If we had to choose a star among vitamins, a star similar to the celebrities that electrify the world of people, vitamin D would have a very high chance of occupying the podium.
When examining the number of scientific articles published about this vitamin, we cannot remain indifferent: since 1922, when the term “vitamin D” was beginning to timidly make its way into the awareness of scientists, until now, when in the Western world vitamin D is available to anyone, no less than 69,485 scientific articles have been dedicated to it. However, with the increase in the number of articles, the disappointments also seem to have multiplied.
Vitamin D: a star among vitamins
If, in 1970, as indicated by Medline (United States National Library of Medicine), 381 scientific articles on vitamin D were published, in 1994 the annual number of articles exceeded 1,000, in 2009 it exceeded 2,000, two years later (in 2011) it exceeded 3,000, and in 2014 it exceeded 4,000. By comparison, the total number of articles published for vitamin A is 50,315, for vitamin C 56,830, for vitamin E 39,375, and for vitamin K 21,526.
Hundreds of observational studies in humans have been carried out in the last decade alone, demonstrating the existence of links between vitamin D deficiency and a range of acute or chronic human conditions, such as rheumatic diseases, inflammatory bowel diseases, autoimmune thyroiditis, cardiovascular diseases, lung diseases, multiple sclerosis, schizophrenia, and even attention deficit hyperactivity disorder diagnosed in children.
What most of these studies found was that in this wide range of human conditions there is a deficiency of vitamin D, but not necessarily that this deficiency would causally contribute to the onset of the respective diseases or that, with an adequate intake of vitamin D, those diseases could be prevented or cured. But the temptation to believe that there is, that there must be a causal connection is very strong, and many in the medical world, as well as some patients, have started using vitamin D supplements in the hope that they will solve those health problems.
Does vitamin D prevent falls in the elderly?
Despite this strong temptation to equate association and causation, this equality does not exist, and after enthusiasm for the benefits of this vitamin has grown within the medical community, it has been tempered for several years with studies evaluating the impact of vitamin D on various ailments. For example, although there was a time when more and more arguments were accumulating indicating a reduction in the risk of falls in people with a sufficient intake of vitamin D, the experimental data that verified this theory is quite scarce.
Theoretically, vitamin D should reduce the risk of falls in the elderly because: (a) vitamin D deficiency is associated with muscle weakness, (b) the vitamin D receptor (the protein through which it exerts its effects) is expressed in human muscle tissue, as most studies indicate, and (c) activation of the vitamin D receptor in the muscles stimulates protein synthesis in muscle fibres involved in preventing falls. But what did the experiments actually find when testing for fall risk reduction after vitamin D intake?
In an optimistic version based on several studies, the only people for whom vitamin D would have a real benefit in preventing the risk of falling are those aged 65 or older, who are vitamin D deficient, in which cases supplements may prevent falls and related fractures (but not in younger populations). Nevertheless, there are other studies that offer an even more pessimistic perspective.
In 2016, Heike A. Bischoff-Ferrari and colleagues published a study in which they evaluated the effects of three doses of vitamin D3 in elderly people with a history of falls in the 12 months prior to the start of the study. The patients included in the study were divided into three groups. One group received a dose of 24,000 international units (IU) per month of vitamin D3 (800 IU per day), another received a dose of 60,000 IU per month (2,000 IU per day), and the third group received a dose of 24,000 IU per month (800 IU per day), plus 300 micrograms of calcifediol (a product formed by metabolising vitamin D in the liver, 2-3 times more potent than vitamin D3).
What did they find? 80% of patients in the two groups who received doses greater than 24,000 IU per month (800 IU) achieved a level of 30 ng/mL of 25-hydroxyvitamin D, which is thought to be necessary to reduce the risk of falls and fractures. So, with higher doses of vitamin D, the optimal level of 25-hydroxyvitamin D was reached, but the conclusions did not stop there. The groups that received the higher doses of vitamin D and achieved the desired level of 30 ng/mL of 25-hydroxy-vitamin D also had the highest proportion of falls and fractures (66.9% and 66.1%, compared to 47.9%), the observed difference being statistically significant. Thus, higher doses of vitamin D were associated with higher risks of falls and fractures than lower doses, although the authors expected the opposite results.
A natural question arises when faced with these results: What if there was a fourth group that did not receive vitamin D at all (and received a placebo instead)? Would the frequency of falls be higher or lower? A clinical trial comparing vitamin D at a dose of 800 IU/day (24,000 IU per month) and placebo observed no statistically significant difference in the frequency of falls in women aged 70 to 80 years. In contrast, exercise reduced the risk of injury in people who fell (both those who received vitamin D and those who did not receive vitamin D). Vitamin D had some positive effects on bone mineral density, but only exercise improved muscle strength and balance.
