This article is about the effects of ketogenesis on COVID-19 and in Preventing Long Haul COVID symptoms and adds more to what we know about the benefits of fasting for COVID-19.
I have written several articles about the benefits of intermittent fasting for COVID-19 that you can find at the bottom.
The study Impaired ketogenesis ties metabolism to T cell dysfunction in COVID-19, by Karagiannis et al., was published in Nature in September 2022. The authors are from research institutions in Germany and the Netherlands. [1]
The authors started with the theory that behaviors associated with an illness, like loss of appetite, are helpful in the host’s immune response to get rid of the infection.
infection ⇒ loss of appetite ⇒ ketogenesis ⇒ infection resolved
But what if the infection is new? Like a zoonotic infection that jumped from bats to humans. (Or if it is a lab manipulated) Will the theory still hold?
The study focused on the production of ketones as a consequence of fasting and how it affects the immune system.
Ketogenesis
Sugar or glucose is needed by almost all cells in the body, including the brain, for fuel. But if someone chooses not to eat or cannot eat due to illness, the body will switch its fuel source by changing fat cells into ketones.
Ketogenesis results in more adenosine triphosphate (ATP) produced than glucose. Ketones also “burn cleaner” because of less free radical formation and helps decrease inflammation in many diseases.
Beta-hydroxybutyrate (BHB) is a form of ketone, which is what the study focused on.
Ketogenesis is impaired in COVID-19
In the study, the authors found that BHB levels differ depending on what caused the infections. They compared three illnesses that can cause Acute Respiratory Syndromes (ARDS): COVID-19, influenza, and bacterial infection.
ARDS is a severe lung infection where they become filled with fluids. The oxygen levels decrease to the point that mechanical ventilation is needed. It has a high mortality rate.
They found that the ketones (BHB) in influenza and bacterial ARDS are increased, whereas in COVID-19 ARDS, the ketogenesis is impaired, and the BHB is low.
Effects of Low Ketones on COVID-19
Low BHB was also associated with lower amounts of antiviral cytokines like the interferon-gamma (IFNγ), interferon-lambda IFNλ, and IFNγ-induced protein-10 (IP-10).
The low interferon affects the immune system, particularly the T cells, from producing the necessary antivirals to eliminate the virus.
T cells have two main types. The CD4+ or Type 1 helper T cells produce cytokines such as interferon-γ (IFNγ) and the CD8+ cytotoxic T cells that kill infected cells.
Another result of a low BHB is that the cytokines that produce lung fibrosis increase. The abnormal lung tissue becomes stiff and difficult to expand while breathing.
This finding explains why some people continue to have shortness of breath weeks to months after an acute SARS-CoV-2 infection. Dyspnea is one symptom of Long COVID.
The cause of the decrease in the BHB is not due to the absence of glucose and insulin since most hospitalized patients are fed either by a tube that goes to the stomach.
Effects of the Ketones on T helper cells
So if the ketones are low in SARS-CoV-2 infected cells, can adding ketones improve the immune response of the cells?
That’s what they did next. They added BHB to T helper cells in cell culture. Here are the effects:
- BHB provided an alternative fuel for the T helper cells
- Increased production of ATP by the mitochondria. ATP is the fuel used by cells. The more ATP, the more work can be done by any cell, particularly the T helper cells.
- Increase in the number of T helper cells
- Increased numbers and enhanced production of interferon-gamma.
- The expression of Programmed cell death protein 1 (PD-1) decreased. PD-1 downregulates the immune system and suppresses T-cell inflammatory activity leading to self-tolerance. A decrease in PD-1 allowed the immune system to eliminate the virus better.
Effects on Ketones in Mice
They extended their study from cell cultures to mice. This time a ketogenic diet consisting of a 4:1 ratio of fat to proteins and carbohydrates was given to a study group of mice infected with the influenza virus.
The diet increased the amount of BHB circulating in the mice. Basically, the effects of the ketogenic diet in mice are similar to their findings in cell culture. Notably, the ketogenic diet reduced lung damage, faster viral clearance, and less weight loss. Moreover, the proteins associated with fibrosis were also reduced in mice fed the ketogenic diet.
To kick it up a notch, they added BHB salts to their drinking water to increase the availability of the ketones. Doing so further enhanced the response of the T helper cells and reduced lung damage and fibrosis-related proteins.
Effects of Ketones on Human Cells
This time they obtained cells from patients with severe COVID-19. Same results. Treatment with BHB resulted in more T helper cells, interferon-gamma production, and decreased PD-1.
Adding ketones to infected human cells also made them use fatty acids and amino acids better than glucose for ATP production and makes for more efficient ketogenesis.
Summary
Infection can decrease the immune response due to impaired ketogenesis. However, adding ketone salts of BHB can restore the functionality of the immune response in viral infections.
Relevance
The role of ketones in improving the immune response against SARS-CoV-2 is very relevant, considering newer SARS-CoV-2 variants of concern are becoming more interferon resistant. [2]
The study by Guo et al., Interferon resistance of emerging SARS-CoV-2 variants, published in the Proceedings of the National Academy of Sciences on August 2022, showed that as the SARS-CoV-2 mutated from the Alpha to the Omicron, the resistance to human interferons became greater.
It is noteworthy that the paper about the lack of ketogenesis in COVID-19 patients came one month before (July 2022). The absence of ketogenesis may explain why the newer concern variants spread faster and continue infecting vaccinated people and those with natural immunity.
As an example, the Omicron variant can still replicate even in the presence of interferon -beta, one of the most potent interferons in the study[2]
Take Away Message
Intermittent fasting and a ketogenic diet can improve the immune response against SARS-CoV-2 interferon-resistant variants by improving the T helper response.
The least expensive ketone salt with a more than four-star review is Magnesium BHB Powder by Bulk Supplements.
The Complete Ketogenic Diet for Beginners Book has more than 29 thousand reviews averaging 4.5 stars.
Ketogenesis happens with Intermittent Fasting. Learn more about it from Dr. Jason Fung’s book, The Complete Guide To Fasting
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The Front Line COVID Critical Care Alliance includes intermittent fasting in its protocol for treating Long COVID syndrome.
The I-RECOVER Management Protocol for Long Haul COVID-19 Syndrome
References:
- Karagiannis F., Peukert K., Surace L., Michla M., Nikolka F., Fox M., Weiss P., Feuerborn C., Maier P., Schulz S., et al. Impaired ketogenesis ties metabolism to T cell dysfunction in COVID-19. Nature. 2022;609:801–807. doi: 10.1038/s41586-022-05128-8.
- Guo K, Barrett BS, Morrison JH, Mickens KL, Vladar EK, Hasenkrug KJ, Poeschla EM, Santiago ML. Interferon resistance of emerging SARS-CoV-2 variants. Proc Natl Acad Sci U S A. 2022 Aug 9;119(32):e2203760119. doi: 10.1073/pnas.2203760119. Epub 2022 Jul 22. PMID: 35867811; PMCID: PMC9371743.
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