Is High Folic Acid Intake a Risk Factor for Autism?—A Review

Abstract

Folate is required for metabolic processes and neural development. Insuring its adequate levels for pregnant women through supplementation of grain-based foods with synthetic folic acid (FA) in order to prevent neural tube defects has been an ongoing public health initiative. However, because women are advised to take multivitamins containing FA before and throughout pregnancy, the supplementation together with natural dietary folates has led to a demographic with high and rising serum levels of unmetabolized FA. This raises concerns about the detrimental effects of high serum synthetic FA, including a rise in risk for autism spectrum disorder (ASD). Some recent studies have reported a protective effect of FA fortification against ASD, but others have concluded there is an increased risk for ASD and other negative neurocognitive development outcomes. These issues are accompanied by further health questions concerning high, unmetabolized FA levels in serum. In this review, we outline the reasons excess FA supplementation is a concern and review the history and effects of supplementation. We then examine the effects of FA on neuronal development from tissue culture experiments, review recent advances in understanding of metabolic functional blocks in causing ASD and treatment for these with alternative forms such as folinic acid, and finally summarize the conflicting epidemiological findings regarding ASD. Based on the evidence evaluated, we conclude that caution regarding over supplementing is warranted.

Review and meta‐analysis found that prenatal folic acid was associated with a 58% reduction in autism but had no effect on mental and motor development

“…However, some studies that evaluated supplementation towards the middle and end of pregnancy found an associated increase in ASD in children . So, although the benefits of early supplementation have been well established, care must be taken in terms of possible overexposure to folic acid in the second and third trimesters of pregnancy, due to the cumulative effect of the use of supplements, especially in relation to ASD . Since DNA methylation is strictly regulated and given that folic acid is heavily involved in that process as methyl donor , hypermethylation could occur as a result of excessive exposure to folates and the presence of considerable amounts of nonmetabolised forms.…”

“…Since DNA methylation is strictly regulated and given that folic acid is heavily involved in that process as methyl donor , hypermethylation could occur as a result of excessive exposure to folates and the presence of considerable amounts of nonmetabolised forms. Consequently, the modulation of gene expression could underlie neuropsychiatric disorders such as ASD .…”

“…There is also growing concern that the prenatal use of high doses of folic acid of more than 1000 lg daily can affect the neurodevelopment of children. It is important to note that in humans the enzyme dihydrofolate reductase, which converts folic acid to useable dihydrofolate and tetrahydrofolate, is not very active (21). It could be expected that repeated exposure to an excessive dose of folic acid could lead to the appearance of folic acid in the bloodstream that has not been metabolised and is not useful and that this may be harmful (53).…”

Changable Environmental Risk Factors in Autism: Vitamin D and Folic Acid

“…It also plays an important role in methionine syntheses. A sufficient amount of folate prevents excessive accumulation of serum homosistein levels [25].…”

“…Dietary folic acid supplementation during pregnancy is a successful community health program instituted to prevent neural tube defects. However, encouraging folic acid intake with supplementation before and during pregnancy and enriching certain grains with folic acid highly increases folic acid levels [25]. Some epidemiological studies show that folic acid supplementation protects against ASD, whereas others report that it increases ASD risk and prevents neurocognitive development in children whose mothers used synthetic folic acid.…”