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Oxidative stress is implicated in the pathogenesis of osteoarthritis. Curcuminoids are natural polyphenols with strong antioxidant capacity and may thus be helpful in the treatment of osteoarthritis. The present randomized double-blind placebo-controlled trial investigated the efficacy of curcuminoids in reducing systemic oxidative burden in patients suffering from knee osteoarthritis. Forty patients with mild-to-moderate primary knee osteoarthritis were given curcuminoid capsules (1500 mg/day in 3 divided doses; n = 19) or matched placebo capsules (n = 21) for a period of 6 weeks. Curcuminoids were co-administered with piperine (15 mg/day) in order to improve the bioavailability. Serum activities of superoxide dismutase (SOD) and concentrations of reduced glutathione (GSH) and malonedialdehyde (MDA) were determined spectrophotometrically at baseline and at the end of the treatment period in both groups. Serum activities of SOD as well as GSH and MDA concentrations were comparable between the study groups at baseline (p > 0.05). There was a significant elevation in serum SOD activities (mean change: 2.94 ± 3.73 vs. −0.38 ± 1.33; p < 0.001), a borderline significant elevation in GSH concentrations (mean change: 1.39 ± 2.78 vs. −0.02 ± 1.62; p = 0.064) and a significant reduction in MDA concentrations (mean change: −5.26 ± 4.46 vs. −2.49 ± 3.81; p = 0.044) in the curcuminoids compared with the placebo group. Changes in serum activities of SOD and concentrations of GSH and MDA during the course of trial were significantly correlated. Short-term supplementation with curcuminoids attenuates systemic oxidative stress in patients with osteoarthritis. These antioxidant effects may account for the reported therapeutic effects of curcuminoids in relieving osteoarthritis symptoms. [ABSTRACT FROM AUTHOR]