Enteral nutrition and partial enteral nutrition
We chose to discuss an enteral diet because of its demonstrated efficacy as a steroid-sparing agent in the treatment of Crohn’s disease [1••]. Exclusive enteral nutrition (EEN) is not effective for UC. EEN is intake of only liquid formulas without the intake of foods usually for a period of 6–8 weeks. It can involve different protein sources and can be classified into three types: elemental (amino acid based), semi-elemental (oligopeptides), and polymeric (whole protein based) formulas. These are hypoallergenic formulas that result in decreased antigen exposure in the intestine. All have similar efficacy . Recent pediatric studies, where the large body of research exists, find that EEN can induce remission in 60–86% of children resulting in decreased biochemical markers of inflammation (CRP, ESR, and fecal calprotectin) [5, 6•, 7,8,9]. This is particularly attractive in pediatrics, because intake of EEN can replace steroid use and therefore result in better bone growth and child development. A recent open-label non-placebo-controlled pediatric study assessed achievement of mucosal healing with the use of 8 weeks of EEN in combination with azathioprine and found mucosal healing was observed in 33% of patients .
However, some challenges to the use of EEN, especially in adults, are its poor tolerability given its taste, and the fact that despite effective remission rates, long-term outcomes like prevention of relapse or complications are no different than with use of steroids [1••]. To tackle the issue of poor taste, researchers have looked into partial EEN when in combination with dietary therapies . Research groups have employed strategies to either use high-volume enteral nutrition (77% energy intake) with ad lib food intake or specific food-group exclusion diets, in order to allow patients free food intake while at the same time providing nutrition through enteral feeds. These studies unfortunately show that intake of some whole foods and partial EEN was not as effective as EEN . One study found similar remission rates in patients treated with either infliximab or EEN (ranging from 73 to 76%) compared to a lower rate in patients treated with partial enteral nutrition (at 50%) . Similarly, fecal calprotectin measurements were lower (< 250 mcg/ml) in those treated with EEN (45%) compared to those treated with partial enteral nutrition (14%). In mild to moderate luminal CD, partial enteral nutrition with adjunctive whole foods following the CD-elimination diet (described in detail below) found clinical remission rates of 70% in children and 69% in adults, with normalization of CRP in 70% of patients in remission .
Recent studies conducted demonstrate that EEN can be useful in the setting of complicated CD with either inflammatory strictures or enterocutaneous fistulas. In one prospective CD study, 65 patients with inflammatory strictures were included and given EEN therapy for 12 weeks. Among patients who completed the EEN (50 patients, 84.7% of participants), inflammatory strictures were noted to improve using average luminal cross-sectional area at the site of the stricture on cross-sectional imaging . Similarly, in a study including 48 CD patients with enterocutaneous fistulas who were treated with short-peptide based EN for 3 months, there was successful closure of E-C fistulas in 62.5% of patients . Finally, there is also a growing body of evidence indicating that EEN can be used in the pre-operative setting to prevent post-operative complications or even surgery altogether [15, 16]. In one retrospective cohort, 13 out of 51 patients (25%) were able to avoid surgery for intestinal resection after employment of EEN for 6 weeks . In those that did progress, EEN prevented post-op abscess formation or leakage to a greater extent than those who did not use EEN. Other studies show similar reduction in post-op complications, including of endoscopic recurrence in the post-op setting [17, 18]. Taken altogether, EEN is effective as induction therapy for severe CD and can be helpful in prevention of post-op complications, as well as in fistula and stricture closure in complicated CD patients. EEN as long-term therapy however remains a challenge given its lack of palatability and also lack of data looking at efficacy of EEN as maintenance.
In our adult practice, we reserve the use of EEN with semi-elemental or polymeric formulas to patients with severe CD, including those with fistulizing disease (for example in those with enterocutaneous fistulas), who are having difficulty achieving clinical and biochemical response despite aggressive biologic therapy. EEN can also be helpful to optimize nutrition in those with severe CD especially with obstructive symptoms that need surgery. More commonly, we recommend generic formulas such as Boost or Ensure as well as specialty formulas free of common allergens (gluten, soy, dairy, corn, preservative free) such as Orgain or Kate Farms for severely ill patients with aggressive disease and who cannot meet their caloric intake because of symptoms as an adjunct to aggressive medical therapy, e.g., biologics.
Crohn’s disease elimination diet
The CD exclusion diet was developed to allow only access to whole foods, with exclusion of foods that presumably alter host barrier function, result in dysbiosis, and influence bacterial/viral factors that allow bacterial translocation. The food items excluded are hypothesized to alter the microbiome or intestinal permeability. Inflammatory food items excluded in this diet include wheat, dairy, emulsifiers, maltodextrins, carrageenans, and sulfites. There are only two uncontrolled clinical studies in the literature that have examined this diet, both with promising results in a total of 68 patients. In the first study, a total of 47 children and young adults were given partial EN with CD-elimination diet for a period of 6 weeks. Disease activity scores were used and CRP was measured at baseline and the end of the study. Crohn’s disease activity index decreased from 27.7 to 5.4 (p < .001) and CRP normalized in 21 of the 30 patients found to be in clinical remission . In a more recent study, 21 CD patients were included who had loss of response to biologics. These patients were given partial EN with 12 weeks of a CD exclusion diet. These patients with severe flares were given an initial 14 days of EEN followed by partial EN with a polymeric formula and the CD-elimination diet for 12 weeks. Clinical remission rates after 6 weeks were reported at 61.9% with normalization of CRP and albumin levels as well.
