Comparison
Melatonin vs Spermidine
Side-by-side of Melatonin 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.
Melatonin
Melatonin as a sleep supplement: 0.3-1 mg matches physiological output, 3-10 mg is pharmacological. Shifts circadian phase, shortens sleep latency.
Spermidine
Spermidine supplement benefits cover autophagy induction, longevity signals, and cognition. Wheat germ extract data, doses, and human trials reviewed.
Effects at a glance
Melatonin
- •Shortens sleep onset latency by ~7 to 12 minutes at physiological 0.3 to 1 mg doses
- •Advances circadian phase when taken 30 to 60 minutes before target bedtime, useful for jet lag and shift work
- •Does not meaningfully increase total sleep time in healthy adults without circadian misalignment
- •Endogenous nighttime production is not suppressed by short-term exogenous supplementation
- •Higher doses (3 to 10 mg) raise plasma levels above physiological range and often increase morning grogginess
- •Effective for delayed sleep-wake phase disorder and reducing jet-lag severity in eastward travel
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 | Melatonin | Spermidine |
|---|---|---|
| Category | supplement | supplement |
| Also known as | N-acetyl-5-methoxytryptamine | spermidine trihydrochloride, wheat-germ-extract spermidine |
| Half-life (hr) ↗ | 0.75 | 6 |
| Typical dose (mg) ↗ | 0.5 | 1.2 |
| Dosing frequency | daily, 30 to 60 minutes before target sleep time | daily, typically morning with food |
| Routes | oral, sublingual | oral |
| Onset (hr) | 0.5 | 2 |
| Peak (hr) | 1 | 4 |
| Molecular weight | 232.28 | 145.25 |
| Molecular formula | C13H16N2O2 | C7H19N3 |
| Mechanism | Agonist at MT1 and MT2 receptors in the suprachiasmatic nucleus, signaling biological night and promoting sleep-onset gating plus circadian phase shifts. | 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 in US; prescription in UK, EU, Japan | OTC dietary supplement (wheat-germ extract has GRAS status in US) |
| WADA status | allowed | allowed |
| DEA / Rx | OTC supplement in US; Rx in UK, EU, Japan, Australia | OTC supplement (not scheduled) |
| Pregnancy | Insufficient data; not routinely recommended | Insufficient data; not routinely recommended at supplemental doses |
| CAS | 73-31-4 | 124-20-9 |
| PubChem CID | 896 | 1102 |
| Wikidata | Q179243 | Q411089 |
Safety profile
Melatonin
Common side effects
- vivid dreams
- morning grogginess (higher doses)
- headache
- dizziness
Contraindications
- autoimmune disease (theoretical)
- concurrent anticoagulant therapy without monitoring
Interactions
- fluvoxamine: CYP1A2 inhibition raises melatonin levels substantially(major)
- warfarin: possible increased bleeding risk(moderate)
- benzodiazepines and alcohol: additive sedation(moderate)
- antihypertensives: may alter blood pressure response(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?
Spermidine 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. Melatonin is the right call when one of the conditionals below applies.
- → If your priority is sleep onset or sleep quality, pick Melatonin.
- → If your priority is circadian regulation, pick Melatonin.
- → If your priority is healthspan extension, pick Spermidine.
- → If your priority is focus or working memory, pick Spermidine.
Edge case: Half-lives differ materially (Melatonin ~0.75 hr vs Spermidine ~6 hr). Spermidine reaches steady state faster; Melatonin is easier to dial in if tolerability is uncertain.
Default choice: Spermidine. Lower friction to source, a Tier-A evidence outcome catalogued, and broader goal coverage. Reach for Melatonin 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 Melatonin and Spermidine?
Melatonin and Spermidine differ in category (supplement vs supplement), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Melatonin or Spermidine?
Melatonin half-life is 0.75 hours; Spermidine half-life is 6 hours.
Can you stack Melatonin 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