- Overview of Dietary Supplements
- Apoaequorin
- Ashwagandha
- Astragalus
- Bacopa
- Black Cohosh
- Cannabidiol (CBD)
- Chamomile
- Chondroitin Sulfate
- Chromium
- Coenzyme Q10 (CoQ10)
- Cranberry
- Creatine
- Dehydroepiandrosterone (DHEA)
- Echinacea
- Feverfew
- Fish Oil
- Garlic
- Ginger
- Ginkgo
- Ginseng
- Glucosamine
- Goldenseal
- Green Tea
- Holy Basil
- Intravenous Vitamin Therapy (Myers' Cocktail)
- Kava
- Licorice
- Melatonin
- Milk Thistle
- Reishi
- Rhodiola
- S-Adenosyl-L-Methionine
- Saw Palmetto
- St. John’s Wort
- Valerian
- Zinc Supplements
Topic Resources
Dietary supplements are the most commonly used of all integrative, complementary, and alternative therapies, primarily because they are widely available, relatively inexpensive, and can be bought without consulting a health care practitioner.
The US Food and Drug Administration (FDA) regulates dietary supplements differently from drugs. The FDA regulates quality control and good manufacturing processes but does not ensure standardization of the active ingredients or efficacy.
See also National Institutes of Health (NIH): Office of Dietary Supplements.
Definition
The Dietary Supplement Health and 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 melatoninmelatonin, are regulated as dietary supplements and not as prescription drugs.
See also US Food and Drug Administration: Questions and Answers on Dietary Supplements.
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.
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 urinary tract infections). Expiration dates may be included on the standardized product labels if this information is supported by valid data demonstrating that it is not false or misleading.
Safety and Efficacy
The FDA does not require manufacturers of dietary supplements to prove safety or efficacy, although supplements must have a history of safety. Manufacturers and distributors of supplements must report serious adverse events to the FDA through the MedWatch system, a medical product safety reporting program.
Most people who use dietary supplements assume that they are good for health generally, are safe and effective for treating and/or preventing specific conditions, or both. People may think this 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.
Although more and more clinically based studies are now being done, most supplements have not been rigorously studied. Information about studies being done is available from the NIH National Center for Complementary and Integrative Health (NCCIH).
For most dietary supplements, evidence suggesting safety or efficacy comes from
Traditional use
In vitro studies
Certain case reports
Animal studies
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, unapproved dyes), 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(s) 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 separate batches produced by the same manufacturer may differ. This product variability is a particular source of difficulty in conducting rigorous clinical 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 or disease states
Contribution to incorrect diagnosis
Most information about these concerns comes from sporadic individual reports (see table Some Possible Dietary Supplement–Drug Interactions) and some research studies.
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 integrative, 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.
Common concerns about the use of supplements include the following:
Placebo effects can simulate true efficacy, particularly if the patient and/or physician strongly believes in the supplement.
Therapeutic responses to supplements, placebo-mediated or otherwise, could be mistaken as evidence that confirms a particular, possibly incorrect, diagnosis.
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 supplements discussed in The Manuals are ones that are most popular, are effective, or have some questions about their safety. More complete information is available through the NIH National Center for Complementary and Integrative Health.
