Women Taking a Folic Acid Supplement in Countries with Mandatory Food Fortification Programs May Be Exceeding the Upper Tolerable Limit of Folic Acid: A Systematic Review.
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ABSTRACT: Background
In preconception and pregnancy, women are encouraged to take folic acid-based supplements over and above food intake. The upper tolerable limit of folic acid is 1000 mcg per day; however, this level was determined to avoid masking a vitamin B12 deficiency and not based on folic acid bioavailability and metabolism. This review's aim is to assess the total all-source intake of folate in women of childbearing age and in pregnancy in high-income countries with folate food fortification programs.Methods
A systematic search was conducted in five databases to find studies published since 1998 that reported folate and folic acid intake in countries with a mandatory fortification policy.Results
Women of childbearing age do not receive sufficient folate intake from food sources alone even when consuming fortified food products; however, almost all women taking a folic acid-based supplement exceed the upper tolerable limit of folic acid intake.Conclusions
Folic acid supplement recommendations and the upper tolerable limit of 1000 mcg set by policy makers warrant careful review in light of potential adverse effects of exceeding the upper tolerable limit on folic acid absorption and metabolism, and subsequent impacts on women's health during their childbearing years.
SUBMITTER: Ledowsky C
PROVIDER: S-EPMC9268323 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Study question: Do short-term and long-term exposures to low dose folic acid supplementation alter DNA methylation in sperm? Summary answer: No alterations in sperm DNA methylation patterns were found following the administration of low dose folic acid supplements of 400 μg/day for 90 days (short-term exposure) or when pre-fortification of food with folic acid and post-fortification sperm samples (long-term exposure) were compared. What is known already: Excess dietary folate may be detrimental to health and DNA methylation profiles due to folate’s role in one carbon metabolism and the formation of S-adenosyl methionine, the universal methyl donor. DNA methylation patterns are established in developing male germ cells and have been suggested to be affected by high dose (5 mg/day) folic acid supplementation. Participants/materials, setting, methods: Blood and seminal plasma folate levels were measured in participants before and following the 90-day treatment with placebo or supplement. Sperm DNA methylation was assessed using the whole genome and genome-wide techniques, MassArray epityper, restriction landmark genomic scanning, methyl-CpG immunoprecipitation and Illumina HumanMethylation450 Bead Array. Main results and the role of chance: Following treatment, supplemented individuals had significantly higher levels of blood and seminal plasma folates compared to placebo. Initial first generation genome-wide analyses of sperm DNA methylation showed little evidence of changes when comparing pre- and post-treatment samples. With Illumina HumanMethylation450 BeadChip arrays, no significant changes were observed in individual probes following low-level supplementation; when compared with those of the post-fortification cohort, there were also few differences in methylation despite exposure to years of fortified foods. Limitations, reasons for caution: This study was limited to the number of participants available in each cohort, in particular those who were not exposed to early (pre-1998) fortification of food with folic acid. While genome-wide DNA methylation was assessed with several techniques that targeted genic and CpG rich regions, intergenic regions were less well interrogated. Wider implications of the findings: Overall, our findings provide evidence that short term exposure to low dose folic acid supplements of 400 μg/day, over a period of 3 months, a duration of time that might occur during infertility treatments, has no major impact on the sperm DNA methylome.
2016-11-12 | GSE89781 | GEO
Project description:Previous studies suggested a causal link between pre-natal exposure to ionizing radiation and birth defects such as microphthalmos and exencephaly. In mice, these defects arise primarily after high-dose X-irradiation during early neurulation. However, the impact of sublethal (low) X-ray doses during this early developmental time window on adult behavior and morphology of central nervous system structures is not known. In addition, the efficacy of folic acid (FA) in preventing radiation-induced birth defects and persistent radiation-induced anomalies has remained unexplored. To assess the efficacy of FA in preventing radiation-induced defects, pregnant C57BL6/J mice were X-irradiated at embryonic day (E)7.5 and were fed FA-fortified food. FA partially prevented radiation-induced (1.0 Gy) anophthalmos, exencephaly and gastroschisis at E18, and reduced the number of pre-natal deaths, fetal weight loss and defects in the cervical vertebrae resulting from irradiation. Furthermore, FA food fortification counteracted radiation-induced impairments in vision and olfaction, which were evidenced after exposure to doses ≥0.1 Gy. These findings coincided with the observation of a reduction in thickness of the retinal ganglion cell and nerve fiber layer, and a decreased axial length of the eye following exposure to 0.5 Gy. Finally, MRI studies revealed a volumetric decrease of the hippocampus, striatum, thalamus, midbrain and pons following 0.5 Gy irradiation, which could be partially ameliorated after FA food fortification. Altogether, our study is the first to offer detailed insights into the long-term consequences of X-ray exposure during neurulation, and supports the use of FA as a radioprotectant and antiteratogen to counter the detrimental effects of X-ray exposure during this crucial period of gestation.
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