Comparison
MOTS-c vs Vitamin D3 + K2
Side-by-side of MOTS-c and Vitamin D3 + K2. Every row below is pulled from the compound schema and will update as our data grows. For deeper reads, follow through to each compound page.
MOTS-c
MOTS-c peptide is a 16-amino-acid mitochondrial-derived peptide. Preclinical signals for insulin sensitivity, exercise capacity, dosage notes.
Vitamin D3 + K2
Vitamin D3 K2 supplement profile: cholecalciferol at 1000-4000 IU/day corrects deficiency, MK-7 directs calcium to bone, away from arteries.
Effects at a glance
MOTS-c
- •16-amino-acid peptide encoded in mitochondrial DNA (12S rRNA region); discovered 2015
- •Activates AMPK in skeletal muscle and liver; improves insulin sensitivity in rodent models
- •Circulating endogenous levels decline with age, motivating the longevity-restoration hypothesis
- •CohBar's MOTS-c analog CB4211 discontinued after phase 1b NASH readout did not meet endpoints
- •Anecdotal protocols use 5 to 10 mg subcutaneously 2 to 3 times weekly
- •Not on the WADA Prohibited List as of 2026; future scrutiny likely given exercise-mimetic mechanism
Vitamin D3 + K2
- •Reduces non-vertebral fractures 10-20% in older adults at 800 IU/day or above when combined with calcium
- •VITAL trial showed neutral results on primary CV and cancer endpoints at 2000 IU/day over 5 years
- •Vitamin D supplementation reduces respiratory infection incidence ~10-20% in deficient populations
- •K2 MK-7 has 72-hour plasma half-life vs 1-2 hours for MK-4; once-daily dosing is sufficient
- •Synergy hypothesis is largely preclinical; dedicated combination RCTs are limited
- •Daily dosing outperforms bolus dosing for immune and infection outcomes
Side-by-side
| Attribute | MOTS-c | Vitamin D3 + K2 |
|---|---|---|
| Category | peptide | supplement |
| Also known as | Mitochondrial Open Reading Frame of the Twelve S rRNA-c, MOTSc | cholecalciferol + menaquinone, D3/K2, vitamin D3 with MK-7 |
| Half-life (hr) ↗ | 0.5 | 360 |
| Typical dose (mg) ↗ | 5 | 0.05 |
| Dosing frequency | 2-3x weekly | daily with a fat-containing meal |
| Routes | subcutaneous | oral |
| Onset (hr) | 1 | 24 |
| Peak (hr) | 4 | 168 |
| Molecular weight | 1880.18 | 384.64 |
| Molecular formula | C82H132N22O25S2 | C27H44O (D3); C46H64O2 (MK-7) |
| Mechanism | Mitochondrial-derived peptide that activates AMPK in skeletal muscle and liver, improves insulin sensitivity, and translocates to the nucleus under metabolic stress to modulate nuclear gene expression in retrograde mitochondrial signaling. | D3 converts to calcidiol then calcitriol, activating the vitamin D receptor (VDR) to increase intestinal calcium absorption and modulate immune and bone gene transcription. K2 carboxylates osteocalcin and matrix Gla protein, directing calcium toward bone and inhibiting vascular calcification. |
| Legal status | Not FDA approved; research-use-only grey market; not currently on WADA Prohibited List | Dietary supplement (global) |
| WADA status | unknown | allowed |
| DEA / Rx | Not scheduled (research chemical) | Not scheduled |
| Pregnancy | Insufficient data; not recommended | Recommended at standard doses for fetal bone development; consult clinician at higher doses |
| CAS | 1627580-64-6 | 67-97-0 |
| PubChem CID | 139599184 | 5280795 |
| Wikidata | Q24832108 | Q139347 |
Safety profile
MOTS-c
Common side effects
- injection-site irritation
- transient fatigue
- headache (anecdotal)
Contraindications
- pregnancy
- lactation
- active malignancy (theoretical)
- severe hypoglycemia risk on concurrent insulin or sulfonylurea
Interactions
- insulin: additive insulin sensitization may increase hypoglycemia risk(moderate)
- metformin: both activate AMPK; theoretical additive metabolic effect, no controlled data(minor)
- sulfonylureas: increased hypoglycemia risk via additive insulin sensitization(moderate)
Vitamin D3 + K2
Common side effects
- GI upset at high doses
- headache (rare)
- hypercalcemia (only at sustained very high D3 doses)
Contraindications
- hypercalcemia
- sarcoidosis
- active hyperparathyroidism
- warfarin therapy (K2 component requires stable intake)
Interactions
- warfarin: K2 component can affect anticoagulation; maintain stable intake and inform anticoagulation clinic(moderate)
- thiazide diuretics: additive calcium retention; hypercalcemia risk with high-dose D3(moderate)
- digoxin and calcium channel blockers: additive effects from D3-induced hypercalcemia(moderate)
- glucocorticoids: reduced vitamin D efficacy and bone effects(moderate)
- cholestyramine and orlistat: bind fat-soluble vitamins; separate dosing by 2 to 4 hours(moderate)
Which Should You Take?
Vitamin D3 + K2 comes out ahead for most readers on the criteria we weight: 3 catalogued goals, OTC dietary supplement, oral dosing, with a Tier-A outcome catalogued. MOTS-c is the right call when one of the conditionals below applies.
- → If your priority is metabolic health and glucose control, pick MOTS-c.
- → If your priority is mitochondrial function, pick MOTS-c.
- → If your priority is bone density, pick Vitamin D3 + K2.
- → If your priority is cardiovascular health, pick Vitamin D3 + K2.
Edge case: If you want to avoid research-only / gray-market sourcing, Vitamin D3 + K2 is the more accessible choice.
Default choice: Vitamin D3 + K2. Lower friction to source, a Tier-A evidence outcome catalogued, and broader goal coverage. Reach for MOTS-c only if your priority sits squarely in the goals it owns above.
This verdict is generated from each compound's schema (goals, legal status, evidence outcomes, dosing route). It updates automatically as our compound data evolves; the deeper read sits on each individual compound page.
Common questions
What is the difference between MOTS-c and Vitamin D3 + K2?
MOTS-c and Vitamin D3 + K2 differ in category (peptide vs supplement), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, MOTS-c or Vitamin D3 + K2?
MOTS-c half-life is 0.5 hours; Vitamin D3 + K2 half-life is 360 hours.
Can you stack MOTS-c with Vitamin D3 + K2?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
Go deeper