Abstract
BACKGROUND: Curcumin is a potent anti-inflammatory and antioxidant herbal medicine that has been shown to exert beneficial effects on knee osteoarthritis (OA). Previous studies revealed that curcumin had a superior effect compared to control treatments in terms of pain intensity and other patient-reported outcomes, including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS), visual analog scale (VAS), and Japanese Knee Osteoarthritis Measure (JKOM). However, it remains unclear whether curcumin has beneficial effects on serum inflammatory biomarkers. This systematic review and meta-analysis (SRMA) aimed to evaluate the effects of curcumin on changes in serum inflammatory biomarkers in patients with knee OA. METHODS: The PubMed, MEDLINE, Embase, Web of Science, Cochrane Library, and EBSCOhost databases were systematically searched from inception to March 28, 2025 to identify all randomized clinical trials (RCTs) that examined the use of curcumin for treating knee OA. Data related to serum inflammatory biomarkers, including C-reactive protein (CRP) levels, the erythrocyte sedimentation rate (ESR), tumor necrosis factor (TNF-alpha) levels, interleukin (IL)-1beta levels, IL-6 levels, and prostaglandin E2 (PGE-2) levels, were extracted and subjected to meta-analysis. RESULTS: Twenty-one studies involving 1705 patients were included. The studies were conducted across seven countries, and their sample sizes ranged from 24 to160. Meta-analysis revealed that the levels of CRP (SMD = -0.906, 95% CI = -1.543 ~ -0.269, P value = 0.005) and TNF-alpha (SMD = -0.921, 95% CI = -1.817 ~ -0.026, P value = 0.044) were significantly lower in the curcumin group than in the placebo group. However, there were no significant differences in the ESR (SMD = -0.064, 95% CI = -0.064 ~ 0.541, P value = 0.836), IL-lbeta (SMD = -0.362, 95% CI = -0.816 ~ 0.092, P value = 0.118), IL-6 level (SMD = -0.218, 95% CI = -0.806 ~ 0.370, P value = 0.467), or PGE-2 level (SMD = 0.413, 95% CI = -0.312 ~ 1.139, P value = 0.264) between the curcumin and control groups. The sensitivity test for CRP indicated that no individual study had a significant influence on the pooled results, while TNF-alpha was not as consistent as that of CRP. The visual analysis of the funnel plots revealed no publication bias. CONCLUSION: Curcumin led to a decrease in the serum CRP and TNF-alpha levels in patients with knee OA. Additional large-scale studies or even synovial fluid analyses are recommended to further evaluate the effects of curcumin on proinflammatory biomarkers in patients with knee OA.