The idea that a cheap, safe, and readily available supplement can help shield people against infection with SARS-CoV-2 and severe disease is appealing.
However, to date, the evidence that vitamin D really does protect against COVID-19 has been mixed.
The vitamin is essential for maintaining healthy bones and muscles, but there is also
So, in theory, it could protect against COVID-19, principally a respiratory infection.
An unpublished study found a link between mean levels of vitamin D in the populations of 20 European countries and the number of COVID-19 cases and mortality rates in the countries.
Several studies have found an association between vitamin D status and subsequent COVID-19 infection.
For example,
However, the scientists behind this research emphasized that only randomized clinical trials could provide definitive evidence that vitamin D supplementation can prevent COVID-19 and therefore save lives.
This is because observational studies like theirs are vulnerable to two statistical problems, known as “confounding” and “reverse causation.”
Confounding occurs when another variable that the researchers have not fully accounted for influences the outcome. For example, older age and chronic disease affect not only a person’s levels of vitamin D but also their risk of COVID-19.
Reverse causation occurs when the outcome itself affects the variable under investigation. For example, severe COVID-19 could reduce an individual’s vitamin D levels.
In a clinical trial, researchers avoid these problems by randomly assigning participants to receive either the treatment or a placebo, then following them to see what happens.
But clinical trials are costly and take a long time to yield any results.
Researchers at McGill University in Montreal, Canada, and collaborators from the University of Siena, Italy, used a technique called Mendelian randomization, which uses genetic variation between people to simulate a randomized controlled trial, to investigate the effects of vitamin D.
They first identified genetic variants known to influence a person’s vitamin D level.
In effect, these variants are randomly assigned to people at their conception by a combination of their parents’ gametes. This avoids any biases to the outcome from confounding variables — as the variants may break the associations with other confounders or from reverse causation — because the variants are determined before infection.
The researchers then used the presence of these variants as a proxy for vitamin D levels in 14,134 individuals from up to 11 countries testing positive for COVID-19 and over 1.2 million individuals without the disease.
They found no significant associations between the predicted vitamin D levels — by each individual’s genetic makeup — and COVID-19 infection, hospitalization, or severity of illness.
The study appears in PLOS Medicine.
“I guess this paper adds further caution to those who think vitamin D supplements will be a magic bullet against COVID-19, and there are many who still think this,” said Professor Naveed Sattar, Ph.D. from the Institute of Cardiovascular and Medical Sciences at the University of Glasgow in the United Kingdom.
Prof. Sattar was not involved in this research, but he and his colleagues recently published an observational study that found no association between vitamin D levels and risk of COVID-19 infection and mortality.
However, he told Medical News Today that the only way to settle the question is to run clinical trials of vitamin D supplementation. A few are already underway.
“One must always be open-minded about the success of any such trial, but, given these new genetic data added to our prior work and that of others, I remain pessimistic we will see any meaningful gain with vitamin D supplements in the prevention or treatment of COVID-19,” he said.
“I may be proven wrong but will be glad, if so,” he added.
The authors of the new paper caution that their study cannot rule out the possibility that people deficient in vitamin D — rather than having insufficient levels — might benefit from supplementation.
“The reason why we can’t specifically say anything about truly vitamin D-deficient individuals is that [Mendelian randomization] really looks at average effects,” said first author Guillaume Butler-Laporte, M.D.
The researchers designed the study to investigate the effects of average vitamin D levels across a population.
“Anytime we look at averages in statistics, there’s a [chance] that outliers may not be well represented,” he told MNT.
However, he pointed out that Mendelian randomization studies have proved very good at predicting the outcomes of clinical trials of vitamin D in other diseases, including cancer and asthma.
In their paper, Dr. Butler-Laporte and his colleagues suggest that the limited funding available for future randomized controlled trials should therefore focus on other potential treatments for COVID-19.
They note that one limitation of their study was that it only looked at individuals of European ancestry. The possibility remains that vitamin D levels may have different effects on COVID-19 outcomes in other populations.
However, they write, clinical trials of vitamin D supplementation for other diseases have yielded similar results in populations of various ancestries.
COVID-19: What role does vitamin D play?
Studies investigating the role of vitamin D in preventing or treating COVID-19 have drawn conflicting conclusions. But should a lack of evidence stop us from topping up our vitamin D levels as the Northern Hemisphere heads toward winter?
