Mechanistic perspective on the actions of vitamin a in autism spectrum disorder etiology

Vitamin A (VA) has many functions in the body, some of which are key for the development and functioning of the nervous system, while some others might indirectly influence neural function. Both hypovitaminosis and hypervitaminosis A can lead to clinical manifestations of concern for individuals and for general global health. Scientific evidence on the link between VA and autism spectrum disorder (ASD) is growing, with some clinical studies and accumulating results obtained from basic research using cellular and animal models. Remarkably, it has been shown that VA deficiency can exacerbate autistic symptomatology. In turn, VA supplementation has been shown to be able to improve autistic symptomatology in selected groups of individuals with ASD. However, it is important to recognize that ASD is a highly heterogeneous condition. Therefore, it is important to clarify how and when VA supplementation can be of benefit for affected individuals. Here we delve into the relationship between VA and ASD, discussing clinical observations and mechanistic insights obtained from research on selected autistic syndromes and laboratory models to advance in defining how the VA signaling pathway can be exploited for treatment of ASD.