Does Vitamin D Protect Against COVID-19?

Does vitamin D protect against COVID-19?

Check out this answer from Consensus:

The current body of research suggests that Vitamin D deficiency is linked to a higher risk of COVID-19 infection and worse outcomes. While Vitamin D supplementation shows promise in reducing the severity and mortality of COVID-19, the evidence remains inconclusive. Further high-quality RCTs are necessary to establish the definitive role of Vitamin D in protecting against COVID-19.

The potential protective role of Vitamin D against COVID-19 has been a topic of significant interest and research. Various studies have explored whether Vitamin D supplementation can reduce the risk of infection, severity, and mortality associated with COVID-19.

Key Insights

• Vitamin D Deficiency and COVID-19 Risk:
  • Individuals with low Vitamin D levels are at a higher risk of contracting COVID-19 compared to those with sufficient levels2 3 6.
• Severity and Mortality:
  • Vitamin D deficiency is associated with increased severity and higher mortality rates in COVID-19 patients2 6.
  • Supplementation with Vitamin D may reduce the severity of the disease and the need for intensive care unit (ICU) admission4 7 8.
• Effectiveness of Supplementation:
  • Vitamin D supplementation has shown potential benefits in reducing ICU admissions and mortality rates among COVID-19 patients4 7 8.
  • High-dose Vitamin D supplementation may improve short-term survival rates in older adults with COVID-19, although the effect may not be sustained over a longer period5.
• Uncertainty and Need for Further Research:
  • There is currently insufficient and inconsistent evidence to conclusively determine the benefits and harms of Vitamin D supplementation for COVID-19 treatment1 10.
  • More well-designed randomized controlled trials (RCTs) are needed to provide definitive evidence on the role of Vitamin D in COVID-19 outcomes1 10.

 

 

Does vitamin D protect against COVID-19?

Gideon Meyerowitz-Katz has answered Uncertain

An expert from University of Wollongong in Epidemiology, Public Health, Diabetes

According to the news media pretty much everywhere, the key to surviving COVID-19 is to start taking Vitamin D supplements and never stop. For example, based on the Daily Mail, you’re twice as likely to die from coronavirus if you have low Vitamin D levels than normal levels. The Irish Times is reporting that Irish Vitamin D is essential to surviving the disease. Today dot com calls Vitamin D a “key nutrient” and recommends that you start taking a supplement now.

All of this sounds rosy, but as soon as you take a glance at the evidence something immediately jumps out.

You see, we actually don’t have any idea whether a Vitamin D supplement will improve COVID-19 outcomes. We don’t even really know if low levels of the vitamin make outcomes worse.

It is, as they say, a bit of a minefield.

The Science

There have been so many studies conducted looking at correlations between Vitamin D and COVID-19 already that it’s hard to summarize them all, but broadly speaking they fall into two categories — the really bad and the truly, unforgivably awful*.

Most of the recent news reports are based on three very similar studies. While there are some differences between the three, they basically did the same thing — and had the same glaring issue — so I think it’s fair to take them as a group.

What these three pieces of research did was look at Vitamin D levels from previous research in a range of countries, and then compare those countries on the death rate from coronavirus. Countries where there is previous evidence that the average Vitamin D level is lower had slightly higher levels of COVID-19 death, which the authors argued was because low Vitamin D increases your risk of respiratory infection. If low Vitamin D is associated with a higher risk of death, increasing Vitamin D might lower your risk of death, thus we should supplement immediately!

Except, of course, this quite clearly makes very little sense. These aren’t studies comparing people who have higher or lower levels of Vitamin D on COVID-19 outcomes. They aren’t even retrospective studies looking at COVID-19 outcomes and seeing if the people who died were more likely to have low Vitamin D. They are just vaguely correlating past measured levels of Vitamin D with the number of deaths a country is now seeing from coronavirus. If nothing else, it is far too premature to do this, because death rates are evolving at an incredibly quick rate — the correlation might disappear entirely over the next month even if you find it today. It’s also just terrible science — lots of things correlate well, but that doesn’t mean anything about whether one causes another.

