Zhu Haidong, Manson JoAnn E, Cook Nancy R, Bekele Bayu B, Chen Li, Kane Kevin J, Huang Ying, Li Wenjun, Christen William, Lee I-Min, Dong Yanbin
Georgia Prevention Institute, Medical College of Georgia, Augusta University, Augusta, GA, United States.
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
Am J Clin Nutr. 2025 Jul;122(1):39-47. doi: 10.1016/j.ajcnut.2025.05.003. Epub 2025 May 21.
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 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.
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.
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.
4-years of supplementation with 2000 IU/day vitamin D reduced telomere attrition by 140 bp, suggesting that vitamin D daily supplementation with or without n-3 FAs might have a role in counteracting telomere erosion or cell senescence.
有限的研究表明，补充维生素D或ω-3脂肪酸（n-3 FAs）可能有助于维持端粒，但缺乏大型随机临床试验的证据。
我们旨在通过维生素D和ω-3脂肪酸试验（VITAL）来确定补充维生素D或n-3 FAs是否能随着时间的推移减少白细胞端粒长度（LTL）的损耗。
VITAL是一项大型、随机、双盲、安慰剂对照试验，采用2×2析因设计，对25871名年龄≥55岁的美国女性和≥50岁的男性代表性样本补充维生素D3（2000国际单位/天）和海洋n-3 FAs（1克/天），为期5年。VITAL端粒研究（NCT04386577）包括1054名参与者，他们在哈佛临床与转化科学中心接受了亲自评估。在基线、第2年和第4年，通过绝对人类端粒长度定量聚合酶链反应（PCR）方法测定LTL。预先指定的主要结局指标是基线、第2年和第4年之间LTL的变化。干预效果分析采用混合效应线性回归模型。
在基线、第2年和第4年，共对1031名参与者的2571个样本进行了LTL测量。与安慰剂相比，补充维生素D3在4年内显著减少了LTL损耗0.14千碱基对（kb）（95%置信区间：0.007，0.27）（p = 0.039）。总体趋势分析表明，与安慰剂组相比，补充维生素D3组在每年随访时的LTL约高0.035 kb（95%置信区间：0.002，0.07，p = 0.037）。补充海洋n-3 FAs在第2年或第4年对LTL均无显著影响。
每天补充2000国际单位维生素D4年可使端粒损耗减少140个碱基对，这表明无论是否补充n-3 FAs，每日补充维生素D可能在对抗端粒侵蚀或细胞衰老方面发挥作用。
