Can Vitamin D Supplementation Slow Cellular Aging?
July 30, 2025 4 minutes read
By Seema Gupta, MD, MSPH
Synopsis: In a large randomized, double-blind, placebo-controlled trial, vitamin D3 supplementation modestly but significantly slowed the rate of leukocyte telomere shortening over four years.
Source: Zhu H, Manson JE, Cook NR, et al. 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. Am J Clin Nutr. 2025;122(1):39-47.
The primary function of telomeres is to protect chromosome ends from degradation, fusion, and inappropriate deoxyribonucleic acid (DNA) damage responses, thereby maintaining genomic stability. Without telomeres, chromosome ends could be mistaken for DNA breaks and joined together, causing genomic instability. Each time a somatic cell divides, its telomeres shorten because of the “end-replication problem” of DNA polymerase. Over time, critically short telomeres trigger cellular senescence or apoptosis, which contributes to aging and age-related diseases.1 Shorter telomere length has been associated with increased all-cause mortality as well as being a key driver in tumorigenesis and higher risk of cardiovascular and autoimmune diseases.2 Therefore, identifying factors that mitigate telomere shortening is essential, since this may help delay premature aging and reduce the risk of age-associated diseases.
Vitamin D and omega-3 fatty acids (n-3 FAs) are essential for various cellular processes, including differentiation, proliferation, and apoptosis, and have been proposed as protective agents against aging and age-related diseases. A few small studies have suggested that supplementation with n-3 FAs may favorably affect telomere length or telomerase activity.3
In their study, Zhu et al attempted to evaluate whether daily supplementation with vitamin D3 (2,000 IU/day) or marine omega-3 fatty acids (1 g/day) reduced leukocyte telomere length (LTL) attrition over four years in adults. Researchers used data from the VITamin D and OmegA-3 TriaL (VITAL) trial, which is a representative sample of 25,871 U.S. females ≥ 55 years of age and males ≥ 50 years of age. In this randomized, double-blind, placebo-controlled, 2×2 factorial study, they analyzed 2,571 samples from 1,031 participants examining LTL measured at baseline, year 2, and year 4. The primary outcome focused on changes in LTL between these time points and were analyzed using mixed-effects linear regression models to determine the intervention’s effect.
Researchers found that, compared to placebo, vitamin D3 supplementation significantly reduced LTL attrition by 0.14 kilobase (kb) pairs (95% confidence interval [CI], 0.007-0.27) over four years (P = 0.039). Further results indicated that the vitamin D3 group maintained LTLs approximately 0.035 kb pairs higher per year of follow-up (95% CI, 0.002-0.07; P = 0.037). In contrast, marine n-3 fatty acid supplementation did not significantly affect LTL at either the two- or four-year mark. The study authors noted that four years of daily vitamin D3 supplementation may help offset telomere shortening and cellular senescence, potentially delaying biological aging by approximately three years.
Commentary
This is the first large-scale and long-term randomized trial to evaluate the anti-aging potential of vitamin D. As demonstrated by Zhu et al, vitamin D supplementation over four years protected telomeres and preserved telomere length, suggesting potential biological mechanisms for vitamin D’s protective effects. Vitamin D may stimulate telomerase, the enzyme responsible for maintaining and extending telomeres, as well as provide cellular protection. This is an interesting finding because, previously, the VITAL study group also had shown the benefits of vitamin D in reducing inflammation and lowering risks of selected chronic diseases of aging, such as advanced cancer and autoimmune disease.4,5
The findings from Zhu et al indicate that targeted vitamin D supplementation could be a promising approach to slowing biological aging, although additional research would be needed to confirm and expand on these results. However, there are three clear implications of this study. Firstly, for patients aged 50 years and older — especially those at risk of vitamin D deficiency — daily supplementation with 2,000 IU of vitamin D3 may offer protective benefits against leukocyte telomere shortening, a biological marker of aging. The 2,000 IU/day dosage of vitamin D3 used in this study was well-tolerated over four years, supporting its use within recommended upper intake levels for most adults without risk of toxicity. Secondly, in middle-aged and older patients, particularly those with chronic inflammatory or age-related conditions, screening for and correcting low vitamin D levels may have cellular aging and systemic health implications. Lastly, although marine n-3 FAs have other cardiovascular and anti-inflammatory benefits, this study did not find evidence that omega-3s prevent telomere shortening. It may be prudent to avoid using omega-3 supplements specifically for anti-aging at this time.
Seema Gupta, MD, MSPH, is Clinical Assistant Professor, Department of Family and Community Health, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV.
References
- Dunn PL, Logeswaran D, Chen JJ-L. Telomerase-mediated anti-ageing interventions. Subcell Biochem. 2024;107:1-20.
- Wang Q, Xi L, Yang N, et al. Association of leukocyte telomere length with risk of all-cause and cardiovascular mortality in middle-aged and older individuals without cardiovascular disease: A prospective cohort study of NHANES 1999-2002. Aging Clin Exp Res. 2024;36(1):131.
- Siopis G, Porter J. Contribution of biological age-predictive biomarkers to nutrition research: A systematic review of the current evidence and implications for future research and clinical practice. Adv Nutr. 2022;13(5):1930-1946.
- Hahn J, Cook NR, Alexander EK, et al. Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial. BMJ. 2022;376:e066452.
- Chandler PD, Chen WY, Ajala ON, et al; VITAL Research Group. Effect of vitamin D3 supplements on development of advanced cancer: A secondary analysis of the VITAL randomized clinical trial. JAMA Netw Open. 2020;3(11):e2025850.
In a large randomized, double-blind, placebo-controlled trial, vitamin D3 supplementation modestly but significantly slowed the rate of leukocyte telomere shortening over four years.
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