The number of people with Crohn’s disease disease is rising, particularly amongst young people.1 (see references below) Katie Keeratut looks at recent developments for managing CD, and discusses the links with diet, nutrition support, research and evidence
CD is characterised by patchy, deep fissuring ulceration affecting anywhere along the GI tract and tends to follow an unpredictable relapsing, remitting course. Symptoms commonly include abdominal pain, bloody diarrhoea, fatigue, loss of appetite and weight loss.2
Malnutrition in CD is common with up to 75% of adult inpatients experiencing weight loss.3 Growth retardation has been reported in up to 40% of children and adolescents and up to 60% have decreased muscle and body fat stores.3 Specific vitamin and mineral deficiencies are common in the acute phase of CD.3 Dietary assessment of 126 IBD patients found vitamin B12, folate, B6 and vitamin D deficiency was common and did not always correlate with inadequate dietary intake. Routine multivitamin supplementation was recommended.4
How does diet link to CD development?
The aetiology of CD remains unclear, but involves a complex interaction of environmental factors including smoking, diet and stress and a dysfunctional immune response to gut microbiota. Over 160 genetic risk loci have been identified with 25% thought to be IBD risk contributors, suggesting the rise in the incidence of CD over the last 50 years cannot be attributed to genetic factors alone.5
Fast food consumption has been shown to confer a three-to-four-fold increased risk of CD development.6 The incidence of IBD in previously low-incidence countries like Japan has increased three-to-five-fold in the last decade creating a strong interest in the link to changing dietary patterns. 7-8 A retrospective Japanese study found patients who developed CD had higher intake of sugars and sweeteners, total fat and oils, fish and shellfish with animal fat the strongest independent factor.9 Fruit, vegetables and fibre were found to be protective against CD development in children.10
Refined sugars and fats have been linked to IBD risk.11 It is suggested links exist between increased sugar intake, insulin resistance and chronic inflammation.12 Saccharin and sucralose have been proposed as key triggers in the rise of IBD through the ‘Bacteria-Protease-Mucus-Barrier hypothesis’ where bacterial dysbiosis leads to impaired inactivation of digestive proteas¬es causing damage to the mucus layer and gut barrier.13 A recent study found no link between total carbohydrate intake and development of CD suggesting that carbohydrate may not be linked to CD development on a macronutrient level.12
Concentrated milk fat is commonly used in processed foods and confectionary and has been found to induce colitis in genetically susceptible mice. Milk fat caused changes in bile acid composition, selectively increasing a rare bacteria Bilophila wadsworthia, which produce substances that disturb immune homeostasis, triggering gut inflammation.14
Geographical variation in CD incidence correlates with emulsifier consumption. Polysorbate 80 (found in ice-cream and dessert toppings) and E466 (found in dairy products and processed meats) increased intestinal permeability and bacterial translocation of E.Coli across the intestinal epithelium 59-fold in animal models.15
Exclusive enteral nutrition (EEN)
EEN is considered first line treatment for induction of remission in paediatrics.16 In adults there is limited, weak evidence that corticosteroids are superior with response rate on an intention-to-treat basis between 53-80% after three to six weeks of EEN.17-18 Adherence and inadequate dietetic provision may be limiting factors in adult success rates.19 EEN avoids the side effects of corticosteroids and immune modulating agents, helps treat under nutrition3 and is superior to corticosteroid treatment at inducing mucosal healing after ten weeks – 74% versus 33% respectively.20 The mechanism of action of EEN remains unclear and may be due to removal of food decreasing the antigenic load, causing a reduction in intestinal permeability.3
