Osteoarthritis is a slow degeneration of the articular cartilage and bone proliferation in joint margins that progressively worsens over time. Rheumatoid arthritis is a chronic inflammatory disease in which the synovial membranes of joints and other tissues are degraded37 via an autoimmune reaction. In both diseases pro-inflammatory cytokines (tumor necrosis factor alpha, interleukin-1) are up-regulated and induce focal loss of cartilage. In osteoarthritis a major source of oxidative stress is related to nitric oxide; in rheumatoid arthritis the radical oxygen intermediates are more prominent.38
In the arthritis diseases, the collagen matrix of the joints is formed from chondroitin sulfate and its precursor, glucosamines, which aggregate to form proteoglycans. Supplements of chondroitin sulfate enhance proteoglycan production as this compound is anti-inflammatory39and diminishes the destruction of cultured articular cartilage cells.40 Glucosamine (GCM) also is effective as it stimulates the activity of human osteoarthritic chondrocytes.41 The combination of these compounds is synergistic and improves efficacy as compared to either alone.42
Manganese is used as a therapeutic agent for both conditions because it activates glycosyltransferases.16 The chondroitin sulfates that are formed become side chains of the proteoglycans.43 Also, manganese is necessary as a transcription and posttranslational activator for SOD.44,45 Infusion of manganese into plasma of conscious horses increased the superoxide scavenging ability in a dose-related manner.46 More recently, a molecular profiling at the proteome level of synovial tissue via Western blots found that SOD2 was reproducibly overex-pressed with rheumatoid arthritis, as compared to those with osteoarthritis.47
The combination of manganese ascorbate with chondroitin sulfate and GCM is efficacious as it attenuates symptoms of knee osteoarthritis. An ascorbate form was given in order to strengthen the cross-linking of the collagen fibers. In 34 Navy men, a 4-month study found relief of symptoms according to disease summary and physical examination scores.48 Das Jr and Hammad also found reduction of severity of symptoms in 72 patients who were classified as being radiographically mild or moderate, as compared to placebo.49
Although rheumatoid arthritis is vastly improved by treatment with Enbrel™ (etanercept, a genetically engineered protein), there is a risk of serious infections, including sepsis, which might preclude its use in those predisposed to infections, such as diabetics.50 Other drugs that target inflammation, such as Kineret™ (anakinra, a blocker of IL-1), may be cost-prohibitive (>$1000 US per month). In a model of collagen-induced autoimmune arthritis with rats treated with GCM, Beren et al. found that two evaluations of arthritis, the arthritis index and histologic index, decreased 54% (p = 0.001) as compared to controls.37 However, there was no change in the antibody response to bovine collagen or proliferation of T-cells. Thus, GCM appeared to increase the ability of the joint to withstand an inflammatory attack and might be considered as adjunct therapy.
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