COVID-19 and Vitamin D

Introduction

The COVID-19 pandemic is the issue of the day.

Some believe that vitamin D may make a difference in terms of getting infected, the severity of infections, and mortality in the event of severe infection.

The goal of this document is to make the science more readily available.

To do this, we have surveyed the scientific literature, gathered abbreviated excerpts from the scientific literature from the abstracts and studies to highlight the basic conclusions, organized the excerpts around ten basic questions (listed below), and provided links to the original texts from which the abstracts were taken in the event that the reader may want to get more information or cross-check the excerpts.

Notes on the work include:

1. The scientific literature if evolving. More research is coming out every day. This document provides information up to the end of June 2020.
2. Many studies are being released in preliminary form without peer review, because of the urgency in making information available. There may be errors in the work, although this is viewed as unlikely. There may be editorial and other corrections in going from preliminary to final form. Because of these changes, some of the excerpts provided here may be different from the final excerpts.
3. To make the documents more readable and comprehensible, minor changes have been made in some documents to address the following:
   1. widespread use of acronyms (these are expanded where not defined in the extracts from the report or abstract);
   2. the use of technical terms (these are defined);
   3. different ways of describing vitamin D in the blood (these are standardized to 25-hydroxyvitamin D);
   4. different units of measurement for vitamin D in the blood, which are standardized to nanomoles per litre [nmol/l], with the nanograms per millilitre indicated through a tooltip while hovering over the nanomole per litre number;
   5. different units for measuring the strength of supplements (international units [IU}versus micrograms [MCG]), which are standardized to international units with micrograms indicated through a tooltip while hovering over the international unit number.
   All changes are indicated by text in different colour (i.e. red or blue).
4. Some articles address more than one questions. These articles are repeated, with excerpts relevant to a specific key question included.

Questions and Answers

1. Does vitamin D make a difference with respiratory track infections generally?

Commentary: If it does, then it will be worth exploring whether it also makes a difference with COVID-19.

Answer: In studies related to viral and bacterial respiratory infections prior to COVID-19, blood levels of vitamin D made a difference.

A concern with COVID-10 come winter is that it could interact with seasonal influenza, and worsen outcomes for those who also have COVID-19. Thus, regardless of Vitamin D's impact on COVID-19, it may be useful for individuals to have adequate levels of Vitamin D to address seasonal influenza.

2. If yes, why does Vitamin D reduce the incidence of or severity of respiratory track infections generally?

Commentary: Many studies can demonstrate relationship between Vitamin D deficiency and respiratory track infections. Understanding mechanisms through which Vitamin D reduces respiratory track infections can help establish the causal relationship between taking Vitamin D and better outcomes from respiratory track infections.

Answer to the Question: Several mechanisms have been identified to explain how Vitamin D works to reduce respiratory track infections and their severity.

3. Do these mechanisms for respiratory track infections in general work also apply to COVID-19?

Commentary: COVID-19 is different from bacterial infections, and other viral infections. This raises the question whether Vitamin D also works for COVID 19

Answer to the Question: Several studies link Vitamin D deficiency to increased risks of COVID-19 infections and their severity.

4. Is there a relationship between vitamin D levels of people infected with COVID 19 and different populations?

Commentary: If there is a relationship, it is worthwhile to look at the impact of Vitamin D levels on COVID-19. To understand the disease, it is also worthwhile to understand why this relationship exists so that outcomes can be improved.

Answer to Question: Studies of the COVID-19 infections and severity suggest a relationship between COVID-19 infections and severity when one looks at populations in terms of geography (e.g. country-level and latitude-level infections), demographics (e.g. age, gender, skin colour), and health status (e.g. obesity).

5. Is there a relationship between vitamin D levels of people who are severely affected and their outcomes e.g death, length of stay in hospital, etc.?

Commentary: If there is a relationship, then it becomes worthwhile to understand whether outcomes are improved with higher Vitamin D levels and reduced with lower levels. If outcomes are improved with higher levels, then the impact of the disease can be reduced.