A recent study looking at the effect of using partial enteral nutrition (PEN) combined with a specially tailored ‘CD Exclusion Diet’ led to induction of remission in 70% of children and 69% of adults. Six out of seven patients achieved remission on the exclusion diet alone.21
Nutrition in disease remission
Exclusion diets for disease maintenance are not currently recognised in any national guideline.22-23 Providing 50% of intake as EN has been shown to be superior to normal diet in prolonging disease remission23 and a high-fibre diet is not effective.17, 25 Food re-introduction diets including the ‘Low-fat fibre limited exclusion’ diet may prolong disease remission in adults with 56% of patients still in remission at a two year endpoint.26
Surgical recurrence requiring Infliximab therapy has been found to be lower in PEN patients compared to controls after a five-year follow-up – two (10%) versus nine (45%) respectively. There was a lower non-significant trend of re-operation in the EN group compared to the controls – one (5 %) versus five (25 %).27 PEN combined with Infliximab for maintenance treatment has been found to be effective in adults with CD. The cumulative remission rate was significantly higher in the EN group and was the only suppressive factor for disease recurrence.28
Other dietary considerations
Faecal calprotectin can be used to distinguish between inflammation and functional symptoms,29 which are common in IBD and persist when inflammatory markers are normal.30 The low FODMAP diet has been shown to help alleviate functional symptoms including abdominal pain, bloating, wind and diarrhoea in 50 % of CD patients but worsened constipation.30
There is no current evidence that probiotics or omega 3 fatty acids can be used to induce or maintain remission in CD.17, 31
Diet in stricturing CD
Strictures lead to localised, persistent narrowing and can be inflammatory or fibrotic.32 Based on expert opinion dietary fibre is contraindicated.17 The distinction between low fibre and low residue remains unclear and is an area warranting further research.
EEN for 12 weeks has been shown to effectively treat inflammatory strictures on an intention to treat analysis. Symptomatic remission was achieved in 81.4% of patients and full clinical remission in 64.6% with the luminal cross sectional area at the stricture site increasing by 331%.33
Conclusion
Diet remains an interesting and credible treatment option in CD. Despite the success of EEN and emerging evidence on use of PEN and exclusion diets to induce and maintain remission, little is known of the exact mechanisms of action. It may be that exclusion of specific dietary components rather than complete dietary exclusion is required.21 In view of adherence issues with EEN in adults there is exciting potential for the role of dietary manipulation in treating CD with larger well designed studies required.
References
1 IBD standards group (2013) Standards for the Healthcare of People who have Inflammatory Bowel Disease (IBD). Available at: www.ibdstandards.org.uk/uploaded_files/ibdstandards.pdf (Accessed 10th November 2014).
2 IBD Audit (2014). National audit of inflammatory bowel disease service provision: UK IBD Audit. Royal college of physicians. Available at: www.rcplondon.ac.uk (Accessed 10th November 2014).
3 ESPEN Guidelines on Enteral Nutrition: Gastroenterology. Lochs, HC. Dejong, F. Hammarqvist, X. Hebuterne, M. Leon-Sanz, T. Schutz, W. Van Gemert, A. Van Gossum, L. Valentini, DGEMH. Lubke, S. Bischoff, N. Engelmann, P. Thul. Clinical Nutrition. 2006. 25: 260–274
4 Vagianos, K., Bector, S., McConnell, J., Bernstein, C.N. Nutrition assessment of patients with inflammatory bowel disease. 2007. Journal of parenteral and enteral nutrition. 31 (4): 311-319.
5 Abraham, C and Cho, JH. (2009). Inflammatory Bowel Disease. New England Journal of Medicine. 2009. 361: 2066-2078.
6 Persson, PG, Ahlbom, A, Hellers, G. Diet and inflammatory bowel disease: A case control study. Epidemiology. 1992. 3: 47-52.
7 Orholm et al, 1991 Orholm M, Munkholm P, Langholz E, et al. Familial occurrence of inflammatory bowel disease. New England Journal of Medicine. 1991;324:84–88.
8 Ahuja, V. and Tandon, RK. Inflammatory bowel disease in the asia-pacific area: a comparison with developed countries. Journal of digestive diseases. 2010. 11:134-147.
