Impact of folic acid supplementation on the epigenetic profile in healthy unfortified individuals - a randomized intervention trial

Folate is an essential mediator in one-carbon metabolism, which provides methyl groups for DNA synthesis and methylation. The availability of active methyl groups can be influenced by the uptake of folic acid. We conducted a randomized intervention trial to test the influence of folic acid supplemen...

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Published in:Epigenetics Vol. 19; no. 1; p. 2293410
Main Authors: Michels, Karin B., Binder, Alexandra M.
Format: Journal Article
Language:English
Published: United States Taylor & Francis 31.12.2024
Taylor & Francis Group
Subjects:
DNA methylation
Epigenetics
folic acid
red blood cell folate
DNA methylation
Epigenetics
folic acid
red blood cell folate
ISSN:1559-2294, 1559-2308, 1559-2308
Online Access:Get full text
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Summary:Folate is an essential mediator in one-carbon metabolism, which provides methyl groups for DNA synthesis and methylation. The availability of active methyl groups can be influenced by the uptake of folic acid. We conducted a randomized intervention trial to test the influence of folic acid supplementation on DNA methylation in an unfortified population in Germany. A total of 16 healthy male volunteers (age range 23-61 y) were randomized to receive either 400 μg (n = 9) or 800 μg (n = 7) folic acid supplements daily for 8 weeks. Infinium Human Methylation 450K BeadChip Microarrays were used to assay site-specific DNA methylation across the genome. Microarray analyses were conducted on PBL DNA. We estimated several epigenetic clocks and mean DNA methylation across all autosomal probes on the array. AgeAccel was estimated as the residual variation in each metric. In virtually all participants, both serum and red blood cell (RBC) folate increased successively throughout the trial period. Participants with a larger increase in RBC folate had a larger increase in DNAmAge AgeAccel (Spearman Rho: 0.56, p-value = 0.03). No notable changes in the methylome resulting from the folic acid supplementation emerged. In this population with adequate folate levels derived from diet, an increase in RBC folate had a modest impact on the epigenetic clock predicting chronologic age.
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ISSN:1559-2294
1559-2308
1559-2308
DOI:10.1080/15592294.2023.2293410