NutriStack
5-HTP and Melatonin, a caution.
5-HTP is a serotonin precursor, and serotonin is converted to melatonin. Taking both may lead to excessive serotonergic/melatonergic activity.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
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What the row says.
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At a glance
- Pair type
- Caution
- Evidence (highest tier)
- Moderate
- Source citations
- 2 sources
- Stack Score effect
- −5 to your Stack Score (per scored caution row).
- Scope
- Supplement × Supplement
- Last verified
- May 30, 2026
Caution · Moderate evidence
Caution
What is happening. 5-HTP is a serotonin precursor, and serotonin is converted to melatonin. Taking both may lead to excessive serotonergic/melatonergic activity.
Mechanism. 5-HTP → serotonin → N-acetylserotonin → melatonin via AANAT and ASMT enzymes. Exogenous melatonin plus 5-HTP-derived melatonin may cause excessive sedation.
Recommendation. Generally redundant to take both. If combining, use low doses and monitor for excessive drowsiness.
Sources (2)
- Turner EH et al. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacol Ther. 2006;109(3):325-38. PMID 16023217
- Ganguly S et al. Control of melatonin synthesis in the mammalian pineal gland: the critical role of serotonin acetylation. Cell Tissue Res. 2002;309(1):127-37. PMID 12111543
Stack Score
How this pair moves the number.
Effect on the composite score
If both 5-HTP and Melatonin are in the same stack, this pair applies −5 to your Stack Score (per scored caution row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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