Reviewed: Onakpoya IJ, Spencer EA, Perera R, Heneghan CJ. Effectiveness of curcuminoids in the treatment of knee osteoarthritis: a systematic review and meta-analysis of randomized clinical trials. Int J Rheum Dis. 2017;20(4):420-433.

Osteoarthritis (OA) is a degenerative joint disease characterized by pain, inflammation, and progressive loss of joint cartilage. OA affects approximately 12% of the global population and causes chronic disability. Curcuminoids are one of the principally active components in turmeric (Curcuma longa syn. C. domestica, Zingiberaceae) rhizome. Evidence from both in vitro and in vivo studies supports the use of curcuminoids in treating OA. However, the results of clinical trials have been equivocal. The purpose of this systematic review and meta-analysis was to critically evaluate the clinical evidence regarding the safety and efficacy of curcuminoids, as concentrated in various turmeric extracts (Table 1), in treating knee OA.

The following databases were searched from inception through November 2016: Medline, Embase, AMED, CINAHL, the Cochrane Library, ISI Web of Science, ClincialTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). There were no language restrictions. Included studies met the following criteria: randomized, controlled trials (RCTs) that assessed the effectiveness of oral curcuminoids in treating adults (at least 40 years of age) with knee OA, treatment duration of at least four weeks, and reported OA outcome measures. Included studies needed to have a curcuminoid-only intervention compared with a placebo, standard care, or no intervention. Combination treatments (e.g., concentrated turmeric extract supplements that contained other herbs or dietary ingredients) were excluded.

A total of 370 non-duplicate citations were found, with seven RCTs meeting all inclusion criteria. All seven studies were conducted in Asia. Overall, the patients were 57-69 years of age and had OA symptoms for six to 20 months, and OA severity was mild to moderate.

The authors point out that in addition to the wide dosage range of curcuminoids (180 mg to 2 g/day) in the tested products, the curcuminoid supplements used were produced using various manufacturing processes (e.g., to improve bioavailability and curcumin content). However, in general, the authors of this meta-analysis and systematic review did not provide adequate details of the contents of the “curcuminoid supplements” used in the seven studies. In one case, the authors not only failed to mention the product name of the “C. longa extract” used by Madhu et al.,³ but also incorrectly described it as containing curcuminoids; the product was a water extract containing predominantly turmeric polysaccharides and no curcuminoids, according to the manufacturer. (Reporting guidelines for clinical trials of herbal medicinal products have been outlined in an elaborated Consolidated Standards of Reporting Trials [CONSORT] statement,⁸ as well as in two previously published HerbalGram articles on the concept of “botanical integrity.”^9,10)

Two studies used ibuprofen as the comparator, and five studies used placebo as the control comparator. Pain, physical function, and quality of life (QoL) were the primary outcome measures. Secondary measures were adverse effects (AEs), dropout rates, and use of rescue medication. The risk of study bias was assessed with the Cochrane Library criteria.

Four of the studies had unclear risk of bias in at least four categories, and three studies had high risk of other bias. Six studies used one or more validated instruments to assess pain; five used the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), five used a visual analog scale (VAS), and one used the Japanese Orthopaedic Association (JOA) tool. Five studies assessed overall global function using WOMAC or JOA total score, and two studies evaluated QoL using the Lequesne’s Pain-Function Index (LPFI). Meta-analyses of the pooled data revealed the following findings.

Results

Pain: Curcuminoids were significantly better at reducing knee pain than placebo (P < .00001), as measured with VAS (n = 366). However, curcuminoids were less effective than ibuprofen (WOMAC; n = 531) at alleviating pain. A dose-effect plot indicated that higher doses of curcuminoids were associated with greater pain reduction (P = .02).

Function: A meta-analysis of total WOMAC scores (n = 498) indicated that curcuminoids were as effective as ibuprofen and significantly more effective than placebo at improving overall global function (P = .03). Based on WOMAC subscores (n = 531), curcuminoids significantly improved physical function compared to controls (P = .04), but there was no significant difference among groups for stiffness scores. Sensitivity analyses revealed that curcuminoids were significantly more effective than placebo (P value not reported), but significantly less effective than ibuprofen, in improving function and stiffness.

QoL, Rescue Medication Use, and Safety: Curcuminoids significantly improved QoL compared to placebo (n = 107; P < .0001). Curcuminoid supplementation was also associated with a significant reduction in use of rescue medication compared with controls (n = 567; P = .02). AEs were detailed in five of the studies. No significant difference in AE frequency was found between turmeric extract treatment and control. However, one study showed a lower occurrence of abdominal pain/distension with curcumin compared to ibuprofen.² Sensitivity analyses revealed that the incidence of AEs did not significantly differ between curcuminoid and ibuprofen groups. 

Conclusion

In summary, the results of the meta-analysis indicate that in patients with knee OA, curcuminoids significantly improve pain, function, and QoL compared with placebo, but curcuminoids are less effective in reducing pain and increasing function compared with ibuprofen. However, curcuminoids are as effective as ibuprofen and significantly more effective than placebo in improving global function scores (pain, stiffness, and function). In addition, curcuminoids significantly reduced the use of rescue medication compared to controls.

Considering the poor bioavailability of curcuminoids, variation in the preparation forms used in these studies, and relatively small sample sizes, the authors caution that the validity of the curcuminoid dose-pain response effect is “uncertain” (data limitations prevented the exploration of other dose-response relationships). A number of other limitations are acknowledged, including the small number of clinical trials, the lack of control for different OA phenotypes, and the fact that all of the included studies were conducted in Asia. Turmeric is a common component of Asian diets, and dietary intake of curcuminoids was not controlled for in these studies.

The authors suggest that future research priorities should include longer-term studies to evaluate curcuminoids as adjuncts to conventional therapy in non-Asian populations using validated outcome measures, and “such trials should be reported in accordance with standardized guidelines, for example, CONSORT.” In addition, research to determine the minimum effective dose of curcuminoids based on extraction techniques and bioavailability is needed.

Overall, the authors conclude that curcuminoids may have beneficial effects on pain, function, and QoL for patients with knee OA; however, curcuminoids seem to have no effect on knee stiffness and are less effective than ibuprofen for pain.

—Heather S. Oliff, PhD

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