Knee osteoarthritis (OA) causes pain and loss of function. Conventional treatment of knee OA often involves the use of non-steroidal anti-inflammatory drugs (NSAIDs); however, NSAIDs can cause serious gastrointestinal (GI) side effects and increase the risk of cardiovascular disease. Healthcare providers and patients are looking for complementary therapies that are safer than NSAIDs and other conventional pain relievers. In Ayurvedic medicine, Boswellia (Boswellia serrata, Burseraceae) resin and curcuminoids from turmeric (Curcuma longa, Zingiberaceae) rhizome have been used to treat inflammatory and degenerative diseases including OA. Evidence from in vitro and in vivo studies suggests that curcuminoids and Boswellia can inhibit inflammatory pathways associated with worsening of OA symptoms and disease progression. Few randomized controlled trials (RCTs) have tested the effect of curcuminoids and Boswellia compared to treatment with NSAIDs. The purpose of this systematic review and meta-analysis was to assess the efficacy and safety of curcuminoid and Boswellia formulations, alone or in combination, in knee OA.
Medline, EMBASE, Google Scholar, Web of Science, and the Cochrane Database were searched from inception to February 21, 2018. The search criteria were not provided in the article. Reference lists of previous reviews and meta-analyses were also searched, as were recent conference proceedings. Included studies were RCTs that compared orally administered curcuminoid or Boswellia formulations (alone or combined) with control groups receiving a matching placebo or an NSAID, in patients with a diagnosis of knee OA. Studies were excluded if they used a non-randomized design or used curcuminoids or Boswellia in combination with other nutraceuticals or supplements, NSAIDS, or other analgesic drugs. Methodological quality of the studies was assessed using the Cochrane Risk of Bias Tool. Outcomes of interest were pain, knee function, use of rescue medications during the trial, GI adverse events (AEs), serious AEs, and patient withdrawal due to AEs.
A total of 92 potentially relevant studies were identified, of which 14 met the inclusion criteria. The included studies enrolled a total of 1215 patients and compared curcuminoid formulations against placebo (n=5 studies; 331 patients), Boswellia extract against placebo (n=4 studies; 216 patients), turmeric extract against ibuprofen (n=2 studies; 438 patients), Boswellia extract against valdecoxib (n=1 study; 66 patients), curcuminoid formulations and Boswellia combined against placebo (n=2 studies; 180 patients), and turmeric extract and Boswellia extract combined against celecoxib (n=1 study; 28 patients). The meta-analysis included 11 studies (n = 1009 patients). Three studies were not included in the meta-analysis because they did not appropriately report pain or function outcomes (n=2) or used a comparator drug that had been removed from the market (n=1). All included studies were published between 2003 and 2018. All were of short duration, ranging from four to 12 weeks. Overall study quality was stated to be low due to selection bias, selective reporting bias, and concerns about sponsorship bias. Six of the studies were sponsored by industry.
Curcuminoids vs. placebo
The effect of curcuminoid formulations on pain relief was significantly better than placebo (P=0.0003, n=5 studies). Function scores were significantly better with curcuminoids compared to placebo (P=0.0003, n=3 studies). No statistically significant differences were found for the number of patients needing rescue medication, patients reporting GI AEs, or patients withdrawing because of AEs. No serious AEs were reported.
Boswellia vs. placebo
The effect of Boswellia formulations on pain relief was significantly better than placebo (P<0.00001, n=4 studies). Function scores were also significantly better with boswellia compared to placebo (P<0.0001, n=4 studies). No significant differences were found for patients reporting GI AEs or withdrawing because of AEs. No serious AEs were reported. Use of rescue medications was not adequately reported.
Curcuminoids vs. NSAIDs
No differences were found between groups for pain scores, function scores, or need for rescue medication. In two studies, patient withdrawal due to AEs was significantly lower for curcuminoid formulations than for the NSAID ibuprofen (relative risk [RR]=0.22, 95% confidence interval [CI]: 0.05-0.99). GI AEs were significantly lower for curcuminoids than ibuprofen (RR=0.74, 95% CI: 0.60-0.91). No serious AEs were reported.
Curcuminoids plus Boswellia vs. placebo or NSAIDs
Combined Boswellia and curcuminoid or turmeric formulations decreased pain with movement significantly better than placebo (P< 0.001, an n=1 study utilizing B. carteri, and P<0.05, n=1 study). Only the latter study reported function (no significant differences) and AEs (variation among three trial arms of unclear significance; no serious AEs). In a third RCT, pain relief was similar between a combined Boswellia and curcuminoid product and the NSAID celecoxib. No adverse events were reported.
The authors state that the results of this meta-analysis “indicate that both curcuminoid and Boswellia formulations administered as mono-therapy are significantly more effective than placebo in relieving symptoms of knee OA and that they do not pose significant safety risks.” There are several limitations to this meta-analysis. The studies had moderate-to-high heterogeneity, which may be due in part to the different curcuminoid and Boswellia products tested. None of the studies had a treatment duration longer than 24 weeks, and 12 or fewer weeks as usual. Knee OA is a chronic disease, and short-term studies are not sufficient to assess long-term safety and efficacy of curcuminoids and Boswellia. The meta-analysis was also limited by the small number of RCTs assessing safety. The authors conclude that the “current body of evidence is not adequate in size or quality to make any meaningful clinical practice recommendations.” Future trials should have higher methodological quality, larger populations, and longer duration to better understand potential benefits of a curcuminoid and Boswellia formulations as a sole treatment for knee OA or as adjuvant treatment for patients who are dependent upon NSAID treatment and want to reduce NSAID risks.
The authors declare that they have no competing interests.
Bannuru RR, Osani MC, Al-Eid F, Wang C. Efficacy of curcumin and Boswellia for knee osteoarthritis: Systematic review and meta-analysis. [Published online March 10, 2018]. Semin Arthritis Rheum. doi: 10.1016/j.semarthrit.2018.03.001.