Administration of partial EN with a CD-elimination diet is a promising approach for patients with severe CD, in those with loss of response to therapeutic doses of biologics. Larger studies with randomization and comparison groups, including a control group with exclusive intake of EEN, or only the elimination diet, are needed before we can recommend this diet more broadly. In general, the additives targeted for elimination make biological sense to avoid in IBD patients (possibly in many people!). We will discuss wheat below.
Specific carbohydrate diet
The specific carbohydrate diet (SCD), an exclusion diet low in carbohydrates and processed foods, is advocated for both UC and CD. It was developed in the early 1920s for the treatment of celiac disease and has found its way as a diet therapy for the IBD population. It is one of the most popular diets in IBD yet evidence for its efficacy in controlling inflammation is still lacking. It is also a very strict diet that is difficult to maintain. The diet consists of consuming monosaccharides, with restricted intake of polysaccharides and disaccharides (excluding sucrose and certain starches). It allows almost all fruits, some vegetables, nuts, meats, and eggs and avoids as mentioned certain starches (specifically all grains), table sugar, and most preservatives/food additives as well as dairy (except for fermented yogurts and hard cheeses). Several retrospective studies and case series have demonstrated improvement of clinical disease activity scores and biochemical markers of inflammation including CRP, fecal calprotectin, and normalization of serum albumin [19, 20]. A prospective study examined for the first time whether the SCD administered over 52 weeks led to mucosal healing as evidenced by administration of capsule endoscopy at the completion of the study. Out of the 10 pediatric CD patients, a total of 4 achieved mucosal healing by the end of the study and 8 of the 10 showed significant mucosal improvement using the Lewis score .
More recently, a prospective non-placebo-controlled study followed the clinical disease activity, biochemical markers, and gut microbiome composition of pediatric CD patients who agreed to consume a SCD for 12 weeks. At the study completion, the authors noted that CRP and clinical disease activity improved in all 12 recruited patients. Serum albumin levels in patients also normalized by the end of the 12-week period. Interestingly, although no clear dysbiosis was observed as a pattern in the 7 patients with stool available for sequencing, the overall diversity of the flora after 12 weeks on the SCD did shift towards gut flora of controls . The above uncontrolled clinical studies suggest that symptomatic and biochemical improvement is present in CD and UC patients exposed to a specific carbohydrate diet. There are now small studies looking at mucosal healing in patients on a SCD and not all of them show that gut inflammation improved. A recent retrospective study of 7 patients showed that, despite improvement and/or normalization of albumin, CRP, stool calprotectin, and hematocrit, patients on a SCD did not achieve complete mucosal healing (defined as the absence of any ulceration) after an average of 26 months . Given the variability of design and the small sample data available to date, these prior studies should be considered preliminary results wherein larger prospective controlled trials are needed to validate this data. At the present time, there are several randomized controlled trials examining the SCD and we should expect results in the coming years. One specifically compares the efficacy of the SCD to the Mediterranean diet in a multicenter RCT (clinical trial NCT03058679).
The anti-inflammatory diet, a modified version of the SCD, is sometimes advocated by patients, but thus far, only a small case series looking at the beneficial impact of this diet has been published . The development of the anti-inflammatory index demonstrated the association between diet and how it can positively or negatively affect CRP, which has been used as a marker of inflammation in conditions such as rheumatoid arthritis as well as many others .
In our adult practice, we do not currently recommend the SCD in our practice due to the lack of controlled studies validating its efficacy in achieving mucosal healing. While there are elements of this diet, such as avoidance of processed foods, that we consider important, the restrictiveness of this diet usually results in weight loss and ultimately difficulty with adherence. In those who still chose to be on the SCD, we monitor for vitamin D deficiency, which can be especially deficient in IBD patients following this diet .
The autoimmune diet
The autoimmune diet is a modified Paleolithic diet which includes avoidance of gluten and dairy. The dietary instructions are to first initiate an elimination phase and once clinical symptoms and inflammation are controlled, the autoimmune diet includes a 5-week maintenance phase followed by eventual reintroduction of foods, one at a time, in order to allow identification of trigger items. The initial phase requires elimination of several items: grains, processed sugars, oils, alcohol, caffeine, nuts, dairy, eggs, and even legumes. In one open-label observational study, the authors evaluated the efficacy of an autoimmune in patients with UC or CD with evidence of clinical and objective evidence of inflammation (biochemical/imaging/endoscopic inflammation). A total of 15 patients completed the study, 9 with CD and 6 with UC. Participants were coached on an autoimmune diet and clinical symptoms as well as markers of inflammation, CRP, fecal calprotectin, and when available endoscopic inflammation were assessed . The authors found that even in this small subset of patients, there was improvement in their clinical symptoms and in their quality of life scores, with 73% achieving clinical remission in a 6-week period, as well as a decrease in fecal calprotectin. All 11 of the 15 maintained remission during maintenance phase.
In our adult practice, we do not recommend this diet at this time. The autoimmune diet is promising but there are insufficient studies to support its use.