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Updated: May 22, 2026

Modifying Levels of Maternal Dietary Folic Acid or Choline to Study the Impact of Deficiencies on Offspring Health Outcomes
Published on: June 28, 2024
Circulating unmetabolized folic Acid: relationship to folate status and effect of supplementation
Carolyn Tam1, Deborah O'Connor, Gideon Koren
1The Motherisk Program, Division of Clinical Pharmacology/Toxicology and Nutrition Sciences, The Hospital for Sick Children, Toronto, ON, Canada M5G 1X8.
Abstract:
There are increasing concerns that exposure to unmetabolized folic acid, which results from folic acid intakes that overwhelm the liver's metabolic capacity, may be associated with adverse effects. In this paper, we examined the folic acid status of women of reproductive age in relation to dietary intake and the effect of folic acid supplementation (1.1 mg or 5 mg). Plasma unmetabolized folic acid was not significantly correlated with folate intake estimated by food frequency questionnaire or biomarkers. The proportion of women with detectable levels of unmetabolized folic acid increased from 65% to 100% after twelve weeks of supplementation (P < 0.05); however, the increase in concentrations did not reach statistical significance and the effect was not sustained. Moreover, there were no significant differences between the two doses. This suggests that there are mechanisms by which the body adapts to high folic acid intakes to limit exposure to unmetabolized folic acid.
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