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Ulcerative colitis: is it in the diet?
  1. Franck Carbonnel,
  2. Marie Christine Boutron
  1. Service d’Hépatogastroentérologie, CHU de Bicêtre, Assistance Publique Hôpitaux de Paris, Université Paris Sud, Le Kremlin Bicêtre, and INSERM unit E3N, Institut Gustave Roussy, Villejuif Cedex, France
  1. Correspondence to Dr Franck Carbonnel, Service d’Hépatogastroentérologie, CHU de Bicêtre, Assistance Publique Hôpitaux de Paris, Université Paris Sud, 94275 Le Kremlin Bicêtre, France; franck.carbonnel{at}bct.aphp.fr

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There is some evidence that environmental factors cause ulcerative colitis. The incidence of ulcerative colitis has increased dramatically between World War II and the 1980s.1 More recent data show that, in several areas, ulcerative colitis incidence decreases.2 3 Such large fluctuations are not consistent with a purely genetic disease, although the increased incidence could be attributed to a better recognition of the disease (coinciding with progress in endoscopy) and the recent decline, to a diagnostic transfer from ulcerative colitis to Crohn’s disease. Migrant studies have shown that ulcerative colitis incidence is at least as high in subjects originating from South Asia living in UK than in native British subjects,4 and has increased recently,5 thus suggesting that the British way of life increases the incidence of ulcerative colitis in migrants from Asia. Another evidence for the role of environment in ulcerative colitis comes from twin studies: disease concordance in monozygotic twins is only 19% in ulcerative colitis, as opposed to 50% in Crohn’s disease.6

What are the candidate environmental factors?

Ulcerative colitis is more frequent in non-smokers or ex-smokers than in current smokers, and in patients who have no history of appendectomy for appendicitis. Other environmental factors are likely to contribute to ulcerative colitis pathogenesis. For unexplained reasons, the variability of geographic distribution is lower for ulcerative colitis than for Crohn’s disease.7 However, geographic distributions of these two diseases are correlated, thus suggesting that they may share one or several environmental factors.8 Analysis of time trends of mortality also suggest the presence of one or several related primary risk factors responsible for the occurrence of ulcerative colitis and Crohn’s disease and one (or several) additional secondary risk factor(s) responsible for Crohn’s disease alone.9 Hygiene is a candidate risk factor for both diseases. It is supported by some10 11 but not all12 13 case–control studies. Additionally, the hygiene hypothesis hardly explains the increased incidence of ulcerative colitis and Crohn’s disease recently observed in Japan, a highly hygienic and developed country. By contrast, there is a temporal relationship between the rising incidence of inflammatory bowel disease (IBD) in Japan and changes in dietary habits.14 In fact, diet composition has long been suspected to contribute to ulcerative colitis. Several retrospective case–control studies have investigated the association between diet and the risk of ulcerative colitis. However, described associations between dietary compounds and IBD are prone to recall bias, because of the retrospective design of these studies.15 Therefore, until now, the role of diet in IBD has been doubtful, at best. The prospective study by The IBD in EPIC Study Investigators published in this issue of Gut (see page 1605) is a step forward in this field.16 It shows a significant positive association between the dietary content of linoleic acid and incidence of ulcerative colitis, and a negative one with intake of docosohexaenoic acid. The results are unlikely to be affected by recall, selection and reverse causation biases. Moreover, the results presented were adjusted for the EPIC study centres, thus reducing the possibility that the associations observed are due to genetic or environmental differences between the European centres.

Box 1: Criteria of causality

  • Association is strong

  • Association is constant (found everywhere and every time)

  • Cause precedes effect

  • Dose–effect relationship

  • Cause is biologically plausible

  • Consistent with current knowledge of natural history of the disease

  • Randomised controlled trial is a strong argument

From: Austin Bradford Hill. Environment and causation. Proc Roy Soc Med 1965;58:295–300.

Is the association between polyunsaturated fatty acids in diet and ulcerative colitis causal?

In 1965, Austin Bradford Hill proposed criteria of causality in medicine17 (box 1). He stated that, to be causative, an association between an environmental factor and a disease must be strong and reproducible, the cause must precede the effect, it has to be biologically plausible and consistent with current knowledge of natural history of the disease. There must also be a dose–effect relationship. Finally, a positive randomised controlled trial is strong argument for causality. The work by the ECPI Study Investigators16 satisfies some of these criteria. The association between dietary content of linoleic acid and ulcerative colitis is strong: the attributable fraction for the highest three quartiles of intake of dietary linoleic acid was 30%, ie, nearly a third of cases of ulcerative colitis could be attributed to the intake of that in the highest three quartiles. The cause (high dietary content of linoleic acid) precedes the effect (ulcerative colitis). As discussed by the authors, there is biological plausibility to support the epidemiological results. Linoleic acid is metabolised to arachidonic acid and then to prostaglandin E2, leukotriene B4 and thromboxane B2 which have proinflammatory effects. Conversely, docosahexaenoic acid may prevent colonic inflammation through the release of phospholipases D from membranes, and inhibition of protein kinase C. The associations described fit with temporal and spatial trends in ulcerative colitis. Indeed, red meat and sunflower oil, but not olive oil, are important sources of linoleic acid; such foods are more characteristic of Northern/Western dietary patterns than of Southern/prudent diets. There is a clear dose–effect relationship, at least for docosohexaenoic acid. On the other hand, other criteria of causality are lacking. This study is the first of its nature and it is too early to say if the results are reproducible. More importantly, several clinical trials have tested the hypothesis that increasing the content in n-6 or n-3 fatty acids may respectively increase or decrease Crohn’s disease or ulcerative colitis activity. Unfortunately, most of them were negative.18 19 20

Future directions

The study of dietary factors in IBD aetiology is only beginning. Linoleic and docosohexaenoic acids are unlikely to be the only nutrients associated with ulcerative colitis. Other associations with foods and nutrients, coming from prospective studies, will be described in a near future. The association between fatty acids and ulcerative colitis will therefore have to be contextualised in the light of new results. Taken together, they will allow a protective diet in ulcerative colitis and also in Crohn’s disease to be built.

Many patients believe that diet plays a role in IBD aetiology and relapses. Most physicians tell their patients to eat a normal diet, the only advice being low in residue during relapses and if they have a tight stricture. Is it time to say our patients to decrease their intake of linoleic acid and increase that of docosohexaenoic acid? The answer is “not yet”, mainly because further associations between nutrients and ulcerative colitis incidence are awaited and available randomised trials are negative.

Environmental factors other than diet may potentially contribute to IBD aetiology. The consequences of these associations are important. Indeed, they may lead to prevention of the disease in high risk individuals (or in the general population in areas with high incidence of IBD) and possibly reduction of disease activity in patients.

REFERENCES

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Footnotes

  • Competing interests None.

  • Provenance and peer review Commissioned; not externally peer reviewed.

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