Impact of Genotype on EPA and DHA Status and Responsiveness to Increased Intakes

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.

The Effect of Walnut Consumption on n-3 Fatty Acid Profile of Healthy People Living in a Non-Mediterranean West Balkan Country, a Small Scale Randomized Study

“…Some evidence suggest that n-6/n-3 ratio may be a potential biomarker for the development of cardiovascular diseases and decreasing the ratio could improve health status of Serbian population [1]. There are published data on the n-6/n-3 ratio in some other countries like Japan (4.00), United Kingdom and Northern Europe (15.00), the United States (16.74), and urban India (38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50) [33]. In general people living in Serbia, a non-Mediterranean West Balkan country, have an inadequate intake of total n-3 fatty acids [34].…”

“…Data presented by Marangoni et al, [31] indicate that the intake of slightly over 1 g ALA/day through walnut significantly and rapidly increased blood ALA and EPA levels. The efficiency of the pathway is inherently low in humans, with an estimated conversion of ALA to EPA of 0.2-6% and <0.1% for DHA, and therefore any changes in bioconversion efficiency have potentially large impacts on LC PUFA status [40]. We hypothesized that ALA from walnuts could correct the low n-3 status and tested this by a short-term intervention pilot study.…”

Both maternal and offspring Elovl2 genotypes determine systemic DHA levels in perinatal mice

“…Moreover, the relative amount of DHA in the offspring liver reached a relatively higher level than in the maternal liver, which is a good illustration of a bio-magnification phenomenon (43). Although there has been a growing interest in the field of diet-genotype interplay and body DHA levels (44), to our knowledge, this is the first report that focuses on the effect of maternal DHA supplementation in a condition of genetically acquired systemic DHA-deficiency and liver at 20 days of pregnancy can contribute to increased long-chain PUFA synthesis and DHA levels during late pregnancy and lactation (35). Moreover, the same group observed an increased Elovl2 expression in adipose tissue within the first half of the lactation period (36), suggesting improved mobilization of DHA from internal sources.…”

Need of Nutrigenomic Studies for the Prevention and Treatment of Mood and Neurodegenerative Disorders

“…Therefore, to be able to recommend "personalized food or nutrition" to individuals it may be necessary to define typical pattern of genes, environmental influences, and individual behavior that describe, how food molecules can be metabolized differently in individual bodies that match one of those patterns. It appears that DHA-rich (docosahexaenoic acid) nutrition is associated with increased risk of Alzheimer's disease for carriers of the apolipoprotein E ε4 (APOE4)-gene [14,15]. While it is contrary to the other studies which indicate that dietary intake of omega-3 fatty acids and weekly consumption of fish may reduce the risk of incident Alzheimer's disease [16].…”