NutriStack
Dexamethasone and St. John's Wort, a conflict.
St. John's Wort can induce CYP3A4, and dexamethasone exposure is strongly affected by CYP3A4 activity. Taking St. John's Wort during dexamethasone therapy may lower steroid exposure and reduce the intended anti-inflammatory, antiemetic, or immunosuppressive effect.
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
- Dexamethasone and St. John's Wort
- Pair type
- Conflict
- Evidence (highest tier)
- Moderate
- Source citations
- 2 sources
- Stack Score effect
- −10 to your Stack Score (per scored conflict row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Conflict · Moderate evidence
Conflict
What is happening. St. John's Wort can induce CYP3A4, and dexamethasone exposure is strongly affected by CYP3A4 activity. Taking St. John's Wort during dexamethasone therapy may lower steroid exposure and reduce the intended anti-inflammatory, antiemetic, or immunosuppressive effect.
Mechanism. High-hyperforin St. John's Wort induces CYP3A4 expression and activity. Dexamethasone is metabolized by CYP3A4, so induction can plausibly increase dexamethasone clearance and lower exposure.
Recommendation. Avoid St. John's Wort while dexamethasone effect is clinically important unless your prescriber specifically approves. Tell your clinician if you recently started or stopped St. John's Wort because steroid response may change over days to weeks.
Sources (2)
- Whitten DL, Myers SP, Hawrelak JA, Wohlmuth H. The effect of St John's wort extracts on CYP3A: a systematic review of prospective clinical trials. Br J Clin Pharmacol. 2006;62(5):512-526. PMID 17010103
- Varis T, Kivisto KT, Backman JT, Neuvonen PJ. The cytochrome P450 3A4 inhibitor itraconazole markedly increases the plasma concentrations of dexamethasone and enhances its adrenal-suppressant effect. Clin Pharmacol Ther. 2000;68(5):487-494. PMID 11103751
Stack Score
How this pair moves the number.
Effect on the composite score
If both Dexamethasone and St. John's Wort are in the same stack, this pair applies −10 to your Stack Score (per scored conflict row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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