Dietary Guidance From the International Organization for the Study of Inflammatory Bowel Diseases

Recent evidence points to a plausible role of diet and the microbiome in the pathogenesis of both Crohn’s disease (CD) and Ulcerative Colitis (UC). Dietary therapies based on exclusion of table foods and replacement with nutritional formulas and/or a combination of nutritional formulas and specific table foods may induce remission in CD. In UC, specific dietary components have also been associated with flare of disease. While evidence of varying quality has identified potential harmful or beneficial dietary components, physicians and patients at the present time do not have guidance as to which foods are safe, may be protective or deleterious for these diseases. The current document has been compiled by the nutrition cluster of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) based on the best current evidence to provide expert opinion regarding specific dietary components, food groups and food additives that may be prudent to increase or decrease in the diet of patients with inflammatory bowel diseases to control and prevent relapse of inflammatory bowel diseases. Recent evidence points to a plausible role of diet and the microbiome in the pathogenesis of both Crohn’s disease (CD) and Ulcerative Colitis (UC). Dietary therapies based on exclusion of table foods and replacement with nutritional formulas and/or a combination of nutritional formulas and specific table foods may induce remission in CD. In UC, specific dietary components have also been associated with flare of disease. While evidence of varying quality has identified potential harmful or beneficial dietary components, physicians and patients at the present time do not have guidance as to which foods are safe, may be protective or deleterious for these diseases. The current document has been compiled by the nutrition cluster of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) based on the best current evidence to provide expert opinion regarding specific dietary components, food groups and food additives that may be prudent to increase or decrease in the diet of patients with inflammatory bowel diseases to control and prevent relapse of inflammatory bowel diseases. The inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), have long been thought to arise from inappropriate and maladaptive stimulation of the immune system. Emerging evidence demonstrates that environmental factors, including diet, may play an important role in the pathogenesis and inflammation. This highlights the need to provide guidance to physicians and patients regarding which foods may be harmful, beneficial, or safe to consume. To address this gap in patient care and education, the International Organization for the Study of Inflammatory Bowel Disease (IOIBD) formed a working group to formulate recommendations for physicians, dietitians, and patients based on best available evidence. These recommendations focus on dietary patterns to control and prevent relapse of IBD. The IOIBD Nutrition Cluster is composed of 12 members from 3 continents (https://www.ioibd.org/clusters/). Following an organizational meeting in March 2018, 7 food groups, dietary components, and 5 food additives were selected as the most important to address for patient dietary guidance. These included dairy, red meat, processed meat, poultry, eggs, fruits and vegetables, fat, refined sugar, wheat and gluten, alcohol, emulsifiers, maltodextrins and artificial sweeteners, gums and thickening agents, and nanoparticles. The group assigned members to review the published literature for each of the chosen foods or additives. The reviewer was to summarize the published data separately for studies involving humans and animal models. Animal data received more attention when human data were absent or the animal models were considered reproducible and of clinical importance. Given the broad scope of the topic and the quality of the existing data, no attempt was made to produce summary risk estimates. The members prepared a concise document that included overall recommendations and a narrative summary. Where there were fewer data from studies in humans, more data were presented from