The world of alternative medicine is in a state of incredible disarray, in case you haven’t noticed.
Over the last five years, a number of natural treatments have been subjected to the same kinds of rigorous double blind studies required of conventional medications, and they have fared poorly. Four of the most commercially popular of these treatments have received particularly harsh treatment from the scientific method:
Ginkgo Biloba for Memory. Ginkgo biloba, the top-selling herbal preparation in the U.S. in recent years, is marketed primarily as a memory and circulation enhancer. But in 2002, JAMA published a double blind placebo controlled study in which 115 healthy elderly people were randomized to ginkgo biloba 40 mg TID or placebo. Six weeks later, all were given 14 different measures of cognitive functioning, and there were no significant differences on any of them based on treatment status ( JAMA 2002;288:835–840).
Echinacea for the Common Cold. We all know somebody who swears by Echinacea as the panacea for cold symptoms. Last year, this botanical was tested in the first well-designed controlled trial. A total of 437 volunteers were exposed to the rhinovirus and were randomized to three different preparations of echinacea or to placebo. They were observed for five days after the viral challenge. There was no difference between echinacea and placebo on rates of infection, severity of symptoms, volume of nasal secretions, concentration of white blood cells in nasal secretions, or virus titer (NEJM 2005;353:341-348).
Saw Palmetto for Benign Prostatic Hyperplasia. Frequently recommended by family practitioners as an effective remedy for BPH, saw palmetto had been studied in controlled trials but mostly with substandard methodology. This year, a definitive study was published in the New England Journal of Medicine. Researchers randomized 225 men with BPH to one year of treatment with either saw palmetto (160 mg BID) or placebo. There were no significant differences between the two groups in maximal urinary flow rates, prostate size, residual volume after voiding, quality of life, or serum PSA (NEJM 2006;354:557-566).
Glucosamine and Chondroitin for Arthritis. Talk about mainstream—these supplements have become so accepted as treatments for arthritis that orthopedists often prescribe them for their patients. As was true for saw palmetto, numerous studies had hinted at clinical efficacy, but they fell short of the methodological standards required of conventional pharmaceuticals. The GAIT trial was a government-funded study that randomized 1583 patients with arthritis of the knee to receive 24 weeks of treatment with glucosamine 1500 mg QD, chondroitin sulfate 1200 mg QD, the two combined, Celebrex (celecoxib) 200 mg QD, or placebo. The only treatment that outperformed placebo overall was Celebrex, although in the subgroup of patients with more severe pain, combined glucosamine/chondroitin yielded a higher response rate than placebo (73% vs. 54%) (NEJM 2006; 354:795-808).
Of course, none of these studies were absolutely perfect and the experts in the relevant specialties have quibbled about aspects of methodology; furthermore, don’t forget that even for FDA-approved drugs, the number of negative trials (in which the drug fails to outperform placebo) will often outnumber positive trials, but the former are more difficult to publish, and therefore do not get as much visibility.
Nonetheless, this litany of negative studies highlights the fact that, in the alternative medicine industry, companies are allowed to market remedies for clinical problems without having to prove their efficacy. High quality studies of the four substances mentioned above were finally conducted decades after they came on the market, and the results imply that they are largely ineffective for the marketed conditions.
How, exactly, are natural treatments regulated in the United States?
In order to understand the answer, you have to go back to 1994, when Congress passed a law called the Dietary Supplement Health and Education Act of 1994 (DSHEA).
Before DSHEA, the FDA had to approve any new “food additives,” which made it difficult for supplement companies to bring new products to market quickly. This 1994 law, however, limited the FDA’s involvement to post-marketing safety evaluation. Thus, manufacturers no longer have to prove the safety of their products before marketing them; instead, the onus is on the FDA to monitor supplement safety and to take action if bad things happen. Thus far, only one supplement has been banned by the FDA—ephedra, a natural stimulant that was withdrawn in 2004 because of post-marketing reports of several cardiovascular deaths linked to the substance.
Beyond the issue of safety, DSHEA broadened the definition of “dietary supplements” to include things like herbs and hormones, and specifically allowed manufacturers to make certain health claims on their labeling. According to the act, as long as the label doesn’t say that the supplement actually cures a specific disease, positive statements are allowed under a category known as “Nutritional Support Statements.”
What does this mean in psychiatry? As an example, our patients are buying products with names like “Brain Focus,” which can legally be advertised as “clinically tested to improve memory and focus” (see http://zlabs.us/brainfocus.html). As long as this mix of various supplements does not claim to actually treat ADHD or dementia, these more general claims are allowed. If asked to, manufacturers are required to produce some sort of “substantiation” for their claims. Unlike the FDA approval process, evidence need not be based on placebo-controlled double-blind trials; case series, small open trials or even suggestive animal trials are sufficient.
Whether or not this new system benefits our patients is a point of heated debate. For the party line, go the “Dietary Supplement” section of FDA’s Center for Food Safety and Applied Nutrition website (http://www.cfsan.fda.gov/~dms/ds-oview.html#safe). Here, you’ll learn that DSHEA allows consumers access to a broad range of health products and that adequate safety regulations are in place. For a dissenting view, go to the Quackwatch website, which posts a paper by Stephen Barrett, M.D., arguing that DSHEA was a product of nutrition industry lobbyists and that it has resulted in consumers being bombarded with fraudulent health claims (http://www.quackwatch.org/02ConsumerProtection/dshea.html).
In the meantime, we would recommend that psychiatrists ask patients whether they are taking dietary supplements and find out what is in them. Many patients will be surprised to learn that the health claims on the labels often are based on tiny unreplicated studies. They may then decide that there are better ways to spend their hard-earned money.
TCPR Verdict: Dietary supplements: scrutinize the claims.