α-Linolenic acid and risk of cardiovascular disease: a systematic review and meta-analysis.
BACKGROUND
Prior studies of α-linolenic acid (ALA), a plant-derived omega-3 (n-3) fatty acid, and cardiovascular disease (CVD) risk have generated inconsistent results.


OBJECTIVE
We conducted a meta-analysis to summarize the evidence regarding the relation of ALA and CVD risk.


METHODS
We searched multiple electronic databases through January 2012 for studies that reported the association between ALA (assessed as dietary intake or as a biomarker in blood or adipose tissue) and CVD risk in prospective and retrospective studies. We pooled the multivariate-adjusted RRs comparing the top with the bottom tertile of ALA using random-effects meta-analysis, which allowed for between-study heterogeneity.


RESULTS
Twenty-seven original studies were identified, including 251,049 individuals and 15,327 CVD events. The overall pooled RR was 0.86 (95% CI: 0.77, 0.97; I² = 71.3%). The association was significant in 13 comparisons that used dietary ALA as the exposure (pooled RR: 0.90; 95% CI: 0.81, 0.99; I² = 49.0%), with similar but nonsignificant trends in 17 comparisons in which ALA biomarkers were used as the exposure (pooled RR: 0.80; 95% CI: 0.63, 1.03; I² = 79.8%). An evaluation of mean participant age, study design (prospective compared with retrospective), exposure assessment (self-reported diet compared with biomarker), and outcome [fatal coronary heart disease (CHD), nonfatal CHD, total CHD, or stroke] showed that none were statistically significant sources of heterogeneity.


CONCLUSIONS
In observational studies, higher ALA exposure is associated with a moderately lower risk of CVD. The results were generally consistent for dietary and biomarker studies but were not statistically significant for biomarker studies. However, the high unexplained heterogeneity highlights the need for additional well-designed observational studies and large randomized clinical trials to evaluate the effects of ALA on CVD.
Department of Nutrition, Harvard School of Public Health, Harvard Medical School, Boston, MA 02115, USA. ephanp@nus.edu.sg
An
A
Pan
Mu
M
Chen
Rajiv
R
Chowdhury
Jason H Y
JH
Wu
Qi
Q
Sun
Hannia
H
Campos
Dariush
D
Mozaffarian
Frank B
FB
Hu
D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology* / Q000209:etiology / Q000517:prevention & control; D004032:Diet / Q000009:adverse effects; D006801:Humans; D015203:Reproducibility of Results; D012306:Risk; D017962:alpha-Linolenic Acid / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use
D015415:Biomarkers; D017962:alpha-Linolenic Acid