“You should publish the article as quickly as possible,” I was advised by Dr. Shaul Lev, who heads the general intensive care unit at Hasharon Hospital in Petah Tikva, and chairman of the Israel Society for Clinical Nutrition, at the conclusion of our interview. “Every week of delay in publishing this information can result in thousands of unnecessary infections, some of them serious and even fatal. It can save lives.”

So here it is.

Increasing scientific evidence from around the world indicates that vitamin D, a vitamin that doesn’t have great public relations, can protect against infection by COVID-19, and that it’s possible that for those suffering from the virus, the symptoms might be lessened and the death verdict annulled simply by taking vitamin D. It’s inexpensive and readily available. Is the solution at hand?

The first studies in the world appeared last April. One of them, which examined a large database, was conducted by the research institute of Israel’s Leumit health maintenance organization in association with Bar-Ilan University, and it came up with impressive results.

“Already at the start of the first wave, when I was working in the HMO’s coronavirus directorate and receiving patients who tested positive, I noticed that in many cases they had low levels of vitamin D,” says Yevgeny Marzon, who is director of the Department of Managed Medicine at Leumit and led the study.

“It was very obvious,” Dr. Marzon continues. “In order to verify this intuition, we collected data from more than 7,000 people who were tested for the coronavirus between February and April, and who also been tested for vitamin D in the past year. The results, after taking into account variables such as age, sex, socioeconomic level and underlying illnesses, were unequivocal: People with low levels of vitamin D were at heightened risk of being infected by the coronavirus, and the lower their vitamin D level, the higher the probability that they would be hospitalized – in other words, that they would develop more serious symptoms. It looked as though higher levels [of vitamin D] could protect people from becoming infected.”

Since then, similar articles have been published in a host of countries: the United States, Germany, France, Italy, China, Iran, South Korea, India, Britain, Switzerland and Israel. Time and again, a significant connection was found between the level of vitamin D in the blood and a susceptibility to infection by the coronavirus. Individuals with a vitamin D deficiency are more disposed to be infected by the virus, and in case of infection a low level of vitamin D increases the likelihood of developing complications. The opposite is also true: Patients with high levels of vitamin D tend to suffer less from serious symptoms and to be less likely to die. In general, it can be said that there is a linear connection: The seriousness of the disease correlates completely with one’s level of vitamin D.

“The effectiveness of vitamin D in protecting against infection and in treating patients is already an established fact,” says Marzon, a specialist in family medicine. “As a physician who is in the field and who speaks to dozens of patients every day, I am very disappointed that the authorized medical personnel have not yet issued recommendations [regarding vitamin D]. I have no explanation as to why there is no systematic policy of preventing infection by the virus and of treating mild and intermediate cases in the community with the aid of vitamin D. I suggest to my patients that they take a vitamin D additive and mention that this is a warm personal recommendation.”

The large disparity between the results of the growing number of studies and what’s happening on the ground is infuriating. Yes, one person will have heard a vague recommendation on television, and someone else will have encountered information about vitamin D’s importance elsewhere – but the general feeling is that it’s some sort of rumor. Amid the chaos that characterizes the pandemic’s management, the array of opinions and assessments and the abundant wrangling and vested interests – no clear voice is stating: Here’s a fruit that grows very low – pick it.

Thirty heads and 70 tails

Correlation is not causality, of course. The fact that there is a correlation between two variables – in this case, between vitamin D levels and the rate of coronavirus infection – is not proof of a causal connection between them. As another example, the fact that a clear-cut correlation exists between the consumption of chocolate in various countries and the per capita rate of Nobel Prize winners in them does not prove that eating chocolate improves one’s cognitive ability.

It’s true that Switzerland consumes the largest amount of chocolate per capita and also has the largest number of Nobel laureates, relative to its population, while China, which has the lowest rate of chocolate consumption, is at the bottom of the list of winners (as of 2011). Nevertheless, these are two non-dependent variables with no convincing causal connection between them. It's likey that the basis for the correlation between the two variables lies in the existence of a third variable, such as the country’s level of affluence. Rich countries invest a great deal of money in scientists, and their citizens can also pamper themselves by eating chocolate.

Sometimes, a correlation is only a correlation, and in order to demonstrate causality between two variables – that is, to prove that one is indeed the cause of the other – a controlled experiment needs to be conducted, in which two similar groups are compared, in only one of which is there intervention involving the element being examined. That, of course, is far more difficult to carry out.

Recently, though, just such an experiment was conducted, which examined directly and under controlled conditions the connection between vitamin D and coronavirus symptoms. The results were dramatic. In Spain, 76 coronavirus patients, who were hospitalized with respiratory difficulties, were divided into two groups immediately upon admission. The patients in the first group received particularly high dosages of vitamin D; those in the second group were treated in the normal way. At the end of the experiment it turned out that only 2 percent of the patients who received vitamin D were subsequently transferred to intensive care – as compared with 50 percent of the patients who did not receive the vitamin (and two of whom died).