All data and statistics are based on publicly available data at the time of publication. Some information may be out of date.
Most people know vitamin D as an essential vitamin for healthy bones and teeth. But
A systematic review and meta-analysis from 2017 in
The international research consortium, led by Prof. Adrian R. Martineau, from the Centre for Primary Care and Public Health and the Asthma UK Centre for Applied Research, at Queen Mary University of London, in the United Kingdom, looked at data from nearly 11,000 study participants.
Prof. Martineau and colleagues concluded that “Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall.”
But does vitamin D have a part to play in COVID-19? By now, a number of studies have looked for links between the vitamin and the condition, and their findings have conflicted.
In this Special Feature, we investigate why some experts have suggested a link between COVID-19 and vitamin D, and we dig deep to explore how convincing the evidence from the latest studies really is.
We also discuss whether taking a vitamin D supplement can have realistic benefits, particularly for those in communities that have been hit the hardest by COVID-19.
A number of experts have cited the 2017 study as circumstantial evidence that vitamin D may have a protective effect against COVID-19.
Their articles have appeared in journals such as
The common thread is that they highlight that adequate vitamin D levels may help our immune systems fight off the SARS-CoV-2 virus, as with other viruses that cause upper respiratory infections. People with vitamin D deficiency may, therefore, not be able to do this as effectively.
One aspect of this is that it provides an elegant excuse about why people from marginalized racial and ethnic groups have been disproportionately affected by COVID-19, as
There is already evidence to suggest that people with darker skin tones who live in Northern latitudes have inadequate vitamin D levels.
To make vitamin D, our bodies
The pigment melanin that gives our skin its color stops UVB light from reaching the cells. Hence, the darker a person’s skin, the more UVB light they need to make adequate levels of vitamin D from sunshine alone.
A study in the
Data from the past few months have shown that in the U.S. and the U.K., Black people are more likely to die if they have COVID-19 than white people.
Given the relationship between vitamin D and respiratory infections, it is perhaps not unsurprising that many people have suggested a tentative link between the vitamin and the disease.
So, let’s look at the studies that have sought to investigate this link in more detail.
Back in June, the National Institute for Health and Care Excellence, in the U.K., reported that “There is no evidence to support taking vitamin D supplements to specifically prevent or treat COVID‑19.”
The organization based their statement on data from a number of published studies, all of which they deemed to contain a “very low quality of evidence.”
In August, a
Once the authors accounted for confounding factors, they concluded that there was no link between vitamin D levels and the likelihood of needing hospitalization for COVID-19 or dying from the disease.
The main limitation, the team noted, was that the vitamin D measurements had been taken roughly 10 years earlier.
Also in August, researchers in Spain reported the results of a small clinical
The team gave one group of patients a supplementary high dose of calcifediol, a precursor molecule to vitamin D, in addition to a range of drugs to treat COVID-19. The other group did not receive calcifediol.
“Of [the] 50 patients treated with calcifediol, one required admission to the ICU (2%), while of [the] 26 untreated patients, 13 required admission (50%),” the researchers reported.
While these numbers seem impressive, the study was small and has several limitations. One is that the vitamin D levels of the participants were not measured before and during the study. There were also differences in confounding factors, such as other health conditions, between the two groups.
In addition, the study was open label, so both the researchers and the participants knew who had received vitamin D, which leaves room for bias.
Writing in
They explain:
“Pending results of such trials, it would seem uncontroversial to enthusiastically promote efforts to achieve reference nutrient intakes of vitamin D, which range from 400 [international units (IU) per day] in the U.K. to 600–800 IU per day in the U.S.A.”
“These are predicated on benefits of vitamin D for bone and muscle health, but there is a chance that their implementation might also reduce the impact of COVID-19 in populations where vitamin D deficiency is prevalent; there is nothing to lose from their implementation, and potentially much to gain,” the authors continue.
Many governments around the world have set recommended daily levels of the vitamin to ensure that people take in enough. This was true before COVID-19.
In the U.S., the
The NIH recommend reaching these targets through a combination of the diet, sunlight exposure, and supplements.
Natural food sources of vitamin D include oily fish, beef liver, cheese, egg yolks, and mushrooms. Many breakfast cereals and milk and non-dairy alternatives are fortified with vitamin D, as are infant formulas.
