The Ketogenic Diet, Ketone Supplements and Covid-19


Well-known member
May 24, 2021
Since the inception of the Covid-19 pandemic the worlds inhabitants have all received mitigating behaviors that we should use to ward off the potentially deadly scourge that we have not seen the likes of in over 100 years. These protective steps have included the now well know recommendations to wear masks, wash hands, socially distance and get vaccinated. There is however a largely and conspicuously absent risk factor and corresponding mitigating behavioral change that could potentially provide great protection from the SARS-CoV-2 virus and at the very least help moderate critical pathological metabolic pathways found in Covid-19.

What is often being overlooked or ignored in the discussion about risk factors and Covid-19? The fact that a profile of obesity and metabolic dysfunction in individuals provides a much greater risk of poor outcomes (including death) for those infected with Covid-19. In parallel to this, there is a dearth of discussion, let alone recommendations about how changing one’s poor diet to a healthier variety, such as a ketogenic diet or the use of ketone supplements, can address much of the underlying pathophysiology and resulting sequalae from the novel viral infection.

On May 13, 2021 the CDC released an updated report entitled “Underlying Medical Conditions Associated with High Risk for Severe COVID-19: Information for Healthcare Providers”. The report provides guidance to healthcare workers caring for patients with underlying conditions that places them at a “higher risk of developing sever outcomes”. Data was collected from two large cohort studies compromising 64,781 Covid patients: “Risk Factors Associated with In-Hospital Mortality in a U.S. National Sample of Patients with COVID-19 (USA)”. The article highlights the many variables associated with severe outcomes from Covid-19. The most common comorbidities were reported to be:
  • Preexisting comorbidities significantly associated with increased odds of in-hospital mortality were:
    • Metastatic solid tumor, 57% increase (adjusted odds ratio [aOR] =1.57; 95% CI, 1.20–2.05)
    • History of myocardial infarction, 47% increase (aOR=1.47; 95% CI, 34–1.62)
    • Cerebrovascular disease, 39% increase (aOR=1.39; 95% CI, 1.25–1.56)
    • Congestive heart failure, 37% increase (aOR=1.37; 95% CI, 1.26–1.49)
    • Hemiplegia, 34% increase (aOR=1.34; 95% CI, 1.05–1.72)
    • Any malignant neoplasm, 27% increase (aOR=1.27; 95% CI, 1.09–1.47)
    • Dementia, 20% increase (aOR=1.21; 95% CI, 1.11–1.32)
    • Diabetes, 20% increase (aOR=1.20; 95% CI, 1.12–1.28)
    • Chronic pulmonary disease, 16% increase (aOR=1.16; 95% CI, 1.08–1.26)
    • Hyperlipidemia, 11% increase (aOR=1.11; 95% CI, 1.03–1.19)
  • The most common comorbidities were hypertension (30,236 [46.7%]), hyperlipidemia (18,744 [28.9%]), diabetes (18,091 [27.9%]), and chronic pulmonary disease (10,434 [16.1%])
  • The risk for inpatient mortality was higher with increasing number of comorbid conditions. Among patients with COVID-19 who died, there was a higher prevalence of all comorbidities (except for metastatic solid tumor) than among patients who survived.
Another report released on March 27, 2020 by the World Obesity Federation in London entitled “Obesity and Covid-19 policy statement” provides further data regarding risk factors associated with obesity. The statement reads in part:
  • Based on emerging data and the patterns of infection we have seen in other viral infections, overweight and obesity are also likely to be risk factors for worse outcomes in those who are infected by COVID-19.
  • In the UK, a report suggests that two thirds of people who have fallen seriously ill with coronavirus were overweight or had obesity.
  • Meanwhile, a report from Italy suggests 99% of deaths have been in patients with pre-existing conditions, including those which are commonly seen in people with obesity such as hypertension, cancer, diabetes and heart diseases.
As can be seen by the provided data, the comorbidities associated with metabolic dysfunction rank very high in the preexisting conditions resulting in severe outcomes from Covid-19 infection. In the current ongoing Covid-19 pandemic environment, it is important to note that obesity and metabolic syndrome have been found to have a significant weaking impact on the immune system: “As research continues to elucidate the mechanisms that underlie obesity and MetS-related immune dysfunction, the potential for developing therapeutic lifestyle, dietary, and pharmaceutical therapies will likely expand in an effort to combat the detrimental effects of obesity on immunity.” (Impact of Obesity and Metabolic Syndrome on Immunity)

The ketogenic diet (KD) has been used for approximately 100 years to help and sometimes permanently resolve refractory childhood epileptic disorders (*). However, the use of the KD has probably become best known for its effectiveness for treating obesity with its use exploding in recent history. Studies have found that with fat loss (and preservation of muscle mass) achieved through a ketogenic diet, many of the metabolic comorbidities (inflammation, T2D, dyslipidemia, insulin resistance, glucose and blood pressure control) associated with obesity and the subsequent identified pathophysiologies concomitant with severe Covid-19 are often resolved as well. (*,**)

“For all these reasons, hyperglycemia and high glycemic variability should be adequately prevented in order to improve the outcomes of COVID-19 patients. It is hence clear that well-controlled blood glucose levels will correlate with lower risk of infection and/or better disease resolution. In consideration of potentially adverse effects of commonly used drugs for type 2 diabetes and its comorbidities, a nutritional approach lowering blood glucose concentrations should be considered as a first option, in order to prevent or reduce Sars-Cov-2 infection risk and related complications.” (*)

When examining the heightened risk of severe outcomes from Covid-19 in individuals with preexisting metabolic disorders, such as obesity and hyperglycemia, researchers in another paper, published in the Journal of Translation Medicine, discuss “the importance of KDs [ketogenic diets] for a rapid reduction of several critical risk factors for COVID-19, such as obesity, type 2 diabetes and hypertension, based on the known effects of ketone bodies on inflammation, immunity, metabolic profile and cardiovascular function. We do believe that a rapid reduction of all modifiable risk factors, especially obesity with its metabolic complications, should be a pillar of public health policies and interventions, in view of future waves of SARS-CoV-2 infection.” (The dark side of the spoon - glucose, ketones and COVID-19: a possible role for ketogenic diet?)

