The Role of Vitamin A in Wound Healing

https://pubmed.ncbi.nlm.nih.gov/31389093/

Abstract

Vitamin A is an essential micronutrient that comes in multiple forms, including retinols, retinals, and retinoic acids. Dietary vitamin A is absorbed as retinol from preformed retinoids or as pro-vitamin A carotenoids that are converted into retinol in the enterocyte. These are then delivered to the liver for storage via chylomicrons and later released into the circulation and to its biologically active tissues bound to retinol-binding protein. Vitamin A is a crucial component of many important and diverse biological functions, including reproduction, embryological development, cellular differentiation, growth, immunity, and vision. Vitamin A functions mostly through nuclear retinoic acid receptors, retinoid X receptors, and peroxisome proliferator-activated receptors. Retinoids regulate the growth and differentiation of many cell types within skin, and its deficiency leads to abnormal epithelial keratinization. In wounded tissue, vitamin A stimulates epidermal turnover, increases the rate of re-epithelialization, and restores epithelial structure. Retinoids have the unique ability to reverse the inhibitory effects of anti-inflammatory steroids on wound healing. In addition to its role in the inflammatory phase of wound healing, retinoic acid has been demonstrated to enhance production of extracellular matrix components such as collagen type I and fibronectin, increase proliferation of keratinocytes and fibroblasts, and decrease levels of degrading matrix metalloproteinases.

Polcz ME, Barbul A. The Role of Vitamin A in Wound Healing. Nutr Clin Pract. 2019 Oct;34(5):695-700. doi: 10.1002/ncp.10376. Epub 2019 Aug 7. PMID: 31389093.

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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

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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.

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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.

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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.

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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.

 

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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.

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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.

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[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.

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Påverkar vitaminer och metaboliter risken för ö-cellsautoantikroppar och utveckling av diabetes? 2021

https://www.teddy.lu.se/resultat-fran-teddy/alla-forskningsartiklar-indelade-i-amnen/autoantikroppar/paverkar-vitaminer-och-metaboliter-risken-o-cellsautoantikroppar-och-utveckling-av-diabetes-2021

Frågeställningen i studien var om ämnesomsättningsprodukter så kallade metaboliter (aminosyror, fettsyror med mera) och vitaminer (vitamin C och D) i plasma var förändrade före det att en första autoantikropp utvecklades.

• Resultatet från studien visar att barn som fick IAA som första autoantikropp vid ett års ålder hade låga nivåer av vitamin C och kolesterol före det att IAA utvecklades.
• Lite äldre barn som fick GADA som första autoantikropp visade sig ha låga nivåer av sfingomyelin, en fosfolipid som finns i mjölkfett och som är mycket viktig för immunsystemet men också för hjärnans celler, centrala nervsystemet samt den neurologiska utvecklingen.
• De barn som utvecklade antingen IAA eller GADA som första autoantikropp och hade låga nivåer av vitamin D, hade störst risk att få en andra autoantikropp och att utveckla diabetes på kort tid. Barn med GADA som första autoantikropp hade också låga plasmanivåer av diglycerider, lysofosfatidylkolin, triglycerider och alanin, vilket ökade deras risk att utveckla en andra autoantikropp och diabetes.

Studien visar att låga nivåer av både vitamin D och C ökade risken att utveckla en första autoantikropp. Andra biomarkörer hade också låga nivåer före uppkomsten av den första autoantikroppen. 

TEDDY har kunnat påvisa att vanliga enterovirusinfektioner kan trigga en första autoantikropp hos vissa men inte alla barn. Låga nivåer av vitamin D och C samt andra metaboliter tycks kunna bidra till att en virusinfektion utvecklar diabetes hos barn.

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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.

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Adenosine and Autism – Recent Research and a New Perspective | IntechOpen

Källa: Adenosine and Autism – Recent Research and a New Perspective | IntechOpen

”Specifically, we propose that persons with autism can benefit from increased levels of adenosine, a powerful inhibitory neuromodulator and the core molecule of adenosine triphosphate (ATP).”

 

Susan A. Masino, Julia Svedova, Masahito Kawamura, Jr., Francis D. DiMario, Jr. and Inge-Marie Eigsti (August 17th 2011). Adenosine and Autism – Recent Research and a New Perspective, Autism – A Neurodevelopmental Journey from Genes to Behaviour, Valsamma Eapen, IntechOpen, DOI: 10.5772/18957. Available from: https://www.intechopen.com/chapters/18064

 

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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.

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Intake of Ultraprocessed Foods Among US YouthsHealth Concerns and Opportunities for Research and Policy

https://jamanetwork.com/journals/jama/article-abstract/2782880

”The potential implications for future health are significant. Childhood is a critical period for biological development and the establishment of dietary behaviors. Recent systematic reviews and meta-analyses have found that higher intake of ultraprocessed foods is associated with a range of adverse health outcomes in adults and with overweight or obesity in children”

Meyer KA, Taillie LS. Intake of Ultraprocessed Foods Among US Youths: Health Concerns and Opportunities for Research and Policy. JAMA.2021;326(6):485–487. doi:10.1001/jama.2021.9845

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