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Med Hypotheses. 2012 Apr;78(4):489-93. doi: 10.1016/j.mehy.2012.01.014. Epub 2012 Jan 28.

Vitamin A, folate, and choline as a possible preventive intervention to fetal alcohol syndrome.

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Department of Internal Medicine, University of Calgary (Foothills Hospital), 1403 - 29 Street NW, Calgary, AB, Canada.


It is recognized that alcohol consumption during pregnancy is associated with fetal alcohol syndrome (FAS). Alcohol can trigger a pattern of neurodegeneration in rat brains similar to other known gamma-aminobutyric acid (GABA) specific agonists. However this does not seem to explain FAS entirely, as impoverished care-giving environments have been shown to increase the risk of FAS. Individuals living under the poverty level are at risk for micronutrient deficiencies due to insufficient intake. In particular, three nutrients commonly found to be deficient are folate, choline and vitamin A. There is evidence to suggest that ethanol alone may not explain the entire spectrum of anomalies seen in individuals with FAS. It is hypothesized that FAS may be caused more by the nutritional deficiencies that are exacerbated by alcohol than by direct alcoholic neurotoxicity. It is known that ethanol inhibits folate, choline, and vitamin A/retinoic acid metabolism at multiple steps. Additionally, mice exposed to ethanol demonstrated epigenetic changes, or variations in the methylation of DNA to control gene expression. Folate is important in the production of methyl groups, which are subsequently used to create and methylate DNA. Choline (which is metabolized to acetylcholine) is important in neurotransmission and neurodevelopment. It is also involved in an alternative pathway in the production of methyl groups. In fact a study by Thomas et al. in 2009 found that nutritional supplementation with choline in rats exposed to ethanol in utero almost completely mitigated the degenerative effects of ethanol on development and behaviour. Lastly, vitamin A and retinoic acid metabolism is associated with the regulation of one sixth of the entire proteome. Thus supplementation of folate, choline and vitamin A to mothers may mitigate the effects of the alcohol and reduce the severity or prevalence of FAS.

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