(See also Complementary and Alternative Medicine.)

Dietary supplements are the most commonly used of all complementary and alternative therapies, primarily because they are widely available and can be bought without consulting a health care practitioner.

The FDA regulates dietary supplements differently from drugs. The FDA regulates only quality control and good manufacturing processes but does not ensure standardization of the active ingredients or efficacy.

Definition

The Dietary Supplement Health Education Act (DSHEA) of 1994 defines a dietary supplement as

• Any product (except tobacco)—in pill, capsule, tablet, or liquid form—containing a vitamin, mineral, herb or other plant product, amino acid, or other known dietary substance that is intended as a supplement to the normal diet

In addition, certain hormones, such as dehydroepiandrosterone (DHEA, a precursor to androgens and estrogens) and melatonin, are regulated as dietary supplements and not as prescription drugs.

Labeling

The DSHEA requires that the product label identify the product as a dietary supplement and notify the consumer that the claims for the supplement have not been evaluated by the FDA. The label must also list each ingredient by name, quantity, and total weight and identify plant parts from which ingredients are derived (see the DSHEA legislation at www.fda.gov/RegulatoryInformation/Legislation/default.htm). Manufacturers are permitted to make claims about the product's structure and function (eg, good for urinary tract health) but cannot make or imply claims for the product as a drug or therapy (eg, treats UTIs).

Safety and efficacy

Most people who use dietary supplements assume that they are good for health generally, are safe and effective for treating specific conditions, or both because dietary supplements are natural (ie, derived from plants or animals) and because some are supported by centuries of use in traditional systems of medicine. However, the FDA does not require manufacturers of dietary supplements to prove safety or efficacy (although supplements must have a history of safety). Most supplements have not been rigorously studied. For most, evidence suggesting safety or efficacy comes from traditional use, in vitro studies, certain case reports, and animal studies. However, manufacturers and distributors of supplements now must report serious adverse events to the FDA through the MedWatch system. There are a few supplements (eg, fish oil, chondroitin/glucosamine, saw palmetto) now proved to be safe and useful complements to standard drugs.

Evidence concerning the safety and efficacy of dietary supplements is increasing rapidly as more and more clinically based studies are being done. Information about such studies is available at the National Institutes of Health's National Center for Complementary and Alternative Medicine (NCCAM) web site (nccam.nih.gov/research/clinicaltrials).

Purity and standardization

Lack of regulation and government monitoring also means that supplements are not monitored to ensure that they contain the ingredients or amount of active ingredient the manufacturer claims they contain. The supplement may have unlisted ingredients, which may be inert or harmful (eg, natural toxins, bacteria, pesticides, lead or other heavy metals), or it may contain variable amounts of active ingredients, especially when whole herbs are ground or made into extracts. Consumers are at risk of getting less, more, or, in some cases, none of the active ingredient, if the active ingredient is even known. Most herbal products are mixtures of several substances, and which ingredient is the most active is not always known. The lack of standardization means not only that products from different manufacturers may vary, but also that different batches produced by the same manufacturer may differ. This product variability is a particular source of difficulty in conducting rigorous scientific trials and comparing the results among different trials. However, some supplements have been standardized and may include a designation of standardization on the label.

New regulations governing supplement production in the US include rules for Good Manufacturing Practices (GMPs). These rules strengthen standards for keeping manufacturing facilities and equipment clean and raw materials pure and uncontaminated. GMPs also ensure proper labeling, packaging, and storage of the finished product.

Other concerns

Additional areas of concern include

• Use of dietary supplements instead of conventional drugs
• Stability of supplements (especially herbal products) once manufactured
• Toxicity
• Interactions between supplements and drugs

Most information about these concerns comes from sporadic individual reports (see Table 1: Dietary Supplements: Some Possible Dietary Supplement–Drug Interactions*) and some references.

