Examining the Safety of Natural Supplements

Jennifer Brooks, PhD, Elizabeth Nagelin-Anderson, MA and Diana Zuckerman, PhD

In their quest for health and beauty, half of all American adults take natural supplements to solve all sorts of problems,¹ such as bodies they think are too big and breasts they think are too small. Billions of dollars are spent every year. But do these products really work, and how much do Americans know about their safety?

The U.S. Food and Drug Administration (FDA) requires that supplement companies label ingredients in their products. Eight chemicals are banned. Otherwise, companies are basically 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 can limit its marketing or sales.² Companies making supplements need not even inform the FDA before producing or selling their products. And, unlike drugs, the FDA does not regulate dietary supplements for purity or quality. Moreover, unlike drug makers, the manufacturers of supplements are not required to report to the FDA health problems that might be related to their products. A supplements' "guarantee" does not mean a guarantee to work or be safe.

When they advertise supplements, manufacturers are required to abide by the Federal Trade Commission's (FTC) regulations, only making claims that are truthful and substantiated. Claims are not allowed to be "misleading," but 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.

Two recent examples show how dietary supplements can be advertised and sold to millions of Americans who are ignorant of their potential risks.

Ephedra

Pills containing ephedra or ephedrine (also known as ma huang, epitonin, or sida cordifolia) were widely touted as effective for weight loss and enhanced performance. While the ephedra industry boasts that 15 million Americans use ephedra every year,⁴ a recent scientific review links ephedra to serious health risks, including heart palpitations, vomiting, and nausea, while providing only limited evidence of health benefits.⁵ As a result, the U.S. Department of Health and Human Services cautioned Americans about using dietary supplements containing ephedra. The FDA also is proposing warning labels for bottles of ephedra, making it clear that the pills could cause heart attacks, strokes or death.

So why is ephedra still on the market? You can thank Congress. It's a Catch 22: 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. Who is supposed to pay for the research to evaluate risks? Is it ethical to conduct such studies if the researchers think the product is dangerous? Meanwhile, companies that make millions selling ephedra products have been lobbying heavily to keep them on the market.⁶

The Skinny Pill For Kids

Another example of a widely advertised weight-loss supplement is the Skinny Pill for Kids. This pill was modeled after the Skinny Pill for adults, and advertised over the Internet as a safe solution to obesity for children ages 6 to 12. Fortunately, many doctors pointed out that some of the ingredients in the pill are diuretics and can cause serious problems for children, including kidney damage.⁷ One of the ingredients has been linked to liver damage and is not recommended for children under age 12.

Nevertheless, the makers of the Skinny Pill for Kids claimed their product was safe. Did they ever test the product on children? No.

In February 2003 the House Committee on Energy and Commerce began investigating the development and marketing behind this product (along with other weight-loss pills, particularly those advertised for children).⁸ The manufacturer had advertised the pill as "coming soon" but had never sold it; it is no longer being advertised. Without the widespread media attention this particular pill received, it might well have been sold to parents worried about their children's weight.

The widespread negative publicity for ephedra and the opposition to The Skinny Pill for Kids show how, despite regulatory loopholes, it is possible to restrict the marketing of dangerous natural supplements. In the case of the Skinny Pill for Kids, the risks were identified before the product ever made it to consumers.

The question remains: how many other supplements are on the market whose efficacy and side effects remain unknown? Three popular dietary supplements -- bitter orange, breast-enhancing pills, and natural alternatives to hormone replacement therapy -- illustrate the problem.

Bitter Orange

Bitter orange has been widely marketed for weight loss and other uses, including as a nasal decongestant and to reduce swelling of the eyelids. With a wide range of alternative names-including sour orange, Seville orange, and Citrus Aurantine -- this product comes from a plant whose peel, flower, leaf and fruit have long been used in Chinese medicine. The "active" ingredient of bitter orange is synephrine, a stimulant.

Despite the fact that bitter orange is often marketed as a safe and effective weight-loss alternative to ephedra, there is little science available to support this claim. Research is insufficient to conclude that bitter orange leads to weight loss, in either the short or long term. Unfortunately, the side effects for humans also are largely unknown, but animal studies, which find that synephrine increases blood pressure, suggest caution.⁹ Some doctors suggest that, at minimum, people with heart problems or hypertension should avoid bitter orange, and some advertising echoes these precautions.¹⁰

It also is not recommended for children and breast-feeding or pregnant women. Individuals taking monoamine oxidase inhibitors (MAOIs), such as certain medications for anxiety and panic disorders, should avoid bitter orange, since
interactions with synephrine could potentially cause health problems.¹¹

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 safety; 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 too large).¹² 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.¹³

Dietary Supplements Providing Alternatives to Hormone Replacement Therapy

With research suggesting serious health risks associated with hormone replacement therapy, we've seen a burgeoning of ads for "natural" alternatives to treat menopausal symptoms. These include herbal remedies, such as black cohosh, caste tree berry, dong quai, 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 available, the authors of a 2002 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."¹⁴ Only slightly more information is available on the individual herbs in these pills. For instance, the authors of the 2002 review note that most studies of black cohosh have found it beneficial for treating hot flashes. They also point out, however, that no studies follow patients over a six-month period and that the long term safety of black cohosh should not be presumed without more study. The authors identified only two studies of red clover, neither of which found that it alleviated hot flashes, and found little information on the effectiveness or safety of dong quai, ginseng or evening primrose. Further, some of these herbs also may have undesirable side effects. For instance, the authors note that dong quai can lead to bleeding when taken with an anticoagulant and may cause sensitivity to the sun.

The 2002 review also examined 11 clinical trials of soy or isoflavone supplementation (taken in food and pill forms) and found that soy reduced hot flashes in less than half of the studies in which it was taken for six weeks or more. The authors also noted that the effects were small and mostly disappeared after six weeks. In the end, the authors note that eating more beans or bean products (a good source of isoflavones) is not likely to cause any harm, though the safety of the pills sold over the counter-which contain isoflavones, sometimes in high doses -- is unknown. Moreover, 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. http://www.fda.gov/bbs/topics/news/2005/NEW01260.html.

This past year, 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.

Conclusion

It is unwise to trust the claims that manufacturers of dietary supplements make about either the effectiveness or safety of their products. Although there undoubtedly are examples of products' being tested and passing some sort of efficacy and safety standard, many other products are being sold with seemingly little regard for the consumer's well-being. The FDA has few options for intervening, and -- as we saw with ephedra -- we may not know about safety problems until millions of consumers have used these products. In some cases -- such as that of the Skinny Pill for Kids -- we may be lucky enough to have skeptics call the product into doubt before it is ever used, but this response will probably be rare.

The most recent fads for miracle drugs suffer from the same problems experienced with ephedra and other dietary supplements: broad marketing with minimal--if any--information about how they work or what they do to our bodies. For this reason, those searching for the latest supplement to cure perceived beauty or health problems would do well to learn from experience: Let the buyer beware.