What are the links between vitamin D and COVID?

Across the internet, I keep reading about some relationships between vitamin D levels and COVID-19. I’ve written about it twice (here and here), but I have never seen reliable, robust, and repeated clinical trial data that supports a link between vitamin D levels or deficiencies and COVID-19.

So, I thought I would take a look at it once again, and see if there’s anything there. I keep wondering if vitamin D is just another “miracle supplement” that, once you scratch the surface of data, you find that there is actually nothing there.

What we know or think we know about COVID-19 seems to change daily, partially because the disease caught us by surprise. But every day we seem to get new data that contradicts something we thought or adds to our knowledge of the disease. And sometimes both.

Let’s take a look at the current data on vitamin D and COVID-19.

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What is vitamin D?

Vitamin D is a group of fat-soluble secosteroids (it’s a scientific name for steroids with a “broken” ring). The most important chemicals in this group are vitamin D3 (known as cholecalciferol) and D2 (known as ergocalciferol).

Generally, when we measure vitamin D levels in the blood, we measure calcifediol (also written as 25(OH)D), which is a form of vitamin D produced in the liver by the hydroxylation of vitamin D3 (cholecalciferol) by the enzyme vitamin D 25-hydroxylase.

Very few foods contain either of the important types of vitamin D. However, some foods can be good sources of the vitamin:

  • Fatty fish, like tuna, mackerel, and salmon
  • Foods fortified with vitamin D, like some dairy products, orange juice, soy milk, and cereals
  • Beef liver
  • Cheese
  • Egg yolks

Many people with broad diets that include a lot of fish, eggs, and other foods can get sufficient vitamin D without supplementation. As I’ve repeated often, short of chronic malnutrition, we get plenty of vitamin D.

Moreover, vitamin D is produced by a process called dermal synthesis. That is, sunlight, specifically UV-B radiation, causes the synthesis of vitamin D in the skin. Technically, vitamin D isn’t a vitamin, because we can manufacture it, it is a hormone. For this article, we’ll just call it a vitamin, even though scientifically it is not.

Although we can manufacture sufficient vitamin D by sunbathing every day, the body has a feedback loop that shuts down production to prevent toxicity. Yes, excess vitamin D is quite dangerous leading to many conditions such as over-absorption of calcium, from hypertension to fatigue. But it also can lead to some dangerous chronic conditions that we’ll discuss later.

Although humans can manufacture vitamin D by sitting in bright sun, there’s one major problem – the risk of skin cancer. As I’ve written before, there are very few ways to prevent cancer, but staying out of the sun is one of them.

Finally, the vitamin D we consume or produce in sunlight is not biologically active. It is generally activated by enzymatic conversion (in a process called hydroxylation) in the kidneys and liver so that the body can use it.

What does vitamin D do or don’t do?

Based on real scientific evidence, vitamin D has a very narrow, but important, set of effects.

First, it is responsible for enhancing intestinal absorption of calcium, iron, magnesium, phosphate, and zinc, important minerals for the continued health of any human being. Many of these minerals (and vitamin D itself) are necessary for good bone health.

Second, since vitamin D is important to calcium homeostasis and metabolism, a deficiency of the vitamin results in rickets, or the adult form of the disease,  osteomalacia. Rickets, because it happens in immature bones, leads to frequent fractures and skeletal deformities. Osteomalacia, because it occurs in adults with fully formed bones, usually only results in numerous fractures.

At this point, that’s it. Robust evidence only supports those two physiological effects.

However, here are a few claims made by the supplement-pushing crowd:

Despite this utter lack of evidence, vitamin D has continued to be the panacea for all that ails humans. For those of us who only care about large, high-quality, peer-reviewed studies, vitamin D is overrated, unless you need to prevent rickets.

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Vitamin D and COVID-19 — clinical evidence

After over two years of this pandemic, I assumed that there would be a lot of clinical evidence that would be published on the links (or lack thereof) between vitamin D levels and COVID-19. I am not going to review every single clinical trial that’s been published because that would take forever. I’m going to focus on high-quality studies (specifically systematic reviews or meta-analyses, which are at the top of the hierarchy of medical research) if any are available.