Answer to Question: Several studies of patients with COVID-19 have shown that better outcomes are associated with higher Vitamin D levels.

6. Do those with "adequate" levels of vitamin D in their blood are less likely to become infected than those who have lower levels?

Commentary: This question gets at the question whether "adequate" levels of Vitamin D in the blood can protect against getting COVID-19. Answering the question requires an understanding of who is infected and who is not. It also requires an understanding of "adequate" levels of Vitamin D in the blood.

Answer to Question: Although the question is difficult to answer, one study tried to address the question by comparing health records and Vitamin D levels in a large group, to determine whether Vitamin D levels were related to health records of confirmed COVID-19 cases.

7. As a treatment for COVID-19, have double blind placebo controlled clinical trials been undertaken?

Commentary: If so, what did they find? If not, when are they due?

Answer to Question: At the time of this report, there were two clinical trials involving Vitamin D supplementation and COVID-19. One trial was looking at older patients with severe forms of the disease, while the other trial was looking at non-severe patients in the 40 to 70 age group.
The clinical trials were not looking at whether "adequate levels" of Vitamin D before acquiring COVID-19 reduced the risks of getting of the disease or reduced the impact of the disease. There are difficulties in designing such as study because ethics prevents a typical clinical trial in which one group is given a Vitamin D supplement, another group is given a placebo, both groups are exposed to the disease, and outcomes are compared.

8. What is a "sufficient" level of vitamin D in the blood for preventing, or reducing the impact, of respiratory diseases in general, and COVID-19 in particular?

Commentary: When one has a blood test for Vitamin D, the normal or sufficiency range defined by blood testing labs appears to be 76 to 250 nanomoles per litre, with deficiency defined as less than 25, insufficiency defined as 25 to 75, and toxicity defined as greater than 250. Some medical organizations suggest 120 nanomoles per litre is optimal. The Mayo Clinic in 2018 defined the normal range for healthy adults as 50 to 125 nanomoles per litre. These numbers were developed before the COVID-19 pandemic, and are presumably set to optimize health in general, rather than health specific to respiratory track infections or COVID-19

Answer to Question: The answer to the question is controversial. The subject has not been conclusively studied, and there is no scientific or medical consensus on the matter. For example, government agencies have not carried out the usual extensive process needed to determine the Recommended Dietary Allowaince (RDA). In this situation, one is left with expert opinions. The best opinion comes from the authors of an authoritative review in 2017 that concluded that blood levels of Vitamin D improve outcomes from respiratory track infections. This opinion was that blood levels should be in the 100 to 150 nanomoles per litre range.

Note that there is a Recommended Dietary Allowance related to Vitamin D, but that amount was determined with regard to conditions other than respiratory tract infections.

9. If one does not know one's blood levels, how is one to determine whether supplementation is warranted?

Commentary: The factors which help determine blood levels of Vitamin D are understood. Natural levels of Vitamin D are created in the skin in response to sunlight. The rule is the more sunlight, the more Vitamin D. Factors affecting the creation of Vitamin D include the latitude at which one lives, whether it is summer or winter, how much one is outdoors, how much clothing one wears, whether one uses sunscreens, one's skin colour, and one's age. Persons that are overweight may be able to create Vitamin D but not utilize it effectively in the body. In addition to natural factors, some countries supplement processed food with Vitamin D, so one's Vitamin D levels in the blood are influenced by the extent to which one consumes these supplemented foods.

Answer to Question: Blood levels of Vitamin D have been studied at the country level. These levels can be useful in determining one's blood levels of Vitamin D.

10. If supplementation is warranted, what does one need to know about dosage and other details?

Commentary: Supplementation over 4,000 international units is not recommended.

Answer to Question: Magnesium levels appear to affect Vitamin D levels in the blood, because the enzumes that synthesize and metabolize Vitamin D are magnesium dependent. There is no simple test for magnesium levels, but many North Americans are believed to be deficient in magnesium.