Researchers make the argument for increasing vitamin D supplementation in low- and middle-income countries, where vaccines and other methods of COVID prevention may be less available.

Maintaining adequate vitamin D levels could play a critical role in protecting against serious illness or death from COVID-19, according to new Israeli research.

The study, published last week in the journal PLOS ONE by researchers from the Azrieli Faculty of Medicine of Bar-Ilan University in Safed and the Galilee Medical Center in Nahariya, offers the most convincing evidence to date of the correlations between vitamin D deficiency and poor COVID-19 outcomes – making a case for supplementation, especially in low- and middle-income countries where vaccines and other prevention methods may be less available.

Vitamin D is a fat-soluble vitamin that has long been understood to affect immune response. However, as much as 70% of the adult population in Israel – and even larger percentages in some countries worldwide –  has insufficient or even deficient levels, according to Dr Amiel Dror, who led the study.

“We know that in countries from Africa to Georgia, and in much of the Middle East, people suffer from deficiency,” he said. “In some places, individuals avoid the sun because it is too hot; they stay inside their tents or huts or cover their bodies. Among some religious communities, like the ultra-Orthodox or traditional Islamic community in Israel, women are at higher risk for deficiency because of how they dress.”

Studies also show that low-income levels affect vitamin D levels due to poor diet or reduced exposure to sun, Dror explained. As such, even before COVID-19, most health authorities recommended supplementation. This new research shows that taking those supplements before contracting the virus could help patients avoid the worst effects of the disease.

People with sufficient vitamin D are 20% less likely to die from COVID-19

The Israeli study examined the records of 1,176 COVID-19-positive patients admitted to Galilee Medical Centre between April 2020 and February 2021 whose vitamin D levels had been evaluated between two weeks and two years prior to infection.

Patients with vitamin D deficiency (less than 20 nanograms per milliliter or ng/mL) were 14 times more likely to have severe or critical cases of COVID-19 than those with more than 40 ng/mL, the study found. Even more strikingly, mortality among patients with sufficient vitamin D levels was 2.3% compared to 25.6% in the vitamin D deficient group.

The study adjusted for age, gender, season (summer/winter) and chronic diseases, and found similar results across the board.

The study was conducted during Israel’s first two COVID waves, before vaccines were widely available, and before the recent Omicron outbreak. Dror said that coronavirus mutations should not negate vitamin D’s effectiveness.

Study checks vitamin D levels before infection

The study builds on a pre-print study that the team published in June on the health sharing server MedRxiv.

Those preliminary results found that people who were deficient in vitamin D were at least 20% more likely to die from COVID-19 than people who were not and that 26% of people who had a pre-infection level of vitamin D of 20 ng/mL died, compared with 3% of those who had higher levels of vitamin D.

However, that study received some pushback as it was unclear whether the vitamin D deficiency found in hospitalized COVID-19 patients was the result of the virus, making low vitamin D levels a symptom rather than a contributing factor to severe disease and death.

The newer study corrected that by analyzing vitamin D levels prior to infection.

“The infection itself alters the inflammatory status of our body and vitamin D is consumed, among other nutrients,” Dror said. As such, “we cannot conclude anything about vitamin D levels” in acute patients.

In October, soon after Dror’s first report, Israel’s Coronavirus National Information and Knowledge Center aggregated research studies that likewise showed a circumstantial relationship between one’s level of vitamin D and coronavirus, recommending supplementation. As a result, the country’s Health Ministry recommended increased vitamin D levels during the pandemic.

Different countries recommend different levels of vitamin D for their citizens, but on average the recommended amounts are as follows: Children under 1 should take 10 micrograms a day, kids and teens between the ages of 1 and 18 should take 15, and adults should consume 20 to 100 depending on their BMI.

There have been interventional studies in which doctors tried to supply high doses of vitamin D to acute patients during hospitalization, but most of those studies did not show positive outcomes.

“The vitamin D we consume in drops, pills or in our food has to be activated in both our kidney and liver in order to be functional,” Dror explained. During COVID-19, liver function is generally impaired, which means that the patient will not necessarily be able to transform the consumed dose.

However, there was one study published last June that showed different results. In that study, scientists provided 447 patients at a Spanish hospital between March and May 2020 with calcifediol – a form of vitamin D that has already undergone liver activation – at admission. Of the patients, 20 required the intensive care unit compared to 82 out of 391 nontreated patients. Likewise, 21 out of the 447 patients treated with calcifediol at admission died compared to 62 patients out of 391 nontreated.

Not a replacement for vaccination

The positive results of the Israeli study have led some individuals “with a conspiracy theory mindset” to accuse the pharma industry of withholding information about the supplement in exchange for expensive vaccines or anti-viral treatments, Dror said.

But he stressed that vitamin D is not a replacement for inoculation and that while the Israeli study shows a strong correlation between vitamin D and severe disease and mortality, this is not the same thing as causation.

“In order to see if vitamin D truly abolishes COVID or makes the outcome so much better, we have to run a randomized, controlled study and give one group of patients vitamin D ahead of time and then measure the outcomes,” he explained.

“It is still unclear why certain individuals suffer severe consequences of COVID-19 infection while others don’t. Our finding adds a new dimension to solving this puzzle,” added study co-author Prof Michael Edelstein.

Dror recommended that countries consider giving out the supplement to get people used to taking it before the next wave, which he said is sure to come. The vitamin is cheap, easy to produce and simple to take, and unlikely to be met with hesitancy.

“We are not saying that vitamin D is the key to all bad coronavirus or that it is the ultimate solution,” Dror cautioned. “But we should take vitamin D to help our bones and our immune system anyway. If we can also benefit against COVID-19, it is a double win.”

Image Credits: Pixabay, Tomasz Solinski, Health Ministry.