Bowel (Colorectal) Wellbeing

Curcumin

Curcumin, an extract from the Indian spice turmeric, is proven to travel to the colonic mucosa, one of the layers in the lining of the bowel [1]. Curcumin has been shown to be anti-inflammatory [2], helping to reduce tumour formation where the colon is inflamed [3]. It has reduced pre-cancerous tumours in patients with familial adenomatous polyposis (FAP), where polyps decreased by around 60% in number and 50% in size after treatment with curcumin [4].
The way curcumin works has been well studied [5]. Despite interfering with the development of cancer, curcumin has been found to be relatively safe at very high doses [6]. In colorectal cancer, curcumin may enhance sensitivity to 5-FU chemotherapy [7] and slow down cell invasion [8]. An ongoing clinical trial of curcumin and FOLFOX chemotherapy called CUFOX will determine the success of adding curcumin to advanced colorectal cancer treatment [9].
Large doses of curcumin may therefore have a positive effect in cancer prevention and perhaps treatment.

References

1. Irving GRB, Howells LM, Sale S et al. Prolonged biologically active colonic tissue levels of curcumin achieved after oral administration – a clinical pilot study including assessment of patient acceptability. Cancer Prev Res (Phila). 2013;6(2):119–128.
2. Su CC, Chen GW, Lin JG, et al. Curcumin inhibits cell migration of human colon cancer colo 205 cells through the inhibition of nuclear factor kappa B /p65 and down-regulates cyclooxygenase-2 and matrix metalloproteinase-2 expressions. Anticancer Res 2006;26:1281-8.
3. Murakami A, Furukawa I, Miyamoto S et al. Curcumin combined with turmerones, essential oil components of turmeric, abolishes inflammation-associated mouse colon carcinogenesis. Biofactors 2013;39(2):221-32.
4. Cruz-Correa M, Shoskes DA, Sanchez P, et al. Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis. Clin Gastroenterol Hepatol 2006;4:1035-8.
5. Aggarwal BB, Sundaram C, Malani N, et al. Curcumin: the Indian solid gold. Adv Exp Med Biol. 2007;595:1–75.
6. Lao CD, Ruffin MTt, Normolle D et al. Dose escalation of a curcuminoid formulation. BMC Complement Altern Med. 2006;6:10.
7. Shakibaei M, Buhrmann C, Kraehe P et al. Curcumin Chemosensitizes 5-Fluorouracil Resistant MMR-Deficient Human Colon Cancer Cells in High Density Cultures. PLoS One. 2014;3:9(1):e85397.
8. Chen A, Xu J, Johnson AC. Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1. Oncogene 2006;25:278-87.
9. Irving GR, Steward WP. A Phase I/IIa Study Combining Curcumin (Curcumin C3-Complex, Sabinsa) With Standard Care FOLFOX Chemotherapy in Patients With Inoperable Colorectal Ca

Curcumin and other gastrointestinal conditions

Curcumin’s therapeutic benefits have been effective in a variety of gastrointestinal conditions, as it has antioxidant activity [1-3] and is able to reduce inflammation [4].

Irritable Bowel Syndrome

Patients with irritable bowel syndrome (IBS) commonly report symptoms involving abdominal pain, bloating and altered bowel habits [5]. It is thought that low-grade inflammation of the intestinal lining is responsible for some symptoms that patients experience [6].
In an eight-week study of IBS patients, turmeric extract was given to 207 people. After four weeks, members of the group reported up to a 60% reduction in IBS prevalence. In post-study analysis, abdominal pain and discomfort reduced by up to 25% [7].
Two other studies found that levels of a form of the neurotransmitter serotonin are different in IBS [8,9]. When curcumin was added to the diets of rats with IBS, the amount of serotonin in the body changed, with the curcumin acting on the bowel through neurotransmitters to reduce the daily number of stools [10].

