Comparison
DHEA vs MOTS-c
Side-by-side of DHEA 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.
DHEA
DHEA supplement profile: adrenal androgen precursor, typical 25-50 mg dose, DHEA-S targets, evidence for adrenal insufficiency and vaginal atrophy, side effec.
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
DHEA
- •Adrenal androgen precursor; serum DHEA-S declines progressively after the third decade of life
- •OTC dietary supplement in US under DSHEA 1994; prescription in EU, UK, Canada, Australia
- •FDA approved as Intrarosa (6.5 mg vaginal insert) for postmenopausal dyspareunia in 2016
- •Acts as tissue-specific prohormone converted intracrinologically to testosterone and estrogens
- •Best evidence: adrenal insufficiency replacement and vaginal atrophy; weaker on cognition and longevity
- •WADA banned in competitive sport; banned in NCAA, MLB, NFL, IOC settings
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 | DHEA | MOTS-c |
|---|---|---|
| Category | hormone | peptide |
| Also known as | dehydroepiandrosterone, prasterone, Intrarosa | Mitochondrial Open Reading Frame of the Twelve S rRNA-c, MOTSc |
| Half-life (hr) ↗ | 12 | 0.5 |
| Typical dose (mg) ↗ | 25 | 5 |
| Dosing frequency | daily, typically morning | 2-3x weekly |
| Routes | oral, vaginal, topical | subcutaneous |
| Onset (hr) | 1 | 1 |
| Peak (hr) | 1 | 4 |
| Molecular weight | 288.42 | 1880.18 |
| Molecular formula | C19H28O2 | C82H132N22O25S2 |
| Mechanism | Steroid prohormone converted intracrinologically to testosterone and estrogens in target tissues; also exerts direct effects via sigma-1 receptor, GABA-A modulation, and glucocorticoid receptor interaction. | 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 | OTC supplement in US (DSHEA 1994); prescription in EU, UK, Canada, Australia | Not FDA approved; research-use-only grey market; not currently on WADA Prohibited List |
| WADA status | banned | unknown |
| DEA / Rx | OTC supplement in US (not scheduled); Rx in EU, UK, Canada, Australia | Not scheduled (research chemical) |
| Pregnancy | Contraindicated in pregnancy | Insufficient data; not recommended |
| CAS | 53-43-0 | 1627580-64-6 |
| PubChem CID | 5881 | 139599184 |
| Wikidata | Q411733 | Q24832108 |
Safety profile
DHEA
Common side effects
- acne
- oily skin
- hirsutism (women)
- gynecomastia (men, higher doses)
- irritability
- insomnia
Contraindications
- hormone-sensitive cancer (breast, ovarian, prostate)
- active liver disease
- uncontrolled lipid disorder
- pregnancy and lactation
Interactions
- warfarin: case reports of altered INR; monitor(moderate)
- estrogens (HRT): additive estrogenic effect via conversion; monitor(moderate)
- insulin: may improve insulin sensitivity slightly; monitor glucose(minor)
- anastrozole: may reduce DHEA-derived estrogen; clinical relevance unclear(minor)
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?
DHEA comes out ahead for most readers on the criteria we weight: 2 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 hormonal optimization, pick DHEA.
- → If your priority is metabolic health and glucose control, pick MOTS-c.
- → If your priority is mitochondrial function, pick MOTS-c.
Edge case: If you want to avoid research-only / gray-market sourcing, DHEA is the more accessible choice.
Default choice: DHEA. 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 DHEA and MOTS-c?
DHEA and MOTS-c differ in category (hormone vs peptide), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, DHEA or MOTS-c?
DHEA half-life is 12 hours; MOTS-c half-life is 0.5 hours.
Can you stack DHEA 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