Baltimore, MD - Another study has found that that low levels of low 25-hydroxyvitamin D levels (25[OH]D) seem to be linked to an increased risk of death, this time in a nationally representative cohort [1]. Dr Michal L Melamed (Albert Einstein College of Medicine, Bronx, NY) and colleagues report their findings in the August 11/25, 2008 issue of the Archives of Internal Medicine.

Melamed told heartwire: "This is one of the largest studies, in 13 000 people, followed for an average of eight years, and is the first study to explore the association between vitamin-D levels and mortality in the overall population. This makes our results more generalizable."

Melamed and colleagues found those in the lowest quartile of vitamin-D levels had a 26% higher risk of all-cause mortality and a similar increased risk of cardiovascular disease (CVD) mortality, although the latter was not statistically significant. They did not find an association between low vitamin-D levels and cancer mortality or other causes of death, however.

She believes the time has now come for a randomized controlled trial with vitamin D looking specifically at cardiovascular events or mortality as an end point.

In their study, Melamed et al tested the association of low 25(OH)D levels with all-cause, cancer, and CVD mortality in 13 331 adults aged 20 or older from the Third National Health and Nutrition Examination Survey (NHANES III). Vitamin-D levels were collected from participants between 1988 and 1994, and individuals were passively followed for mortality through 2000.

Increasing age, female gender, nonwhite race/ethnicity, diabetes, current smoking, and higher body-mass index (BMI) were all independently associated with higher odds of vitamin-D deficiency (lowest quartile of 25[OH]D levels <17.8 ng/mL).

During 8.7 years of follow-up, there were 1806 deaths, including 777 from CVD. After multivariate adjustment, being in the lowest quartile compared with the highest quartile of vitamin D (>32.1 ng/mL) was associated with a mortality rate ratio of 1.26 (95% CI 1.08-1.46) and a population-attributable risk of 3.1%.

The mortality rate ratio for CVD mortality in the lowest vs the highest quartile was 1.20 (95% CI 0.87-1.64) and for cancer mortality 0.91 (95% CI 0.62-1.31).

Melamed explained that when they analyzed subgroups, they found that the risk for mortality in those in the lowest quartile of vitamin D was more evident in those who did not have CVD at the beginning of the study compared with those who did have CVD.

"This suggests to us that maybe, if vitamin D is playing a role in CVD, it is acting before the disease is established," she said, adding that this whole issue will require further study.

Also, like other studies, they found that very high vitamin-D levels may be detrimental in some subgroups—in this particular study it was in women. "This suggests that, like anything in the body, there is an 'optimum' level of vitamin D," Melamed noted.

With regard to what doctors should do currently in terms of assessing vitamin-D levels, she said, "They should definitely be checked in people at risk of osteoporosis and perhaps in the other subgroups who are at risk of vitamin-D deficiency, such as women, those with high BMI, and ethnic minorities."

She said she would not advise people to take supplements without knowing their vitamin-D levels and that the most sensible advice for those wanting to ensure their levels remain optimal is to spend 10 to 15 minutes per day in the sun and to eat vitamin-D-fortified foods, such as milk and oily fish.