Potential Benefits of Curcumin in Rheumatoid Arthritis

Abstract

Widely known as a curry spice, curcumin has a long history of use in the treatment of inflammatory conditions in Eastern Medicine. The spice is gaining interest in modern medicine for a diverse array of conditions, including rheumatoid arthritis. Evidence indicates curcumin can effectively suppress inflammation through inhibition of pro-inflammatory cytokine production as well as modulate B cell and T cell differentiation and function. The following article will evaluate the existing clinical trial literature assessing the impact of curcumin on patients with rheumatoid arthritis. Potential mechanisms of action, bioavailability issues, and effective dosing will be described.

“Clinical trial data demonstrates improvements in VAS, DAS, and ACR-20 in patients receiving curcumin supplementation for RA.”

Introduction

Turmeric is widely used as a curry spice in Asian food. It is also known as the “golden spice” because of its use as a yellow-dye.^1-3 Turmeric is comprised of three curcuminoids: curcumin, desmethoxycurcumin, and bisdemethoxycurcumin.^2,4 Of these, the most active component is curcumin.^2,4

Traditionally, curcumin has been used in Chinese, Indian, and Southeast Asian medicine for pain and inflammation. More recently, the spice has been studied for its potential anti-carcinogenic, anti-coagulant, antimicrobial, and antioxidant properties.^1,2,5,6 The purpose of this manuscript is to describe curcumin, summarize the available evidence related to its effect on rheumatoid arthritis (RA), and discuss its clinical utility as a treatment option in this progressive joint disease.

Potential Mechanisms of Action

Curcumin is most commonly known for its anti-inflammatory effects. Several mechanisms by which curcumin impart these effects have been described. Isolated curcumin extract has been shown to downregulate the expression of a number of pro-inflammatory cytokines including interluekins, phospholipase A2, 5-lipoxygenase, and cyclooxygenase-2 (COX-2), through modulation of nuclear factor kappa-B (NF-κB).^7,8 A second major pathway involves tumor necrosis factor-alpha (TNF-α).^2,4,5 Curcumin has been shown to both block the production of TNF-α as well as the production of downstream inflammatory mediators signaled through the TNF-α pathway.^2,5

More recently, curcumin has been studied for its effect on the immune system. Curcumin has been shown to influence a variety of immune cells including macrophages, dendritic cells, B cells and T cells. ⁹ Evidence from in vitro and experimental studies indicate that curcumin suppresses activation and cytokine production of auto-reactive T cell subsets as well as inhibits production of autoantibodies by B cells. ⁹ These immunomodulating properties are among the hypothesized pathways curcumin may be beneficial in reducing the immunopathogenesis of RA.

Clinical Trial Data in Rheumatoid Arthritis

A study by Chandran et al. evaluated the efficacy of curcumin supplementation in 45 patients diagnosed with RA. ¹⁰ Participants were randomized to one of three groups and were followed for eight weeks. The groups received either curcumin 500 mg daily, diclofenac 50 mg daily or a combination of curcumin 500 mg and diclofenac 50 mg daily. All three groups demonstrated improvement in disease activity scores (DAS) as well as improvement in joint tenderness and swelling. Interestingly, the greatest improvement in DAS was observed in the curcumin-only group. This improvement was significantly better than that demonstrated by the diclofenac-only group. Furthermore, there were fewer and less severe adverse events reported in curcumin-only group.

A double-blind, placebo-controlled trial by Amalraj et. al. evaluated the impact of curcumin supplementation on RA outcomes in 36 patients. ¹¹ Patients received curcumin 250 mg twice a day, curcumin 500 mg twice a day or placebo for 90 days. At the end of the trial, the visual analog scale (VAS), DAS and American College of Rheumatology (ACR-20) criteria improved in both curcumin treated groups while no statistically significant change from baseline was observed in the placebo group. No adverse effects were shown within any of the three groups.

A major setback in the use of curcumin as an anti-inflammatory agent comes with its low oral bioavailability.^6,12 Jacob et al. studied the impact of a hydrogenated curcumin product (CuroWhite^TM) formulated to increase bioavailability in twenty-four patients with confirmed RA over a three-month time period. ¹³ Patients were randomized to one of 3 groups: 250 mg of CuroWhite^TM, 500 mg CuroWhite^TM, or placebo once daily. Compared to baseline, the groups treated with the hydrogenated curcumin product demonstrated significant improvements in DAS, VAS, and ACR-20, with the highest dose experiencing the greatest change. Comparatively, the placebo group showed no significant changes from baseline. The study also evaluated impact on laboratory markers of inflammation including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and rheumatoid factor (RF). Both doses of the CuroWhite^TM product significant decreased ESR, CRP and RF from baseline.

Nanoencapsulation is another strategy to increase the bioavailability of curcumin. Javadi et al. evaluated the effect of curcumin nanomicelle on the symptoms of patients with RA. ¹⁴ The study randomized 65 patients to receive either curcumin nonmicelle 40 mg or placebo three times daily for 12 weeks. Compared to baseline, DAS and the number of tender and swollen joints improved significantly in both groups. The difference in between group change was not significant and no significant changes in ESR were observed.

Conclusion

Clinical trial data demonstrates improvements in VAS, DAS, and ACR-20 in patients receiving curcumin supplementation for RA.^10,11,13,14 Doses of 250–1000 mg daily appeared to be effective, with greater improvements in RA symptoms observed at higher doses. Importantly, the reviewed trials have a number of notable limitations including small sample size and short duration of follow-up. Additionally, patients enrolled in the studies did not receive the standard of care for RA (treatment with disease-modifying anti-rheumatic drugs (DMARDs) was an exclusion criteria). ¹⁵ As such, additional studies are needed to determine the utility of curcumin in place of and/or in addition to standard DMARD therapy. Despite these limitations, curcumin’s tolerability, safety profile, and promising efficacy as monotherapy, make it a reasonable supplement for patients with RA to incorporate into their regimen.