The Research Gap

When dietary supplements show promise for treating diabetes and other aging-related conditions, who should perform the studies needed to determine whether they're safe and effective?

In his laboratory at the Albert Einstein College of Medicine in the Bronx, medical scientist Michael Brownlee no longer answers the phone. Scores of callers have been besieging him, all wanting to know how to get their hands on a little known substance that has sparked tremendous excitement in the American diabetes community. In a study published in the March issue of Nature Medicine, Brownlee and his colleagues showed that benfotiamine, a fat-soluble derivative of Vitamin B1 that's more readily absorbed than the natural version, can block the damage triggered when cells are exposed to high concentrations of sugar. Such cellular injury likely underlies many of the complications associated with diabetes, including kidney failure, nerve damage, and even blindness. What's more, benfotiamine also prevented the development of blindness, or retinopathy, in diabetic rats, raising hope that the compound would do the same for people. According to the American Diabetes Association, 17 million Americans suffer from the disease, and 12,000 to 24,000 of them go blind each year because of it.

Although the research is in its earliest stages, patients contacting Brownlee want to start taking the vitamin now. "No conventional treatment worked," says Brownlee, "and they're willing to try anything." This demand for benfotiamine dramatizes a problem faced by those who seek new treatment alternatives for diabetes and other aging-related conditions: How should scientists and health-care professionals deal with dietary supplements that show promise in the laboratory, but have not yet demonstrated their effectiveness in humans, and thus aren't ready to be included in a physician's medical arsenal?

Dietary supplements--as defined by Congress--are products such as herbs, vitamins, and amino acids that are taken orally to "supplement the diet." Although they can have powerful medicinal properties--as well as side effects--nutritional supplements are much less heavily regulated than prescription drugs. They also aren't generally protected by patents. "Most of the time, materials that are used in nutritional supplements are well established, well known, and not proprietary," says James T. O'Reilly, a food and drug safety law expert at the University of Cincinnati College of Law.

This lack of patent protection poses a problem: If a pharmaceutical company cannot claim exclusive rights to a supplement, it has little incentive to invest in the costly clinical trials needed to prove the compound's effectiveness. According to the Pharmaceutical Research and Manufacturers of America (PhRMA), carrying a drug from the lab bench, through clinical trials, and to the Food and Drug Administration (FDA) for approval can run upwards of $800 million. With a simple, unpatentable vitamin derivative such as benfotiamine, "a drug company would not be interested," says Richard Furlanetto, a pediatric endocrinologist and scientific director of the Juvenile Diabetes Research Foundation. "If you spend all the money to prove [a supplement is effective] and somebody can just come along and market the thing, you're not going to make any profit."

If cheap dietary supplements were shown to be effective, they could reduce health care insurance costs. Moreover, food safety advocates stress the testing of supplements as a matter of public health. "To determine whether supplements are safe, you have to do a risk benefit analysis," says Ilene Ringel Heller, senior staff attorney at the Center for Science in the Public Interest. "If it's not effective, why should anybody undergo any risks?"

But there's a long way to go before benfotiamine, used as a treatment for diabetic retinopathy, will be backed by the same kind of clinical research as an FDA-approved drug. First, Brownlee's study was done in animals, not people, says Eugene Barrett, president elect of the American Diabetes Association and a professor of internal medicine at the University of Virginia. Second, Brownlee doesn't yet know what dose would be required to prevent the onset of diabetic retinopathy in patients. Once a dosage has been determined, expensive, time-consuming large-scale clinical trials are needed to prove that the compound works.

Although there's little reward for testing a supplement, profit-wise, there's also little punishment for selling one that hasn't been proved safe and effective--a situation that helps to explain the recent slew of deaths linked to the herb ephedra. And benfotiamine might soon be available in the United States. A Calgary-based dietary supplement manufacturer called Advanced Orthomolecular Research already sells it in Canada, and is seeking FDA approval to market the substance here.

Brownlee sees pluses and minuses in this development. If people start taking supplements that haven't been clinically tested without discussing it with their doctors, "that's a public health problem." From the perspective of an individual with diabetes, however, "there's a calculated risk, but you may be benefiting," he says. And because benfotiamine is already being used in Germany and elsewhere to treat nerve damage, the supplement is probably safe. As an added benefit, Brownlee says, a public rush to use benfotiamine could force the government to devote research dollars to test it.

At present, the government doesn't invest much in studying supplements. NIH's Office of Dietary Supplements has a budget of only $19.9 million for 2003. Even so, researchers at NIH are showing interest in benfotiamine. Judith Fradkin, an endocrinologist who directs the diabetes division at the NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), says that NIH is looking into how to pursue this "potentially very exciting research." Until then, the question, as Furlanetto sees it, remains: "Just because the substance is available, does that mean it's good for you?"

That's something older Americans, whether diabetic or not, need to be concerned about. Seniors tend to use dietary supplements more frequently than the general population, and many supplements can react adversely with prescription medications. It's hard to repress the hope for a diabetes cure. But if benfotiamine is not that magic bullet, someone had better tell the patients--because they aren't waiting to find out. "I've gotten five thousand e-mails," says Brownlee. "[Now] a number of people are writing back to me and saying, 'I got it from Germany…'"

Chris Mooney is a freelance journalist in Washington, D.C. If he had a lawn, he would mow it and market the clippings as a dietary supplement.