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(7):1-16.
To assess the safety and efficacy of curcumin extract alone and in combination with boswellic acid in the treatment of knee osteoarthritis (OA).
This was a comparative, randomized, double-blind, placebo-controlled trial. Individuals were randomized into 1 of 3 groups: curcumin only, curcumin in combination with boswellic acid, and placebo.
The study enrolled 201 men and women ages 40 to 77 years (mean: 56.2 y) with radiography-verified degenerative hypertrophic OA of the knee joints. Individuals were enrolled between September 2014 and May 2016 from health centers in Yerevan, Armenia. The cohort was predominantly female (93%), and the average body mass index (BMI) was 29 (range: 18-49).
Participants were excluded if they had secondary or inflammatory arthritis, history of meniscal tear, grade 2 to 3 synovitis, or recent (within the preceding 3 months) intra-articular injection of hyaluronate or glucocorticoids. Individuals who were smokers, addicted to narcotics, pregnant, lactating, or had major chronic disease were also excluded. The researchers prohibited the use of analgesics for 2 weeks before the study and the use of glucosamine or chondroitin supplements for 3 months before the study.
The curcumin intervention was BCM-95, a patented extraction, containing 500 mg of curcuminoids and 50 mg volatile oils per capsule. The curcumin/boswellia intervention contained 350 mg of curcuminoids (BCM-95) and 150 mg of Boswellia serrata gum resin extract (75% boswellic acid) per capsule.
Placebo capsules were a mix of excipients intended to replicate the appearance and odor of the intervention capsules. These excipients included maltodextrin, calcium phosphate, gelatin, magnesium stearate, silica dioxide, FD&C yellow 5, FD&C yellow 6, and titanium dioxide.
These benefits exceeded the placebo effect after 12 weeks of supplementation, and AEs were uncommon and minor.
All participants took 1 capsule (containing either curcumin, the combination, or placebo) 3 times a day for 12 weeks.
Study Parameters Assessed
Investigators assessed arthritis symptoms (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), physical performance (Osteoarthritis Research Society International [OARSI]), serum inflammatory markers (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]), and BMI. Each parameter was assessed at baseline, 4 weeks, and 12 weeks. To assess safety/adverse effects, they asked participants to contact investigators if they experienced side effects or illness over the course of the study.
The WOMAC is a questionnaire that scores joint pain (0-20), morning stiffness (0-8), and physical function (0-68), with higher scores representing more severe OA symptoms. The OARSI physical performance assessment includes the following: maximum number of chair stand repetitions (chair stand test [CST]) in 30 seconds (30s-CST); time it takes to walk 40 meters (40 m fast-paced walk test [FPWT]); time it takes to stand up from a chair, walk 3 meters, walk back to the chair, and sit down (“timed up and go” [TUG]); and time it takes to ascend and descend a 9-step staircase (stair-climb test [SCT]).
Primary Outcome Measures
The primary outcome measures related to efficacy included the WOMAC index score and results of the OARSI physical performance tests. The primary measure of safety was participants' reports of adverse events (AEs).
Only the combination curcumin/boswellia group showed a statistically significant decrease in total WOMAC score compared to placebo; the index scores fell from an average of 33.06 to 26.49 after 12 weeks of treatment. When the investigators analyzed the subsections of WOMAC they found statistically significant reductions in pain score in both treatment groups; the effect size compared to placebo was 0.50 for curcumin and 0.37 for the combination of curcumin/boswellia. In terms of morning stiffness and physical function, investigators noted statistically significant improvement via within-group comparison for the treatment groups, but there was no significant improvement when each group was compared with placebo. This is partly attributed to placebo effect, which was observed with WOMAC index scores between baseline and week 4 (placebo group showed significantly improved scores at week 4 but insignificant improvement at week 12).
All OARSI clinical performance measures improved with the combination supplement intervention. The curcumin group showed improvement in every measure except for the TUG test. The effect size of improvement over placebo for each measure was as follows:
- 30s-CST: Curcumin-only, 0.50; curcumin/boswellia, 0.63
- 40 m FPWT: Curcumin-only, 0.38; curcumin/boswellia, 0.32
- TUG: Curcumin-only, 0.53; curcumin/boswellia, 0.38 (not statistically significant)
- SCT: Curcumin-only, 0.38; curcumin/boswellia, 0.45
In total, 13 AEs were reported over the course of the study, none of them serious. Adverse events were distributed over the 3 groups (placebo, 4 events; curcumin, 7 events; curcumin/boswellia, 2 events); however, nausea was reported in treatment groups only.
Blood markers of chronic inflammation did not vary significantly between treatment and control groups. All groups had a significant increase in ESR and CRP over the course of the study, but levels remained within normal limits (ESR, 2-15 mm/h; CRP<5 mg/L).
