Black and Latinx communities have disproportionately borne the burden of the COVID-19 pandemic in the United States. This inequity is rooted in a tangle of social, political, and health-related factors that researchers are still seeking to unravel and elucidate. In particular, environment- and gene-based interactions may put Black and Latinx patients at a heightened risk of experiencing severe COVID-19 infections.
Charles Serhan, PhD, DSc, of the Department of Anesthesiology, Perioperative and Pain Medicine, is the co-author of a recent article in Molecular Aspects of Medicine that highlights the importance of understanding the gene-nutrient connection. Serhan’s research focuses on inflammation-fighting molecules in the body derived from essential fatty acids. His two co-authors, Richard Bazinet, PhD, of the University of Toronto, and Artemis Simopoulos, MD, founder and president of the Center for Genetics, Nutrition and Health, study the presence of these fatty acids in the body and how nutrition impacts their availability, respectively. Together, the three authors posit that a more personalized approach to nutrition could help optimize an individual’s ability to control excessive inflammation as in the cytokine storms associated with COVID-19.
Serhan, the director of the Center for Experimental Therapeutics and Reperfusion Injury, sat down with CRN to discuss his perspective on promoting greater precision in nutrition.
In the context of treating COVID-19, why is it important to think about nutrition?
CS: Many scientific papers have shown that in severe COVID-19 infections, the body responds with an excessive ‘cytokine storm.’ Cytokines are very important protein mediators that regulate the inflammatory response. Inflammation is protective — it protects the body from invading organisms, microbes, bacteria, and viruses — but cytokine activity is elevated in the airway and in the lungs of individuals with COVID-19 to an extent that can be dangerous. Our research focuses on molecules that we collectively call the specialized pro-resolving mediators (SPMs), which control and regulate those cytokines and could be important for treating COVID-19 by dampening the excessive inflammatory response that the body has to the virus.
SPMs are derived principally from the essential omega-3 fatty acids, DHA and EPA, which human bodies don’t produce in large quantities. We take these in almost exclusively in our diet, especially in marine oils. Individuals who primarily consume what’s considered a ‘Western diet,’ which is often abundant in processed oils and poor in fruits and vegetables, have much lower levels of these essential fatty acids. If we could increase those nutritional components in COVID-19 patients, we would have a better chance in regulating the cytokine storm and the excessive inflammatory response in these individuals.
What are advantages of focusing on SPMs in particular as a therapeutic approach to targeting inflammation?
CS: Most of the tools we have to control inflammation now are inhibitors or antagonists that suppress inflammation. These work very well up to a certain point, but individuals taking them for a longer amount of time start to see unwanted side effects of immune suppression. What’s exciting about SPMs is that they stimulate the innate immune response that helps clear infections. Reports from other groups that have studied viral infections have found that SPMs can help clear viral infections in animal models, which is very encouraging.
How do genetic profiles interact with nutrition in the context of inflammation and COVID-19?
CS: Enzymes regulated by what are called the FAD genes control the production of some essential fatty acids in humans, which are the precursors of SPMs. There are different varieties of those genes clustered in different populations. One variety, found in about 80 percent of African Americans and in about 43 percent of European Americans, is associated with lower levels of fatty acids. Our paper suggests that the combination of a Western-type of diet deficient in marine-oil intake plus the higher frequency of this genetic profile magnifies the vulnerability of Black and Latinx individuals to COVID-19, exacerbating the cytokine storm in individuals with this genetic background. Therefore, precision-nutrition in the form of nutritional supplementation could be useful in helping people achieve the right levels of the fatty acids that serve as precursors for SPMs.
What is meant by the term ‘precision-nutrition,’ and what does a precision-nutrition approach entail?
CS: The term ‘precision-nutrition’ can cover a wide terrain, from the vitamins a person takes to their daily meals. Missing key nutrients creates stress for the body, which causes unresolved inflammation. This is what appears to be the case in many widely occurring diseases, including conditions that increase the risk of heart disease, stroke and diabetes.
Having the means to measure vital nutrients and the products of those nutrients is a tough challenge. We know about the enzymes and pathways involved in inflammation, and we have sequenced the human genome; the next horizon is to understand how intermediary metabolism is directly influenced by nutrition. Our little piece of improving precision nutrition is targeted at SPMs, because we think that they’re important in the control of inflammation. In our precision nutrition approach, we hope to measure SPMs in individuals and then think about how to increase their production. But to be holistic about wellness, we need to take into account much more than just the essential fatty acids. They’re a small piece of a really enormous puzzle of nutrition.
Your article highlights inequities laid bare by COVID-19. What public health actions does your article suggest we explore with a renewed focus?
CS: What we need to do is measure the SPM pathways of as many individuals as possible, and then look at the influence of changing dietary and nutritional intake. That needs to happen at an operational scale that is beyond the capabilities of our lab. But I hope that this pandemic, the crisis that we have fallen into, and the lack of understanding of how the body responds to a virus have illuminated the need for public health initiatives to improve nutrition. On a large-scale, we need to monitor food intake, genetics, metabolomics and SPM status in a diverse range of healthy individuals and those with specific diagnoses. Armed with this information, we can than target excesses or deficiencies in an individual’s specific profile of nutrients and metabolome.
To me, it’s compelling that SPMs are helping regulate immune traffic. People have argued for decades about the benefits of increasing marine-oil intake. That mystery has largely been solved, and our findings have revealed the molecular pathways involved. Now it really gets down to thinking about monitoring the nutritional needs of an individual. This may sound like a fiction today, but we do have the tools to accomplish this.