Obesogenic and Ketogenic Diets Distinctly Regulate the SARS-CoV-2 Entry Proteins ACE2 and TMPRSS2 and the Renin-Angiotensin System in Rat Lung and Heart Tissues

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541329/

 

Conclusion:

Diet-induced obesity increased the levels of viral entry proteins in the lungs, providing a mechanism whereby SARS-CoV-2 infectivity can be enhanced in obese individuals. Conversely, by maintaining low levels of ACE2 and TMPRSS2 and by exerting an anti-inflammatory effect, the KD can potentially attenuate the severity of infection and migration of SARS-CoV-2 to other ACE2-expressing tissues.

 

Da Eira D, Jani S, Ceddia RB. Obesogenic and Ketogenic Diets Distinctly Regulate the SARS-CoV-2 Entry Proteins ACE2 and TMPRSS2 and the Renin-Angiotensin System in Rat Lung and Heart Tissues. Nutrients. 2021;13(10):3357. Published 2021 Sep 25. doi:10.3390/nu13103357

Annons

A Machine-Generated View of the Role of Blood Glucose Levels in the Severity of COVID-19 – PubMed

Källa: A Machine-Generated View of the Role of Blood Glucose Levels in the Severity of COVID-19 – PubMed

 

”The machine-driven framework we developed repeatedly pointed to elevated blood glucose as a key facilitator in the progression of COVID-19. Indeed, when we systematically retraced the steps of the SARS-CoV-2 infection, we found evidence linking elevated glucose to each major step of the life-cycle of the virus, progression of the disease, and presentation of symptoms. Specifically, elevations of glucose provide ideal conditions for the virus to evade and weaken the first level of the immune defense system in the lungs, gain access to deep alveolar cells, bind to the ACE2 receptor and enter the pulmonary cells, accelerate replication of the virus within cells increasing cell death and inducing an pulmonary inflammatory response, which overwhelms an already weakened innate immune system to trigger an avalanche of systemic infections, inflammation and cell damage, a cytokine storm and thrombotic events. We tested the feasibility of the hypothesis by manually reviewing the literature referenced by the machine-generated synthesis, reconstructing atomistically the virus at the surface of the pulmonary airways, and performing quantitative computational modeling of the effects of glucose levels on the infection process. We conclude that elevation in glucose levels can facilitate the progression of the disease through multiple mechanisms and can explain much of the differences in disease severity seen across the population.”

 

Logette E, Lorin C, Favreau C, Oshurko E, Coggan JS, Casalegno F, Sy MF, Monney C, Bertschy M, Delattre E, Fonta PA, Krepl J, Schmidt S, Keller D, Kerrien S, Scantamburlo E, Kaufmann AK, Markram H. A Machine-Generated View of the Role of Blood Glucose Levels in the Severity of COVID-19. Front Public Health. 2021 Jul 28;9:695139. doi: 10.3389/fpubh.2021.695139. PMID: 34395368; PMCID: PMC8356061.

Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice – PubMed

Källa: Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice – PubMed

 

”Aged mCoV-A59-infected mice have increased mortality and higher systemic inflammation in the heart, adipose tissue, and hypothalamus, including neutrophilia and loss of γδ T cells in lungs. Activation of ketogenesis in aged mice expands tissue protective γδ T cells, deactivates the NLRP3 inflammasome, and decreases pathogenic monocytes in lungs of infected aged mice. These data establish harnessing of the ketogenic immunometabolic checkpoint as a potential treatment against coronavirus infection in the aged.”

 

Ryu S, Shchukina I, Youm YH, Qing H, Hilliard B, Dlugos T, Zhang X, Yasumoto Y, Booth CJ, Fernández-Hernando C, Suárez Y, Khanna K, Horvath TL, Dietrich MO, Artyomov M, Wang A, Dixit VD. Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice. Elife. 2021 Jun 21;10:e66522. doi: 10.7554/eLife.66522. PMID: 34151773; PMCID: PMC8245129.

Clinical efficacy of eucaloric ketogenic nutrition in the COVID-19 cytokine storm: A retrospective analysis of mortality and intensive care unit admission – PubMed

Källa: Clinical efficacy of eucaloric ketogenic nutrition in the COVID-19 cytokine storm: A retrospective analysis of mortality and intensive care unit admission – PubMed

 

”Conclusions: These results show a possible therapeutic role of an EKD in the clinical management of COVID-19. Currently, a prospective controlled randomized trial is running to confirm these preliminary data.”

 

Sukkar SG, Cogorno L, Pisciotta L, Pasta A, Vena A, Gradaschi R, Dentone C, Guiddo E, Martino E, Beltramini S, Donini LM, Carmisciano L, Sormani MP, Bassetti M; GECOVID Study Group. Clinical efficacy of eucaloric ketogenic nutrition in the COVID-19 cytokine storm: A retrospective analysis of mortality and intensive care unit admission. Nutrition. 2021 Sep;89:111236. doi: 10.1016/j.nut.2021.111236. Epub 2021 Mar 7. PMID: 33895559; PMCID: PMC7937042.

Can ketone bodies inactivate coronavirus spike protein? The potential of biocidal agents against SARS-CoV-2 – PubMed

Källa: Can ketone bodies inactivate coronavirus spike protein? The potential of biocidal agents against SARS-CoV-2 – PubMed

 

”Also, a new prophylactic and therapeutic measure against SARS-CoV-2 using acetoacetate is proposed, suggesting that it could similarly break the viral spike through Schiff base reaction with lysines of the spike protein.”

