High Dietary Folic Acid Intake Is Associated with Genomic Instability in Peripheral Lymphocytes of Healthy Adults
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 heal...
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MDPI AG
2022-09-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/14/19/3944 |
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| author | Khadijah I. Alnabbat Ali M. Fardous Aiman Shahab Andrew A. James Manhel R. Bahry Ahmad R. Heydari |
| author_facet | Khadijah I. Alnabbat Ali M. Fardous Aiman Shahab Andrew A. James Manhel R. Bahry Ahmad R. Heydari |
| author_sort | Khadijah I. Alnabbat |
| collection | DOAJ |
| description | 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 18–40 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 (<i>p</i> = 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. |
| first_indexed | 2024-03-09T21:21:02Z |
| format | Article |
| id | doaj.art-a4cfa46ceeb2465da5bcb4e76a745929 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-09T21:21:02Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-a4cfa46ceeb2465da5bcb4e76a7459292023-11-23T21:22:57ZengMDPI AGNutrients2072-66432022-09-011419394410.3390/nu14193944High Dietary Folic Acid Intake Is Associated with Genomic Instability in Peripheral Lymphocytes of Healthy AdultsKhadijah I. Alnabbat0Ali M. Fardous1Aiman Shahab2Andrew A. James3Manhel R. Bahry4Ahmad R. Heydari5Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USADepartment of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USADepartment of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USADepartment of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USADepartment of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USADepartment of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USAMandatory 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 18–40 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 (<i>p</i> = 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.https://www.mdpi.com/2072-6643/14/19/3944folatefolic acidexcessUMFAlymphocytemicronuclei |
| spellingShingle | Khadijah I. Alnabbat Ali M. Fardous Aiman Shahab Andrew A. James Manhel R. Bahry Ahmad R. Heydari High Dietary Folic Acid Intake Is Associated with Genomic Instability in Peripheral Lymphocytes of Healthy Adults Nutrients folate folic acid excess UMFA lymphocyte micronuclei |
| title | High Dietary Folic Acid Intake Is Associated with Genomic Instability in Peripheral Lymphocytes of Healthy Adults |
| title_full | High Dietary Folic Acid Intake Is Associated with Genomic Instability in Peripheral Lymphocytes of Healthy Adults |
| title_fullStr | High Dietary Folic Acid Intake Is Associated with Genomic Instability in Peripheral Lymphocytes of Healthy Adults |
| title_full_unstemmed | High Dietary Folic Acid Intake Is Associated with Genomic Instability in Peripheral Lymphocytes of Healthy Adults |
| title_short | High Dietary Folic Acid Intake Is Associated with Genomic Instability in Peripheral Lymphocytes of Healthy Adults |
| title_sort | high dietary folic acid intake is associated with genomic instability in peripheral lymphocytes of healthy adults |
| topic | folate folic acid excess UMFA lymphocyte micronuclei |
| url | https://www.mdpi.com/2072-6643/14/19/3944 |
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