NutriStack
Losartan and St. John's Wort, a conflict.
Losartan is a prodrug metabolized by CYP2C9 and CYP3A4 to its active metabolite E-3174, which is 10-40 times more potent than the parent compound. St. John's Wort induces CYP3A4 and potentially CYP2C9, which could accelerate losartan metabolism. However, because St. John's Wort induces the activating enzymes, it could paradoxically either increase or decrease the active metabolite, making the net clinical effect unpredictable and warranting caution.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
Same shape as the other 1,729 pairs in the public database.
From the interaction database
What the row says.
Every entry follows the same shape: what is happening, the mechanism, the recommendation, and the primary literature.
At a glance
- Substances
- Losartan and St. John's Wort
- Pair type
- Conflict
- Evidence (highest tier)
- Moderate
- Source citations
- 3 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. Losartan is a prodrug metabolized by CYP2C9 and CYP3A4 to its active metabolite E-3174, which is 10-40 times more potent than the parent compound. St. John's Wort induces CYP3A4 and potentially CYP2C9, which could accelerate losartan metabolism. However, because St. John's Wort induces the activating enzymes, it could paradoxically either increase or decrease the active metabolite, making the net clinical effect unpredictable and warranting caution.
Mechanism. Hyperforin in St. John's Wort induces CYP3A4 via PXR activation and may induce CYP2C9 (evidence conflicting). Losartan requires CYP2C9 and CYP3A4 for conversion to active E-3174 metabolite. Enzyme induction may alter the balance between parent drug and active metabolite formation versus elimination, making the clinical outcome unpredictable.
Recommendation. Avoid combining St. John's Wort with losartan. The unpredictable effect on losartan's activation pathway makes monitoring difficult. If blood pressure control deteriorates, consider St. John's Wort as a possible cause. Allow 10-14 days for enzyme induction effects to develop or resolve.
Sources (3)
- Zhou SF et al. Herb-drug interactions with St John's Wort (Hypericum perforatum): an update on clinical observations. AAPS J. 2004;6(4):e34. PMID 15760089
- Stearns V et al. Common herbal dietary supplement-drug interactions. Am Fam Physician. 2017;96(2):101-107. PMID 28762701
- Xie M, Tang T, Liang H. Efficacy of single-pill combination in uncontrolled essential hypertension: A systematic review and network meta-analysis. Clinical Cardiology. 2023. PMID 37432701
Stack Score
How this pair moves the number.
Effect on the composite score
If both Losartan 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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