Folic acid and autism: What do we know?

Abstract

Autism spectrum disorders (ASD) consist in a range of neurodevelopmental conditions that share common features with autism, such as impairments in communication and social interaction, repetitive behaviors, stereotypies, and a limited repertoire of interests and activities. Some studies have reported that folic acid supplementation could be associated with a higher incidence of autism, and therefore, we aimed to conduct a systematic review of studies involving relationships between this molecule and ASD. The MEDLINE database was searched for studies written in English which evaluated the relationship between autism and folate. The initial search yielded 60 potentially relevant articles, of which 11 met the inclusion criteria. The agreement between reviewers was κ = 0.808. The articles included in the present study addressed topics related to the prescription of vitamins, the association between folic acid intake/supplementation during pregnancy and the incidence of autism, food intake, and/or nutrient supplementation in children/adolescents with autism, the evaluation of serum nutrient levels, and nutritional interventions targeting ASD. Regarding our main issue, namely the effect of folic acid supplementation, especially in pregnancy, the few and contradictory studies present inconsistent conclusions. Epidemiological associations are not reproduced in most of the other types of studies. Although some studies have reported lower folate levels in patients with ASD, the effects of folate-enhancing interventions on the clinical symptoms have yet to be confirmed.

Autism genes are selectively targeted by environmental pollutants including pesticides, heavy metals, bisphenol A, phthalates and many others in food, cosmetics or household products

“…These are grouped by general function in Fig 9. They include compounds related to oxidative stress and folate/methionine/homocysteine metabolism which play key roles in autism [192][193][194][195] as do cholesterol and fatty acid metabolism [196][197][198][199] or inflammation [200][201][202][203]..…”

Excess perigestational folic acid exposure induces metabolic dysfunction in post-natal life

“…To date, several studies report the programing effects of maternal FA supplementation on the offspring's health, mainly regarding autism (Castro et al 2014), asthma, insulin resistance, and cancer (see Burdge & Lillycrop (2012) for a review). Results of studies of fetal programing of cancer by high FA exposure are somewhat conflicting.…”

The Genetic and Epigenetic Basis Involved in the Pathophysiology of ASD: Therapeutic Implications

“…Some studies have reported that periconceptional folic acid supplementation, depending on timing and dose, could be associated with a higher incidence of autism. But nevertheless, a recent meta-analysis shows that the few and contradictory studies present inconsistent conclusions, and epidemiological associations are not reproduced in most of the other types of studies [294]. On the other hand, a well-controlled epidemiological study including a sample of 85,176 children disconfirms this claim and reports a lower incidence of ASD in children whose mothers received prenatal folic acid supplementation around the time of conception (0.10%) compared with those unexposed to folic acid (0.21%) [295].…”

“…Also, some studies have reported lower folate levels in patients with ASD [299,300] and high levels of homocysteine [299,301]. Folic acid supplementation may have a certain role in the treatment of children with autism, and this treatment also improved the concentrations of folic acid, homocysteine, and normalized glutathione redox metabolism [302]; but the effects of folate-enhancing interventions on the clinical symptoms have yet to be confirmed [294].…”