Inflammatory Bowel Disease (IBD)

Curcumin has also been studied in relation to the inflammatory bowel diseases Ulcerative Colitis (UC) and Crohn’s Disease (CD).
Patients in one trial were tested for tolerance, with doses being increased over several weeks. All patients tolerated curcumin well, apart from two who complained of gassiness [11]. Researchers then conducted a small study of five patients with Ulcerative Colitis and five with Crohn’s Disease A significant reduction in symptoms was reported after taking increasing doses of curcumin over several months [12]. In an individual case study of a 60-year-old woman suffering from UC, curcumin was trialled after all other therapies were ineffective. After a year of treatment she had no ulcerations and the UC was inactive [13]. Another study concluded that curcumin, when combined with standard drug therapy, led to a reduced risk of relapse in UC patients [14].
Pure curcumin preparation has been used in a pilot study of five patients with ulcerative proctitis and five with Crohn’s Disease. All proctitis patients improved and four were able to reduce their medication [15]. Four of the five CD patients had lowered disease activity scores [15].
Results of a study published in 2010 revealed that curcumin appeared to have suppressed unwanted immune responses and enhanced more beneficial responses in IBD patients [16].
The most exciting research was published in 2015. It showed that the addition of 3g curcumin to mesalamine therapy was more effective than the mesalamine combined with a placebo in bringing about remission in UC patients [17]. The study also concluded there were no apparent adverse effects [17].

References

1. Sharma OP. Antioxidant activity of curcumin and related compounds. Biochem Pharmacol 1976;25(15):1811–1812.
2. Ruby AJ, Kuttan G, Babu, KD et al. Anti-tumour and antioxidant activity of natural curcuminoids. Cancer Lett 1995;94(1):79–83.
3. Sugiyama Y, Kawakishi S, Osawa T. Involvement of the-diketone moiety in the antioxidative mechanism of tetrahydrocurcumin. Biochem Pharmacol 1996;52(4):519–25.
4. Srimal RC, Dhawan BN. Pharmacology of diferuloyl methane (curcumin), a non-steroidal anti-inflammatory agent. J Pharm Pharmacol 1973;25(6):447–52.
5. Camilleri M. Dyspepsia, irritable bowel syndrome, and constipation: review and what’s new. Rev Gastroenterol Disord 2001;1:2-17.
6. Barbara G, De Giorgio R, Stanghellini V, et al. A role for inflammation in irritable bowel syndrome? Gut 2002;51:i41-i44.
7. Bundy R, Walker AF, Middleton RW et al. Turmeric extract may improve irritable bowel syndrome symptomology in otherwise healthy adults: a pilot study. J Altern Complement Med 2004;10:1015-1018.
8. Dunlop SP, Coleman NS, Blackshaw E et al. Abnormalities of 5-hydroxytryptamine metabolism in irritable bowel syndrome. Clin Gastroenterol Hepatol 2005; 3: 349–357
9. Wheatcroft J, Wakelin D, Smith A et al. Enterochromaffin cell hyperplasia and decreased serotonin transporter in a mouse model of post-infectious bowel dysfunction. Neurogastroenterol Motil 2005; 17 863–870.
10. Yu Y, Wu S, Li J et al. The effect of curcumin on the brain-gut axis in rat model of irritable bowel syndrome: involvement of 5-HT-dependent signalling. Metab Brain Dis; 2014; DOI 10.1007/s11011-014-9554-z
11. Suskind, DL, Wahbeh, G, Burpee, T et al. Tolerability of curcumin in pediatric inflammatory bowel disease: A forced-dose titration study. J. Pediatr. Gastroneterol. Nutr. 2013, 56, 277–279. 162. Lahiff, C.; Moss, A.C.M. Curcumin for clinical and endoscopic remission in ulcerative colitis. Inflamm. Bowel Dis. 2011, 17, E66.
12. Suskind, DL, Wahbeh, G, Burpee, T et al. Tolerability of curcumin in pediatric inflammatory bowel disease: A forced-dose titration study. J. Pediatr. Gastroneterol. Nutr. 2013, 56, 277–279.
13. Lahiff C, Moss AC. Curcumin for clinical and endoscopic remission in ulcerative colitis. Inflamm Bowel Dis. 2011;17(7): E66.25.
14. Hanai, H, Iida, T, Takeuchi, K et al. Curcumin maintenance therapy for ulcertive colitis: Randomized, multicenter, double-blind, placebo-controlled trial. Clin. Gastroenterol. Hepatol. 2006, 4, 1502–1506.
15. Holt PR, Katz S, Kirshoff R. Curcumin therapy in inflammatory bowel disease: a pilot study. Dig Dis Sci. 2005 Nov;50(11):2191-3.
16. Epstein J, Docena G, MacDonald TT et al. Curcumin suppresses p38 mitogen-activated protein kinase activation, reduces IL-1beta and matrix metalloproteinase-3 and enhances IL-10 in the mucosa of children and adults with inflammatory bowel disease. Br J Nutr. 2010;103(6):824–32.
17. Lang A, Salomon N, Wu JC 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;24 pii: S1542-3565(15)00158-5.

