IBS and IBD
Increasingly vitamin D has evidence for benefit in such inflammatory gut disorders. In a recent study sixty patients with IBS and 100 healthy individuals had their vitamin D blood level assessed. There was a statistically significant difference in the mean vitamin D level between healthy and IBS patients, with vitamin D deficiency detected in 49 patients (82%) in the IBS group and 31 patients (31%) in the control group. A subsequent study found that there was a significant association between circulating vitamin D level and quality of life (“How much has IBS affected your life?”) when people were enrolled onto the study. Supplementation of vitamin D3 had a beneficial effect.
Another recent study of 90 IBS patients participated in a double-blind, randomised, placebo-controlled study where participants were randomised to receive either 50,000 IU vitamin D3 or a placebo fortnightly for a period of 6 months. Over the 6-month intervention period, a significantly greater improvement in IBS symptoms such as abdominal pain and distention, flatulence, rumbling, and overall gastrointestinal (GI) symptoms (except dissatisfaction with bowel habits) was observed in the patients receiving vitamin D as compared to the placebo group. The IBS-QoL scores in the vitamin D group significantly improved compared to the placebo group afterwards, and average IBS-QoL score change was significantly improved.
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). Vitamin D levels change according to the seasons[5-9] 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.[8,9] In a recent study, researchers found a link between vitamin D deficiency/insufficiency and disease activity in IBD patients.
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.
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.
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.
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. After 24 weeks, a significant reduction of the CDAI and an improvement of the IBDQ score were observed.
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.
Turmeric is a plant, traditionally cultivated in Asia for its use as a spice in curry. It is the root of the turmeric plant that provides the dietary compound, curcumin (diferuloylmethane). It is a polyphenol which has anti-inflammatory properties and therapeutic benefit have been well publicized for decades.
An 8 week study of IBS patients using a dose of 72 mg turmeric extract was given to 102 subjects and a double dose of 144 mg was given to 105 subjects. After 4 weeks, those in the 72-mg group reported a 53% reduction in IBS prevalence, and the 144-mg group experienced a 60% decrease. In post-study clinical symptom analysis, abdominal pain and discomfort scores were reduced by 22% in the 72mg group and 25% in the 144mg group.
In a trial attempting to increase curcumin absorption, 121 patients with mild-to-moderate symptoms of IBS were randomly assigned to curcumin and fennel oil, or placebo (2 capsules twice a day for 30 days). Curcumin and fennel oil was safe, well-tolerated and induced symptom relief in patients with IBS as shown by a reduced symptom severity score. The percentage of symptom-free patients was significantly higher in the curcumin and fennel oil group than in the placebo group (25.9% vs. 6.8%). Patients quality of life improved after taking curcumin and fennel oil as shown through the IBS QoL questionnaire.
A recent double blinded randomised placebo-controlled trial of a food supplement containing curcumin, peppermint oil, fish oil and caraway oil involved giving 99 patients with Rome III classified IBS a placebo or food supplement. A difference in IBS symptom severity score (IBS-SSS) was seen after 4 weeks, but this continued to improve with a significant difference in score at 8 weeks without serious adverse side effects.
Curcumin mitigates inflammatory responses by inhibiting cyclooxygenase-2 (COX-2), lipoxygenase, nuclear factor (NF)-kappa B, inducible nitric oxide IFN-γ-, or TNF-α-activated macrophages and NK cells.[20-22] For this reason it has also been used in IBD alone, and alongside regular medications.
A recent study found turmeric extract reduces inappropriate epithelial cell transport and increases anti-inflammatory cytokines thus reducing inflammation associated with IBD.
In an early study of 10 IBD patients, 5 UC patients receiving curcumin 1000-16000 mg daily had a significant reduction of both the symptoms and the inflammatory indices. Of 5 CD patients consuming 360 mg three or four times per day, 4 patients had a reduction of both the CD activity index and symptomatic parameters. Case reports have demonstrated benefit in UC associated with enteropathic arthropathy.
A randomised controlled trial on 89 UC patients revealed that when combined with standard drug therapy, adding 2g/day of curcumin significantly reduced risk relapse (4.65% vs 20.51%) and improved clinical activity index and endoscopic index after 6 months. More recently a study assessed the effect of curcumin on the levels of enzymes and signalling proteins that stimulate immune responses in the gut of children and adults with IBD. Results indicated suppression of unwanted immune response and enhancement of beneficial immune response.
The most recent placebo controlled, double blind randomised study of 50 patients with mild to moderate UC showed that the addition of 3g curcumin to unsuccessful mesalamine therapy was superior to the combination of placebo and mesalamine in inducing clinical and endoscopic remission in patients after 1 month (53.8% curcumin group obtained remission v’s 0% in the placebo).
Conversely, a randomized, double-blind, single-centre pilot trial was conducted in patients with distal UC (<25 cm involvement) and mild-to-moderate disease activity. Forty-five patients were randomized to either NCB-02 (standardized curcumin preparation) enema plus oral 5-ASA or placebo enema plus oral 5-ASA. Though the outcome difference was not statistically significant on intention-to treat analysis, there was a trend towards better outcomes in the NCB-02 group, which highlights the need for further investigations on this novel promising therapy for IBD patients.
