MOTS-C

MOTS-C (Inj)

MOTS-c is a 16–amino acid mitochondria-derived peptide encoded within mitochondrial 12S rRNA that has been studied as a metabolic regulator. In preclinical models, MOTS-c has been linked to improved insulin sensitivity, enhanced glucose utilization, and adaptive stress responses.

Dosing Protocols

— 5 mg Vial —

Reconstitute: Add 3.0 mL bacteriostatic water → ~1.67 mg/mL concentration.
Typical daily range: 500–1500 mcg once daily (gradual titration from 500 mcg).
Easy measuring: At 1.67 mg/mL, 1 unit = 0.01 mL ≈ 16.7 mcg on a U-100 insulin syringe.
Storage: Lyophilized: freeze at −20 °C; reconstituted: refrigerate at 2–8 °C, use within 2–4 weeks.

Schedule: Daily subcutaneous injections for 4–8 weeks, followed by an equal-length break (cycling approach).
Cycle Length: 4–8 weeks on, followed by 4–8 weeks off; avoid continuous long-term use without breaks.
Goal: Support metabolic homeostasis, enhance insulin sensitivity, and promote healthy aging through AMPK activation.

Frequency: Inject once daily subcutaneously (morning administration preferred). Alternate protocol: Some users employ 2–3 injections per week at higher per-dose amounts (e.g., 3–5 mg twice weekly).

Phase	Dose	Syringe (U-100)
Weeks 1–2	500 mcg (0.5 mg)	30 units (0.30 mL)
Weeks 3–4	1000 mcg (1.0 mg)	60 units (0.60 mL)
Weeks 5–6	1500 mcg (1.5 mg)	90 units (0.90 mL)
Weeks 7–8	2000 mcg (2.0 mg)	120 units (two 60-unit injections)

— 10 mg Vial —

Reconstitute: Add 3.0 mL bacteriostatic water → ~3.33 mg/mL concentration.
Typical daily range: 200–1,000 mcg once daily (gradual titration over 10 weeks).
Easy measuring: At 3.33 mg/mL, 1 unit = 0.01 mL ≈ 33.3 mcg on a U-100 insulin syringe.
Storage: Lyophilized: freeze at −20 °C; reconstituted: refrigerate at 2–8 °C, use within 7 days for best potency.

Schedule: Daily subcutaneous injections for 8–12 weeks.
Cycle Length: 8–12 weeks; optional extension to 16 weeks.
Goal: Support metabolic homeostasis, insulin sensitivity, and age-related physical performance.

Frequency: Inject once daily subcutaneously. Stay at each dose level for approximately 2 weeks before increasing.

Phase	Dose	Syringe (U-100)
Weeks 1–2	200 mcg	6 units (0.06 mL)
Weeks 3–4	400 mcg	12 units (0.12 mL)
Weeks 5–6	600 mcg	18 units (0.18 mL)
Weeks 7–8	800 mcg	24 units (0.24 mL)
Weeks 9–10+	1,000 mcg	30 units (0.30 mL)

— 20 mg Vial —

Reconstitute: Add 3.0 mL bacteriostatic water → ~6.67 mg/mL concentration.
Typical daily range: 200–1,000 mcg once daily (gradual titration over 10 weeks).
Easy measuring: At 6.67 mg/mL, 1 unit = 0.01 mL ≈ 66.7 mcg on a U-100 insulin syringe.
Storage: Lyophilized: freeze at −20 °C; reconstituted: refrigerate at 2–8 °C, use within 7 days for best potency.

Schedule: Daily subcutaneous injections for 8–12 weeks.
Cycle Length: 8–12 weeks; optional extension to 16 weeks.
Goal: Support metabolic homeostasis, insulin sensitivity, and age-related physical performance.

Frequency: Inject once daily subcutaneously.

Phase	Dose	Syringe (U-100)
Weeks 1–2	200 mcg	3 units (0.03 mL)
Weeks 3–4	400 mcg	6 units (0.06 mL)
Weeks 5–6	600 mcg	9 units (0.09 mL)
Weeks 7–8	800 mcg	12 units (0.12 mL)
Weeks 9–10+	1,000 mcg	15 units (0.15 mL)

— 40 mg Vial —

Reconstitute: Add 3.0 mL bacteriostatic water → ~13.33 mg/mL concentration.
Typical daily range: 200–1,000 mcg once daily (gradual titration over 10 weeks).
Easy measuring: At 13.33 mg/mL, 1 unit = 0.01 mL ≈ 133.3 mcg on a U-100 insulin syringe.
Storage: Lyophilized: freeze at −20 °C; reconstituted: refrigerate at 2–8 °C, use within 7 days for best potency.

Schedule: Daily subcutaneous injections for 8–12 weeks.
Cycle Length: 8–12 weeks; optional extension to 16 weeks.
Goal: Support metabolic homeostasis, insulin sensitivity, and age-related physical performance.

Frequency: Inject once daily subcutaneously.

Phase	Dose	Syringe (U-100)
Weeks 1–2	200 mcg	1.5 units (0.015 mL)
Weeks 3–4	400 mcg	3 units (0.03 mL)
Weeks 5–6	600 mcg	4.5 units (0.045 mL)
Weeks 7–8	800 mcg	6 units (0.06 mL)
Weeks 9–10+	1,000 mcg	7.5 units (0.075 mL)

Benefits

• Improved insulin sensitivity and glucose tolerance in animal models (preclinical).
• May enhance skeletal muscle glucose uptake and metabolic flexibility (preclinical).
• Associated with AMPK activation and cellular stress-response signaling.
• Studied for potential effects on fat mass and energy expenditure in diet-induced obesity models.
• Investigated in aging-related research as a mitochondria-to-nucleus signaling peptide.

Mechanism of Action

MOTS-c is reported to translocate to the nucleus under metabolic stress and influence gene expression related to metabolism. Mechanistically, it has been linked to AMPK activation and regulation of folate/methionine cycle intermediates, promoting glucose utilization and insulin sensitivity in preclinical systems.

Side Effects

Potential adverse effects reported in literature and/or anecdotally include:

• Injection-site irritation.
• Fatigue or lethargy.
• Headache.
• Transient nausea.
• Hypoglycemia-like symptoms in those with tight glycemic control (theoretical).

Side Effect Management

• Dose conservatively and monitor glucose metrics if available.
• Ensure adequate hydration and electrolytes.
• If symptoms suggest low blood sugar, reduce dose and consider timing with meals.
• Use sterile technique and rotate injection sites.

Contraindications

• Pregnancy or breastfeeding.
• Type 1 diabetes or insulin-treated diabetes without oversight.
• Severe liver/kidney disease (limited clearance data).
• Active malignancy (unknown risk).

Research Citations

PubMed-linked citations for verification. Many studies are preclinical (animal/in-vitro).

1. A mitochondrial-encoded peptide, MOTS-c, regulates metabolic homeostasis and insulin sensitivity. Cell Metab. 2015. PMID: 26073495 (doi: 10.1016/j.cmet.2015.05.009)
2. Mitochondria-derived peptides and retrograde signaling in metabolic regulation and aging. Trends Endocrinol Metab. 2016. PMID: 27287036 (doi: 10.1016/j.tem.2016.05.006)
3. Circulating MOTS-c and metabolic phenotypes in humans (observational). Endocrine. PubMed

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