No 'Alternative' By JEROME GROOPMAN
Some 60 million Americans use supplements, megavitamins, herbs and other so-called "alternative" treatments. Their out-of-pocket costs approach $40 billion a year. Their therapies are promoted by a vast number of self-help books, Web sites and talk shows that feature thrilling testimonials of benefits for maladies that mainstream medicine cannot remedy. But we are now learning what happens when the testimonials are subjected to objective testing. In February, the results of a large clinical trial of the supplements glucosamine and chondroitin sulfate for osteoarthritis were released. These data came on the heels of a rigorous assessment of the herb saw palmetto for symptoms of an enlarged prostate gland. Both studies failed to show clinical efficacy. All this should mark a sea change in how the public views such treatments.
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In the first case, some 1,583 patients with symptomatic osteoarthritis of the knee were randomly assigned to receive glucosamine, chondroitin sulfate, both supplements, the anti- inflammatory Celebrex, or placebo. The trial was sponsored by the National Center for Complementary and Alternative Medicine, NCCAM, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The study found there was no overall statistical benefit except for Celebrex. Of note, 60% of the patients receiving placebo reported significant improvement.
This result was greeted without surprise by a colleague of mine who is a primary care physician. Many of her patients swear by the benefits of the supplement for their arthritis; and one of them, a woman in her 70s, never failed to press the physician to take it for her own aches and pains. When the doctor demurred, the patient eyed her with some disdain. "You doctors are so close-minded," she said. "You won't accept a treatment that comes from outside of your own world." One day, a package arrived at her office. It was a large container of glucosamine, which still sits in a cabinet, unopened. "Despite all my patients' testimonials, it didn't make sense," she told me. "Glucosamine is absorbed from the digestive tract and rapidly broken down in the body. How could this supplement survive digestion, travel through the circulation, deposit in worn-down joints, and rebuild cartilage?"
My colleague is a caring and competent clinician, and I was struck by the barb from her patient about being "close-minded." Most physicians I know feel triangulated in caring for people who pursue alternative therapies. Pointed questioning of the probity of the treatments casts the doctor in the role of adversary rather than ally. Glibly endorsing such therapies may be politically correct but, in essence, patronizes the patient, since the doctor has no objective basis to assess the value of the herb or supplement being promoted for the problem. An honest clinician questions all treatments -- ranging from an antibiotic from a pharmacy to an elixir from a health food store -- and asks if they pose real risks, offer real benefits, or both. When I was a patient with a serious problem of uncertain outcome, I felt the powerful temptation to seek a magical solution. Most doctors are sympathetic to this sensibility. But a good doctor distinguishes magic from medicine.
The widespread misconception among the public is that what is "natural" is necessarily salubrious and safe, while in fact, the natural world is filled with poisons and toxins. Some of those natural poisons, of course, can be used therapeutically: Two of the most important chemotherapy drugs, vincristine and taxol, are derived, respectively, from the periwinkle plant and the Pacific yew tree.
The patients I care for with cancer or AIDS take multiple prescription medications, and how these drugs interact with each other can be no simple matter; throw into the mix an herb of unclear composition and unknown metabolism, as well as unknown side effects, and there is a recipe for trouble. I witnessed this as the first group of pharmaceuticals against HIV were being tested during the late 1980s. There was a groundswell of demand among understandably desperate patients for alternatives to medicines like AZT that can have serious side effects and, as single agents, only modest benefit. One "natural" alternative was an extract from a Chinese cucumber termed compound Q. It was imported from Asia and taken by a number of desperate AIDS patients based on testimonials that it could eradicate HIV. The fact that the cucumber extract was used as an abortifacent in China seemed not to register, until several patients developed severe toxic reactions, including coma. Physicians and researchers who challenged compound Q were vilified as being ignorant, wed to the pharmaceutical-medical complex, or envious that a cure had arrived from outside of "mainstream" medicine.
Then there was St. John's wort. This popular herb was touted as a treatment for depression and alleged to have antiviral activity in people with HIV. It was shown to be no better than placebo for depression and, most worrisome, to interfere with the activity of the lifesaving anti-HIV protease drugs.