Green Tea

Green tea polyphenols mainly consist of epigallocatechin-3-gallate (EGCG) which provides up to 40% of the most purified green tea extracts. Polyphenols such as EGCG are metabolised by the bacteria in the gut, which break them down into health-promoting phenolic acids. These are then absorbed into the blood and excreted in the urine [1].
The anti-cancer benefits of EGCG have not only been shown in the laboratory [2-5], but in human studies. Consumption of green tea was associated with a 40% reduction in colorectal cancer risk in a cohort of 69,710 Chinese women [6]. In 60,567 non-smoking Chinese men, an intake of at least three cups of green tea a week reduced risk, and each 2g increment of dry green tea leaves per day (roughly the amount of tea in a tea bag) was linked to a 12% reduction in the risk of colorectal cancer [7]. EGCG is thought to exert its cancer-preventive activity in the bowel by interrupting signalling pathways [8].
While large doses of green tea or its extract may have a positive effect in the general population, it is not advised during chemotherapies.

References

1. Henning SM, Wang P, Abgaryan N et al. Phenolic acid concentrations in plasma and urine from men consuming green or black tea and potential chemopreventive properties for colon cancer. Mol Nutr Food Res. 2013;57(3):483-93.
2. Scalbert A, Manach C, Morand C, et al. Dietary polyphenols and the prevention of diseases. Crit Rev Food Sci Nutr 2005;45:287-306.
3. Yang CS. Inhibition of carcinogenesis by tea. Nature 1997;389:134-5.
4. Yang CS, Chung JY, Yang GY, et al. Mechanisms of inhibition of carcinogenesis by tea. Biofactors 2000;13:73-9.
5. Sánchez-Tena S, Alcarraz-Vizán G, Marín S et al. Epicatechin gallate impairs colon cancer cell metabolic productivity. J Agric Food Chem. 2013 May 8;61(18):4310-7.
6. Yang G, Shu XO, Li H, et al. Prospective cohort study of green tea consumption and colorectal cancer risk in women. Cancer Epidemiol Biomarkers Prev 2007;16:1219-23.
7. Yang G, Zheng W, Xiang YB et al. Green tea consumption and colorectal cancer risk: a report from the Shanghai Men’s Health Study. Carcinogenesis. 2011;32(11):1684-8.
8. Oh S, Gwak J, Park S et al. Green tea polyphenol EGCG suppresses Wnt/β-catenin signaling by promoting GSK-3β- and PP2A-independent β-catenin phosphorylation/degradation. Biofactors. 2014 Nov-Dec;40(6):586-95.

Green Tea in other Gastrointestinal Conditions

Inflammatory Bowel Disease (IBD)

Due to the anti-inflammatory effects of EGCG in green tea extracts and success in IBD animal trials, a team of researchers tested the concept in humans. The pilot trial showed that patients with mild to moderate ulcerative colitis could reach remission by taking 400 mg or 800 mg of EGCG daily for 56 days [1]. Nineteen patients received more than one dose of EGCG and 53.3% of patients gained remission status, compared to 0% in the placebo group, which didn’t consume any [1].

