More threads by David Baxter PhD

David Baxter PhD

Late Founder
Glucosamine Trials Show Little Benefit Against Arthritis
By E.J. Mundell, HealthDay
June 30, 2007

Although millions of arthritis sufferers buy glucosamine supplements to ease their joint pain, there's still no convincing proof the product works, according to a major new analysis.

In fact, the results of 15 trials of over-the-counter glucosamine vary so widely that industry bias may be a factor influencing the more positive outcomes, concludes a team writing in the July issue of Arthritis & Rheumatism.

"There's a big difference between trials, much more than you would expect by chance," explained lead investigator Dr. Steven Vlad, a fellow in rheumatology at Boston University Medical Center.

But an editorialist in the journal refutes those claims.

Dr. Jean-Yves Reginster, of the World Health Organization's Collaborating Center for Public Health Aspects of Rheumatic Disease, in Liege, Belgium, counters that industry trials are typically more stringent than independent academic research. He also believes that Vlad's group included trials in their analysis that were very unalike in terms of timeframes and methodology, confusing the results.

So, the years-long scientific debate on glucosamine continues. The popular supplement did take a major hit earlier this year, when a major U.S. study published in the New England Journal of Medicine found glucosamine hydrochloride to be of little help for knee osteoarthritis.

But Vlad also knew that other studies had found a real benefit to regular glucosamine use. Why the differences between trials?

To find out, he and his team combed through the available literature and selected 15 double-blind, placebo-controlled, randomized clinical trials that looked at the use of glucosamine for more than four weeks to help fight hip or knee osteoarthritis pain.

Trials involved either of the two major glucosamine preparations: glucosamine hydrochloride or glucosamine sulfate. Each delivers glucosamine bound to a different chemical salt.

First of all, the team determined one of the preparations to be useless.

"I think we have shown pretty conclusively that glucosamine hydrochloride doesn't work," Vlad said. "The data there is all consistent, it goes together -- there's just no evidence that it works."

But that wasn't the story with the other preparation, glucosamine sulfate.

In that case, results varied widely between the randomized trials. However, that variance went far beyond random chance. In fact, according to Vlad, the spread in results among various trials was four times that which would be normally expected.

No particular feature of the studies' design helped explain this disparity, except for differences among trials in what's known as "allocation concealment" -- the fact that some trials were more lax than others at concealing from the researchers involved which patients would get the drug and which would get a placebo.

One factor did appear to play a role in the variance between the glucosamine sulfate trial results: industry involvement.

"It's really hard to know just how big a factor that is," Vlad said, "whether it's manufacturing the whole effect or just exaggerating an effect that's there." He also stressed that, "If there is a bias from industry, I doubt very much that it is intentional. People want to sell their product, but I think that they rarely go into a study with the intention of twisting the results."

But Reginster, in his editorial, believes Vlad's own analysis is flawed. He agreed with the Boston group that industry involvement can, and often does, influence trial results. But he also notes that many of the industry studies included in the Boston analysis had to pass muster with the European League Against Rheumatism, the expert body which vouched for many of the trials' high quality.

That's important, he said, because -- unlike in the United States -- glucosamine sulfate is approved for sale as a prescription drug by regulatory agencies in Europe. To gain approval, industry-funded trials must conform to regulatory oversight and are often better designed than independent studies, he noted.

But Vlad doesn't buy that argument. "I would agree with [Reginster] that, in general, drug manufacturers do produce better trials," he said. "But I also believe it is too simplistic to say that academic researchers aren't as good at weeding out confounding factors and things that would influence the results. They can produce trials that are every bit as good."

Another expert weighed in on the issue.

"I have worked on both sides [industry and independent]," said Malachy McHugh, director of research at the Nicholas Institute of Sports Medicine and Athletic Trauma, at Lenox Hill Hospital, in New York City. He said one issue at play is the dire lack of quality independent studies.

"In the nutritional supplement area, the bigger problem is that there is a disincentive for companies to have their products tested," he said. "If they can convince people that their product works, why run the risk of proving otherwise? There are also many negative studies that never see the light of day."

Reginster lobbed another major criticism at the Vlad study. In his opinion, the Boston group mixed together trials with widely varying timeframes (four-week studies and three-year trials), glucosamine delivered in both injections and pills, and studies of greatly differing quality. This type of heterogeneity was bound to lead to variety in results, he wrote.

Vlad agreed that his team's analysis did cast a wide net, but he said that's the way meta-analyses are typically performed. "You try and capture all the trials that may be relevant to your question," he said. Select too few trials, he said, and you lose statistical power.

The system is "never going to be perfect," Vlad said.

He stressed that the new analysis does not close the book on glucosamine. And given the supplement's good safety profile, patients who really believe they are reaping a benefit from the glucosamine sulfate should feel free to continue to take it.

Vlad and McHugh remain dubious, however, that the pricey supplement does ease osteoarthritis pain.

"From my perspective," McHugh said, "the New England Journal of Medicine paper provides the most objective take on the efficacy. The bottom line is that there is limited efficacy."

In a related study in the same issue of the journal, U.S. researchers surveyed more than 6,000 people with rheumatoid arthritis and found that most are reluctant to switch to a new medication as long as their condition does not worsen.

The team from the National Data Bank for Rheumatic Diseases in Wichita, Kan., found three-quarters of respondents were happy with their current medications, and almost two-thirds (64 percent) said they wouldn't try a new drug unless their symptoms deteriorated. The findings may explain why many patients hold off trying promising new medications, the researchers said.
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