This past October, the office of the inspector general of the Department of Health and Human Services issued two reports underscoring the need for improved oversight of the marketing of dietary supplements and improved surveillance of their effects. The reports add to a mounting body of evidence documenting a serious public-health problem.
Use of dietary and herbal supplements has grown dramatically in recent years in the United States. In 2007, according to the National Center for Complementary and Alternative Medicine, $14.8 billion was spent on nonvitamin, nonmineral, natural products, such as fish oil, glucosamine, and Echinacea—equivalent to approximately one-third of total out-of-pocket spending on prescription drugs. Of that total, $4.4 billion was spent on herbal supplements. Data from the National Health and Nutrition Survey for 2003 to 2006 indicate that one-half of American adults use dietary supplements and 20 percent use a supplement with at least one botanical ingredient.
Many people think that because herbs are natural, and because they are being marketed and sold legally, they must be safe and effective. Furthermore, surveys of the public indicate that most people believe these products are regulated by the U.S. Food and Drug Administration. In fact, both assumptions are mistaken.
In 1994, Congress passed the Dietary Supplement Health and Education Act, with heavy backing from the dietary supplements industry. By defining herbal supplements and botanicals as dietary supplements, DSHEA exempted them from the more rigorous standards used by the FDA in regulating food, drugs, and medical devices—essentially leaving it up to the industry to regulate itself. This single piece of legislation opened the floodgates to a rapid expansion in the sale of dietary supplements.
Between 1994 and 2008, the number of dietary supplement products on the market increased from 4,000 to 75,000. In the first 10 months of 2008, the FDA received nearly 600 reports of serious adverse events (including hospitalization, disability, and death) from these products and 350 reports of moderate or mild adverse events. However, the FDA believes that these reports are drastically underreported and estimates that the annual number of all adverse events is 50,000.
Two highly-respected physician-scientists, Donald Marcus of Baylor College of Medicine and Arthur Grollman of Stony Brook University, have been drawing attention to the dangers of herbal supplements for more than a decade. In a recent article in the Archives of Internal Medicine, they noted, “Even when the agency [FDA] identifies an unsafe product, it lacks authority to mandate its removal from the market because it must meet the very high legal requirement to demonstrate a ‘significant or unreasonable’ risk. That is why it took FDA more than 10 years to remove from the market ephedra-containing herbal weight-loss products that had caused hundreds of deaths and thousands of adverse events.”
Marcus and Grollman point to a number of major deficiencies in the regulation of herbal supplements: There is a lack of standardization to guard against adulteration and ensure a consistent level of the active ingredients. Herbal supplements can interact adversely with prescribed drugs. Herbal supplements do not need to be tested before marketing, as is required for prescription and over-the-counter drugs. Producers of dietary supplements engage in deceptive marketing and do not adequately label products to inform consumers about their nature and regulation. Finally, there is no requirement to report all adverse effects promptly to the FDA.
This lack of safeguards creates a situation in which unwitting consumers are exposed to herbal products that in most cases have no proven effectiveness but often have serious toxicities. Though we tend to equate natural with healthy, plants have developed toxins to protect themselves against predators. The perception that herbal supplements and botanicals are inherently safe is belied by extensive evidence of the danger posed by such products, including kava, ephedra, comfrey, and aristolochic acid. However, intensive advertising by the dietary supplements industry exploits and reinforces the illusion that plant products are inherently beneficial and harmless. In addition, the field of complementary and alternative medicine, which came to prominence in the 1990s, has helped to give a veneer of legitimacy to the use of supplements, even though this discipline is held in disrepute by scientists like Marcus and Grollman.
The most dramatic instance of the potential for harm from the unregulated use of botanicals occurred in Brussels, Belgium. Women attending a weight-loss clinic participated in a program that involved taking a combination of Chinese herbs. The program had been in operation for 15 years with no ill effects. However, in the early 1990s, the company that supplied the herbs substituted Aristolochia for another, benign, herb with a similar sounding name in Chinese. Aristolochia has been widely used in herbal medicine, but it contains aristolochic acid—a powerful kidney toxin and a carcinogen. As a result of including Aristolochia in the regimen (for a period of two years), 105 women attending the clinic developed rapidly progressing kidney failure and had to go on dialysis or have kidney transplants. Many of the women went on to develop cancer of the upper urinary tract. Cases of kidney failure due to the ingestion of herbal products containing aristolochic acid have also been reported in the United States, Europe, and Asia.
This dramatic case led the FDA to issue a warning regarding products containing aristolochic acid and some countries banned these products, including the United Kingdom, the Netherlands, Germany, and Japan. However, in spite of these restrictions, products containing aristolochic acid are still available on Internet. What is essential to realize is that the effects of Aristolochia were identified only thanks to the large cluster of cases of kidney failure occurring in young women who had attended the same spa. It is much more likely that isolated cases will go unnoticed, as happened with ephedra, and it could take years to identify a common cause.
People failed to recognize the nephrotoxic effects of Aristolochia in spite of its use in many cultures worldwide over thousands of years. In an interview, Grollman explained why: “The reason, of course, is quite simple. It’s painless, and the damage happens much later, so you don’t put together the fact that you took this medicine and four years later, you have kidney failure. It’s been part of Ayurvedic, European, Chinese, and South American medicine for centuries. All of the great civilizations have used it. And not one reported its toxicity until the Belgians did 20 years ago. There are certain things that tradition can’t tell you.”
In the political campaign that just ended, we heard a lot about the evils of regulation. But regulation cannot be judged in the abstract, without reference to the pertinent facts in the real world or the lives of real people. The recent outbreak of fungal meningitis caused by contamination of a steroid produced by a compounding company in Massachusetts underscores the potential for lapses even in the case of products that do come under the purview of the FDA. All the more reason why dietary and herbal supplements ought to be subject to at least as rigorous safeguards as those that apply to prescription and over-the-counter medications.