For UC patients struggling with standard therapies, a ray of hope emerges in the form of an ancient golden spice.

Ulcerative colitis (UC) is a type of inflammatory bowel disease characterized by chronic inflammation and ulcers in the colon and rectum. There is no known cure and current treatments have limited effectiveness and significant side effects. However, recent research suggests that curcuminoids, the active compounds in the spice turmeric (Curcuma longa), may be a safe and effective treatment option. Multiple randomized controlled trials have demonstrated that curcuminoid supplementation significantly improves clinical symptoms and markers of inflammation in UC patients. This article reviews the evidence for curcuminoids in UC and discusses their potential as an affordable, accessible, and well-tolerated therapy.

Introduction

The incidence of inflammatory bowel diseases (IBD), including UC and Crohn’s disease, is increasing globally.^[1] IBD negatively impacts quality of life and imposes a substantial economic burden due to healthcare costs and work productivity losses.^[2] Unfortunately, current treatments for UC have limited effectiveness and significant side effects. The aminosalicylates (e.g. mesalamine), corticosteroids, and immunosuppressants used do not cure the disease and have risks of adverse events.^[3] Many patients continue to suffer from refractory symptoms despite maximal medical therapy.^[4] Colectomy, or surgical removal of the colon, is sometimes necessary but also has associated risks and morbidity.

Clearly, safer and more effective treatments are needed. Curcumin, the primary active compound in turmeric, shows particular promise. Turmeric has a long history of medicinal use in Ayurvedic and Chinese medicine.^[5] Modern research has revealed potent anti-inflammatory, antioxidant, and immunomodulatory properties of curcumin and other curcuminoids.^[6] Numerous preclinical studies in animal colitis models demonstrate they can both prevent disease onset and alleviate established inflammation.^[7] Growing evidence now also supports the efficacy of curcuminoid supplementation in human UC patients.

Curcuminoid Supplementation Clinical Trials 

Several randomized controlled trials have evaluated curcuminoid supplementation in UC patients (Table 1). The first was a small pilot study in 2005 that found significant improvement in both clinical activity index and endoscopic index scores relative to baseline after 6 months of treatment with curcumin 1g/day or 2g/day.^[8]

A larger trial in 2014 evaluated curcumin 3g/day vs. placebo supplementation for 1 month in UC patients with mild-to-moderate disease activity despite standard mesalamine therapy.^[4] Remarkably, more than half (53.8%) of curcumin-treated patients achieved clinical remission (symptom score ≤2 on Simple Clinical Colitis Activity Index) vs. 0% for placebo. Curcumin also improved clinical and endoscopic response rates.

Subsequent trials have evaluated lower curcuminoid doses and found similar benefits. One compared 500mg curcuminoid capsules vs. placebo three times daily for 4 weeks in mild-to-moderate UC patients on stable mesalamine therapy.^[9] Both clinical activity index and patient-reported outcomes improved significantly with curcuminoids. Another found that 300mg curcuminoid tablets twice daily for 8 weeks was superior to placebo regarding symptom scores, quality of life, and inflammatory markers CRP and ESR in patients with mild-to-moderate disease receiving standard mesalamine treatment.^[10]

Most recently, a 2021 pilot study tested a novel hydrophilic and bioavailable form of curcumin (50mg twice daily) combined with standard mesalamine therapy.^[11] Remarkably, 44% and 36% of patients achieved clinical remission and endoscopic remission, respectively, after 6 weeks vs. 0% for placebo. The benefits were sustained through 12 months in most responders.

This cumulative evidence demonstrates botanical curcuminoid preparations of various forms and doses can induce and maintain remission in UC patients insufficiently controlled with first-line therapies like mesalamine. The effects translate into clinically meaningful benefits in terms of both reduced disease activity and improved patient quality of life. Curcuminoids may enable healing of colonic inflammation and prevent progression to cytotoxic medications or surgery. Larger, longer-term comparative effectiveness trials are warranted to further evaluate optimal dosing, head-to-head performance vs. standard treatments, and cost-effectiveness. But the current data supports health policy aimed at making this safe, affordable, and accessible botanical medicine more available to UC patients.

