Study Shows Vitamin D Protects Lungs From COVID-19 Infection. Vitamin D Supplementation More Relevant Now Since BA.5 Variant Exhibits Lung Tropism!
: A new study by researchers from Pennsylvania State University has found that Vitamin D effectively protects the lungs during viral infection by the SARS-CoV-2 pathogen.
Considering that the world is currently entering a new wave involving the more transmissible and more immune evasive SARs-CoV-2 BA.5 variant that has been found to be more pathogenic and exhibits even stronger tropism towards the lungs, the relevance of Vitamin D supplementation is even more important now. https://www.biorxiv.org/content/10.1101/2022.05.26.493539v1
Supplementation with Vitamin D has been linked to improved outcomes from respiratory virus infection, and the COVID19 pandemic has renewed interest in understanding the potential role of vitamin D in protecting the lung from viral infections.
The COVID-19 Supplements
study team hence evaluated the role of Vitamin D using animal models of pandemic H1N1 influenza and SARS-CoV-2 infection.
The study findings showed that in mice, dietary induced vitamin D deficiency resulted in lung inflammation that was present prior to infection.
Vitamin D sufficient (D+) and deficient (D-) wildtype (WT) and D+ and D-Cyp27B1 (Cyp) knockout (KO, cannot produce 1,25(OH)2D) mice were infected with pandemic H1N1.
The study found that D- WT, D+ Cyp KO, and D- Cyp KO mice all exhibited significantly reduced survival compared to D+ WT mice.
Importantly, survival was not the result of reduced viral replication as influenza M gene expression in the lungs was similar for all animals.
Based on these findings, additional experiments were performed using the mouse and hamster models of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection.
Importantly, in these studies, high dose vitamin D supplementation reduced lung inflammation in mice but not hamsters. A trend to faster weight recovery was observed in 1,25(OH)2D treated mice that survived SARS-CoV-2 infection. There was no effect of vitamin D on SARS-CoV-2 N gene expression in the lung of either mice or hamsters.
Hence the study findings showed that vitamin D deficiency enhanced disease severity, while vitamin D sufficient/supplementation reduced inflammation following infections with H1N1 influenza and SARS-CoV-2.
The study findings were published on a preprint server and are currently being peer reviewed. https://www.biorxiv.org/content/10.1101/2022.06.29.498158v1
It has already been known that low vitamin D levels lead to poor outcomes following acute respiratory infection (e.g., influenza). This is why high doses of vitamin D supplements have been recommended to reduce the severity of seasonal influenza.
In the ongoing COVID-19 pandemic, caused by the SARS-CoV-2, scientists renewed their interest in studying the role of vitamin D in protecting individuals from severe infection.
Past studies have shown that vitamin D supplementation is beneficial for treat
ing COVID-19. These studies have shown that low levels of vitamin D circulation (serum 25(OH)D, 25D) were correlated with a high mortality rate among COVID-19 patients.
Medical researchers reported that vitamin D and the active form of vitamin D (1,25(OH)2D, 1,25D) play a significant role in the anti-viral response. However, the extent of the effect may vary with different viruses.
A past in vitro study revealed that 1,25D treatment of T cells from individuals infected with human immunodeficiency virus (HIV) showed a significant decrease in viral RNA transcription by direct decrease of NF-kB, which reactivates proviral HIV. However, similar in vitro treatment on epithelial cells of patients infected with respiratory syncytial virus (RSV) did not affect viral replication.
Researchers revealed that the production of cytokines (e.g., TNFa, IL-5, IL-1b, IL-6, IL-10 and type I interferons) and antimicrobial peptides (e.g., cathelicidin, b-defensin, etc.,) at mucosal surface play an important role in the innate immune response against viruses. Many studies have reported that 1,25D and other vitamin D analogs induce the production of cathelicidin in response to viral infection.
As a result of studies reporting that cathelicidin LL-37 can effectively kill viruses, such as influenza, researchers believe it could also inhibit the SARS-CoV-2 virus.
An important attribute of 1,25D is that it reduces IFNg, IL-6, and TNF levels and restricts inflammatory responses.
Past research has also shown that vitamin D targets lung epithelial cells due to the presence of vitamin D receptors (VDR). A previous study using a mice model demonstrated that mice treated with 1,25D precursors were also protected from subsequent H1N1 influenza infection.
The study team utilizing animal models focused on determining Vitamin D's role in SARS-CoV-2 and H1N1 influenza. The study team determined the effect of vitamin D supplements on the lung anti-viral response in animal models.
The team utilized two animal models, i.e., mice and hamsters. The experimental findings from both the animal models suggested that vitamin D supplements effectively reduced lung inflammation following SARS-CoV-2 and H1N1 influenza infection.
Past studies have already shown that D- mice had lung infections even without viral infection. A previous study by the same group of researchers reported that feeding D- diets to mice inhibited the production of 1,25D (Cyp KO), which resulted in severe vitamin D deficiency. The current study reported severe influenza infection in D- Cyp KO, while minimal infection was observed in D+ WT mice.
The stud team reported that following influenza infection, the survival of D+ Cyp KO mice was significantly less compared to D+ WT mice. Similarly, the study team observed that the introduction of vitamin D supplement significantly lowered lung inflammation and Ifnb expression in the lung of mice after SARS-CoV-2 infection.
The study findings showed that vitamin D treatments did not show any effect on the expression of viral RNA (SARS-CoV-2 or H1N1 influenza) in the lungs of both hamsters and mice. However, it controlled the hosts’ inflammatory response to viruses in the lungs.
It was found that a high dose of vitamin D treatment (D++) exhibited a similar level of protection from SARS-CoV-2 in mice.
Furthermore, 25D treatment supported a faster recovery in SARS-CoV-2 infected mice. The finding of this study is supported by previous studies that reported 25D treated mice exhibited a reduction in lung inflammation.
Vitamin D treatment however showed an insignificant effect on weight loss and lethality following H1N1 infection.
The study team reported that SARS-CoV-2 infection-induced Cyp27B1 and Cyp24A1 in the lungs of mice infected with SARS-CoV-2.
The team stated that the ability of the host to produce Cyp27B1 is essential for the survival of mice with H1N1 infection. The dietary supplements, i.e., only a high dose of vitamin D supplement (D++), increased the concentration of 25D in serum.
The research findings strongly indicated that vitamin D and 1,25D treatment could effectively protect the lungs from COVID-19 infection. More clinical studies are required to understand better the underlying mechanism by which vitamin D regulates anti-viral response in the lungs.
As the world is just entering a new wave involving the BA.5 variant that has a stronger tropism towards the lungs, readers are advised to take high doses of Vitamin D during this phase but only after consulting a doctor.
When procuring Vitamin D supplements, be careful to choose the right brands and manufacturers as many contain substandard ingredients or forms that are either not bioactive or cannot be properly absorbed by the human gut. Stay away from supplements made in India, Myanmar, Thailand, Philippines, Indonesia and worse brand whose owners are ethnic Indians as the have a bad track record of thinking about profits over product quality. The best brands in the market are Now, Nature’s Bounty, Doctor’s Best, Nature Made, Sigform, Solaray, Piping Rock, Solgar and Puritan’s Pride.
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