Niacinamide therapy for osteoarthritis - does it inhibit nitric oxide synthase induction by interleukin-1 in chondrocytes?

Fifty years ago, Kaufman reported that high-dose niacinamide was beneficial in osteoarthritis (OA) and rheumatoid arthritis. A recent double-blind stu dy confirms the efficacy of niacinamide in OA. It may be feasible to interp ret this finding in the context of evidence that synovium-generated interle ukin-1 (IL-1), by inducing nitric oxide (NO) synthase and thereby inhibitin g chondrocyte synthesis of aggrecan and type II collagen, is crucial to the pathogenesis of OA. Niacinamide and other inhibitors of ADP-ribosylation h ave been shown to suppress cytokine-mediated induction of NO synthase in a number of types of cells; it is therefore reasonable to speculate that niac inamide will have a comparable effect in IL-1-exposed chondrocytes, bluntin g the anti-anabolic impact of IL-1. The chondroprotective antibiotic doxycy cline may have a similar mechanism of action. Other nutrients reported to b e useful in OA may likewise intervene in the activity or synthesis of IL-1. Supplemental glucosamine can be expected to stimulate synovial synthesis o f hyaluronic acid; hyaluronic acid suppresses the anti-catabolic effect of IL-1 in chondrocyte cell cultures, and has documented therapeutic efficacy when injected intra-articularly. S-adenosylmethionine (SAM), another proven therapy for OA, upregulates the proteoglycan synthesis of chondrocytes, pe rhaps because it functions physiologically as a signal of sulfur availabili ty. IL-1 is likely to decrease SAM levels in chondrocytes; supplemental SAM may compensate for this deficit. Adequate selenium nutrition may down-regu late cytokine signaling, and ample intakes of fish oil can be expected to d ecrease synovial IL-1 production; these nutrients should receive further ev aluation in OA, These considerations suggest that non-toxic nutritional reg imens, by intervening at multiple points in the signal transduction pathway s that promote the synthesis and mediate the activity of IL-1, may provide a substantially superior alternative to NSAIDs (merely palliative and often dangerously toxic) in the treatment and perhaps prevention of OA. (C) 1999 Harcourt Publishers Ltd.