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Enteral nutritional therapy for induction of remission in Crohn's disease

  • Review
  • Intervention


  • Mary Zachos,

    Corresponding author
    1. The Hospital for Sick Children, Division of Gastroenterology, Hepatology & Nutrition, Toronto, Ontario, Canada
    • Mary Zachos, Division of Gastroenterology, Hepatology & Nutrition, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8, Canada.

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  • Melody Tondeur,

    1. The Hospital for Sick Children, Division of Gastroenterology, Hepatology & Nutrition, Toronto, Ontario, Canada
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  • Anne Marie Griffiths

    1. The Hospital for Sick Children, Division of Gastroenterology, Hepatology & Nutrition, Toronto, Ontario, Canada
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The role of enteral nutrition in Crohn's disease is controversial. Increasing research on the mechanisms by which nutritional therapy improves the clinical well being of patients with Crohn's disease has led to novel formula design and trials comparing two different forms of enteral nutrition. This meta-analysis aims to provide an update on the existing effectiveness data for both corticosteroids versus enteral nutrition and for one form of enteral nutrition versus another for inducing remission of active Crohn's disease.


To evaluate the effectiveness of exclusive enteral nutrition (EN) as primary therapy to induce remission in Crohn's disease and to examine the importance of formula composition on effectiveness.

Search methods

Studies were selected using a computer-assisted search of the on-line bibliographic databases MEDLINE (1966-2006) and EMBASE (1984-2006), as well as the Science Citation Index on Web of Science. Additional citations were sought by manual search of references of articles retrieved from the computerized search, abstracts submitted to major gastroenterologic meetings and published in the journals: American Journal of Gastroenterology, Gut, Gastroenterology, Journal of Pediatric Gastroenterology and Nutrition, and Journal of Parenteral and Enteral Nutrition, and from the reviewers' personal files or contact with leaders in the field.

Selection criteria

All randomized and quasi-randomized controlled trials involving patients with active Crohn's disease defined by a clinical disease activity index were considered for review. Studies evaluating the administration of one type of enteral nutrition to one group of patients and another type of enteral nutrition or conventional corticosteroids to the other group were selected for review.

Data collection and analysis

Data were extracted independently by two authors and any discrepancies were resolved by rereading and discussion. For the dichotomous variable, achievement of remission, individual and pooled trial statistics were calculated as odds ratios (OR) with 95% confidence intervals (CI); both fixed and random effect models were used. The results for each analysis were tested for heterogeneity using the chi square statistic. The studies were separated into two groups: A. one form of enteral nutrition compared with another form of enteral nutrition and B. one form of enteral nutrition compared with corticosteroids. Subgroup analyses were conducted on the basis of clinical or disease criteria and formula composition. Sensitivity analyses were conducted on the basis of the inclusion of abstract publications, methodologic quality and by random or fixed effects models.

Main results

In part A, of the 15 included eligible trials (one abstract) comparing different formulations of EN for the treatment of active CD, 11 compared one (or more) elemental formula to a non-elemental one, three compared enteral diets of similar protein composition but different fat composition, and one compared non-elemental diets differing only in glutamine enrichment. Meta-analysis of ten trials comprising 334 patients demonstrated no difference in the efficacy of elemental versus non-elemental formulas (OR 1.10; 95% CI 0.69 to 1.75). Subgroup analyses performed to evaluate the different types of elemental and non-elemental diets (elemental, semi-elemental and polymeric) showed no statistically significant differences. Further analysis of seven trials including 209 patients treated with EN formulas of differing fat content (low fat: < 20 g/1000 kCal versus high fat: > 20 g/1000 kCal) demonstrated no statistically significant difference in efficacy (OR 1.13; 95% CI 0.63 to 2.01). Similarly, the effect of very low fat content (< 3 g/1000 kCal) or type of fat (long chain triglycerides) were investigated, but did not demonstrate a difference in efficacy in the treatment of active CD, although a non significant trend was demonstrated favoring very low fat and very low long chain triglyceride content. This result should be interpreted with caution due to statistically significant heterogeneity and small sample size. Sensitivity analyses had no significant effects on the results. The role of specific fatty acids or disease characteristics on response to therapy could not be evaluated. In part B, eight trials (including two abstracts) comparing enteral nutrition to steroid therapy met the inclusion criteria for review. Meta-analysis of six trials that included 192 patients treated with enteral nutrition and 160 treated with steroids yielded a pooled OR of 0.33 favouring steroid therapy (95% CI 0.21 to 0.53). A sensitivity analysis including the abstracts resulted in an increase in the number of participants to 212 in the enteral nutrition group and 179 in the steroid group but the meta-analysis yielded a similar result (OR 0.36; 95% CI 0.23 to 0.56). There were inadequate data from full publications to perform further subgroup analyses by age, disease duration and disease location.