animal models. Although it would be ideal to know the exact amount of each food that patients with IBD should consume, this could vary by age, sex, weight, and so forth. Additionally, there generally were insufficient published data for such specific recommendations. Therefore, recommendations were provided separately for CD and UC, and were chosen from 4 categories (prudent to increase consumption, to decrease or avoid consumption, safe to consume, or insufficient evidence to make a claim). During group discussion, some items were modified to state that it “may be prudent to increase or decrease consumption.” The cluster chairs (AL and JDL), in collaboration with the workgroup co-leads (JOL and JMR) edited the first drafts to create a common format. The IOIBD cluster members reviewed the data and the recommendations at a face-to-face meeting in March 2019 and voted on the recommendations and wording, with consensus defined as >75% agreement. Following the meeting, the chairs slightly revised the wording of a few of the recommendations during the manuscript drafting in response to comments by the authors. Subsequently, a final vote was taken via a REDCap survey in July 2019, using the same definition of consensus. The evidence level (EL) supporting the recommendation was categorized loosely based on the following scale: randomized controlled trials (RCTs) provide high-level evidence, observational studies in humans provide low-level evidence, and everything else is very-low-level evidence. Level of evidence could be increased or decreased based on the strength of association and reproducibility of findings, or quality of studies. Because the objective of the guidance document is to help patients with established diagnosis of IBD, studies examining the role of diet in the etiology of IBD were categorized as EL very low. When possible, the review focused on the effect of diet on inflammation and symptoms, although in some cases, data were only available for symptom control. Exclusive enteral nutrition, a known effective therapy for CD, was not addressed. All recommendations were made without consideration of other comorbid conditions that may influence choice of dietary patterns. Consensus was achieved for all food types except pasteurized dairy consumption (Table 1).Table 1IOIBD Dietary Recommendations for Patients With IBDsDietary componentRecommendation UC (evidence level, % agreement)Recommendation CD (evidence level, % agreement)Source of evidenceClarificationsFruitsInsufficient evidence to recommend specific dietary changes (very low, 100%)Prudent to increase exposure (low, 84.6%)EpidemiologyClinical studiesReduce insoluble fiber if stricture present (evidence level very low)VegetablesInsufficient evidence to recommend any specific changes (very low, 100%)Prudent to increase exposure (low, 84.6%)EpidemiologyClinical studiesReduce insoluble fiber if stricture present (evidence level very low)Refined sugars and carbohydratesInsufficient evidence to recommend any specific changes in refined sugar or complex carbohydrate intake (low, 92.3%)Insufficient evidence to recommend specific changes in refined sugar or complex carbohydrates (low, 100%)EpidemiologyWheat/glutenInsufficient evidence to recommend restriction of wheat and gluten (low, 100%)Insufficient evidence to recommend restriction of wheat and gluten (low, 100%)EpidemiologyAnimal modelsGluten has been associated with ileitis in a mouse model of CDRed/processed meatPrudent to reduce intake of red and processed meat (low, 100%)Insufficient evidence to recommend restriction of intake (high, 100%)EpidemiologyAnimal ModelsPoultryInsufficient evidence to recommend dietary changes (low, 100%)Insufficient evidence to recommend restriction of intake (high, 100%)EpidemiologyLean chicken breast is a low animal fat and low taurine source of protein and is allowed in the CD exclusion dietPasteurized dairy productsUnable to reach consensus (92.3%)Unable to reach consensus (92.3%)EpidemiologyAnimal modelsDairy products encompass a wide range of productsLactase deficiency and lactose intolerance is common among patients with IBDPrudent to reduce dairy fat and processed dairy rich in maltodextrins and emulsifiersUnpasteurized dairy