- 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 professional.
In the United States, the Food and Drug Administration (FDA) regulates dietary supplements differently from prescription and over-the-counter medications. The FDA regulates quality control and good manufacturing processes of dietary supplements, but it does not ensure standardization of the active ingredients or efficacy. In contrast, prescription and over-the-counter medications are regulated by the Kefauver-Harris Amendment of 1962, which requires that manufacturers provide evidence of both safety and efficacy of drugs.
Definition of Dietary Supplements
In the United States, the Dietary Supplement Health and Education Act (DSHEA) of 1994 defines a dietary supplement as follows (1):
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 medications.
Labeling of Dietary Supplements
The labeling of dietary supplements is not standardized globally, and there is significant variability depending on the country or region. For example, in the United States, 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 medication 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 of Dietary Supplements
The regulation of the safety and efficacy of dietary supplements varies greatly worldwide.
For example, in the United States, the FDA does not require that manufacturers of dietary supplements prove safety or efficacy, although supplements must have a history of safety (eg, the ingredient is present in the food supply). 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 beneficial for general health, and that they are both safe and effective for treating and/or preventing specific conditions. This favorable perception may be because dietary supplements are natural (ie, derived from plants or animals) and because some have been used for centuries in traditional medicine practices.
Although the number of clinically based studies is increasing, most supplements have not been rigorously studied. Information about some ongoing clinical trials 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
Case reports
Animal studies
Purity and Standardization of Dietary Supplements
Lack of regulation and government monitoring of dietary supplements raises concerns about the reliability of product claims made by manufacturers. The supplements may not contain the ingredients or amount of active ingredient the manufacturer claims they contain. The supplement may also 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 is even known. Most herbal products are mixtures of several substances, and the most active ingredient is not always known.
The lack of standardization leads to variability not only among products from different manufacturers, but also among separate batches produced by the same manufacturer. This product variability is a particular source of difficulty in conducting rigorous clinical trials and comparing the results among trials. However, some supplements have been standardized and may include a designation of standardization on the label.
Regulations governing supplement production in the United States include Current Good Manufacturing Practices (CGMPs) for Food and Dietary Supplements and Current Good Manufacturing Practice in Manufacturing, Packing, or Holding Human Food. These rules strengthen standards for keeping manufacturing facilities and equipment clean and raw materials pure and uncontaminated. CGMPs also ensure proper labeling, packaging, and storage of the finished product.
Other Concerns for Dietary Supplements
Additional areas of concern include
Use of dietary supplements instead of conventional medications
Stability of supplements (especially herbal products) once manufactured
Toxicity
Interactions between supplements and medications or disease states
Contribution to incorrect diagnosis
Most information about these concerns comes from sporadic individual reports (see table Some Possible Dietary Supplement–Medication 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. Some physicians incorporate 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.
The supplements discussed in The Manuals include those that are commonly used, those that have some evidence of efficacy, or those that have safety concerns. More complete information is available through the NIH National Center for Complementary and Integrative Health.
Some Possible Dietary Supplement–Medication Interactions
Dietary Supplement | Affected Medications | Selected Interaction(s) |
|---|---|---|
Thyroid hormones | May increase thyroid hormone levels | |
Antihyperglycemics | May decrease blood glucose to unsafe levels | |
Antihypertensives | May augment antihypertensive and blood pressure–lowering effects | |
Immunosuppressants (eg, cyclosporine, mycophenolate, tacrolimus, prednisone, corticosteroids)Immunosuppressants (eg, cyclosporine, mycophenolate, tacrolimus, prednisone, corticosteroids) | May interfere with medications that suppress immune function | |
Sedatives | May lead to excessive sedation | |
Immunosuppressants (eg, cyclosporine, mycophenolate, tacrolimus) Immunosuppressants (eg, cyclosporine, mycophenolate, tacrolimus) | May stimulate the immune system and thereby decrease the effectiveness of medications 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 | |
Anticholinergics or medications that can increase acetylcholine (eg, glaucoma or Alzheimer disease medications) | May decrease the effect of anticholinergic medications or increase the adverse effects of cholinergic medications. | |
Thyroid hormones | May increase thyroid hormone levels | |
Medications metabolized by the cytochrome P450 system (eg, warfarin, calcium channel blockers, antiseizure medications)Medications 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) | May increase the effect of these medications and cause excessive sedation | |
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 | |
WarfarinWarfarin | May increase warfarin levels and thus possibly result in bleedingMay increase warfarin levels and thus possibly result in bleeding | |