Some Possible Dietary Supplement–Drug Interactions*
Dietary Supplement | Affected Drugs | Interaction(s) |
|---|---|---|
Thyroid hormones | May increase thyroid hormone levels | |
Antihyperglycemic drugs | May decrease blood glucose to unsafe levels | |
Antihypertensive drugs | May augment antihypertensive and blood pressure-lowering effects | |
Immunosuppressant drugs (eg, cyclosporine, mycophenolate, tacrolimus, prednisone, corticosteroids)Immunosuppressant drugs (eg, cyclosporine, mycophenolate, tacrolimus, prednisone, corticosteroids) | May interfere with drugs that suppress immune function | |
Sedatives | May lead to excessive sleepiness | |
Immunosuppressants (eg, cyclosporine, mycophenolate, tacrolimus) Immunosuppressants (eg, cyclosporine, mycophenolate, tacrolimus) | May stimulate the immune system and thereby decrease the effectiveness of drugs that suppress the immune system such as those used after organ transplant | |
LithiumLithium | May decrease excretion of lithium which can result in increased blood levels and possible serious adverse effectsMay decrease excretion of lithium which can result in increased blood levels and possible serious adverse effects | |
Anticholinergic drugs or drugs that can increase acetylcholine (eg, glaucoma or Alzheimer disease drugs) | May decrease the effect or anticholinergic drugs or increase the adverse effects of cholinergic drugs. | |
Thyroid hormones | May increase thyroid hormone levels | |
Drugs metabolized by the cytochrome P450 system (eg, warfarin, calcium channel blockers, antiseizure medications)Drugs metabolized by the cytochrome P450 system (eg, warfarin, calcium channel blockers, antiseizure medications) | May increase the risk of bleeding or lower blood pressure with calcium channel blockers or sedation with antiseizure medications | |
Sedatives and antidepressants (eg, benzodiazepines, phenobarbital, morphine, alcohol, SSRIs, tricyclic antidepressants)Sedatives and antidepressants (eg, benzodiazepines, phenobarbital, morphine, alcohol, SSRIs, tricyclic antidepressants) | Can increase the effect of these drugs and make people too drowsy | |
Acetaminophen and valproic acidAcetaminophen and valproic acid | May increase the chance of liver injury | |
Antiseizure medications | May increase effect of these medications and may increase adverse effects | |
Lithium Lithium | May increase lithium toxicityMay increase lithium toxicity | |
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 | |
WarfarinWarfarin | May increase risk of bleeding because chamomile contains phytocoumarins, which may have additive effects | |
Drugs with estrogenic effects (eg, tamoxifen, hormone replacement therapy, oral contraceptives containing estrogens)effects (eg, tamoxifen, hormone replacement therapy, oral contraceptives containing estrogens) | May interfere with the estrogenic effects of these drugs | |
CyclosporineCyclosporine | May increase cyclosporine serum concentrationsMay increase cyclosporine serum concentrations | |
Insulin, sulfonylureas | May lower blood glucose | |
Thyroid replacement therapy | May decrease levothyroxine serum levels May decrease levothyroxine serum levels | |
WarfarinWarfarin | May decrease response to warfarinMay decrease response to warfarin | |
Antihypertensives | May augment antihypertensive and blood pressure-lowering effects | |
Chemotherapy drugs | May interfere with the action of chemotherapy drugs due to antioxidant effects | |
Anticoagulants (eg, warfarin)Anticoagulants (eg, warfarin) | Increases the risk of bleeding | |
Antidepressants | May trigger mania | |
Drugs with anti-estrogenic effects (eg, tamoxifen, anastrozole, and fulvestrant)Drugs with anti-estrogenic effects (eg, tamoxifen, anastrozole, and fulvestrant) | May decrease the anti-estrogenic effects | |
Triazolam (a benzodiazepine).Triazolam (a benzodiazepine). | May increase the sedative effect | |
Bacille Calmette-Guerin (BCG) vaccine (for tuberculosis) | May decrease the effectiveness of the BCG vaccine | |
Ephedra† | Stimulant drugs (eg, caffeine, epinephrine, phenylpropanolamine, pseudoephedrine)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 adverse effects (eg, headache, tremors, irregular or rapid heartbeat, hypertension) | |
Antimigraine drugs (eg, ergotamine—see table Antimigraine drugs (eg, ergotamine—see tableSome Characteristics of Headache Disorders by Cause) | May increase heart rate and blood pressure because it has additive vasoconstrictive effects | |
Antiplatelet drugs | May increase risk of bleeding because feverfew inhibits platelet aggregation (has additive effects) | |
NSAIDs | Increased risk of bleeding, because both feverfew and NSAIDs may potentially cause bleeding | |
WarfarinWarfarin | May increase risk of bleeding because warfarin may have additive effectsMay increase risk of bleeding because warfarin may have additive effects | |
