Diet 'causes bowel disease'

A high intake of polyunsaturated fat “may lead to inflammatory bowel disease”, BBC News has reported. According to the website, experts believe that a high intake of linoleic acid, found in foods such as margarines may be implicated in a third of ulcerative colitis cases. 

The study underlying this report looked at the diet and lifestyle of over 200,000 people and compared those who developed ulcerative colitis with a sample of those who remained healthy. It found that dietary linoleic acid may play a role in the development of ulcerative colitis. The findings need confirmation in studies of a more robust design as there are some shortcomings with this methodology. However, the results show a ‘dose-response’ relationship, with a higher dose of linoleic acid linked with an increased risk of disease. This supports the idea of a causal relationship.

Even if a causal link between linoleic acid and ulcerative colitis is confirmed, the disease is complex and there are likely to be other factors playing a part too: even this study found that the highest intake levels when grouped were responsible for only 30% of the cases seen. It is important to note that ulcerative colitis is rare, affecting only 1 in 1600 subjects in this study.

Where did the story come from?

Dr Andrew Hart from the University of East Anglia carried out this study. This analysis of data from a larger study was funded by the Sir Halley Stewart Trust, The National Association for Colitis and Crohn’s Disease and the NHS Executive Eastern Region. The study was published in the peer-reviewed medical journal, Gut.

What kind of scientific study was this?

This was a nested case-control study investigating the role of dietary linoleic acid intake and the risk of ulcerative colitis.

Ulcerative colitis, or UC, is a chronic inflammatory bowel condition characterised by ulcers in the colon and a variety of symptoms, including diarrhoea and pain. These symptoms tend to adversely affect a person’s quality of life. Treatment depends on the extent and severity of the disease and often includes drugs or sometimes surgery to remove parts of the bowel.

The data analysed in this research was collected as part of the European Prospective Investigation into Cancer and Nutrition (EPIC) study, set up to examine the role of dietary factors in cancer. The people available for this analysis were a subgroup of those enrolled in the EPIC study between 1991 and 1998. In total 203,193 men and women aged between 30 and 74 years and living in five European countries (Italy, Sweden, Denmark, Germany and the UK) were enrolled.

When they entered the study, the participants provided dietary information through country-specific food-frequency questionnaires and information about their lifestyle, including factors such as physical activity, smoking habits and alcohol intake. Responses to the food questionnaires  were used to calculate intake of a number of fatty acids such as linoleic acid (n-6 PUFA), a-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid (n-3 PUFAs) and oleic acid (an n-9 monounsaturated fatty acid).

New cases of ulcerative colitis up until 2004 were identified using disease registries in Italy, Sweden and Denmark and through follow-up questionnaires and hospital and pathology records in Germany and the UK. People who had UC at the beginning of the EPIC study and those who were diagnosed less than 18 months after recruitment into EPIC were excluded from this analysis.

Each new case of UC was matched with four randomly selected control subjects from the same treatment centre. These were matched on the basis of gender, date of birth and study recruitment date.

Fatty acid intake was divided into quartiles (where intake is divided into four ranges) and the relationship between each quartile and the risk of UC was calculated. The author also calculated the attributable risk, which is a measure of the proportion of the cases that are due to exposure to the fatty acids in question, based on the assumption they can cause UC.

When performing his analysis the author took into account the influence of confounding factors such as age, total energy intake, physical activity, smoking, gender and treatment centre. When investigating the effect of one particular fatty acid, the researchers adjusted for intake of the other acids: oleic acid and α-linolenic acid affect the way the body metabolises linoleic acid and there are anti-inflammatory properties associated with two of the fatty acids, eicosapentaenoic acid and docosahexaenoic acid.

What were the results of the study?

During the course of the follow-up, 126 people initially free of the disease developed ulcerative colitis. These were matched with 504 control subjects. People in the highest quartile of reported linoleic acid intake had a 2.5 times greater risk of ulcerative colitis after adjustment for confounding factors [odds ratio 2.49 (95%CI, 1.23 to 5.07, p=0.01)].

When the analysis was split by gender, this increased risk was only apparent in women. There was a statistically significant trend across the quartiles, suggesting a response that was sensitive to the dose of linoleic acid eaten, i.e. the greater the intake the greater the risk.

The researchers determined that 30% of the cases of ulcerative colitis (around 38 cases) seen were due to intakes of linoleic acid within the highest three quartiles. Intake of docosahexaenoic acid was found to reduce the risk of ulcerative colitis, with the highest quartile of intake being associated with a 77% reduction in risk. There were no significant associations with the other fatty acids.

What interpretations did the researchers draw from these results?

The researchers say that these data ‘support a role for dietary linoleic acid’ in the causes of ulcerative colitis.

What does the NHS Knowledge Service make of this study?

This nested case-control study provides some evidence of a link between intake of linoleic acid and the risk of ulcerative colitis. Importantly, only a small number of people developed this disease over the follow-up period in this study showing that regardless of diet, the disease is a rare one. There are several other points to highlight when considering the results of this study:

• A nested case-control study such as this has some advantages over a usual case-control study. As the data comes from an underlying prospective cohort study, researchers can be sure that the measure of exposure (i.e. consumption of fatty acids) happened before the disease developed.
• However, there are also some shortcomings, such as the study relying only on measures of diet, taken at the beginning of the study. It is unlikely that participants had exactly the same diet throughout the approximately four years of follow-up, and any dietary changes from the baseline and their effects would not have been captured in this methodology.
• Similarly, smoking data was not available during the follow-up.
• The researchers determine that 30% of the cases of ulcerative colitis that developed (i.e. 38 cases) could be attributed to the highest three quartiles of intake of linoleic acid. This leaves 70% of cases, 88 people, whose UC had nothing to do with how much linoleic acid they ate.
• The research does not take into account several other factors that may play a role in the development of this disease, including other aspects of diet such as fibre and milk intake or factors such as genetics and socioeconomic factors.
• The researchers also note that the people in the EPIC study were largely middle-aged to elderly so it may not be appropriate to generalise these findings to those of younger age. This also raises further questions as UC often first presents itself in those of a younger age,

Ulcerative colitis is a complex disease that is likely to have a number of causes, one of which may be diet. This study suggests that a high intake of linoleic acid may increase the risk of ulcerative colitis, which is an important finding as the link is biologically plausible and there is some other epidemiological evidence to support the theory.