Vitamin D Supplementation: A Potential Approach for Coronavirus/COVID-19 Therapeutics?

Arboleda, John F.; Urcuqui-Inchima, Silvio

doi:10.3389/fimmu.2020.01523

Cited by 52 publications

(54 citation statements)

References 60 publications

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“…Several studies have shown that vitamin D decreases the severity of dengue fever (151). Oral vitamin D supplements of 4,000 IU for 10 days were significantly more effective than 1,000 IU in reducing dengue virus replication and controlling the damaging cytokine hyper-reaction (151)(152)(153)(154). Vitamin D supplementation also reduced rotavirus replication in pigs (154).…”

Section: Vitamin D Enhances Resistance To Viral Illnessesmentioning

confidence: 99%

A Basic Review of the Preliminary Evidence That COVID-19 Risk and Severity Is Increased in Vitamin D Deficiency

Benskin

2020

Front. Public Health

133

137

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As the world's attention has been riveted upon the growing COVID-19 pandemic, many researchers have written brief reports supporting the hypothesis that vitamin D deficiency is related to the incidence and severity of COVID-19. The clear common thread among the top risk groups-vitamin D deficiency-may be being overlooked because of previous overstated claims of vitamin D benefits. However, the need to decrease COVID-19 fatalities among high-risk populations is urgent. Early researchers reported three striking patterns. Firstly, the innate immune system is impaired by vitamin D deficiency, which would predispose sufferers to viral infections such as COVID-19. Vitamin D deficiency also increases the activity of the X-chromosome-linked "Renin-Angiotensin" System, making vitamin D deficient individuals (especially men) more susceptible to COVID-19's deadly "cytokine storm" (dramatic immune system overreaction). Secondly, the groups who are at highest risk for severe COVID-19 match those who are at highest risk for severe vitamin D deficiency. This includes the elderly, men, ethnic groups whose skin is naturally rich in melanin (if living outside the tropics), those who avoid sun exposure for cultural and health reasons, those who live in institutions, the obese, and/or those who suffer with hypertension, cardiovascular disease, or diabetes. And thirdly, the pattern of geographical spread of COVID-19 reflects higher population vitamin D deficiency. Both within the USA and throughout the world, COVID-19 fatality rates parallel vitamin D deficiency rates. A literature search was performed on PubMed, Google Scholar, and RSMLDS, with targeted Google searches providing additional sources. Although randomized controlled trial results may be available eventually, the correlational and causal study evidence supporting a link between vitamin D deficiency and COVID-19 risks is already so strong that it supports action. The 141 author groups writing primarily about biological plausibility detailed how vitamin D deficiency can explain every risk factor and every complication of COVID-19, but agreed that other factors are undoubtedly at work. COVID-19 was compared with dengue fever, for which oral vitamin D supplements of 4,000 IU for 10 days were significantly more effective than 1,000 IU in reducing virus replication and controlling the "cytokine storm" (dramatic immune system over-reaction) responsible for fatalities. Among the 47 original research studies summarized here, chart reviews found that serum vitamin D levels predicted COVID-19 mortality Benskin Evidence Linking Vitamin D, COVID-19 rates (16 studies) and linearly predicted COVID-19 illness severity (8 studies). Two causal modeling studies and several analyses of variance strongly supported the hypothesis that vitamin D deficiency is a causal, rather than a bystander, factor in COVID-19 outcomes. Three of the four studies whose findings opposed the hypothesis relied upon disproven assumptions. The literature review also found that prophylactically correcting possible ...

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Section: Vitamin D Enhances Resistance To Viral Illnessesmentioning

confidence: 99%

A Basic Review of the Preliminary Evidence That COVID-19 Risk and Severity Is Increased in Vitamin D Deficiency

Benskin

2020

Front. Public Health

133

137

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“…In light of accruing evidence that vitamin D3 status is inversely correlated with severity of COVID-19 ( 23 – 26 ), it is significant that, via its hormone-like actions on gene expression, D3 has been shown to be a potent activator of both TXNRD1 and GCLC. In a microarray study, 6 h after exposure to 1,25-dihydroxyvitamin D3, TXNRD1 mRNA was upregulated 7.1X, and GCLC was upregulated 2.5X ( 27 ).…”

Section: The Potential M Pro Targets Txnrd1 and Gcmentioning

confidence: 99%

Understanding Selenium and Glutathione as Antiviral Factors in COVID-19: Does the Viral Mpro Protease Target Host Selenoproteins and Glutathione Synthesis?

Taylor

Radding

2020

Front. Nutr.

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Glutathione peroxidases (GPX), a family of antioxidant selenoenzymes, functionally link selenium and glutathione, which both show correlations with clinical outcomes in COVID-19. Thus, it is highly significant that cytosolic GPX1 has been shown to interact with an inactive C145A mutant of M pro , the main cysteine protease of SARS-CoV-2, but not with catalytically active wild-type M pro . This seemingly anomalous result is what might be expected if GPX1 is a substrate for the active protease, leading to its fragmentation. We show that the GPX1 active site sequence is substantially similar to a known M pro cleavage site, and is identified as a potential cysteine protease site by the Procleave algorithm. Proteolytic knockdown of GPX1 is highly consistent with previously documented effects of recombinant SARS-CoV M pro in transfected cells, including increased reactive oxygen species and NF-κB activation. Because NF-κB in turn activates many pro-inflammatory cytokines, this mechanism could contribute to increased inflammation and cytokine storms observed in COVID-19. Using web-based protease cleavage site prediction tools, we show that M pro may be targeting not only GPX1, but several other selenoproteins including SELENOF and thioredoxin reductase 1, as well as glutamate-cysteine ligase, the rate-limiting enzyme for glutathione synthesis. This hypothesized proteolytic knockdown of components of both the thioredoxin and glutaredoxin systems is consistent with a viral strategy to inhibit DNA synthesis, to increase the pool of ribonucleotides for RNA synthesis, thereby enhancing virion production. The resulting “collateral damage” of increased oxidative stress and inflammation would be exacerbated by dietary deficiencies of selenium and glutathione precursors.

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“…Nowadays, and pending the results of appropriate studies (antimalarial drugs, vitamin D, trained immunity, etc.) (16)(17)(18)(19), the only preventive measures that have been proven effective are the implementation of precautions and hygienic measures to minimize human transmission of the virus, especially in highrisk populations. The investigation focused on "healthy" people who have contacted the virus and did not develop the disease, or those who have been cured without problems (including the asymptomatic carriers) is a crucial issue (9).…”

Section: Discussionmentioning

confidence: 99%

Thoughts From the Trenches: Should We Look at the “Healthy”?

Martínez‐Taboada

López‐Hoyos

Crespo

et al. 2020

Front. Public Health

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Vitamin D Supplementation: A Potential Approach for Coronavirus/COVID-19 Therapeutics?

Cited by 52 publications

References 60 publications

A Basic Review of the Preliminary Evidence That COVID-19 Risk and Severity Is Increased in Vitamin D Deficiency

A Basic Review of the Preliminary Evidence That COVID-19 Risk and Severity Is Increased in Vitamin D Deficiency

Understanding Selenium and Glutathione as Antiviral Factors in COVID-19: Does the Viral Mpro Protease Target Host Selenoproteins and Glutathione Synthesis?

Thoughts From the Trenches: Should We Look at the “Healthy”?

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