In a systematic review published in June 2021, the researchers examined 31 peer-reviewed observational studies that examined potential links between COVID-19 and vitamin D. There results did not find any statistically significant associations between vitamin D levels and COVID-19 outcomes. Many of the studies were of poor design or poor quality.

The authors concluded:

While the available evidence to-date, from largely poor-quality observational studies, may be viewed as showing a trend for an association between low serum 25(OH)D levels and COVID-19 related health outcomes, this relationship was not found to be statistically significant. Calcifediol supplementation may have a protective effect on COVID-19 related ICU admissions. The current use of high doses of vitamin D in COVID-19 patients is not based on solid evidence. It awaits results from ongoing trials to determine the efficacy, desirable doses, and safety, of vitamin D supplementation to prevent and treat COVID-19 related health outcomes.

Another systematic review, published on 28 June 2021, showed a similar lack of association between vitamin D levels and COVID-19 outcomes. They examined five studies, which included a total of 467 patients (an incredibly small number), vitamin D levels were not linked to reduced mortality, reduced ICU admissions, and reduced requirements for ventilation.

The authors concluded:

No significant difference with vitamin-D supplementation on major health related outcomes in COVID-19. Well-designed RCTs are required addressing this topic.

In a meta-analysis published on 10 October 2020, the researchers were a bit more enthusiastic about vitamin D and COVID-19. The researchers analyzed six clinical studies. They found that patients with significantly lower serum levels of vitamin D had statistically higher risks of poorer COVID-19 outcomes.

The authors concluded that:

Serum vitamin D levels could be implicated in the COVID-19 prognosis. Diagnosis of vitamin D deficiency could be a helpful adjunct in assessing patients’ potential of developing severe COVID-19. Appropriate preventative and/or therapeutic intervention may improve COVID-19 outcomes.

In a meta-analysis published on 19 May 2021, researchers examined results from 532 patients in three separate studies. There appeared to be a statistically lower ICU requirement in those who received vitamin D supplementation compared to those that didn’t.

In one more meta-analysis published on 23 September 2021, the researchers examined 21 studies that were found to be relevant to the relationship between vitamin D and COVID-19 infection/outcomes. This included 205,869 total patients. I would consider this to be the most robust of the meta-analyses and systematic reviews that I have examined.

The results of this meta-analysis were:

  • Individuals with low serum vitamin D levels were 1.64X more likely to contract COVID-19.
  • The researchers found that people with serum 25(OH)D levels below 20 ng/mL or 50 nmol/L were 2.42X more likely to have severe COVID-19.
  • However, the researchers found that low vitamin D levels did not affect COVID-19 mortality.

Summary

So what are our takeaways from all of this data?

It’s a bit all over the place, though the final meta-analysis I reviewed seemed to provide good (but not great) evidence that supports the hypothesis that lower blood vitamin D levels may lead to worse outcomes from COVID-19.

But that leads to two important claims made about vitamin D:

  1. There is no evidence vitamin D can prevent COVID-19 except when used as a supplement when someone has a known vitamin D deficiency.
  2. Megadoses of vitamin D can be dangerous and do not improve COVID-19 outcomes.

And we don’t know why low vitamin D levels are linked to worse COVID-19 outcomes. It could be that individuals with low vitamin D levels have a lower immune response compared to those with normal vitamin D levels. And no, this does not mean that more vitamin D is going to miraculously boost your immune system so that COVID-19 will never strike. Get that out of your thinking immediately, because none of this evidence supports such a claim.

And one more thing — we have zero evidence regarding vitamin D levels and outcomes from the new omicron variants. Maybe it’s the same as COVID-19 in general, or maybe there’s a difference. We will see.

Citations


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The Original Skeptical Raptor
Chief Executive Officer at SkepticalRaptor
Lifetime lover of science, especially biomedical research. Spent years in academics, business development, research, and traveling the world shilling for Big Pharma. I love sports, mostly college basketball and football, hockey, and baseball. I enjoy great food and intelligent conversation. And a delicious morning coffee!