Introduction

Gastrointestinal (GI) diseases are substantial clinical and economic burdens accounting for extensive morbidity and mortality among humans worldwide. The incidence of many GI conditions, such as inflammatory bowel disease (IBD) and gastrointestinal infections, has increased dramatically in western countries over the past few decades. Solely in the USA, of the 122 million emergency department visits in 2007, 15 million (12%)  were diagnosed with GI diseases.¹ This influx of GI patients has led to the total spending on GI diseases estimated at $142 billion per year with $27.9 billion spent on emergency department billings.² Apart from being a substantial economic burden, GI diseases also worsen the quality of life and significantly impair work and daily activity of the patients. It is now increasingly recognized that certain modifications in diet and lifestyle that occurred in the last few decades synchronize with an amplified rise in GI diseases. Therefore, change in dietary habits and incorporation of micro nutrients, such as antioxidants may be beneficial in prevention and/or treatment of GI disorders.

One of such antioxidant molecules is curcumin, the major constituent of turmeric that has been consumed as a part of the human diet for centuries. It has long been viewed as a key therapeutic bio molecule with armamentarium of health benefits. It is the center of modern clinical curiosity since its isolation in the early 19^th century followed by crystalline purification in the 1870 s, and structural elucidation in early 20^th century. Its wide spectrum of therapeutic potential has sparked interest in its clinical application for several GI disorders. This interest is also backed by the fact that curcumin preferentially accumulates in the intestine, colon and liver leading to its higher bio availability in the gastrointestinal than other organs.³ In two clinical studies of curcumin, IBD patients have achieved encouraging results showing potent medicinal undertakings.^4,5 However, the further rigorous randomized controlled trials in larger samples of IBD patients needed to validate the results of these clinical studies have not been undertaken yet. Likewise, curcumin extended significant therapeutic effects in irritable bowel syndrome and exhibited potential to increase bowel motility and to activate hydrogen-producing bacterial flora in the colon.^6,7 In colorectal cancer (CRC) trials, curcumin was well tolerated and no dose-limiting toxicity was detected. Interestingly, curcumin intake attenuated the amplified levels of prostaglandin E2, M₁G and a daily dose of 3.60 g of curcumin was found to be pharmacologically effective in CRC patients.^8,9 Likewise, observations were made in the familial adenomatous polyposis (FAP) patients, where curcumin suppressed adenomas.¹⁰

Furthermore, clinical trials have also confirmed the therapeutic efficacy of curcumin in peptic ulcers and Helicobacter pylori infection .¹¹ Although several clinical trials have been concluded, various trials are still evaluating the efficacy of curcumin against GI ailments. A search on www.clinicaltrials.gov (accessed in November 2014) indicated that about 25 clinical trials with curcumin are ongoing in GI disorders. These include trials evaluating efficacy of curcumin in FAP, CRC, IBD and ulcerative colitis.

Since, the study published by Schraufstätter and Bernt, 1949¹² in Nature publication showing the therapeutic effect of curcumin, copious amount of research have strengthened the curcumin’s candidacy as a silver bullet medication but its low bio availability has plagued its clinical use. However, strategies such as structural modification, micro encapsulation and nano particles have been undertaken to improve the bio availability of curcumin. A few clinical trials have been also conducted to access the improved bio availability of modified curcumin or its combination with other bio actives. A clinical trial addressing the effect of curcumin and piperine oral administration in human patients with tropical pancreatitis resulted in reduced oxidative stress markers along with surge in glutathione levels.¹³ Recently, two clinical trials (NCT01982734, NCT01925287) reported that incorporation of curcumin into micelles improved the bio availability of curcumin. It is essential to understand that these strategies to increase bio availability of curcumin should be followed by its effectiveness in GI diseases as well. Furthermore, the improved curcumin formulations should be assessed for toxicity profiles. Even though multiple clinical studies have not reported toxicity by curcumin even at doses up to 8.00 g per day; but the encapsulated/modified curcumin must be assessed for its physiological safety. Comparative studies are also required to investigate parent molecule and encapsulated/formulated curcumin to ultimately advance to large clinical trials focused on GI disorders. This will also unveil important insights into metabolomics and pharmacokinetics of the novel formulations or modifications of curcumin. These are the imperative steps which must be undertaken before curcumin or its modified/formulated version can be translated to the clinics for the treatment of various GI disorders.

List of abbreviations

CRC- colorectal cancer; FAP- familial adenomatous polyposis; GI- Gastrointestinal; IBD- inflammatory bowel disease

References

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