Reference

1. Dryden GW, Lam A, Beatty K et al. A pilot study to evaluate the safety and efficacy of an oral dose of (-)-epigallocatechin-3-gallate-rich polyphenon E in patients with mild to moderate ulcerative colitis. Inflamm Bowel Dis. 2013;19(9):1904-12.

Vitamin D

Vitamin D can be made by the body if exposed to sunlight, but other good sources are supplements and some foods. In 1980, a paper proposed that lower levels of vitamin D could account for the increase in deaths from colon cancer in higher latitudes [1]. Studies of populations in the northern hemisphere since have showed that deaths from colorectal cancer were higher in areas with less sunlight [2].
Evidence suggests that vitamin D impacts on colorectal tissue. Both normal and cancerous colon linings express an enzyme that converts inactive vitamin D to the active vitamin D hormone [3,4]. A higher concentration of vitamin D is linked to lower rates of colorectal cell growth and division, which in turn decreases the risk of cancer [5]. The lower the vitamin D blood concentration, the higher the colorectal cancer risk [6-9].

References

1. Yang G, Zheng W, Xiang Y-B et al. Green tea consumption and colorectal cancer risk: a report from the Shanghai Men’s Health Study. Carcinogenesis 2011; 32(11): 1684–1688.
2. Garland CF, Garland FC. Do sunlight and vitamin D reduce the likelihood of colon cancer? Int J Epidemiol 1980;9:227-31.
3. Tangpricha V, Flanagan JN, Whitlatch LW et al. 25-hydroxyvitamin D-1alpha-hydroxylase in normal and malignant colon tissue. Lancet 2001; 357: 1673-4.
4. Zehnder D, Bland R, Williams MC et al. Extrarenal expression of 25-hydroxyvitamin d(3)-1 alpha-hydroxylase. J Clin Endocrinol Metab 2001; 86: 888–894.
5. Palmer HG, Gonzalez-Sancho JM et al. Vitamin D(3) promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of beta-catenin signaling. J Cell Biol 2001; 154: 369–387.
6. Holt PR, Arber N, Halmos B et al. Colonic epithelial cell proliferation decreases with increasing levels of serum 25-hydroxy vitamin D. Cancer Epidemiol Biomarkers Prev 2002; 11: 113–119.
7. Ma Y, Zhang P, Wang F et al. Association between vitamin D and risk of colorectal cancer: a systematic review of prospective studies. J Clin Oncol 2011; 29: 3775–3782.
8. Gandini S, Boniol M, Haukka J et al. Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. Int J Cancer 2011; 128: 1414–1424.
9. Touvier M, Chan DS, Lau R, et al. Meta-analyses of vitamin D intake, 25-hydroxyvitamin D status, vitamin D receptor polymorphisms, and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 2011; 20: 1003–1016

Vitamin D in other Gastrointestinal Conditions

Inflammatory Bowel Disease (IBD)

