Low Vitamin D Levels Linked to Longer Life
Laurie Barclay, MD
Nov 05, 2012
New genetic findings in those predisposed to longevity cast doubt on whether low levels of vitamin D cause age-related diseases and mortality, according to an analysis from the Leiden Longevity Study published online November 5 in the Canadian Medical Association Journal.
"Vitamin D plays a critical role in bone formation, immune cell differentiation, and in the inhibition of proliferation and angiogenesis in cancer," write Raymond Noordam, MSc, from the Department of Gerontology and Geriatrics at Leiden University Medical Center in the Netherlands, and coauthors. "Low serum levels of 25-hydroxyvitamin D3 (25[OH] vitamin D) are associated with increased mortality, cardiovascular disease, diabetes mellitus, cancer, multiple sclerosis, allergy, asthma, infection, depression, mental illness and musculoskeletal pain. However, because of design limitations, previous studies have not been able to infer causality."
The goal of this study was to examine a possible causal association between low levels of 25(OH) vitamin D and various age-related diseases and mortality. The Leiden Longevity Study allowed assessment of vitamin D levels in the middle-aged offspring of nonagenarians who had 1 or more nonagenarian siblings, using a sample of 380 white families with 2 or more siblings at least 89 years of age for men or 91 years of age for women. This was useful because the prevalence of age-related diseases is lower in these offspring than in the general population, and they are more likely to survive to old age.
Control patients (n = 461) were the partners of the offspring (n =1038) and were of similar age and had similar environmental exposures that could affect vitamin D levels. In addition to anthropometric measurements, 25(OH) vitamin D levels, parathyroid hormone levels, and dietary vitamin D intake, the investigators studied single nucleotide polymorphisms (SNPs) in 3 genes known to be associated with vitamin D levels.
Compared with the control participants, the offspring had significantly lower levels of vitamin D (64.3 nmol/L vs 68.4 nmol/L; P= .002). These findings were independent of possible confounding factors (age, sex, body mass index, month of blood sampling, tanning bed use, dietary and supplemental vitamin D intake, and creatinine levels). Levels of parathyroid hormone did not differ between groups.
The rs2060793 genetic variant in the CYP2R1 gene occurred less frequently in the offspring than in the control participants (P= .04). Across the 2 most prevalent genotypes of this SNP, there was a persistent difference in vitamin D levels between offspring and control patients.
"Compared with controls, the offspring of nonagenarians who had at least one nonagenarian sibling had a reduced frequency of a common variant in the CYP2R1 gene, which predisposes people to high vitamin D levels; they also had lower levels of vitamin D that persisted over the 2 most prevalent genotypes," the study authors write. "These results cast doubt on the causal nature of previously reported associations between low levels of vitamin D and age-related diseases and mortality."
Limitations of this study include the availability of data on tanning bed use and sun exposure for only a small, but random, subpopulation of participants. In addition, the analyses excluded 36% of participants because of missing data on possible confounding factors. However, the excluded participants also showed similar differences in vitamin D levels between offspring and control patients, suggesting they were representative of the total study group.
The investigators put forth a theory that the offspring of nonagenarians may have increased expression of the klotho protein, which is thought to be an "aging suppressor" protein.
"We found that familial longevity was associated with lower levels of vitamin D and a lower frequency of allelic variation in theCYP2R1 gene, which was associated with higher levels of vitamin D," the study authors conclude. "Future research should focus on elucidating the mechanisms that explain the lower 25(OH) vitamin D levels in familial longevity and other genetic variants associated with vitamin D metabolism, such as the vitamin D receptor."
The study was supported by the Innovation Oriented Research Program on Genomics, the Center for Medical Systems Biology, and the Netherlands Genomics Initiative/Netherlands Organisation for Scientific Research. The study authors have disclosed no relevant financial relationships.
CMAJ. Published online November 5, 2012. Abstract
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Cite this article: Low Vitamin D Levels Linked to Longer Life. Medscape. Nov 05, 2012.