The conclusion seems to be clear: Vitamin D wields a dramatic influence on improving the condition of COVID-19 patients. It can reduce the severity of the symptoms, lower the likelihood of needing intensive care and, it follows, also reduce the risk of death.

That conclusion could upend all we know about treatment of the disease. But is it correct?

Can we draw such far-reaching conclusions from a single experiment, carried out under the limitations of a surging pandemic and with a small number of participants? After all, it could be solely the hand of chance that fomented those impressive results. There is always the possibility that even though the patients were divided into two groups randomly, according to the order of their arrival in the hospital, it was only by chance that the condition of those who received the vitamin didn’t deteriorate. This is comparable to flipping a coin 100 times, when you expect it to come out 50 times heads and 50 times tails, but perhaps getting landing 30 on heads and 70 times on tails.

“In normal times, it would in fact be better to wait for more research,” says Saar Wilf, an Israeli high-tech entrepreneur who half a year ago dropped most of what he was doing and began devoting his time, on a voluntary basis, to deciphering the coronavirus riddle. “But these are not normal times. There’s a pandemic out there.” Wilf is currently funding a number of clinical trials and initiating projects that are looking for possible solutions.

Several years ago, together with another local tech person, Aviv Cohen, who today is also working on a volunteer basis on behalf of the mission, he founded Rootclaim, a nonprofit that uses models and probabilistic tools to shed light on issues about which there is abundant evidence, often contradictory and sometimes partial, to try to identify the “signal” within the “noise.”

“In light of the plentiful studies about vitamin D and the results of the Spanish experiment, with all its weaknesses, we wanted to estimate the benefit and the risk of adopting vitamin D treatment for coronavirus patients, as compared with the benefit and the risk of the conservative approach, which says we should wait,” Cohen says. “With the help of mathematical models, which try to challenge research results, and based on a rigorous approach, we reached the conclusion that it’s irresponsible to wait for more studies, and that it’s important to start treating patients now with vitamin D. Despite the limitations of the Spanish experiment, it can be concluded with a very high probability, above 80 percent, that a significant effect exists – although perhaps less than that of the results of the experiment – in reducing the severity of the symptoms.”

Everyone knows that you can use statistics to prove just about anything, right?

Wilf: “Our assessment doesn’t take into account only the Spanish study, detached from any context. The Spanish study joins a very large mass of evidence from several disciplines – epidemiological, biological and medical – all of which point to vitamin D as the ‘prime suspect.’ If the Spanish study had found that a five-minute massage of the left leg cures coronavirus, it would be reasonable to assume that a mistake had occurred, even if the results were clear-cut. But in the case of vitamin D, we have a high a priori probability, which is based on the abundance of other evidence that was collected even before this particular experiment. For example, the fact that a new study shows that vitamin D exercises an antiviral effect on the coronavirus in a test tube, raises the a priori probability a great deal.”

An examination of the large number of existing data in the light of the hypothesis about the role of vitamin D in the coronavirus epidemic, suddenly sheds new light on epidemiological observations. Some will say that vitamin D is the “missing piece of the puzzle,” others that it’s like a detective story, in which findings pointing to the murderer were discovered, but it wasn’t clear how, or how they were connected. Until someone suddenly pointed to the factor that connects all the facts, which until now were separate and opaque, and creates a coherent picture. Aha! It was the postman!

The involvement of vitamin D in the disease can explain, for example, why dark-skinned people in the West are more vulnerable than light-skinned people, both to infection with COVID-19 and to severe symptoms. The density of melanin in dark skin inhibits the manufacture of vitamin D, and if so, which could explain why, in the United States, the principal sufferers from vitamin D deficiency are Blacks and Hispanics, and why they are the major sufferers from the coronavirus. In Israel, the population groups most vulnerable to vitamin D deficiency are Arabs and the ultra-Orthodox – two populations that tend to wear long clothing, and they are also the groups that have been most affected by the pandemic. It can also be said, of course, that the high rate of illness in those groups is due to their lower socioeconomic status, and that the vitamin D levels are only an indicator, not a cause. Poor nutrition, obesity, predisposition to diabetes, overcrowding – all these can in and of themselves explain the incidence of the disease.