Which brings us to the second group of studies that’s hitting headlines everywhere. Again, the sheer number makes it hard to go through everything, but broadly speaking these are studies that look at people who’ve had COVID-19, and what their Vitamin D levels were. And while this sounds good — it’s a much better way to look at the issue than useless country-level correlations — the actual studies that have so far been published seem to all be, well, terrible.

There’s this piece of research from Indonesia, where they picked a group of patients — with no information on how — conducted somewhat inappropriate statistical tests, and misdefined their methodology. Another study looking at the question got their analysis entirely the wrong way around, so instead of looking at whether Vitamin D prevented death from coronavirus they looked at whether death from coronavirus impacted Vitamin D levels. Both of these studies appear to have been done without ethical approval, which if true is immensely problematic and may very well be illegal.

But being bad is no barrier to impact — one study that has been downloaded 10,000s of times already found that low Vitamin D levels were more common people who admitted to ICU, but included just 20 patients. Meanwhile, the biggest study of this kind so far found no difference in Vitamin D levels between people who were or were not infected with COVID-19, but was extremely preliminary and has only seen a few thousand views, never mind downloads.

One thing you’ll note about all the research above is that pretty much every study is a pre-print. Pre-prints are a way of getting research out quickly to get rapid responses, without waiting for peer-review, but they have some really important limitations. It’s not surprising, perhaps, that research that hasn’t been peer-reviewed might make very basic errors in statistical design, but it does mean that you should take all of this with a HUGE pinch of salt.

This doesn’t mean pre-prints are useless or scientifically invalid, but it does make caution really important when you read them. Unfortunately, the media has taken entirely the opposite view, with hundreds of stories about the presumed benefits of Vitamin D despite these studies being extremely flawed and very unlikely to show anything of the sort.

The other issue with all of these studies is that they are very simple observational research. Most of them don’t even adjust for age, which we know influences both Vitamin D levels and your risk of dying from COVID-19. It’s hard to know whether the results seen are the result of confounding factors, study design, or might have something to do with Vitamin D itself.

It’s also always worth being wary about studies proclaiming benefits from Vitamin D based on observational research, because the last 2 decades are littered with similar hypothesized benefits that have turned out to be wrong. Based on studies like these, Vitamin D has been tested rigorously for everything from heart disease to asthma, and failed to help pretty much every time.

There may be an association between Vitamin D levels and coronavirus outcomes, and it’s certainly possible that lower Vitamin D could cause you to get sicker, but at this point we have no possible way of knowing if that’s the case or not. The research just isn’t there to support it either way.

Should You Supplement?

Ultimately, the question is about supplements, because as I said we all want that silver bullet. Vague correlations are interesting, but we want to know whether we should start popping pills or not. The problem is that, so far, we don’t have any research that even begins to look at this question.

In all of this research, there isn’t anything— not a single study I can find anywhere — actually looked at Vitamin D supplementation and COVID-19. There may be an increased risk associated with having low Vitamin D levels, but that doesn’t necessarily mean that taking a supplement will help, especially when you consider the potential harms that supplementation can bring.

We do know that Vitamin D supplementation may help reduce the risk of having a respiratory infection, based on a very rigorous 2017 systematic review, but even this has some caveats. At best, the benefit was tiny — a 3% absolute reduction in risk over the course of roughly 1 year — and not consistent across all populations. In fact, half of the studies included in this review looked at children, which is a problem given that for COVID-19 we’re really worried about adults. On top of this, the review found no benefit at all for serious outcomes like hospitalization and/or death from Vitamin D.

To put it another way, let’s take the results at face value. Say out of 10,000 people 1,000 will get COVID-19 over the next 12 months. Of these, 200 will be hospitalized, and 10 will die. If they all took Vitamin D, we might expect to see only 970 get COVID-19, but we’d still see 200 hospitalized and 10 dying, based on the results of the systematic review.

The best evidence we have for non-COVID-19 infections seems to indicate that the benefit, if any, from Vitamin D supplementation is pretty negligible. It’s hard to say if this is applicable to the coronavirus — the respiratory infections examined in this study were very diverse and may not translate — but even so it’s not great news.

