Periconceptional intake of folic acid is known to reduce a woman's risk of having an infant affected by a neural tube birth defect (NTD). National programs to mandate fortification of food with folic acid have reduced the prevalence of NTDs worldwide. Uncertainty surrounding possible unintended consequences has led to concerns about higher folic acid intake and food fortification programs. This uncertainty emphasizes the need to continually monitor fortification programs for accurate measures of their effect and the ability to address concerns as they arise. This review highlights the history, effect, concerns, and future directions of folic acid food fortification programs.

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Folic Acid Food Fortification—Its History, Effect, Concerns, and Future Directions

BackgroundAfter randomized, controlled trials established that consumption of folic acid before pregnancy and during the early weeks of gestation reduces the risk of a neural tube defect (NTD)-affected pregnancy, the United States Public Health Service recommended in 1992 that all women capable of becoming pregnant consume 400 μg folic acid daily. In 1998, folic acid fortification of all enriched cereal grain product flour was fully implemented in the United States and Canada.ObjectiveTo provide guidance on national fortification of wheat and maize flours to prevent 50 to 70% of the estimated 300,000 NTD-affected pregnancies worldwide.MethodsAn expert workgroup reviewed the latest evidence of effectiveness of folic acid flour fortification and the safety of folic acid.ResultsRecent estimates show that in the United States and Canada, the additional intake of about 100 to 150 μg/day of folic acid through food fortification has been effective in reducing the prevalence of NTDs at birth and increasing blood ...

https://journals.sagepub.com/doi/pdf/10.1177/15648265100311S103

Fortification of Flour with Folic Acid

Maternal folic acid (FA) supplementation is well recognised to protect against neural tube defects. Folate is a critical cofactor in one-carbon metabolism involved in the epigenetic regulation of transcription that underpins development. Thus, it is possible that maternal FA supplementation may have additional, unforeseen persistent effects in the offspring. This is supported by the modification by maternal supplementation with one-carbon donors and FA of the epigenetic regulation of offspring phenotype in mutant mice. The present article reviews studies in human subjects and experimental animals of the effect of maternal FA intake and phenotypic outcomes in the offspring. Maternal FA intake was associated with a short-term increased incidence of allergy-related respiratory impairment in children and multigenerational respiratory impairment in rats. Higher maternal folate status during pregnancy was associated positively with insulin resistance in 6-year-olds. In rats, maternal FA supplementation modified hepatic metabolism and vascular function through altered transcription, in some cases underpinned by epigenetic changes. FA supplementation in pregnant rats increased mammary tumorigenesis, but decreased colorectal cancer in the offspring. Maternal FA supplementation decreased a range of congenital cardiac defects in children. These findings support the view that maternal FA supplementation induces persistent changes in a number of phenotypic outcomes in the offspring. However, the number of studies is limited and insufficient to indicate a need to change current recommendations for FA intake in pregnancy. Nevertheless, such effects should be investigated thoroughly in order to support firm conclusions about the risk of unanticipated long-term negative effects of maternal FA supplementation in humans.

/pdf/folic-acid-supplementation-in-pregnancy-are-there-devils-in-46tbjfqsjm.pdf

Folic acid supplementation in pregnancy: are there devils in the detail?

IT HAS BEEN KNOWN for some time that macrocytosis and macrocytic anemia may occur during the course of anticonvulsant medication in epilepsy and that this is somehow related to a deficiency of folic acid.l.2 However, more recently, attempts have been made to relate folate deficiency to various neuropsychiatric disturbances ranging from dementia3 to schizophrenia-like psychoses, failure of seizure control, and even spinal cord and cerebellar disease.4,5 In view of the large numbers of epileptics currently receiving treatment with anticonvulsant drugs, it is of great practical importance to know whether folate deficiency is an integral part of seizure control and whether correction of this deficiency may result in the potentially fatal complication of status epilepticus, as has been suggested.6 Since most of the evidence for this association rests upon sporadic case reports, we have performed a controlled drug trial comparing the number of fits occurring during folic acid administration to those occurring during placebo administration. In view of the interrelationship between vitamin B,, and folic acid and since there have been reports of a fall in serum vitamin B,, levels after folate administration,T we also measured serum levels of this vitamin before and after folic acid administration. It was originally planned to perform a double-blind crossover study on each patient using placebo versus active folate. However, since man’s ability to store folate is not accurately known, the possibility of continuing release of active folate during the placebo period in patients receiving folate prior to placebo could not be excluded. It was, therefore, decided to give all patients placebo for the first three months and folic acid for the subsequent three months. By allowing the patients, who were unaware of this substitution, to record their own seizures, observer bias was excluded.

A controlled study of folic acid in epilepsy

The association between folic acid supplementation, prior to conception and/or during pregnancy and pregnancy outcomes, has been the subject of numerous studies. The worldwide recommendation of folic acid is at least 0.4 mg daily for all women of reproductive age, and 4–5 mg in high-risk women. In addition, evidence shows that folic acid supplementation could modulate other adverse pregnancy outcomes, specifically, in pregnancies complicated by seizure disorders, preeclampsia, anemia, fetal growth restriction and autism. This review summarizes the available national and international guidelines, concerning the indications and dosage of folic acid supplementation during pregnancy. In addition, it describes the potential preventive benefits of folic acid supplementation on multiple maternal and fetal outcomes, as well as potential risks.

https://www.future-science.com/doi/pdfplus/10.4155/fsoa-2015-0015

J.F. Dunne

Papers

Toxicity of folic acid.