Impact of Supplementation with Curcuminoids on Systemic Inflammation in Patients with Knee Osteoarthritis: Findings from a Randomized Double-Blind Placebo-Controlled Trial
Drug Res. 2015;65(10):521-25
Osteoarthritis (OA) is a degenerative joint disease associated with inflammation. Inflammatory response activates chondrocytes and synoviocytes to produce matrix degrading enzymes, which causes OA related degeneration of collagen and cartilage. It has also been reported that over expression of proinflammatory cytokines in activated chondrocytes makes the “cause and effect” association of inflammation and OA further complicated.
In previous published preclinical and clinical studies Curcuminoids have shown to possess anti-arthritic acitivity; which was attributed to its anti-inflammatory, anti-oxidant, anti-catabolic and anti-apoptopic activities. Previous clinical trials of Curcumin C3 Complex® (Patented product of Sabinsa Corporation) in patients with OA, has shown symptomatic relief proving its efficacy in OA. .
To investigate if clinical benefits with Curcuminoids are associated with a significant alteration in circulating biomarkers of systemic inflammation including pro-inflammatory cytokines.
This study was a sub study of the previous randomized double-blind placebo-control parallel-group clinical trial. Forty subjects with mild-to-moderate degree knee OA were randomly allocated to receive either pure Curcuminoids (1500 mg/day in 3 divided dose; n=19) or matched placebo (n=21) for 6 weeks. A natural bioavailability enhancer Piperine (15 mg/day in 3 divided dosage along with Curcuminoids) was added to the treatment regimen. Naproxen was allowed during the study for managing intolerable pain. Efficacy measures determined in this sub study were - changes in serum levels of interleukin-4 (IL-4), IL-6, tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), highsensitivity C-reactive protein (hs-CRP), and erythrocyte sedimentation rate (ESR).
Results and Discussion:
- In Curcuminoids group at the end of trial, a significant decline in serum concentration of IL-4 (P=0.001), IL-6 (P=0.006) and hs-CRP (P=0.004) was seen. However, serum levels of TNF-α and TGF-β and mean ESR remained unaltered.
- In placebo group, serum concentrations of IL-4 (P=0.001), IL-6 (P=0.003), TNF-α (P=0.003) and TGF-β (P=0.005) were significantly reduced but mean hs-CRP and ESR values remained unchanged.
- Comparison of the magnitude of changes in the evaluated inflammatory biomarkers did not indicate any significant difference in the Curcuminoids and placebo groups.
- Changes in all of the evaluated hematological parameters during the course of study were comparable between the Curcuminoids and placebo groups.
- According to patient’s reports, 84% of subjects reduced the use of naproxen in Curcuminoids group whereas only 19% subjects in placebo group reduced the use of this analgesic. This difference was significant between the study groups (P=0.001)
This study showed that systemic biomarkers of inflammation could not be correlated with the observed improvement in symptoms of OA. It is more plausible that the beneficial effects of Curcuminoids are because of a local anti-inflammatory effect in the osteo-cartilagenous tissue. The author of the study also recommended future studies to measure the concentrations of inflammatory mediators in the synovial fluid following treatment with Curcuminoids.