Diet-Gene Interactions and PUFA Metabolism: A Potential Contributor to Health Disparities and Human Diseases


The “modern western” diet (MWD) has increased the onset and progression of chronic human diseases as qualitatively and quantitatively maladaptive dietary components give rise to obesity and destructive gene-diet interactions. There has been a three-fold increase in dietary levels of the omega-6 (n-6) 18 carbon (C18), polyunsaturated fatty acid (PUFA) linoleic acid (LA; 18:2n-6), with the addition of cooking oils and processed foods to the MWD. Intense debate has emerged regarding the impact of this increase on human health. Recent studies have uncovered population-related genetic variation in the LCPUFA biosynthetic pathway (especially within the fatty acid desaturase gene (FADS) cluster) that is associated with levels of circulating and tissue PUFAs and several biomarkers and clinical endpoints of cardiovascular disease (CVD). Importantly, populations of African descent have higher frequencies of variants associated with elevated levels of arachidonic acid (ARA), CVD biomarkers and disease endpoints. Additionally, nutrigenomic interactions between dietary n-6 PUFAs and variants in genes that encode for enzymes that mobilize and metabolize ARA to eicosanoids have been identified. These observations raise important questions of whether gene-PUFA interactions are differentially driving the risk of cardiovascular and other diseases in diverse populations, and contributing to health disparities, especially in African American populations.

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Alex’s notes: It is estimated that over two-thirds of the foods in the modern Western Diet (MWD) were not present in the diets of our ancestors, and many of these changes in dietary habits have led to great health burdens upon the human race. But define ancestor. This is an issue because as challenging as obesity and gene-diet interactions have been for overall populations of developed countries such as the US, they manifest themselves in a particularly negative way for certain populations and ethnic groups. One of the most notable changes in the human diet that occurred within the last century was the inclusion of significant amounts of industrial seed oils and polyunsaturated fatty acid (PUFA) intake, particularly linoleic acid (o-6). The free review at hand examines the genetic differences in PUFA metabolism in distinct human populations.

Major differences in the frequencies of genetic variants that enhance the synthesis and metabolism of omega-6 fatty acids within Americans of different ethnic descents make the possibility of uniform nutrition recommendation unlikely. The impact of genetic variants are likely to be population-specific as both the frequency of the variants in PUFA biosynthetic genes and the dietary precursor PUFA environment are typically quite different from population to population. A precursor environment with relatively high concentrations of omega-3s relative to omega-6s together with high efficiency/capacity variants may shift the balance of bodily PUFAs toward a wide array of protective omega-3 containing compounds. Alternatively, higher concentrations of dietary omega-6s together with a high frequency of high efficiency/capacity variants likely shifts the balance back to proinflammatory compounds, chronic inflammation, and associated human disease.

To put these points into perspective, the review compares African Americans to Caucasians. African Americans have higher rates of hypertension, type 2 diabetes, stroke, and CVD and certain types of cancer than Caucasians, and not only is the incidence of these diseases elevated among African Americans, but the diseases themselves are more severe in African Americans than in Caucasians. Moreover, there is a high frequency of a haplotype with an increased capacity to synthesize long-chained PUFAs in African and African ancestry populations and a loss of that converting capacity across Asia into North and South American native populations.

Genetics plays a role in every aspect of our lives. There is no doubt to this, and it gets more complex when thinking about the environmental influences that manipulate gene expression. Dietary PUFA intake is only one tiny fish in a sea of influences, but given the potential risks of excessive PUFA intake on health, further research is needed before dietary recommendations for PUFA intake should be made for heterogeneous populations that make up this planet. We are far from understanding the complete impact of the MWD on health and disease, but what can be said with certainty is that given the differences in ancestry of populations, the MWD will effects some people more negatively than others.


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