Having established the some of the most common comorbidities found with severe outcomes from Covid-19 infection are associated with obesity and metabolic dysfunction, let’s take a deeper look at the relevant mechanisms involved and how implementing a ketogenic diet or ketone supplements could potentially provide significant protection and mitigation from experiencing the worst Covid-19 has to offer.

As most of us are probably painfully too aware of, from the shortage of ventilators that was encountered at the height of the Covid-19 pandemic, the virus (SARS-CoV-2) that causes Covid-19 is considered a respiratory illness in humans (though it can impact many other physiological and psychological systems in the body). SARS-CoV-2 stands for: Severe Acute Respiratory Syndrome Corona Virus 2. There are many respiratory viruses that can affect the lungs and cause a potentially fatal condition referred to as acute respiratory distress syndrome (ARDS). In addition to SARS-CoV-2 and the perennial Influenza A, these are some of the viruses that can cause ARDS and may sound familiar from previous viral outbreaks: 2003 severe acute respiratory syndrome (SARS)-CoV, 2004 N5N1 influenza, 2009 H1N1/09 influenza, 2012 Middle East respiratory syndrome (MERS)-CoV.

On July 15, 2020 an extensive paper entitled “Investigating Ketone Bodies as Immunometabolic Countermeasures against Respiratory Viral Infections” was published suggesting the induction of a state of ketosis as a novel and promising metabolic therapy “to target viral disease progression” such as SARS-CoV-2. The authors state: “the field of immunometabolism research has uncovered multiple points where metabolism influences host-pathogen interactions, not only in altering infection risk and viral replication but also affecting the response of specific immune cell types, thus profoundly controlling disease outcomes.”

The researchers identified numerous bodily functions that the major ketone body Beta-Hydroxybutyrate (BHB) could influence and mitigate involved in viral respiratory disease declaring: “several known molecular mechanisms of the ketone body BHB have been implicated in respiratory virus life cycles and molecular pathogenesis (Figure 1). Most of these mechanisms are specifically implicated in viral replication.”

The identified relevant molecular mechanisms and cellular biology that BHB could influence and deserve further examination include:
  • BHB Protects against Oxidative Stress
  • BHB Directly Inhibits Proinflammatory NLRP3 Activation
  • BHB Has Additional Anti-inflammatory Effects Mediated by HCAR2 and NF-κB
  • BHB Reduces Apoptosis via Mitochondrial Permeability Transition Pore (mPTP) Closure
  • BHB Interacts with RNA-Binding Ribonucleoprotein hnRNPA1
  • BHB Inhibits Glycolysis
The authors then expounded on the potential effects of beta-hydroxybutyrate regulated mechanisms and their role in on respiratory viruses making a persuasive argument for further investigation.

Beyond the viral replication processes discussed the authors continued on to identify resulting physiological interactions that BHB could potentially mitigate in the progression of severe respiratory virus infection revealing that “these disproportionately affect both mortality and long-term outcomes in survivors, such as cognitive and functional decline. Here, we review how the molecular mechanisms of ketone bodies described above may impact these crucial, complex manifestations of severe respiratory viral infection (Figure 2)”. The physiological interactions recognized and potentially influenced by BHB include:
  • Immunometabolic Modulation in ARDS
  • BHB Preserves Cardiac Function
  • BHB Improves Tolerance to Tissue Hypoxemia
  • BHB Improves Systemic Glycemic Control and Mitigates Insulin Resistance
  • BHB Alters Gut Microbiome to Modulate Inflammation
  • Ketone Bodies Attenuate Muscle Catabolism and Functional Decline
  • Immunometabolic Modulation in Delirium
The researchers in this paper primarily suggest that the consumption of exogenous ketones may be a potential intervention for severe respiratory viral infections exploiting the highlighted effects of beta-hydroxybutyrate on the viral replication and physiological interactions in these disease states. They summarize that the “evidence across various model systems and/or clinical contexts support potentially relevant molecular mechanisms of ketone bodies, including provision of energetic support, attenuation of inflammation and oxidative stress, apoptosis resistance, maintenance of metabolic homeostasis, and others.”

However, the authors also do caution that more preclinical and clinical research needs to be completed to resolve any potential complications and adverse outcomes from this application. The biological processes involved are very complex and careful attention should be paid to conceivable resulting complications that could be elicited from the ensuing mechanistic modifications manifested via BHB.

The research appears to be clear that one of the most important things (possibly the most important thing?) we can do to protect ourselves from current and future respiratory viral infections, like Influenza A and SARS-CoV-2, is to get our metabolic health in order and the ketogenic diet may be the ideal away for many of us to do just that!
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