In the 1990’s, the association of neural tube defects in newborns and low folic acid intake was recognized. It was found that folic acid given prior to conception prevented 70% of neural tube defects in newborns. A previous blog on the Beaute website (October, 2009) discussed this strong association. Of more recent interest is the coincidental finding of the link between folate deficiency and autism.
What is folate?
Folate is a water soluble B vitamin commonly found in bread, green leafy vegetables, breakfast cereals, legumes, fruits and juices, and grain products. The recommended dosage in pregnancy is 400 mcg. Prescription prenatal vitamins are all supplemented with 1 mg of folate. A chart at the end of this article provides folate content in common foods from the US Dept. of Agriculture which pregnant women can use as a valuable resource.
Why is folate important?
Folate is an essential ingredient in the manufacture of DNA. It is also critical in gene expression or the way genetic information gets processed into physical characteristics. In pregnancy, a time of rapid growth, folate demand increases. Nervous system and brain development require adequate folate availability. The FDA has mandated fortification of grain products with folate since January, 1998 because of the fact that half of all pregnancies are unplanned and by the time the pregnancy is recognized, the time when folate demand is highest has passed.
What is autism?
Autism in the United States is on the rise with an incidence of one in 88 children. Autism is a spectrum of behavioral and cognitive disturbances of childhood development that is manifested by deficits in social interaction, impaired communication and repetitive behaviors. Autism incidence has increased in the last decade and there may be both environmental and genetic reasons leading to this increase.
How is folate deficiency related to autism?
Several studies point to the importance of folate in development of the nervous system in infants. Autism is a neurodevelopmental disorder that possibly originates in early pregnancy (first month) when the consumption of folate is critical.
In the Journal of the American Medical Association by Suren in Feb., 2013 it was shown that folate deficiency in pregnancy may be associated with autism. The article is from a Norwegian Mother and Child Cohort Study where 85,000 babies were followed and recordings were made of the amount of folate consumed by the mothers. It was found that mothers supplemented with folate 4 weeks before pregnancy was diagnosed and during the eight weeks after pregnancy has been diagnosed, had about a 40% reduced risk of autism in their offspring. The risk of autism was .1% in children who took supplements and .21% in children whose mothers took no supplements. No association was found between autistic disorders and taking folic acid mid-pregnancy, or any relationship between autism and consuming fish oil supplementation.
Previous studies reported in June, 2012 in the American Journal of Clinical Nutrition, by Schmidt, also found that folate supplementation of at least 600 mcg before pregnancy lowered a women’s risk of having a fetus with autism and Asperger’s Syndrome by 38%. Maternal folic acid intake during pregnancy also resulted in fewer behavioral problems in the offspring, reduced risk of severe language delay, improved scores on several neurodevelopmental tests including verbal, attention, and social competence. Children also had fewer issues of childhood hyperactivity and peer problems. This study again points to the importance of folate in development of the nervous system in infants.
Low maternal folate status during early pregnancy is associated with a higher risk of emotional and behavioral problems in the offspring. ( Steenweg de Graaff, Am J Clin Nutr., 2012)
Moretti in 2008, Journal of Autism Developmental Disorders, reported on seven children with CNS folate deficiency who had psychomotor retardation, regression, cognitive delay, and dyskinesia and were on the autistic spectrum.
What are the ways that mothers can be deficient in folate?
Whether it is the lack of the vitamin or difficulty in processing the vitamin is unknown. The autism associated with folate deficiency can be different in that it is commonly associated with neurologic features such as seizures, hypotonia, movement disorders, regression, dyskinesia and ataxia. In addition cerebral folate deficiency with autism occurs at different points during development compared to regular autism that generally occurs prior to 3 years of age.
CAUSES OF deficiency include:
1) Isolated folate deficiency in the CNS of infants due to deficient maternal diet;
2) Defects in the enzyme NEEDED to allow folate to be absorbed (hereditary folate malabsorption) There is a specific genetic disorder (MTFHR) that require higher amounts of folate ingestion for normal neurodevelopment. Autistic children tend to have a higher incidence of these genetic disorders;
3) Defective folate transport genes-defective transport into the brain from the bloodstream;
4) Autoimmune causes of folate deficiency.
Does it help to supplement with folic acid after a diagnosis of autism is made if it is believed to be due to folate deficiency in utero?
Clinical improvement with folic acid highlights the importance of considering this diagnosis. Clinical improvement occurs in cognitive, language and motor skills with little amelioration in autistic features despite treatment. Folate given to children with fragile X syndrome and Rett syndrome, which are genetic disorders with autistic symptoms, also have had benefits. Children who are autistic due to an immune disorder from serum folate autoantibodies blocking folate transport into the brain have also derived benefit with improvement in ASD symptoms after folate supplementation.
Is there a danger with too much folic acid in pregnancy?
Can excessive folic acid cause autism? There is also a concern that there may be an upper limit to safe folic acid consumption. Little is known about the effect of too much folic acid in humans. Excess iron can cause hemochromotosis, too much Vitamin A can cause liver damage and too much vitamin C can cause GI problems. What can excessive folic acid cause? — we do not know….
There are even several reports in the literature that discuss excess folic acid as a cause of autism.
One report by Rogers in 2008 in Medical Hypothesis mentions that mothers can possess a genetic enzyme defect of folate called MTFHR –This can often be associated with elevated homocysteine levels which leads to higher risks of pregnancy losses and separation of the placenta.
When folate is increased in the early stages of women with this disorder in pregnancy—the loss is prevented and more children are born with the same enzymatic defect. These children have an increased requirement for folic acid for normal neurodevelopment and if that supplementation does not occur, there is an increased risk of autism
Summary: Folate consumption both before and during pregnancy is essential for proper neurodevelopment. Taking folic acid prior to conception may reduce the risk of autism and other related disorders, especially when a mother or child has a genetic disorder of deficiency. There is a key interaction between genetics, environment and nutrition that can interplay causing disorders of the central nervous system.
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