The first reported outcome of a long-awaited government study into the ability of glucosamine and chondroitin sulfate supplements to relieve arthritis pain is not the news that most patients or doctors had hoped to see.

Preliminary results of the National Institutes of Health (NIH) study, presented last week at the American College of Rheumatology's annual scientific meeting, showed that in most people with osteoarthritis of the knee, the supplements worked no better for relieving pain than a placebo. This was the case whether the products, one usually made from shellfish shells and the other from shark or cow cartilage, were taken individually or together.

Among those in the study whose arthritis was moderate to severe, a combination of the supplements were somewhat more effective. But researchers said that this secondary finding was less than conclusive and that further research was needed to confirm it.

On safety, the study was more definitive, showing that side effects associated with the products were minimal -- mostly gas and softened stools.

"The first take-home message is that in the overall study population, none of the supplements were better than placebo," said principal investigator Daniel Clegg, chief of the division of rheumatology at the University of Utah Hospital. "In an exploratory analysis of a subgroup with moderate to severe knee pain, the combination of glucosamine and chondroitin sulfate appeared to be effective." Clegg said no industry funding was accepted for the study.

David Felson, chair of the clinical epidemiology unit at the Boston University Medical School and author of several landmark arthritis studies, called the results of the $16 million Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) "sad news."

"The main effect is unfortunately null, meaning there's no effect," he said. "For those of us who had hoped we'd find a wedge into effective treatment of arthritis -- a very difficult disease to treat -- I think it's a disappointment."

But some groups, especially those with industry ties, took away a more upbeat message.

The Arthritis Foundation issued a statement saying "the research demonstrates that the combination of glucosamine and chondroitin may be a beneficial part of an overall treatment plan in individuals with moderate to severe knee OA [osteoarthritis]." Among the group's sponsors is U.S. Nutrition, maker of Osteo Bi-Flex, a glucosamine/chondroitin supplement.

Leiner Health Products, another glucosamine product maker, placed an announcement prominently on its Web site that began: "For 21 million Americans hobbled by osteoarthritis, new science confirms nutritional supplements glucosamine and chondroitin are the right combination for effective knee pain relief."

Results of the GAIT study are considered preliminary because they have not yet been published in a peer-reviewed journal. The NIH has refused comment on the study prior to its publication. An abstract of the study is accessible at (enter "GAIT" in the search field).

Osteoarthritis, the most common form of arthritis, is marked by the breakdown of cartilage between joints. According to the Centers for Disease Control and Prevention, an estimated 21 million Americans have osteoarthritis. There is no cure for the degenerative disease and few good treatments beyond common painkillers.

Glucosamine and chondroitin sulfate are found naturally in the body. Glucosamine is believed to play a role in cartilage formation and chondroitin sulfate helps give cartilage elasticity.

Although a few studies have suggested that glucosamine may slow the rate of narrowing in the joint space of the knee, the first phase of the GAIT study did not explore this question. Clegg said another phase will follow patients over two years to see if the supplements produce changes in X-ray measurements of the knee joint.

Over the past 25 years, the popularity of glucosamine/chondroitin supplements has grown. U.S. sales reached $734 million in 2004, according to the Nutrition Business Journal, making it one of the 10 top-selling supplements.

For the study, researchers at 16 U.S. academic rheumatology centers studied 1,583 people with knee osteoarthritis over six months. Participants took one of four doses: 500 milligrams three times daily of glucosamine; 400 milligrams three times daily of chondroitin sulfate; 500 milligrams three times daily of both supplements; 200 milligrams daily of celecoxib (Celebrex, a prescription nonsteroidal anti-inflammatory drug). A fifth group took a daily placebo.

Participants were also allowed to take up to 4,000 milligrams of acetaminophen for pain, except within 24 hours of study visits. Researchers measured knee arthritis pain five times over the six months via an index that uses a series of questions to assess pain, disability and joint stiffness.

The researchers found that for the entire study group, glucosamine, chondroitin sulfate or a combination of the two had no more effect on pain than a placebo pill.

When researchers looked at the 20 percent of participants with moderate to severe pain, they found that 79 percent of those taking a combination of the supplements experienced pain relief, compared with 69 percent of those who took Celebrex and 54 percent of those who took placebo. The combination was also better than either supplement alone.

But Felson cautioned against putting too much credence in the subgroup analysis because research experts consider it risky to use the data collected for one set of questions to answer other ones.

"That's a recipe for mistakes," Felson said. "If you do enough subgroup analyses, sooner or later you will turn something up. Whether that is legitimate or not, or real, you don't know. It's usually not real. There's no way of knowing."

Marc Hochberg, head of the division of rheumatology and clinical immunology at the University of Maryland School of Medicine, agreed that the subgroup findings "shouldn't be used to make therapeutic decisions."

But Andrew Shao, vice president of scientific and regulatory affairs for the Council for Responsible Nutrition, a supplement-industry group, said he saw no reason to doubt the subgroup findings, given that participants were divided into different pain groups at the beginning of the study. "To learn about how these products are acting and what's actually going on, there's no reason why you can't look at a secondary outcome," he said.

"We can talk about all the jargon and the details as scientists, but consumers are the bottom line," he said. "I think this trial helps to reinforce that these are safe and beneficial supplements."

Rheumatologist David Borenstein, a clinical professor of medicine at the George Washington University Medical Center, and Stephen Trippel, a professor of orthopedic surgery at Indiana University School of Medicine and deputy editor of the Journal of Orthopaedic Research, reacted with guarded optimism.

Said Borenstein, "It is encouraging that glucosamine and chondroitin seem to help some people who have a significant knee disease -- it's something to consider -- but to think that it has replaced anything or works better across the board wouldn't be correct."

He also said he was concerned that 60 percent of all those taking a placebo said their pain had decreased. This very high response rate "means the measurement scales that they used were easily reached," he said.

Borenstein said the new findings wouldn't change the advice he already gives patients: If they want to try glucosamine/chondroitin, he tells them to go ahead, but only if the supplements are used as an adjunct to regular pain-relief treatment.

Until now, Trippel said, he has discouraged patients from taking glucosamine/chondroitin, saying there wasn't enough evidence of efficacy. If the preliminary study findings withstand peer review, he said, he'll change his advice.

"This will enable me to tell my patients that if they use these two agents together, and they do have relatively higher levels of pain, that they can expect to have a good chance of experiencing pain relief," Trippel said.


Elizabeth Agnvall wrote recently for Health about disease containment efforts in the Gulf after Hurricane Katrina. To comment on this article, send e-mail to