Leukocyte Telomere Length and Vitamin D: A Systematic Review of Observational Research

Introduction: Interest in biological markers of healthy aging has grown, particularly vitamin D (VD) and leukocyte telomere length (LTL). Telomeres shorten with age and are linked to chronic disease, while VD may influence this process through effects on inflammation and oxidative stress. Clarifying the VD–LTL relationship could inform their value as biomarkers of longevity. Methods: A PRISMA-guided systematic review of observational studies was conducted, searching PubMed, EMBASE, Cochrane Library, and Scopus in April 2025. Eligible studies enrolled adults and reported serum/plasma VD and LTL measured with validated techniques. Risk of bias was appraised using the Newcastle–Ottawa Scale. Results: From 521 records, 32 full texts were assessed, and 11 observational studies were included (10 cross-sectional, 1 cohort) spanning Europe, the Americas, and Asia (2007–2023). VD was measured via CLIA/RIA, ELISA, or LC-MS/MS; LTL predominantly by qPCR (one Southern blot). Findings were heterogeneous: 4 studies reported longer LTL with higher 25-hydroxyvitamin D [25(OH)D], 1 showed a U-shaped association (shorter LTL at very low and very high 25(OH)D), and 6 found no significant relationship. Positive signals appeared more often in female or middle-aged subgroups, but variability in exposure/outcome definitions and covariate adjustment limited comparability and precluded meta-analysis. Risk of bias was generally low-to-moderate (2 “very good,” 8 “good,” 1 “unsatisfactory” on NOS). Discussion: Findings varied across studies. While some studies reported positive associations between vitamin D levels and telomere length—particularly in female and middle-aged populations—the majority found no significant relationship, and one study reported a U-shaped association. Substantial methodological heterogeneity in study design, vitamin D measurement methods, and covariate adjustment limits the ability to draw definitive conclusions. Based on current evidence, vitamin D supplementation cannot be recommended solely for telomere preservation, though the observed associations in specific subgroups warrant further investigation through well-designed longitudinal and interventional studies.