9 Sakamoto, N., Kono,S Wakai,K Fukuda,Y. Satomi,M Shimoyama, T., Inaba,Y Miyake, Y Sasaki, S,Okamoto,K Kobashi,G Washio,M Yokoyama,T Date,C, Tanaka, H. (2005). Inflammatory Bowel Disease. 11:2
10 Reif, S. Klein, I. Lubin, F. Pre-illness dietary factors in inflammatory bowel disease. Gut. 1997. 40:754-760.
11 Amre, DK, D’souza, S. Morgan, K. Imbalances in dietary consumption of fatty acids, vegetables and fruits are associated with risk for Crohn’s disease in children. American Journal of gastroenterology. 2007. 102:2016-2025.
12 Chan, SM, Chir, B, Luben, R, Van Schaik, F, Oldenburg, B, Bas Bueno-de-Mesquita H, Hallmans, G, Karling P, Lindgren S, Grip O, Key T, Crowe FL, Bergmann MM, Overvad K, Palli D, Masala G, Khaw KT, Racine A, Carbonnel F, Boutron-Ruault MC, Tjonneland A, Kaaks R, Tumino R, Trichopoulou A, and Hart AR. Carbohydrate Intake in the Aetiology of Crohn’s Disease and Ulcerative Colitis. Inflammatory Bowel Disease. 20 (11). 2014. 2013-2021.
13 Qin X. Aetiology of inflammatory bowel disease: A unified hypothesis. World Journal of Gastroenterology. 2012. 18 (15) 1708-1722
14 Devkota, S., Wang, Y., Musch, M.W, Leone, V., Fehlner-Peach, H., Nadimpalli A, Antonopoulos DA, Jabri B, Chang E.B. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il102/2 mice. Nature. 2012. 104: 487
15 Roberts CL, Rushwoerth SL, Richman E, Rhodes JM. Hypothesis: Increased consumption of emulsifiers for the rising incidence of Crohn’s Disease. Journal of Crohn’s and Colitis. 2013. 7:338-341.
16 Ruemmelea F.M, Veres G K, Kolho L, Griffiths A, Levineg A, Escher C, Amil Dias J, Barabinoj A, Braegger CP, Bronskyl J, Buderus S, Martín-de-Carpi J, De Ridder L, Fagerberg UL, Hugot P, Kierkus J, Kolacekt S, Koletzko S, Lionetti P, Miele E, Navas López VM, Paerregaardy A, Russell RK, Serbanaa DE, Shaoul R, Van Rheenenac P, Veeremanad G, Weiss ae Wilsonaf B, Dignass A, Eliakimaj A, Winter, Turner, D. Consensus guidelines of ECCO/ESPGHAN on the medical management of paediatric Crohn's disease.Journal of Crohn's and Colitis. 2014. 8: 1179–1207
17 Lee J, Allen R, Ashley S, Becker S, Cummins P, Gbadamosi A, Gooding O, Huston J, Le Couteur J, O’Sullivan D, Wilson S, Lomer, M. (2014). On behalf of gastroenterology specialist group of the British dietetic association. British dietetic association evidence-based guidelines for the dietary management of Crohn’s disease in adults. Journal of human nutrition and dietetics. 27:207-218.
18 Zachos M, Tondeur M, Griffiths AM. Enteral nutritional therapy for induction of remission in Crohn’s disease (Review). The Cochrane Library. 2008, Issue 4. Accessed at: www.thecochranelibrary.com
19 Lomer M.C.E, Gourgey R. and Whelan K. Current practice in relation to nutritional assessment and dietary management of enteral nutrition in adults with Crohn’s disease. Journal of Human Nutrition and Dietetics. 2014. 27 (Suppl. 2): 28–35
20 Borrelli O, Cordischi L, Cirulli M, Paganelli M, Labalestra V, Uccini S. Polymeric diet alone versus corticosteroids in the treatment of active pediatric Crohn's disease: a randomized controlled open-label trial. Clinical Journal of Gastroenterology and Hepatology. 2006. 4(6):744–53
21 Sigall-Boneh, R, Pfeffer-Gik T, Segal I, Zangen T, Boaz M. and Levine A. Partial enteral nutrition with a crohn’s disease exclusion diet is effective for induction of remission in children and young adults with Crohn’s disease. Inflammatory bowel disease. 2014. 20 (8): 1353-1360.