Antihypertensives | May augment antihypertensive and blood pressure-lowering effects | |
Antiplatelet drugs | May increase risk of bleeding because these drugs enhance garlic’s inhibition of platelet aggregation and fibrinolytic effectsMay increase risk of bleeding because these drugs enhance garlic’s inhibition of platelet aggregation and fibrinolytic effects | |
Isonicotinylhydrazide (isoniazid, or INH)Isonicotinylhydrazide (isoniazid, or INH) | May lower levels | |
Protease inhibitors (eg, saquinavir)Protease inhibitors (eg, saquinavir) | Blood level of protease inhibitors reduced by garlicBlood level of protease inhibitors reduced by garlic | |
WarfarinWarfarin | May increase risk of bleeding by augmenting warfarin’s anticoagulant effectsMay increase risk of bleeding by augmenting warfarin’s anticoagulant effects | |
Tacrolimus (oral)Tacrolimus (oral) | Can increase blood levels of tacrolimus, possibly enough to injure the liverCan increase blood levels of tacrolimus, possibly enough to injure the liver | |
Antiplatelet drugs | May increase risk of bleeding by augmenting inhibition of platelet aggregation | |
WarfarinWarfarin | May increase risk of bleeding by augmenting warfarin’s anticoagulant effectsMay increase risk of bleeding by augmenting warfarin’s anticoagulant effects | |
Antiseizure medications (eg, phenytoin) Antiseizure medications (eg, phenytoin) | May reduce efficacy of antiseizure medications because contaminants in ginkgo preparations may reduce antiseizure effectsMay reduce efficacy of antiseizure medications because contaminants in ginkgo preparations may reduce antiseizure effects | |
Antidepressants | May precipitate serotonin syndrome in patients on other antidepressant medications | |
MAOIs (eg, tranylcypromine)MAOIs (eg, tranylcypromine) | May intensify effects of these drugs and increase risk of adverse effects (eg, headache, tremors, manic episodes) | |
NSAIDs | May increase risk of bleeding by augmenting inhibition of antiplatelet aggregation | |
WarfarinWarfarin | May increase risk of bleeding by augmenting warfarin’s anticoagulant effectsMay increase risk of bleeding by augmenting warfarin’s anticoagulant effects | |
Antihyperglycemic drugs (eg, glipizide) Antihyperglycemic drugs (eg, glipizide) | May intensify effects of these drugs, causing hypoglycemia | |
Aspirin and other NSAIDsAspirin 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 effectsMay intensify adverse effects of corticosteroids because ginseng has anti-inflammatory effects May have immunostimulant effects and thus may attenuate the immunosuppressive effects of corticosteroids | |
DigoxinDigoxin | May increase digoxin levelsMay 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 | |
WarfarinWarfarin | May increase risk of bleeding by augmenting warfarin’s anticoagulant effectsMay increase risk of bleeding by augmenting warfarin’s anticoagulant effects | |
Antihypertensives | Berberine content may increase antihypertensive effects | |
Antihyperglycemics | Berberine may increase hypoglycemic effects | |
Warfarin and heparinWarfarin and heparin | May increase effects of warfarin and heparin, increasing risk of bleedingMay increase effects of warfarin and heparin, increasing risk of bleeding | |
WarfarinWarfarin | May reduce efficacy of warfarin, increasing risk of thromboembolismMay reduce efficacy of warfarin, increasing risk of thromboembolism | |
Thyroid hormones | May decrease the efficacy of thyroid hormone drugs | |
Anticoagulants and antiplatelets | May increase risk of bleeding | |
Sedatives (eg, barbiturates, benzodiazepines) | May intensify or prolong the effects of sedatives | |
Antiparkinsonian medications | May antagonize effects of levodopa and worsen Parkinson diseaseMay antagonize effects of levodopa and worsen Parkinson disease May reduce metabolism of ropinirole and thus cause dopamine toxicityMay reduce metabolism of ropinirole and thus cause dopamine toxicity | |
Hepatotoxic drugs | May increase hepatotoxicity | |
Antihypertensives | May increase salt and water retention and increase blood pressure, making antihypertensives less effective | |
Chemotherapeutics | May decrease effects of paclitaxel and cisplatinMay decrease effects of paclitaxel and cisplatin | |
Corticosteroids | May increase adverse effects of corticosteroids | |
DigoxinDigoxin | May decrease levels of potassium, which increases risk of digoxin toxicityMay decrease levels of potassium, which increases risk of digoxin toxicity | |
Diuretics | May intensify the potassium-wasting effects of most diuretics and interfere with the effectiveness of potassium-sparing diuretics (eg, spironolactone)May intensify the potassium-wasting effects of most diuretics and interfere with the effectiveness of potassium-sparing diuretics (eg, spironolactone) | |
