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.
Objectives
Dietary supplements are increasingly used by people with osteoarthritis. Boswellia serrata extract, curcumin, pine bark extract and methylsulfonylmethane have been identified as having the largest effects for symptomatic relief in a systematic review. It is important to understand whether any pharmacokinetic interactions are among the major constituents of these supplements so as to provide information when considering the combination use of these supplements. The aim of this study was to investigate the pharmacokinetics of the constituents alone and in combination.
Methods
This study was a randomized, open‐label, single‐dose, four‐treatment, four‐period, crossover study with 1‐week washout. The pharmacokinetics of the constituents of these supplements when dosed in combination with methylsulfonylmethane were compared to being administered alone. Plasma samples were obtained over 24 h from 16 healthy participants. Eight major constituents were analysed using a validated ultra‐high‐performance liquid chromatography–tandem mass spectrometry assay.
Key findings
The pharmacokinetics of each constituent was characterized, and there were no significant differences in the pharmacokinetic profiles of the constituents when administered as a combination, relative to the constituents when administered alone (P > 0.05).
Conclusions
These data suggest that interactions between the major constituents of this supplement combination are unlikely and therefore could be investigated to manage patients with osteoarthritis without significant concerns for possible pharmacokinetic interactions.
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