Too much synthetic folic acid from supplements and fortified foods may harm brain development and could be involved in rising rates of neurodevelopmental disorders in children.
Story at a Glance
- It’s extremely rare to get too much folate from foods, but it is possible to get too much folic acid, the synthetic version of folate found in supplements and fortified foods.
- In pregnant mice, high levels of folic acid harmed brain development in offspring, and low levels of vitamin B12 made the damage worse.
- The combination of low vitamin B12, which often occurs in people eating vegan or vegetarian diets, along with high folic acid, could be increasing neurodevelopment disorders in children.
- Due to prenatal supplements and fortified foods, many people have abnormally high levels of folic acid.
- Studies looking into the effects of folic acid on autism development are conflicting, with some showing a protective effect, but a growing body of evidence points to potential harms when consumed in excess.
The terms folate and folic acid are often used interchangeably, but they’re not the same. Folic acid is the synthetic version of folate, or vitamin B9. While folate is found naturally in foods like leafy greens, folic acid is found in supplement form and in fortified foods, such as cereal and bread.
Folic Acid Food Fortification May Have a Dark Side
In the 1990s, U.S. health officials recommended that women who may become pregnant should take 400 micrograms (mcg) of folic acid daily to reduce the risk of having a baby with neural tube defects. However, since the neural tube closes early on during pregnancy—about 28 days after conception—some women may miss the vulnerable period during which folate is critical.Many People Have Abnormally High Levels of Folic Acid
“The food industry has been adding folic acid to breakfast cereals, snack foods, and vitamins, and that has likely increased intake above recommended guidelines,” Mr. Green said. “The safe upper limit for folate is 1,000 micrograms per day. The National Health and Nutrition Examination Survey data showed that a substantial percentage of women’s diets were above that limit.”9Neurodevelopmental Disorders Skyrocketed Since Folic Acid Fortification
As folic acid in foods has increased, so, too, have neurodevelopmental disorders. “Data collected by the Centers for Disease Control and Prevention suggest that in recent decades several neurodevelopmental disorders have seen considerable rises in prevalence, chief amongst them autism spectrum disorder (ASD), but also attention deficit hyperactivity disorder (ADHD) and epilepsy,” according to the Communications Biology study.15“Some of the latest research in this area using data from the Boston Birth Cohort uncovered a positive association between maternal plasma folate levels and autism risk. Autism incidence was greatest in children born to mothers with the highest maternal plasma folate levels, exceeding the cutoff suggested by the WHO (>45.3 nmol/L).
“Moreover, subsequent work showed that children with cord blood levels of unmetabolized FA (UMFA) in the highest, versus lowest quartile, had a greater risk for developing ASD.
“Similarly, a Swedish study testing association of 62 maternal blood biomarkers during early pregnancy with later ASD diagnosis identified total folate as having the highest odds ratio at 1.7. These results are supported by epidemiological investigations from the Rochester Epidemiological Project in Rochester, MN and earlier CDC data.”
Even Moderately High Folic Acid May Harm Brain Development
For the study, researchers investigated folic acid intake in mice on brain development in their offspring, specifically the cerebral cortex, which plays a role in cognitive and emotional functions, as well as psychiatric disorders. One group of mice was fed normal levels of folic acid and B12, while four other groups were fed diets including:20- High folic acid
- Low vitamin B12
- High folic acid and low vitamin B12
- High folinic acid, a natural folate
“These different dietary conditions appear to influence the way neurons arise in the developing brain. With high levels of folic acid or B12 deficiency, there was a change in neural development.
“Cortical neurons that usually emerge during a later stage of brain development were produced over a longer period of time and required a longer period to settle in and assume their proper position in the developing brain. In addition, both high folic acid and B12 deficiency appear to cause many neurons to develop fewer interconnections.”The team found that “even moderately excessive amounts” of folic acid had a detrimental effect on prenatal cortical development, which was made worse by vitamin B12 deficiency.22
The Folate Cycle Depends on Vitamin B12
The findings highlight the complex interplay that occurs between various nutrients in your body and why proper balance is so critical to optimal health. This is particularly true for folic acid and vitamin B12. According to the Communications Biology study:23“The folate cycle is critically dependent on the availability of the essential micronutrient, vitamin B12, which is a required cofactor for the methionine synthase reaction in which homocysteine is converted to methionine through transfer of a methyl group from N-5-methyltetrahydrofolate (CH3-THF). B12 is needed for this reaction to enable folate cycle progression and regeneration of tetrahydrofolate (THF) from CH3-THF.
“In the absence of B12, folate becomes functionally trapped in the form of CH3-THF. This suggests that the effects of FA excess, which paradoxically may decrease functional folate availability, can be further exacerbated by B12 deficiency, as studies on cognitive performance of older adults have suggested.”Vitamin B12, also known as cobalamin, is necessary for your body to make red blood cells as well as for proper nerve function and DNA synthesis. Without adequate levels, a number of physical symptoms, ranging from numbness to fatigue, can occur. Mental health can also suffer significantly, as vitamin B12 plays an important role in neurological function.
Where to Find Natural Folate
While too much synthetic folic acid in fortified processed foods and supplements may be problematic, your body needs natural folate in your diet for optimal mitochondrial function,28 protein metabolism, and breaking down homocysteine, which can be harmful in high amounts.29The best way to increase your levels of this important micronutrient is to eat foods rich in natural folate, which include asparagus, avocados, Brussels sprouts, broccoli, and spinach. Meanwhile, vitamin B12-rich foods include grass-fed beef liver, wild rainbow trout, and wild sockeye salmon. If you suspect you may be deficient, weekly B12 shots or a high-dose, daily supplement may be necessary.
◇ References
- 1, 3, 5, 29 Harvard School of Public Health, The Nutrition Source, Folate (Folic Acid) — Vitamin B9
- 2, 27 X, Nina Teicholz January 7, 2024
- 4, 6 U.S. CDC, Folic Acid Fortification and Supplementation
- 7, 9, 20, 21 UC Davis Health January 4, 2024
- 8 Communications Biology volume 6, Article number: 1133 (2023)
- 10, 12, 14, 15, 17, 18, 23 Communications Biology volume 6, Article number: 1133 (2023), Intro
- 11 Communications Biology volume 6, Article number: 1133 (2023), Abstract
- 13 JAMA Pediatr. 2014 Nov;168(11):e142611. doi: 10.1001/jamapediatrics.2014.2611. Epub 2014 Nov 3
- 16 MMWR Surveillance Summaries / March 24, 2023 / 72(2);1–14
- 19, 22 Communications Biology volume 6, Article number: 1133 (2023), Discussion
- 24 Open Neurol J. 2013; 7: 44–48
- 25 Compr Psychiatry. 1997 Nov-Dec;38(6):305-14
- 26 Neurosciences (Riyadh). 2017 Jul;22(3):228-232
- 28 BitChute February 17, 2022