Despite these concerns, many patients strongly believe in the benefits of supplements and continue to use them with or without a physician's involvement. Patients may not think to disclose or may wish to conceal their use of dietary supplements. For this reason, the outpatient history should periodically include explicit questions about past and new use of complementary and alternative therapies, including dietary supplements. Many physicians incorporate some supplement use into their practice; their reasons include proven benefit of the supplement, a desire to ensure that supplements are used safely by patients who will use supplements anyway, and the physician's belief that the supplements are safe and effective. There are few data to guide patient counseling regarding supplement safety. But some experts believe that the overall number of problems due to dietary supplements is rare compared with the overall number of doses taken and that the supplement, if correctly manufactured, is likely to be safe. As a result, these experts advise purchase of supplements from a well-known manufacturer, and many recommend buying supplements made in Germany because there they are regulated as drugs and thus oversight is stricter than in the US.

The following supplements are ones that are most popular, are effective, or have some questions about their safety. More complete information is available through the NCCAM web site (www.nccam.nih.gov/).

Table 1
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Some Possible Dietary Supplement–Drug Interactions* Dietary Supplement Affected Drugs Interaction Chamomile Barbiturates and other sedatives May intensify or prolong effects of sedatives because its volatile oils have additive effects Iron supplements May reduce iron absorption via tannins in the plant Warfarin May increase risk of bleeding because chamomile contains phytocoumarins, which may have additive effects Echinacea Potentially hepatotoxic drugs metabolized by cytochrome P-450 enzymes (eg, amiodarone, anabolic steroids, ketoconazole, methotrexate) May slow metabolism of these drugs and increase risk of hepatotoxicity if taken for > 8 wk Immunosuppressants (eg, corticosteroids, cyclosporine) May lessen immunosuppressive effects via T-cell stimulation Ephedra† Stimulant drugs (eg, caffeine, epinephrine, phenylpropanolamine, pseudoephedrine) Increases the stimulant effects of other drugs, increasing risk of irregular or rapid heartbeat and hypertension MAOIs May intensify effects of these drugs and increase risk of side effects (eg, headache, tremors, irregular or rapid heartbeat, hypertension) Feverfew Antimigraine drugs (eg, ergotamine—see Table 2: Headache: Some Characteristics of Headache Disorders by Cause) May increase heart rate and BP because it has additive vasoconstrictive effects Antiplatelet drugs May increase risk of bleeding because feverfew inhibits platelet aggregation (has additive effects) Iron supplements May reduce iron absorption via tannins in the plant NSAIDs Feverfew's efficacy in preventing and managing migraine headaches reduced by NSAIDs Warfarin May increase risk of bleeding because warfarin may have additive effects Garlic Antihypertensives May augment antihypertensive effect Antiplatelet drugs May increase risk of bleeding because these drugs negate garlic's inhibition of platelet aggregation and fibrinolytic effects Protease inhibitors (eg, saquinavir) Blood level of protease inhibitors reduced by garlic Warfarin May increase risk of bleeding by augmenting warfarin's anticoagulant effects Ginger Antiplatelet drugs May increase risk of bleeding by augmenting inhibition of platelet aggregation Warfarin May increase risk of bleeding by augmenting warfarin's anticoagulant effects Ginkgo Anticonvulsants (eg, phenytoin) May reduce efficacy of anticonvulsants because contaminants in ginkgo preparations may reduce anticonvulsant effects MAOIs (eg, tranylcypromine) May intensify effects of these drugs and increase risk of side effects (eg, headache, tremors, manic episodes) NSAIDs May increase risk of bleeding by augmenting inhibition of antiplatelet aggregation Warfarin May increase risk of bleeding by augmenting warfarin's anticoagulant effects Ginseng Antihyperglycemic drugs (eg, glipizide) May intensify effects of these drugs, causing hypoglycemia Aspirin and other NSAIDs May increase risk of bleeding by augmenting inhibition of antiplatelet aggregation Corticosteroids May intensify adverse effects of corticosteroids because ginseng has anti-inflammatory effects Digoxin May increase digoxin levels Estrogens May intensify adverse effects of estrogen MAOIs Can cause headache, tremors, and manic episodes Opioids May reduce the effectiveness of opioids Warfarin May increase