Keto diet can mitigate SARS-CoV-2 systemic inflammation
Ketones a fuel for the brain, and the soul
I did NOT expect to cover this subject so soon. Before delving any further, this is how far back (late 2020 on Twitter), I and many others were suggesting dietary intervention to “treat” SARS-CoV-2 infection and its deleterious effects. For future reference and because I don’t like the feeling of laziness, I will also refer to other positive effects of the topic at hand.
Highlights of the paper are below. Many other effects are cited outside the boundaries of this paper after the image of a painting, you should check those too.
The ketogenic diet mitigates the inflammatory responses of SARS-CoV-2 at a systemic level
It “primes” the body to changes the virus induces, mitigating its negative metabolic effects
Rescue cell and bioenergetic metabolism, affecting NAD and Kynurenine Pathway
Rescues mitochondrial function, protects organs
A ketogenic diet can mitigate SARS-CoV-2 induced systemic reprogramming and inflammation
After being “rediscovered” by a small, but smart group of doctors after almost 100 years of being “dormant”, the Ketogenic Diet has been explored as a potential intervention or adjuvant treatment to treat a myriad of conditions, with recent focus lying most on psychological, neuroinflammatory and metabolic conditions. Some doctors argue our civilization finds itself in a “ketones deficient” state and I tend to agree with them.
Here the authors tested if the KD was able to mitigate the systemic inflammatory response of SARS-CoV-2, not merely in the form of severe disease, but the systemic inflammation is what induces the damage after all.
We observed reduced metalloproteases and increased inflammatory homeostatic protein transcription in the heart, with decreased serum pro-inflammatory cytokines (i.e., TNF-α, IL-15, IL-22, G-CSF, M-CSF, MCP-1), metabolic markers of inflammation (i.e., kynurenine/tryptophane ratio), and inflammatory prostaglandins, indicative of reduced systemic inflammation in animals infected under a KD. Taken together, these data suggest that a KD can alter the transcriptional and metabolic response in animals following SARS-CoV-2 infection with improved mice health, reduced inflammation, and restored amino acid, nucleotide, lipid, and energy currency metabolism.
The first step was to analyze the broad gene expression reprograming exerted by a Keto Diet, similar to insulin, ketones (especially BHB) are a systemic molecule, that will affect the entire body, broadly. Mice fed the keto diet had fewer differentially expressed genes (DEGs) than CD (Chow Diet, normal diet with more carbs), knowing which genes are expressed in which way, such as more or fewer leads to insight into the mechanisms and pathways of whatever a research team or la is working on.
This means that the KD reduces the impact of SARS-CoV-2 infection at a gene level, thus cascading into a systemic one. The authors also found that uninfected mice on the KD had similar gene changes as rats under a normal diet and were infected by SARS-CoV-2. The keto diet preemptively primed the mice into some of the transcriptional changes induced by infection. Their focus was mainly on the changes in the heart, liver, spleen, and kidney, the KD modulates the response to SARS-CoV-2 potentially protecting the organs from viral damage.
Some of the changes are reflected below.
In relation to the heart, they found the gene Nmrk2 was significantly downregulated in the KD-infected group. This gene is involved in NAD+ (cell energy) synthesis, they also found several genes related to matrix remodeling (structural and compositional changes around the cells in tissue and organs) were decreased in the KD-infected group. Both of these are usually found in inflammatory states and tissue damage, thus the KD-infected mice had less inflammation and heart injury.
Do you know what else is an essential part of the NAD synthesis pathway ? The Kynurenine Pathway.
As proposed by me, and many researchers, the KD directly modulated the Kynurenine/Tryptophan ratio and IDO2, the sister of IDO1, IDO2 is rarely expressed under normal circumstances but found to be abundant in very severe cases of Covid and in a subset of Long Covid patients.
The authors last finding was one a few of my readers are familiar with. The Ketogenic Diet directly positively influences mitochondrial health and function and rewires how and what it uses as a source of energy, and here the authors found KD mitigates the negative changes brought by SARS-CoV-2. The paper ends here, anything below this point is my own interjection, analysis, etc.
As once said at some point in late 2021, the world could have avoided a lot of damage, death, and suffering if a mere dietary intervention was enacted at a systematic level, or people just exercise. Most of us are not farmers working our asses in a field for 12 hours a day to be able to eat 300-500 grams of carbohydrates and still be “healthy”.
I will now cite a number of positive effects the Ketogenic Diet or BHB has, especially in relation to SARS-CoV-2 and Spike-induced damage (mRNA, endotoxins).
This last one bears a lot more significance to severe cases of Covid, and mRNA-induced dysfunction/damage.
The ketogenic diet favors the production of glutamine, while also improving the neuronal damage induced by NMDA. It directly promotes autophagy (cellular house cleaning), and helps the body remove misfolded and aggregated proteins. One of the enzymes responsible for the control of ketogenesis can also inhibit the deposition of Amyloid Beta.
A recent pilot study had significant success in ameliorating bipolar disorder by using the Ketogenic Diet. The KD has been proposed for years as means to treat depression, it can help MS symptoms, depression and anxiety being two of these symptoms.
A recent trial on 40 critically ill adult septic patients found the “ketogenic diet effectively reduced the necessity of mechanical ventilation, vasopressor support, and insulin therapy, without significant side effects. These clinical data suggest that a ketogenic diet can improve recovery from sepsis-associated organ dysfunction conferring promising therapeutic potential.”
Ketogenesis promotes tolerance to Pseudomonas aeruginosa pulmonary infection, one of the most opportunistic pathogens and often found in severe pneumonia cases, including SARS-CoV-2
Lastly, and deserves to be on its own, a problem many Long Covid and a problem some may experience after going through a systemic inflammatory state.
The ketone body β-hydroxybutyrate mitigates ILC2-driven airway inflammation by regulating mast cell function
BHB attenuates ILC2-mediated type 2 allergic airway inflammation
BHB indirectly suppresses ILC2s by inhibiting mast-cell-derived IL-2
Inhibition of IL-2 limits ILC2 proliferation and CD25 expression but not function
BHB inhibits IL-2 production by mast cells in part through GPR109A activation
Mechanistically, BHB directly inhibits mast cell function in part through GPR109A activation. Similar effects are achieved with either the KD or 1,3-butanediol. Our data reveal the protective role of BHB in ILC2-driven airway inflammation, which underscores the potential therapeutic value of ketone body supplementation for the management of asthma.
I suspect perhaps some of you may not be aware, but besides adopting the diet, you can also use BHB as a supplement, and use it to aid in your own diet, modulate responses, or otherwise adapt to the ketogenic diet. I still highly recommend you try the dietary change first rather than resorting to the supplement.
The average starting dosage is 3 grams, but some go as high as 8 grams, once a day. The older you are, the higher your dosage should be. Usually first thing in the morning, with a lower carbohydrate meal, it can upset more sensible stomachs (like mine) if taken on an empty stomach.
As a reminder, when adopting a ketogenic diet, depending on your health, and lifestyle, supplementation with electrolytes, magnesium, potassium, and salt is highly recommended, because a ketogenic state can make you pee. A LOT.
If you chose to support or supported me at any time, thank you. And thanks for reading =) !
I wish everyone a great Sunday.
Professor - Excellent work. Terpenes are your friend, but being a purveyor of darkness, there is a potential downside... in a diabetic, +ketone body acetoacetate = + oxygen radicals = + endothelial lipid peroxidation = potential + vascular disease. As with all things equilibrium is essential and elementary.