Sales of Food supplements, which were already high, soared with the pandemic. In the UK, the multivitamin market grew by almost 100% in March of last year. In the United States, the demand for zinc supplements was 400% higher in the first week of that month. All this without any isolated complement having been shown to improve immunity, except in cases of particular deficiency.
Now, a new study with more than 300,000 volunteers shows that taking multivitamins, probiotics, omega3 pills, or vitamin D supplements is associated with a reduction in about the 10% of becoming infected with the new coronavirus.
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Vitamins against Covid-19?
Are there reasons to get rid of skepticism, to take to the streets and supplement ourselves? For many reasons, no. As the authors of the work themselves say: “The design of our study does not allow us to infer causality”, other types of trials are needed “before any type of recommendation can be made.”
His work, however, is a good opportunity to analyze what type of studies allow to draw according to what conclusions. And to remember what we do know can improve immunity.
Researchers from King’s College London collaborated to launch an app and study the symptoms of covid at the beginning of the pandemic. Among the many data collected from the volunteers was if at any time they tested positive for covid, but also if they took some type of nutritional supplement (almost half of them did).
With this information they saw that there was a reduction in the risk of being positive between 9 and 14% if supplements such as probiotics, omega 3 acids, multivitamins or vitamin D were taken. On the contrary, they did not see that the risk was lower with the vitamin C, zinc or garlic extract supplements.
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“This type of study allows hypotheses to be formulated, but not conclusions,” he says. Moses Labrador, specialist in immunology and allergology at the Vall d’Hebron Hospital in Barcelona. They are called observational studies and, as pointed out Jose Antonio Riancho, professor of medicine and head of the Internal Medicine section at the Valdecilla Hospital in Santander, generally “does not allow us to establish that there is a causal relationship: people who take supplements may not be the same or comparable to those who do not take them.
In lingo, this is known as confounders. For example, people who take supplements may be more concerned about their health, so they take more precautions to avoid infection and even, quite possibly, have healthier habits. In addition, there could be a socioeconomic factor: those who buy supplements are likely to belong to a social class higher in general and, for different reasons, infections are more frequent among the underprivileged classes. In the words of statistician Kevin McConway, “The differences in contagion risk could be due, at least in part, to the supplements. But it is also possible that they are entirely due to other things. “
“When I explain this to my students, I usually give a silly example, but I think it’s useful,” says Riancho. “Most of the bullfighters are brown. Does this mean that brown hair influences being a bullfighter? Obviously not. What happens is that bullfighting is something more typical of Latin countries, where there are fewer blond people ”.
Although statistics can be used to correct for some of these variations, “the study fit is very partial,” notes Labrador, “and there are many more variables that cannot be taken into account.”
There is more limitations at work, as the fact of the data is through polls, that the doses of the supplements are not taken into account and, in many cases, their composition. Or that the association takes place only in women, and not in men. “The authors try to formulate hypotheses to explain it, but there is no clear biological basis, really,” explains Riancho.
How should it be checked, then? Ideally, through a clinical trial sufficiently powerful and well designed —Actually, through several— to confirm what was observed. In this type of study, two groups of volunteers would be established a priori and at random, which would make them more homogeneous. Their social class, their worries and habits would be distributed randomly. So one group would be given a known dose of a supplement and the other a placebo. No one would know what they were taking (not even whoever gave them the pills), so they wouldn’t alter their behaviors based on it. After a while, the results would be analyzed.
This is what has been done on many other occasions, although it has barely had time with the covid. And in general, it has led to disappointments. An example of a book has been precisely that of the vitamin D.
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Vitamin D had a fascinating and almost unsurpassed presentation narrative. It is hardly obtained from the diet, but is produced on the skin in contact with the sun. As we moved away from life outdoors and spent more time indoors, it was logical to think that their levels were going to suffer.
In addition, it is not a vitamin as such, but a hormone with multiple functions beyond its well-known role on calcium and bone health, including a relationship with immunity. Observational studies found that lower levels of vitamin D were associated with all sorts of ills: from cancer to diabetes, to depression, the risk of infections, or even Alzheimer’s. Would it be so easy to improve the global health using a simple supplement?
