Linoleic acid, a dietary n-6 polyunsaturated fatty acid, and the aetiology of ulcerative colitis: a nested case–control study within a European prospective cohort study
- The IBD in EPIC Study Investigators
- Correspondence to Dr A Hart, University of East Anglia, Norwich, NR4 7TJ, UK;
- Revised 21 May 2009
- Accepted 6 June 2009
- Published Online First 23 July 2009
Objective: Dietary linoleic acid, an n-6 polyunsaturated fatty acid, is metabolised to arachidonic acid, a component of colonocyte membranes. Metabolites of arachidonic acid have pro-inflammatory properties and are increased in the mucosa of patients with ulcerative colitis. The aim of this investigation was to conduct the first prospective cohort study investigating if a high dietary intake of linoleic acid increases the risk of developing incident ulcerative colitis.
Design and setting: Dietary data from food frequency questionnaires were available for 203 193 men and women aged 30–74 years, resident in the UK, Sweden, Denmark, Germany or Italy and participating in a prospective cohort study, the European Prospective Investigation into Cancer and Nutrition (EPIC). These participants were followed up for the diagnosis of ulcerative colitis. Each case was matched with four controls and the risk of disease calculated by quartile of intake of linoleic acid adjusted for gender, age, smoking, total energy intake and centre.
Results: A total of 126 participants developed ulcerative colitis (47% women) after a median follow-up of 4.0 years (range, 1.7–11.3 years). The highest quartile of intake of linoleic acid was associated with an increased risk of ulcerative colitis (odds ratio (OR) = 2.49, 95% confidence interval (CI) = 1.23 to 5.07, p = 0.01) with a significant trend across quartiles (OR = 1.32 per quartile increase, 95% CI = 1.04 to 1.66, p = 0.02 for trend).
Conclusions: The data support a role for dietary linoleic acid in the aetiology of ulcerative colitis. An estimated 30% of cases could be attributed to having dietary intakes higher than the lowest quartile of linoleic acid intake.
Funding This analysis was funded by The Sir Halley Stewart Trust, The National Association for Colitis and Crohn’s Disease and The NHS Executive Eastern Region. EPIC-Norfolk is supported by Cancer Research UK and The Medical Research Council, UK. EPIC-Malmö is supported by The Swedish Cancer Society, The Swedish Research Council and The Region of Skane. EPIC-Denmark is supported by The Danish Cancer Society. EPIC-Heidelberg is supported by “Stiftung Landesbank Baden-Württemberg”, the European Union and Deutsche Krebshilfe. EPIC-Potsdam is supported by the Federal Ministry of Research and Technology, the European Union and Deutsche Krebshilfe. EPIC-Florence is supported by the Associazione Italiana per la Ricerca contro il Cancro (AIRC-Milan) and Regione Toscana.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.
See Commentary, p 1577
Ethics approval The names and locations of the ethics committees that approved the collection of data were: Norwich District Ethics Committee, UK; Ethical Committee of the Medical Faculty at the University of Heidelberg, Germany; Regionala etikprövningsnämnden i Umeå, Sweden; De Videnskabsetiske Komitéer for Region Hovedstaden, Regionsgården, Denmark; Comitato Etico Locale dell ‘Azienda Sanitaria di Firenze, Italy; Ethics Committee at The Medical Association of the State of Brandenburg in Cottbus, Germany; and Lund University Ethics Committee, Sweden.
List of collaborators and authors
A Tjonneland (Head of Department) and A Olsen (Post-doctoral Researcher), Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark
K Overvad (Professor of Clinical Epidemiology), Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark
MM Bergmann (Scientist) and H Boeing (Head of the Department of Epidemiology), Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Nuthetal, Potsdam, Germany
G Nagel (Senior Researcher), Division of Clinical Epidemiology, DKFZ-Heidelberg, Heidelberg, Germany; and Institute of Epidemiology, Ulm University, Ulm, Germany
J Linseisen (Principal Investigator EPIC-Heidelberg), Division of Clinical Epidemiology, Division of Clinical Epidemiology, DKFZ-Heidelberg, Heidelberg, Germany
G Hallmans (Professor of Nutritional Research) and Å Danielsson (Professor of Gastroenterology), Department of Public Health & Clinical Medicine, Umeå University, Umeå, Sweden
R Palmqvist (Senior Lecturer), Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden
H Sjodin (Statistician Medical Biobank), Umeå University Hospital, Umeå, Sweden
G Hägglund (Research Assistant), Department of Nutritional Research, Umeå University, Umeå, Sweden
G Berglund (Professor of Medicine), S Lindgren (Professor of Gastroenterology) and O Grip (Consultant Gastroenterologist), Department of Clinical Sciences, University Hospital MAS, Malmö, Sweden
D Palli (Head of Department) and G Masala (Research Scientist), Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Centre – ISPO, Florence, Italy
NE Day (Emeritus Professor of Epidemiology), R Luben (Head of Bioinformatics), and A Welch (Former Head Research Nutritionist), Strangeways Research Laboratory, Cambridge, UK
K-T Khaw (Professor of Clinical Gerontology), Clinical Gerontology Unit, Addenbrooke’s Hospital, Cambridge, UK
S Bingham (Group Leader, Diet and Cancer), MRC Dunn Human Nutrition Unit, Cambridge, UK
E Riboli (Head, Division of Epidemiology, Public Health and Primary Care), Faculty of Medicine, Imperial College London, London, UK
H Kennedy (Consultant Gastroenterologist), Norfolk & Norwich University Hospital NHS Trust, Norwich, UK
A Hart (Senior Lecturer in Gastroenterology), University of East Anglia, Norwich, UK