Vitamin D for COVID-19

Last updated: 9 April 2020 18:00EST by Frank Cusimano

Summary

Vitamin D supplementation may be beneficial during the coronavirus pandemic. Although several nutrition groups are recommending supplementation, it is important to note that Vitamin D has not been studied in patients with COVID-19. Previous research supports the use of Vitamin D for prevention and as an adjuvant therapy. Vitamin D plays an important role in both the immune response, inflammatory response, and in the prevention of sepsis. There is some research to suggest it may exacerbate the inflammatory response during active infection, however, there is more data showing it may do the exact opposite. All of the previous research has been focused on patients with vitamin D deficiency. There is no data to support the need for supplementation for those without a deficiency. If you are unsure if you are deficient, experts are recommending against testing at this time due to the increased risk of SARS-CoV2 exposure. Instead, they recommend supplementing with a dose of 1000-2000IU daily during the pandemic. For more information, please check below.

Background

Before we dive into the science of Vitamin D, it is important to note that supplemental Vitamin D has NOT been studied in patients with COVID-19. One scientific ‘review article’ on nutritional considerations commented on Vitamin D use for the treatment of COVID-19 and several other well known nutrition sites have posted about it, but no official studies have been done. In the various published guidelines for the treatment of COVID-19, Vitamin D has not been mentioned. Many experts agree, however, it is an important vitamin to consider.

There are several potential ways that Vitamin D may help in this pandemic of SARS-CoV2. I am going to break it up into four stages:

1. Infection: when the virus infects an individual
2. Replication: when the virus replicates in a host
3. Immune Response: the way the body attempts to fight the virus
4. Advanced Disease: sepsis, septic shock, acute respiratory distress syndrome

For previous posts, I tried to explain when and how a specific vitamin might work. Vitamin D will be no different. Several clinical trials show positive results with Vitamin D for acute respiratory tract infections while the mechanistic data is conflicting. Although the data is the same, many experts are interpreting the data differently.

First, let’s look big picture – Vitamin D has been extensively studied. There has been 27 Cochrane Systematic reviews looking at different clinical conditions – 10 assessing Vitamin D for prevention and 17 assessing Vitamin D for treatment. Of the 27, only three were found to have moderate to high-quality evidence. These reviews showed benefits of Vitamin D for pregnant women and asthma patients and another showed no benefits in the prevention of fractures. Of these three, the beneficial relationship of Vitamin D for asthma patients may be important in the COVID-19 pandemic, and something to be considered. The only other Cochrane Systematic review that could be useful for COVID-19 is the prevention of infections in children under the age of 5 years old, however the data was low evidence and they found no difference with or without supplementation of 400-2500IU/day . Before we move on the science and the four stages: it is important to note that Cochrane has not done a systematic review for upper respiratory infections with Vit D or for patients with sepsis or ARDS. There are, however, several clinical trails looking at these.

Science

Vitamin D is an important secosteroid hormone that can be made or absorbed . Rather than go through the synthesis, absorption, etc. I’ll go over its affects on the body. For biosynthesis see this image. Vitamin D is crucial for maintaining bone integrity and for the maturation of different immune cells . Vitamin D plays an important pleiotropic effect in the lungs, simultaneously supporting the respiratory system while modulating cathelicidin transcription . Vitamin D has both a modulatory and regulatory role in host defense, inflammation, immunity, and epithelial repair .

On a cellular level, Vitamin D performs multiple functions. For one, it binds both the Vitamin D Receptor (VDR) and the Retinoid X Receptor (RXR) initiating different signaling cascades and acting as a potent transcription factor. The vitamin D receptor is constitutively expressed on macrophages, monocytes, and epithelial cells of the lungs. One point of interest is that circulating white blood cells carry the VDR. In a meta-analysis of 23 in vitro studies, Vitamin D was consistently anti-inflammatory suppressing TLR2, TLR4, MCP1, IL-6, and IL-8 . Vitamin D has also been found to induce LL37, a potent anti-microbial. Although SARS-CoV2 is a virus (not a bacteria), virologists have started looking at LL37 as an antiviral .

One of the most important things to consider is Vitamin D deficiency. Vitamin D deficiency can occur through a number of different ways including malabsorption, reduced synthesis, and more. One of the largest issues of Vitamin D deficiency is that it is common amongst older adults with the lowest levels during the winter months. Vitamin D deficiency is also commonly seen in those who are housebound or institutionalized.

