Integrator Adviser Speaks: Levin on Whether Supplement Quality May Be Influencing Clinical Outcomes

Summary: Another recent Integrator post reports outcomes of a survey of media coverage of dietary supplements in 2006. The outcomes were not pretty for the industry. Integrator editorial adviser Michael Levin noted two recent reports which might explain some of that negativity. Levin, who has held executive level positions for both Big Pharma and supplement companies, focuses on a Consumerlab.com quality study and an Annals of Internal Medicine efficacy study, both on chondroitin products. Is there a picture emerging?

The survey which analyzed the negative media coverage of supplements, covered here in the Integrator, found that roughly 50% focused on efficacy or quality issues.

Integrator adviser Michael Levin

Integrator editorial advisor Michael Levin observed the deep nodal, double-negative crossing of those two themes recently regarding the same product: chondroitin. This natural agent is recommended by many integrated care practitioners, as well as by supplement store owners, for arthritis. Levin, a consultant whose career has included stints as an executive for both Big Pharma and for supplement companies, was last seen in the Integrator in his effort to get the New York Times from inappropriately shooting the supplement industry in the face. Here Levin focuses on how a deeper wounding may be self-inflicted.

The Annals of Internal Medicine article is entitled Meta-Analysis: Chondroitin foir Osteoarthritis for the Knee or Hip, Reichenbach S, et al,

"Consumerlab.com's recently released survey of chondroitin products coincided with a meta-analysis published in the April issue of the Annals of Internal Medicine (146,8:580-90, 2007). The study of product quality found that 73% of chondroitin-containing products failed.  The Annals article concluded chondroitin has 'minimal to no effect on osteoarthritis' (OA).

"How timely!

"In their meta-analysis of the literature on chondroitin for OA of the knee or hip, the authors correctly observed that their study is 'limited by the quality of the included trials.' They disclosed that 'several relevant variables were poorly reported.' They further disclosed that 'most trials had poor methodological or inadequate reporting.'

"Fine. But what they did NOT comment on was the lack of controls over the primary experimental variable, i.e., the quality of the product being studied.

"Let's connect the dots. Consumerlabs.com says: '73% of chondroitin products studied are subpotent.' Annals of Internal Medicine authors state: "No robust evidence supports the use of chondroitin in OA.'

"Gee. Do you think there might be some connection here?

 

"Here's a little tech-talk, to help you understand some of the subtle complexities. There are several analytical methods used to assay chondroitin. Some are more specific than others. An inferior, non-specific method, used by some companies, is called 'size exclusion chromatography' (SEC). It doesn't measure potency, per se. Rather, the measure is of the hydrodynamic volumes in a substance. This makes it easy to include non-chondroitin macromolecules to inflate the assay value and make it look like there is more chondroitin available. This is not unlike putting melamine in wheat gluten to inflate the nitrogen content, thus increasing the appearance of higher protein content. This is the pet food issue, in a nut shell.

"In contrast, a more exacting method to assay potency, enzymatic HPLC, is molecule-specific. Some companies use SEC, others use HPLC. Quality is a matter of choice, and often times, dictated by economics.

"Furthermore, only a subset of quality companies disclose chondroitin potency on the label, rather than simply the compound weight (eg, 400 mg) of the product.  Some firms actually do guarantee proven authenticity, potency and purity. Some don't. Did the product contain 400mg of 70% material, 400mg of 90% material, or 400mg of 8% material? Was potency confirmed by HPLC or by SEC? These questions must be asked - and answered -in order to evaluate results reported from clinical trials.

"Not surprisingly, the press release - see below - containing the industry's response to the Annals article didn't mention variations in raw material potency. (See below.)

"The take home: Had the ingredient being studied been controlled as to it's authenticity, potency and purity, the outcomes from clinical trials would have meaning. Absent that, the outcomes are meaningless. In the case of the Annals article on chondroitin, and the publicity it generated, the advancement of integrative medicine is undermined by questionable product quality and poor experimental design."

BERN, Switzerland—A meta-analysis published in the April issue of the Annals of Internal Medicine (146, 8:580-90, 2007) concluded chondroitin supplementation has minimal to no effect on osteoarthritis (OA); but, nutrition industry insiders point to many flaws in the review design, including undefined OA endpoints and a severely limited number of trials used to reach its conclusion.

The meta-analysis authors searched the Cochrane Central Register of Controlled Trials (1970 to 2006), MEDLINE (1966 to 2006), EMBASE (1980 to 2006), CINAHL (1970 to 2006) and conference proceedings, narrowing the list of randomized or quasi-randomized controlled trials on chondroitin and OA pain to 20 trials, involving a total of 3,846 patients. The smaller trials not employing an intent-to-treat protocol showed greater benefits from chondroitin than did the other trials reviewed. When the researchers narrowed the review to three large-scale trials—representing only 40 percent of the patients—they found symptomatic benefit of chondroitin was minimal or nonexistent, and concluded the use of chondroitin in routine clinical practice should be discouraged.

"Among other objections to this meta-analysis, the Council for Responsible Nutrition (CRN) took issue with the reviewers basing their decision on three trials, excluding 17 other trials selected and ignoring the approximately 300 scientific reports on chondroitin available. 'Meta-analysis can be a valid tool for scientific evaluation, but also has recognized limitations, said Andrew Shao, Ph.D., vice president, scientific and regulatory affairs for CRN. 'One can include and exclude studies in various combinations, but the bottom line is consumers use glucosamine and chondroitin supplements because they work.'

"CRN reiterated that chondroitin is a safe, affordable and beneficial option for helping maintain mobility and reduce discomfort associated with osteoarthritis, particularly when combined with glucosamine. 'With over 21 million osteoarthritis sufferers in the United States alone, a conclusion based on only three studies hardly seems representative of the population in question,' the group responded.

"A similar statement was released by the Natural Products Association (NPA), which noted the reviewers made no distinction between mild, moderate and severe OA, which all involve very different treatment regimens. In contrast, they noted the 2006 National Institutes of Health (NIH) Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) showed positive benefits of chondroitin by itself for mild osteoarthritis, and statistically significant benefit in combination with glucosamine for patients with severe osteoarthritis.

“'Bottom line: Chondroitin, especially when combined with glucosamine, is safe and effective, and compared to the other options for arthritis pain, it’s one of the few options without dangerous side effects,' said Daniel Fabricant, Ph.D., vice president of scientific and regulatory affairs for NPA. “It’s important to keep in mind that most consumers use a combination of glucosamine and chondroitin, not just chondroitin by itself.”