It was not. The dozens and dozens of clinical trials that have been conducted have generally failed. “There are different hypotheses that could explain it,” says Riancho. One of the ones that would best fit and that is becoming more and more widespread is that low values vitamin D would not act as a clear causal factorInstead, it would be “a marker of poor health, a marker of frailty.” In fact, its levels decrease when diseases with significant inflammation occur, but it is not the decrease that causes the disease.
Other non-exclusive hypotheses have to do with the metabolism of the vitamin, which is complex and comprises a whole series of activation and regulation steps. “Perhaps the supplements used do not improve their activity,” says Riancho. Furthermore, “it could be that it had a threshold effect: when a level is reached, there are no improvements no matter how much we increase it. It is as if we give iron to correct anemia.
Once there is enough, no more red blood cells are produced, no matter how much iron you add ”. On the other hand, “it does not make much sense to talk about the fact that in countries in latitudes like Spain there are 70% of people with vitamin D deficiency. There is much discussion about what normal values really are,” adds Labrador.
No evidence against covid
Curiously, one of the few effects shown by the clinical trials of vitamin D was to reduce the risk of respiratory infection, although “the effect is very moderate and it is not entirely accepted,” says Riancho. With the pandemic, it was logical to investigate your role on Covid-19.
It began with observational studies, in the style of the one carried out with the app and supplements. Although some did not find a relationship, others did see that low levels of vitamin D were associated with increased risk of infection and severity Although many factors are actually common, such as obesity, and it is not always easy to separate them.
At the moment there are hardly two clinical trials administering supplements that have been published, both as treatment and not as prevention. One carried out in Córdoba (Spain) showed spectacular results, greatly reducing the risk of hospitalized patients of having to enter the ICU. Although preliminary, it had some shortcomings and the control group seemed to have more baseline risk, their findings sparked a debate on its use in the UK parliament.
The other trial, using a type of supplement with a different protocol, found no benefit. There was a third, published as a prepublication in The Lancet magazine, carried out in Barcelona and with the participation of some of the authors of the Córdoba trial. Although it offered positive results, it was quickly criticized for containing multiple errors and the magazine removed it.
“There is no evidence right now that allows recommending the use of vitamin D supplements against covid,” acknowledges Riancho. In general, there are not any to take them in general, “unless there is a case of clear deficiency, such as taking certain medications or not being able to go out in the open enough.” Recommendations in countries like Spain are exposing face and arms to the sun during 15 minutes at least three days a week. “That should be enough,” Labrador sums up.
Although the toxicity of the supplements is not high, “they should be prescribed by a doctor,” adds Riancho. In Spain, for example, pharmacies often sell hydroferol, which is a more active form of vitamin D than the classic one and which could raise levels excessively.
How to optimize immunity
In general, “unless there is a deficiency, no isolated supplement has been shown to improve immunity”, Sums up Labrador. For example, on the supplements that the study with the app found that they could be useful: among everything studied, isolated vitamin C has only been shown to influence very slightly in the time with symptoms of cold (shortens it to less than a day), and it is still disputed that the effect is real. The various multivitamin complexes have not shown any clear benefit.
The omega 3 acids they have been mainly associated with cardiovascular disease. A diet rich in them such as the Mediterranean seems protective, but its benefit when given alone in pills is not clear. “The diet is complex, it is not easy to identify and separate specific components and think that they will work separately,” admits Labrador.
Probiotics cannot be considered a single entity: they comprise many different microorganisms and studied at different doses. For now, “only some of them have shown benefits,” says Labrador, “and only on certain types of diarrhea, such as the one that follows taking antibiotics.”
Although “at the usual doses taking supplements does not usually cause side effects”, Riancho acknowledges, if they are recommended or taken in a generalized way “we could find them. What they are, of course, is a waste of money ”.
What to do, then, to optimize our immunity? “What we know works are the general recommendations of always”, Sums up Labrador. “You have to follow a varied diet such as the Mediterranean, practice moderate exercise, avoid tobacco and have adequate sleep patterns.” That simple, although not so simple.
Said the critic George steiner that “a commonplace is a tired truth.” On immunity, for the moment, this is still the only safe place we know of.