Vitamin D3 and marine ω-3 fatty acids supplementation and leukocyte telomere length: 4-year findings from the VITamin D and OmegA-3 TriaL (VITAL) randomized controlled trial.

2025-07
The American journal of clinical nutrition 122(1)
- Haidong Zhu
- JoAnn E Manson
- Nancy R Cook
- Bayu B Bekele
- Li Chen
- Kevin J Kane
- Ying Huang
- Wenjun Li
- William Christen
- I-Min Lee
- Yanbin Dong

PubMed: 40409468
DOI: 10.1016/j.ajcnut.2025.05.003

Study Design

Type: Randomized Controlled Trial (RCT)
Sample size: n = 1,054
Population: 1054 participants who were evaluated in person at the Harvard Clinical and Translational Science Center
Methods: Double-blind, placebo-controlled trial with a 2x2 factorial design of vitamin D3 (2,000 IU/day) and marine n-3 FAs (1 g/day) supplements for 5 years
Blinding: Double-blind
Duration: 5 years
Funding: Unclear

Large Human Trial

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.

Objective

We aimed to determine whether vitamin D or n-3 FAs supplementation reduce leukocyte telomere length (LTL) attrition over time by leveraging the VITamin D and OmegA-3 TriaL (VITAL) trial.

Methods

VITAL is a large, randomized, double-blind, placebo-controlled tr ial 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) (95%CI: 0.007, 0.27) over 4 years (p = 0.039). Overall trend analysis showed that the vitamin D3 supplementation group had LTLs that were about 0.035 kb higher per year of follow-up compared to placebo group (95%CI: 0.002, 0.07, p=0.037). Marine n-3 FAs supplementation had no significant effect on LTL at either year 2 or year 4.

Conclusion

4-years of supplementation with 2000 IU/day vitamin D₃ reduced telomere attrition by 140 bp, suggesting that vitamin D₃ daily supplementation with or without n-3 FAs might have a role in counteracting telomere erosion or cell senescence.