title: Niacinamide therapy for osteoarthritis--does it inhibit nitric oxide synthase induction by interleukin 1 in chondrocytes?
abstract: Fifty years ago, Kaufman reported that high-dose niacinamide was beneficial in osteoarthritis (OA) and rheumatoid arthritis. A recent double-blind study confirms the efficacy of niacinamide in OA. It may be feasible to interpret this finding in the context of evidence that synovium-generated interleukin-1 (IL-1), by inducing nitric oxide (NO) synthase and thereby inhibiting chondrocyte synthesis of aggrecan and type II collagen, is crucial to the pathogenesis of OA. Niacinamide and other inhibitors of ADP-ribosylation have been shown to suppress cytokine-mediated induction of NO synthase in a number of types of cells; it is therefore reasonable to speculate that niacinamide will have a comparable effect in IL-1-exposed chondrocytes, blunting the anti-anabolic impact of IL-1. The chondroprotective antibiotic doxycycline may have a similar mechanism of action. Other nutrients reported to be useful in OA may likewise intervene in the activity or synthesis of IL-1. Supplemental glucosamine can be expected to stimulate synovial synthesis of 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, perhaps because it functions physiologically as a signal of sulfur availability. IL-1 is likely to decrease SAM levels in chondrocytes; supplemental SAM may compensate for this deficit. Adequate selenium nutrition may down-regulate cytokine signaling, and ample intakes of fish oil can be expected to decrease synovial IL-1 production; these nutrients should receive further evaluation in OA. These considerations suggest that non-toxic nutritional regimens, by intervening at multiple points in the signal transduction pathways 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.
authors.affiliation: Nutrition 21/AMBI, San Diego, CA 92037, USA.
authors.forename: M F
authors.initials: MF
authors.lastname: McCarty
authors.forename: A L
authors.initials: AL
authors.lastname: Russell
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D002358:Cartilage, Articular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005395:Fish Oils / Q000494:pharmacology; D005944:Glucosamine / Q000494:pharmacology; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D009536:Niacinamide / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D010003:Osteoarthritis / Q000188:drug therapy*; D012436:S-Adenosylmethionine / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D005395:Fish Oils; D007375:Interleukin-1; D009536:Niacinamide; D012436:S-Adenosylmethionine; D006820:Hyaluronic Acid; D019001:Nitric Oxide Synthase; D005944:Glucosamine