January 31st, 2022

After having a dysfunctional discussion with one of my ICU colleagues about the efficacy of lifestyle modification and the lack of need to push it, I am even more determined to push this message. The message that modern medicine is here to save you is not lost on the 840,000+ deceased Americans and counting. Could they have reduced their risk had they known and chosen to change the antecedent physiology that put them at risk in the first place? I, resoundingly, think so for many.

Understanding the pathogenesis of the virus has taken some time but is the key to making educated choices to support immune responses. The bottom line is twofold with regard to prevention of SARS2. First, support immune surveillance by making sure that the immune system is fine tuned to recognize and destroy the virus early on so that it has minimal opportunity to replicate and hijack our immune system. Secondly, support survival if you get ill and the virus has had the ability to replicate. This means that we want adequate and functional responses from natural killer cells and T helper type 1 cells. Then you need a low starting inflammation point so that when your immune system begins to inflame and attack the virus, you are not pushed into a place of over inflammation and death.

Now, we know that obesity, cardiovascular disease and type 2 diabetes are risk factors for a negative COVID outcome. We also know that these diseases are associated with significant flares in innate immune inflammasome activity. Therefore, one leap of faith seems to be that if we reduce the triggers of baseline inflammasome activity, then we could mitigate some of the downstream risk if we contract SARS2. For example, reducing fructose and high fructose corn syrup consumption would reduce the metabolite uric acid, a known trigger of inflammasome formation and activity system wide. This occurs notoriously in the mitochondria of the liver, muscles and kidneys inducing adipose deposition, insulin resistance, high blood pressure and nephron damage. Inflammasomes also worsen cardiac coronary artery damage which is seen with many COVID deaths. Panoptosis is a term used to describe cell death globally in a human body via the simultaneous activation of pyroptosis, apoptosis and necroptosis in the same cell, leading to its inflammatory death. This appears to happen in a subset of severe COVID19 patients who have severe obesity and inflammation.

The greatest risk for all cause human mortality appears to be the overconsumption of refined foods that are loaded with poor quality fatty acids and huge glucose loads that drive insulin resistance via diacylglycerol inhibition of the transcription of the muscle’s GLUT4 receptor as well as fat deposition of the secondary hyperglycemia/insulinemia response. Large volume fructose ingestion in these same refined foods drives fat deposition via the metabolite uric acid through historically beneficial survival pathways in the mitochondria and liver. These processes lead to obesity which is notorious for having immunologically activated fat cells that slant toward dysfunctional inflammatory macrophages, T cells that are activated and notorious for presenting antigen to the immune system for reaction leading to autoimmunity. These same fat cells also drive inflammasome responses and suppress NK cell activity as is well noted in diabetics, the poster humans for hyperglycemia in general. There are many other nutrition based issues to discuss but for the sake of this piece I will only add this, corn and grain fed animal meats are loaded with pro-inflammatory omega 6 fatty acids that are potentially driving excessive arachidonic acid production and cytokine responses. These and many other nutrition based events conspire to reduce viral surveillance and killing while paradoxically increasing inflammation through inflammasome formation and cytokine release. This is the perfect storm for a bad outcome. This is only a small representation of the many changes that lifestyle modification could have on immune function and COVID risk as discussed over the last 20 months.

I truly think that this virus is a wake up call for all of us to eat whole foods that are minimally processed, mostly vegetables, fruits, legumes, seeds and nuts spiked with wild caught naturally raised meat, fish and eggs. Sleep more, stress less, exercise and move often, laugh, live and prepare for the future. That is a dramatic recipe for inflammation reduction and protection.


Dr. M