How Safe are Dietary Supplements?

Jennifer Brooks, PhD, Sasha Milbeck, BA, Elizabeth Nagelin-Anderson, MA, Emma Roy, BS, and Diana Zuckerman, PhD, National Center for Health Research

In their quest for health and beauty, almost 80% of American adults take dietary supplements to “solve” all sorts of problems — such as taking Vitamin D to boost immunity and prevent COVID-19 infection or taking supplements to lose weight or improve their appearance. Americans spend billions of dollars every year on these supplements, but do these products really work? How much do Americans know about the supplements they are putting into their bodies?

The U.S. Food and Drug Administration (FDA) requires that supplement companies label ingredients in their products. However, the FDA doesn’t regulate dietary supplements before they are sold to ensure they are safe or effective. The FDA has only 6 ingredients on their Advisory List “that consumers may wish to avoid purchasing or consuming”. 1 However, the FDA requires dietary supplement companies to report serious adverse events associated with their supplements after they are on the market, but this only applies to serious adverse events and not all adverse events.2 Companies that manufacture supplements do not need to inform the FDA before producing or selling their products, so they are free to sell any product that isn’t proven dangerous. In other words, companies making drugs to prevent, diagnose, treat, or cure disease must first prove the drugs safe and effective, but the FDA must show evidence that a supplement is unsafe before it restricts its sales. And, unlike drugs, the FDA doesn’t regulate dietary supplements for purity or quality.   A supplement’s “guarantee” does not mean a guarantee that it works or is safe.

According to FTC regulations, advertisements by supplement manufacturers may only include claims that are truthful and substantiated. In reality, advertisements often stretch the truth. A 2002 FTC report on 300 weight-loss ads — two-thirds of which were for dietary supplements — found many false or misleading claims, including claims of safety made without any scientific data to back them up.3 These ads often implied safety by highlighting “natural” ingredients. Unfortunately, “natural” and “safe” are not the same thing; arsenic is natural, for example, as are lead and mercury, but it is not safe to eat them.

FDA considers a product misbranded “if its labeling proves false or misleading in any particular”4, yet the FDA’s oversight of the supplement industry continues to lag on misbranded supplements that put consumers at risk of serious health problems. For example, a study published in October 2018 in the Journal of the American Medical Association (JAMA) reviewed 776 supplements that the FDA found to contain unapproved and sometimes dangerous pharmaceutical ingredients.5  Most of these adulterated products were for sexual enhancement, weight loss, or muscle-building. Drugs found in sexual enhancement dietary supplements included Viagra or other key ingredients in prescription medications for erectile dysfunction. These ingredients can cause serious health problems, especially if the individual is unaware that he is consuming them. The adulterated weight loss products were likely to contain a laxative or sibutramine, a drug previously sold under the name Meridia but removed from the U.S. market in 2010 due to cardiovascular risks. Many of the adulterated muscle building products contained anabolic steroids that were not listed on the label. These can cause dangerous changes in thoughts or behaviors and serious psychiatric symptoms in the short term and kidney problems, liver damage, and heart problems in the long term. Other adulterated supplements contained antidepressants or antihistamines, which may cause dangerous side effects and can interact with other medications.

In March 2021, a study by researchers at Harvard Medical School found that weight loss and sports enhancement supplements contained 9 chemicals that are not approved by the FDA and are prohibited for use in supplements.6 One of these, Deterenol, is banned by the FDA because it can cause cardiovascular problems and even cause cardiac arrest. A 2022 study evaluated 30 dietary products and found.7 Seventeen products had inaccurate labels, of which 13 were considered misbranded due to “ingredients listed on the labels that were not detected through analysis”. On the other hand, 9 contained substances in the product that were not listed on the labels.  A 2022 study of 190 adults found that six dietary supplements commonly taken for heart health did not lower cholesterol after 29 days of use.8

Why Are Supplement Policies So Inadequate?

Why are there basically no safeguards to protect Americans from dietary supplements that don’t work, are contaminated, or don’t contain the ingredients listed on the bottle? In 1994, Congress passed the “Dietary Supplement Health and Education Act,” or DSHEA.  This legislation classified supplements as foods rather than drugs. This meant their ingredients were not subject to the same approval, testing or regulations that apply to drugs. That controversial legislation classified supplements as foods rather than drugs, a decision that permitted untested stimulants in these products without being approved or regulated as drugs.  The bill also prevented the FDA from enforcing traditional regulatory requirements, such as manufacturers having to list on their products’ labels what ingredients were included, and in what amounts. As a result, many ineffective, or even bogus supplement products were legally marketed, making questionable or phony claims about health effects or curing diseases. Below are a few common examples of these flaws.