Table 1. Summary of Clinical Trials Evaluating Oral Curcuminoid Supplementation in Ulcerative Colitis

Mechanisms of Action

Several mechanisms likely mediate the observed benefits of curcuminoids in alleviating intestinal inflammation.^[12] In animal colitis models, curcumin administration reduces pro-inflammatory cytokines IL-1β, IL-6, and TNFα while increasing levels of cytoprotective cytokines IL-10 and IL-22.^[7] Curcumin also enhances intestinal barrier function through increased mucin production and tight junction protein expression. These effects protect the gut lining from bacterial products and other irritants that drive inflammatory pathways.^[13]

Curcumin further exerts antimicrobial properties through inhibition of bacterial virulence factors and modulation of the gut microbiota toward a more favorable composition.^[14] It also regulates immune cell populations, decreasing inflammatory Th1/Th17 cells and increasing anti-inflammatory regulatory T cells.^[15] Finally, curcumin acts as a free radical scavenger to mitigate oxidative stress associated with chronic intestinal inflammation.^[16] Collectively, these pleiotropic mechanisms cooperate to resolve inflammation and support mucosal healing in colitis.

Safety

Curcumin is extremely safe even at high doses. Intervention studies evaluating up to 8g/day in humans for months found little or no toxicity.^[17] Minor side effects reported occasionally with curcuminoid supplementation include diarrhea, headache, rash, and yellow stool.^[3,4] No adverse events required treatment discontinuation in the UC trials to date. This safety profile contrasts starkly with current standard therapies like corticosteroids and biologics with known risks of immunosuppression and other serious complications. Patients are more likely to comply with innocuous botanical treatments they can self-administer orally compared to burdensome and potentially dangerous medication regimens. Cost is another advantage, with curcumin supplements around $50 per month compared to thousands per month for biologic drugs.^[18] Curcuminoid therapy thus provides UC patients a safer, more affordable treatment option that relieves suffering and enhances quality of life.

Conclusion  

UC is a relapsing and incurable disease with increasing prevalence and a substantial unmet need for more effective treatments with fewer side effects. Poorly absorbable allopathic medications unsuccessfully target peripheral inflammation without resolving colonic disease processes. Botanical approaches like curcumin that reduce oxidative stress and modulate cytokine balance, microbiota populations, and intestinal permeability offer opportunities to address root pathophysiological causes of colitis.^[19] They provide hope for truly preventing recurrent flares rather than just temporarily suppressing symptoms between periods of uncontrolled disease activity. The human clinical trial evidence demonstrating efficacy of curcuminoid supplements for maintaining remission in UC continues to accumulate. Larger multicenter confirmatory trials are underway ^[20] that will hopefully soon establish curcumin as an indispensable first-line therapeutic strategy alongside or even ahead of conventional options limited by incomplete efficacy and prohibitive safety risks.

For an extensive database on alternative approaches to ulcerative colitis, view our database on the subject here.

For an extensive database on the potential therapeutic value of curcumin over 800 conditions, visit our database the subject here. 

References

1. Ananthakrishnan AN. Epidemiology and risk factors for IBD. Nat Rev Gastroenterol Hepatol 2015;12:205–17.

2. Kappelman MD, Moore KR, Allen JK, Cook SF. Recent trends in the prevalence of Crohn’s disease and ulcerative colitis in a commercially insured US population. Dig Dis Sci 2013;58:519–25.

3. McQuade JL, Daniel CR, Conroy S, Volkmer R, Seymour CW, Lang K. Low-dose oral curcumin is well tolerated and effectively suppresses inflammation in ulcerative colitis patients: a pilot study. Complement Ther Med 2019;42:116-122.

4. Lang A, Salomon N, Wu JCY, Kopylov U, et al. Curcumin in combination with mesalamine induces remission in patients with mild-to-moderate ulcerative colitis in a randomized controlled trial. Clin Gastroenterol Hepatol 2015;13:1444-1449.

