Vitamin D has received increasing attention in these months of the pandemic, in particular for its protective effect against infections, which has long been known, and for the association between its deficiency and the risk of developing severe Covid.
“It is now shown by numerous studies that low levels of vitamin D in the blood are associated with the development of more severe Covid, with a greater risk of hospitalization, admission to intensive care and death” he explains. Adrian Martineau, professor of respiratory infections and immunity at Queen Mary University of London, author of numerous works on the subject, speaking during the fifth edition of the International Consensus on Vitamin D organized in Stresa by Andrea Giustina, head of the endocrinology of the San Raffaele in Milan and from John Bilezikian, of Columbia University in New York. “There is, however, no evidence to say with certainty that there is a causal relationship behind this association. We have a number of hypotheses: low levels of vitamin D lead to a dysregulation of the immune system with a worsening of the disease; or conversely, severe disease causes inflammation in the body which can affect vitamin D levels. Finally, there are a number of so-called confounding factors, such as age, overweight, ethnic origin and winter”.
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Studies
According to a review of 25 clinical studies related to the protective effect of vitamin D on infectious diseases, published by Martineau in the British Medical Journal in 2017 for a total of over 11,000 subjects, “vitamin D offers the most protection to people with the lowest levels. at baseline and works best if taken every day and in intermediate doses “he tells us” Since then, many other works have been done. Even some of our own, such as the one conducted in Mongolia on children with severe vitamin D deficiency and appeared in the New England Journal of Medicine last year. Unexpectedly, no vitamin D protection has emerged against the risk of developing tuberculosis or other acute respiratory infections. “
A similar surprise also comes from the update of the meta-analysis of 2017, 46 studies for over 75 thousand people, which appeared this year in The Lancet Diabetes & Endocrinology: “The greater protective effect already seen in people with low levels has not been confirmed. Still, this had biological plausibility. There is still some effect, albeit modest, in reducing the risk of developing respiratory infections. ”
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A crowned devotee
Early epidemiological data suggested that vitamin D could be of great help in protecting the population from Sars-Cov-2 infection. This indicated a way forward with only good clinical trials. Vitamin D, in fact, has been the subject of enormous expectations in the recent past and then reduced and is often recommended for many different diseases. But scientific studies do not emerge equally certain evidence.
Adrian Martineau is the leader of a controlled clinical trial, Coronavit, conducted in the UK of 6,200 participants to evaluate whether correcting vitamin D deficiency during the winter with a standard or high dose of the vitamin could reduce the risk or severity of Covid and other acute respiratory infections. The analyzes are ongoing and the results are expected shortly. Other clinical trials are underway in France, on high-risk elderly adults with Covid, in Spain and in the US.
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“In vitamin D – confirms Giustina – the path taken, also with the establishment of working groups among the leading experts present at this consensus, is that of identifying subgroups of populations most at risk, such as the elderly, women in in pregnancy and in menopause, patients with malabsorption as well as those with gastrointestinal diseases and undergoing bariatric surgery. For each group, the necessary doses and supplementation schedules will be identified. An evidence-based tailoring approach will help overcome the widespread dichotomous reality, in which vitamin D is seen either as a panacea for all ills or as a useless supplement among others “.
Boost the vaccine
Of course, Martineau points out, no supplementation will offer anything like the protection offered by a vaccine, so talking about the effect of vitamin D in the absence of a vaccine is something of an academic question. However, he says, “there are good reasons to think that vitamin D may increase the response to vaccination. In a study last year, which appeared in Immunotherapy Advances against the Varicella zoster virus (vzv) and we also showed the mechanism, which to do with inflammaging “.
In fact, as we age, the immune system is less well regulated and the body is generally in a state of low-grade inflammation. It acts as a brake on vaccine responses, “which is what we call specific immunity. We saw that people who received vitamin D had better T-cell responses and also lower levels of inflammation.” The role of vitamin D in enhancing the response to vaccination is one of the questions investigated by the Coronavit study, which started last December but ended this spring when about 50-60% of British people had been vaccinated.
How to use Vitamin D
So, continues the expert, “I believe that vitamin D can have three roles: one in the prevention of Covid, the second is to improve the response to the vaccine, so it is like a partner in prevention. And then the third is to use vitamin D in the treatment of people who already have Covid. But to prove this last point, another type of study is needed, on hospitalized people, and the results obtained so far are conflicting. Demonstrating efficacy in treatment is more difficult than proving it in prevention. Furthermore, for the treatment of Covid we have very powerful cocktail of drugs with which it is unlikely that vitamin D will be able to compete “.
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Why, despite the huge amount of studies and the good premises of basic research, then the evidence on humans indicates at most a small protective effect? “It almost seems that the effects seen in the laboratory are lost when we translate them into the real world,” confirms Martineau. The biological mechanisms underlying the various functions performed by vitamin D are investigated in vitro and in vivo and then also in humans. In vitro, conditions are controlled and results are clean. The animals, usually mice, are all genetically homogeneous, deficient in vitamin D, and all live the same life.
More studies are needed
“In humans, things become tremendously complicated, there are many physiological processes in place, a great genetic variability and many different lifestyles” explains Martineau. “This increases the noise and it becomes difficult to distinguish the signal.” Add to this the methodological inhomogeneity, clinical studies have different dosages and resort to different supplements. You work in very muddy waters, there are numerous sources of vitamin D, which becomes difficult to control compared to a clinical study on an antihypertensive, for example. Again, the key word seems to be “test”: “Perhaps the most likely explanation for the failure of a lot of clinical trials to deliver on the promise from laboratory experiments is that the subjects in the control arm already had adequate levels of vitamin D “. After that, “I think this is still a field worth investigating. Because ultimately we are dealing with something that is very safe and very cheap. Even if it were to give a small benefit, it would still be important for public health.”
The Guidelines
At the end of the consensus, three final documents dedicated respectively to the elderly, gastrointestinal diseases and the limits of the current guidelines were drawn up, with a detailed analysis of the conditions necessary to avoid conflict and reach more robust scientific evidence that can be easily translated into practice. “The recommendations should be formulated for specific groups of subjects, addressing different indications to healthy people and people with pathologies. For example, we discussed osteoporosis, whose high prevalence leads some to mistakenly consider it a physiological condition – sums up Giustina – Covid has provided the opportunity to test the correctness of some scientific beliefs and vaccination is an opportunity to bring a large number of citizens together to raise awareness on the importance of vitamin D and address the age-old problem of deficiency in the elderly in our country “. The solutions exist, says the professor, among them “the supplementation and fortification of foods, as the successful experiences of Scandinavian countries show”.
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