Circulating Unmetabolized Folic Acid: Relationship to Folate Status and Effect of Supplementation

Abstract

<jats:p>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 (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>P</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.05</mml:mn></mml:math>); 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.</jats:p>

Folic Acid Supplements During Pregnancy and Child Psychomotor Development After the First Year of Life

“…[38][39][40] In contrast to natural dietary folate, FA is a synthetic oxidized form that must be metabolized to coenzymatic tetrahydrofolate derivatives 41 to be biologically active. In recent studies, the concern about the presence of unmetabolized FA has been increasing because of the intake of high dosages, especially in women who take supplements during pregnancy.…”

Folic acid supplementation in vitro induces cell type–specific changes in BRCA1 and BRCA 2 mRNA expression, but does not alter DNA methylation of their promoters or DNA repair

“…To address this, normal and cancer cells were treated in vitro with concentrations of FA that were within the range of unmetabolized FA in plasma (0-100 nmol/L) [33][34][35][36][37] reported in humans taking 200 μg/day FA or more on the mRNA expression of BRCA1 and BRCA2. Cells arising from different tissues were tested to determine whether any effects of FA on BRCA1 and BRCA2 were specific to a specific cancer type or subtype.…”

Folate therapy optimization in complicated pregnancy

“…решить проблему профилактики фолиевого дефицита путем добавления синтети-ческой фолиевой кислоты к широко употребляе-мым продуктам (макароны, хлеб) в количествах 100-300 мкг на 100 г продукта. Хотя благодаря так называемой «фортификации» фолиевой кис-лотой продуктов питания частота появления ДНТ в большинстве стран уменьшилась, у многих уче-ных существует обеспокоенность в отношении возможных побочных эффектов длительного по-вышения в крови содержания фолиевой кислоты у значительных групп населения этих стран [42]. Несмотря на то, что в США фортификация про-водится уже с 1998 года, развитые европейские страны (особенно Франция, Италия, Финляндия, Германия, Швейцария) намного более осторож-ны в этом вопросе.…”

“…Фолиевая кислота имеет гораздо большую био доступность, чем натуральные фолаты, и быстро абсорбируется в тонком кишечнике [30,42]. Содержание фолиевой кислоты в плазме крови достигает максимума уже через 2-3 часа после перорального приема.…”