  • Some supplements are advertised as a cure for diabetes. They claim to “lower your blood sugar naturally,” or “replace your diabetes medication.”  These are false or unproven claims.  Don’t be fooled by them.
  • Many supplements that claim to enhance sexual performance contain unknown stimulants in unknown quantities. These could interact with other medications and harm your health.
  • The FDA found weight-loss products that contain active ingredients found in approved prescription anti-seizure medications and antidepressants.9
  • Some supplements promise to treat or cure autism. FDA warns these are deceptive claims and the products may be very risky, stating “Products or treatments claiming to cure autism are deceptive and misleading, because there is no cure for autism. The same is true of many products claiming to “treat” autism or autism-related symptoms. Some may carry significant health risks.”9
  • Other supplements, such as “superfood powders”, claim they bind to toxins in your body to then help flush out these harmful substances. However, most of these supplements don’t list the toxins they will help “detox”, and, in fact, there hasn’t been any randomized control trial to test the efficacy of any detox diet or supplement in humans, so these claims are incorrect.10

When shopping for dietary supplements “let the buyer beware.” Some companies provide accurate information about their products, but others do not.  For example, supplements currently on the market have been advertised as being opioid abuse treatments, when there is no clinical proof of such claims.  A drug making that claim would have to provide scientific proof of that claim, but supplements can get away with it unless or until the FTC investigates. Here are just a few examples of how dietary supplements can be advertised and sold to millions of Americans who are uninformed of their potential risks.

Ephedra:

Pills containing ephedra or ephedrine (also known as ma huang, epitonin, Brigham’s tea, or sida cordifolia) have been widely touted as effective for weight loss and enhanced performance for bodybuilders. While the ephedra industry boasts that millions of Americans have used ephedra, scientific research indicates it can cause serious health risks, including heart palpitations, vomiting, and nausea, while providing only limited evidence of health benefits. 11 As a result, the U.S. Department of Health and Human Services cautioned Americans about using dietary supplements containing ephedra. In 2004, the FDA prohibited the sale of dietary supplements containing ephedrine, aka the alkaloids from the ephedra plant, but supplements that contain ephedra are sold online by other names.12

Why is ephedra still on the market? You can thank Congress. The products can’t be banned unless proven unsafe, but U.S. law doesn’t require companies to publish studies alerting the public to safety concerns. Unfortunately, if companies aren’t required to conduct the studies, it can be difficult to find funding for researchers to do those studies.  Meanwhile, companies that make millions selling ephedra products lobbied heavily to keep them on the market. 13

Breast-Enhancing Pills:

These products are marketed as offering a non-surgical solution for women who want to enlarge their breasts. The manufacturers suggest that the pills work because their herbs contain phytoestrogen (estrogenic compounds found in plants) and therefore stimulate the growth of breast tissue. The many different pills contain a variety of herbs, but some of the more common ones are fennel seed, saw palmetto, dong quai, blessed thistle, and wild yam. As with many dietary supplements, the marketing of these pills emphasizes “natural” ingredients, seeming to suggest safety. Some manufacturers state, “There are no known side effects”. Having no known side effects doesn’t necessarily mean a product is safe; it may mean an absence of studies on women to find out whether the product causes problems. In fact, we could find no research on either the effectiveness or the safety of any of these products. Although some claims have been made about the health-enhancing effects of phytoestrogens for women, research is still unclear on the effects on humans and what dosages are optimal and which are unsafe.14   Some doctors express concern that pills containing enough estrogen to stimulate breast growth might also increase the risk of breast cancer, since greater exposure to estrogen is related to increased risk of breast cancer.15

Alternatives to Hormone Replacement Therapy:

With warnings about the risks of hormone replacement therapy, many women have turned to “natural” alternatives to treat menopausal symptoms. These include herbal remedies, such as black cohosh, caste tree berry, dong quai, flax seed, ginseng, evening primrose oil, motherwort, red clover and licorice. They also include supplements with soy or isoflavones.

Unfortunately, this is another case of scant knowledge about the safety or effectiveness of widely-sold supplements. With regard to the herbal mixtures, a review of alternative medicine for menopause symptoms noted that these products “should be avoided until research data are available; currently, no safety or efficacy data on such combinations have been published.”16

