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Vitamin D3 and Marine Omega-3 Fatty Acids Supplementation and Leukocyte Telomere Length: 4-Year Findings from the VITAL Randomized Controlled Trial

Hai-Dong Zhu, J. Manson, N. Cook, Bayu B. Bekele, Li Chen, Kevin J. Kane, Ying Huang, Wenjun Li et al.

American Journal of Clinical Nutrition, 2025

1,054 participants · 19 citations

Abstract

BACKGROUND

Limited studies suggest that vitamin D or omega 3 fatty acids (n-3 FAs) supplementation may be beneficial for telomere maintenance, however, evidence from large randomized clinical trial is lacking. We hypothesized that vitamin D or n-3 FAs supplementation reduce leukocyte telomere length (LTL) attrition overtime by leveraging the VITamin D and OmegA-3 TriaL (VITAL) trial.

METHODS

VITAL is a large, randomized, double-blind, placebo-controlled trial with a 2 x 2 factorial design of vitamin D3 (2,000 IU/day) and marine n-3 FAs (1 g/day) supplements for 5 years among a representative sample of 25,871 US females ≥55 and males ≥50 years of age. The VITAL Telomere study (NCT04386577) included 1054 participants who were evaluated in person at the Harvard Clinical and Translational Science Center. LTL was determined by the Absolute Human Telomere Length Quantification quantitative Polymerase Chain Reaction (PCR) method at baseline, Year 2, and Year 4. The pre-specified primary outcome measures were changes in LTL between baseline, Year 2 and Year 4. Analyses of intervention effect used mixed-effects linear regression models.

RESULTS

LTL was measured in a total of 2,571 samples from the 1031 participants at baseline, year 2, and year 4. Compared to placebo, vitamin D3 supplementation significantly decreased LTL attrition by 0.14 kilo base pairs (kb) (0.01, 0.27) over 4 years (p = 0.039). Overall trend analysis showed that the vitamin D3 supplementation group had LTLs that…

How strong is the evidence?

Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 1,054 participants or records.

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