Infection

In terms of prevention, vitamin D deficiency has consistently been shown to increase one’s risk of acute respiratory tract infections and viral infections. Taking more Vitamin D than needed, however, has no affect on prevention. While epidemiological associations are great, it is important to understand the underlying mechanisms. Several studies have shown that pathways activated by the binding of Vitamin D, can inhibit viral infection. Rather than go through all of the mechanisms, the review by Teymoori-Rad et al, lists all of the mechanisms and discusses much of the research .

Replication

After infection occurs, the virus begins to replicate. Although not tested with SARS-CoV2, several studies have looked at viral replication with Vitamin D. It is important to note that Vitamin D itself isn’t anti-viral, but the downstream pathways of it’s binding can be. For example, Vitamin D induces human B-defensins which interferes with viral glycoprotein synthesis and viral replication for viruses like HIV-1, adenovirus, RV, and influenza . Other research has suggested that vitamin D may inhibit viral replication through its enhanced secretion of the chemokines CXCL8 and CXCL10 which effect monocyte maturation/differentiation and also through a TLR8-mediated mechanism in macrophages .

Immune Response

In terms of the immune response that occurs when the body is infected with SARS-CoV2, Vitamin D may play multiple important roles. For one, most of the affects of Vitamin D on the immune system seems to be positive. In the activation of the immune response, in COVID-19, we see a hyperimmune response leading to a cytokine storm . In this case, The activation of the immune system is too strong. From most accounts, Vitamin D may reduce the inflammation response by suppressing the activation of INF gamma, TNF alpha, IL12, and IL6. Other mechanisms have also been described on the role of Vitamin D on the activation and modulation of different immune cells including CD8+T cells, B cells, Dendritic cells, monocytes, macrophages, and CD4+T cells . For the best reviews of the effect of VitD on the immune system see Dankers et al., Teymoori-Rad et al, Zdrenghea et al, and Calton et al .

There are some studies, however, that show that Vitamin D may increase IL1b, an important cytokine in the pro-inflammatory response to the virus . Although I do not think this research is particularly robust, some experts are still advising against taking vitamin D supplementation after infection occurs to prevent the cytokine storm . This is controversial as there is even more research suggesting it may inhibit the inflammatory response and prevent decompensation to sepsis and septic shock.

Advanced Disease

I think some of the most promising research comes from studies looking at the effect of Vitamin D on sepsis prevention, treatment, and mortality. In most cases, these studies looked at the effect of vitamin D deficiency or the effect of vitamin D as an adjuvant therapy. Three independent meta-analyses concluded similar results that vitamin D deficiency either increases ones’ susceptibility to sepsis or increases mortality in adult patients with sepsis . Takeuti et al discussed the application of vitamin D for sepsis prevention and other researchers have looked at outcomes of Vitamin D for those that do develop sepsis . An overview of the role that vitamin D deficiency plays in sepsis can be found by Watkins et al .

Lastly, Vitamin D may play a role in thrombosis, coagulation, and hemostasis although this is debated. Many providers, who are working on the front lines, have noted a hypercoaguable state for patients with COVID-19 with thrombi noted in multiple organs. Although Vitamin D deficiency itself was studied in human clinical trials as a precursor of induced hyper-coagulation and/or thrombin generation, the results from this trail, and previous trials did not appear convincing to other experts . At this point, I would say it is a potential area of interest, but lacks definitive data.

Dosing

With the increased risk of becoming vitamin D deficient during these times of social isolation, the Harvard School of Public Health recommends supplementing with 1000-2000IU of Vitamin D per day to maintain adequate vitamin D levels. While personally, I do not think you need to supplement, unless you are deficient, experts are pointing out that spending the money and resources to test your vitamin D levels right now may increase your risk of SARS-CoV2 exposure. For those with darker skin, you may require up to 4000IU of vitamin D. If Vitamin D supplementation is unavailable, you can increase your body’s production of it by staying in the sun for 15 mins or for those with darker skin, 3-4 times that.

As a word of caution: Vitamin D toxicity is a real thing causing confusion, vomiting, abdominal pain, polyuria, polydipsia and effecting calcium absorption . Although the prevalence of acute vitamin D toxicity is unknown, and many have shown one can consume up to 20,000IU a day without toxicity, there have not been studies showing that higher levels prevent infection or further support your immune system . For these reasons, there is no need to take over the recommended dose by Harvard’s School of Public Health.

❌❌❌

Disclaimer: Opinions on this site or on social media do not reflect that of my institutions. I do not provide medical advice. If you have a medical question please see your doctor or if you have a medical emergency, please go to the nearest emergency room.. I have a PhD in Nutrition and Metabolic Biology and three masters degrees including two master’s in nutrition & metabolism. I am a personal trainer & have researched nutrition for 12 years. The info I post is my interpretation of the medical and scientific literature.

References: