Comparison
DHEA vs Spermidine
Side-by-side of DHEA and Spermidine. 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.
Spermidine
Spermidine supplement benefits cover autophagy induction, longevity signals, and cognition. Wheat germ extract data, doses, and human trials reviewed.
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
Spermidine
- •Endogenous polyamine that induces autophagy via EP300 acetyltransferase inhibition and TFEB activation
- •Concentrated in wheat germ, soybeans, aged cheese, and mushrooms; ~10 to 15 mg/day in Mediterranean diets
- •Eisenberg 2016 reported dietary spermidine extended mouse lifespan and improved cardiac function
- •Wirth 2018 pilot (n=28) reported cognitive signal at 0.9 mg/day in older adults at risk for dementia
- •Larger Wirth 2019 follow-up (n=85) did not replicate the memory benefit at 12 months
- •Generally regarded as safe at supplemental doses; food-source position is reassuring
Side-by-side
| Attribute | DHEA | Spermidine |
|---|---|---|
| Category | hormone | supplement |
| Also known as | dehydroepiandrosterone, prasterone, Intrarosa | spermidine trihydrochloride, wheat-germ-extract spermidine |
| Half-life (hr) ↗ | 12 | 6 |
| Typical dose (mg) ↗ | 25 | 1.2 |
| Dosing frequency | daily, typically morning | daily, typically morning with food |
| Routes | oral, vaginal, topical | oral |
| Onset (hr) | 1 | 2 |
| Peak (hr) | 1 | 4 |
| Molecular weight | 288.42 | 145.25 |
| Molecular formula | C19H28O2 | C7H19N3 |
| 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. | Induces macroautophagy via inhibition of EP300 histone acetyltransferase and activation of TFEB-mediated lysosomal biogenesis. Substrate for hypusination of eIF5A, required for translation of mitochondrial respiration proteins. |
| Legal status | OTC supplement in US (DSHEA 1994); prescription in EU, UK, Canada, Australia | OTC dietary supplement (wheat-germ extract has GRAS status in US) |
| WADA status | banned | allowed |
| DEA / Rx | OTC supplement in US (not scheduled); Rx in EU, UK, Canada, Australia | OTC supplement (not scheduled) |
| Pregnancy | Contraindicated in pregnancy | Insufficient data; not routinely recommended at supplemental doses |
| CAS | 53-43-0 | 124-20-9 |
| PubChem CID | 5881 | 1102 |
| Wikidata | Q411733 | Q411089 |
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)
Spermidine
Common side effects
- mild GI upset (rare)
- headache (rare)
Contraindications
- wheat-germ allergy or celiac disease (for wheat-germ-extract products)
- active cancer (theoretical)
- pregnancy and lactation (insufficient data)
Interactions
- DFMO (difluoromethylornithine): competing polyamine metabolism; do not combine without oncology guidance(moderate)
Which Should You Take?
DHEA and Spermidine score evenly on the criteria we weight (goal breadth, legal accessibility, evidence depth). The conditionals below should drive the decision more than any aggregate score.
- → If your priority is hormonal optimization, pick DHEA.
- → If your priority is focus or working memory, pick Spermidine.
- → If your priority is healthspan extension, pick DHEA.
Edge case: DHEA is contraindicated in pregnancy; Spermidine is the safer pick if that applies.
Default choice: either is defensible. DHEA edges out on goal breadth + legal accessibility; Spermidine is the right call if your priority sits in the goals listed 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 Spermidine?
DHEA and Spermidine differ in category (hormone vs supplement), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, DHEA or Spermidine?
DHEA half-life is 12 hours; Spermidine half-life is 6 hours.
Can you stack DHEA with Spermidine?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
Go deeper