Serum 25-Hydroxyvitamin D Has a Modest Positive Association with Leukocyte Telomere Length in Middle-Aged US Adults

Background: Vitamin D deficiency has been linked to all-cause mortality and cancer. However, the biological plausibility of these associations is not well established. Leukocyte telomere length (LTL) shortening is associated with aging and is a hallmark of genomic instability and carcinogenesis. Objective: We aimed to investigate the association between serum 25-hydroxyvitamin D [25(OH) D] concentrations and LTL in the general US population. Methods: We analyzed data from the US NHANES 2001-2002. The study population comprised 1542 younger adults (aged 20-39 y), 1336 middle-aged adults (aged 40-59 y), and 1382 older adults (aged >= 60 y). LTL was measured by using quantitative polymerase chain reaction. Serum 25(OH) D concentrations >= 50 nmol/L were considered optimal. Linear regression, adjusted for age, sex, race/ethnicity, body mass index (BMI), total energy and sugar intakes, calcium intake, socioeconomic status, milk and dietary supplement consumption, and physical activity, was applied to investigate the association between serum 25(OH) D and LTL. Results: In the total population, age, sex, BMI, and non-Hispanic black race/ethnicity were significant predictors of LTL. In the participants aged 40-59 y, an increment in serum 25(OH) D of 10 nmol/L was associated with a 0.03- +/- 0.01-kbp longer LTL, adjusted for age, sex, race/ethnicity, and other factors (P = 0.001). In the same age group, 25(OH) D concentrations >= 50 nmol/L were associated with a 0.13- +/- 0.04-kbp longer LTL than those for 25(OH)D concentrations <50 nmol/L (P = 0.01). The association was independent of age, sex, race/ethnicity, BMI, and other factors. Conclusions: In a nationally representative population of adults, serum 25(OH) D was positively associated with LTL in middle-aged participants (aged 40-59 y), independently of other factors. These findings suggest that decreased 25(OH) D concentrations are associated with genomic instability, although the clinical impact of this observation remains unclear.