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Original research
Lifestyle factors for the prevention of inflammatory bowel disease
  1. Emily W Lopes1,2,
  2. Simon S M Chan3,4,
  3. Mingyang Song1,2,5,6,
  4. Jonas F Ludvigsson7,8,
  5. Niclas Håkansson9,
  6. Paul Lochhead1,2,
  7. Allan Clark4,
  8. Kristin E Burke1,2,
  9. Ashwin N Ananthakrishnan1,2,
  10. Amanda J Cross10,11,
  11. Domenico Palli12,
  12. Manuela M Bergmann13,
  13. James M Richter1,
  14. Andrew T Chan1,2,14,
  15. Ola Olén15,16,
  16. Alicja Wolk9,17,
  17. Hamed Khalili1,2,18
  18. EPIC-IBD investigators
    1. 1 Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
    2. 2 Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA
    3. 3 Department of Gastroenterology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK
    4. 4 Norwich Medical School, University of East Anglia, Norwich, UK
    5. 5 Department of Epidemiology, Harvard University T.H. Chan School of Public Health, Boston, Massachusetts, USA
    6. 6 Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA
    7. 7 Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
    8. 8 Department of Pediatrics, Orebro universitet, Orebro, Sweden
    9. 9 Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
    10. 10 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
    11. 11 Cancer Screening & Prevention Research Group, Department of Surgery & Cancer, Imperial College London, London, UK
    12. 12 Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network—ISPRO, Florence, Italy
    13. 13 Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrucke, Nuthetal, Germany
    14. 14 Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
    15. 15 Department of Medicine, Solna, Clinical Epidemiology Unit, Karolinska institutet, Stockholm, Sweden
    16. 16 Pediatric Gastroenterology Unit, Sachs' Children's Hospital, Stockholm, Sweden
    17. 17 Department of Surgical Sciences, Uppsala Universitet, Uppsala, Sweden
    18. 18 Broad Institute, of MIT and Harvard, Cambridge, MA, USA
    1. Correspondence to Dr Hamed Khalili, Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA; hkhalili{at}


    Objective To estimate the proportion of cases of Crohn’s disease (CD) and ulcerative colitis (UC) that could be prevented by modifiable lifestyle factors.

    Design In a prospective cohort study of US adults from the Nurses’ Health Study (NHS; n=72 290), NHSII (n=93 909) and Health Professionals Follow-up Study (HPFS; n=41 871), we created modifiable risk scores (MRS; 0–6) for CD and UC based on established lifestyle risk factors, and healthy lifestyle scores (HLS; 0–9) derived from American healthy lifestyle recommendations. We calculated the population attributable risk by comparing the incidence of CD and UC between low-risk (CD-MRS≤1, UC-MRS≤2, HLS≥7) and high-risk groups. We externally validated our findings in three European cohorts: the Swedish Mammography Cohort (n=37 275), Cohort of Swedish Men (n=40 810) and European Prospective Investigation into Cancer and Nutrition (n=404 144).

    Results Over 5 117 021 person-years of follow-up (NHS, HPFS: 1986–2016; NHSII: 1991–2017), we documented 346 CD and 456 UC cases. Adherence to a low MRS could have prevented 42.9% (95% CI 12.2% to 66.1%) of CD and 44.4% (95% CI 9.0% to 69.8%) of UC cases. Similarly, adherence to a healthy lifestyle could have prevented 61.1% (95% CI 16.8% to 84.9%) of CD and 42.2% (95% CI 1.7% to 70.9%) of UC cases. In our validation cohorts, adherence to a low MRS and healthy lifestyle could have, respectively, prevented 43.9%–51.2% and 48.8%–60.4% of CD cases and 20.6%–27.8% and 46.8%–56.3% of UC cases.

    Conclusions Across six US and European cohorts, a substantial burden of inflammatory bowel diseases risk may be preventable through lifestyle modification.

    • crohn's disease
    • ulcerative colitis
    • diet
    • epidemiology

    Data availability statement

    Data are available upon reasonable request. Further information including the procedures to obtain and access data from the Nurses’ Health Studies and Health Professionals Follow-up Study is described at (contact email: and

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    Data availability statement

    Data are available upon reasonable request. Further information including the procedures to obtain and access data from the Nurses’ Health Studies and Health Professionals Follow-up Study is described at (contact email: and

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    • Contributors EWL and HK were involved in the study concept and design. EWL, SC, KEB, PL, ANA, MMB, JMR, ATC and HK participated in acquisition of data. EWL, SC, MS, NH, AClark and HK were involved in statistical analysis. All authors participated in interpretation of data. EWL and HK performed drafting of the manuscript. All authors participated in critical revision of the manuscript. Authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. HK acts as guarantor for this work.

    • Funding Funded by UM1 CA186107 NHS cohort infrastructure grant, U01 CA176726 NHSII cohort infrastructure grant and U01 CA167552 HPFS cohort infrastructure grant; the content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work is also funded by the VR 2017-00644 SMC and CoSM cohorts Swedish research infrastructure (SIMPLER) grant. The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the department of epidemiology and biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS)—Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology—ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom). This study was also funded by a senior research award from the Crohn’s and Colitis Foundation to HK and a senior research award from the Crohn’s and Colitis Foundation to ATC. EWL was funded from NIH T32 DK007191 during work on this manuscript and is currently funded by an American College of Gastroenterology junior faculty development award.

    • Competing interests HK is supported by the American College of Gastroenterology Senior Research Award and the Beker Foundation; HK has received consulting fees from Abbvie and Takeda; HK has also received grant funding from Pfizer and Takeda. ATC is the Stuart and Suzanne MGH Research Scholar. JFL reports funding from Janssen corporation for work unrelated to this manuscript. OO has been PI on projects at Karolinska Institutet, partly financed by investigator-initiated grants from Janssen, Takeda and Ferring, and Karolinska Institutet has received fees for lectures and participation on advisory boards from Janssen, Ferring, Takeda and Pfizer; OO also reports a grant to Karolinska Institutet from Pfizer in the context of a national safety monitoring program. ATC has received consulting fees from Bayer Pharma AG, Pfizer and Boehringer Ingelheim for work unrelated to this manuscript. SC has received travel grants from Abbvie and Takeda.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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