So should you take a Vitamin D supplement? Here’s where it gets complicated. There are some risks associated with supplementation — every medical intervention has some level of risk — but they are generally accepted to be pretty small. The benefit is probably negligible, and certainly no silver bullet, but given that very few things seem to help with COVID-19, some people might be keen to take any benefit they can find.

Unfortunately, I can’t give you an easy answer. At this point in time, we really have no idea if supplementation is helpful or harmful in this case. If you want to shell out a few dollars on a multivitamin, it’s probably not going to hurt you, but the likelihood that it will make a huge difference in your coronavirus risk is incredibly small.

One thing I would say is that, with many of the hardest-hit areas heading into summer, there might be a better solution than supplements anyway. If you aren’t already, going outside for a brisk walk/run every day in the morning (when it’s not too sunny and/or hot) will up your Vitamin D levels and get some exercise in to boot. It’s a win/win.

Sadly, Vitamin D is probably not a silver bullet against COVID-19.

If only it were.

You can read more about this and more on my Medium blog.

*Note: there may be a decent study out there somewhere, but the media attention has very much focused on some of the most meaningless research.

 

Does vitamin D protect against COVID-19?

Elina Hypponen has answered Uncertain

An expert from University of South Australia in Genetics, Nutrition, Epidemiology

Recent headlines have suggested vitamin D deficiency could increase the risk of dying from COVID-19, and in turn, that we should consider taking vitamin D supplements to protect ourselves.

Is this all just hype, or could vitamin D really help in the fight against COVID-19?

Vitamin D and the immune system

At least in theory, there may be something to these claims. Nearly all immune cells have vitamin D receptors, showing vitamin D interacts with the immune system.

The active vitamin D hormone, calcitriol, helps regulate both the innate and adaptive immune systems, our first and second lines of defence against pathogens.

And vitamin D deficiency is associated with immune dysregulation, a breakdown or change in the control of immune system processes.

Many of the ways calcitriol affects the immune system are directly relevant to our ability to defend against viruses.

For example, calcitriol triggers the production of cathelicidin and other defensins – natural antivirals capable of preventing the virus from replicating and entering a cell.

Calcitriol can also increase the number of a particular type of immune cell (CD8+ T cells), which play a critical role in clearing acute viral infections (such as influenza) in the lungs.

Calcitriol also suppresses pro-inflammatory cytokines, molecules secreted from immune cells which, as their name suggests, promote inflammation. Some scientists have suggested vitamin D might help to alleviate the “cytokine storm” described in the most severe COVID-19 cases.

Evidence from randomised controlled trials suggests regular vitamin D supplementation may help protect against acute respiratory infections.

A recent meta-analysis brought together results from 25 trials with more than 10,000 participants who were randomised to receive vitamin D or a placebo.

It found vitamin D supplementation reduced the risk of acute respiratory infections, but only when it was given daily or weekly, rather than in a large single dose.

The benefits of regular supplementation were greatest among participants who were severely vitamin D deficient to begin with, for whom the risk of respiratory infection went down by 70%. In others the risk decreased by 25%.

Large one-off (or “bolus”) doses are often used as a quick way to achieve vitamin D repletion. But in the context of respiratory infections, there were no benefits if participants received high single doses.

In fact, monthly or annual vitamin D supplementation has sometimes had unexpected side effects, such as increased risk of falls and fractures, where vitamin D was administered to protect against these outcomes.

It’s possible intermittent administration of large doses may interfere with the synthesis and breakdown of the enzymes regulating vitamin D activity within the body.

Vitamin D and COVID-19

We still have relatively little direct evidence about the role of vitamin D in COVID-19. And while early research is interesting, much of it may be circumstantial.

For example, one small study from the United States and another study from Asia found a strong correlation between low vitamin D status and severe infection with COVID-19.

But neither study considered any confounders.

In addition to the elderly, COVID-19 generally has the greatest consequences for people with pre-existing conditions.

Importantly, people with existing medical conditions are also often vitamin D deficient. Studies assessing ICU patients have reported high rates of deficiency even before COVID-19.