It’s possible that a new study by the Clalit HMO can shed a little more light on the subject. This research project examined more than half a million people from 200 Israeli locales, and as in earlier studies found an impressive correlation between vitamin D deficiency and the risk of contracting COVID-19. Places that were found to suffer from a deficiency in the vitamin are the “red cities,” the locales where the infection rate is especially high. Because these are all Arab and ultra-Orthodox cities and towns, the phenomenon is usually attributed to a low socioeconomic situation. However, the study also found large differences between Arab men and women. The women tend to fall ill at a far higher rate than the men, and the women’s vitamin D levels are also lower. A possible explanation is that women in Arab society are more covered up than men, and also tend to stay at home more and so are less exposed to sunlight. This difference neutralizes to some degree the socioeconomic factor (as these are men and women from the same population).

'Causing death by conservatism'

“The vitamin D story did not begin with the impressive epidemiological studies of the past few months,” says Shaul Lev, whose ICU at Petah Tikva’s Sharon Hospital was turned over completely to treatment of COVID-19 patients in the first wave.

“For some years, patients with lung and viral diseases have been treated with vitamin D, because they are known to have a deficiency of that vitamin. So the idea of using it to treat the coronavirus is quite natural,” Dr. Lev continues. “In its mild form, COVID-19 is a simple viral lung disease, with which the regular cells of the immune system cope well. Frequently, no symptoms at all develop. Only 1 percent to 5 percent – the rates are low in the summer – of all those who are infected develop the disease in its serious form. That happens because of a secondary response by the immune system, which sometimes lurches out of control and starts to function in an exaggerated way – it has to do with the hypercytokinemia [severe immune response] that people have been talking about lately. It results in inflammation that causes massive damage to the lungs and afterward multi-systemic damage.”

What is the role of vitamin D in this disease?

Lev: “Vitamin D, or more precisely one of its derivatives, regulates the immune system. It encourages the initial response of the immune system, which occurs immediately at the start [after exposure], and it moderates the secondary response, if it occurs, so that it does not become an overly severe inflammatory response.

“In addition, vitamin D is important for preserving the tight structure of the lung walls, and because it also has an effect on the number of receptors in the walls, through which the virus enters the lungs, it can also influence the disposition to infection. There is no doubt that the central role of vitamin D in the activity of the immune system reinforces the suspicion of its involvement in the coronavirus and justifies the studies conducted about it.”

“Why isn’t vitamin D being administered to the general population and to patients?” Wilf, the high-tech entrepreneur, asks. To provoke and stimulate the discussion, he is betting $100,000 that in another half a year medical experts will be in agreement that treatment of COVID-19 patients with vitamin D is effective in reducing the risk that they will develop severe symptoms.

Wilf: “There is a deluge of findings and evidence that attest to the vitamin’s involvement in the pandemic, but the news spread so slowly. It’s irresponsible. We are trying with all our might to induce the decision makers – physicians, the Health Ministry, the politicians – to break out of the conservative pattern of doing things that characterizes their usual behavior, and to issue a call to the people: ‘Take vitamin D, it can save lives.’ And to the hospitals: ‘Start treating patients with vitamin D.’

“It’s true that most of the studies to date show only correlations and have been published in journals without undergoing peer review (the long process in which scientists with similar competencies scrutinize a scholarly article) because of the urgency of the issue. To date, only one controlled experiment has been conducted, which showed the causal connection between vitamin D and the course of the disease. But even so, this is about saving lives.”

So you want to shake up the system?

Wilf: “Yes. Physicians are educated on the basis of the approach, ‘First, do no harm.’ In other words, it’s better to do nothing than to do something you’re not sure of. That is a welcome approach, of course, in light of the history of rash decisions that caused tremendous damage, such as the thalidomide disaster, where a medication intended to prevent nausea in pregnancy caused the birth of deformed infants. Over the years, important rules of thumb have developed: Don’t rely on a lone study, be suspicious of small samples and beware of any departure from the accepted protocol of the experiment.”

However, Wilf continues, “Our approach is somewhat different. We need to remember that it’s not the rules that are sacred, but the original purpose for which they were laid down: to improve treatment and reduce risk. In a singular situation such as we are now in, with the pandemic raging and the number of dying increasing – a decision needs to be made quickly, one that makes use of the most powerful tools of analysis and deduction that we have, in order to save lives.

“At the moment the picture is clear,” he says. “The probability that vitamin D is effective is high, its potential benefit is vast and the risk is very low – toxicity as a result of excess [ingestion] of vitamin D is rare, especially if you monitor the patients. Perhaps in another six months more comprehensive studies will be published, showing that the treatment is not effective – in our estimation the likelihood of that is low, but it’s definitely possible – in which case a different decision will be the right one. As of now, every day in which patients are not given vitamin D puts them at risk for no reason. I call it ‘causing death by conservatism.’”

Dr. Lev is also awestruck when he shows me the graphs that display the amazing correlation between vitamin D levels and the rate of infection by the coronavirus. He, too, is convinced that vitamin D should be dispensed in the community, especially to those with a deficiency, as a coronavirus preventive. Indeed, he argues, it is urgent to do this before the coming winter.