risk of bleeding by augmenting warfarin's anticoagulant effects Goldenseal Warfarin and heparin May oppose effects of warfarin and heparin, increasing risk of thromboembolism Green tea Warfarin May reduce efficacy of warfarin, increasing risk of thromboembolism Kava Sedatives (eg, barbiturates, benzodiazepines) May intensify or prolong the effects of sedatives Licorice (glycyrriza glabra)‡ Antiarrhythmics May increase risk of an abnormal heart rhythm, making antiarrhythmic therapy less effective Antihypertensives May increase salt and water retention and increase BP, making antihypertensives less effective Digoxin May decrease levels of K, which increases risk of digoxin toxicity Diuretics May intensify the K-wasting effects of most diuretics and interfere with the effectiveness of K-sparing diuretics (eg, spironolactone) MAOIs May intensify effects of these drugs and increase risk of adverse effects (eg, headache, tremors, manic episodes) Milk thistle Antihyperglycemic drugs May intensify effects of these drugs, causing hypoglycemia Protease inhibitors (eg, indinavir, saquinavir) May interfere with metabolizing enzymes, lowering blood levels of indinavir Saw palmetto Estrogens (eg, oral contraceptives) May augment effects of these drugs St. John's wort Cyclosporine May reduce blood level of cyclosporine, increasing risk of organ transplant rejection Digoxin May reduce blood level of digoxin, making it less effective, with potentially dangerous results Iron supplements May reduce iron absorption MAOIs May augment effects of MAOIs, possibly causing very high BP requiring emergency treatment Nonnucleoside reverse transcriptase inhibitors Increases metabolism of these drugs, reducing their efficacy Oral contraceptives Increases metabolism of these drugs, reducing their efficacy Photosensitizing drugs (eg, lansoprazole, omeprazole, piroxicam, sulfonamide antibiotics) May increase sun sensitivity Protease inhibitors May reduce blood level of protease inhibitors, reducing their efficacy SSRIs (eg, fluoxetine, paroxetine, sertraline) May augment effects of these drugs Tricyclic antidepressants May augment effects of these drugs Warfarin May reduce blood level of warfarin, increasing risk of thromboembolism Valerian Sedatives (eg, barbiturates, benzodiazepines) May intensify effects of sedatives *Caution is required when dietary supplements are used because these products are not standardized and thus vary considerably and because information about their use is continually changing. The theoretical status of many published interactions does not obviate the need for cautious use. Before prescribing any drug, health care practitioners should ask patients whether they are taking dietary supplements and, if so, which ones. Practitioners must identify any potential adverse interactions of drugs and supplements taken by a patient and then determine appropriate drugs and dosages. †Sale of supplements containing ephedra is banned in the US. ‡This substance is true, natural licorice, not the more common, artificially flavored licorice candy. MAOIs = monoamine oxidase inhibitors. Some Possible Dietary Supplement–Drug Interactions* Dietary Supplement Affected Drugs Interaction Chamomile Barbiturates and other sedatives May intensify or prolong effects of sedatives because its volatile oils have additive effects Iron supplements May reduce iron absorption via tannins in the plant Warfarin May increase risk of bleeding because chamomile contains phytocoumarins, which may have additive effects Echinacea Potentially hepatotoxic drugs metabolized by cytochrome P-450 enzymes (eg, amiodarone, anabolic steroids, ketoconazole, methotrexate) May slow metabolism of these drugs and increase risk of hepatotoxicity if taken for > 8 wk Immunosuppressants (eg, corticosteroids, cyclosporine) May lessen immunosuppressive effects via T-cell stimulation Ephedra† Stimulant drugs (eg, caffeine, epinephrine, phenylpropanolamine, pseudoephedrine) Increases the stimulant effects of other drugs, increasing risk of irregular or rapid heartbeat and hypertension MAOIs May intensify effects of these drugs and increase risk of side effects (eg, headache, tremors, irregular or rapid heartbeat, hypertension) Feverfew Antimigraine drugs (eg, ergotamine—see Table 2: Headache: Some Characteristics of Headache Disorders by Cause) May increase heart rate and BP because it has additive vasoconstrictive effects Antiplatelet drugs May increase risk of bleeding because feverfew inhibits platelet aggregation (has additive effects) Iron supplements May reduce iron absorption via tannins in the plant NSAIDs Feverfew's efficacy in preventing and managing migraine headaches reduced by NSAIDs Warfarin May increase risk of bleeding because warfarin may have