Editorials

Dietary treatment of active Crohn's disease

Oral corticosteroids (usually prednisolone) have long been the standard treatment for active Crohn's disease, being used within 10 years of diagnosis in 55% of patients. Their efficacy has been established in two multicentre, placebo controlled trials.^{1 2} After four months, remission was shown in 60-83% of patients compared with 30-38% of those receiving placebo. However, there is currently much concern over side effects. In the short term these trials showed that corticosteroid treatment significantly increased the prevalence of cutaneous problems (moon face, acne, bruising, and striae), hypertension, and infections. In the long term there is concern over osteoporosis. Although the exact incidence is not known, substantial bone loss has been shown in patients taking at least 7.5 mg prednisolone daily, and about a quarter of patients receiving long term treatment will experience a fracture.³

For these reasons, other treatments have been sought. In the past 12 years dietary treatment has been investigated in several centres with diets differing in their presentation of nitrogen: elemental diets containing nitrogen as free amino acids, oligopeptide diets containing short chain peptides of 4-5 amino acids, and polymeric diets containing whole protein. Such diets are given orally or by nasogastric tube for two to four weeks, and all other food and drink except water is withheld. The theory is that an elemental diet might induce remission by reducing the immunological stimulation caused by whole protein while at the same time providing both nutrition and, by virtue of low residue, bowel rest.

View larger version (26K): [in this window] [in a new window]   Pooled data from trials comparing dietary treatment with corticosteroids for treating active Crohn's disease. Bars show 95% confidence intervals for difference in percentage of patients receiving each treatment going into remission

The issue is not whether dietary treatment is better than corticosteroids, which are undoubtedly effective, but whether it is as good as corticosteroids at inducing remission while causing fewer side effects and being more acceptable to the patient. Several studies have compared dietary treatment with corticosteroids,^{4 5 6 7 8 9} and the results are shown in the figure. Each bar represents pooled data from all similar trials and is presented both in "intention to treat" form and after exclusion of all patients who could not tolerate either treatment. The dropout rate due to intolerance to the diets was high (11/33 on elemental diet, 7/55 on oligopeptide diet, and 23/75 on polymeric diet), giving a significant advantage for corticosteroids in all the trials. If intolerant patients are excluded the studies do show (at least for the elemental and polymeric diets) that diet may be as effective as corticosteroids. To show with adequate certainty that dietary treatment is as good as, or at least no more than 10% worse than, corticosteroids at inducing remission (with a level of significance of 10% and a power of 80%), we estimate that 145 patients would need to receive each treatment. A trial of this size is unlikely to be carried out given the poor tolerance of diet.

The intolerance was investigated by Teahon et al in a questionnaire survey of 89 patients receiving elemental diet.¹⁰ Nausea and postural hypotension were common in the first week, but after that only six patients found taste to be a problem. The main obstacle was usually the large volume of the diet (more than two litres a day), and only 65% of the patients said they would opt for the same treatment again. In our experience patients usually find the diet more tolerable if taken chilled. Alternatively, it can be taken by nasogastric tube. Manufacturers are trying to improve palatability, and the most commonly used elemental diet (E028, Scientific Hospital Supplies) is now available in prepared cartons with a taste similar to that of many soft drinks.

We think that, unless dietary treatment can be made more acceptable, a definitive trial comparing it with corticosteroids is not warranted. However, dietary treatment may still have a role as an adjunct to corticosteroid treatment,¹¹ and confirmatory studies would be useful. Meanwhile, dietary treatment as a single agent should be available for those patients who do not want, or cannot tolerate, corticosteroids. Patients with Crohn's disease are often malnourished, and at the very least an elemental diet, which is absorbed high in the small bowel, is likely to be helpful at maintaining nutrition. If dietary treatment is used there are unproved but theoretical reasons to prefer elemental diet over polymeric diet.

Recently, oral budesonide has been shown to be better than placebo and similar to prednisolone in treating small bowel disease,¹² and it seems to be largely free from many of the common short term side effects of corticosteroids. If it also proves to be freer of long term effects such as osteoporosis, it will have many of the hoped for advantages of an elemental diet and further reduce the need for dietary treatment.

Nick Wright, Registrar,^a Brian B Scott, Consultant ^a

^a Department of Gastroenterology, County Hospital, Lincoln LN2 5QY

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