Lifestyle Genom. , 2021., Feb 2:1-6. doi: 10.1159/000513886.

Genetic Variation, Diet, Inflammation, and the Risk for COVID-19.

Simopoulos AP.

Abstract

COVID-19, which is caused by SARS-CoV-2, is characterized by various symptoms, ranging from mild fatigue to life-threatening pneumonia, “cytokine storm,” and multiorgan failure. The manifestation of COVID-19 may lead to a cytokine storm, i.e., it facilitates viral replication that triggers a strong release of cytokines, which then modulates the immune system and results in hyperinflammation. Today’s diet is high in omega-6 fatty acids and deficient in omega-3 fatty acids; this, along with a high fructose intake, leads to obesity, which is a chronic state of low-grade inflammation. Omega-6 fatty acids are proinflammatory and prothrombotic whereas omega-3 fatty acids are less proinflammatory and thrombotic. Furthermore, omega-3 fatty acids make specialized lipid mediators, namely resolvins, protectins, and maresins, that are potent anti-inflammatory agents. Throughout evolution there was a balance between omega-6 and omega-3 fatty acids with a ratio of 1-2/1 omega-6/omega-3, but today this ratio is 16-20/1 omega-6/omega-3, leading to a proinflammatory state. In addition, genetic variants in FADS1, FADS2, ELOV-2, and ELOV-5 lead to a more efficient biosynthesis of long-chain polyunsaturated fatty acids (PUFAs), e.g., of linoleic acid (LA) to arachidonic acid (ARA), and (alpha-linolenic acid) (ALA) to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), leading to higher ARA levels. Because the US diet is already high in omega-6 fatty acids, the increased biosynthesis of ARA in people with the derived FADS haplotype (haplotype D) leads to an increased production of leukotrienes, thromboxanes, C-reactive protein (CRP), and eventually elevated levels of cytokines, like interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF), which may increase susceptibility to COVID-19. About 80% of African Americans, 50% of Hispanics, and 45% of European Americans have the FADS haplotype D and are thus efficient metabolizers, which could account for the higher vulnerability of these populations to COVID-19. Therefore, another reason that African Americans and Hispanics are more susceptible to COVID-19 is that they have a higher frequency of haplotype D, which is no longer beneficial in today’s environment and diet. Genetic variation must be considered in all studies of disease development and therapy because it is important to the practice of precision nutrition by physicians and other health professionals. The objective of this commentary is to emphasize the importance of genetic variation within populations and its interaction with diet in the development of disease. Differences in the frequency of genes and their interactions with nutrients in various population groups must be considered among the factors contributing to health disparities in the development of COVID-19. A balanced omega-6/omega-3 ratio is essential to health. Physicians should measure their patients’ fatty acids and recommend decreasing the intake of foods rich in omega-6 fatty acids and increasing the intake of omega-3 fatty acids along with fruits and vegetables.

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Key Points

The review presents evidence that changes in the food supply over a relatively short period of time since World War II have had dire consequences worldwide. Our genes are programmed to respond to a diet consistent with our diet during human evolution. The enormous increase in the intake of omega-6 fatty acids, the decrease in omega-3 fatty acid intake, and the increase in the intake of fructose and ultra-processed foods have led to the prevalence of metabolic disease of the brain, obesity and a chronic proinflammatory state that may increase the susceptibility to and severity of COVID-19 infection. Genetic variation must be considered in all studies of disease development and therapy. Today’s diet is prothrombotic and proinflammatory; it is therefore dangerous to the homeostasis of populations with a high frequency of genes that were beneficial during evolution but are detrimental in today’s environment and with the current food supply. It is essential that the food supply is balanced in omega-6 and omega-3 fatty acids by (1) lowering the intake of oils rich in omega-6 fatty acids (e.g., corn oil, sunflower oil, safflower oil, and soybean oil), (2) increasing the intake of oils rich in omega-3 fatty acids (e.g., canola, flaxseed, perilla, and chia), (3) increasing the intake of monounsaturated oils (olive oil, hazelnut oil, and macadamia nut oil), and (4) decreasing the consumption of ultra-processed foods that have an omega-6/omega-3 ratio >4:1. It is essential that physicians and other health professionals measure the omega-6 and omega-3 fatty acids in their patients’ red blood cell membrane phospholipids to ensure a healthy omega-6/omega-3 ratio, in order to decrease chronic low inflammation and maintain a normal/less inflammatory immune system that would decrease the risk for contracting COVID-19.