Comparison
Ashwagandha vs MOTS-c
Side-by-side of Ashwagandha and MOTS-c. 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.
Ashwagandha
Ashwagandha supplement guide: KSM-66 and Sensoril extracts at 300-600 mg/day cut morning cortisol and stress in RCTs. Dose, side effects, testosterone data.
MOTS-c
MOTS-c peptide is a 16-amino-acid mitochondrial-derived peptide. Preclinical signals for insulin sensitivity, exercise capacity, dosage notes.
Effects at a glance
Ashwagandha
- •Reduces morning serum cortisol by ~20 to 30% at 300 to 600 mg/day standardized extract over 8 weeks
- •Lowers subjective stress on DASS-21 and PSS scales versus placebo in chronically stressed adults
- •Modest grip-strength and 1-RM gains of ~5 to 8% in trained men when paired with resistance training
- •Improves self-reported sleep quality and onset latency in adults with insomnia symptoms
- •Small testosterone increases (~10 to 15%) reported in stressed or subfertile men, less clear in healthy populations
- •May raise free T3 and T4; can interact with levothyroxine and unmask subclinical hyperthyroidism
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
Side-by-side
| Attribute | Ashwagandha | MOTS-c |
|---|---|---|
| Category | natural | peptide |
| Also known as | Withania somnifera, KSM-66, Sensoril | Mitochondrial Open Reading Frame of the Twelve S rRNA-c, MOTSc |
| Half-life (hr) ↗ | 10 | 0.5 |
| Typical dose (mg) ↗ | 600 | 5 |
| Dosing frequency | daily | 2-3x weekly |
| Routes | oral | subcutaneous |
| Onset (hr) | 2 | 1 |
| Peak (hr) | - | 4 |
| Molecular weight | - | 1880.18 |
| Molecular formula | - | C82H132N22O25S2 |
| Mechanism | GABAergic modulation and HPA-axis attenuation; withanolides reduce cortisol secretion and inhibit NF-kB signaling. | 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. |
| Legal status | Dietary supplement in most jurisdictions; regulated in Denmark | Not FDA approved; research-use-only grey market; not currently on WADA Prohibited List |
| WADA status | allowed | unknown |
| DEA / Rx | OTC supplement | Not scheduled (research chemical) |
| Pregnancy | Not recommended | Insufficient data; not recommended |
| CAS | - | 1627580-64-6 |
| PubChem CID | - | 139599184 |
| Wikidata | Q310109 | Q24832108 |
Safety profile
Ashwagandha
Common side effects
- mild GI upset
- drowsiness
- headache
Contraindications
- pregnancy
- autoimmune disease (theoretical immune stimulation)
- hyperthyroidism
- concurrent sedative use
Interactions
- benzodiazepines: additive CNS depression(moderate)
- thyroid hormone (levothyroxine): may raise T3/T4, altering dose requirements(moderate)
- immunosuppressants: theoretical antagonism via immune stimulation(moderate)
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)
Which Should You Take?
Ashwagandha comes out ahead for most readers on the criteria we weight: 3 catalogued goals, OTC dietary supplement, oral dosing, with a Tier-B outcome catalogued. MOTS-c is the right call when one of the conditionals below applies.
- → If your priority is stress and HPA-axis regulation, pick Ashwagandha.
- → If your priority is focus or working memory, pick Ashwagandha.
- → If your priority is healthspan extension, pick MOTS-c.
- → If your priority is metabolic health and glucose control, pick MOTS-c.
Edge case: If you want to avoid research-only / gray-market sourcing, Ashwagandha is the more accessible choice.
Default choice: Ashwagandha. Lower friction to source, 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 Ashwagandha and MOTS-c?
Ashwagandha and MOTS-c differ in category (natural vs peptide), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Ashwagandha or MOTS-c?
Ashwagandha half-life is 10 hours; MOTS-c half-life is 0.5 hours.
Can you stack Ashwagandha with MOTS-c?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
Go deeper