So we would expect to see relatively high rates of vitamin D deficiency in seriously ill COVID-19 patients – whether vitamin D has a role or not.

Some researchers have noted high rates of COVID-19 infections in ethnic minority groups in the UK and US to suggest a role for vitamin D, as ethnic minority groups tend to have lower levels of vitamin D.

However, analyses from the UK Biobank did not support a link between vitamin D concentrations and risk of COVID-19 infection, nor that vitamin D concentration might explain ethnic differences in getting a COVID-19 infection.

Although this research adjusted for confounders, vitamin D levels were measured ten years earlier, which is a drawback.

Researchers have also suggested vitamin D plays a role by looking at the average vitamin D levels of different countries alongside their COVID-19 infections. But in the hierarchy of scientific evidence these types of studies are weak.

Should we be trying to get more vitamin D?

There are several registered trials on vitamin D and COVID-19 in their early stages. So hopefully in time we’ll get some more clarity about the potential effects of vitamin D on COVID-19 infection, particularly from studies using stronger designs.

In the meantime, even if we don’t know whether vitamin D can help mitigate the risk of or outcomes from COVID-19, we do know being vitamin D deficient won’t help.

It’s difficult to get enough vitamin D from food alone. A generous portion of oily fish can cover much of our need, but it’s neither healthy nor palatable to eat this every day.

In Australia we get most of our vitamin D from the sun, but about 70% of us have insufficient levels during winter. The amount of exposure we need to get enough vitamin D is generally low, only a few minutes during summer, while during the winter it might take a couple of hours of exposure in the middle of the day.

If you don’t think you’re getting enough vitamin D, speak to your GP. They may recommend incorporating daily supplements into your routine this winter.

I have adapted this answer from my original article in The Conversation

 

Does vitamin D protect against COVID-19?

Claire Hastie has answered Unlikely

An expert from University of Glasgow in Public Health, Cardiovascular Disease, Data Science

There is currently no evidence that vitamin D protects against COVID-19, either in terms of initial infection or severity of disease once infected.

Studies that suggest a link have either failed to take confounding variables into account (factors that are associated with both lower 25 hydroxyvitamin D (25(OH)D) concentration and greater risk of COVID-19, for example black and Asian ethnicity, obesity, socioeconomic deprivation), or they measured 25(OH)D once patients are already ill. This introduces the possibility of reverse causation, i.e. COVID-19 leading to lower vitamin D rather than low vitamin D leading to COVID-19, because vitamin D is a negative acute phase reactant. All existing evidence is limited due to its observational nature. For a definitive answer on whether there is a link we await the results of randomised controlled trials (RCTs), of which there are several underway.

https://www.nice.org.uk/advice/es28/evidence

https://www.cebm.net/covid-19/vitamin-d-a-rapid-review-of-the-evidence-for-treatment-or-prevention-in-covid-19/

 

Does vitamin D protect against COVID-19?

Karin Amrein has answered Uncertain

An expert from Medical University of Graz, Austria in Vitamins, Medicine

We do not know, but we hope so. The first appearance of COVID-19 during the winter months in the Northern hemisphere, the higher incidence in non-white populations and worse outcomes would suggest a role of vitamin D. There are very good data that vitamin D reduces acute respiratory infections (https://www.bmj.com/content/356/bmj.i6583) and asthma exacerbations. Recent US data from a large dataset clearly showed a higher rate of COVID-19 positivity in vitamin D deficient individuals.

 

Does vitamin D protect against COVID-19?

Reinhold Vieth has answered Uncertain

An expert from University of Toronto in Nutrition, Vitamins

Certainty on the topic will probably only come in a year or two, after it is too late to make any difference to people. As of September 2020, there are at least 4 good quality publications surveying COVID-19 patients that conclude that low 25(OH)vitamin D levels are in themselves a risk factor for COVID-19 infection and hospitalization. Low vitamin D status relates to higher risk of COVID-19 positivity and severity to a degree that is comparable to effects of age or race or gender. I consider additional vitamin D (up to 4000 IU/day) a “no lose proposition”, i.e. a potential benefit with no risk.