Abstract (as published in BMJ)
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.
Authors’ 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.
O-3s & Cerebrovascular Disease
Chowdhury R Stevens S Gorman D Pan A Warnakula S Chowdhury S Ward H Johnson L Crowe F Hu FB and Franco OH (2012). Association between fish consumption, long chain omega 3 fatty acids, and risk of cerebrovascular disease: systematic review and meta-analysis. BMJ 345:e6698.
Results from the current publication do not change the totality of the publicly available scientific evidence demonstrating a cardiovascular benefit of EPA and DHA in healthy populations, as well as in many populations with pre-existing cardiovascular ailments. Therefore, consumers should continue to eat fish and take their omega-3 products for heart health.
What Else Should You Know?
The studies included in the meta-analyses were not specifically designed to detect an effect on stroke.
The paper reports on three separate meta-analyses and the results must be interpreted as three separate findings. Specific to the analysis of the effects of long-chain O3 supplementation on cerebrovascular risk, in general, the population of interest was diseased, not healthy. More specifically, of the 12 RCTs, only two were primary prevention (subjects w/no CVD at baseline), while the other ten were secondary prevention (subjects w/CVD at baseline). For primary prevention, there are too few studies to draw a supportable conclusion. For secondary prevention, subjects in more recent trials (compared to earlier trials) have been maintained on better and more extensive pharmaceutical regimens which reduce the risk of stroke and make it difficult to detect an O3 benefit.
While the authors concluded that “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”, this conclusion is based on four studies only. In September, two additional studies concluding the opposite were published (Kim et al., 2012; Ikeya et al., 2012).
While not reported in the current publication, a subanalysis of JELIS with respect to stroke incidence demonstrated that EPA administration reduced the risk of stroke in a Japanese population of hypercholesterolemic patients receiving low-dose statin therapy (Tanaka et al., 2008).
The accompanying editorial from De Goede and Geleijnse (2012) provides a much more balanced review.
Accumulating evidence in animal models demonstrates a post-stroke benefit of DHA in attenuating neuronal damage.
Global Organization for EPA and DHA Omega-3s (2012). Omega-3s & Cerebrovascular Disease [Peer commentary on the paper “Association between fish consumption, long chain omega 3 fatty acids, and risk of cerebrovascular disease: systematic review and meta-analysis” by Chowdhury R Stevens S Gorman D Pan A Warnakula S Chowdhury S Ward H Johnson L Crowe F Hu FB and Franco OH (2012). BMJ 345:e6698.].
De Goede J and Geleijnse J (2012). The role of fatty acids from fish in the prevention of stroke. BMJ 345:e7219.
Ikeya Y Fukuyama N Kitajima W Ogushi Y and Mori H (Epub ahead of print 2012 Sept 22). Comparison of eicosapentaenoic acid concentrations in plasma between patients with ischemic stroke and control subjects. Nutrition.
Kim YJ Kim OY Cho Y Chung JH Jung YS Hwang GS and Shin MJ (Epub ahead of print 2012 Sept 20). Plasma phospholipid fatty acid composition in ischemic stroke: Importance of docosahexaenoic acid in the risk for intracranial atherosclerosis stenosis. Atherosclerosis.
Tanaka K Ishikawa Y Yokoyama M Origasa H Matsuzaki M Saito Y Matsuzawa Y Sasaki J Oikawa S Hishida H Itakura H Kita T Kitabatake A Nakaya N Sakata T Shimada K and Shirato K on behalf of the JELIS Investigators (2008). Reduction in the recurrence of stroke by eicosapentaenoic acid for hypercholesterolemic patients: subanalysis of the JELIS trial. Stroke 39:2052-2058.