productsPrudent to avoid in all patients (100%)Prudent to avoid in all patients (100%)Expert opinion Case reportsAvoid infections that can result from consumption of unpasteurized dairy productsDietary fatsPrudent to reduce consumption of myristic acid (palm oil, coconut oil, dairy fats) (low, 100%)Prudent to avoid trans fat (very low, 100%)Prudent to increase dietary consumption of omega-3 fatty acids (DHA and EPA) from marine fish (low) but not from dietary supplements (high, 100%)Prudent to reduce exposure to saturated fats (GRADE low, 100%) and avoid trans fat (very low, 100%)Prospective, observational studiesMyristic acid linked to UC is found in palm and coconut oil, dairy fat, and meat from grain-fed as opposed to grass-fed animalsNatural omega-3 fatty acids are found mainly in wild marine fishAlcoholic beveragesInsufficient evidence to recommend changes in low-level alcohol consumption (low, 100%)Insufficient evidence to recommend changes in low-level alcohol consumption (low, 100%)EpidemiologyA trial of avoidance of alcohols containing high levels of sulfites (ie, beer and wine) is reasonable (evidence level 3b)Food additivesMaltodextrins/artificial sweetenersIt may be prudent to limit intake of maltodextrin-containing foods and artificial sweeteners (very low, 92.3%)It may be prudent to limit intake of maltodextrin-containing foods and artificial sweeteners (very low, 92.3%)EpidemiologyAnimal modelsEmulsifiers and thickenersIt may be prudent to limit intake of carboxymethylcellulose and polysorbate-80 (very low, 92.3%)It may be prudent to limit intake of carboxymethylcellulos and polysorbate-80 (very low, 92.3%)Animal models EpidemiologyE433, polysorbate-80E466, carboxymethylcelluloseCarrageenansIt may prudent to reduce intake of processed foods containing carrageenan (very low, 92.3%)It may prudent to reduce intake of processed foods containing carrageenan (very low, 92.3%)EpidemiologyAnimal modelsOne very small RCTFound in dairy-based desserts, frozen meals, and processed meatsTitanium dioxide and other nanoparticlesIt may prudent to reduce intake of processed foods containing titanium dioxide and sulfites (very low, 92.3%)It may prudent to reduce intake of processed foods containing titanium dioxide and sulfites (low, 92.3%)Clinical trial in CDAnimal models and translational studies in UCThe inconsistent results of the 2 clinical trials of low-nanoparticle diets led to a downgrading of the evidenceNOTE. Bold text refers to a recommendation to increase consumption. Italic text refers to a recommendation to reduce consumption.CD, Crohn’s disease; IBD, inflammatory bowel disease; IOIBD, International Organization for the Study of Inflammatory Bowel Disease; RCT, randomized controlled trial; UC, ulcerative colitis. Open table in a new tab NOTE. Bold text refers to a recommendation to increase consumption. Italic text refers to a recommendation to reduce consumption. CD, Crohn’s disease; IBD, inflammatory bowel disease; IOIBD, International Organization for the Study of Inflammatory Bowel Disease; RCT, randomized controlled trial; UC, ulcerative colitis. In CD, it is prudent to recommend moderate to high consumption of fruits and vegetables (EL low). In patients with symptomatic or significant fibrostricturing disease, insoluble fiber intake should be restricted (EL very low). In UC, there is insufficient evidence to recommend any specific change or restriction in intake of fruit and vegetables. (EL very low). Fruits and vegetables are a diverse group of foods that generally have in common high-fiber content. Fibers are undigested in the human small intestine, but most are fermented by bacterial enzymes within the colon, soluble fiber usually more rapidly than insoluble. Fermentation produces short-chain fatty acids (SCFA), such as butyrate, that act as carbon and energy sources for the colonic epithelium. Decreased production of SCFA may occur in patients with active IBD.1Gill P.A. van Zelm M.C. Muir J.G. et al.Review article: short chain fatty acids as potential therapeutic agents in human gastrointestinal and inflammatory disorders.Aliment Pharmacol Ther. 2018; 48: 15-34Crossref PubMed Scopus (50) Google Scholar Significant dietary restriction of fiber leads to greater bacterial