Results Of Joint Pain Supplement Study Inflame Debate On Efficacy

Research might soon determine the efficacy of the use of glucosamine and chondroitin for reducing joint pain, says the lead author in an analysis of studies on the dietary supplements.

In a meta-analysis the British Medical Journal published online Sept. 17, researchers conclude that neither glucosamine nor chondroitin, alone or combined, reduced joint pain or preserved joint space.

Supplement industry stakeholders, however, do not agree these findings push glucosamine and chondroitin research to a make-or-break point.

Sales Soar Despite Evidence

According to the BMJ study led by Peter Jüni, an epidemiologist at the University of Bern, Switzerland, global sales of glucosamine and chondroitin have more than doubled since 2003 despite a growing body of recent evidence showing the ingredients to be ineffective.

As of 2008, sales of these supplements approached $2 billion and are projected to reach $2.3 billion in 2013, according to the same research team, which published its findings from a meta-analysis of data from 10 RCTs.

The paradox of a market for a supplement growing as its evidence base shrinks is probably merely the result of a predictable delay between evidence and adoption, Jüni says.

High-quality evidence from large RCTs is relatively recent in the field of osteoarthritis, he said in an interview. "Only in the last five to 10 years has it become established in this field to do large-scale clinical trials," he said.

Of the 10 published randomized placebo-controlled trials Jüni and colleagues identified for their analysis, one was published in 1994 and the rest in the past decade, with the most recent in 2008.

"At the end of the 1990s and beginning of the 2000s, there were moderately small studies that actually made it into meta-analysis and into treatment guidelines" showing favorable results from glucosamine and chondroitin, Jüni said.

He added that while physicians "were very reluctant to accept these" when positive trials for the substances initially became known, eventually they did. However, "it will take time for the bad news to sink in, just as it took time for the good news in the 1990s," Jüni added.

Currently, Jüni noted, two more large non-industry trials of glucosamine and chondroitin are underway. These "could put the nail in the coffin - or, you never know, could re-open the book," he said.

A grant from Swiss National Science Foundation's National Research Program funded the study. Neither Jüni nor his colleagues declared conflicts of interest.

Studies With Positive Results Omitted

Council for Responsible Nutrition executive Andrew Shao says the BMJ meta-analysis, like others before it, omits numerous studies showing positive results for the ingredients.

The meta-analysis excluded RCTs with less than 100 subjects or studies with less than 800 mg per day of chondroitin or less than 1,500 mg per day of glucosamine.

Jüni and colleagues included data from 10 RCTs out of the 58 reports they identified, "conveniently excluding a large portion of the evidence base," said Shao, CRN's senior VP of scientific and regulatory affairs.

Additionally, the researchers combined studies with different designs and pre-specified outcomes too dissimilar to be combined in a meta-analysis, he added.

"The present analysis suffers from some of the same limitations that have been observed with other meta-analyses," Shao said.

He also pointed out both glucosamine and chondroitin are approved drugs for osteoarthritis in some countries in Europe, though no drug has been shown to effectively treat the condition, and the substances' safety is well documented, even in the BMJ meta-analysis.

Shao further elaborated that "nearly all the available options" address only pain symptoms while providing no structural or disease-delaying benefit, and all are associated with side effects, including death.

"The bottom line for consumers is that overall the evidence indicates that glucosamine, chondroitin or the combination is effective for improving mobility and joint discomfort in OA patients, while also demonstrating a strong safety profile," he said.

The researchers noted consumers are aware glucosamine and chondroitin are demonstrably safe while few truly safe long-term treatments for joint pain are known. They also point out as much as 30 percent of the adult population suffers joint pain.

Variety Of Studies, Locations

For their research, Jüni and colleagues analyzed results from randomized, placebo-controlled trials - seven of them industry-sponsored - including 200 or more patients with knee or hip osteoarthritis, with 3,803 patients total.

Using statistical modeling that allowed for comparisons at varied time points, the team assessed changes in levels of perceived pain after patients took glucosamine, chondroitin or placebo daily for between one month and three years. Six of the trials also measured joint narrowing.

The trials' design differences include one enrolling patients with osteoarthritis of the hip or knee and another only patients with osteoarthritis of the hip, while the majority enrolled patients with osteoarthritis of the knee only.

Supplements used included different combinations of glucosamine sulfate, glucosamine hydrochloride and chondroitin sulfate or one of the substances alone. While the glucosamine supplements were tested at 1,500 mg daily, the chondroitin supplements varied from 800 and 1,200 mg daily.

Patients ranged in age from 58 to 66 years, and the median percentage of women participants was 68 percent.

Further, some trials took place in the U.S., where supplements are not standardized for quality, and some in Europe, where they are.

In eight trials, the supplements were evaluated to ensure correct concentrations of glucosamine or chondroitin, and in two the quality of the supplements was unclear.

"Differences In Changes ... All Minute"

On a 10-cm visual analogue scale - where 0 cm represents no pain - the researchers found the overall difference in pain intensity compared with placebo was -0.4 cm for glucosamine, -0.3 for chondroitin and -0.5 for a combination.

The BMJ study says the results showed a 95 percent confidence interval for each finding.

"For none of the estimates did the 95 percent credible intervals cross the boundary of the minimal clinically important difference," the investigators wrote.

"The differences in changes in minimal width of joint space were all minute, with 95 percent credible intervals overlapping zero."

The seven industry-sponsored trials were more likely to detect an effect, although limited, than the non-industry trials (P = .02 for interaction).

In industry independent trials, estimated treatment effects "were minute to zero and by no means clinically relevant," Jüni and colleagues wrote.

A possible reason glucosamine and chondroitin are perceived widely as effective, Jüni said, is because osteoarthritic pain tends to fluctuate naturally.

He observed that if people take a supplement when their symptoms are worse, "it leads you to perceive that it works perfectly," as the symptoms gradually subside and the theoretical mechanism of the supplement is biologically plausible.

[Editor's note: This story appears courtesy of Elsevier Global Medical News. For more information, please call 240-221-4530.]

- Jennie Smith