There is much evidence to show that patients with inflammatory bowel disease (IBD) benefit from vitamin D3 supplements. Up to 72% of Crohn’s Disease (CD) sufferers worldwide have been found to have insufficient vitamin D, and up to 64% of people with ulcerative colitis (UC) [1]. Vitamin D levels change according to the seasons [2-6] and clinical deficiency was seen in up to 76% of patients in winter and up to 19% in the summer months. Vitamin insufficiency, where reported, was up to 100% in winter and 59% in the summer [5-6]. In a recent new study, researchers found a link between vitamin D deficiency/insufficiency and disease activity in IBD patients [7].
A number of studies have therefore aimed to improve vitamin D levels as a means of IBD therapy.
One group of researchers found disease activity decreased in 78% of patients on a 24-week vitamin D3 supplementation programme. Sixty-seven per cent of patients were in remission and their quality of life had significantly improved [8].
Another study compared the effects of vitamin D3 supplementation vs vitamin D2 in CD patients. After six weeks the D3 group was experiencing more positive effects, but by week 52 there was no difference between the groups. [9].
Elsewhere, ninety-four CD patients in remission received either vitamin D3 with 1200 mg of calcium or 1200 mg of calcium alone. During a one-year follow-up, serum 25(OH)D3 levels increased significantly in vitamin D-supplemented patients, but free serum calcium did not change. The relapse rate was not significantly lowered [10].
In an uncontrolled clinical trial, 18 active CD patients were treated with vitamin D3 daily over two weeks, after which the dose was steadily increased until a serum concentration of 40 ng/mL of 25(OH)D3 was reached [11]. After 24 weeks, a significant reduction of the CDAI and an improvement of the IBDQ score were observed [11].
A recent clinical trial involved 141 CD patients and 79 UC patients. Twenty six of these took vitamin D3 supplements for over three months. In all patients, health-related quality of life was measured along with serum vitamin D levels at the outset and approximately six months later. Results showed that a higher concentration of vitamin D in the blood related to a higher health-related quality of life, but was reliant on the season and amount of sun exposure. 800IU of vitamin D per day for up to six months was not enough to raise serum levels and it did not affect quality of life [12].

References

1. Ardesia M, Ferlazzo G, Fries W. Vitamin D and Inflammatory Bowel Disease. BioMed Research International. 2015;2015:470805.
2. McCarthy D, Duggan P, O’Brien M, et al. Seasonality of vitamin D status and bone turnover in patients with Crohn’s disease. Alimentary Pharmacology & Therapeutics. 2005;21(9):1073–1083.
3. Alkhouri R H, Hashmi H, Baker RD et al. Vitamin and mineral status in patients with inflammatory bowel disease. Journal of Pediatric Gastroenterology and Nutrition. 2013;56(1):89–92.
4. Gilman J, Shanahan F, Cashman KD. Determinants of vitamin D status in adult Crohn’s disease patients, with particular emphasis on supplemental vitamin D use. European Journal of Clinical Nutrition. 2006;60(7):889–896.
5. Kini GP, Young B, Herbison P et al. Does seasonal level of serum 25-OH vitamin D correlate with the activity of Crohn’s disease? New Zealand Medical Journal. 2014;127(1394):51–59.
6. Hlavaty T, Krajcovicova A, Koller T, et al. Higher vitamin D serum concentration increases health related quality of life in patients with inflammatory bowel diseases. World Journal of Gastroenterology. 2014;20(42):15787–15796.
7. Torki M, Gholamrezaei A, Mirbagher L et al. Vitamin D Deficiency Associated with Disease Activity in Patients with Inflammatory Bowel Diseases. Dig Dis Sci. 2015 Jun 2. [Epub ahead of print].
8. Yang L, Weaver V, Smith JP et al. Therapeutic effect of vitamin d supplementation in a pilot study of Crohn’s patients. Clin Transl Gastroenterol 2013; 4: e33 [PMID: 23594800 DOI: 10.1038/ctg.2013.1]
9. Miheller P, Muzes G, Hritz I, et al. Comparison of the effects of 1,25 dihydroxyvitamin D and 25 hydroxyvitamin D on bone pathology and disease activity in Crohn’s disease patients. Inflammatory Bowel Diseases. 2009;15(11):1656–1662.
10. Jørgensen SP, Agnholt J, Glerup H, et al. Clinical trial: vitamin D3 treatment in Crohn’s disease—a randomized double-blind placebo-controlled study. Alimentary Pharmacology and Therapeutics. 2010;32(3):377–383.
11. Yang L, Weaver V, Smith J. P et al. Therapeutic effect of vitamin D supplementation in a pilot study of Crohn’s patients. Clinical and Translational Gastroenterology. 2013;4, article e33.
12. Hlavaty T, Krajcovicova A, Koller T et al. Higher vitamin D serum concentration increases health related quality of life in patients with inflammatory bowel diseases. World J Gastroenterol. 2014;20(42):15787-96.

For extended reading, you can download examinations of the relationship between diet, food supplements and health conditions here