consumption of colonic mucus, which might contribute to inflammation.2Desai M.S. Seekatz A.M. Koropatkin N.M. et al.A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility.Cell. 2016; 167: 1339-1353Abstract Full Text Full Text PDF PubMed Scopus (472) Google Scholar Specific soluble fibers, including plantain (banana) and broccoli pectins, reduce bacterial adherence and translocation by the epithelium3Roberts C.L. Keita A.V. Duncan S.H. et al.Translocation of Crohn's disease Escherichia coli across M-cells: contrasting effects of soluble plant fibres and emulsifiers.Gut. 2010; 59: 1331-1339Crossref PubMed Scopus (120) Google Scholar; fiber may also serve as growth substrates for important SCFA-producing commensal bacteria. Epidemiologic studies suggested that patients with IBD consume less fruit and vegetables before disease onset, particularly for CD.4D'Souza S. Levy E. Mack D. et al.Dietary patterns and risk for Crohn's disease in children.Inflamm Bowel Dis. 2008; 14: 367-373Crossref PubMed Scopus (75) Google Scholar, 5Ananthakrishnan A.N. Khalili H. Konijeti G.G. et al.A prospective study of long-term intake of dietary fiber and risk of Crohn's disease and ulcerative colitis.Gastroenterology. 2013; 145: 970-977Abstract Full Text Full Text PDF PubMed Scopus (197) Google Scholar, 6Thornton J.R. Emmett P.M. Heaton K.W. Diet and Crohn's disease: characteristics of the pre-illness diet.Br Med J. 1979; 2: 762-764Crossref PubMed Google Scholar In the prospective Nurses’ Health Study, women in the highest quintile for fruit fiber had approximately half the risk for subsequent CD development.6Thornton J.R. Emmett P.M. Heaton K.W. Diet and Crohn's disease: characteristics of the pre-illness diet.Br Med J. 1979; 2: 762-764Crossref PubMed Google Scholar However, in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, no association between fiber intake and subsequent risk for CD or UC was found.7Andersen V. Chan S. Luben R. et al.Fibre intake and the development of inflammatory bowel disease: a European prospective multi-centre cohort study (EPIC-IBD).J Crohns Colitis. 2018; 12: 129-136Crossref PubMed Scopus (15) Google Scholar Higher intake of fruits and vegetables has been associated with lower endoscopic activity of UC.8Magee E.A. Edmond L.M. Tasker S.M. et al.Associations between diet and disease activity in ulcerative colitis patients using a novel method of data analysis.Nutr J. 2005; 4: 7Crossref PubMed Scopus (53) Google Scholar An Internet-based prospective study found that, among people with CD in remission, those in the highest quartile for fiber consumption were nearly half as likely to flare during 6-months follow-up, but there was no such association in UC.9Brotherton C.S. Martin C.A. Long M.D. et al.Avoidance of fiber is associated with greater risk of Crohn's disease flare in a 6-month period.Clin Gastroenterol Hepatol. 2016; 14: 1130-1136Abstract Full Text Full Text PDF PubMed Google Scholar Patients with stricturing CD tend to avoid high-fiber foods. An RCT of 2-years high-fiber/low-sugar diet showed no significant benefit or harm in adults with inactive or mildly active CD.10Ritchie J.K. Wadsworth J. Lennard-Jones J.E. et al.Controlled multicentre therapeutic trial of an unrefined carbohydrate, fibre rich diet in Crohn's disease.Br Med J (Clin Res Ed). 1987; 295: 517-520Crossref PubMed Scopus (86) Google Scholar In another trial among patients with CD, symptoms were worse with supplementation of inulin than placebo.11Benjamin J.L. Hedin C.R. Koutsoumpas A. et al.Randomised, double-blind, placebo-controlled trial of fructo-oligosaccharides in active Crohn's disease.Gut. 2011; 60: 923-929Crossref PubMed Scopus (171) Google Scholar Data from additional studies are presented in Supplementary Table 1. In CD, there is insufficient evidence to recommend any specific change of intake of complex carbohydrates or refined sugars and fructose (EL low). It may be prudent to use a low FODMAP diet for patients with persistent symptoms despite resolution of inflammation and absence of strictures (EL low). In UC, there is insufficient evidence to recommend any specific change of intake of complex carbohydrates or refined sugars and fructose (EL very low). It may be prudent to use a low FODMAP diet for patients with persistent symptoms despite resolution of inflammation (EL low). Several cross-sectional and case-control studies have observed increased sugar consumption in patients with CD,6Thornton J.R. Emmett P.M. Heaton K.W. Diet and Crohn's disease: characteristics of the pre-illness diet.Br Med J. 1979; 2: 762-764Crossref PubMed Google Scholar,12Martini G.A. Brandes J.W. Increased consumption of refined carbohydrates in patients with Crohn's disease.Klin Wochenschr. 