A number of studies looked at the role of dong quai, ginseng, kava, black cohosh, red clover and soy in relieving menopause symptoms.16,17 Researchers found that dong quai did not help reduce hot flashes, but can be dangerous because it interacts with the blood-thinning medicine warfarin, which may cause bleeding in women taking the drug. Research on ginseng showed that it did not help relieve hot flashes, but it did help improve a woman’s mood and overall sense of well-being. Kava also did not help with hot flashes, but it did reduce many feelings of anxiety among menopausal women. A study conducted by the National Center for Complementary and Alternative Medicine (NCCAM) and the National Institute on Aging found that black cohosh does not relieve hot flashes, either when taken alone or in combination with other supplements.16  Experts at the United States Pharmacopeia, a non-governmental public standards-setting authority for healthcare products, suggest that women who do take black cohosh to relieve menopause symptoms should stop as soon as possible because there is no known benefit.16  It is also important to note that both kava and black cohosh are thought to be hepatotoxins, meaning they are toxic to the liver.17  As with the other herbal supplements, red clover did not reduce hot flashes. Researchers warn that because red clover is a phytoestrogen, it might cause harmful effects in hormone-sensitive tissue such as breast and uterus tissue. Women who are already at risk for diseases and conditions affected by estrogen, such as breast or ovarian cancer, are advised not to take red clover supplements. 12

There has been some debate over the effects of soy on menopause symptoms, because the results of studies have been inconsistent.  A meta-analysis published in 2015 found a small but significant reduction in hot flashes.18 Research findings revealing the risks of hormone replacement therapy serve as an important reminder that even products widely believed to be beneficial are sometimes found to be dangerous when subjected to well-designed, objective research. The research indicating serious health risks from hormone therapy also has generated new interest and more research on natural supplements that contain hormones or phytoestrogens. Phytoestrogens are naturally occurring estrogen-like compounds that may contribute to diseases such as breast and ovarian cancer.

Both the Food and Drug Administration (FDA) and the Federal Trade Commission (FTC) have required several companies to stop making claims that products containing phytoestrogens are safe and effective in preventing or treating serious or life-threatening diseases or conditions like cancer, heart disease, and osteoporosis.15

Melatonin Supplements

Melatonin supplements have also been investigated due to safety and regulation concerns. A 2023 study published in the Journal of American Medical Association (JAMA) found that 22 of 25 different melatonin gummy products tested had either much more (up to 347%) or much less (one had no detectable melatonin, others had up to 26% less) than the dosage listed on the bottle.19 In other words, nearly 90% of the products were mislabeled, and only 3 melatonin products contained melatonin content within 10% of the listed amount. Although 20% of the products had CBD (the active ingredient in cannabis) listed as an ingredient, all were at somewhat higher levels than listed. 18 Similarly, a Canadian study discovered that of the 31 melatonin products tested, more than two-thirds of the supplements did not meet the melatonin content labeled on the bottle, with the rest having within 10% of the listed amount. 20 In addition, more than a quarter of the melatonin products in the Canadian study contained serotonin, a substance used to treat neurological disorders, which can be potentially harmful for some people, especially those also taking SSRIs (antidepressants).20

Conclusions:

It is unwise to trust the claims that manufacturers of dietary supplements make about either the effectiveness or safety of their products. Many other products are being sold with seemingly little regard for the consumer’s well-being. The FDA has few options for intervening, and we may not know about safety problems until millions of consumers have used these products. The most recent fads for miracle drugs suffer from the same problems experienced with ephedra and other dietary supplements: many advertisements but little–if any–information about how they work or how they interact with our bodies.

FDA’s ability to protect consumers is limited when it comes to dietary supplements.  While the agency has recently cracked down on some claims made for these products, it’s important that consumers research what is in these products, and in what amounts, before ingesting them.

Additional Resources:

  • Dietary Supplements. FDA. Click here.
  • Dietary Supplements Ingredient Advisory List can be found here.

 

All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.

The National Center for Health Research is a nonprofit, nonpartisan research, education and advocacy organization that analyzes and explains the latest medical research and speaks out on policies and programs. We do not accept funding from pharmaceutical companies or medical device manufacturers. Find out how you can support us here.

 

References:

