Addition of curcumin to mesalamine therapy increases its ability to induce clinical and endoscopic remission in patients with mild-to-moderate active ulcerative colitis (UC), researchers show in the August issue of Clinical Gastroenterology and Hepatology.
Patients with mild-to-moderate UC are usually treated with oral and/or topical mesalamine. Those who do not respond to mesalamine require corticosteroids and/or immunomodulators, which have detrimental side effects. New compounds are needed to induce remission in patients with mild-to-moderate UC without systemic immunosuppression.
Curcumin is a natural phytochemical derived from the Indian spice tumeric, a member of the ginger family. It has been used for centuries in ayurvedic and traditional Chinese medicine to treat a wide range of inflammatory diseases. Curcumin prevents and reduces trinitrobenzene sulfonic acid-induced colitis in mice, and was reported to be superior to placebo in maintaining remission in UC patients for up to 12 months. However, it is not clear whether this agent can induce remission in patients with UC.
Alon Lang et al investigated the ability of curcumin, as an add-on therapy to mesalamine, to induce remission in 50 patients with active mild-to-moderate UC (defined by the Simple Clinical Colitis Activity Index) who did not respond to an additional 2 weeks of the maximum dose of mesalamine.
In the double-blind study, patients were randomly assigned to groups given curcumin capsules (3 g/day) or an identical placebo for 1 month, with continued mesalamine. The primary outcome was the rate of clinical remission (Simple Clinical Colitis Activity Index score 2 or less) at week 4.
Remarkably, 54% of those receiving curcumin achieved clinical remission at week 4 compared with none of the patients receiving placebo. A clinical response (reduction of 3 or more points in Simple Clinical Colitis Activity Index score) was observed in 65% of subjects receiving curcumin compared with only 13% in the placebo group. Endoscopic remission (partial Mayo score of ≤1) was observed in 38% in the curcumin group compared with none of those receiving placebo. Adverse events were rare in both groups.
The authors explained that they tested curcumin as an add-on therapy to mesalamine treatment to adhere to guidelines, which recommend it for first-line therapy. Furthermore, curcumin and mesalamine seem to have different but potentially synergistic mechanisms, which could increase efficacy beyond that of either agent alone.
In an editorial that accompanies the article, Charles N. Bernstein explains that when the limited options for treating mild-to-moderate UC with mesalamine fail, the next step is immunomodulating therapies (with thiopurine, anti-tumor necrosis factor agents, or a combination of both, or vedolizumb). All of these approaches require a step up—emotionally, financially, and in monitoring, and therefore require substantial commitment. For patients with mild-to-moderate UC that is resistant to oral and rectal mesalamine, a safe, oral, inexpensive alternative therapy that requires little monitoring would be a significant advance.
Patients with inflammatory bowel diseases frequently report using cannabis, herbal therapies, and other supplements to relieve symptoms—gastroenterologists have been waiting for evidence for or against any of these approaches.
Bernstein points out that the study participants appeared to have very mild UC, and that the low rate or response among patients in the placebo group raises questions about how blinded the participants were. Another limitation was that endoscopy results were available from only 38 of the 50 patients (22 in the curcumin group and 16 in the placebo group).
What makes curcumin (diferuloymethane) a treatment for inflammatory disorders? It has been shown to inhibit NF-κB, STAT3, p38 mitogen-activated protein kinase, and cytokines produced by T-helper 1 cells. It also has anti-oxidative properties in human lymphocytes and gut epithelial cell lines.
Bernstein states that Lang et al have provided evidence for a well-tolerated, inexpensive, oral therapy for mild to moderate UC that is resistant to mesalamine that has at least some track record of study in UC. Phase 2 and 3 studies are needed, although a comparable placebo must be developed to ensure that participants and providers can truly remain blinded throughout the study.