Authors' conclusions

Corticosteroid therapy is more effective than enteral nutrition for inducing remission of active Crohn's disease as was found in previous systematic reviews. Protein composition does not influence the effectiveness of EN in the treatment of active CD. A non significant trend favouring very low fat and/or very low long chain triglyceride content exists but larger trials are required to explore the significance of this finding.




腸道營養對於克隆氏症的功效目前還是有爭議的。由於有越來越多關於營養治療對於克隆氏症患者臨床改善機制的研究, 因此出現了新穎的配方設計,並且有研究比較兩種不同的腸道營養形式。本統合分析主要希望能夠提供對於類固醇治療和腸道營養治療,以及兩種不同形式腸道營養治療,對於緩解活性克隆氏症效果的更新數據。




利用電腦輔助搜尋線上書目型資料庫 MEDLINE (1966年–2006年)以及EMBASE (1984–2006年),還有Science Citation Index on Web of Science以挑選出研究。此外並以人工的方式,搜尋從:電腦搜尋、主要腸胃道研討會摘要、期刊刊物:American Journal of Gastroenterology、Gut、 Gastroenterology、Journal of Pediatric Gastroenterology and Nutrition、 Journal of Parenteral and Enteral Nutrition以及所獲文章的參考文獻。






在A部分,有15個可納入的試驗(一篇是摘要),這些試驗是比較使用不同配方的腸道營養來治療活性克隆氏症,其中有11個研究(或是更多)是將元素配方和非元素配方進行一對一比較,3個研究是比較具有相近蛋白質成分但是具有不同脂肪成分的腸道飲食,而另一個研究則是比較不同的非元素飲食,其中各組的差別僅在於麩醯胺酸的含量。對於包括334病患的10個試驗進行統合分析可以證實使用元素或非元素配方的組別在功效上並沒有差異(OR值為1.10,95%CI介於0.69至1.75間),次組別分析的結果顯示對於不同類別的元素和非元素(元素、半要素和聚合)飲食進行評估,顯示並沒有統計上顯著差異;針對包含209名病患的7個試驗進行進一步的分析顯示,使用具有不同脂肪含量(低脂肪:每1000大卡熱量小於20克脂肪,高脂肪:每1000大卡熱量大於20克脂肪)的腸道配方,並沒有在功效上產生統計學上的明顯差異(OR值為1.13,95%CI介於0.63至2.01間),十分相似的,也針對非常低脂肪含量(每1000大卡熱量小於3克脂肪)或是不同類型的脂肪(長鏈三酸甘油脂)進行研究,但是也無法證明對於活性克隆氏症的治療會產生不同效果,雖然使用非常低含量的脂肪或是長鏈三酸甘油脂對於緩解克隆氏症顯示有效的趨勢但卻無統計上顯著的差異,因為研究結果具有統計上顯著異質性,且研究規模較小,所以這個研究應該要被謹慎解釋。 敏感度分析也沒有對結果產生明顯影響,且無法對特定脂肪酸的角色或是對治療產生反應的疾病特徵進行評估。在B部分中,本文獻回顧納入了8個比較腸道營養和類固醇治療效果的試驗(包含兩篇摘要),針對6個試驗進行的統合分析中,有 192名患者使用腸道營養治療,160名患者使用類固醇,其中總合勝率比為0.33,且結果傾向於類固醇治療(95%CI介於0.21至0.53間),針對包括摘要在內進行的敏感度分析中使用腸道營養治療的患者人數增加至212人,使用類固醇的患者人數則增加至179人,但是統合分析結果仍十分相近(OR值為0.36,95%CI介於0.23至0.56間),從公開發表的全文中因無足夠的數據,故無法進一步依年齡、患病期間和患病部位完成次組別分析。



Plain language summary

Enteral nutritional therapy for treatment of active Crohn's disease

Evidence continues to indicate that corticosteroids are more effective than enteral nutrition (liquid food) for treating active Crohn's disease. Comparing one form of enteral nutrition to another has not shown any difference in effectiveness for treating active Crohn's disease, but a non significant trend favouring low fat formulations has emerged. Further research is required.