High dose vitamin D fights Folate gene changes by COVID, autoimmune, CVD, ALZ – Oct 2022

A Novel Immunomodulatory Mechanism by Which Vitamin D Influences Folate Receptor 3 Expression to Reduce COVID-19 Severity

Anticancer Res . 2022 Oct;42(10):5043-5048. doi: 10.21873/anticanres.16013.
Rosy J Lu 1 , Purusha Shirvani 1 , Michael F Holick 2

Background/aim:
Identify potential mechanisms involving gene expression changes through which vitamin D supplementation could be beneficial in preventing adverse COVID-19 outcomes.

Materials and methods:
We performed a literature review to identify differentially expressed genes (DEGs) in the blood between severe and mild COVID-19 patients. We compared these with the top DEGs induced by6 months of 10,000 IU/day vitamin D supplementation in healthy adults who were vitamin D deficient/insufficient. We used bioinformatic tools to look for a vitamin D response element (VDRE) in DEGs.

Results:
FOLR3, RGS1, GPR84, and LRRN3 were the most significantly altered genes by 6 months of 10,000 IU/day vitamin D supplementation whose expression levels were also involved in COVID-19 severity. FOLR3 and GPR84 were found to be consistently up-regulated and RGS1 and LRRN3 consistently down-regulated in severe COVID-19 infection. FOLR3 and LRRN3 were down-regulated and RGS1 and GPR84 were up-regulated by 10,000 IU/day vitamin D supplementation.

Conclusion:
FOLR3 and RGS1 are expressed in neutrophils and lymphocytes, respectively. Vitamin D supplementation may decrease the neutrophil-lymphocyte ratio as has been reported in patients admitted with severe symptoms. There is evidence that vitamin D directly influences the expression of the RGS1 gene through vitamin D receptor binding. A potential negative VDRE (nVDRE) in an intron of the FOLR3 gene was found, which was homologous with two known nVDREs. Combined with other transcription factor elements near the newly identified nVDRE, these observations may explain the mechanism by which vitamin D regulates these genes, thus influencing COVID-19 outcomes.
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COVID-19 is not the only disease associated with increased expression of the FOLR3 gene. FOLR3 has been found to be over-expressed in

• autoimmune diseases, such as rheumatoid arthritis and psoriasis (24),
• cardiovascular diseases, such as coronary artery disease (25),
• various cancers (26), and
• Alzheimer’s disease and mild cognitive impairment (27).

Therefore, decreasing FOLR3 expression could be a way through which being vitamin D sufficient with a 25(OH)D of at least 30 ng/ml has a protective effect against other diseases as well. Indeed, considering how 10,000 IU/day of vitamin D supplementation decreased FOLR3 expression nearly trifold but severe COVID-19 raised it five-fold, further studies should be conducted to determine the effects of higher than 10,000 IU/day of vitamin D supplementation on FOLR3 expression to potentially reduce severity of COVID-19 in at-risk patients.

Vitamin D Life speculates cancellation by 15 ,000 daily. or loading dose >300,000 + 50,000 weekly

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See also web

• Folate receptors and transporters: biological role and diagnostic/therapeutic targets in cancer and other diseases - 2019 PDF