January 30 (HealthDay News) -- Eager to relieve joint pain and repair the cushioning between bones, millions of arthritis sufferers reach for glucosamine, an over-the-counter dietary supplement.

Despite its popularity, studies examining the effectiveness of this natural therapy have yielded mixed results.

"There is still a lot of uncertainty about glucosamine," said Dr. Steven C. Vlad, a fellow in clinical epidemiology and rheumatology at Boston University School of Medicine.

So what is glucosamine, anyway? It's a type of sugar that the body produces and distributes in cartilage and other connective tissue. Chondroitin sulfate, often taken in combination with glucosamine, is a complex carbohydrate that helps cartilage retain water, according to the U.S. National Center for Complementary and Alternative Medicine.

These substances are derived from animal tissues, according to the Arthritis Foundation. Glucosamine is extracted from crab, lobster or shrimp shells, and chondroitin sulfate comes from animal cartilage, such as tracheas or shark cartilage.

Vlad's own study tried to determine why the results of glucosamine trials differed so widely. Of the 15 studies he reviewed, there was one clear finding: A particular glucosamine preparation, called glucosamine hydrochloride, doesn't work.

Results among trials involving another common preparation, glucosamine sulfate, showed wide variation -- more than would be expected by chance. Based on the evidence, Vlad concluded that supplement industry support could be a source of bias in some of these studies.

Although critics questioned Vlad's finding, he stands by the results. "Numerous analyses have showed that industry funding is correlated with stronger findings and selective publication of positive results," he noted.

More recently, researchers at the University of Utah School of Medicine reported results from a follow-up to an earlier glucosamine trial. Arthritis patients in this leg of the study took glucosamine; a combination of glucosamine and chondroitin; the anti-inflammatory drug celecoxib (Celebrex), or a placebo. X-rays were taken of patients' knees before the trial began and one and two years later to determine whether glucosamine alone, or in combination with chondroitin, would slow the loss of cartilage.

Lead author Dr. Allen D. Sawitzke, an associate professor of internal medicine at the University of Utah School of Medicine, said he and his colleagues had hoped to have enough patients and measurement accuracy to be able to show some slowing of the damage, but in the end, the results were inconclusive.

"So, it's an example of a null study, that is, a study where there is no difference detected, which isn't the same as saying there is no difference," Sawitzke said.

Dr. Jason Theodosakis, an assistant professor at the University of Arizona College of Medicine and author of the book, The Arthritis Cure, said the study was flawed in many ways, including the small sample size, short duration and imprecise X-ray methodology. "I really can't believe it was even published," he said.

Like many physicians, Theodosakis continues to recommend glucosamine and chondroitin. "This study does nothing to discourage that," he said.

Trying glucosamine for 60 days makes sense, especially for patients who can't tolerate ibuprofen or other nonsteroidal anti-inflammatory drugs, said Dr. Stephen Dahmer, a former fellow in integrative medicine at Beth Israel Medical Center in New York City, and now a staff physician at the VA San Diego Medical Center.

Sawitzke said he sees some merit in the supplement for pain relief, but there's a lot less evidence to support glucosamine as a way to slow cartilage damage.

Vlad, however, tells patients he's doubtful it works very well, if at all. "But I also tell them that it is safe and will not hurt them. If they want to try it, they are more than free to do so at any time, with the understanding that no insurance company will pay for it."

SOURCES: Steven C. Vlad, M.D., fellow, clinical epidemiology and rheumatology, Boston University School of Medicine; Allen D. Sawitzke, M.D., associate professor, medicine, University of Utah School of Medicine, Salt Lake City; Jason Theodosakis, M.D., assistant professor, University of Arizona College of Medicine, and author, The Arthritis Cure; Stephen Dahmer, M.D., staff physician, VA San Diego Medical Center; U.S. National Center for Complementary and Alternative Medicine, Bethesda, Md.; Arthritis Foundation, Atlanta; July 2007 and October 2008 Arthritis & Rheumatism; Aug. 15, 2008, American Family Physician