Folic acid during early neurodevelopment is important, but too much is not good.

 I wrote this post for the website called Women in Science in 2017.

I am a female Canadian Neuroscientist interested in how nutrition, specifically B-vitamins and age impact brain function. The B-vitamin I work closely with is called folic acid, it is well known for its role during early neurodevelopment. Specifically, for the closure of the neural tube in utero. The neural tube in embryos is the first step to forming the brain and spinal cord. If the neural tube does not close, it leads to the development of neural tube defects (NTDs) in babies, such as spina bifida. To prevent the NTDs, mandatory folic acid fortification laws were put into place in 1998 in the US and Canada, as well as other countries. Since 1998 there has been a reduction in the number of NTDs in both Canada and the US.

Recently, there have been concerns about over supplementation of folic acid in countries like Canada where mandatory folic acid fortification laws are in place and supplement use is high (Patel and Sobczynska-Malefora, 2017). In epidemiological studies, too much folic acid has been associated with increased risk of cancer (Boyles et al., 2016). Interestingly, too much maternal folic acid intake has been associated with autism spectrum disorder (Beard et al., 2011), but the data is not clear as other studies have reported the protective effects (Wang et al., 2017). Furthermore, too much maternal folic acid has been reported to impair other neurodevelopmental aspects of the brain and behavior in offspring (Roth et al., 2011).

We recently published a study (Bahous et al., 2017) investigating whether too much maternal folic acid is associated with changes in the neurodevelopment of offspring. Using a mouse model of maternal over supplementation of folic acid we report that male offspring from mothers that were fed high levels of folic acid had impaired memory and brain development.

The amount of folic acid in the diet of mothers was minimal (5mg/kg of folic acid) and comparable to human supplementation. Mothers were supplemented for 6 weeks prior to pregnancy and throughout lactation. Once we weaned the pups from mothers they were maintained on supplemented diet until we collected experimental data. We assessed short-term memory of mice using a test called the novel object recognition, animals from mothers with too much folic acid did not remember seeing a familiar object as well as control animals did. Furthermore, they had reduced levels of a neurotransmitter that is important in learning and memory called acetylcholine. The pups from mothers over supplemented folic acid mothers had altered development of the cortex. Interestingly the offspring from maternally over supplemented folic acid mother showed a similar phenotype to that of mice with in born error of metabolism (Jadavji et al., 2012). These are some of the first results showing how maternal over supplementation with folic acid may affect early neurodevelopment. More studies are required to further dissect the mechanisms as well as determine if the benefits continue into adulthood. As someone wise once said, everything in moderation