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Glucosamine & Chondroitin

Both Glucosamine (as an obligate and rate-limiting precursor for connective tissue glycosaminoglycan (GAG) synthesis) and Chondroitin (as a structural GAG component of proteoglycans in cartilage) are normally found in joint tissues and some foods. Glucosamine and Chondroitin exert benefits for joint health via multiple mechanisms, mostly as biological response modifiers at usual oral doses and less as precursors of cartilage structures. Actions as biological response modifiers have been found at concentrations seen after typical oral doses (1500 mg Glucosamine and 800-1200 mg Chondroitin). Responses include decreased levels of IL-1beta, TNF-alpha, matrixmetalloproteinases, other degradative enzymes and other degradative signals.

Numerous human clinical studies have reproducibly found improvements in joint discomfort, joint function and quality of life for both Glucosamine and Chondroitin when administered singly. EULAR (the European medical group specializing in joint health) has given both Glucosamine and Chondroitin 1A status for maintaining joint health – the highest available level of evidence based on human clinical studies and expert consensus (Pendleton 2002). When Glucosamine and Chondroitin are used together (abbreviated as GC), several human clinical studies have also found joint health benefits.

Identity of efficacious forms of Glucosamine has resulted in some reviews favoring Glucosamine Sulfate over Glucosamine Hydrochloride (HCL). However, these opinions neglect to mention a direct, head-to-head, human clinical comparison study of Glucosamine HCL and Glucosamine Sulfate for joint health (Qiu, 2005). This study showed equivalent results for equimolar amounts of each form of Glucosamine. In vitro studies have also shown equivalence in biological effects between the two forms of Glucosamine. Glucosamine HCl contains more Glucosamine by weight than Glucosamine Sulfate (80% vs. ~60%). Also, absorption studies have shown that Glucosamine Sulfate is converted into Glucosamine HCL during digestion, and Glucosamine base is the molecular entity actually absorbed and distributed to tissues, not Glucosamine Sulfate (Setnikar 1991a). Schiff Nutrition prefers to use Glucosamine HCL in Move Free® Advanced products as this form delivers equivalent efficacy and more Glucosamine than Glucosamine Sulfate.

Importantly, long-term use of Glucosamine or Chondroitin (over 2 years) has exhibited significant halting of structural cartilage loss (deterioration) over time. In fact, some subjects showed rebuilding or regeneration of cartilage (Altman 2005; Bruyere 2003; Bruyere 2004; Bruyere 2008; Michel 2005a; Pavelka 2002; Pavelka 2003; Reginster 2001a; Reginster 2005; Rovati 2006; Uebelhart 2004; Uebelhart 2008).

NIH Glucosamine / Chondroitin Arthritis Intervention Trial (GAIT)

Recently, the United States National Institutes of Health sponsored a multi-center human clinical study (NIH GAIT trial) comparing placebo, Glucosamine, Chondroitin, GC and celecoxib (Celebrex®) for joint health and structural measurements in over 1500 subjects (Clegg 2006; Sawitzke 2008). Unfortunately, uptake of Chondroitin (in both the Chondroitin and GC groups) was not found from GAIT study pills (Jackson 2005; Jackson 2006). Combined with a level of rescue medication use in all groups that would reduce joint discomfort more than the primary outcome measurement (% responders with 20% or greater decrease in joint comfort by subjective VAS scale), it is easy to see why significant results were not obtained for this measurement for nutrients. This so-called “ceiling effect” limited the ability of this study to find differences between groups. However, the subgroup of subjects with moderate joint discomfort (as opposed to mild discomfort) did exhibit a significant improvement over the placebo group from GC after six months of supplementation.

A subset of subjects in the NIH GAIT trial continued taking test agents for a duration of two years, and had radiological imaging performed to measure cartilage loss. The rate of cartilage loss in the placebo group was less than half that expected over the time period, inhibiting the ability of the NIH GAIT study to be able to statistically discern any change in cartilage loss (unlike European studies of Glucosamine and Chondroitin using the same measurement). Accordingly, the overall results, including the celecoxib group, did not show statistically different cartilage loss from the placebo group. However, when subjects with mild joint discomfort were analyzed separately, Glucosamine HCL showed a slowing of cartilage loss that was very close to statistical significance. The magnitude of slowing was similar to long-term European studies of Glucosamine. Nevertheless, the NIH GAIT study, although exhibiting serious flaws that hampered the ability to find statistically significant changes, did show that GC and Glucosamine HCL provided clinically important joint benefits.
THESE STATEMENTS HAVE NOT BEEN EVALUATED BY THE FOOD AND DRUG ADMINISTRATION.
THIS PRODUCT IS NOT INTENDED TO DIAGNOSE, TREAT, CURE OR PREVENT ANY DISEASE.