Vitamin D and death risk

The Daily Express today reports that a “ground-breaking study has shown that people with higher levels of the sunshine vitamin D dramatically slash their risk of dying early from heart disease or other health problems.” These results come from an eight-year study of over 3,200 men and women with angina, whose levels of vitamin D were measured. During this time, about 22% of the participants died, and the newspaper reports that “those who died were in the bottom half of vitamin D blood test readings”. The newspaper suggests that two or three 10–15 minute periods of sun exposure each week without sun cream is enough to achieve adequate levels of vitamin D. However, they warn that longer exposures can actually lead to breakdown of vitamin D, and that excessive sun exposure can cause skin ageing and skin cancer.

This study was well-conducted but, as the researchers acknowledge, it cannot prove that low levels of vitamin D directly caused an increased risk of death. It should also be pointed out that people with high levels of vitamin D also died during the study, not just those with low levels. The study participants all had acute coronary syndrome (signs and symptoms which indicate the heart is being starved of oxygen, e.g. a typical heart attack), and they are not representative of the general population. Most of the vitamin D in the body is made in response to sunlight, and people need some sun exposure for this reason, particularly the elderly. However, excessive sun exposure may lead to skin cancer, therefore people should follow sensible exposure rules, such as staying out of the midday sun and avoiding burning.

Where did the story come from?

Dr Harald Dobnig and colleagues from the University of Graz in Austria, and universities and laboratory diagnostic centres in Germany carried out this research. The study was funded by unrestricted grants from Sanofi-Aventis, Roche, Dade Behring, and AstraZeneca. It was published in the peer-reviewed journal Archives of Internal Medicine .

What kind of scientific study was this?

The study was a prospective cohort study, the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. The researchers enrolled 3,316 consecutive white patients who attended a cardiac centre in southwest Germany for a special X-ray examination using a dye to visualise the heart and surrounding blood vessels (coronary angiography). The patients were receiving coronary angiography because other symptoms or test results had suggested there was a lack of oxygen reaching the heart muscle (myocardial ischaemia). In order to be included in the study, patients had to have a stable clinical condition. Patients with active illnesses other than acute coronary syndrome, non heart-related chronic diseases or who had malignant cancer in the previous five years were excluded.

The patients underwent a thorough assessment and filled in questionnaires about their lifestyle. Researchers also took a blood sample from 3,258 of these patients (average age of 62 years) and measured the levels of two different forms of vitamin D (25-hydroxyvitamin D and 1,25-hydroxyvitamin D) in these samples. Some patients reported taking vitamin D supplements, but their vitamin D levels were not much higher than people who did not, so they were included in the analyses. The patients were divided into four groups according to their vitamin D level, with each group containing 25% of the participants (quartiles). The first quartile had the lowest vitamin D levels, the fourth quartile had the highest vitamin D levels, and the two groups in the middle contained the 25% of participants with levels just below or the 25% with levels just above average respectively.

The researchers followed-up the patients using local registries for an average of just over seven and a half years. They recorded who died, and the cause of death (judged independently by two experienced clinicians, using death certificates). The researchers were particularly interested in deaths from heart and cardiovascular causes. They compared overall deaths and deaths from cardiovascular causes over the follow-up period between the four different groups of patients with different vitamin D levels. They took into account factors that might affect results in their analyses, including other risk factors for cardiovascular death (e.g. age, gender, the presence of coronary artery disease, physical activity level, cholesterol level, smoking, diabetes, blood pressure), presence of other illnesses and levels of calcium metabolism.

What were the results of the study?

During the study, 463 of the participants died from cardiovascular causes (about 14%), and 274 participants died from other or unknown causes (about 8%), giving a total of 737 deaths.

People with the lowest levels of one form of vitamin D (25-hydroxyvitamin D) were about twice as likely to die from any cause or from cardiovascular causes during follow-up than those with the highest levels of vitamin D, after adjustment for other possible risk factors (hazard ratio 2.08, 95% confidence intervals 1.60 to 2.70). The researchers found similar results when they looked at people with different levels of the 1,25-hydroxyvitamin D (hazard ratio 1.61, 95% confidence intervals 1.25 to 2.07).

What interpretations did the researchers draw from these results?

The researchers concluded that low levels of vitamin D in the blood are associated with an increased risk of death from any cause or from cardiovascular causes, independent of other risk factors. However, studies have yet to show that vitamin D supplementation can reduce risk of death.

What does the NHS Knowledge Service make of this study?

This was a well-conducted study, which has some limitations:

• Vitamin D levels were measured only once during the study. These levels may not have been representative of a person’s vitamin D status throughout their lifetime.
• People included in this study had signs of heart problems, were on average aged in their 60s and were all white. The results of this study may not apply to a healthier group of people, younger people or people from different ethnic groups.
• In this type of study, where groups are not randomly assigned, the results may be a result of differences between the groups other than the differences in the factor being studied (in this case vitamin D levels). For example, the group with the lowest levels of vitamin D in this study were older, had more co-existing medical conditions and were more likely to be women than those with higher vitamin D levels. In this study, the authors adjusted their results for a number of possible risk factors, which increases confidence in the results. However, these adjustments may not have fully removed the effects of these other factors, and there may still be unknown or unmeasured factors that differed between groups and could contribute to the difference seen in risk of death.
• As the researchers acknowledge, their study is not able to prove conclusively that low vitamin D levels increased a person’s risk of death.

Vitamins and minerals have an important role to play in maintaining health. Most vitamin D is made by the body in response to sunlight, and people need some sun exposure for this reason, particularly the elderly. However, excessive sun exposure may lead to skin cancer, therefore people should follow sensible sun exposure rules, such as staying out of the midday sun and avoiding burning.

Sir Muir Gray adds...

As a sixty-four-year-old male I believe in vitamin D and try to take it; remembering  is the problem.