Vitamin D Actions: The Lung Is a Major Target for Vitamin D, <scp>FGF23</scp>, and Klotho

Gayan‐Ramirez, Ghislaine; Janssens, Wim

doi:10.1002/jbm4.10569

Cited by 13 publications

(16 citation statements)

References 178 publications

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“…Other actions include the stimulation of proliferation, alveolar cell differentiation and the expression of some essential lung genes (including surfactant protein) [32]. VDES is also involved in the functional regulation of the cardiovascular system [33,34] and is clearly involved via several pathways in coagulation mechanisms [35].…”

Section: Vitamin D Endocrine System-calcifediolmentioning

confidence: 99%

Vitamin D Endocrine System and COVID-19: Treatment with Calcifediol

et al. 2022

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The COVID-19 pandemic is the greatest challenge facing modern medicine and public health systems. The viral evolution of SARS-CoV-2, with the emergence of new variants with in-creased infectious potential, is a cause for concern. In addition, vaccination coverage remains in-sufficient worldwide. Therefore, there is a need to develop new therapeutic options, and/or to optimize the repositioning of drugs approved for other indications for COVID-19. This may include the use of calcifediol, the prohormone of the vitamin D endocrine system (VDES) as it may have potential useful effects for the treatment of COVID-19. We review the aspects associating COVID-19 with VDES and the potential use of calcifediol in COVID-19. VDES/VDR stimulation may enhance innate antiviral effector mechanisms, facilitating the induction of antimicrobial peptides/autophagy, with a critical modulatory role in the subsequent host reactive hyperinflammatory phase during COVID-19: By decreasing the cytokine/chemokine storm, regulating the renin–angiotensin–bradykinin system (RAAS), modulating neutrophil activity and maintaining the integrity of the pulmonary epithelial barrier, stimulating epithelial repair, and directly and indirectly decreasing the increased coagulability and prothrombotic tendency associated with severe COVID-19 and its complications. Available evidence suggests that VDES/VDR stimulation, while maintaining optimal serum 25OHD status, in patients with SARS-CoV-2 infection may significantly reduce the risk of acute respiratory distress syndrome (ARDS) and severe COVID-19, with possible beneficial effects on the need for mechanical ventilation and/or intensive care unit (ICU) admission, as well as deaths in the course of the disease. The pharmacokinetic and functional characteristics of calcifediol give it superiority in rapidly optimizing 25OHD levels in COVID-19. A pilot study and several observational intervention studies using high doses of calcifediol (0.532 mg on day 1 and 0.266 mg on days 3, 7, 14, 21, and 28) dramatically decreased the need for ICU admission and the mortality rate. We, therefore, propose to use calcifediol at the doses described for the rapid correction of 25OHD deficiency in all patients in the early stages of COVID-19, in association, if necessary, with the new oral antiviral agents.

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Section: Vitamin D Endocrine System-calcifediolmentioning

confidence: 99%

Vitamin D Endocrine System and COVID-19: Treatment with Calcifediol

et al. 2022

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“…The latter cells also express CYP27B1 after stimulation by toll-like receptors, interferon-gamma, or LPS. (5) These epithelial barrier cells also express cathelicidin (as described in "Monocytes and macrophages") after exposure to 1,25(OH)2D with beneficial defense against foreign pathogens.…”

Section: B Lymphocytesmentioning

confidence: 99%

“…In addition, VDR activation decreased viral-induced inflammatory responses even in the absence of effects on some specific viruses. (5) These data at least suggest that vitamin metabolites may be beneficial in clearing pathogens (bacterial or viral) and decrease the inflammatory response of the host against these invaders. Other studies suggest that 1,25 (OH)2D may decrease disease-induced increased remodeling and fibrosis of lung tissues, most likely linked to the well-known antiproliferative and anti-inflammatory effects of the vitamin D endocrine system (Fig.…”

Section: B Lymphocytesmentioning

confidence: 99%

“…This includes the stimulation of proliferation, differentiation of alveolar cells, and the expression of some essential lung genes (including surfactant protein). (5) The VDES also participates in the functional regulation of the cardiovascular system (6) and is involved by several pathways in coagulation mechanisms. (7) Therefore, the lung epithelium, immune, and cardiovascular systems that play a critical role in coronavirus disease 2019 (COVID-19) infections (8) are targets of vitamin D. Mild to severe vitamin D deficiency is highly prevalent around the world (9) and has been associated with a large number of human diseases, including immune disorders and lung and cardiovascular diseases, (1,10) and associated with idiopathic lower-extremity deep vein thrombosis.…”