At the same time, Lev finds exaggerated, almost missionary-like, the fervor of people who are not physicians, and their demand to start dealing with patients. “As head of the coronavirus ICU in the first wave, I received a great many phone calls from mathematicians, physicists and high-tech people who swore that they had a cure for the coronavirus,” he says.

“You have to understand that the picture is far broader than it appears at first glance. To begin with, as a doctor who is very familiar with the first wave, I can say that the Spanish study, which is considered a supposed game changer in the treatment of the seriously ill, suffered from quite a number of weaknesses, and not only the small number of participants. Second, a distinction needs to be made between giving vitamin D to the healthy population as a food additive in order to prevent infection, and the use of the vitamin as medication for patients. It is impossible to recommend therapeutic intervention without sufficient evidence, and for that more intervention studies need to be conducted, which will show the effect clearly.”

But why wait? If the chance of toxicity is so low, what is there to lose?

Lev: “In principle, you’re right, but in managing an epidemic, it’s important to see the big picture. First, if the Health Ministry’s coronavirus management team were to issue an official declaration about the success of treatment with vitamin D too early – people would think that it’s all behind us, that they don’t need face masks and that there’s no point to maintaining social distancing. That is dangerous. The foundation for getting control over the coronavirus is the public’s behavior. Let’s say the vitamin reduces morbidity by 20 percent – which is a great deal – and at the same time the population feels safe and thinks that anything goes. That whole 20 percent will collapse and be erased.

“Every effect that you create can generate an opposite effect. So it’s best to treat vitamin D as something of great potential, but with caution. We also wouldn’t want people to start drinking bottles of vitamin D and reaching toxic levels. That can heighten the risk of falling and fractures, and it’s especially dangerous for those with kidney or liver problems and for those with high calcium levels.”

If you receive a patient who is seriously ill with COVID-19, will you not give him a large dose of vitamin D?

“At the moment, patients’ vitamin D levels are not being tested, and that is what I am trying to accomplish: to get the hospitals to check those levels, and based on the result to give them or not give them vitamin D. If a patient has a low level of vitamin D, I would definitely give him high vitamin doses while he is hospitalized, in order to bring him to a standard, normal level.”

Everyone I spoke to who is up-to-date on the subject – Dr. Marzon, who conducted one of the first studies, the high-tech people who are urging the vitamin’s use as a medication, and undoubtedly you, too – is taking vitamin D and recommending it to their loved ones. Dr. Anthony Fauci, the White House team’s senior expert on the coronavirus, says he’s taking 6,000 units a day, and President Trump reported from his hospital bed that he was taking vitamin D. Why isn’t the Health Ministry requiring people to be tested and starting to make up the deficiencies?

“I think that much progress has been made in the subject. The Health Ministry’s nutrition department issued a letter to the HMOs recommending that they prescribe vitamin D for people with a deficiency. That doesn’t yet mean that family doctors have taken note of it. From their viewpoint, maybe it’s just another routine message. In addition, it’s one of the expensive tests, and it’s impossible to increase its use all at once. Already today it constitutes 2 percent to 3 percent of all the tests in the hospitals.”

And the recommended dosage?

“In Israel, a totally sun-drenched country, there is paradoxically a tremendous vitamin D deficiency. Only 25 percent of the population has the standard level – possibly because people go outside less than in the rest of the Western world, or maybe because of the high awareness of risk of contracting skin cancer from exposure to the sun. But to recommend a dosage is like a shot in the dark. People live in different places, where there is more sun or less sun. Even people who live in the same area are exposed to the sun to different degrees, depending on the work they do – high-tech or gardening – and how they dress.

“And there are other factors: skin color, percentage of fat (because the adipose [fatty] tissue absorbs the vitamin and prevents it from reaching all parts of the body, obese people suffer more from a deficiency of the vitamin), age and nutrition (milk, liver and fish contain a fine amount of vitamin D). The general recommendation is for 2,000 units a day; 1,000 for young, thin, healthy people; and 4,000 for older people, overweight people and those who have minimal exposure to the sun. Taking that dosage for two to three months can help prevent infection by coronavirus, and in cases where they are infected, it can tilt it toward its mild form. Because winter is approaching, it’s worth thinking about treatment already in these months.”

Is there a large enough supply of vitamin D in Israel?

“Before speaking with you, I checked with the chief pharmacist’s office, and there’s enough for at least four months. There are also manufacturers, so there shouldn’t be a problem.”

Do you not have a word about the lockdown?

“The restriction on going outside reduces the exposure to the sun and thus, paradoxically, heightens the risk of coronavirus infection.”