Disjointed & Disinformed

Can the missteps of the past and the presumed positive outcome of the biggest joint health study create incremental business and resurrect consumer confidence?

ByAnthony Almada, B.Sc., M. Sc.

Caring for cartilage is big league. Foods, beverages, over-the-counter (OTC) topical drugs and dietary supplements that are positioned to aid the aches and diminish the pain represent billions of consumer dollars annually. If we assign the pioneer title to glucosamine sulfate (not hydrochloride) we see its inception (as an OTC natural product) being in the early-mid 1990s, with chondroitin sulfate drafting behind in proximity. Next on the scene was methylsulfonylmethane (MSM), which unfortunately lacked any randomized controlled (clinical) trials (RCT) in its formative years. The former two comprise the Dynamic Duo, whereas the latter is often found as a complementary companion, with only one short-term peer reviewed RCT suggesting that MSM interacts favorably with glucosamine. This chondroprotective (chondro- cartilage) Trio has paved the yellow brick road, which has not been without an array of distinctive diversions and visitors.

Along the way to visit the Wizard of Knees the ancient mariner Green Lipped Mussel (GLM) resurrected like a marine diving mammal, ostensibly a denizen of the dark depths of abandoned products. The inter­necine wars that continue between different GLM suppliers, and the less than robust clinical evidence, may have been the electric fence that kept them from being a part of the chondro collective. Collagen derivatives, too, have merged onto the brickyard, both crude and refined. This secret sauce approach has yielded a handful of small, short pilot clinical trials worthy of a modicum of acclaim, but the cost per kilogram remains high and the absence of any data trumping the Duo or the Trio make the selling proposition challenging, at the very least. Another class of collagen derivatives, aimed at the inferior numbers suffering the autoimmune ravages of rheumatoid arthritis, failed in the largest clinical trial when pursuing a drug path. A dietary supplement powder variant of the former composition (which was dispensed as a liquid) apparently failed when subjected to another clinical trial—but the data were never reported despite the trial concluding over a year ago.

Collagen extracts harbor variable amounts of a bioactive called hya­luronic acid (HA). This more recent darling of the chondroprotective community appears to lack any RCTs demonstrating that the pure bioactive is orally active in humans with chronic (or acute) joint pain. Animal and human studies suggesting “bioavailability” do not substitute for efficacy or safety. Nevertheless, since the Trio is generic and off patent, the search for any measure of novelty and superiority is relentless and given to disinformation. Since when does the addition of HA, collagen extract or a plant extract confer synergism in the absence of any evidence thereto? Taking the contrarian position, an academic rheumatologist could scrutinize the vast majority of foods, beverages and dietary supplements that reside on the chondroprotective “houseboat” and assert that because no evidence exists to support the safety and efficacy of A + B + C + D…then the interactions could be antagonistic and potentially adverse. The absence of evidence (of safety or efficacy) is not the evidence of absence (of toxicity and antagonism). There are few exceptions, and these exceptions (finished products—dietary supplements) enjoy only short-term studies with relatively small populations of patients.

A paucity of (ingredient and finished product) marketers have taken the strategic approach of crafting finished product compositions em­ploying the patchwork tactic of formulation and subjecting them to head-to-head comparisons against glucosamine. But these studies are very limited in number, duration and size and arguably suffer the disadvantage that glucosamine and chondroitin did before the 2000 meta-analysis in JAMA and the publication of two separate three-year studies with glucosamine sulfate: a lack of credibility. Some have gone as far as saying their ingredient or product will create a purchase shift among chronic users of the Dynamic Duo or the Trio, relying upon RCTs that are anemic in comparison. Ah, the beauty of hubris among the scientifically under-informed/illiterate.

These potential missteps lead us into the next inflection point for the chondroprotective products: the GAIT study. The Glucosamine (and Chondroitin) Arthritis Intervention Trial began collecting patients (a total of 1588!) five years ago. It is four years in duration and has collected over 1200 variables of data. The results are imminent and have tectonic plate shifting potential. It will be positioned as the definitive study in relation to a branded glucosamine (hy­drochloride) and a specific, branded chondroitin sulfate (this is NOT a generic ingredient, as ALL chondroitin sulfate ingredients are chemically different and only 1-2 have ANY RCTs). They are being compared alone or together to placebo and the first selective COX-2 in­hibitor drug, celecoxib (Celebrex). How these findings (if positive), expected at the end of 2005, alter the chondroprotective landscape will be provocative. The yellow brick road may become golden or the Wizard of Knees may be cut down to his knees.NW