating, and not adverse

Risk & Side Effects

  • High: Absence of human safety data
  • Medium: Contaminated, mislabelled or non-sterile product; injection-site reactions
  • Low: Immunogenicity and anti-drug antibodies; hypoglycaemia with concurrent glucose-lowering treatment
  • Speculative: Effects on tumour biology; amplification of the senescent-cell inflammatory signal; blunting of training adaptations; systemic symptoms reported in unregulated use; accumulation in impaired kidney function

Monitoring

Marker Target Why
Fasting insulin 2–5 µIU/mL Earliest marker of the insulin resistance MOTS-c is proposed to improve
Fasting glucose 75–86 mg/dL The only demonstrated human metabolic effect
HOMA-IR Below 1.0 Single index combining fasting glucose and insulin
HbA1c 4.8–5.3% Three-month average glycaemia; secondary endpoint of the running trial
ALT 10–26 U/L (men), 10–19 U/L (women) Moved most clearly in the only human trial of this compound class
AST 10–26 U/L Paired with ALT to separate liver from muscle
GGT Below 20 U/L (men), below 15 U/L (women) Hepatic oxidative stress and alcohol effect
eGFR Above 90 mL/min/1.73 m² Clearance governs exposure; basis of trial exclusions
hs-CRP Below 0.5 mg/L Tracks the inflammation the peptide is proposed to reduce
Triglycerides and the triglyceride-to-HDL ratio Below 80 mg/dL; ratio below 1.5 Surrogate for insulin resistance without insulin testing
Complete blood count Within laboratory reference range Detects the additive folate-pathway effect predicted with antifolates
Liver fat by MRI-PDFF Below 5% Failed to separate from placebo in the analogue trial
Circulating MOTS-c No validated range exists Should not be used to judge response

Cadence: Baseline within four weeks before a first dose, with diet, training and weight stable; core panel repeated at 4 and 12 weeks, then every 3–6 months if use continues.

Qualitative Assessment

  • Perceived exercise capacity and time to fatigue during habitual training sessions
  • Recovery between training sessions, and next-day soreness
  • Afternoon energy, particularly the post-meal dip that tracks glucose handling
  • Sleep continuity and morning alertness
  • Injection-site tolerance: redness, hardening, itching, and time to resolve
  • Appetite and satiety after meals
  • Symptoms of low blood sugar — tremor, sweating, hunger, poor concentration — especially the first two weeks