Disruption of methylation is often a characteristic feature of children with ASD. In this study, researchers sought to measure the levels of magnesium and homocysteine in this population group, and evaluated the potential role of magnesium in homocysteine metabolism.
Hair magnesium status, along with blood serum magnesium and homocysteine levels, were analysed in 140 children with autism (53 girls and 87 boys) with an average age of 9.5 years. In all cases, blood magnesium levels were in the normal range; however, hair tissue mineral analysis showed very low levels of magnesium, which decreased with age. They also found significantly high homocysteine levels.
Higher homocysteine levels in ASD have been shown to decrease glutathione peroxidase activity and vitamin B12 levels, inactivate gene transcription and lower synaptic plasticity. These factors cause increased oxidative stress and and an diminished ability to methylate, which could be linked to the clinical manifestations of autism.
It is well known that vitamins B6, B12 and folic acid are important for methylation and homocysteine metabolism; with one study showing supplementation normalised metabolic imbalances consistent with impaired ability to methylate and increased oxidative stress, in children with ASD.
However, energy is also required for the remethylation of homocysteine to methionine. It is in the production of ATP that these researchers hypothesise that magnesium may play a role in methylation processes. Without adequate ATP production there may be lowered methionine, increased homocysteine, and reduced gene transcription and synaptic plasticity.
Additionally, magnesium is required as a cofactor alongside vitamin B6, for the production of neurotransmitters including dopamine, with a magnesium deficiency directly affecting neurotransmitter metabolism.
The researchers hypothesise that magnesium deficiency and high homocysteine levels are crucial epigenetic factors, with long-term supplementation of magnesium in children with ASD seeming justified. They further suggest that hair magnesium analysis and serum homocysteine levels may be useful markers for identification of children with ASD, as well as for treatment.
- Jozefczuk J, Kasprzycka W, Czarnecki R, et al. Homocysteine as a diagnostic and etiopathogenic factor in children with autism spectrum disorder. J Med Food 2017;20(8):744-749. [Abstract]