Reviewed: Haroyan A, Mukuchyan V, Mkrtchyan N, et al. Efficacy and safety of curcumin and its combination with boswellic acid in osteoarthritis: a comparative, randomized, double-blind, placebo-controlled study. BMC Complement Altern Med. 2018;18(1):7. doi: 10.1186/s12906-017-2062-z.
Symptoms of osteoarthritis (OA), including pain, morning stiffness, joint swelling, limited range of motion, and decreased physical function, typically are treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and cortisone. Although those drugs help manage pain and inflammation, they are associated with adverse effects, drug interactions, and are contraindicated in certain populations. Curcumin, a component of turmeric (Curcuma longa, Zingiberaceae) root and rhizome, has been reported to be a potent anti-inflammatory agent. The boswellic acids found in boswellia (Boswellia serrata, Burseraceae) possess anti-inflammatory and anti-arthritic properties.
The primary objective of this randomized, double-blind, placebo-controlled study was to compare the efficacy of curcumin, a combination of boswellic acid and curcumin, and placebo in treating OA by assessing their effects on joint pain, morning stiffness, and limitations of physical function. The secondary objective was to investigate the safety of the treatments.
The study was conducted between September 2014 and May 2016 and included 201 patients (40-77 years of age) from the Erebuni Medical Center in Yerevan, Armenia, who had been diagnosed with degenerative hypertrophic OA of the knee.
The active treatments were Curamin and CuraMed (both from EuroPharma USA; Green Bay, Wisconsin). Each 500-mg Curamin capsule contained 350 mg BCM-95 (Arjuna Natural Ltd.; Kerala, India) and 150 mg boswellia gum resin extract (BosPure; DolCas Biotech, LLC; Landing, New Jersey) consisting of 75% total organic and boswellic acids, including 10% 3-O-acetyl-11-keto-boswellic acid. Each 500 mg placebo capsule contained maltodextrin, calcium phosphate, gelatin, magnesium stearate, silica dioxide, FD&C yellow 5, FD&C yellow 6, and titanium dioxide. Each 750-mg capsule of the curcumin supplement CuraMed* contained 552-578 mg of BCM-95, a dry turmeric extract with 500 mg curcuminoids and 49-52 mg essential oil from turmeric rhizome. Excipients (120-149 mg) included phosphatidylcholine, medium-chain triglycerides, glycerol, gelatin, and yellow beeswax.
The patients were randomly assigned to the Curamin (n = 67), CuraMed (n = 66), or placebo group (n = 68), and were instructed to take one capsule three times daily for 12 weeks. No significant differences in demographic and other measured characteristics were observed among the patients at baseline. The mean age was 56.2 years, the average body mass index was 29 kg/m2, and 93% of the patients were female.
In the Curamin group, dropouts during the study included two patients who did not return, one who lost interest because of lack of improvement, one who was injured, and one who reported nausea and vomiting. In the CuraMed group, dropouts included three patients who did not return, one who was unable to attend the study visits, one who lost interest because of lack of improvement, and three who did not trust the medication. In the placebo group, three patients did not return, three lost interest because of lack of improvement, and three reported adverse effects (weight gain, stomach pain, dyspepsia, rash, and itching).
During the study visits at baseline, four weeks, and 12 weeks, the patients underwent radiography and sonography, completed the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and physical performance measures (PPM) tests, and provided blood samples.
After four weeks of treatment, significant decreases were seen in total WOMAC index scores in all groups (P < .05 for all). The scores gradually decreased in the Curamin and CuraMed groups until the end of the study. However, in the placebo group, no significant changes were seen at 12 weeks. At the end of the study, the improvements in the CuraMed (P < .001) were 3.6-fold and Curamin (P < .001) 2.7-fold greater than the improvement seen in the placebo group (P = .154).
Statistically significant pain relief was observed in all groups, as reported on the WOMAC index. In the placebo group, the pain index decreased significantly after four weeks of treatment (P < .01); however, after 12 weeks, the change was not significant (P > 0.05). Significant decreases in pain were seen in the Curamin and CuraMed groups (P < 0.001 for both) after 12 weeks of treatment.
