KEY POINTS
■ Dietary supplements are commonly used by US adults, but many adults who took a dietary supplement concurrently with a prescription medication did not inform their health care professional of such use.
■ Although the number of potential interactions is high, the number of observed interactions is relatively low. This is likely because of underreporting and a lack of awareness. It may also indicate that theoretical interactions do not always manifest clinically.
■ Of significant concern to clinicians is the interaction between medications that prolong bleeding time, either directly or as an adverse effect, and dietary supplements that potentiate or inhibit such medications.
■ When prescribing medications to a patient who has reported use of dietary supplements, access a peer-reviewed electronic database to check for dietary supplement-drug interactions.
As defined by the Dietary Supplement Health Education Act of 1994, a
dietary supplement
is any of the following: vitamin, mineral, herb or botanical, amino acid, enzyme, organ tissues, glandular substance, metabolites, or other "dietary ingredient" (eg, essential fatty acid, lycopene, probiotic).
1 Dietary supplements do not include homeopathic remedies, which are regulated separately by the FDA.
Dietary supplements are commonly used by adults in the United States. According to the 2007 National Health Interview Survey (NHIS), 17.7% of adults had taken a nonvitamin, nonmineral product in the previous 12 months.2 The 2002 NHIS found that 19% of adults had used an herbal product in the prior 12 months.3 A survey of patients attending six specialty clinics at the Mayo Clinic found that an average of 39.6% used dietary supplements; usage ranged from 32% in the physical medicine clinic to 51% in the fibromyalgia clinic.4
The number of older adults who take a dietary supplement concurrently with a prescription medication is significant. Interviews of 3,005 community-dwelling adults aged 57 to 85 years in the National Social Life, Health and Aging Project (NSHAP) revealed that 52% took at least one dietary supplement concurrently with a prescription medication.5 An analysis of 3,070 ambulatory adults aged 75 years and older who were enrolled in the Ginkgo Evaluation of Memory Study found that 74% used at least one dietary supplement concurrently with one or more prescription medications.6
The rate of disclosure of dietary supplement use to conventional health care providers is low. Sixty-nine percent of adults who took a dietary supplement concurrently with a prescription medication in the previous 12 months did not inform their conventional health care professional of such use.7 Considering the ubiquity of dietary supplement use and the lack of disclosure by patients, the potential for significant interactions between dietary supplements and prescription medications is an important issue for clinicians to consider with each patient encounter.
REPORTS OF DIETARY SUPPLEMENT-DRUG
INTERACTIONS
The number of reported dietary supplement-drug interactions is low. A chart review of 804 outpatients attending six clinics associated with the Santa Clara Valley Medical Center in California found that 6% had taken a supplement and a drug that had the potential for an adverse interaction; 1% had an observed adverse interaction that was rated as mild in severity.8 When the analysis was limited to those patients who used herbs rather than any other type of supplement, the observed adverse interaction rate was 7%.8 A 1-year prospective surveillance study conducted at the San Francisco division of the California Poison Control System determined that 2% of calls related to dietary supplements were likely attributable to dietary supplement-drug interactions.9 In the previously described Mayo Clinic survey, 29% of potential dietary supplement-drug interactions (N = 369) were identified as clinically significant; 68% of those involved garlic, ginkgo, kava, St. John's wort, or valerian.4 Although the number of potential interactions is high, the number of observed interactions is relatively low. This difference is likely the result of underreporting or a lack of awareness. It may also indicate that theoretical interactions do not always manifest clinically.
Adverse dietary supplement-drug interactions are reported in several ways: (1) as case reports, (2) as surveillance data that are part of a clinical trial, (3) as in vitro and in vivo experimental data, and (4) as a clinical trial in healthy subjects. The interactions are also described in terms of pharmacodynamic and pharmacokinetic processes. Because dietary supplement-drug interactions are reported in so many ways, health care professionals may find themselves faced with conflicting information.
Of significant concern to clinicians is the interaction between medications that prolong bleeding time, either directly or as an adverse effect, and dietary supplements that potentiate or inhibit such medications. Reports of the effects of garlic and ginkgo on bleeding time are examples of the contradictory information that clinicians encounter in daily practice. Garlic, the third highest-selling herbal supplement in 2008, is noted to have antiplatelet, antithrombotic, and fibrinolytic activity.10,11 A 51-year-old male who consumed 1,200 mg of aged garlic per day and no other drugs developed a kidney hematoma after undergoing extracorporeal shock wave lithotripsy (ESWL).12 Ginkgo, the fifth highest-selling herbal supplement in 2008, inhibits platelet activating factor (PAF).10,13 Spontaneous bleeding and a prolonged bleeding time of greater than 15 minutes were reported in a 73-year-old male who consumed 75 mg/day of a standardized extract of ginkgo. The bleeding and prolonged bleeding time resolved with discontinuation of the supplement.14 Given the mechanisms of action of garlic and ginkgo, the prolonged bleeding and hemorrhage seen in these patients were likely a result of their consuming those supplements.
EVIDENCE FROM PHARMACODYNAMIC STUDIES
In contrast to the case reports, an in vivo PFA-100 assay of platelet function in 10 healthy adults found that consumption of GNC brand garlic or ginkgo herbal product for 2 weeks had no effect on platelet function.15 Another study, a randomized, double-blind, placebo-controlled trial, looked at the use of Ginkgo biloba (EGb 761) at a dose of 300 mg/day combined with aspirin at 325 mg/day for 4 weeks in 60 adults with peripheral arterial disease. Results showed that compared with the use of aspirin alone, ginkgo had no additive effect on platelet function.16