22 Mowat C, Cole A, Windsor AL, Ahmad T, Arnott I, Driscoll R, Mitton S, Orchard T, Rutter M, Younge L, Lees C, Ho G, Satsangi J, Bloom S. On behalf of the british society of gastroenterology (2008). Guidelines for the management of inflammatory bowel disease in adults. 2011. Gut. 60:57.
23 National Institute for Clinical Excellence. Crohn's disease management in adults, children and young People. 2012. NICE clinical guideline 152 guidance.nice.org.uk/cg152. Available from: www.nice.org.uk/guidance/cg152/resources/guidance-crohns-disease-pdf (Accessed on 10th November 2014).
24 Akobeng AK, Thomas AG. Enteral nutrition for maintenance of remission in Crohn’s disease (Review). The Cochrane Library. 2009. Issue 4. Accessed at: http://www.thecochranelibrary.com
25 Jones et al 1985 GastroAlun Jones, V., Dickinson, R.J., Workman, E., enterology 96, A224. Wilson, A.J., Freeman, A.H. & Hunter, J.O. (1985) Crohn’s disease: maintenance of by diet. Lancet ii, 177–180.
26 Woolner, T. J. Parker, G. A. Kirby and J. O. Hunter. The development and evaluation of adiet for maintaining remission in Crohn’s disease. Journal of Human Nutrition and Dietetics. 1998. 11: 1–11
27 Yamamoto T, Shiraki M, Nakahigashi M, Umegae S, Matsumoto K. Enteral nutrition to suppress postoperative Crohn’s disease recurrence: a five-year prospective cohort study. International Journal of Colorectal Disease. 2012.1587-3.
28 Hirai F, Ishihara H, Yada S, Esaki M, Ohwan T, Nozaki R, Ashizuka S, Inatsu H, Ohi H, Aoyagi K, Mizuta Y, Matsumoto T, Matsui T. Effectiveness of Concomitant Enteral Nutrition Therapy and Infliximab for Maintenance Treatment of Crohn’s Disease in Adults. Digestive Diseases and Sciences. 2013. 58(5):1329-34
29 NICE diagnostic guidance. 2013. GD11 Faecal calprotectin diagnostic tests for inflammatory diseases of the bowel. Available at: https://www.nice.org.uk/guidance/dg11/resources/guidance-faecal-calprotectin-diagnostic-tests-for-inflammatory-diseases-of-the-bowel-pdf (Accessed 10th november 2014)
30 Gearry RB. Reduction of dietary poorly absorbed short chain carbohydrates FODMAPs improves abdominal symptoms in patients with inflammatory bowel disease a pilot study. Journal of Crohn’s and Colitis. 2008. 3 (1):8-14.
31 Farrukh A and Mayberry JF. Is there a role for fish oil in inflammatory bowel disease. World Journal of Clinical cases. 2014. 2 (7): 250-252.
32 Silverberg MS, Satsangi J, Ahmad T, Arnott ID, Bernstein CN, Brant SR, Caprilli R, Colombel JF, Gasche C, Geboes K, Jewell DP, Karban A, Loftus EV, Pena AS, Riddell RH, Sachar DB, Schreiber DB, Steinhart AH, Targan SR, Vermeire S, and Warren BF. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a working party of the 2005 montreal world congress of gastroenterology. Canadian journal of gastroenterology. 19 (Suppl A). 5-36
33 Hu D, Ren J, Wang G, Guanwei L, Song L, Yan D, Gu G, Zhou B, Xiuwen W, Chen J, Ding C, Wu Y, Wu Q, Liu N, and Li J. Exclusive enteral nutritional therapy can relieve inflammatory bowel stricture in Crohn’s disease. Journal of Clinical Gastroenterology. 2014. 48 (9): 790-795.