NutriStack
L-Tryptophan and Venlafaxine, contraindicated.
L-Tryptophan is the upstream dietary precursor for serotonin, and venlafaxine blocks serotonin reuptake. Concentrated tryptophan supplements can add serotonergic substrate on top of venlafaxine's reuptake blockade, raising the risk of serotonin syndrome. Food sources of tryptophan are not the issue; high-dose supplements are.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
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At a glance
- Substances
- L-Tryptophan and Venlafaxine
- Pair type
- Contraindicated
- Evidence (highest tier)
- Moderate
- Source citations
- 3 sources
- Stack Score effect
- −25 to your Stack Score (per scored contraindication row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Contraindicated · Moderate evidence
Contraindicated
What is happening. L-Tryptophan is the upstream dietary precursor for serotonin, and venlafaxine blocks serotonin reuptake. Concentrated tryptophan supplements can add serotonergic substrate on top of venlafaxine's reuptake blockade, raising the risk of serotonin syndrome. Food sources of tryptophan are not the issue; high-dose supplements are.
Mechanism. L-Tryptophan is converted by tryptophan hydroxylase to 5-HTP and then to serotonin. Venlafaxine inhibits SERT, especially at lower doses, reducing serotonin clearance from the synapse while precursor supply is increased.
Recommendation. Do not combine L-tryptophan supplements with venlafaxine. If you are using L-tryptophan for sleep or mood, stop it and ask your prescriber for a safer alternative. Watch for tremor, sweating, agitation, diarrhea, fever, or muscle jerking if exposure occurred.
Sources (3)
- Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120. PMID 15784664
- Young SN. Use of tryptophan in combination with other antidepressant treatments: a review. J Psychiatry Neurosci. 1991;16(5):241-246. PMID 1797098
- Sansone RA, Sansone LA. Serotonin norepinephrine reuptake inhibitors: a pharmacological comparison. Innov Clin Neurosci. 2014;11(3-4):37-42. PMID 24800132
Stack Score
How this pair moves the number.
Effect on the composite score
If both L-Tryptophan and Venlafaxine 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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