In the U.K., Public Health England (PHE) recommend 400 IU or 10 mcg per day for people of all ages. Most people are able to get sufficient vitamin D from their diet and sunlight exposure in the spring and summer. This is not necessarily so during the rest of the year.
“Since it is difficult for people to meet the 10 [mcg] recommendation from consuming foods naturally containing or fortified with vitamin D, people should consider taking a daily supplement containing 10 [mcg] of vitamin D in autumn and winter,” PHE recommend.
They also say that people with little or no sunlight exposure due to work or personal circumstances and “Ethnic minority groups with dark skin from African, Afro-Caribbean, and South Asian backgrounds may not get enough vitamin D from sunlight in the summer and therefore should consider taking a supplement all year round.”
In light of the COVID-19 pandemic, the U.K. government is actively encouraging everyone to take a daily supplement of the vitamin, as many people may be spending more time indoors.
Of course, it makes sense for governments and public health bodies to recommend supplements for those struggling to get enough vitamin D.
But the consumption of dietary supplements is not ubiquitous, and there is variability among different racial and ethnic groups.
A 2016 study in
It is worth mentioning that excessive levels of vitamin D are toxic. “Vitamin D toxicity almost always occurs from overuse of supplements,” the
The upper daily limit of vitamin D for children aged 1–8, they report, is 63–75 mcg or 2,500–3,000 IU. For children aged 9 or over, teens, and adults, it is 100 mcg or 4,000 IU.
The risk of dying from COVID-19 is disproportionately high among people from marginalized ethnic and racial backgrounds.
In May, MNT reported on large study from the U.K. that found that preexisting conditions could not explain this increase in risk — but that there was a clear association with being a part of a racial or ethnic minority group or having experienced poverty.
Considering this data about COVID-19 risk and the fact that many people with darker skin in Northern climates do not have adequate vitamin D levels: Is the sunshine vitamin the reason that people from marginalized ethnic and racial groups are experiencing worse COVID-19 outcomes?
So far, the hypothesis remains just that.
Future scientific investigations into the suggested link between vitamin D status, COVID-19 outcomes, and skin color may provide clarity.
“Since African American and Hispanic populations in the U.S. have both high rates of vitamin D deficiency and bear a disproportionate burden of morbidity and mortality from COVID-19, they may be particularly important populations to engage in studies of whether vitamin D can reduce the incidence and burden of COVID-19,” the authors of the JAMA Network Open study discussed above note in their paper.
Yet vitamin D is likely only going to be one part of the complex puzzle that is COVID-19.
In a letter published in the
“The usual explanation for these differences is the low socioeconomic status and educational levels, the social environment, lifestyle habits, and less access to healthcare services,” they write. “However, there are pieces of evidence that these non-favorable conditions are not enough, and there are other influential factors that may help [lead researchers] to a better approach to the real problem, like some genetic [factors].”
However, Dr. Winston Morgan, from the University of East London, in the U.K., has pointed to the lack of “evidence that the genes used to divide people into races are linked to how our immune system responds to viral infections,” in an opinion piece in The Guardian.
Instead, there is mounting evidence that structural racism is a crucial factor in why marginalized communities are harder hit by COVID-19.
In an exclusive opinion piece for MNT, Dr. Morgan discussed the outcomes of a recent PHE review into why COVID-19 disproportionately affects people from marginalized racial and ethnic groups.
He notes that the review’s recommendations focus on the need to address structural problems in health outcome disparities.
Vitamin D does get a mention. The review’s authors highlight the need for “further evidence as a matter of urgency” in order to deepen our understanding of why people of color are disproportionately experiencing negative outcomes of COVID-19.
In an interview with MNT, Assistant Prof. Tiffany Green, from the University of Wisconsin-Madison School of Medicine and Public Health, explained that “Those of us who work in the health disparities space are saddened but not surprised at the race-based disparities that the COVID-19 crisis has brought to light.”
She pointed to the “racialized class and occupational structures of the U.S.” as a major factor that contributes to who is exposed to the SARS-CoV-2 virus.
To conclude, it makes sense to look after our vitamin D levels as part of our general health, and by extension our ability to fight off infections. But science rarely has easy answers.
In order to navigate our way out of the COVID-19 pandemic, we would be better served if we were able to accept that we are up against a complex interplay of societal and immunological factors.
Fonte: MNT
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