Another study, also published in 2015, also compared two doses of vitamin D3 (24,000 IU monthly and 50,000 IU monthly) with a placebo. The conclusion? High-dose vitamin D3 increased calcium absorption by 1% (in the low-dose vitamin D3 group and in the placebo group, calcium absorption decreased to a statistically significant level, by 2% and 1.3%, respectively), but this small effect did not result in any benefit in terms of bone mineral density, muscle function, muscle mass, or fall frequency. The authors thus questioned expert recommendations to achieve a level of at least 30 ng/ml of 25-hydroxyvitamin D.
Taking into account the results of similar studies, as well as those of meta-analyses showing contradictory results regarding the benefits of vitamin D in elderly people living in the community (not in institutions) and with positive results in institutionalised people, an editorial accompanying the article by H. A. Bischoff-Ferrari and collaborators expressed scepticism about the potential benefits of vitamin D in other categories of people than those institutionalised.
Somewhat simultaneously with these published materials, a group of Canadian authors reviewed the scientific literature on several “beliefs” related to the health effects of vitamin D. The first “belief” analysed was the one related to the effect on the risk of falls, and the second, that of the effect on fracture risk. This paper could not include the study by H. A. Bischoff-Ferrari et al and has a somewhat more positive conclusion in that there is an effect of reducing the number of falls in the elderly, but this effect is not higher than 15%. As for the risk of reducing fractures, these authors conclude, based on the studies published so far, that when the initial risk of fractures is about 15%, it is necessary for a number of 45-67 people to take vitamin D and calcium every day for 10 years to prevent a fracture. This is indeed a benefit, but probably a smaller one than many patients, and even medical professionals, realise.
Vitamin D: what effects does it have when considering other conditions?
The results are not more encouraging when checking for effects of vitamin D supplementation on other conditions. Meta-analyses based on data published up to 2016 (namely 40 randomised controlled clinical trials) have shown that vitamin D, with or without calcium, has no effect on heart attacks, ischemic heart disease, strokes, or cerebrovascular disease. The initial concentrations of 25-hydroxy-vitamin D, the concentrations of 25-hydroxy-vitamin D reached after supplementation, or the duration of treatment did not in any way influence the results of these analyses. The results were not different in terms of effects on cancer or on mortality in general.
Several studies have found that people with low levels of vitamin D in their blood serum have a higher incidence of respiratory tract infections. As in other cases, the tempting conclusion was that the use of vitamin D supplements in such people would prevent respiratory tract infections. And, as in other cases, the experimental verification of this hypothesis has failed. A meta-analysis based on seven randomised clinical trials using 4,827 participants found virtually no difference in the risk of respiratory tract infections between subjects who received vitamin D supplements and those in the control groups. Neither age, vitamin D dose, nor the length of time the subjects were followed had any impact on this conclusion.
The benefits of vitamin D supplementation in patients with depression are less clear. Three meta-analyses published in 2014 (1 | 2) and 2015 concluded that the use of the vitamin does not reduce symptoms of depression, although they acknowledged that most of the studies conducted so far looked at subjects with reduced levels of depression and sufficient vitamin D levels at the start of the study. A single meta-analysis, which attempted to extract from the existing studies on depression those having a strong design from the point of view of the biology of the hypotheses, claimed that quality studies would support an improvement in depressive symptoms in patients who were given vitamin D, versus studies with “biological” deficiencies, which tended to indicate a negative effect of vitamin D on depression symptoms.
What do we do with vitamin D?
It would not be impossible that some benefits of vitamin D (e.g. for pain or asthma) did exist, but these require confirmation and clarification regarding target populations and administration conditions (dose, duration, etc.). Existing proven benefits do not justify constant and uniform use of vitamin D in all categories of people, regardless of age and health status. Until more recent studies indicated that vitamin D—even at doses considered “therapeutic”—could actually have harmful effects on the body, the prevalent perception was that if vitamin D was somehow ineffective, at least it was “not harmful.”
In light of the accumulated data, we are no longer so sure. And these data add to the many that indicate that various vitamin and multivitamin supplements either have no benefit or even have a negative impact on health. This makes many medical experts seriously wonder if for most of us the best solution remains to get our vitamins from a balanced variety of foods and through adequate sun exposure, rather than from tablets or pills. And, as we saw in passing, a bit of physical exercise can sometimes have a greater effect than a good dose of vitamin D.
Robert Ancuceanu is a doctoral professor at the Faculty of Pharmacy within the “Carol Davila” University of Medicine and Pharmacy in Bucharest, Romania.