Abstract MP003: Alpha-linolenic Acid Intake and Biomarker in Relation to Risk of Cardiovascular Disease: A Meta-analysis and Systematic Review

Introduction: Several studies have investigated the association between the plant-based omega-3 alpha-linolenic acid (ALA) and risk of cardiovascular disease (CVD); however, results remain largely inconsistent. We have conducted a meta-analysis of all available epidemiological studies reporting on association between ALA consumption or its biomarker composition and risk of CVD. Methods: A search of MEDLINE, EMBASE, Web of Science, Cochrane Library and clinical trial registry databases (to February 2011) was supplemented by manual searches of bibliographies of retrieved articles and relevant reviews. Prospective cohort or case-control studies were included if they reported the association between ALA (assessed in dietary intake, and as circulating blood or adipose tissue biomarker) and CVD (including myocardial infarction [MI], sudden cardiac arrest, acute coronary syndrome, and stroke). Multivariate-adjusted risk estimate in each study was converted to relative risk (RR) comparing the top vs. bottom thirds of ALA, and were combined using fixed-effect models given that heterogeneity was not detected in most situations. A fixed-effect dose-response meta-analysis was conducted if data were available. Results: Fifteen prospective cohort and 12 case-control studies were identified with aggregate data on 188,896 individuals and 12,233 total CVD events. Comparing the top to bottom thirds, a higher ALA intake was associated with a lower risk of CVD death (RR=0.80; 95% CI 0.67–0.96; 6 cohort studies), but not non-fatal MI (RR=0.95; 95% CI 0.85–1.06; 1 cohort and 2 case-control studies), or total CVD (RR=0.93; 95% CI 0.85–1.02; 1 case-control and 6 cohort studies). Higher ALA biomarker levels in adipose tissues, plasma or serum (top vs. bottom thirds) were inversely associated with non-fatal MI (RR=0.75; 95% CI 0.62–0.92; 7 case-control studies), but not CVD death (RR=1.20; 95% CI 0.98–1.46; 1 case-control and 2 cohort studies) or total CVD (RR=0.89; 95% CI 0.75–1.04; 4 cohort and 3 case-control studies). In the dose-response meta-analyses, each 1 g/d increment of ALA intake was associated with a 10% lower risk of CVD death (RR=0.90; 95% CI 0.83–0.99; 5 cohort studies), and each 0.5% increment of adipose tissue ALA concentration was associated with a 21% (RR=0.79; 95% CI 0.70–0.89; 5 case-control studies) lower risk of non-fatal MI. Conclusion: Higher dietary ALA intakes are associated with a lower risk of CVD death, while higher ALA biomarker levels are associated with a lower risk of non-fatal MI. These findings highlight the need for additional well-designed observational studies as well as large randomized clinical trials to evaluate effects of ALA on CVD.