Overview of Dietary Supplements: Dietary Supplements: Merck Manual Professional

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	Dietary Supplements
		Overview of Dietary Supplements
			Definition
			Labeling
			Safety and efficacy
			Purity and standardization
			Other concerns

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Overview of Dietary Supplements

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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
	WarfarinSome Trade Names COUMADIN Click for Drug Monograph	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, amiodaroneSome Trade Names CORDARONE Click for Drug Monograph , anabolic steroids, ketoconazoleSome Trade Names NIZORAL Click for Drug Monograph , methotrexateSome Trade Names RHEUMATREX Click for Drug Monograph )	May slow metabolism of these drugs and increase risk of hepatotoxicity if taken for > 8 wk
Echinacea	Immunosuppressants (eg, corticosteroids, cyclosporineSome Trade Names NEORAL SANDIMMUNE Click for Drug Monograph )	May lessen immunosuppressive effects via T-cell stimulation
Ephedra^†	Stimulant drugs (eg, caffeine, epinephrineSome Trade Names ADRENALIN PRIMATENE MIST Click for Drug Monograph , phenylpropanolamine, pseudoephedrineSome Trade Names AFRINOL SUDAFED Click for Drug Monograph )	Increases the stimulant effects of other drugs, increasing risk of irregular or rapid heartbeat and hypertension
Ephedra^†	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, ergotamineSome Trade Names ERGOMAR Click for Drug Monograph —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
	WarfarinSome Trade Names COUMADIN Click for Drug Monograph	May increase risk of bleeding because warfarinSome Trade Names COUMADIN Click for Drug Monograph 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, saquinavirSome Trade Names FORTOVASE INVIRASE Click for Drug Monograph )	Blood level of protease inhibitors reduced by garlic
	WarfarinSome Trade Names COUMADIN Click for Drug Monograph	May increase risk of bleeding by augmenting warfarinSome Trade Names COUMADIN Click for Drug Monograph 's anticoagulant effects
Ginger	Antiplatelet drugs	May increase risk of bleeding by augmenting inhibition of platelet aggregation
Ginger	WarfarinSome Trade Names COUMADIN Click for Drug Monograph	May increase risk of bleeding by augmenting warfarinSome Trade Names COUMADIN Click for Drug Monograph 's anticoagulant effects
Ginkgo	Anticonvulsants (eg, phenytoinSome Trade Names DILANTIN Click for Drug Monograph )	May reduce efficacy of anticonvulsants because contaminants in ginkgo preparations may reduce anticonvulsant effects
	MAOIs (eg, tranylcypromineSome Trade Names PARNATE Click for Drug Monograph )	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
	WarfarinSome Trade Names COUMADIN Click for Drug Monograph	May increase risk of bleeding by augmenting warfarinSome Trade Names COUMADIN Click for Drug Monograph 's anticoagulant effects
Ginseng	Antihyperglycemic drugs (eg, glipizideSome Trade Names GLUCOTROL Click for Drug Monograph )	May intensify effects of these drugs, causing hypoglycemia
	AspirinSome Trade Names BUFFERIN ECOTRIN GENACOTE Click for Drug Monograph 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
	DigoxinSome Trade Names DIGITEK LANOXIN Click for Drug Monograph	May increase digoxinSome Trade Names DIGITEK LANOXIN Click for Drug Monograph levels
	EstrogensSome Trade Names PREMARIN Click for Drug Monograph	May intensify adverse effects of estrogen
	MAOIs	Can cause headache, tremors, and manic episodes
	Opioids	May reduce the effectiveness of opioids
	WarfarinSome Trade Names COUMADIN Click for Drug Monograph	May increase risk of bleeding by augmenting warfarinSome Trade Names COUMADIN Click for Drug Monograph 's anticoagulant effects
Goldenseal	WarfarinSome Trade Names COUMADIN Click for Drug Monograph and heparinSome Trade Names HEPFLUSH-10 Click for Drug Monograph	May oppose effects of warfarinSome Trade Names COUMADIN Click for Drug Monograph and heparinSome Trade Names HEPFLUSH-10 Click for Drug Monograph , increasing risk of thromboembolism
