The Case for Keto: Primer Biochemical Activities of Ketosis

(Michael - When reality fails to meet expectations, the problem is not reality.) #1

@brownfat linked to a very informative study in another topic here:

I think this study deserves a Topic of its own to enable more folks to be aware of it and read it. Although the specific subject of the study is neurodegenerative diseases, particularly AD and PD, this study hits all the bases of ketosis. It provides a substantive and fundamental biochemical primer on ketosis, how and why it works and I think provides the rationale for why it’s a preferred metabolic state overall. While very technical I think the study overall understandable. I have many questions so I’m hoping some of you will read it and let us all know whether you’d like to discuss details. Thanks.


(Michael - When reality fails to meet expectations, the problem is not reality.) #2


Yes, this study relates to the treatment of COVID-19. But please do not discuss COVID-19 here. If you want to discuss this study as it relates specifically to COVID-19 treatment, please repost the article link in the COVID category of your choice.

I post this study because it’s a great discussion of how ketosis maintains/restores energy balance.


Human SARS-CoV-2 infection is characterized by a high mortality rate due to some patients developing a large innate immune response associated with a cytokine storm and acute respiratory distress syndrome (ARDS). This is characterized at the molecular level by decreased energy metabolism, altered redox state, oxidative damage, and cell death. Therapies that increase levels of ( R )-beta-hydroxybutyrate (R-BHB), such as the ketogenic diet or consuming exogenous ketones, should restore altered energy metabolism and redox state. R-BHB activates anti-inflammatory GPR109A signaling and inhibits the NLRP3 inflammasome and histone deacetylases, while a ketogenic diet has been shown to protect mice from influenza virus infection through a protective γδ T cell response and by increasing electron transport chain gene expression to restore energy metabolism. During a virus-induced cytokine storm, metabolic flexibility is compromised due to increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that damage, downregulate, or inactivate many enzymes of central metabolism including the pyruvate dehydrogenase complex (PDC). This leads to an energy and redox crisis that decreases B and T cell proliferation and results in increased cytokine production and cell death. It is hypothesized that a moderately high-fat diet together with exogenous ketone supplementation at the first signs of respiratory distress will increase mitochondrial metabolism by bypassing the block at PDC. R-BHB-mediated restoration of nucleotide coenzyme ratios and redox state should decrease ROS and RNS to blunt the innate immune response and the associated cytokine storm, allowing the proliferation of cells responsible for adaptive immunity…