The Association of Vitamin D Supplementation with the Rate of Epigenetic Aging

by | May 2, 2024 | 2022, Aging, Recent Articles, Vitamin D - General

Written by Harold Oster, MD. Results suggest that vitamin D supplementation in deficient individuals is associated with slower epigenetic aging.

vitamin D capsulesVitamin D deficiency leads to bone loss and the increased likelihood of fractures. Severe deficiency is associated with an increased risk of overall mortality, infections, and various medical conditions. Vitamin D supplementation in deficient individuals may be beneficial in preventing and treating these conditions1. Epigenetic age, an individual’s degree of aging determined by patterns of DNA methylation, changes with diet, lifestyle, and disease. An increase in DNA methylation more than expected based on chronologic age (methylated DNA age acceleration, or DNAmAA) is associated with disease states and overall mortality2.

Valentin Max Vetter et al. studied the beneficial effects of vitamin D supplementation on DNAmAA in vitamin D-deficient older adults. The authors analyzed data gathered as part of the Sex-and gender-sensitive prevention of cardiovascular and metabolic disease in older adults in Germany study (GendAge), which was completed in 2020. Gendage was a follow-up evaluation of participants in the Berlin Aging Study II (BASE-II), a study completed in 2014 evaluating 1671 individuals over sixty years old to determine factors involved in aging and the development of age-related diseases3. The participants were assessed at baseline (BASE-II) and in the GendAge study for demographics, medical history, vitamin D levels, and the use of vitamin D supplementation. DNAmAA was determined at baseline and follow-up by five validated methods: 7-CpG clock, Horvath’s clock, Hannum’s clock, Phenoage4, and GrimAge5.

The authors noted the following:

  • Based on inclusion criteria, data from 1,036 participants was analyzed.
  • The average age of participants was 75.6 years.
  • The average follow-up was 7.4 years.
  • At baseline, 46.43% of individuals were vitamin D deficient. At follow-up, 22.20% were deficient.
  • At follow-up, 20.37% of participants were taking vitamin D supplements, of whom 82% started taking them after baseline testing.
  • The authors previously reported a 0.9-year higher DNAmAA in vitamin D-deficient BASE-II participants than those with sufficient vitamin D levels.
  • Vitamin D-deficient individuals whose levels normalized after taking vitamin D supplements had a lower DNAmAA than vitamin D-deficient participants who did not take vitamin D supplements. (A difference of 2.61 years for the 7-CpG clock and 1.27 years for the Horvath clock) The association persisted after adjustment for covariables.
  • There was no significant difference in DNAmAA between participants whose levels normalized after taking vitamin D supplements and those who were never deficient.
  • There was an inverse correlation between vitamin D levels and DNAmAA tested with the 7-CpG clock and GrimAge.

Results suggest that vitamin D supplementation in older individuals with vitamin D deficiency is associated with slower epigenetic aging. The study’s limitations include a mostly healthy population, lack of randomization of vitamin D supplementation, and possible residual confounding.

Source: Vetter, Valentin Max, Yasmine Sommerer, Christian Humberto Kalies, Dominik Spira, Lars Bertram, and Ilja Demuth. “Vitamin D supplementation is associated with slower epigenetic aging.” Geroscience 44, no. 3 (2022): 1847-1859.

© The Author(s) 2022

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Posted May 2, 2024.

Harold Oster, MD graduated from medical school in Miami, Florida in 1992 and moved to Minnesota in 2004. After more than 25 years of practicing Internal Medicine, he recently retired. Dr. Oster is especially interested in nutrition, weight management, and disease prevention. Visit his website at haroldoster.com.

References:

  1. Amrein K, Scherkl M, Hoffmann M, et al. Vitamin D deficiency 2.0: an update on the current status worldwide. Eur J Clin Nutr. Nov 2020;74(11):1498-1513. doi:10.1038/s41430-020-0558-y
  2. Li A, Koch Z, Ideker T. Epigenetic aging: Biological age prediction and informing a mechanistic theory of aging. J Intern Med. Nov 2022;292(5):733-744. doi:10.1111/joim.13533
  3. Demuth I, Banszerus V, Drewelies J, et al. Cohort profile: follow-up of a Berlin Aging Study II (BASE-II) subsample as part of the GendAge study. BMJ Open. Jun 23 2021;11(6):e045576. doi:10.1136/bmjopen-2020-045576
  4. Vetter VM, Kalies CH, Sommerer Y, Bertram L, Demuth I. Seven-CpG DNA Methylation Age Determined by Single Nucleotide Primer Extension and Illumina’s Infinium MethylationEPIC Array Provide Highly Comparable Results. Front Genet. 2021;12:759357. doi:10.3389/fgene.2021.759357
  5. McCrory C, Fiorito G, Hernandez B, et al. GrimAge Outperforms Other Epigenetic Clocks in the Prediction of Age-Related Clinical Phenotypes and All-Cause Mortality. The journals of gerontology Series A, Biological sciences and medical sciences. Apr 30 2021;76(5):741-749. doi:10.1093/gerona/glaa286