1976; 54: 367-371Crossref PubMed Scopus (130) Google Scholar, 13Miller B. Fervers F. Rohbeck R. et al.[Sugar consumption in patients with Crohn's disease].Verh Dtsch Ges Inn Med. 1976; 82: 922-924PubMed Google Scholar, 14Kasper H. Sommer H. Dietary fiber and nutrient intake in Crohn's disease.Am J Clin Nutr. 1979; 32: 1898-1901Crossref PubMed Google Scholar, 15Katschinski B. Logan R.F. Edmond M. et al.Smoking and sugar intake are separate but interactive risk factors in Crohn's disease.Gut. 1988; 29: 1202-1206Crossref PubMed Google Scholar, 16Mayberry J.F. Rhodes J. Newcombe R.G. Breakfast and dietary aspects of Crohn's disease.Br Med J. 1978; 2: 1401Crossref PubMed Google Scholar, 17Mayberry J.F. Rhodes J. Newcombe R.G. Increased sugar consumption in Crohn's disease.Digestion. 1980; 20: 323-326Crossref PubMed Google Scholar, 18Rawcliffe P.M. Truelove S.C. Breakfast and Crohn's disease--I.Br Med J. 1978; 2: 539-540Crossref PubMed Google Scholar, 19Reif S. Klein I. Lubin F. et al.Pre-illness dietary factors in inflammatory bowel disease.Gut. 1997; 40: 754-760Crossref PubMed Google Scholar, 20Tragnone A. Valpiani D. Miglio F. et al.Dietary habits as risk factors for inflammatory bowel disease.Eur J Gastroenterol Hepatol. 1995; 7: 47-51PubMed Google Scholar although others suggest that this reflects a “modern lifestyle” and is not necessarily causal. Evidence is lacking for UC. A randomized, controlled, multicenter study, including 352 patients with CD compared diets rich either in carbohydrate in its refined form or carbohydrate in its natural unrefined form without finding a significant difference in worsening clinical disease activity.10Ritchie J.K. Wadsworth J. Lennard-Jones J.E. et al.Controlled multicentre therapeutic trial of an unrefined carbohydrate, fibre rich diet in Crohn's disease.Br Med J (Clin Res Ed). 1987; 295: 517-520Crossref PubMed Scopus (86) Google Scholar Another randomized, controlled, multicenter dietary study, including 134 patients with CD in remission21Lorenz-Meyer H. Bauer P. Nicolay C. et al.Omega-3 fatty acids and low carbohydrate diet for maintenance of remission in Crohn's disease. A randomized controlled multicenter trial. Study Group Members (German Crohn's Disease Study Group).Scand J Gastroenterol. 1996; 31: 778-785Crossref PubMed Scopus (184) Google Scholar who were instructed either to adhere to a low-carbohydrate diet (of <84 g per day), mainly in a fiber-rich form, or diet as usual. The intention-to-treat analysis showed no significant difference relative to the control group for prevention of relapse after 1 year, although patients seemed to have a symptomatic benefit during time that they adhered to the diet. A small uncontrolled study of the specific carbohydrate diet that excludes sucrose and other refined sugars, fructose, and other refined sugars demonstrated reductions in symptoms and mucosal inflammation as assessed by capsule endoscopy among children with CD.22Cohen S.A. Gold B.D. Oliva S. et al.Clinical and mucosal improvement with specific carbohydrate diet in pediatric Crohn disease.J Pediatr Gastroenterol Nutr. 2014; 59: 516-521Crossref PubMed Scopus (86) Google Scholar There is no evidence of a role for altering the intake of slowly absorbed and nondigestible short-chain carbohydrates (collectively known as FODMAPs) in modulating inflammatory activity of IBD.23Cox S.R. Prince A.C. Myers C.E. et al.Fermentable carbohydrates [FODMAPs] exacerbate functional gastrointestinal symptoms in patients with inflammatory bowel disease: a randomised, double-blind, placebo-controlled, cross-over, re-challenge trial.J Crohns Colitis. 