Greater regulatory control required for dietary supplements - Part One

In Part One of this article Henry Miller and David Longtin look at the overall regulation of dietary supplements across the Western world and highlight the many shortfalls.

Herbal dietary supplements, or botanicals as they are correctly called, are very big business. In the United States the retail market is about $5 billion annually and growing about 18 per cent a year. About one-third of Americans use products like echinacea, ginseng and St. John’s wort. They are advertised everywhere, for all manner of ailments. Thousands of products cram the shelves of health food stores, food markets and pharmacies nationwide and are also widely available through catalogs and the Internet. Even major pharmaceutical companies are adding dietary supplements to their lines. Western regulations Regulation of dietary supplements varies considerably among developed countries, even among member states of the European Union, which has yet to adopt any transnational standards for these products. Under the most extensive legal framework, Germany has tested more than 300 herbal remedies since 1980, finding about two- thirds of these products to be safe and at least minimally effective (under a very liberal standard). It controls these substances as drugs. But consumers in other Western societies receive little protection. Last year, Canada allotted $7 million (Canadian) to establish an Office of Natural Health Products over a three-year period. Although this new agency will govern the premarket assessment, labeling, licensing, and monitoring of herbal supplements, the precise scope of its mandate has yet to be determined. And in the meantime, these products are blooming and booming in a regulatory vacuum. In Britain, the majority of herbal remedies are classified as food supplements and are thus unlicensed. Others, sold by herbalists, are specifically exempt from licensing under a 1968 law. Only a small number of herbs that are regulated as drugs by the Medicines Control Agency carry any real assurance that they are safe and effective. But few places in the industrialized world, if any, have a more permissive environment than the United States. US DSHA falls short The U.S. Congress has virtually exempted herbal remedies from government oversight. When the Food and Drug Administration considered regulating these products in the early 1990s, manufacturers and health food stores orchestrated a massive letter-writing campaign and other lobbying efforts against stricter controls. The result was the Dietary Supplement and Health Act of 1994, which created a new product class, the dietary supplement, that was not subject to regulations applied to drugs. Now any substance that can be found in foods, regardless of amount or action and including chemicals that act as hormones or toxins, can be produced and sold without any premarket testing or approval. The FDA can restrict the sale of an herbal product only if the agency receives well-documented reports of health problems with it. The number of medical emergencies linked to dietary supplements is both large and underreported. Unlike the monitoring system for regulated drugs, which requires manufacturers to report side effects and illnesses, the dietary supplement system relies on voluntary reports of adverse reactions from the makers of herbal products. Not surprisingly, manufacturers are not eager to admit to the hazards of their products, and some have failed to report thousands of medical problems linked to their brands. Depositions in a recent court case involving the death of a woman from Sacramento, California, show that E'ola, a Utah multilevel marketing firm, received 3,500 customer complaints about its Amp II, a diet formula containing the herbal stimulant ephedra. Not one of those incidents was ever revealed to the FDA, according to an article in The San Francisco Chronicle. Consumers lack guarantees In a regulation that went into effect earlier this year, the FDA worsened the situation by freeing supplement manufacturers to make all manner of dubious health claims - that their products treat conditions such as premenstrual syndrome and acne, for example, although there is little or no evidence to support these assertions. Consumers have no real guarantee that dietary supplements are safe or effective, that the information about dosage on the label is correct, or even that the substance in the container is genuine. Only a few herbal supplements - saw palmetto for treating enlarged prostates and ginkgo for improving memory slightly in Alzheimer's patients - have been shown to be at all efficacious. Moreover, because the demand for some herbal remedies exceeds the supply from natural sources, unscrupulous manufacturers occasionally have switched to cheaper look-alike substances that are pharmacologically different. In February of this year, researchers in Britain discovered that eight brands of herbal skin ointments sold as "natural" treatments for eczema illegally contained dexamethasone, a potent prescription steroid. At about the same time, the FDA ordered four California supplement distributors to recall herbal compounds that illegally contained glyburide or phenformin, prescription drugs that lower blood-sugar levels. The action came after a diabetic in California developed hypoglycemia after he took some of the products which the manufacturers said contained only natural Chinese herbs. Scientific analyses reveal gulf between label and content When ConsumerLab.com, a new private company, tested various herbal remedies, it said that many of the products did not deliver what the manufacturers promised. It found fault with 10 of 27 brands of saw palmetto studied, and discovered that in one-quarter of the 30 brands of ginkgo biloba, the levels of the active ingredient were less than indicated on the labels. Chemists at the Good Housekeeping Institute recently analyzed eight brands of SAMe, an herbal preparation advertised as a "natural Prozac" to relieve depression, and found that two had only half the promised levels of active ingredient, while another contained none at all. Consumer Reports also examined 10 brands of ginseng and concluded that several contained almost none of the active ingredient. Proof required There is no shortage of information available to consumers about dietary supplements, but it is heavy on advocacy and light on scientific proof. Putting it another way, until there is evidence that rises to the standards of the medical and scientific communities that a preventative or therapeutic nostrum actually works, we do not know that it does work. We might just as well take a pinch of herbes de Provence along with a multivitamin pill each morning. Worse yet, many of these products are already known to be toxic, carcinogenic, or otherwise hazardous, causing high blood pressure, deadly allergic reactions, cardiac arrhythmias, and kidney or liver failure. Some also can exacerbate autoimmune diseases like arthritis and lupus. In February, articles in the medical journal The Lancet identified life-threatening side effects of St. John's wort: interference with the protease inhibitor indinavir, which can lead to treatment failure in AIDS patients; and rejection of heart transplants by an interaction with the immune suppressant cyclosporine. Chinese herb causes kidney failure In June, The New England Journal of Medicine reported that a Chinese herb that caused kidney failure in dozens of Belgian dieters in the early 1990s appears to have even deadlier long-term effects -- cancer and precancerous lesions. The subjects in this study were an unlucky subset of some 10,000 Belgian dieters, who between 1990 and 1992 took a combination of Chinese herbs and conventional drugs prescribed by weight-loss clinics. After dozens of victims suffered kidney failure, investigators discovered that Belgian pharmacists had been using mislabeled Chinese herbs to produce the diet pills. Instead of using Stephania tetrandra, the pharmacists had filled the pills with derivatives of the herb Aristolochia fangchi, which has long been known to damage kidneys and to cause cancer in animals. At least 70 people experienced complete kidney failure, while another 50 suffered kidney damage serious enough to require treatment. The first urinary tract cancers were found among these victims in 1994. To prevent the onset of the disease in others, doctors in Brussels advised patients whose kidneys and ureters had stopped functioning to have the organs surgically removed. Thirty-nine people chose to have the operation over the past several years. When researchers studied the excised tissue, they were shocked to discover that 18 of the patients had already developed cancer, while 19 others had precancerous lesions. Authorities ignore evidence Belgium banned the importation of Aristolochia in 1992. In May of this year, the FDA distributed warnings to health professionals and the supplements industry about the dangers of Aristolochia, and it plans to block the herb's entry into the United States in the near future. For many critics of the present U.S. policies on dietary supplements, this action is long overdue, considering that Germany banned Aristolochia in 1981 and that the World Health Organization issued a warning about the herb in 1982. Medical organizations also have advised people to stop using herbal remedies such as St. John's wort, ginkgo biloba, and ginseng at least two or three weeks before any scheduled surgery to avoid dangerous interactions with the anesthesia. In Part Two the authors investigate models to improve the current state of dietary supplement legislation.

Dr Henry Miller is an academic researcher and regulatory consultant. From 1979-1994 he was an official at the US Food and Drug Administration. From 1989-1994 he was the founding director of the FDA's Office of Biotechnology. Mr. Miller is currently Senior research fellow at Stanford University.