The effect of St John’s wort extracts on CYP3A: a systematic review of prospective clinical trials

Abstract

AimThe aim of this systematic review was to assess the quality and outcomes of clinical trials investigating the effect of St John's wort extracts on the metabolism of drugs by CYP3A. MethodsProspective clinical trials assessing the effect of St John's wor t (SJW) extracts on metabolism by CYP3A were identified through computer-based searches (from their inception to May 2005) of Medline, Cinahl, PsycINFO, AMED, Current Contents and Embase, hand-searches of bibliographies of relevant papers and consultation with manufacturers and researchers in the field. Two reviewers selected trials for inclusion, independently extracted data and recorded details on study design. ResultsThirty-one studies met the eligibility criteria. More than two-thirds of the studies employed a before-and-after design, less than one-third of the studies used a crossover design, and only three studies were double-blind and placebo controlled. In 12 studies the SJW extract had been assayed, and 14 studies stated the specific SJW extract used. Results from 26 studies, including all of the 19 studies that used high-dose hyperforin extracts ( > 10 mg day − 1 ), had outcomes consistent with CYP3A induction. The three studies using low-dose hyperforin extracts ( < 4 mg day − 1 ) demonstrated no significant effect on CYP3A. ConclusionThere is reasonable evidence to suggest that high-dose hyper forin SJW extracts induce CYP3A. More studies are required to determine whether decreased CYP3A induction occurs after low-dose hyperforin extracts. Future studies should adopt study designs with a control phase or control group, identify the specific SJW extract employed and provide quantitative analyses of key constituents.

Reversal of NO-induced nociceptive hypersensitivity by St. John’s wort and hypericin: NF-κB, CREB and STAT1 as molecular targets

“…Recently, interactions of SJW with prescription drugs have been reported. SJW, at the dose recommended for the treatment of mild to moderate depression, is a potent inducer of cytochrome P450 enzymes resulting in decrease plasma concentration of a number of drugs used in co-medication (Whitten et al 2006). Recent studies show that the degree of enzyme induction by SJW correlates strongly with the amount of hyperforin found in the product.…”

“…Recent studies show that the degree of enzyme induction by SJW correlates strongly with the amount of hyperforin found in the product. High-dose hyperforin extracts (>10 mgday −1 ) had outcomes consistent with CYP3A induction whereas low-dose hyperforin extracts (<4 mgday −1 ) demonstrated no significant effect on CYP3A (Whitten et al 2006;Madabushi et al 2006). We observed that SJW reduced NO induced nociceptive behavior at very low doses containing an amount of hyperforin (0.21 mg) unable to produce clinical significant interactions.…”

No clinically relevant CYP3A induction after St. John’s wort with low hyperforin content in healthy volunteers

“…Clinically relevant drug interactions of Hypericum extracts have been reported in several case reports and drug interaction studies and have been systematically reviewed [12,13]. The underlying mechanism is an induction of mainly intestinal CYP3A and p-glycoprotein [14] leading to decreased plasma concentration and potential therapeutic failure of substrates of CYP3A and p-glycoprotein.…”

“…As reviewed by Whitten et al [12] and Madabushi et al [6], most clinical studies investigating drug interactions by St. John's wort in general and specifically CYP3A induction used St. John's wort extracts with high hyperforin content. While the studies using hyperforin-rich St. John's wort extracts consistently reported clinically relevant interaction consistent with CYP3A induction, only a few studies with extracts with low hyperforin content have been performed [6,12].…”

“…The hyperforin content of 33 different Hypericum products marketed in Germany ranged from <0.5 to 24.87 mg per unit [5][6][7][8][9]. Clinical efficacy has been demonstrated in St. John's wort extracts with high hyperforin content but also in those with negligible hyperforin content [10][11][12].…”