2017; 11: 1420-1429Crossref PubMed Scopus (30) Google Scholar Placebo-controlled trials involving 15 g/day fructo-oligosaccharides in patients with CD11Benjamin J.L. Hedin C.R. Koutsoumpas A. et al.Randomised, double-blind, placebo-controlled trial of fructo-oligosaccharides in active Crohn's disease.Gut. 2011; 60: 923-929Crossref PubMed Scopus (171) Google Scholar and challenge for 3 days with specific FODMAPs in patients with quiescent IBD did not significantly change inflammatory activity,24Prince A.C. Myers C.E. Joyce T. et al.Fermentable carbohydrate restriction (Low FODMAP Diet) in clinical practice improves functional gastrointestinal symptoms in patients with inflammatory bowel disease.Inflamm Bowel Dis. 2016; 22: 1129-1136Crossref PubMed Scopus (69) Google Scholar although fructans in both induced symptoms. Lowering of FODMAP intake in patients with symptomatic but quiescent IBD was associated with amelioration of functional gastrointestinal symptoms in an uncontrolled study25Gibson P.R. Use of the low-FODMAP diet in inflammatory bowel disease.J Gastroenterol Hepatol. 2017; 32: 40-42Crossref PubMed Scopus (22) Google Scholar in comparison with those on a placebo diet without change in inflammatory status,24Prince A.C. Myers C.E. Joyce T. et al.Fermentable carbohydrate restriction (Low FODMAP Diet) in clinical practice improves functional gastrointestinal symptoms in patients with inflammatory bowel disease.Inflamm Bowel Dis. 2016; 22: 1129-1136Crossref PubMed Scopus (69) Google Scholar, 25Gibson P.R. Use of the low-FODMAP diet in inflammatory bowel disease.J Gastroenterol Hepatol. 2017; 32: 40-42Crossref PubMed Scopus (22) Google Scholar, 26Cox S.R. Lindsay J.O. Fromentin S. et al.Effects of Low FODMAP Diet on symptoms, fecal microbiome, and markers of inflammation in patients with quiescent inflammatory bowel disease in a randomized trial.Gastroenterology. 2020; 158: 176-188Abstract Full Text Full Text PDF PubMed Google Scholar suggesting that these patients suffered from concomitant irritable bowel syndrome. Similar findings were noted in a feeding crossover study.27Halmos E.P. Christophersen C.T. Bird A.R. et al.Consistent prebiotic effect on gut microbiota with altered FODMAP intake in patients with Crohn's disease: a randomised, controlled cross-over trial of well-defined diets.Clin Transl Gastroenterol. 2016; 7: e164Crossref PubMed Google Scholar In CD, there is insufficient evidence to recommend restriction of wheat and gluten (EL Low). In UC, there is insufficient evidence to recommend restriction of wheat and gluten (EL Low). Current evidence for restriction is based largely on 3 cross-sectional surveys where the prevalence of presumed gluten-associated symptoms was 5%–28% in patients with IBD (Supplementary Table 2).28Aziz I. Branchi F. Pearson K. et al.A study evaluating the bidirectional relationship between inflammatory bowel disease and self-reported non-celiac gluten sensitivity.Inflamm Bowel Dis. 2015; 21: 847-853Crossref PubMed Scopus (27) Google Scholar, 29Herfarth H.H. Martin C.F. Sandler R.S. et al.Prevalence of a gluten-free diet and improvement of clinical symptoms in patients with inflammatory bowel diseases.Inflamm Bowel Dis. 2014; 20: 1194-1197Crossref PubMed Scopus (58) Google Scholar, 30Limketkai B.N. Sepulveda R. Hing T. et al.Prevalence and factors associated with gluten sensitivity in inflammatory bowel disease.Scand J Gastroenterol. 2018; 53: 147-151Crossref PubMed Scopus (7) Google Scholar Presumed gluten-associated symptoms were more common among those with stricturing or more severe CD and active disease.28Aziz I. Branchi F. Pearson K. et al.A study evaluating the bidirectional relationship between inflammatory bowel disease and self-reported non-celiac gluten sensitivity.Inflamm Bowel Dis. 2015; 21: 847-853Crossref PubMed Scopus (27) Google Scholar,30Limketkai B.N. Sepulveda R. Hing T. et al.Prevalence and factors associated with gluten sensitivity in inflammatory bowel disease.Scand J Gastroenterol. 