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Meta-analysis associates reduced vitamin D levels with greater risk of dying over follow-up periods of up to 27 years

Meta-analysis associates reduced vitamin D levels with greater risk of dying over follow-up periods of up to 27 years

Tuesday, December 20, 2011. The results of a meta-analysis published online on December 14, 2011 in the American Journal of Clinical Nutrition reaffirm an increased risk of all-cause mortality over follow-up periods ranging from 1.3 to 24 years in association with having reduced serum levels of vitamin D.

For their review, Sara Gandini of the European Institute of Oncology and her associates selected 14 prospective cohort studies in which serum 25-hydroxyvitamin D [25(OH)D] levels were determined for a total of 62,548 men and women with an average age of 45 to 80 years. Over the studies' varying follow-up periods, 5,562 deaths occurred.

When the studies were analyzed according to highest versus lowest vitamin D levels, a 29 percent lower average risk of dying was observed for those whose levels were highest. A separate, nonlinear analysis of 11 studies which utilized approximately 27.5 nanomoles per liter(nmol/L) 25-hydroxyvitamin D as the reference range found reductions of 14, 23 and 31 percent in association with increases of 12.5, 25 and 50 nmol/L above this level, however no further reduction in mortality was associated with increases of 87.5 nmol/L. (An increase of 87.5 nmol/L above the reference range of 27.5 nmol/L equals 115 nmol/L which is equivalent to 46.1 nanograms per milliliter.)

Although the mechanism of vitamin D involved in life span is not clear, the authors mention that mice in which the vitamin D receptor has been knocked out exhibit cardiovascular and metabolic disturbances and have shorter lives than normal mice. Vitamin D deficiency in humans has been associated with cardiovascular disease, cancer, type 2 diabetes and respiratory infections and diseases. Additionally, vitamin D levels have been positively associated with the length of telomeres, which protect the ends of the chromosomes and shorten during aging.

"In summary, this meta-analysis of prospective cohort studies offers further support that concentrations of 75–87.5 nmol 25(OH)D/L are desirable," the authors conclude. "Because many adults do not achieve this 25(OH)D value, large prospective randomized trials are urgently needed to investigate whether vitamin D supplementation is able to reduce mortality risk in the general population."

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High parathyroid, low vitamin D levels associated with greater risk of sudden cardiac death

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In the December, 2011 issue of Hypertension, Rajat Deo of the University of Pennsylvania and associates report a greater risk of sudden cardiac death among men and women with low levels of vitamin D and high parathyroid hormone levels.

"Disturbances in calcium-phosphorus metabolism, 25-hydroxyvitamin D, and parathyroid hormone (PTH) have been implicated as novel risk factors for cardiovascular events," the authors write. "Disruption of the vitamin D receptor stimulates the renin-angiotensin system, provoking vasoconstriction, oxidative stress, and left ventricular hypertrophy. Parathyroid hormone excess increases intracellular calcium and increases protein synthesis and total cell mass within cardiac myocytes. These mechanisms also contribute to the pathogenesis of sudden cardiac death (SCD), but associations of vitamin D deficiency and PTH with SCD have not been reported."

The study evaluated 2,312 men and women who were free of cardiovascular disease upon enrollment in the Cardiovascular Health Study, which studied the risk of the disease in older individuals. Blood samples stored between 1992 and 1993 were analyzed for serum 25-hydroxyvitamin D and parathyroid hormone levels. Participants were followed for a median of 14 years, during which 73 sudden cardiac deaths occurred.

While only two sudden cardiac deaths per 1000 occurred among those whose 25-hydroxyvitamin D levels were at least 20 nanograms per milliliter, the amount doubled in those whose levels were lower. Similarly, high parathyroid levels of 65 picograms per milliliter or more were associated with twice the number of SCDs compared to lower levels. For the 11.7 percent who had low vitamin D and high parathyroid levels, the risk of sudden cardiac death was more than twice that of subjects with normal levels.

The authors conclude that low vitamin D and high parathyroid hormone levels are independently associated with SCD risk in men and women without cardiovascular disease and recommend further studies.

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