Abstract
The role of the major plant-derived n-3 PUFA, alpha-linolenic acid (ALA), on the risk of atherosclerotic cardiovascular (ASCVD) remains unclear, but most studies have reported no association. However, the association between intake of ALA and the risk of ASCVD may depend on the intake of marine n-3 PUFAs. We investigated this hypothesis among more than 53,909 middle-aged, Danish men and women followed for a median of 13.4 years. We found a statistically significant inverse association between ALA intake modelled as a restricted cubic spline and the rate of ASCVD in subjects with a low intake of marine n-3 PUFAs, while no association was observed among subjects with a higher intake of marine n-3 PUFAs. Our findings suggest that the intake of ALA may be associated with a lower risk of total ASCVD, but only among subjects with a low intake of marine n-3 PUFAs.
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Key Points
The major plant-derived n-3 PUFA, alpha-linolenic acid (ALA) is a precursor for EPA and DHA and might, therefore, provide a more sustainable, plant-based alternative to marine n-3 PUFAs. ALA is the most abundant n-3 PUFA in Western populations and is believed to be an important mediator of the protective effect on vascular disease provided by the Mediterranean diet. However, no previous studies have investigated the association between ALA intake stratified by intake of EPA+DHA and the risk of a composite of total ASCVD, which may be of greater public health relevance than one of its component outcomes. The association between intake of ALA and the risk of ASCVD among participants enrolled into the Danish Diet, Cancer and Health Cohort consuming below and above the 10th percentile of EPA+DHA, respectively. 57,053 men and women between 50 and 65 years of age were enrolled between 1993 and 1997 and for this study followed through nationwide Danish registries for a median of 13.4 years. During follow-up, 3958 incident ASCVD cases including 366 cases (213 men and 153 women) were identified among 5390 subjects in the lowest 10th percentile of consumption of EPA+DHA (< 252 mg/day). In multivariate analyses, a statistically significant inverse association between ALA intake modelled as a restricted cubic spline and the rate of ASCVD (p = 0.005) in subjects with a low intake of EPA+DHA, while no association was observed among subjects with a higher intake of EPA+DHA. These novel findings suggest that an association between ALA and total ASCVD may be present also at markedly higher intakes of marine n-3 PUFAs than seen in the Health Professionals Follow-up study.
In conclusion, this study suggests that intake of the major plant-derived n-3 PUFA, ALA, may be associated with a lower risk of total ASCVD, but only among subjects with a low intake of marine n-3 PUFAs. An increased intake of ALA might, therefore, be a sustainable alternative to intake of marine-derived n-3 PUFAs and this hypothesis warrants further investigation.