The significant decrease in pain reported in the placebo group after four weeks is similar to results from other studies that have reported placebo effects of OA treatments; meta-analyses have indicated that more than 50% of OA study subjects respond positively to placebo treatment.1,2 Placebo effects can be influenced by the strength of the active treatment, the severity of disease at baseline, the route of medication delivery, and the study’s sample size.1
After 12 weeks of treatment, patients in the Curamin and CuraMed groups reported significantly less difficulty in moving their knees and less stiffness compared with baseline (P < .05 for both groups). In the placebo group, significant improvement was seen only after four weeks (P < .05) of treatment. Differences in changes during the study between the Curamin and placebo groups, and between the CuraMed and placebo groups, were not significant at any time point.
Among the PPM tests was the chair stand test. The maximum number of chair stand repetitions in 30 seconds increased significantly during the study in the Curamin and CuraMed groups (P < .001 for both). Significant differences between the Curamin and placebo groups (P < .05) and between the CuraMed and placebo groups (P < .01) were observed, with greater improvements in the Curamin and CuraMed groups. A timed walking test (40-m walking speed) revealed significantly increased walking speeds from baseline to week 12 only in the Curamin (P < .001) and CuraMed (P < .01) groups. Comparing the changes from baseline among the groups revealed significant differences between the CuraMed and placebo groups (P < .05) and between the Curamin and placebo groups (P < .01), with faster speeds reported in the active treatment groups.
In a separate walking test, patients were timed as they rose from a chair, walked three meters, turned around, walked back to the chair, and sat down. They wore regular footwear and used a walking aid if needed. The time to complete this task significantly decreased only in the Curamin (P < .001) and CuraMed (P < .05) groups. Comparing the changes from baseline to the end of the study revealed greater improvement in the Curamin group compared with the placebo group (P < .01); improvements in the CuraMed and placebo groups were not significantly different (P > .05).
The time required to go up and down a flight of stairs significantly decreased by week 12 only in the Curamin (P < .001) and CuraMed (P < .01) groups. Comparing the changes from baseline to the end of the study revealed greater improvement in the Curamin group compared with the placebo group (P < .01); improvements in the CuraMed and placebo groups were not significantly different.
Inflammation markers (i.e., erythrocyte sedimentation rate index and C-reactive protein levels) significantly increased (P < .05) in all groups compared with baseline, but were still within normal ranges, with no significant differences seen among the groups.
Adverse effects were observed in 13 of the 201 patients: four in the placebo group, two in the Curamin group, and seven in the CuraMed group. None of these effects were serious. The types and frequency of adverse effects were similar in all groups and were not considered related to the treatment.
Compared with placebo, Curamin significantly improved the patients’ performance on all physical performance tests and factors of the WOMAC index, and patients treated with CuraMed saw improvements in two physical performance tests and in the WOMAC joint pain index. These results suggest that “these plant extracts are more effective in combination,” wrote the authors, possibly because “boswellic acid may increase the bioavailability of curcumin. However, to our knowledge, there is no published study demonstrating the effect of boswellic acid on the bioavailability of curcuminoids.”
In this study, the 12-week use of curcumin complex (BCM-95) or its combination with boswellic acids reduced pain-related symptoms in patients with OA. The authors conclude that the combination of curcumin and boswellia extracts “increases the efficacy of treatment of OA, presumably due to synergistic effects of curcumin and boswellic acid.”
* In the journal article, the authors list two different amounts of curcuminoids for the “500 mg CuraMed” capsules. In the abstract, they state that each capsule contains “333 mg curcuminoids,” whereas each capsule is later described as containing “500 mg curcuminoids.” Company representatives clarified that a 750-mg CuraMed capsule was used that contains 500 mg curcuminoids.
- Zhang W, Robertson J, Jones AC, Dieppe PA, Doherty M. The placebo effect and its determinants in osteoarthritis: meta-analysis of randomized controlled trials. Ann Rheum Dis. 2008;6712):1716-1723.
- Zou K, Wong J, Abdullah N, et al. Examination of overall treatment effect and the proportion attributable to contextual effect in osteoarthritis: meta-analysis of randomized controlled trials. Ann Rheum Dis. 2016;75(11):1964-1970.