NutriStack
5-HTP and St. John's Wort, contraindicated.
St. John's Wort inhibits serotonin reuptake while 5-HTP floods serotonin synthesis. Combined use risks serotonin syndrome: a potentially fatal condition.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
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From the interaction database
What the row says.
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At a glance
- Substances
- 5-HTP and St. John's Wort
- Pair type
- Contraindicated
- Evidence (highest tier)
- Moderate
- Source citations
- 4 sources
- Stack Score effect
- −25 to your Stack Score (per scored contraindication row).
- Scope
- Supplement × Supplement
- Last verified
- May 30, 2026
Contraindicated · Moderate evidence
Contraindicated
What is happening. St. John's Wort inhibits serotonin reuptake while 5-HTP floods serotonin synthesis. Combined use risks serotonin syndrome: a potentially fatal condition.
Mechanism. Hyperforin in St. John's Wort blocks serotonin reuptake. 5-HTP bypasses rate-limiting enzyme to increase serotonin production. Dual mechanism creates dangerous serotonin excess.
Recommendation. Do NOT combine. Both increase serotonergic activity through different mechanisms.
Sources (4)
- Borrelli F et al. Herb-drug interactions with St John's wort (Hypericum perforatum): an update on clinical observations. AAPS J. 2009;11(4):710-27. PMID 19859815
- Singer A et al. Hyperforin, a major antidepressant constituent of St. John's Wort, inhibits serotonin uptake by elevating free intracellular Na+1. J Pharmacol Exp Ther. 1999;290(3):1363-8. PMID 10454515
- Turner EH et al. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacol Ther. 2006;109(3):325-38. PMID 16023217
- Boyer EW et al. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20. PMID 15784664
Stack Score
How this pair moves the number.
Effect on the composite score
If both 5-HTP and St. John's Wort are in the same stack, this pair applies −25 to your Stack Score (per scored contraindication row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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