α-Linolenic acid and risk of cardiovascular disease: a systematic review and meta-analysis.
α-Linolenic acid and risk of cardiovascular disease: a systematic review and meta-analysis.
Year: 2012
Authors: Pan, A. Chen, M. Chowdhury, R. Wu, J.H. Sun, Q. Campos, H. Mozaffarian, D. Hu, F.B.
Publication Name: Am. J. Clin. Nutr.
Publication Details: doi: 10.3945
Abstract:
Prior studies of alpha linolenic acid (ALA), a plant-derived omega 3 (n3) fatty acid, and cardiovascular disease (CVD) risk have generated inconsistent results. We conducted a meta analysis to summarize the evidence regarding the relation of ALA and CVD risk. Design: 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. Twenty-seven original studies were identified, including 251,049 individuals and 15,327 CVD events. The overall pooled RR was 0.86 (95 percent CI: 0.77, 0.97; I2 = 71.3percent). The association was significant in 13 comparisons that used dietary ALA as the exposure (pooled RR: 0.90; 95 percent CI: 0.81, 0.99; I2 = 49.0 percent), with similar but non significant trends in 17 comparisons in which ALA biomarkers were used as the exposure (pooled RR: 0.80; 95 percent CI: 0.63, 1.03; I2 = 79.8 percent). 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. (Authors abstract)
ALA from plant sources is more affordable and widely available globally. Thus, whether ALA can reduce the risk of CVD is of considerable public health importance. Given the inconsistency of prior results and the potential for global impact of ALA on CVD outcomes, we performed a systematic review and meta analysis of the current evidence for the association between ALA exposure, including studies of dietary ALA and ALA biomarker concentrations, with risk of incident CVD. Overall ALA exposure was associated with a modestly lower risk of CVD.
Evaluation of subtypes of studies showed that dietary ALA was associated with a lower risk of CVD, particularly CHD death. The pooled risk estimate was generally similar for ALA biomarker
concentrations, but the results were not statistically significant. Overall, these data support potential cardiovascular benefits of ALA. However, significant unexplained heterogeneity was seen, and there were too few studies that evaluated specific combinations of ALA exposure measurements (eg, diet, serum, plasma, phospholipids, cholesterol esters, and adipose tissue) and disease subtypes (eg, CHD death, nonfatal MI, and stroke) to evaluate potential causes of this heterogeneity. This analysis suggests that ALA consumption may confer cardiovascular benefits, and each 1 g/d increment of ALA intake was associated with a 10 percent lower risk of CHD death. Prior reviews evaluating ALA and CVD risk found only non significant trends toward potential benefits. This work considerably expands on these prior reviews by evaluating both dietary and biomarker studies and by including several recent investigations. Dietary estimates of ALA consumption do not correlate strongly with biomarker concentrations (average correlation of 0.35 for adipose tissue and 0.24 for blood concentrations). Blood biomarker concentrations may also be limited in that they generally reflect exposures over the prior few weeks, rather than longer periods, which may be most relevant for risk of chronic diseases.
A strengthen of this meta analysis was that both dietary and biomarker estimates were assessed. The findings support the need for further experimental and clinical studies to elucidate potential pathways of effects of ALA on CVD outcomes. Limited evidence suggests that ALA could have some independent role in cardiovascular health. A direct or indirect antiarrhythmic effect of ALA could partially explain why ALA appeared protective against CHD death in this analysis. ALA intake is also correlated with the overall intakes of other PUFAs (ie, n6 fatty acids and EPA/DHA), which may provide beneficial effects on CVD. A previous investigation reported that the association between ALA intake and CHD risk was not influenced by background n6 fatty acids intake, but may be modified by EPA/DHA intake. Further studies are needed to investigate whether ALA has independent effects on cardiovascular health, or the effects can be modified by intake of other fatty acids. In conclusion, this systematic review and meta analysis of both dietary and biomarker studies suggests that ALA exposure is associated with a moderately lower risk of CVD. The findings suggest that ALA consumption may be beneficial and highlight the need for additional well designed observational studies and randomized clinical trials to evaluate the effects of ALA on CVD risk. (Editors comments)
