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Glucosamine Trials Show Little Benefit Against Arthritis
June 29, 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
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
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
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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