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Reviewed by MyPeptideMatch Editorial TeamLast reviewed February 2026Updated February 2026

MOTS-C Dosing Protocol: 5 mg Vial — Mitochondrial Hormone & Exercise Guide

MOTS-C mitochondrial-derived peptide dosing guide — AMPK activation, insulin sensitization, and exercise performance via the one-carbon metabolic cycle.

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Quickstart highlights

MOTS-C (Mitochondrial Open reading frame of the Twelve S rRNA-c) is a 16-amino acid peptide encoded within the 12S rRNA region of the mitochondrial genome — one of the few mitochondria-encoded peptides with known systemic endocrine function.

  • Concentration: 2 mg/mL (5 mg vial + 2.5 mL bacteriostatic water).
  • At 2 mg/mL: 5 mg = 250 units (2.5 mL); use 3 mL syringe per injection.
  • Kim et al. 2015: MOTS-C reverses diet-induced insulin resistance via AMPK-FOXO1 activation.
  • Inject before exercise sessions; MOTS-C is elevated endogenously during intense exercise.
  • Store lyophilized at -20 °C; reconstituted at 2–8 °C, use within 14 days.

Dosing table

For educational reference only. Your prescribing provider may adjust doses based on your clinical profile and response.

WeekDose (µg)UnitsFrequencyNotes
1-450002503x weekly (Mon/Wed/Fri)5 mg 3x/week — 250 units each; one 5 mg vial = 1 injection at this dose; starting protocol
5-1250002505x weekly (Mon–Fri)5 mg 5x/week — research protocol used in Bharat Bhakta lab data; weekend rest allows physiological integration

Reconstitution steps

  1. Draw 2.5 mL bacteriostatic water; inject slowly down the vial wall.
  2. Swirl gently until dissolved; do not shake.
  3. Final concentration: 2 mg/mL. At 2 mg/mL: 5 mg = 250 units — use a 1 mL insulin syringe filled to 100 units x 2.5 draws, or a 3 mL syringe.
  4. Label with date; refrigerate at 2–8 °C. Use within 28 days.

Supplies needed

12-week plan

  • 36 vials
  • 36 syringes
  • 90 mL bac water
  • 36 alcohol swabs
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Protocol overview & cycle notes

Activate the mitochondrial-derived MOTS-C hormone pathway to improve insulin sensitivity, enhance AMPK signaling, and promote exercise-adapted metabolic gene programs through regular subcutaneous injections before training sessions.

Cycle length: 12 weeks on.

Off-cycle: 4 weeks off after 12-week cycle.

Storage & handling

Lyophilized: store at -20 °C for maximum potency. Reconstituted at 2 mg/mL: refrigerate 2–8 °C; use within 14 days. MOTS-C is a 16-amino acid peptide encoded by mitochondrial DNA — more sensitive to degradation than typical synthetic peptides.

Injection & tracking tips

  • Inject subcutaneously 30–60 minutes before exercise to maximize AMPK-mediated glucose uptake and fat oxidation during the training session.
  • MOTS-C penetrates the nucleus during stress and directly activates AMPK-dependent gene programs — injection timing with exercise amplifies this metabolic programming.
  • Weekend rest from injection (if using weekday-only protocol) aligns with lower training stimulus; mitochondrial adaptations continue during rest days.

Tracking

Logging helps you and your provider spot patterns and adjust dose or timing.

  • Measure HOMA-IR and fasting insulin at baseline and 8 weeks.
  • Track exercise performance weekly (same workout, record time/weight lifted/reps).
  • Monitor body weight and waist circumference weekly.
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How this works & references

MOTS-C (Mitochondrial Open reading frame of the Twelve S rRNA-c) is a 16-amino acid peptide encoded within the 12S rRNA region of the mitochondrial genome — one of the few mitochondria-encoded peptides with known systemic endocrine function. Circulating MOTS-C declines with age. Kim et al. (2015, Cell Metabolism) demonstrated: (1) MOTS-C activates the AMPK-FOXO1 pathway; (2) Inhibits the de novo purine synthesis/folate pathway, diverting one-carbon metabolism toward AICAR production (natural AMPK activation); (3) Reverses diet-induced insulin resistance in mice. Bharat Bhakta's lab (2021, Nature Aging) showed MOTS-C administration improved exercise capacity and muscle function in aging mice.

Sources

Frequently asked questions

What is MOTS-C and why is it called a mitochondrial hormone?
MOTS-C is a 16-amino acid peptide encoded within the mitochondrial genome (12S rRNA region) — one of only a handful of mitochondria-derived peptides known to circulate systemically. Circulating MOTS-C responds to metabolic stress like a hormone, increasing during exercise and decreasing with aging and metabolic disease. This makes it a mitochondria-to-nucleus communication signal — hence 'mitochondrial hormone.'
Is MOTS-C available as a supplement?
MOTS-C cannot be taken orally — it is a peptide that would be degraded in the stomach. It is available only as a compounded injectable through licensed compounding pharmacies. Research grade MOTS-C is also used in laboratory settings. No oral supplement form with meaningful bioavailability exists.
How does MOTS-C generate AICAR endogenously?
MOTS-C inhibits the enzyme ATIC (5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase) in the de novo purine synthesis pathway. This causes AICAR (5-aminoimidazole-4-carboxamide ribonucleotide) to accumulate within the cell — the same molecule as the exogenous compound AICAR. MOTS-C thus activates AMPK through endogenous AICAR accumulation rather than requiring exogenous AICAR administration.
Can MOTS-C improve age-related muscle loss (sarcopenia)?
Kim et al. (2021, Nature Aging) demonstrated that MOTS-C administration to aged mice improved grip strength, treadmill capacity, and muscle mitochondrial biogenesis. The age-related decline in circulating MOTS-C is proposed as a contributing factor to sarcopenia. Human studies are not yet available; the sarcopenia application is a primary target for ongoing MOTS-C clinical development.
Is MOTS-C on the WADA prohibited list?
MOTS-C is not specifically listed on the WADA Prohibited List as of 2026. However, it may be captured under the category S4 (Hormone and Metabolic Modulators) if deemed to enhance performance. Athletes should verify with their national anti-doping organization before competitive use.

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This content is for informational purposes only and does not constitute medical advice. Consult a licensed healthcare provider before starting any peptide therapy. Dosing and protocols may vary by formulation and prescriber.

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