This study demonstrated modest but statistically significant benefits of curcuminoids alone and in combination with boswellic acid on knee OA pain and associated functional limitations. These benefits exceeded the placebo effect after 12 weeks of supplementation, and AEs were uncommon and minor.
The combination of curcumin/boswellia was more consistently effective for the primary outcome measures, and this higher performance may be attributable to the synergistic effects of the individual constituents on disease pathophysiology. In vitro and animal studies have shown that curcuminoids modulate inflammation, decrease chondrocyte catabolism and apoptosis, and increase apoptosis of synovial adherent cells.1-3 Boswellic acid reduces leukocyte infiltration into the knee joint (thereby reducing inflammation), prevents collagen degradation, and inhibits pro-inflammatory mediators.4-6
In developing a treatment plan, integrative medicine practitioners often utilize multiple modalities to achieve synergistic benefits. Nutraceutical therapies can be weaker than their pharmaceutical counterparts, and they often require more frequent dosing for longer periods to achieve full therapeutic effect. This generally also means the natural products have fewer serious side effects. So, when an individual presents wanting an alternative to nonsteroidal anti-inflammatory drugs for their OA symptoms, an integrative medicine practitioner is unlikely to swap this medication for a single nutraceutical intervention without any additional recommendations.
Exercise is an effective nonpharmacologic intervention for knee OA. There is strong evidence it improves pain, function, and quality of life for individuals with this disease.7 Similarly, weight optimization is essential both for reducing load on the joints and decreasing inflammatory cytokines produced by adipose tissue.8
An integrative medicine practitioner may also look at additional natural therapies that target other aspects of knee OA pathogenesis, with the goal of having synergistic benefits. For example, oral glucosamine sulfate and chondroitin sulfate have been shown to slow disease progression,9and acupuncture may help reduce pain from OA of peripheral joints.10
In the present study, neither curcumin alone nor the curcumin/boswellia combination was a miracle supplement for knee OA, but both were modestly beneficial for pain and function. They would be helpful additions to a comprehensive integrative medicine treatment plan.
Limitations of the study include its sample size (N=201) and short duration (12 weeks).
- Shakibaei M, John T, Schulze-Tanzil G, Lehman I, Mobasheri A. Suppression of NF-kappa-B activation by curcumin leads to inhibition of expression of cyclooxygenase-2 and matrix metalloproteinase-9 in human articular chondrocytes: implication for the treatment of osteoarthritis. Biochem Pharmacol. 2007;73(9):1434-1445.
- Henrotin Y, Clutterbuck AL, Allaway D, et al. Biological actions of curcumin on articular chondrocytes. Osteoarthritis Cartilage. 2010;18(2):141-149.
- Mathy-Hartert M, Jacquemond-Collet I, Priem F, Sanchez C, Lambert C, Henrotin Y. Curcumin inhibits pro-inflammatory mediators and metalloproteinase-3 production by chondrocytes. Inflamm Res. 2009;58(12):899-908.
- Moussaieff A, Mechoulam R. Boswellia resin: from religious ceremonies to medical uses; a review of in-vitro, in-vivo and clinical trials. J Pharm Pharmacol. 2009;61(10):1281-1293.
- Takada Y, Ichikawa H, Badmaev V, Aggarwal BB. Acetyl-11-Ketob-boswellic acid potentiates apoptosis, inhibits invasion, and abolishes osteoclastogenesis by suppressing NF-kB and NF-kB regulated gene expression. J Immunol. 2006;176(5):3127-3140.
- Blain EJ, Ali AY, Duance VC. Boswellia frereana (frankincense) suppresses cytokine-induced matrimetalloproteinase expression and production of pro-inflammatory molecules in articular cartilage. Phytother Res. 2010;24(6):905-912.
- Fransen M, McConnell S, Harmer AR, Van der Esch M, Simic M, Bennell KL. Exercise for osteoarthritis of the knee: a Cochrane systematic review. Br J Sports Med. 2015;49(24):1554-1557.
- de Boer TN, van Spil WE, Huisman AM, et al. Serum adipokines in osteoarthritis; comparison with controls and relationship with local parameters of synovial inflammation and cartilage damage. Osteoarthritis Cartilage. 2012;20(8):846-853.
- Fransen M, Agaliotis M, Nairn L, et al. Glucosamine and chondroitin for knee osteoarthritis: a double-blind randomised placebo-controlled clinical trial evaluating single and combination regimens. Ann Rheum Dis. 2015;74(5):851-858.
- Lee MS, Ernst E. Acupuncture for pain: an overview of Cochrane reviews. Chin J Integr Med. 2011;17(3):187-189.