Emerging Role of Vitamin D and its Associated Molecules in Pathways Related to Pathogenesis of Thrombosis

Mohammad, Sameer; Mishra, Aastha; Ashraf, Mohammad Zahid

doi:10.3390/biom9110649

Cited by 117 publications

(131 citation statements)

References 118 publications

(145 reference statements)

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“…Vitamin D enhances the innate immune response while, paradoxically, protecting against excessive inflammation by suppressing TNFα and the cytokines (e.g., IL-6, IL-17) implicated in severe COVID-19, and elevating anti-inflammatory IL-10 (19,28,31,33,45,91,149,(160)(161)(162)(163)(164)(165)(166)(167)(168)(169). Many of the articles referenced here include detailed descriptions of the role of vitamin D in preventing a "cytokine storm" and several authors, including Meftahi et al, and Biesalski, added a series of cartoons to their papers to simplify the concept (167,168).…”

Section: How Vitamin D May Decrease Serious Covid-19-associated Complmentioning

confidence: 99%

“…Vitamin D also helps prevent viral infections from progressing to pneumonia by tightening cell junctions (19,28,165,172) And, vitamin D's influence on the coagulation pathway decreases risk of acute respiratory distress syndrome as it decreases thrombosis risks (114,127,157,162,169,173). Therefore, correcting vitamin D deficiency might help prevent COVID-19 illness AND help limit complications when prevention is unsuccessful (25,28,114,169).…”

Section: How Vitamin D May Decrease Serious Covid-19-associated Complmentioning

confidence: 99%

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

Benskin

2020

Front. Public Health

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: How Vitamin D May Decrease Serious Covid-19-associated Complmentioning

confidence: 99%

Section: How Vitamin D May Decrease Serious Covid-19-associated Complmentioning

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

137

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“…Recent evidence suggests that vitamin D also has anti-inflammatory and anti-thrombotic effects. Mohammad et al (2019) describe the role of vitamin D in inflammatory and coagulation pathways as well as its role in endothelial activation. They discuss the close connection between vascular inflammation and thrombosis in the context of vitamin D. The anti-inflammatory effects of vitamin D have been demonstrated by treating peripheral blood mononuclear cells from asthmatics with 1,25(OH)2D3 (Zhang et al, 2014).…”

Section: Anti-inflammatory and Anti-thrombotic Effects Of Vitamin Dmentioning

confidence: 99%

“…VDR is expressed in the heart, lungs, kidneys, and other organs. It is distributed throughout the body in endothelial cells, macrophages, dendritic cells, and lymphocytes (Mohammad et al, 2019;Teixeira et al, 2017). Using immunohistochemistry, Wong et al (2008) detected VDR in endothelial and vascular smooth muscle cells of the aortic ring of rats.…”

Section: Vitamin D Receptor and Vdr Ligandmentioning

confidence: 99%

Vitamin D deficiency in association with endothelial dysfunction: Implications for patients with COVID-19

Zhang

McCullough²,

Tecson

2020

Rev. Cardiovasc. Med.

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There is emerging evidence to suggest that vitamin D deficiency is associated with adverse outcomes in COVID-19 patients. Conversely, vitamin D supplementation protects against an initial alveolar diffuse damage of COVID-19 becoming progressively worse. The mechanisms by which vitamin D deficiency exacerbates COVID-19 pneumonia remain poorly understood. In this review we describe the rationale of the putative role of endothelial dysfunction in this event. Herein, we will briefly review (1) anti-inflammatory and anti-thrombotic effects of vitamin D, (2) vitamin D receptor and vitamin D receptor ligand, (3) protective role of vitamin D against endothelial dysfunction, (4) risk of vitamin D deficiency, (5) vitamin D deficiency in association with endothelial dysfunction, (6) the characteristics of vitamin D relevant to COVID-19, (7) the role of vitamin D on innate and adaptive response, (8) biomarkers of endothelial cell activation contributing to cytokine storm, and (9) the bidirectional relationship between inflammation and homeostasis. Finally, we hypothesize that endothelial dysfunction relevant to vitamin D deficiency results from decreased binding of the vitamin D receptor with its ligand on the vascular endothelium and that it may be immune-mediated via increased interferon 1 α. A possible sequence of events may be described as (1) angiotensin II converting enzyme-related initial endothelial injury followed by vitamin D receptor-related endothelial dysfunction, (2) endothelial lesions deteriorating to endothelialitis, coagulopathy and thrombosis, and (3) vascular damage exacerbating pulmonary pathology and making patients with vitamin D deficiency vulnerable to death.

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“…Vitamin D supplementation has been shown to increase T helper (CD4 + ) cells that play a key role in the adaptive immune system in HIV infection (37) . Venous thromboembolism is common in those with severe COVID-19 infection (38,39) and hypovitaminosis D has been reported to correlate with increased thrombosis, which may reflect a direct aetiological effect of vitamin D deficiency or be a surrogate marker of relative immobility for those at most risk (40,41) . Furthermore, protracted activation of the renin-angiotensin-aldosterone system may contribute to chronic cardiorespiratory disease with decreased lung function in patients with hypovitaminosis D (42) .…”

mentioning

confidence: 99%

COVID-19: the older adult and the importance of vitamin D sufficiency

O’Shea¹,

Griffin

Brennan

et al. 2020

J Nutr Sci

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In December 2019, in Wuhan, China, the novel coronavirus ‘severe acute respiratory syndrome 2’ (SARS-CoV-2) was discovered as the cause of a pneumonia-like illness and subsequently named coronavirus disease 2019 (COVID-19). COVID-19 spread and is now a global pandemic. With few exceptions, countries in the Northern hemisphere have higher mortality rates from COVID-19. This may be due to an increased prevalence of older people in Northern Europe at higher risk of having cardio-pulmonary and metabolic comorbidities as well as hypovitaminosis D. With increasing age, immunosenescence and ‘inflammaging’ lead to impaired and maladaptive immune responses to SARS-CoV-2 infections, contributing to the enhanced prevalence of severe COVID-19 in older patients. The association of ageing with increased vitamin D deficiency, which is associated with cardiovascular risk factors and disease and worse prognosis in COVID-19 infection, is discussed. Considerable experimental evidence demonstrates the immuno-modulatory properties of vitamin D, in particular, its role in regulating and suppressing the inflammatory cytokine response to viral respiratory infections links the importance of vitamin D sufficiency as a potential protective factor in COVID-19. There is an urgent need for prospective randomised studies to examine whether hypovitaminosis D correlates with severity of COVID-19 disease and the actual benefit of repletion. Moreover, given what has been described as a ‘pandemic of vitamin D deficiency’, especially in Europe, and in the context of the SARS-CoV-2 contagion, the authors support the call for public health doctors and physicians, with support from Governments, to prioritise and strengthen recommendations on vitamin D intake and supplementation.

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Emerging Role of Vitamin D and its Associated Molecules in Pathways Related to Pathogenesis of Thrombosis

Cited by 117 publications

References 118 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

Vitamin D deficiency in association with endothelial dysfunction: Implications for patients with COVID-19

COVID-19: the older adult and the importance of vitamin D sufficiency

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