MAOIs | May intensify effects of these drugs and increase risk of adverse effects (eg, headache, tremors, manic episodes) | |
WarfarinWarfarin | May decrease effectiveness of warfarinMay decrease effectiveness of warfarin | |
Anticoagulants (such as warfarin)Anticoagulants (such as warfarin) | May increase risk of bleeding | |
Antiseizure medications | May decrease the effectiveness of antiseizure medications | |
Benzodiazepines | May increase sedative effect | |
MethamphetamineMethamphetamine | May increase the adverse effects of methamphetamineMay increase the adverse effects of methamphetamine | |
Antihyperglycemic drugs | May intensify effects of these drugs, causing hypoglycemia | |
Protease inhibitors (eg, indinavir, saquinavir)Protease inhibitors (eg, indinavir, saquinavir) | May interfere with metabolizing enzymes, lowering blood levels of indinavirMay interfere with metabolizing enzymes, lowering blood levels of indinavir | |
SirolimusSirolimus | May decrease sirolimus clearance in renal transplant patients with hepatic impairmentMay decrease sirolimus clearance in renal transplant patients with hepatic impairment | |
WarfarinWarfarin | May increase risk of bleeding by increasing effects | |
Antidepressants | May cause a rapid heart rate | |
Anticoagulants (eg, warfarin)Anticoagulants (eg, warfarin) | May increase blood levels causing increased risk of bleeding | |
Anti-inflammatory drugs | Increased blood levels and possibly adverse effects | |
Immunosuppressants | May decrease effectiveness of immunosuppressants | |
Antihyperglycemic medications | Can decrease blood glucose, triggering hypoglycemia | |
Antihypertensive medications | Can decrease blood pressure further | |
Antidepressants | May increase serotonin levels causing serotonin syndrome when given with serotonergic drugs, manifested by a rapid heart rate, anxiety, gastrointestinal symptoms, severe muscle rigidity, and possible seizures | |
LevodopaLevodopa | May decrease the effectiveness of levodopaMay decrease the effectiveness of levodopa | |
Antiplatelets and anticoagulants (eg, warfarin) Antiplatelets and anticoagulants (eg, warfarin) | May increase effects and may cause bleeding | |
Estrogens (eg, oral contraceptives and other products) | May decrease effectiveness of estrogens | |
Cyclosporine and tacrolimusCyclosporine and tacrolimus | May reduce blood level of cyclosporine, increasing risk of organ transplant rejectionMay reduce blood level of cyclosporine, increasing risk of organ transplant rejection | |
DigoxinDigoxin | May reduce blood level of digoxin, making it less effective, with potentially dangerous resultsMay 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 blood pressure 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 | |
Oxycodone, methadone, and tramadolOxycodone, methadone, and tramadol | Decreases serum concentrations and analgesic effects of these drugs | |
Photosensitizing drugs (eg, lansoprazole, omeprazole, piroxicam, sulfonamide antibiotics)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)SSRIs (eg, fluoxetine, paroxetine, sertraline) | May augment effects of these drugs | |
Tricyclic antidepressants | May augment effects of these drugs | |
Warfarin and other anticoagulants (eg, direct-acting oral anticoagulants)Warfarin and other anticoagulants (eg, direct-acting oral anticoagulants) | May reduce blood level of warfarin and rivaroxaban, increasing risk of thromboembolismMay reduce blood level of warfarin and rivaroxaban, increasing risk of thromboembolism | |
Sedatives (eg, barbiturates, benzodiazepines) | May intensify effects of sedatives | |
Antibiotics (eg, cephalexin, tetracyclines, quinolones) Antibiotics (eg, cephalexin, tetracyclines, quinolones) | May decrease absorption and effect of the antibiotics when taken within hours of zinc | |
Cisplatin, penicillamine, and chelate integrase inhibitors (eg, dolutegravir)Cisplatin, penicillamine, and chelate integrase inhibitors (eg, dolutegravir) | May be inhibited or inactivated | |
* 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; NSAIDs = nonsteroidal anti-inflammatory drugs; SSRIs = selective serotonin reuptake inhibitors. | ||
More Information
The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
U.S. Food & Drug Administration (FDA), Dietary Supplements: General information about the FDA's regulation of finished dietary supplement products and dietary ingredients
U.S. Food & Drug Administration (FDA), MedWatch: Access to the FDA’s medical product safety reporting program for health professionals, patients and consumers
National Institutes of Health (NIH), National Center for Complementary and Integrative Health: General information on research and information about complementary health products and practices
National Institutes of Health (NIH), Office of Dietary Supplements: Dietary Supplement Health And Education Act of 1994 (DSHEA)
