{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T12:17:35Z","timestamp":1780661855256,"version":"3.54.1"},"reference-count":84,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T00:00:00Z","timestamp":1663891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA121298"],"award-info":[{"award-number":["CA121298"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Mandatory fortification of food with synthetic folic acid (FA) was instituted in 1998 to reduce the incidence of neural tube defects. Adequate folate status is correlated with numerous health benefits. However, elevated consumption of FA is controversially associated with deleterious effects on health. We previously reported that excess FA mimicked folate depletion in a lymphoblastoid cell line. To explore the impact of FA intake from fortified food, we conducted an observational human study on 33 healthy participants aged 18\u201340 not taking any supplements. Food intake, anthropomorphic measurements, and blood samples were collected and analyzed. Our results show that individuals belonging to the highest tertile of folic acid intake, as well as ones with the highest folic acid to total folate intake ratio (FAR), display a significantly greater incidence of lymphocyte genomic damage. A decrease in global DNA methylation is observed in the highest tertile of FAR compared to the lowest (p = 0.055). A downward trend in the overall gene expression of select DNA repair and one carbon cycle genes (MGMT, MLH1, UNG, MTHFR, MTR) is noted with increased folate status and FA intake. These results provide supporting evidence that high consumption of FA from fortified foods can precipitate genomic instability in peripheral lymphocyte in vivo.<\/jats:p>","DOI":"10.3390\/nu14193944","type":"journal-article","created":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T03:34:17Z","timestamp":1664163257000},"page":"3944","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["High Dietary Folic Acid Intake Is Associated with Genomic Instability in Peripheral Lymphocytes of Healthy Adults"],"prefix":"10.3390","volume":"14","author":[{"given":"Khadijah I.","family":"Alnabbat","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USA"},{"name":"Department of Food and Nutrition Sciences, King Faisal University, Al Huf\u016bf 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali M.","family":"Fardous","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiman","family":"Shahab","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew A.","family":"James","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manhel R.","family":"Bahry","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad R.","family":"Heydari","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USA"},{"name":"Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1002\/bdra.20553","article-title":"Insights into metabolic mechanisms underlying folate-responsive neural tube defects: A minireview","volume":"85","author":"Beaudin","year":"2009","journal-title":"Birth Defects Res. 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