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

Clin Pharmacol Ther. 2020 Aug;108(2):212-227. doi: 10.1002/cpt.1811. Epub 2020 Mar 25.

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Brassicaceae* / adverse effects
  • Clinical Trials as Topic
  • Cytochrome P-450 CYP1A2 / metabolism
  • Diet* / adverse effects
  • Food-Drug Interactions*
  • Glutathione Transferase / metabolism
  • Humans
  • Isoenzymes / metabolism
  • Metabolic Detoxication, Phase I
  • Metabolic Detoxication, Phase II
  • Nutritive Value
  • Pharmaceutical Preparations / metabolism*
  • Risk Assessment
  • Risk Factors
  • Substrate Specificity
  • Vegetables* / adverse effects

Substances

  • Isoenzymes
  • Pharmaceutical Preparations
  • CYP1A2 protein, human
  • Cytochrome P-450 CYP1A2
  • Glutathione Transferase
  • glutathione S-transferase alpha