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

Abstract

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, I2 = 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.

The efficacy of curcumin in relieving osteoarthritis: A meta‐analysis of meta‐analyses

“…MCID is critical for establishing whether or not a meta‐analysis's observed effect is clinically relevant. From 8 inputted meta‐analyses for this study, only two studies (Dai et al, 2021; Feng et al, 2022a) had calculated the MCID. Therefore, we were unable to report the overall MCID.…”

“…Dai et al observed that the VAS for pain and WOMAC pain score effect sizes surpassed the MCID, which means that curcumin supplementation could be considered a meaningful improvement from a clinical perspective (Dai et al, 2021). On the other hand, Feng et al indicated that only the VAS for pain and the WOMAC total score gained clinical significance by exceeding their MCID (Feng et al, 2022a). More research is needed to produce more nuanced and thorough results about MCID.…”

“…Further studies need to provide more nuanced and comprehensive results that solve the complexities related to curcuminoid extracts and bioavailability while reinforcing the potential implications for patient outcomes and future research directions. In addition, since only two studies (Dai et al, 2021; Feng et al, 2022a) calculated the MCID, the overall MCID could not be analyzed or reported.…”

“…As well, in most studies, curcumin was shown to reduce inflammation and side effects, yet some studies did not observe such effects, especially when compared to other compounds such as NSAIDs (Hsiao et al, 2021; Onakpoya et al, 2017; White et al, 2019). Furthermore, most meta‐analyses were unable to provide definitive and clinically relevant conclusions due to the low quality and heterogeneity of the articles (del Grossi et al, 2017; Feng et al, 2022b; Wang et al, 2021). Hence, we assessed curcumin's effects on improving knee function and pain in an umbrella meta‐analysis.…”

The effects of manual therapy in pain and safety of patients with knee osteoarthritis: a systematic review and meta-analysis

“…Primary and secondary outcomes were collected, and the data were analyzed after randomization and at the end of treatment. Minimum clinically important difference (MCID) thresholds for the VAS and WOMAC scores were defined as a 20% fluctuation from the baseline of the included studies based on previous studies and were calculated as follows: 1.18/10 for the VAS for pain and 2.12/20 for the WOMAC pain score [ 25 ].…”