Abstract
At a population level, cardioprotective and cognitive actions of the fish oil (FO) derived long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been extensively demonstrated. In addition to dietary intake, which is limited for many individuals, EPA and DHA status is dependent on the efficiency of their biosynthesis from α-linolenic acid. Gender and common gene variants have been identified as influencing the rate-limiting desaturase and elongase enzymes. Response to a particular intake or status is also highly heterogeneous and likely influenced by genetic variants which impact on EPA and DHA metabolism and tissue partitioning, transcription factor activity, or physiological end-point regulation. Here, available literature relating genotype to tissue LC n-3 PUFA status and response to FO intervention is considered. It is concluded that the available evidence is relatively limited, with much of the variability unexplained, though APOE and FADS genotypes are emerging as being important. Although genotype × LC n-3 PUFA interactions have been described for a number of phenotypes, few have been confirmed in independent studies. A more comprehensive understanding of the genetic, physiological and behavioural modulators of EPA and DHA status and response to intervention is needed to allow refinement of current dietary LC n-3 PUFA recommendations and stratification of advice to “vulnerable” and responsive subgroups.
Highlights
Randomised controlled trials (RCT) are inconsistent [1,2,3,4], there is a large body of cell, animal and human prospective cohort data demonstrating the cardiovascular and cognitive benefits of increased fish consumption and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)
Unlike typical nutrients, which cannot be synthesised in vivo, EPA and DHA can to some extent be synthesised from the precursor plant derived shorter chain n-3 fatty acids, α-linolenic acid [13,14], with gender [15] and variants [16] in the rate limiting enzymes of the biosynthetic pathway emerging as important determinants of the biosynthetic efficiency (Figure 1)
ELOVL2 encodes elongase 2 which is critical in the elongation of docosapentaenoic acid (DPA) to DHA [39] (Figure 2) The associations were independent of fatty fish intake, with an absence of interaction consistent with the Koala Birth Cohort who observed similar slopes of plasma EPA and DHA in those with 0, 1 or 2 minor FADS1-FADS2 alleles [40]
Summary
Randomised controlled trials (RCT) are inconsistent [1,2,3,4], there is a large body of cell, animal and human prospective cohort data demonstrating the cardiovascular and cognitive benefits of increased fish consumption and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Rather than attempt attempt to be exhaustive and report on all of the majority of which require confirmation in independent studies, the review will largely focus on a select number of genes genes and and genotypes genotypes which which have have been been relatively relatively consistently consistently shown to regulate and status or responsiveness. Such genotypes may in the future bebe useful in in thethe targeting of EPA and DHA status or responsiveness.
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