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Association between fish consumption, long chain omega 3 fatty acids, and risk of cerebrovascular disease: systematic review and meta-analysis

BMJ 2012; 345 doi: (Published 30 October 2012) Cite this as: BMJ 2012;345:e6698
  1. Rajiv Chowdhury, research associate1,
  2. Sarah Stevens, public health registrar5,
  3. Donal Gorman, PhD candidate1,
  4. An Pan, research associate2,
  5. Samantha Warnakula, PhD candidate1,
  6. Susmita Chowdhury, research associate6,
  7. Heather Ward, research fellow4,
  8. Laura Johnson, epidemiologist1,
  9. Francesca Crowe, nutritional epidemiologist3,
  10. Frank B Hu, professor2,
  11. Oscar H Franco, professor17
  1. 1Department of Public Health and Primary Care, University of Cambridge, UK
  2. 2Department of Nutrition, Harvard School of Public Health, Boston, USA
  3. 3Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, UK
  4. 4Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, UK
  5. 5Public Health Directorate, NHS Midlands and East, Fulbourn, Cambridge, UK
  6. 6Public Health Genomics Foundation, Cambridge, UK
  7. 7Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands
  1. Correspondence to: O H Franco o.franco{at}
  • Accepted 24 September 2012


Objective To clarify associations of fish consumption and long chain omega 3 fatty acids with risk of cerebrovascular disease for primary and secondary prevention.

Design Systematic review and meta-analysis.

Data sources Studies published before September 2012 identified through electronic searches using Medline, Embase, BIOSIS, and Science Citation Index databases.

Eligibility criteria Prospective cohort studies and randomised controlled trials reporting on associations of fish consumption and long chain omega 3 fatty acids (based on dietary self report), omega 3 fatty acids biomarkers, or supplementations with cerebrovascular disease (defined as any fatal or non-fatal ischaemic stroke, haemorrhagic stroke, cerebrovascular accident, or transient ischaemic attack). Both primary and secondary prevention studies (comprising participants with or without cardiovascular disease at baseline) were eligible.

Results 26 prospective cohort studies and 12 randomised controlled trials with aggregate data on 794 000 non-overlapping people and 34 817 cerebrovascular outcomes were included. In cohort studies comparing categories of fish intake the pooled relative risk for cerebrovascular disease for 2-4 servings a week versus ≤1 servings a week was 0.94 (95% confidence intervals 0.90 to 0.98) and for ≥5 servings a week versus 1 serving a week was 0.88 (0.81 to 0.96). The relative risk for cerebrovascular disease comparing the top thirds of baseline long chain omega 3 fatty acids with the bottom thirds for circulating biomarkers was 1.04 (0.90 to 1.20) and for dietary exposures was 0.90 (0.80 to 1.01). In the randomised controlled trials the relative risk for cerebrovascular disease in the long chain omega 3 supplement compared with the control group in primary prevention trials was 0.98 (0.89 to 1.08) and in secondary prevention trials was 1.17 (0.99 to 1.38). For fish or omega 3 fatty acids the estimates for ischaemic and haemorrhagic cerebrovascular events were broadly similar. Evidence was lacking of heterogeneity and publication bias across studies or within subgroups.

Conclusions Available observational data indicate moderate, inverse associations of fish consumption and long chain omega 3 fatty acids with cerebrovascular risk. Long chain omega 3 fatty acids measured as circulating biomarkers in observational studies or supplements in primary and secondary prevention trials were not associated with cerebrovascular disease. The beneficial effect of fish intake on cerebrovascular risk is likely to be mediated through the interplay of a wide range of nutrients abundant in fish.


  • Contributors: OHF and RC conceived the study. RC, SS, and DG did the analyses. SS, RC, DG, SW, SC, HW, and OHF did the literature searches and data extraction. RC, SS and OHF wrote the manuscript. AP, FBH, FC, and LJ contributed to the initial revision of the manuscript. RC, OHF, FC, LJ, AP, and FBH contributed to the critical revision of the manuscript before publication. SS and DG contributed equally to the study. OHF is the guarantor.

  • Funding: RC is recipient of a Gates Cambridge PhD scholarship, DG and SW are supported by funding from MRC studentships, and OHF is the recipient of a grant from Pfizer Nutrition to establish a new centre on aging research focused on nutrition and lifestyle.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Not required.

  • Data sharing: No additional data available.

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