Efficacy and safety of curcuminoids alone in alleviating pain and dysfunction for knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials

Background Curcuminoids (CURs) are the principal ingredients of Curcuma longa L. [Zingiberaceae] (CL)-an herbal plant used in east Asia to alleviate pain and inflammation. Thus far, the therapeutic effects of CURs for knee osteoarthritis (OA) uncovered by multiple reviews remained uncertain due to broadly involving trials with different agents-combined or CURs-free interventions. Therefore, we formed stringent selection criteria and assessment methods to summarize current evidence on the efficacy and safety of CURs alone in the treatment of knee OA. Methods A series of databases were searched for randomized controlled trials (RCTs) evaluating the efficacy and safety of CURs for knee OA. Clinical outcomes were evaluated using meta-analysis and the minimum clinically important difference (MCID) for both statistical and clinical significance. Results Fifteen studies with 1670 patients were included. CURs were significantly more effective than placebo in the improvements of VAS for pain ( WMD: - 1.77, 95% CI: - 2.44 to - 1.09), WOMAC total score ( WMD: - 7.06, 95% CI: - 12.27 to - 1.84), WOMAC pain score ( WMD: - 1.42, 95% CI: - 2.41 to - 0.43), WOMAC function score ( WMD: - 5.04, 95% CI: - 7.65 to - 2.43), and WOMAC stiffness score ( WMD: - 0.54, 95% CI: - 1.03 to - 0.05). Meanwhile, CURs were not inferior to NSAIDs in the improvements of pain- and function-related outcomes. Additionally, CURs did not significantly increase the incidence of adverse events (AEs) compared with placebo ( RR: 1.03, 95% CI: 0.69 to 1.53, P = 0.899, I-2 = 23.7%) and NSAIDs (RR: 0.71 0.65, 95% CI: 0.57 0.41 to 0.90 1.03). Conclusions CURs alone can be expected to achieve considerable analgesic and functional promotion effects for patients with symptomatic knee OA in short term, without inducing an increase of adverse events. However, considering the low quality and substantial heterogeneity of present studies, a cautious and conservative recommendation for broader clinical use of CURs should still be made. Further high-quality studies are necessary to investigate the impact of different dosages, optimization techniques and administration approaches on long-term safety and efficacy of CURs, so as to strengthen clinical decision making for patients with symptomatic knee OA.