Are large doses of vitamin D any good?

Vitamin D is also involved in immune response, and in population studies, low levels of vitamin D have been linked to an increased risk of upper respiratory tract infections. Indeed, outbreaks are more common in winter when vitamin D levels get lower. “Vitamin D supplementation has been shown to prevent upper respiratory tract infections among those with significant vitamin D deficiency. For this purpose, a dosage of 20 micrograms per day has been sufficient, and higher doses have not provided any additional benefit.”

During the past year, a lot of studies have addressed the association between vitamin D status and the risk of COVID-19. “In Europe, the COVID-19 situation has been among the worst in Spain and Italy where low serum levels of vitamin D are common. In these countries, there’s plenty of sunshine almost all year round, but sun exposure is avoided, and as no foods are fortified with vitamin D, intake from food is low. In Finland, on the other hand, both the population’s vitamin D levels and the COVID-19 situation are among the best in Europe. Of course, there are other differences between countries that can affect the situation as well, such as differences in housing density and health care capacity,” Virtanen says.

A pilot study carried out in Spain showed that vitamin D supplementation could help to prevent severe forms of COVID-19. Among patients hospitalised with COVID-19, those who were given 25-hydroxyvitamin D, also called calcidiol, which is the storage form of vitamin D in the body, were less likely to need intensive care. “This small-scale study has been followed by a larger trial, the results of which are yet to be published.”

As Virtanen points out, there is yet no evidence that vitamin D supplementation could prevent you from contracting the virus. In any case it’s reasonable to ensure proper intake, given the role of vitamin D in the immune system.

In Finland, the Helsinki and Uusimaa Hospital District (HUS) has issued its own vitamin D recommendations to prevent severe COVID-19. HUS recommends 20 micrograms per day for everyone over 70 and in assisted living as well as for dark-skinned adults. In these groups, obese persons with a body mass index of 30 or more are recommended a dose of 50 micrograms per day. This is due to the fact that vitamin D is stored in adipose tissue and hence obesity reduces the availability of vitamin D in the body.

“In addition to obesity, many other risk factors of severe COVID-19, such as higher age, sedentary behaviour, diabetes and other chronic diseases are associated with lower vitamin D levels. From this perspective, low levels of vitamin D might not be such an important risk factor in itself, but rather a marker of these other risk factors. It can also be the result of coronavirus infection instead of being the cause, because infection lowers vitamin D levels in the body.”

Researchers from the University of Eastern Finland will soon publish the first results from the Finnish Vitamin D Trial (FIND). The five-year study with 2,500 participants investigated the effects of vitamin D supplementation on cardiovascular disease and cancer incidence and mortality. “We have compared groups using either 40 or 80 micrograms of vitamin D, or a placebo supplement,” says Virtanen, who is one of the principal investigators.

For ethical reasons, trial studies can’t keep placebo groups in vitamin D deficiency, either. That’s why participants are allowed to use their own vitamin D supplements in dosages following the official recommendations, in addition to the supplements provided in the trial. “However, this evens out differences between study groups, and as the majority of participants have good vitamin D levels to start with, it’s more difficult to demonstrate the benefits of larger doses.”

Vitamin D became a hot topic some years ago after its many potential health benefits were brought into the limelight. Experts debated the sufficiency of the official intake recommendations, and many laymen concluded that more must be better. A full consensus is still lacking regarding the optimal intake and blood levels of vitamin D. “However, those using or recommending very high doses are fewer now, since evidence has not backed them up,” Virtanen says.

Instead, it is known that taking too high doses of vitamin D supplements can harm your health in the long run. “Over time, excess intake increases blood calcium levels, which can increase the risk of life-threatening arrhythmias and kidney failure.”

Excess vitamin D can accumulate in the body, causing fatigue, headache and nausea, among other things. “In some trials, participants have been given mega-doses of vitamin D once a month or even once a year, instead of daily doses. However, the results have shown more risks than benefits. For example, single doses of several thousands of micrograms have been shown to increase the risk of falls and fractures.”

A hundred micrograms a day is considered a safe upper limit for vitamin D intake for adults. “No harmful effects have been reported even after years of using a daily supplement of 100 micrograms.”

To assess the adequacy of an individual’s vitamin D intake, their vitamin D status can be determined by measuring the level of calcidiol in the blood. In clinical trials and in the treatment of diseases such as osteoporosis, the dosages of vitamin D supplements are determined according to target blood levels. Views on the optimal levels differ. According to the Finnish Current Care Guidelines for the treatment of osteoporosis, less than 25 nanomoles per litre (nmol/l) indicates severe insufficiency, less than 50 nmol/l indicates insufficiency and 50–75 nmol/l is usually adequate. For patients with osteoporosis, the target level is 75–120 nmol/l. In order to achieve this level in winter, a daily dosage of 25 to 100 micrograms of vitamin D is needed, according to the Finnish Medical Society Duodecim’s database.

