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Overview of Dietary Supplements

by Ara DerMarderosian, PhD

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 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/ ).

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: 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.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • FELDENE
  • NIZORAL
  • INVIRASE
  • ZOLOFT
  • LANOXIN
  • PROZAC, SARAFEM
  • PRILOSEC
  • PREVACID
  • AFRINOL, SUDAFED
  • NEORAL, SANDIMMUNE
  • No US brand name
  • ERGOMAR
  • PANHEPRIN
  • GLUCOTROL
  • CRIXIVAN
  • PARNATE
  • CORDARONE
  • ADRENALIN
  • COUMADIN
  • PAXIL
  • OTREXUP
  • DILANTIN
  • ALDACTONE

* This is a professional Version *