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A cross-sectional study found that adults with higher serum folate had fewer age-related changes to epigenetics and patterns of DNA methylation.
August 13, 2025
By: Mike Montemarano
Associate Editor, Nutraceuticals World
A cross-sectional study found that among a population of older adults who participated in the National Health and Nutrition Examination Survey (NHANES), those with higher serum folate were more likely to have reduced amounts of epigenetic deviations associated with aging. The findings were published in the American Journal of Clinical Nutrition.
Epigenetics refers to modifications that influence how and where genes are expressed, without changing their genetic code. One of the most common epigenetic modifications is DNA methylation, the addition of CH3 or methyl groups to DNA which helps regulate genomic stability, gene expression, and more. Epigenetics and patterns of DNA methylation change with age, and these changes may impact health and well-being later in life. For this reason, methylation and markers of epigenetic health are of growing interest to longevity researchers.
The present study analyzed participants of the National Health and Nutrition Examination Survey from 1999 to 2002, and analyzed their blood tests via machine learning tools known as epigenetic clocks. These tools examine levels of DNA methylation at points in the genome that change with age. Variations between chronological age, and how these age-related biomarkers typically appear at a given chronological age, are known as epigenetic age deviation (EAD).
“Put simply, our DNA and our cells can ‘look’ older than we actually are,” said Eric Ciappio, PhD, senior manager of nutrition science at Balchem Human Nutrition and Health, a manufacturer specializing in folate ingredients. “The good news is a number of lifestyle factors can influence epigenetic age and EAD, including nutrients that help contribute to the body’s methyl pool and support healthy epigenetic function. This recent study was particularly interesting as it tested for associations between EAD and nutritional biomarkers linked to one-carbon metabolism – an interconnected biochemical network with various molecules accepting and donating methyl groups to support balanced methylation where it’s needed most.”
Data was analyzed from over 2,000 adults between the ages of 50 and 85. Serum folate, which promotes one carbon metabolism, was associated with lower EAD in several of the epigenetic clock tools examined. Conversely, increased levels of homocysteine, which is associated with one carbon metabolism deficiencies, were associated with higher EAD in several epigenetic clock tests.
“These findings underscore the importance of folate in epigenetic health, as it supplies methyl groups to be used in DNA methylation,” said Ciappio. “As we age, our global DNA methylation levels decrease. This is where folate’s methyl-donor function comes into play, helping to maintain cellular health and optimize the integrity of our genetic material.”
Balchem is investing in nutritional solutions targeting methylation and epigenetic health, in order to promote longevity.
“In recent years, terms like ‘cellular health’ and ‘epigenetic health’ have started to move from scientific literature into the healthy aging mainstream,” said Lauren Eisen, senior marketing and business development manager of minerals and nutrients at Balchem. “This study signals the potential for folate to drive innovation in this space, as a crucial supplier of methyl (CH3) groups for methylation of DNA and throughout the body. The key point here is that every methyl counts. That’s why we developed our first-of-its-kind, choline-enriched folate salt, Optifolin+, which delivers seven times the methyl groups found in standard folate forms.”
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