Green tea	WarfarinSome Trade Names COUMADIN Click for Drug Monograph	May reduce efficacy of warfarinSome Trade Names COUMADIN Click for Drug Monograph , 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
	DigoxinSome Trade Names DIGITEK LANOXIN Click for Drug Monograph	May decrease levels of K, which increases risk of digoxinSome Trade Names DIGITEK LANOXIN Click for Drug Monograph toxicity
	Diuretics	May intensify the K-wasting effects of most diuretics and interfere with the effectiveness of K-sparing diuretics (eg, spironolactoneSome Trade Names ALDACTONE Click for Drug Monograph )
	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
Milk thistle	Protease inhibitors (eg, indinavirSome Trade Names CRIXIVAN Click for Drug Monograph , saquinavirSome Trade Names FORTOVASE INVIRASE Click for Drug Monograph )	May interfere with metabolizing enzymes, lowering blood levels of indinavirSome Trade Names CRIXIVAN Click for Drug Monograph
Saw palmetto	EstrogensSome Trade Names PREMARIN Click for Drug Monograph (eg, oral contraceptives)	May augment effects of these drugs
St. John's wort	CyclosporineSome Trade Names NEORAL SANDIMMUNE Click for Drug Monograph	May reduce blood level of cyclosporineSome Trade Names NEORAL SANDIMMUNE Click for Drug Monograph , increasing risk of organ transplant rejection
	DigoxinSome Trade Names DIGITEK LANOXIN Click for Drug Monograph	May reduce blood level of digoxinSome Trade Names DIGITEK LANOXIN Click for Drug Monograph , 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, lansoprazoleSome Trade Names PREVACID Click for Drug Monograph , omeprazoleSome Trade Names PRILOSEC Click for Drug Monograph , piroxicamSome Trade Names FELDENE Click for Drug Monograph , sulfonamide antibiotics)	May increase sun sensitivity
	Protease inhibitors	May reduce blood level of protease inhibitors, reducing their efficacy
	SSRIs (eg, fluoxetineSome Trade Names PROZAC SARAFEM Click for Drug Monograph , paroxetineSome Trade Names PAXIL Click for Drug Monograph , sertralineSome Trade Names ZOLOFT Click for Drug Monograph )	May augment effects of these drugs
	Tricyclic antidepressants	May augment effects of these drugs
	WarfarinSome Trade Names COUMADIN Click for Drug Monograph	May reduce blood level of warfarinSome Trade Names COUMADIN Click for Drug Monograph , 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
	WarfarinSome Trade Names COUMADIN Click for Drug Monograph	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, amiodaroneSome Trade Names CORDARONE Click for Drug Monograph , anabolic steroids, ketoconazoleSome Trade Names NIZORAL Click for Drug Monograph , methotrexateSome Trade Names RHEUMATREX Click for Drug Monograph )	May slow metabolism of these drugs and increase risk of hepatotoxicity if taken for > 8 wk
Echinacea	Immunosuppressants (eg, corticosteroids, cyclosporineSome Trade Names NEORAL SANDIMMUNE Click for Drug Monograph )	May lessen immunosuppressive effects via T-cell stimulation
Ephedra^†	Stimulant drugs (eg, caffeine, epinephrineSome Trade Names ADRENALIN PRIMATENE MIST Click for Drug Monograph , phenylpropanolamine, pseudoephedrineSome Trade Names AFRINOL SUDAFED Click for Drug Monograph )	Increases the stimulant effects of other drugs, increasing risk of irregular or rapid heartbeat and hypertension
Ephedra^†	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, ergotamineSome Trade Names ERGOMAR Click for Drug Monograph —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
	WarfarinSome Trade Names COUMADIN Click for Drug Monograph	May increase risk of bleeding because warfarinSome Trade Names COUMADIN Click for Drug Monograph 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, saquinavirSome Trade Names FORTOVASE INVIRASE Click for Drug Monograph )	Blood level of protease inhibitors reduced by garlic
	WarfarinSome Trade Names COUMADIN Click for Drug Monograph	May increase risk of bleeding by augmenting warfarinSome Trade Names COUMADIN Click for Drug Monograph 's anticoagulant effects
Ginger	Antiplatelet drugs	May increase risk of bleeding by augmenting inhibition of platelet aggregation
Ginger	WarfarinSome Trade Names COUMADIN Click for Drug Monograph	May increase risk of bleeding by augmenting warfarinSome Trade Names COUMADIN Click for Drug Monograph 's anticoagulant effects
