Initial research has suggested that vitamin D may reduce the risk of developing cardiovascular disease and cancer.However, there have been few large, higher-quality randomized controlled trials (RCTs) to corroborate this.A recent RCT examined the effects of vitamin D supplementation in Finland.It found no association between vitamin D supplementation and reduced risk of cardiovascular disease or cancer.Vitamin D helps the body absorb calcium, which improves bone strength. Among other roles, it also contributes to the functioning of muscles, nerves, and the immune system.Many scientists have set out to understand how vitamin D deficiency and supplementation may influence disease. According to the World Health Organization (WHO), there is some evidence that vitamin D may help protect against respiratory tract infections, for example.Over the past 2 years, researchers have also explored whether vitamin D reduces the risks associated with COVID-19. Although investigations are ongoing, there seems to be some evidence that these supplements might improve intensive care unit admission rates.Two other areas of particular interest are vitamin Ds potential effects on cardiovascular disease and cancer risk. However, few RCTs have looked into this. These types of studies are the gold standard for identifying causal relationships in scientific research.A recent study, which appears in The American Journal of Clinical Nutrition, goes some way toward addressing this knowledge gap.Speaking with Medical News Today, Vimal Karani, a professor of nutrigenetics and nutrigenomics at the University of Reading, in the United Kingdom, confirmed that there has been a gap between the initial research and findings from clinical trials. Prof. Karani was not involved in the recent study but has worked with some of its authors.He explained that past large epidemiological studies have established a link between vitamin D deficiency and the risk of [cardiovascular disease] traits in various ethnic groups. This, he said, suggests that vitamin D supplements might lower cardiovascular risk.However, he continued, clinical trials have not provided convincing evidence of the blood pressure-lowering effect of vitamin D supplementation.Prof. Karani said that there could be a wide range of reasons for this, including differences in the sample size, duration of supplementation, dose of the supplementation, age of the participants, geographical location, sun exposure, and the outcome measures. Further research is required to replicate the findings in multiple ethnic groups.To provide further evidence of the relationship between vitamin D, cardiovascular disease, and cancer, the researchers behind the present study conducted the Finnish Vitamin D Trial. This took place between 2012 and 2018, and it was double-blind, randomized, and placebo-controlled.When we started to plan the trial, there was a lot of evidence from observational studies that vitamin D deficiency would be associated with nearly all major chronic diseases, such as [cardiovascular disease], cancer, type 2 diabetes, and also mortality, said Dr. Jyrki Virtanen in an interview with Medical News Today. Dr. Virtanen is an associate professor of nutrition and public health at the University of Eastern Finland, and a co-principal investigator of the study.Also, we had shown that among [the] Eastern Finnish population, low vitamin D content of the body was associated with higher risk of mortality and glucose metabolism disturbances. However, these kinds of studies do not give evidence for causality.At that time, there was little evidence from RCTs that improvement of [the] vitamin D status of the body with vitamin D supplementation reduced the risk of diseases.Therefore, our aim was to start a long-term vitamin D supplementation trial in Finland, where vitamin D insufficiency had been quite prevalent due to the long winter, and investigate whether vitamin D supplementation could reduce the risk of major chronic diseases and death.The researchers looked at data from 2,495 people, including male participants 60 years or older and female participants who were postmenopausal and 65 years or older. The participants also had no history of cardiovascular disease or cancer.The participants either took a placebo, vitamin D at a dosage of 1,600 international units (IU) each day, or vitamin D at a dosage of 3,200 IU each day.Compared with the placebo, neither dosage of vitamin D reduced the incidence of cardiovascular disease or cancer in this cohort, the team determined.One factor that complicated this analysis was that the participants tended to have high levels of vitamin D at the start of the study. This, the authors believe, stems from the implementation of policies to fortify foods with vitamin D in Finland, which began in 20032011.It is likely that vitamin D supplementation does not provide major health benefits, especially in populations where the vitamin D situation is already good at the start of the trial. Dr. Jyrki VirtanenA problem with most large vitamin D supplementation trials has been that the starting levels of vitamin D have been pretty high in a large part of the study populations, explained Dr. Virtanen. This may reflect the well-known fact that people who take part in these kinds of studies tend to be more health-conscious and more interested in their health, so they are, on average, healthier than the average population. They may have a better diet and are more likely to take supplements and exercise, which all are associated also with higher serum vitamin D levels, he told MNT.Those who might benefit from the vitamin D supplementation i.e., those with low serum vitamin D levels are a small minority in the trials. It is tricky to target this deficient population, though, because