 

Shaheen A. Can ketone bodies inactivate coronavirus spike protein? The potential of biocidal agents against SARS-CoV-2. Bioessays. 2021 Jun;43(6):e2000312. doi: 10.1002/bies.202000312. Epub 2021 Apr 15. PMID: 33857328; PMCID: PMC8250295.

 

Ketogenic Diet as a Preventive and Supportive Care for COVID-19 Patients – PubMed

Källa: Ketogenic Diet as a Preventive and Supportive Care for COVID-19 Patients – PubMed

 

”The association of obesity and COVID-19 prognosis may be related to many different factors, such as chronic systemic inflammation, the predisposition to severe respiratory conditions and viral infections. The ketogenic diet is an approach that can be extremely effective in reducing body weight and visceral fat in the short term, preserving the lean mass and reducing systemic inflammation. Therefore, it is a precious preventive measure for severely obese people and may be considered as an adjuvant therapy for patients with respiratory compromise.”

 

Gangitano E, Tozzi R, Gandini O, Watanabe M, Basciani S, Mariani S, Lenzi A, Gnessi L, Lubrano C. Ketogenic Diet as a Preventive and Supportive Care for COVID-19 Patients. Nutrients. 2021 Mar 20;13(3):1004. doi: 10.3390/nu13031004. PMID: 33804603; PMCID: PMC8003632.

Ketogenesis restrains aging-induced exacerbation of COVID in a mouse model – PubMed

Källa: Ketogenesis restrains aging-induced exacerbation of COVID in a mouse model – PubMed

 

”Highlights: – Natural MHV-A59 mouse coronavirus infection mimics COVID-19 in elderly.- Aged infected mice have systemic inflammation and inflammasome activation.- Murine beta coronavirus (mCoV) infection results in loss of pulmonary γδ T cells.- Ketones protect aged mice from infection by reducing inflammation.

etoc blurb: Elderly have the greatest risk of death from COVID-19. Here, Ryu et al report an aging mouse model of coronavirus infection that recapitulates clinical hallmarks of COVID-19 seen in elderly. The increased severity of infection in aged animals involved increased inflammasome activation and loss of γδ T cells that was corrected by ketogenic diet.”

 

 

Ryu S, Shchukina I, Youm YH, Qing H, Hilliard BK, Dlugos T, Zhang X, Yasumoto Y, Booth CJ, Fernández-Hernando C, Suárez Y, Khanna KM, Horvath TL, Dietrich MO, Artyomov MN, Wang A, Dixit VD. Ketogenesis restrains aging-induced exacerbation of COVID in a mouse model. bioRxiv [Preprint]. 2020 Sep 12:2020.09.11.294363. doi: 10.1101/2020.09.11.294363. Update in: Elife. 2021 Jun 21;10: PMID: 33236006; PMCID: PMC7685240.

[Obesity, inflammation and COVID-19: preventive interest of ketogenic diet?] – PubMed

Källa: [Obesity, inflammation and COVID-19: preventive interest of ketogenic diet?] – PubMed

 

Numerous studies suggest that obesity could be defined as key to the onset of severe forms of this emerging disease. Indeed, SARS-CoV2 infects the host by binding to ACE2 receptors present on the surface of the cells and causes excessive secretion of pro-inflammatory cytokines including IL-1, IL-6 and TNF-α, which lead to developing acute respiratory distress syndrome (ARDS). It therefore seems essential to make up effective preventive strategies to protect this part of the population from the risk of developing a severe form of COVID-19. The ketogenic diet, which is low in sugars and high in fat, has interesting properties, both in the fight against obesity but also against severe infections.

 

Charlot A, Boumiza R, Roux M, Zoll J. Obésité, inflammation et COVID-19 : intérêt préventif de l’alimentation cétogène ? [Obesity, inflammation and COVID-19: preventive interest of ketogenic diet?]. Biol Aujourdhui. 2021;215(1-2):63-72. French. doi: 10.1051/jbio/2021004. Epub 2021 Aug 16. PMID: 34397376.

Adenosine and Ketogenic Treatments – PubMed

Källa: Adenosine and Ketogenic Treatments – PubMed

 

”In addition, KD treatment elevates extracellular adenosine and tissue adenosine content in brain.”

 

Ruskin DN, Kawamura M, Masino SA. Adenosine and Ketogenic Treatments. J Caffeine Adenosine Res. 2020 Sep 1;10(3):104-109. doi: 10.1089/caff.2020.0011. Epub 2020 Sep 16. PMID: 32954218; PMCID: PMC7499891.

Ketogenic diet with medium-chain triglycerides restores skeletal muscle function and pathology in a rat model of Duchenne muscular dystrophy – PubMed

Källa: Ketogenic diet with medium-chain triglycerides restores skeletal muscle function and pathology in a rat model of Duchenne muscular dystrophy – PubMed

”We found that the MCT-KD significantly increased muscle strength and fiber diameter in these rats. The MCT-KD significantly suppressed the key features of DMD, namely, muscle necrosis, inflammation, and subsequent fibrosis.”

 

Fujikura Y, Sugihara H, Hatakeyama M, Oishi K, Yamanouchi K. Ketogenic diet with medium-chain triglycerides restores skeletal muscle function and pathology in a rat model of Duchenne muscular dystrophy. FASEB J. 2021 Sep;35(9):e21861. doi: 10.1096/fj.202100629R. PMID: 34416029.