According to the working group for the Nordic nutrition recommendations for vitamin D, a daily intake of 10 micrograms is usually enough to maintain a blood level of 50 nmol/l. Meta-analyses of clinical trials showed a reduction in cancer mortality with attained levels of 54–135 nmol/l, and diabetes progression was prevented with attained levels of at least 75 nmol/l.

Virtanen points out there isn’t one standard test to measure vitamin D status, which makes it challenging to compare patient measurements as well as trial results. “Results even from the same blood sample can differ by tens of nanomoles depending on the laboratory and the method used, so they should be considered only indicative.”

In addition, it looks like the need for vitamin D supplementation depends on individual responsiveness to vitamin D. Research at the University of Eastern Finland has shown that some individuals need bigger doses of vitamin D than others to achieve the same responses on the molecular level. Carsten Carlberg, Professor of Biochemistry at UEF’s Institute of Biomedicine, estimates that one in four individuals is a low responder, and others are either medium or high responders. Vitamin D responsiveness doesn’t usually correlate with blood calcidiol levels, so it can’t be determined with a common vitamin D status test.

In an ongoing trial, Carlberg’s research group aims to use the vitamin D response index to tests participants with multiple sclerosis. This way, the effects of vitamin D supplementation can be compared between groups with different vitamin D responses. “The vitamin D response index is a useful research tool, but it’s too expensive to become a routine measurement in health care.”

“A better solution for public health would be to substantially increase the recommended vitamin D intake for adults. One microgram of vitamin D per kilogram of body weight all year round is safe for all and ensures sufficient intake even for those with a low vitamin D response. In my opinion, Finns follow guidelines quite carefully, and such an increase in the recommended intake would probably not lead to excessive use,” Carlberg says.

“Small children are given even higher doses relative to their body weight. Why not aim at good vitamin D levels even after the first years of life?”

According to Carlberg, suitable target levels can be found from Africa where humankind originated and where those who spend a lot of time outside have blood levels exceeding 100 nmol/l.

Fortifying foods with vitamin D has improved the vitamin D intake of the Finnish population in the recent decades. According to the results of the FinDiet study published in 2017, 71 per cent of men and 82 per cent of women had sufficient vitamin D levels, in other words more than 50 nmol/l. The average level was 67 nmol/l in men and 77 nmol/l in women. The average daily vitamin D intake was 22 micrograms among men and 25 micrograms among women, which exceeds the current recommendations. “Still, one in five gets too little vitamin D from food. If you use fortified dairy products and margarines or eat a lot of fish, it’s easy to get the recommended amount. However, if your diet contains none of these and you don’t use vitamin D supplements, your intake remains really low,” Virtanen says.

The current Finnish recommendations for vitamin D intake were published in 2014. Virtanen says it will soon be time to assess if recent research evidence gives cause for updates. “In the light of results published so far, the recommended intakes will probably not be substantially increased. However, higher recommendations could be considered for more targeted groups in the future, in relation to glucose metabolism disorders or cancer, for example.”

Virtanen and Carlberg both point out that research has not proven vitamin D to be any kind of wonder pill. “Of course, no single study is sufficient to confirm the effect of vitamin D supplementation on disease risks. In the future, the focus of interest will be on meta-analyses that combine the results of various trials and are sufficiently powered to detect potential effects,” Virtanen says.

Carlberg notes that vitamin D is a nutrient needed to maintain health, not a curative medicine. Accordingly, the benefits of vitamin D in disease prevention are probably easier to show in healthy persons than in those who already have lifestyle diseases or their risk factors. For example, in the large VITAL trial, the use of vitamin D supplementation was associated with a smaller cancer risk among those with normal weight, but not among those with overweight or obesity. A similar observation relating to diabetes risk was observed in a meta-analysis which showed that vitamin D supplementation prevented diabetes progression only in normal-weight individuals.

Researchers have only begun to understand the wider role of vitamin D in the body in the recent decades. It has been shown to take part in the regulation of more than a thousand genes. “Bones are the first to suffer from vitamin D deficiency, because vitamin D is the most important regulator of calcium homeostasis. However, vitamin D also has functions in the immune system and in energy metabolism, and these are the potential links to cardiovascular diseases, diabetes and cancer. As vitamin D is just one of many factors contributing to the normal functioning of these systems, the harmful effects of its deficiency are more indirect and harder to see than in the skeletal system,” Carlberg sums up.