for ethical reasons it would not be possible to screen people and only admit people with low vitamin D levels in the trial. It would not be ethical to keep a part of the study population, the placebo group, deficient [in] vitamin D for several years.MNT spoke with Prof. Sean Strain, Dr. Emeir McSorley, and Dr. Pamela Magee, of the Nutrition Innovation Centre for Food and Health, at Ulster University, in Northern Ireland. They explained that despite the low recruitment levels the study authors had hoped to recruit 30,000 participants the results showed some signs that vitamin D had health benefits.Even though recruitment was challenging and didnt meet expectations, there is some indication that the cohort investigated had lower incidence of both [cardiovascular disease] and cancer, compared to national statistics, which would have been gathered prefortification.This may indicate that improvements to vitamin D status nationally are having benefits to the overall health of the population over and above the well-known bone and muscle health effects. Because of the low numbers recruited, the cohort may not be nationally representative, and care should be taken when interpreting these findings, said the scientists.According to Prof. Karani: The unique feature of this RCT was the use of two different vitamin D doses to see the dose-response effect over a period of 5 years. Despite the large doses, the study failed to see any effect of the supplementation on lowering the incidence of [cardiovascular disease] and cancer.The findings have significant public health implications, continued Prof. Karani. However, the findings cannot be generalized to other populations, given that [the] Finnish population is a well-known example of an isolated population, where multiple bottlenecks resulting from consecutive founder effects have led to the gene pool of current-day Finns. Dr. Virtanen said that while there is some evidence of broader health benefits from vitamin D supplementation, there were also conflicting findings.At the moment, there is no consensus [about] what would be the optimal vitamin D intake and [whether it is] the same for all health outcomes and for all people. For example, there is some evidence that high-dose vitamin D supplementation may modestly reduce the risk of cancer death, but not overall cancer incidence.And although there, so far, is no evidence that vitamin D supplementation could prevent [SARS-CoV-2] infection, it is well-documented that those, especially with the severe form of COVID-19, have low serum vitamin D levels.It is also possible that this is a consequence of the [SARS-CoV-2] infection rather than the cause, because it is known that acute infection leads to lower serum vitamin D levels, and many of the COVID-19 patients are overweight or obese or have a chronic disease like type 2 diabetes, which all are associated with lower serum vitamin D levels, explained Dr. Virtanen.Prof. Strain, Dr. McSorley, and Dr. Magee highlighted the role that vitamin D may play in a healthy immune system.There is recent strong evidence that vitamin D supports your immune system, and given the global pandemic, it does appear that those who are vitamin D replete dont have as severe a response to COVID-19 as those who are deficient and importantly, recover quicker.Vitamin D plays a key role in musculoskeletal health. Vitamin D can be obtained via sunlight and dietary sources. However, a vitamin D supplement may be required to meet the recommended dietary intakes that is, 600 IU per day in the United States for those aged 170 years, and 800 IU per day for those over 70 years in order to maintain a sufficient status.Supplementation may be particularly relevant in populations residing at northerly latitudes, where vitamin D cannot be synthesized from sunlight during the winter months, and in populations that spend little time outdoors and/or obtain limited amounts of vitamin D from food sources.It is very difficult to obtain vitamin D from food intake alone, unless that food is fortified with vitamin D. Furthermore, those with illnesses that affect vitamin D absorption may require vitamin D supplementation, said the scientists.Prof. Strain, Dr. McSorley, and Dr. Magee suggested that the research could be developed by studying a population with low levels of vitamin D.This research needs to be undertaken in a suitable population, where many have a low vitamin D status and can therefore benefit from vitamin D supplementation.It would be important to explore whether vitamin D supplementation can decrease the incidence of [cardiovascular disease] and cancers, as that would make a strong case for mandatory vitamin D fortification or promotion of fortified foods in the population.There is some tantalizing evidence that the Finnish national [vitamin D] fortification program is having benefits by decreasing the incidence of [cardiovascular disease] and cancers, as well as the expected beneficial effects on bone health.Another very important area that needs to be explored further is the link between sufficient vitamin D status and a fully functional immune system, especially in light of the current COVID-19 pandemic.As Prof. Karani notes, A similar RCT with a longer duration of vitamin D supplementation is highly warranted in ethnically diverse populations to see if the findings from the present study could be generalized.Dr. Virtanen told MNT that his current focus is on further analyzing the results from the Finnish Vitamin D Trial.At the moment, we dont have plans to start another vitamin D trial, but we are of course going to publish several other results from the Finnish Vitamin D Trial, for example effects [on] heart arrhythmias, infections, type 2 diabetes, falls and fractures, pain, [and] mood changes.