Ginkgo	Anticonvulsants (eg, phenytoinSome Trade Names DILANTIN Click for Drug Monograph )	May reduce efficacy of anticonvulsants because contaminants in ginkgo preparations may reduce anticonvulsant effects
	MAOIs (eg, tranylcypromineSome Trade Names PARNATE Click for Drug Monograph )	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
	WarfarinSome Trade Names COUMADIN Click for Drug Monograph	May increase risk of bleeding by augmenting warfarinSome Trade Names COUMADIN Click for Drug Monograph 's anticoagulant effects
Ginseng	Antihyperglycemic drugs (eg, glipizideSome Trade Names GLUCOTROL Click for Drug Monograph )	May intensify effects of these drugs, causing hypoglycemia
	AspirinSome Trade Names BUFFERIN ECOTRIN GENACOTE Click for Drug Monograph 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
	DigoxinSome Trade Names DIGITEK LANOXIN Click for Drug Monograph	May increase digoxinSome Trade Names DIGITEK LANOXIN Click for Drug Monograph levels
	EstrogensSome Trade Names PREMARIN Click for Drug Monograph	May intensify adverse effects of estrogen
	MAOIs	Can cause headache, tremors, and manic episodes
	Opioids	May reduce the effectiveness of opioids
	WarfarinSome Trade Names COUMADIN Click for Drug Monograph	May increase risk of bleeding by augmenting warfarinSome Trade Names COUMADIN Click for Drug Monograph 's anticoagulant effects
Goldenseal	WarfarinSome Trade Names COUMADIN Click for Drug Monograph and heparinSome Trade Names HEPFLUSH-10 Click for Drug Monograph	May oppose effects of warfarinSome Trade Names COUMADIN Click for Drug Monograph and heparinSome Trade Names HEPFLUSH-10 Click for Drug Monograph , increasing risk of thromboembolism
Green tea	WarfarinSome Trade Names COUMADIN Click for Drug Monograph	May reduce efficacy of warfarinSome Trade Names COUMADIN Click for Drug Monograph , 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
	DigoxinSome Trade Names DIGITEK LANOXIN Click for Drug Monograph	May decrease levels of K, which increases risk of digoxinSome Trade Names DIGITEK LANOXIN Click for Drug Monograph toxicity
	Diuretics	May intensify the K-wasting effects of most diuretics and interfere with the effectiveness of K-sparing diuretics (eg, spironolactoneSome Trade Names ALDACTONE Click for Drug Monograph )
	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
Milk thistle	Protease inhibitors (eg, indinavirSome Trade Names CRIXIVAN Click for Drug Monograph , saquinavirSome Trade Names FORTOVASE INVIRASE Click for Drug Monograph )	May interfere with metabolizing enzymes, lowering blood levels of indinavirSome Trade Names CRIXIVAN Click for Drug Monograph
Saw palmetto	EstrogensSome Trade Names PREMARIN Click for Drug Monograph (eg, oral contraceptives)	May augment effects of these drugs
St. John's wort	CyclosporineSome Trade Names NEORAL SANDIMMUNE Click for Drug Monograph	May reduce blood level of cyclosporineSome Trade Names NEORAL SANDIMMUNE Click for Drug Monograph , increasing risk of organ transplant rejection
	DigoxinSome Trade Names DIGITEK LANOXIN Click for Drug Monograph	May reduce blood level of digoxinSome Trade Names DIGITEK LANOXIN Click for Drug Monograph , 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, lansoprazoleSome Trade Names PREVACID Click for Drug Monograph , omeprazoleSome Trade Names PRILOSEC Click for Drug Monograph , piroxicamSome Trade Names FELDENE Click for Drug Monograph , sulfonamide antibiotics)	May increase sun sensitivity
	Protease inhibitors	May reduce blood level of protease inhibitors, reducing their efficacy
	SSRIs (eg, fluoxetineSome Trade Names PROZAC SARAFEM Click for Drug Monograph , paroxetineSome Trade Names PAXIL Click for Drug Monograph , sertralineSome Trade Names ZOLOFT Click for Drug Monograph )	May augment effects of these drugs
	Tricyclic antidepressants	May augment effects of these drugs
	WarfarinSome Trade Names COUMADIN Click for Drug Monograph	May reduce blood level of warfarinSome Trade Names COUMADIN Click for Drug Monograph , 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

Content last modified November 2012

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