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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




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.

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.

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.

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


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VitaminDWiki pages with FOLATE in title (16 as of Oct 2022)

This list is automatically updated

Items found: 18
Title Modified
Dementia (vascular) risk increase 60% if take Folate with other B vitamins - Dec 2023 16 Dec, 2023
Folate in VitaminDWiki - many studies 08 Jul, 2023
High dose vitamin D fights Folate gene changes by COVID, autoimmune, CVD, ALZ – Oct 2022 06 Oct, 2022
Folate and Vitamin B6 decrease mortality – May 2022 27 May, 2022
Important Role of Micronutrients during COVID-19 (Zinc, Vitamin D, C, Folate) – May 5, 2021 06 May, 2021
Higher vitamin D is associated with higher Folate or higher Vitamin B-12 – June 2020 13 Jul, 2020
Sweat types, folate, binding protein, lighter skin in females and Vitamin D – Jan 2020 19 Jan, 2020
Glyphosate (Roundup) kills both weeds and the microbes in your gut that produce Folate – July 2019 11 Jul, 2019
Dr. Coimbra interview covering Vitamin D, Magnesium, Folate, Vaccines - Oct 2018 24 Nov, 2018
Neural tube defects more likely due to low vitamin D than low Folate – April 2017 15 Sep, 2018
Off topic – Folate can be produced by micro-organisms, can avoid synthetic Folic Acid – Aug 2018 02 Aug, 2018
First-Episode Psychosis associated with low Vitamin D, Vitamin C and Folate – meta-analysis Nov 2017 22 Dec, 2017
Increased cows milk allergy if Folic acid or Folate added to vitamin D during pregnancy – June 2016 05 Apr, 2017
Autism 17 times more likely with excessive Folate and B-12 (now added to bread) – May 2016 09 Jun, 2016
Autism 17X more likely when have excessive levels of Folate and B-12 – May 2016 12 May, 2016
Vitamin D and Folate fortification of foods - April 2012 25 Apr, 2015
Neural tube defects of pregnant mice reduced by Vitamin D (perhaps less Folate needed) – April 2015 25 Apr, 2015
Hypothesis – Increasing Folate or vitamin D decreases probability of skin cancer – July 2012 02 Aug, 2012

See also web

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


Created by admin. Last Modification: Wednesday January 18, 2023 17:59:44 GMT-0000 by admin. (Version 8)

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