BEWARE DRUG INTERACTIONS WITH DIETARY SUPPLEMENTS

The widespread use of dietary supplements may be even (and substantially) higher among those with established medical conditions. Evidence suggests that 67% of patients with cancer and 77% of patients with osteoporosis take supplements.^[1] About one third (34%) of people who take a prescription medication also take at least one dietary supplement, a rate that increases to 61% in adults older than 60 years.^[1] It is in these populations where the greatest concern is warranted, given the risk for potential drug-supplement interactions. Identifying and managing them can be a challenge, however, as most patients do not voluntarily report their use of dietary supplements, and few supplements have documented clinical evidence of such interactions.

Pharmacodynamic Interactions 

In some cases, supplements have pharmacologic effects similar to those of drugs prescribed to patients. Adding a supplement may then result in increased side effects of the drug in the form of pharmacodynamic interactions (Table 1). For example, several supplements marketed for diabetes or blood sugar control have hypoglycemic effects. Combining these with conventional diabetes drugs may increase the risk for hypoglycemia.

How meaningful or severe the interaction potentially is depends on the doses taken, supplement product–specific factors (eg, form of product or type of extract), and patient-specific factors. Proper management often requires discontinuing the supplement or decreasing the conventional drug dose.

Although potential pharmacodynamic interactions can be identified when supplements are used for the same medical condition as a prescribed drug, they also can occur when supplements are used for other conditions. For example, glucosamine and turmeric are frequently used for osteoarthritis but can interact with drugs such as anticoagulants, which are used for other indications.

The widespread use of dietary supplements may be even (and substantially) higher among those with established medical conditions. Evidence suggests that 67% of patients with cancer and 77% of patients with osteoporosis take supplements.^[1] About one third (34%) of people who take a prescription medication also take at least one dietary supplement, a rate that increases to 61% in adults older than 60 years.^[1] It is in these populations where the greatest concern is warranted, given the risk for potential drug-supplement interactions. Identifying and managing them can be a challenge, however, as most patients do not voluntarily report their use of dietary supplements, and few supplements have documented clinical evidence of such interactions.

Pharmacodynamic Interactions 

In some cases, supplements have pharmacologic effects similar to those of drugs prescribed to patients. Adding a supplement may then result in increased side effects of the drug in the form of pharmacodynamic interactions (Table 1). For example, several supplements marketed for diabetes or blood sugar control have hypoglycemic effects. Combining these with conventional diabetes drugs may increase the risk for hypoglycemia.

How meaningful or severe the interaction potentially is depends on the doses taken, supplement product–specific factors (eg, form of product or type of extract), and patient-specific factors. Proper management often requires discontinuing the supplement or decreasing the conventional drug dose.

Although potential pharmacodynamic interactions can be identified when supplements are used for the same medical condition as a prescribed drug, they also can occur when supplements are used for other conditions. For example, glucosamine and turmeric are frequently used for osteoarthritis but can interact with drugs such as anticoagulants, which are used for other indications.

Pharmacokinetic Interactions

Identifying potential pharmacokinetic interactions between supplements and drugs (Table 2) is more challenging than identifying pharmacodynamic interactions. Pharmacokinetic interactions occur when the absorption, distribution, metabolism, or elimination of a drug is altered. These interactions typically occur when drug-metabolizing cytochrome P450 (CYP) enzymes are inhibited or induced. This may result in increased or decreased drug levels. Interactions also can occur from alterations of drug transport proteins (eg, P-glycoprotein or organic anion transporting polypeptide) or from physical drug binding in the gastrointestinal tract.

Over 100 different supplement ingredients have been found to affect CYP enzymes, but much of this research is based on in vitro or animal studies.^[9]Although these data raise red flags about the potential for interactions, such preclinical findings often do not accurately predict what happens when a supplement is ingested by humans.^[10] Relatively few supplements have human data confirming clinical meaningful interactions with drugs.

Most documented pharmacokinetic drug-supplement interactions involve the CYP3A4 or CYP2D6 enzymes. For patients who are taking drugs metabolized by these enzymes, checking for potential interactions with supplements is warranted.

Narrow Therapeutic Index Drugs

Small changes in the systemic levels of narrow therapeutic index drugs, such as warfarin, lithium, digoxin, theophylline, and carbamazepine, can result in increased side effects or ineffectiveness. Therefore, adding supplements is much more likely to result in clinically significant negative interactions. Extra caution is advised for patients who are prescribed these drugs and wish to take dietary supplements.