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 | |
Medications 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 medications | |
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 agents | May interfere with the action of chemotherapy medications due to antioxidant effects | |
Anticoagulants (eg, warfarin)Anticoagulants (eg, warfarin) | Increases the risk of bleeding | |
Antidepressants | May trigger mania | |
Medications with anti-estrogenic effects (eg, tamoxifen, anastrozole, and fulvestrant)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* | Stimulants (eg, caffeine, epinephrine, phenylpropanolamine, pseudoephedrine)Stimulants (eg, caffeine, epinephrine, phenylpropanolamine, pseudoephedrine) | Increases the stimulant effects of other medications, increasing risk of irregular or rapid heartbeat and hypertension |
MAOIs | May intensify effects of these medications and increase risk of adverse effects (eg, headache, tremors, irregular or rapid heartbeat, hypertension) | |
Antimigraine medications (eg, ergotamine—see table Antimigraine medications (eg, ergotamine—see tableSome Characteristics of Headache Disorders by Cause) | May increase heart rate and blood pressure because it has additive vasoconstrictive effects | |
Antiplatelet medications | 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 medications | May increase risk of bleeding by enhancing garlic’s inhibition of platelet aggregation and fibrinolytic effectsMay increase risk of bleeding by enhancing 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) | May increase blood levels of tacrolimus, possibly enough to injure the liverMay increase blood levels of tacrolimus, possibly enough to injure the liver | |
Antiplatelet medications | 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 medications 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 medications (eg, glipizide) Antihyperglycemic medications (eg, glipizide) | May intensify effects of these medications, 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 | |
AtorvastatinAtorvastatin NadololNadolol WarfarinWarfarin | Green tea may decrease the levels and effects of atorvastatin, thus decreasing any lipid-lowering benefitGreen tea may decrease the levels and effects of atorvastatin, thus decreasing any lipid-lowering benefit Green tea may decrease the levels and effects of nadolol, thus decreasing its blood pressure–lowering effectGreen tea may decrease the levels and effects of nadolol, thus decreasing its blood pressure–lowering effect 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 medications | 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 medications 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 medications | May intensify effects of these medications, 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 | |
Reishi | Anticoagulants and antiplatelet medications | May increase the risk of bleeding in patients treated with anticoagulants and antiplatelet medications |
Antihypertensives | May produce hypotension in patients on antihypertensive medications | |
Antihyperglycemic medications | May contribute to additive hypoglycemia in patients on antihyperglycemic medications | |
Antidepressants | May cause a rapid heart rate | |
Anticoagulants (eg, warfarin)Anticoagulants (eg, warfarin) | May increase blood levels causing increased risk of bleeding | |
Anti-inflammatory medications | Increased blood levels and possibly adverse effects | |
Immunosuppressants | May decrease effectiveness of immunosuppressants | |
Antihyperglycemic medications | May decrease blood glucose, triggering hypoglycemia | |
Antihypertensive medications | May decrease blood pressure further | |
Antidepressants | May increase serotonin levels causing serotonin syndrome when given with serotonergic medications, 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 | |
Benzodiazepines (eg, alprazolam, lorazepam, diazepam)Benzodiazepines (eg, alprazolam, lorazepam, diazepam) | May decrease the effectiveness of benzodiazepines | |
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 | |
KetamineKetamine | May decrease the effectiveness of ketamineMay decrease the effectiveness of ketamine | |
Nonnucleoside reverse transcriptase inhibitors (eg, nevirapine, efavirenz)Nonnucleoside reverse transcriptase inhibitors (eg, nevirapine, efavirenz) | Increases metabolism of these medications, reducing their efficacy | |
Oral contraceptives | Increases metabolism of these medications, reducing their efficacy | |
Oxycodone, methadone, and tramadolOxycodone, methadone, and tramadol | Decreases serum concentrations and analgesic effects of these medications | |
PhenobarbitalPhenobarbital | May decrease the effectiveness of phenobarbitalMay decrease the effectiveness of phenobarbital | |
Photosensitizing medications (eg, amiodarone, naproxen, sulfonamide antibiotics)Photosensitizing medications (eg, amiodarone, naproxen, sulfonamide antibiotics) | May increase sun sensitivity | |
Protease inhibitors (eg, indinavir, saquinavir)Protease inhibitors (eg, indinavir, saquinavir) | 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 medications | |
Statins (eg, atorvastatin, lovastatin, rosuvastatin) Statins (eg, atorvastatin, lovastatin, rosuvastatin) | May decrease the effectiveness of statins | |
Tricyclic antidepressants (eg, desipramine, amitriptyline)Tricyclic antidepressants (eg, desipramine, amitriptyline) | May augment effects of these medications | |
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 | |
* Sale of supplements containing ephedra is banned in the United States. | ||
† 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. | ||
Reference
1. National Institutes of Health (NIH), Office of Dietary Supplements. Dietary Supplement Health And Education Act of 1994 (DSHEA)
More Information
The following English-language resources may be useful. Please note that The Manual is not responsible for the content of these resources.
Drugs Mentioned In This Article