additive effects Garlic Antihypertensives May augment antihypertensive effect Antiplatelet drugs May increase risk of bleeding because these drugs negate garlic's inhibition of platelet aggregation and fibrinolytic effects Protease inhibitors (eg, saquinavir) Blood level of protease inhibitors reduced by garlic Warfarin May increase risk of bleeding by augmenting warfarin's anticoagulant effects Ginger Antiplatelet drugs May increase risk of bleeding by augmenting inhibition of platelet aggregation Warfarin May increase risk of bleeding by augmenting warfarin's anticoagulant effects Ginkgo Anticonvulsants (eg, phenytoin) May reduce efficacy of anticonvulsants because contaminants in ginkgo preparations may reduce anticonvulsant effects MAOIs (eg, tranylcypromine) May intensify effects of these drugs and increase risk of side effects (eg, headache, tremors, manic episodes) NSAIDs May increase risk of bleeding by augmenting inhibition of antiplatelet aggregation Warfarin May increase risk of bleeding by augmenting warfarin's anticoagulant effects Ginseng Antihyperglycemic drugs (eg, glipizide) May intensify effects of these drugs, causing hypoglycemia Aspirin and other NSAIDs May increase risk of bleeding by augmenting inhibition of antiplatelet aggregation Corticosteroids May intensify adverse effects of corticosteroids because ginseng has anti-inflammatory effects Digoxin May increase digoxin levels Estrogens May intensify adverse effects of estrogen MAOIs Can cause headache, tremors, and manic episodes Opioids May reduce the effectiveness of opioids Warfarin May increase risk of bleeding by augmenting warfarin's anticoagulant effects Goldenseal Warfarin and heparin May oppose effects of warfarin and heparin, increasing risk of thromboembolism Green tea Warfarin May reduce efficacy of warfarin, increasing risk of thromboembolism Kava Sedatives (eg, barbiturates, benzodiazepines) May intensify or prolong the effects of sedatives Licorice (glycyrriza glabra)‡ Antiarrhythmics May increase risk of an abnormal heart rhythm, making antiarrhythmic therapy less effective Antihypertensives May increase salt and water retention and increase BP, making antihypertensives less effective Digoxin May decrease levels of K, which increases risk of digoxin toxicity Diuretics May intensify the K-wasting effects of most diuretics and interfere with the effectiveness of K-sparing diuretics (eg, spironolactone) MAOIs May intensify effects of these drugs and increase risk of adverse effects (eg, headache, tremors, manic episodes) Milk thistle Antihyperglycemic drugs May intensify effects of these drugs, causing hypoglycemia Protease inhibitors (eg, indinavir, saquinavir) May interfere with metabolizing enzymes, lowering blood levels of indinavir Saw palmetto Estrogens (eg, oral contraceptives) May augment effects of these drugs St. John's wort Cyclosporine May reduce blood level of cyclosporine, increasing risk of organ transplant rejection Digoxin May reduce blood level of digoxin, making it less effective, with potentially dangerous results Iron supplements May reduce iron absorption MAOIs May augment effects of MAOIs, possibly causing very high BP requiring emergency treatment Nonnucleoside reverse transcriptase inhibitors Increases metabolism of these drugs, reducing their efficacy Oral contraceptives Increases metabolism of these drugs, reducing their efficacy Photosensitizing drugs (eg, lansoprazole, omeprazole, piroxicam, sulfonamide antibiotics) May increase sun sensitivity Protease inhibitors May reduce blood level of protease inhibitors, reducing their efficacy SSRIs (eg, fluoxetine, paroxetine, sertraline) May augment effects of these drugs Tricyclic antidepressants May augment effects of these drugs Warfarin May reduce blood level of warfarin, increasing risk of thromboembolism Valerian Sedatives (eg, barbiturates, benzodiazepines) May intensify effects of sedatives *Caution is required when dietary supplements are used because these products are not standardized and thus vary considerably and because information about their use is continually changing. The theoretical status of many published interactions does not obviate the need for cautious use. Before prescribing any drug, health care practitioners should ask patients whether they are taking dietary supplements and, if so, which ones. Practitioners must identify any potential adverse interactions of drugs and supplements taken by a patient and then determine appropriate drugs and dosages. †Sale of supplements containing ephedra is banned in the US. ‡This substance is true, natural licorice, not the more common, artificially flavored licorice candy. MAOIs = monoamine oxidase inhibitors.

Last full review/revision May 2009 by Ara DerMarderosian, PhD