NSTK · 01.2026Independent supplement reference
NutriStack
Edition 1.0Updated August 1, 2026

Supplement × Supplement·Evidence index

L-Tryptophan and St. John's Wort: what the published research says

PubMed indexes 8 records that name L-Tryptophan and St. John's Wort together, either in the title or in an interaction, co-administration, or pharmacokinetic context. Each one is listed below with its study design and, where the abstract states one, the authors’ own conclusion, quoted and linked. This page reports that literature. It does not tell you whether to combine them.

Read this first

An evidence index, not guidance.

Every statement below is attributed to a named, dated, linked source.

This page lists published research relevant to L-Tryptophan and St. John's Wort. It deliberately does not state whether the combination is safe, whether it interacts, in which direction, at what dose, or how far apart to take them.

The research

8 studies naming L-Tryptophan and St. John's Wort.

Strongest relevance first: papers naming both substances in the title, then human trials and systematic reviews.

Hypericum perforatum L. attenuates depression by regulating Akkermansia muciniphila, tryptophan metabolism and NFκB-NLRP2-Caspase1-IL1β pathway.

Phytomedicine : international journal of phytotherapy and phytopharmacology · 2024 · PMID 38996505

Animal study

“The promising therapeutic role of HPL in treating depression is primarily attributed to its regulation of the NFκB-NLRP2-Caspase1-IL1β pathway, specifically by targeting AKK and tryptophan metabolites.”

Jiang et al. · Authors' conclusion

Names both L-Tryptophan and St. John's Wort in its title.

Auxin driven indoleamine biosynthesis and the role of tryptophan as an inductive signal in Hypericum perforatum (L.).

PloS one · 2019 · PMID 31622392

“The established paradigm of thought views tryptophan primarily as a precursor for auxin and indoleamines, among other metabolites, and mediation of auxin action by the indoleamines as a one-way interaction. We propose that these processes run in both directions with auxin modifying indoleamine biosynthesis and the melatonin:serotonin balance contributing to its effects on plant morphogenesis, and that tryptophan also functions as an inductive signal to mediate diverse…”

Erland et al. · From the abstract

Names both L-Tryptophan and St. John's Wort in its title.

Hypericum Perforatum Decreased Hippocampus TNF-α and Corticosterone Levels with No Effect on Kynurenine/Tryptophan Ratio in Bilateral Ovariectomized Rats.

The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2014 · PMID 24976763

“It is concluded that increased tryptophan metabolism toward kynurenine secondary to elevated corticosterone and TNF-α might be one of the pathohphysiological mechanisms that could explain depression like state observed in this rat model. Further, the observed attenuating effect of HP on TNF-α and corticosterone could contribute in its antidepressant effect in this animal model by other ways than their effects on tryptophan-kynurenine metabolism pathway.”

El-Bakly et al. · From the abstract

Names both L-Tryptophan and St. John's Wort in its title.

Antidepressants for smoking cessation.

The Cochrane database of systematic reviews · 2014 · PMID 24402784

Meta-AnalysisResearch Support, N.I.H., ExtramuralSystematic ReviewHuman subjects

“The antidepressants bupropion and nortriptyline aid long-term smoking cessation. Adverse events with either medication appear to rarely be serious or lead to stopping medication. Evidence suggests that the mode of action of bupropion and nortriptyline is independent of their antidepressant effect and that they are of similar efficacy to nicotine replacement.”

Hughes et al. · Authors' conclusion

Names L-Tryptophan and St. John's Wort together in an interaction, co-administration, or pharmacokinetic context.

Interactions between herbal medicines and prescribed drugs: an updated systematic review.

Drugs · 2009 · PMID 19719333

Systematic ReviewHuman subjects

“Numerous interactions between herbal medicines and conventional drugs have been documented. While the significance of many interactions is uncertain, several interactions, particularly those with St John's wort, may have serious clinical consequences.”

Izzo et al. · From the abstract

Names L-Tryptophan and St. John's Wort together in an interaction, co-administration, or pharmacokinetic context.

Limitations

What this evidence cannot tell you.

Search-based evidence indexes have real limits, and it is worth being explicit about them:

NutriStack

Track what you actually take.

NutriStack is a free iPhone app for organising a supplement routine: what you take, when, and what the published record says about it. Its exploratory interaction checker covers L-Tryptophan, St. John's Wort, and several hundred other substances.

The checker is a research and organisation tool, not a clinical decision aid, and its per-pair assessments are excluded from search until they pass claim-level review.

NutriStack is an informational and organizational tool, not a medical service, and not a substitute for professional advice. Always consult a qualified healthcare professional before starting, stopping, or changing any supplement or medication.