The Effects of Cruciferous Vegetable‐Enriched Diets on Drug Metabolism: A Systematic Review and Meta‐Analysis of Dietary Intervention Trials in Humans

Abstract

Relatively few studies exist in the literature that discuss the effects of diet on drug metabolism and how this can affect interindividual differences in systemic drug exposure. Several studies have investigated the effects of cruciferous vegetables (Cruciferae) or their constituents on drug‐metabolizing activity, as these vegetables form an important part of many peoples’ diets. In general, the ingestion of cruciferous vegetables is associated with induction of cytochrome P450 (CYP) 1A2 activity in vivo; however, there is contention between reports, and the clinical significance of potential diet–drug interactions remains unclear. This study reports a systematic review, critical appraisal, and meta‐analysis of the published literature in this area, and discusses the clinical significance of Cruciferae‐enriched diets in the context of diet–drug interactions. Twenty‐three dietary intervention trials with drug metabolism end points were identified across Embase, Medline, and the Cochrane Controlled Register of Trials (CENTRAL). Cruciferous vegetables represented in the literature included broccoli, Brussels sprout, cabbage, cauliflower, radish, and watercress. A range of phase I and II drug‐metabolizing enzymes and phenotyping metrics were represented in the literature. The meta‐analyses performed demonstrated a significant effect on CYP1A2 and glutathione S‐transferase‐alpha (GST‐α), with consumption of Cruciferae increasing the activities of these enzymes by 20–40% and 15–35%, respectively. The results herein suggest that patients undergoing pharmacotherapy with CYP1A2 or GST‐α substrates could have altered drug exposure profiles if they regularly eat large or variable amounts of cruciferous vegetables. Recommendations regarding the design of future randomized, controlled trials to test hypotheses in this area are included.

Complementary and alternative medicine (CAM) supplements in cancer outpatients: analyses of usage and of interaction risks with cancer treatment

“…Hypokalemia is reported (Baretta et al 2009 ; Guo and Mei 2016 ). Due to the laxative effect, a changed absorption of orally applied anticancer medication is also conceivable Unlikely: Plasma levels probably too low to achieve relevant potential inhibition of CYP2D6 or CYP3A4 (Djuv and Nilsen 2012 ) Angocin Nasturtium and horseradish root Unlikely Beetroot See: Calcium, vitamin C Possible: Reduction in effects of anthracyclines and other regimes by antioxidative action of betanin (Nestora et al 2016 ) Brazil nuts Unlikely Broccoli Likely: Reduction in effects of cisplatin by GST-α induction (Allocati et al 2018 ; Eagles et al 2020 ) Possible: Reduction in effects of other regimes through GST modulation and e.g., resulting conferring of resistance to chemotherapy (Allocati et al 2018 ) Possible: Reduction in effects of anthracyclines and other regimes by antioxidative action of sulphoraphane (Ferreira et al 2018 ; Zeller et al 2013 ) Chinese herbs mixtures Likely: Cytochrome (CYP) interactions (Zeller et al 2013 ) depending on the different ingredients Likely: Interactions with endocrine therapy by phytoestrogens (Zeller et al 2013 ) Possible: Other interactions (Zeller et al 2013 ) depending on the different ingredients Curcuma longa Possible: Interactions by multiple cytochrome (CYP) effects and an inhibition of Pgp (Al-Jenoobi et al 2015 ; Cho and Yoon 2015 ; Volak et al 2008 ) Possible: Interactions with immunotherapy by multiple effects on the immune system and immunosuppressive action (Fahey et al 2007 ; Kang et al 1999 ; Skyvalidas et al 2020 ) Possible: Reduced chemotherapy-induced apoptosis in cancer cells for camptothecin, cyclophosphamide, doxorubicin, mechlorethamine (Somasundaram et al 2002 ), and other regimes by antioxidative effects * * Due to the broad spectrum of interactions, especially due to antioxidative action, interactions with other chemotherapeutic agents than with the regimes investigated so far also seem possible Garlic …”

“…Likely: Reduction in effects of cisplatin by GST-α induction (Allocati et al 2018 ; Eagles et al 2020 )…”

“…Yet, the use of individual parameters as predictors of CAM usage should be treated with caution. Calculated effect sizes, when indicated, were small and the models could only explain a small part between 6 and 26% of the difference between the groups of CAM users and non-CAM Likely: Reduction in effects of cisplatin by GST-α induction (Allocati et al 2018;Eagles et al 2020) Possible: Reduction in effects of other regimes through GST modulation and e.g., resulting conferring of resistance to chemotherapy (Allocati et al 2018) Possible: Reduction in effects of anthracyclines and other regimes by antioxidative action of sulphoraphane (Ferreira et al 2018;Zeller et al 2013) Chinese herbs mixtures Likely: Cytochrome (CYP) interactions (Zeller et al 2013) depending on the different ingredients Likely: Interactions with endocrine therapy by phytoestrogens (Zeller et al 2013) Possible: Other interactions (Zeller et al 2013) depending on the different ingredients -Jenoobi et al 2015;Cho and Yoon 2015;Volak et al 2008) Possible: Interactions with immunotherapy by multiple effects on the immune system and immunosuppressive action (Fahey et al 2007;Kang et al 1999;Skyvalidas et al 2020) Possible: Reduced chemotherapy-induced apoptosis in cancer cells for camptothecin, cyclophosphamide, doxorubicin, mechlorethamine (Somasundaram et al 2002), and other regimes by antioxidative effects * * Due to the broad spectrum of interactions, especially due to antioxidative action, interactions with other chemotherapeutic agents than with the regimes investigated so far also seem possible Garlic Possible: Interactions with bortezomib (CYP1A2), cisplatin (CYP2E1), and others by inhibition of CYP1A2, CYP2C9, and CYP2E1 (Cho and Yoon 2015;Foster et al 2001;Ho et al 2010;JANS-SEN-CILAG INTERNATIONAL NV 2019;Lu and Cederbaum 2006;Quintanilha et al 2017) Unlikely: Effects on Pgp, if existing, are rated as very low (Cho and Yoon 2015;Foster et al 2001). No interactions regarding CYP2D6 or CYP3A4 (Cox et al 2006;Markowitz et al 2003) Ginger…”

Green sweet potato leaves increase Nrf2-mediated antioxidant activity and facilitate benzo[a]pyrene metabolism in the liver by increasing phase II detoxifying enzyme activities in rats

“…It has been demonstrated that the consumption of large amounts of cruciferous vegetables, such as broccoli, Brussels sprouts, cabbage, cauliflower, and radishes, can induce CYP1A2 and glutathione S-transferase-alpha (GST-α) in humans, 30 which may have chemopreventive effects against chemical or toxic compound-induced cell damage and carcinogenesis. However, the effects of SPL consumption on hepatic detoxification systems have not been reported.…”

Interest of Fluvoxamine as an Add-On to Clozapine in Children With Severe Psychiatric Disorder According to CYP Polymorphisms: Experience From a Case Series

“…The targeted clozapine plasma level was 350 ng/mL (55). If the clozapine plasma level was under 350 ng/mL, we systematically searched for all possible causes of low clozapine plasma level such as poor compliance, inflammatory syndrome, tobacco or caffeine consumption, drug (phenytoin, carbamazepine, and rifampicin), and food (char-grilled meat and cruciferous vegetables such as cabbage, Brussels sprouts, turnips, spinach, or broccoli), all known for their possible interaction leading to enzyme induction (55)(56)(57)(58)(59). After eliminating these causes, we performed pharmacogenetics testing for CYP.…”