Section: Introductionmentioning

confidence: 99%

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Vitamin D Endocrine System and COVID‐19

Bouillon

Quesada‐Gómez

2021

JBMR Plus

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Preclinical data strongly suggest that the vitamin D endocrine system (VDES) may have extraskeletal effects. Cells of the immune and cardiovascular systems and lungs can express the vitamin D receptor, and overall these cells respond in a coherent fashion when exposed to 1,25-dihydroxyvitamin D, the main metabolite of the VDES. Supplementation of vitamin D-deficient subjects may decrease the risk of upper respiratory infections. The VDES also has broad anti-inflammatory and anti-thrombotic effects, and other mechanisms argue for a potential beneficial effect of a good vitamin D status on acute respiratory distress syndrome, a major complication of this SARS-2/COVID-19 infection. Activation of the VDES may thus have beneficial effects on the severity of COVID-19. Meta-analysis of observational data show that a better vitamin D status decreased the requirement of intensive care treatment or decreased mortality. A pilot study in Cordoba indicated that admission to intensive care was drastically reduced by administration of a high dose of calcifediol early after hospital admission for COVID-19. A large observational study in Barcelona confirmed that such therapy significantly decreased the odds ratio (OR) of mortality (OR = 0.52). This was also the conclusion of a retrospective study in five hospitals of Southern Spain. A retrospective study on all Andalusian patients hospitalized because of COVID-19, based on realworld data from the health care system, concluded that prescription of calcifediol (hazard ratio [HR] = 0.67) or vitamin D (HR = 0.75), 15 days before hospital admission decreased mortality within the first month. In conclusion, a good vitamin D status may have beneficial effects on the course of COVID-19. This needs to be confirmed by large, randomized trials, but in the meantime, we recommend (rapid) correction of 25 hydroxyvitamin D (25OHD) deficiency in subjects exposed to this coronavirus.

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“…1-alphahydroxylase activity in lung tissue may explain the actions of calcifediol and its higher efficiency with respect to cholecalciferol in respiratory diseases, as calcifediol restores normal blood levels of 25(OH)D more quickly than cholecalciferol, with a 3-to 5-fold greater potency for raising these levels [19]. Moreover, observational and intervention studies suggest that the 25(OH)D status may have clinical implications for the respiratory system [20]. From this rationale, the aim of this narrative revision is to report the current evidence on the role of calcifediol, the major circulating metabolite of vitamin D, for respiratory diseases.…”

Section: Introductionmentioning

confidence: 99%

Calcifediol for Use in Treatment of Respiratory Disease

et al. 2022

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Calcifediol is the prohormone of the vitamin D endocrine system (VDES). It requires hydroxylation to move to 1,25(OH)2D3 or calcitriol, the active form that exerts its functions by activating the vitamin D receptor (VDR) that is expressed in many organs, including the lungs. Due to its rapid oral absorption and because it does not require first hepatic hydroxylation, it is a good option to replace the prevalent deficiency of vitamin D (25 hydroxyvitamin D; 25OHD), to which patients with respiratory pathologies are no strangers. Correcting 25OHD deficiency can decrease the risk of upper respiratory infections and thus improve asthma and COPD control. The same happens with other respiratory pathologies and, in particular, COVID-19. Calcifediol may be a good option for raising 25OHD serum levels quickly because the profile of inflammatory cytokines exhibited by patients with inflammatory respiratory diseases, such as asthma, COPD or COVID-19, can increase the degradation of the active metabolites of the VDES. The aim of this narrative revision is to report the current evidence on the role of calcifediol in main respiratory diseases. In conclusion, good 25OHD status may have beneficial effects on the clinical course of respiratory diseases, including COVID-19. This hypothesis should be confirmed in large, randomized trials. Otherwise, a rapid correction of 25(OH)D deficiency can be useful for patients with respiratory disease.

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Vitamin D Actions: The Lung Is a Major Target for Vitamin D, FGF23, and Klotho

Cited by 13 publications

References 178 publications

Vitamin D Endocrine System and COVID-19: Treatment with Calcifediol

Vitamin D Endocrine System and COVID-19: Treatment with Calcifediol

Vitamin D Endocrine System and COVID‐19

Calcifediol for Use in Treatment of Respiratory Disease

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