2018; 53: 147-151Crossref PubMed Scopus (7) Google Scholar In one study of gluten restriction, a high prevalence (65%) of patients observed improvements in 1 or more IBD symptoms, 38% described reduced frequency and severity of disease flares, and strict dietary adherence was associated with marked improvement in fatigue.29Herfarth H.H. Martin C.F. Sandler R.S. et al.Prevalence of a gluten-free diet and improvement of clinical symptoms in patients with inflammatory bowel diseases.Inflamm Bowel Dis. 2014; 20: 1194-1197Crossref PubMed Scopus (58) Google Scholar There are no data to indicate whether mucosal healing can be achieved via this dietary approach. Because gluten coexists in cereals with FODMAPs, improved symptoms might be related to reduced FODMAP intake. Gluten is hypothesized to modulate immune pathways in the small intestine,31Levine A. Sigall Boneh R. Wine E. Evolving role of diet in the pathogenesis and treatment of inflammatory bowel diseases.Gut. 2018; 67: 1726-1738Crossref PubMed Scopus (39) Google Scholar but the only supportive evidence comes from tumor necrosis factor knockout mice.32Wagner S.J. Schmidt A. Effenberger M.J. et al.Semisynthetic diet ameliorates Crohn's disease-like ileitis in TNFDeltaARE/WT mice through antigen-independent mechanisms of gluten.Inflamm Bowel Dis. 2013; 19: 1285-1294Crossref PubMed Scopus (19) Google Scholar Other wheat-protein components, such as amylase trypsin inhibitors, may drive intestinal inflammation.33Junker Y. Zeissig S. Kim S.J. et al.Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4.J Exp Med. 2012; 209: 2395-2408Crossref PubMed Scopus (332) Google Scholar In CD, there is evidence that it is unnecessary to restrict moderate consumption of unprocessed red meat, lean chicken meat (breast of chicken), and eggs (EL high). In UC, it is prudent to reduce intake of red and processed meat (EL low). In a systematic review, 6 of 8 studies demonstrated an association between red meat intake and incidence or worsening of UC, 2 of which were statistically significant. In a prospective French inception cohort of 67,581 people,34Jantchou P. Morois S. Clavel-Chapelon F. et al.Animal protein intake and risk of inflammatory bowel disease: the E3N prospective study.Am J Gastroenterol. 2010; 105: 2195-2201Crossref PubMed Scopus (173) Google Scholar high animal protein intake was associated with a significantly increased risk of IBD, CD, and UC for the highest versus the lowest tertile of consumption (IBD overall hazard ratio, 3.03; 95% confidence interval [CI], 1.45–6.34; Ptrend = .005 corrected for energy intake). Red meat intake was also associated with a greater than 5-fold increase in the odds of a UC relapse in 1 prospective study,35Jowett S.L. Seal C.J. Pearce M.S. et al.Influence of dietary factors on the clinical course of ulcerative colitis: a prospective cohort study.Gut. 2004; 53: 1479-1484Crossref PubMed Scopus (226) Google Scholar but not in a recent smaller study that combined patients with CD and UC.36Opstelten J.L. de Vries J.H.M. Wools A. et al.Dietary intake of patients with inflammatory bowel disease: a comparison with individuals from a general population and associations with relapse.Clin Nutr. 2019; 38: 1892-1898Abstract Full Text Full Text PDF PubMed Google Scholar A cross-sectional study in 103 adults in remission37Tasson L. Canova C. Vettorato M.G. et al.Influence of diet on the course of inflammatory bowel disease.Dig Dis Sci. 2017; 62: 2087-2094Crossref PubMed Scopus (9) Google Scholar also demonstrated a higher risk of relapse with an odds ratio (OR) of 3.6 for the highest quartile of red meat consumption. However, a more recent study38Barnes E.L. Nestor M. Onyewadume L. et al.High dietary intake of specific fatty acids increases risk of flares in patients with ulcerative colitis in remission during treatment with aminosalicylates.Clin Gastroenterol Hepatol. 2017; 15: 1390-1396Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar in 412 adults with UC in remission and followed until relapse demonstrated that the intake of fats and specifically myristic acid was associated with flares, whereas processed meats were not. Myristic acid is a saturated fatty acid enriched in coconut oils and dairy fats, but also in beef from grain-fed cattle.39Daley C.A. Abbott A. Doyle P.S. et al.A review of fatty acid profiles and antioxidant content in grass-fed and grain-fed beef.Nutr J. 2010; 9: 10Crossref PubMed Scopus (345) Google Scholar Red meat was not assessed independently in this study. One prospective clinical trial comparing high versus low levels of consumption of red