  1. US Food and Drug Administration. Dietary Supplement Ingredient Advisory List. 2022. https://www.fda.gov/food/dietary-supplement-products-ingredients/dietary-supplement-ingredient-advisory-list
  2. US Food and Drug Administration. Guidance for Industry: Question and Answers Regarding Adverse Event Reporting and Recordkeeping for Dietary Supplements as Required by the Dietary Supplement and Nonprescription Drug Consumer Protection Act. 2018.  https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-industry-questions-and-answers-regarding-adverse-event-reporting-and-recordkeeping-dietary#:~:text=FDA%20has%20determined%20that%20dietary,the%20FDA%20Safety%20Repor
  3. Federal Trade Commission Weight- loss advertising: An analysis of current trends. https://www.ftc.gov/reports/weight-loss-advertisingan-analysis-current-trends. Published 2002.
  4. US Food and Drug Administration. Labeling Requirements-Misbranding https://www.fda.gov/medical-devices/general-device-labeling-requirements/labeling-requirements-misbranding#:~:text=PMA%20or%20IDE.-,False%20or%20Misleading%20Labeling,or%20misleading%20in%20any%20particular. Updated October 27, 2017.
  5. Tucker J, Fischer T, Upjohn L, et al. Unapproved pharmaceutical ingredients included in dietary supplements associated with US Food and Drug Administration warnings. JAMA Network Open. 2018;1(6):e183337. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2706496
  6. Cohen PA, Travis JC, Vanhee C, at al. Nine prohibited stimulants found in sports and weight loss supplements: deterenol, phenpromethamine (Vonedrine), oxilofrine, octodrine, beta-methylphenylethylamine (BMPEA), 1,3-dimethylamylamine (1,3-DMAA), 1,4-dimethylamylamine (1,4-DMAA), 1,3-dimethylbutylamine (1,3-DMBA) and higenamine, Clinical Toxicology. 2021. https://www.tandfonline.com/doi/full/10.1080/15563650.2021.1894333
  7. Crawford C, Avula B, Lindsey AT, et al. Analysis of Select Dietary Supplement Products Marketed to Support or Boost the Immune System. JAMA Netw Open. 2022;5(8):e2226040. doi:10.1001/jamanetworkopen.2022.26040
  8. Laffin L, Bruemmer D, Garcia M, et al. Comparative Effects of Low-Dose Rosuvastatin, Placebo and Dietary Supplements on Lipids and Inflammatory Biomarkers. J Am Coll Cardiol. null2022, 0 (0). https://doi.org/10.1016/j.jacc.2022.10.013
  9. US Food and Drug Administration. Dietary Supplements. Current as of April 22, 2019. https://www.fda.gov/consumers/consumer-updates/dietary-supplementsKlein,
  10. A. V., & Kiat, H. (2015). Detox diets for toxin elimination and weight management: a critical review of the evidence. Journal of human nutrition and dietetics : the official journal of the British Dietetic Association, 28(6), 675–686. https://doi.org/10.1111/jhn.12286
  11. Shekelle P, Morton S, Maglione M, et al. Ephedra and ephedrine for weight loss and athletic performance enhancement: Clinical efficacy and side effects. Evidence Report/Technology Assessment No. 76 (Prepared by Southern California Evidence-based Practice Center, RAND, under Contract No 290-97-0001, Task Order No. 9). AHRQ Publication No. 03-E022. Rockville, MD: Agency for Healthcare Research and Quality. 2003. https://www.ncbi.nlm.nih.gov/books/NBK36915/
  12. US Food and Drug Administration. FDA acts to remove ephedra-containing dietary supplements from market. 2004. https://wayback.archive-it.org/7993/20170111185913/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2004/ucm108379.htm
  13. Wolfe SM. Ephedra – Scientific evidence versus money/politics. Science Magazine. 2003; 300(5621):905. https://www.ncbi.nlm.nih.gov/pubmed/12702860/
  14. Cassidy A. Potential risks and benefits of phytoestrogen-rich diets. International Journal for Vitamin and Nutrition Research. 2003;73(2):120-126. https://www.ncbi.nlm.nih.gov/pubmed/12747219
  15. See discussions in “Playing to our vanity”, Los Angeles Times, January 14, 2002, http://articles.latimes.com/2002/jan/14/health/he-fads14, and “A pill touted for breast enhancement”, Newsday, May 13, 2003.
  16. Kronenberg F, Fugh-Berman A. Complementary and alternative medicine for menopausal symptoms: A review of randomized, controlled trials. Annals of Internal Medicine. 2002;137:805-813. https://www.ncbi.nlm.nih.gov/pubmed/12435217
  17. Woo SM, Davis WD, Aggarwal S, Clinton JW, Kiparizoska S, Lewis JH. Herbal and dietary supplement induced liver injury: Highlights from the recent literature. World J Hepatol. 2021;13(9):1019-1041. doi:10.4254/wjh.v13.i9.1019
  18. M-n. Chen, C-c. Lin, C-f. Liu. Efficacy of phytoestrogens for menopausal symptoms: a meta-analysis and systematic review. Climacteric. 2015;18(2):260-269. https://www.tandfonline.com/doi/full/10.3109/13697137.2014.966241
  19. Cohen PA, Avula B, Wang Y, Katragunta K, Khan I. Quantity of Melatonin and CBD in Melatonin Gummies Sold in the US. JAMA. 2023;329(16):1401–1402. doi:10.1001/jama.2023.2296
  20. Erland LA, Saxena PK. Melatonin natural health products and supplements: presence of serotonin and significant variability of melatonin content. J Clin Sleep Med. 2017;13(2):275–281. https://jcsm.aasm.org/doi/10.5664/jcsm.6462