Low vitamin D levels linked to mortality

“D stands for 'death-defying' in the vitamin stakes” is the headline in the Daily Mail . A study has found that “people with low vitamin D levels are at greater risk of dying from all causes”. Those with the lowest levels were found to be at a “26 per cent extra risk of death after nine years” compared with those with the highest levels, the newspaper says. It reports that the Food Standards Agency (FSA) does only recommends a specific daily dose of vitamin D in people who are elderly, pregnant, Asian, get little sun exposure and eat no meat or oily fish; these people are advised to take 10 micrograms daily.

These results come from a large observational study in the US. Although the study was well conducted, because of the way it was designed, it is not certain that increase in deaths seen was due to vitamin D levels. In the absence of definitive research indicating that taking extra vitamin D can reduce risk of death, it is advisable to try and maintain vitamin D levels naturally through diet and sensible sun exposure, and if you do take supplements, to follow the advice of the FSA.

Where did the story come from?

Dr Michal Melamed and colleagues from the Albert Einstein College of Medicine in New York, and Johns Hopkins University carried out this research. The study was funded by the National Institutes of Health. It was published in the peer-reviewed medical journal: Archives of Internal Medicine .

What kind of scientific study was this?

This was a cohort study, looking at the link between vitamin D levels in the blood and mortality (death). The researchers used data from participants who were enrolled in a larger study in the USA: the third National Health and Nutrition Examination Survey (NHANESIII). Only those participants aged 20 years or above, who provided blood samples and had a physical examination when they enrolled for the NHANESIII between 1988 and 1994, and whose vital status (whether they were alive or dead) was known in 2000 were included. This left 13,331 people for analysis in the current study.

The participants all completed questionnaires about their demographic characteristics, medical history, medication and supplement usage (including vitamin D) and lifestyle. To ensure comparable conditions, people in northern states were surveyed during the summer and those in southern states were surveyed in the winter. The blood samples taken at enrolment were tested for vitamin D levels. People were divided into four groups based on their vitamin D levels: those with levels in the lowest 25% of measurements, those with levels in the highest 25% of measurements, and two groups each containing the 25% of participants with levels either just above or below the median (middle or average) measurement.

The researchers used the National Death Index to identify participants who had died up to the end of 2000 and their cause of death. They then compared mortality among people with different levels of vitamin D in their blood. They adjusted their analyses for a wide range of factors that might affect the results, such as the season in which the blood sample was taken, age, race, gender, smoking, BMI, physical activity, use of vitamin D supplements and medical problems such as high blood pressure, cardiovascular disease, kidney problems and diabetes. Because non-Hispanic black people had lower vitamin D levels than non-Hispanic white people, they were underrepresented in the group with the highest levels of vitamin D. The researchers therefore decided to analyse them separately.

What were the results of the study?

The researchers found that older people, women and non-Hispanic black people had lower levels vitamin D in their blood than other groups. People with lower levels of vitamin D in their blood tended to have higher blood pressure and BMI, to be more likely to have diabetes, to be less likely to be taking vitamin D supplements, to be taking less physical activity and to be from lower socioeconomic groups.

People were followed up for an average (median) of 8.7 years. During this time there were 1,806 deaths (13.5%). Overall, people who had the lowest levels of vitamin D (in the bottom 25% of measurements) were about 26% more likely to die than those with the highest levels of vitamin D (in the top 25% of measurements) after adjusting for potential confounders.

When the researchers looked at the causes of death, they noted an increase in cardiovascular deaths, but this increase did not reach statistical significance after it was adjusted to consider other factors. There were no significant associations between vitamin D levels and deaths from cancer or infectious causes.

What interpretations did the researchers draw from these results?

The researchers conclude that in the general population in the US, having vitamin D levels in the lowest 25% of measurements is associated with an increased risk of all-cause death, independent of other risk factors.

What does the NHS Knowledge Service make of this study?

This was a large study, which was generally well conducted, but with some limitations:

• The authors themselves note that because this study was observational in nature it cannot prove that low vitamin D levels are causing the increase in death. This is because there could be other factors that differ between the low and high vitamin D groups that are having an effect. Although the authors did try to take these into account by making adjustments for known risk factors, they acknowledge that this may not have removed all confounding effects.
• Vitamin D levels were measured only once in each participant, and may not be representative of their vitamin D levels over their entire lifetime.
• The NHANESIII population was designed to be representative of the US population. However, it may not be representative of people from different countries, particularly those with different ethnic backgrounds.

Because of these limitations, it is not possible to know whether vitamin D supplementation would have any effect on overall mortality. Randomised controlled trials would be needed to assess whether this is the case, and if so, to determine the optimal level of supplementation.

Sir Muir Gray adds...

This looks like the one vitamin which I will take regularly, or try to remember to take regularly.