Green tea (Camelia sinesis) is of such interest to health researchers as it typically contains 98% green tea polyphenols. Of most interest are the catechins, of which epigallocatechin-3-gallate (EGCG) is the most abundant and well-studied. Polyphenols such as EGCG are metabolised by the bacteria in the gut, which break them down into phenolic acids. These are then absorbed into the blood and excreted in the urine. Green tea and green tea extracts have been studied in a variety of settings.
The anti-cancer benefits of EGCG have not only been shown in the laboratory,[31-34] 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. 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. EGCG is thought to exert its cancer-preventive activity in the bowel by interrupting signalling pathways.
In vitro and animal studies have demonstrated anti-inflammatory responses in intestinal epithelial cells with subsequent studies in man demonstrating a reduction in inflammatory activity in mild-moderate ulcerative colitis.[38,39] With 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. Nineteen patients received more than one dose of EGCG and 53.3% of patients gained remission status, compared to 0% in the placebo group, who didn’t consume any.
- Khayyat Y, Attar S. Vitamin D Deficiency in Patients with Irritable Bowel Syndrome: Does it Exist? Oman Medical Journal. 2015;30(2):115-118. doi:10.5001/omj.2015.25.
- Tazzyman S, Richards N, Trueman AR et al. Vitamin D associates with improved quality of life in participants with irritable bowel syndrome: outcomes from a pilot trial. BMJ Open Gastroenterol. 2015 Dec 21;2(1):e000052.
- Abbasnezhad A, Amani R, Hajiani E et al. Effect of vitamin D on gastrointestinal symptoms and health-related quality of life in irritable bowel syndrome patients: a randomized double-blind clinical trial. Neurogastroenterol Motil. 2016 May 7.
- Ardesia M, Ferlazzo G, Fries W. Vitamin D and Inflammatory Bowel Disease. BioMed Research International. 2015;2015:470805.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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].
- 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]
- 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.
- 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.
- 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.
- 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.
- Srimal RC, Dhawan BN. Pharmacology of diferuloyl methane (curcumin), a non-steroidal anti-inflammatory agent. J Pharm Pharmacol 1973;25(6):447–52.
- 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.
- Portincasa P, Bonfrate L, Scribano ML Et al. Curcumin and Fennel Essential Oil Improve Symptoms and Quality of Life in Patients with Irritable Bowel Syndrome. J Gastrointestin Liver Dis. 2016;25(2):151-7.
- Alt F, Chong P, Teng E, Uebelhack R. Evaluation of Benefit and Tolerability of IQP‐CL‐101 (Xanthofen) in the Symptomatic Improvement of Irritable Bowel Syndrome: A Double‐Blinded, Randomised, Placebo‐Controlled Clinical Trial. Phytotherapy Research. 2017;31(7):1056-1062. doi:10.1002/ptr.5826.
- Bhaumik, S, Jyothi, M D, Khar, A. Differential modulation of nitric oxide production by curcumin in host macrophages and NK cells. FEBS Lett 2000; 483, 78-82.
- Brouet, I., Ohshima, H. 1995. Curcumin, an anti-tumour promoter and anti-inflammatory agent, inhibits induction of nitric oxide synthase in activated macrophages. Biochem Biophys Res Commun 206, 533-540.
- Surh YJ, Chun, KS, Cha HH et al. Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation. Mutat Res 2001 480-481, 243-268.
- McCann MJ, Johnston S, Reilly K, et al. The Effect of Turmeric (Curcuma longa) Extract on the Functionality of the Solute Carrier Protein 22 A4 (SLC22A4) and Interleukin-10 (IL-10) Variants Associated with Inflammatory Bowel Disease. Nutrients. 2014;6(10):4178-4190. doi:10.3390/nu6104178.
- 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.
- Lahiff C, Moss AC. Curcumin for clinical and endoscopic remission in ulcerative colitis. Inflamm Bowel Dis. 2011;17: E66.25.
- Hanai, H, Iida, T, Takeuchi, K et al. Curcumin maintenance therapy for ulcerative colitis: Randomized, multicenter, double-blind, placebo-controlled trial. Clin. Gastroenterol. Hepatol. 2006, 4, 1502–1506.
- 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.
- 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.
- Singla V, Pratap Mouli V et al. Induction with NCB-02 (curcumin) enema for mild-to-moderate distal ulcerative colitis – a randomized, placebo-controlled, pilot study. J Crohns Colitis. 2014;8:208-14.
- 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.
- Scalbert A, Manach C, Morand C, et al. Dietary polyphenols and the prevention of diseases. Crit Rev Food Sci Nutr 2005;45:287-306.
- Yang CS. Inhibition of carcinogenesis by tea. Nature 1997;389:134-5.
- Yang CS, Chung JY, Yang GY, et al. Mechanisms of inhibition of carcinogenesis by tea. Biofactors 2000;13:73-9.
- 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.
- 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.
- 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.
- 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.
- Sergent T Piront N, Meurice J et al. Anti-inflammatory effects of dietary phenolic compounds in an in vitro model of inflamed human intestinal epithelium. Chem Biol Interact. 2010;188(3):659-67. doi: 10.1016/j.cbi.2010.08.007.
- Watson J.L. Ansari S, Cameron H et al. Green tea polyphenol (−)-epigallocatechin gallate blocks epithelial barrier dysfunction provoked by IFN-γ but not by IL-4. Am J Physiol Gastrointest Liver Physiol. 2004 >287 (5), G954-G961.
- 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 Aug;19(9):1904-12.