Foods and Nutrients That Interact with Medications by Altering the Function of Metabolism and/or Transport Pathways

Clinicians are trained to review prescription drugs with patients during their clinic visits and hospital admissions. However, less emphasis is placed on appropriate review and documentation of foods and nutrients that are known or suspected to interact with medications. This scenario places kidney disease patients at significant risk, given the 10 to 12 different medications that are typically prescribed (1). Although the clinician’s time is a limiting factor in conducting nutrient reviews, an even greater problem is the lack of knowledge by clinicians of what nutrients can interact with which drugs and the mechanisms for the interactions. The purpose of this article is to inform clinicians caring for patients with kidney disease by providing a concise overview of nutrients—defined as vitamins, minerals, herbs, and food supplements—that can interact with prescribed medications.

When patients purchase prescription medications from a retail or mail-order pharmacy, either they are counseled by a pharmacist or they receive medication information handouts that address drug–drug interactions. However, patients who purchase over-the-counter nutrients are not counseled by a professional with training about the interactions between nutrients and medications. Further complicating the clinical scenario is the lack of dose standardization between the various over-the-counter nutrient products. Patients are also unaware of the safety issues related to nutrients, such as co-contamination with drugs or toxins. Recent reports suggest that approximately one-third of patients who are prescribed medications consume over-the-counter nutrients, demonstrating the need to understand and screen for potential drug–nutrient interactions (2).

The common understanding of nutrient interactions with drugs is usually limited to warfarin, whereby patients are counseled about the need to maintain the same daily amount of green leafy vegetables in their diet to limit fluctuations in the international normalized ratio. This fairly well-known interaction is secondary to increases in the amount of vitamin K substrate available for blood clotting. The interaction between warfarin and green leafy vegetables is well known to clinicians, and this information is usually forwarded to patients taking warfarin.

Beyond warfarin, clinicians have limited knowledge regarding drug–nutrient interactions and the mechanisms of these interactions. Although several mechanisms can account for drug–nutrient interactions, the remainder of this article will focus on the interactions known to occur with the drug disposition pathways of metabolism and transport.

The liver and kidney are the primary organs for drug metabolism. Mechanistically, nutrients can alter the function of drug-metabolizing enzymes and transporters (39). Nutrients can cause induction or inhibition of metabolizing enzymes, leading to reduced or increased activity, respectively, of victim drugs. Common drug metabolizing enzymes are cytochrome P450s, glutathione S-transferases, and uridine diphosphate glucuronosyltransferases. Transporters move drugs across membranes and are commonly found in the liver, kidney, and intestine. Common drug transporters are P-glycoprotein and organic anion transporting polypeptides. Induction and inhibition of transporters by nutrients can occur. However, the effect on transport of the victim drug is dependent on whether uptake or efflux transporters are affected. For uptake transporters, induction would increase and inhibition would decrease intracellular drug exposures. For efflux transporters, induction would decrease and inhibition would increase drug intracellular exposures. Intestinal absorption is a special transport case whereby enhanced efflux from inside the enterocyte interior and back to the intestinal lumen leads to decreased absorption.

Metabolism and transport pathways often work in concert, whereby increased transport uptake function and decreased efflux function would enable the enhanced presence of drug available to intracellular metabolizing enzymes. Some examples of induction and inhibition of drug metabolism and transport pathways by nutrients are provided in Table 1 (39). Although the table primarily includes interactions that have been specifically assessed, the reader is cautioned that extensive studies documenting all the victim drugs that could be affected by each nutrient have not been conducted.

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Drug–nutrient interactions in patients with kidney diseases require extensive study secondary to the number of medications prescribed to these patients. Evolving literature also suggests changes to drug metabolism and transport function secondary to kidney diseases per se (10, 11). The triad of polypharmacy, altered function of drug disposition pathways, and ingestion of over-the-counter nutrients with potential for drug interaction predisposes patients with kidney disease to adverse reactions and outcomes. More emphasis on screening and education of kidney disease patients regarding potential drug–nutrient interactions is needed.

Notes

[1] Melanie S. Joy, PharmD, PhD, is affiliated with the University of Colorado School of Pharmacy and Pharmaceutical Sciences and School of Medicine in Aurora, CO.

References

1. Manley HJ, et al. Medication prescribing patterns in ambulatory haemodialysis patients: comparisons of USRDS to a large not-for-profit dialysis provider. Nephrol Dial Transplant 2004; 19:1842–1848.

2. Gardiner P, et al. Factors associated with dietary supplement use among prescription medication users. Arch Intern Med 2006; 166:1968–1974.

3. Detampel P, et al. Drug interaction potential of resveratrol. Drug Metab Rev 2012; 44:253–265.

4. Gurley BJ. Pharmacokinetic herb-drug interactions (part 1): origins, mechanisms, and the impact of botanical dietary supplements. Planta Med 2012; 78:1478–1489.

5. Gurley BJ, et al. Pharmacokinetic herb-drug interactions (part 2): drug interactions involving popular botanical dietary supplements and their clinical relevance. Planta Med 2012; 78:1490–1514.

6. Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs 2009; 69:1777–1798.

7. Li Y, Paxton JW. The effects of flavonoids on the ABC transporters: consequences for the pharmacokinetics of substrate drugs. Expert Opin Drug Metab Toxicol 2013; 9:267–285.

8. Nakamura Y, et al. Zerumbone, a tropical ginger sesquiterpene, activates phase II drug metabolizing enzymes. FEBS Lett 2004; 572:245–250.

9. Zhang W, Lim LY. Effects of spice constituents on P-glycoprotein-mediated transport and CYP3A4-mediated metabolism in vitro. Drug Metab Dispos 2008; 36:1283–1290.

10. Joy MS, et al. In vivo alterations in drug metabolism and transport pathways in patients with chronic kidney diseases. Pharmacotherapy 2013; 34:114–122.

11. Nolin TD, et al. Emerging evidence of the impact of kidney disease on drug metabolism and transport. Clin Pharmacol Ther 2008; 83:898–903.


May 2014 (Vol. 6, Number 5)