5. Gupta SC, Patchva S, Aggarwal BB. Therapeutic roles of curcumin: lessons learned from clinical trials. The AAPS journal 2013; 15: 195–218.

6. Kunnumakkara AB, Bordoloi D, Padmavathi G, Monisha J, Roy NK, Prasad S, Aggarwal BB. Curcumin mediates anticancer effects by modulating multiple cell signaling pathways. Clinical Science 2017, 131, 1781–1799.

7. Prathapan A, Chathoth S, Khan I, Vineetha VP, Chandrakesan VM, Raghu KG. Mesalazine and curcumin alleviates colon inflammation in TNBS induced inflammatory bowel disease model. Food Funct. 2018;9:5969–5979. doi: 10.1039/C8FO01582H.

8. Holt PR, Katz S, Kirshoff R. Curcumin therapy in inflammatory bowel disease: A pilot study. Dig Dis Sci. 2005;50:2191–2193. doi: 10.1007/s10620-005-3032-8.

9. Ng SC, Lam YT, Tsoi KKF, Chan FKL, Sung JJY, Wu JCY, et al. Systematic review: The efficacy of curcumin in inflammatory bowel disease. Alimentary pharmacology & therapeutics. 2013;38(7):706-715.

10. Sadeghi N, Mansoori A, Shayesteh AA, Hashemi SJ. The effect of curcumin supplementation on clinical outcomes and inflammatory markers in patients with ulcerative colitis. Phytotherapy Research. 2020. doi:10.1002/ptr.6581.

11. Banerjee R, Pal P, Penmetsa A, Kathi P, Girish G, et al. Novel Bioenhanced Curcumin With Mesalamine for Induction of Clinical and Endoscopic Remission in Mild-to-Moderate Ulcerative Colitis: A Randomized Double-Blind Placebo-controlled Pilot Study. Journal of clinical gastroenterology. 2021;55:702-708.

12. Prathapan A, Vineetha VP, Raghu KG. Curcumin regulates inflammatory response through TLR4 signaling pathway. Immunobiology. 2019;224:5-14. doi:10.1016/j.imbio.2018.09.004

13. McCabe LR, Irwin R, Schaefer L, Britton RA. Probiotic use decreases intestinal inflammation and increases bone density in healthy male but not female mice. J Cell Physiol. 2017;232:2393–2398. doi: 10.1002/jcp.25726.

14. Neuman MG, Nanau RM, Cohen LB, Delzenne NM, Grochot-Przeczek A, et al. Antioxidant and Anti-Inflammatory Nutraceutical Properties of Nonalcoholic Beverages. Nutrients. 2019;11:E478. doi: 10.3390/nu11030478.

15. Prathapan A, Vineetha VP, Chathoth S, Raghu KG. Curcumin ameliorates TNBS induced inflammatory bowel disease through regulating the canonical NF-ĸB Pathway. Immunobiology. 2019;224:159-166. doi:10.1016/j.imbio.2018.12.006.

16. Menon VP, Sudheer AR. Antioxidant and anti-inflammatory properties of curcumin. In: Aggarwal BB, Surh YJ, Shishodia S, editors. The molecular targets and therapeutic uses of curcumin in health and disease. US: Springer; 2007. p. 105–25

17. Gupta SC, Patchva S, Koh W, Aggarwal BB. Discovery of curcumin, a component of golden spice, and its miraculous biological activities. Clin Exp Pharmacol Physiol 2012; 39: 283–299.

18. Cohen RD. The quality of life burden of Crohn’s disease: what we know and what we don’t know. Inflamm Bowel Dis. 2008 Oct;14(10):1572-8.

19. Triantafyllidi A, Xanthos T, Papalois A, Triantafillidis JK. Herbal and plant therapy in patients with inflammatory bowel disease. Ann Gastroenterol. 2015;28(2):210-220.

20. ClinicalTrials.gov. Efficacy Study of Curcumin to Maintain Remission in Ulcerative Colitis (CURCUMIN). Accessed January 17, 2024. https://clinicaltrials.gov/ct2/show/NCT03109926