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That alternative therapies are coming under the sharp lamp of science is of some irony. In 1991, Congress passed a bill to create an Office of Alternative Medicine within the National Institutes of Health. Seven years later, this became NCCAM. Sen. Tom Harkin of Iowa was one of the main drivers behind the legislation. Mr. Harkin was said to believe that nontraditional potions and procedures were important therapies, his faith stemming in part from friends and family who testified to their importance. A collective groan was heard in the halls of university hospitals and research centers. Precious federal dollars were being diverted from "real science" to shamanism. Some alternative medicine gurus also objected, worried that their therapies would be tested "the NIH way."
The academic opponents were proven wrong -- because the fears of the gurus came true. The reason for this can largely be attributed to Stephen Straus, who directs the NCCAM. Dr. Straus is neither a naysayer nor a believer, but rather a scientist, meaning that he is agnostic about any particular therapy. Dr. Straus explained that the same rigorous metrics used to evaluate normal medicine are applied to the numerous unproven alternative treatments -- "the NIH way." The justification for spending federal funds is still hotly debated, as evidenced by an impassioned article in a recent issue of the journal Science, with a call for the Congress to re-examine the issue. But rigorous testing of popular alternative therapies is a matter of public health and informs proper medical practice. On the wall of Dr. Straus's office is a framed quote: "The plural of anecdotes is not evidence." A billion Chinese cannot be wrong, goes the old saw, but in fact they can and often are.
But it is not a matter of geography or culture. Until the 19th century, Western practitioners were badly wrong, attributing diseases to an imbalance in humors, bleeding patients and prescribing poultices and purgatives. Modern Western medicine has also embraced therapies that were later disproven. In the 1960s, surgeons tied off an artery under the breastbone in patients with angina, believing this increased circulation to the diseased heart. Many patients swore by the surgery, but when the procedure was subjected to a clinical trial, it turned out that the sham operation was equally beneficial.
Placebos are very powerful. Beyond yoga for lower back pain and acupuncture for analgesia, there has not been a study showing an unequivocal benefit of an alternative therapy when subjected to the rigor of an NIH trial. This negative outcome should not be greeted smugly, because most experimental drugs developed by pharmaceutical or biotechnology companies fail to fulfill their promise. The difference is that these companies rely on biological mechanisms to select candidate drugs for testing, rather than unsubstantiated testimonials and anecdotes.
Dr. Straus believes the public should acquire an historical perspective on the urban legends of alternative therapy. Beyond compound Q and St. John's wort, he recalled the euphoria around laetrile, the extract from apricot pits promoted as a cancer cure, that brought Steve McQueen to Mexico and to his death, and also the story that shark cartilage caused tumors to melt away because sharks never develop cancer (not true). On the other hand, one of the most important new therapies for leukemia is an arsenic derivative identified in western China as part of traditional practice that resulted in well-documented remissions; its effects on key molecules in the malignant cells have been elegantly mapped by scientists. And qualified researchers are testing components of tumeric and other spices than can inhibit melanoma and breast cancer cell growth. Science is enthusiastic when it meets reality.
Still, the failure to prove that so many popular alternative treatments have any benefit has generated resistance among the believers. The promoters of saw palmetto objected to the study, saying that the dose and preparation used in the trial were not optimal. But, in fact, the most frequently used preparation was the one studied. The clinical trial of glucosamine and chondroitin sulfate will be extended, but lacking a scientific rationale for the treatment should lower expectations about a different outcome.
How long does it take for a false messiah to be abandoned when redemption does not arrive? "Things that are wrong are ultimately set aside," Dr. Straus said, "and things that are right gain traction. There are the conflicting tides of belief and fact, and each has its own chronology. Things don't change quickly, but over time a cumulative body of evidence becomes compelling." I reflected on this when I read that one major vendor of saw palmetto asserted he would continue to promote the herb despite the new data. As science spreads in his world, doubt will chip away at blind faith, and he will find a shrinking group of believers.
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Dr. Groopman is the Recanati Professor at Harvard Medical School.