Abnormally high plasma levels of vitamin B-6 in children with autism not taking supplements compared to controls not taking supplements

Background: There have been many studies of the effect of high-dose supplementation of vitamin 136 on children and adults with autism, with all but one reporting benefits. Objective: The aim of this study was to investigate the biochemical basis for vitamin B-6 therapy by measuring the level of total vitamin B-6 in the plasma of unsupplemented children with autism spectrum disorder compared to unsupplemented control subjects. Participants: Children with autism spectrum disorders (n = 35, age 3-9 years) and unrelated typical children (n = 11, age 6-9 years), all from Arizona, were studied. (This includes the data from 24 children with autism from our previous study.) Methodology: A microbiologic assay was used to measure the level of total vitamin 136 (including phosphorylated and unphosphorylated forms), in a blinded fashion. Results: Children with autism had a 75% higher level of total vitamin B-6 than the controls (medians of 56 versus 32 ng/mL, respectively, p = 0.00002). Most of the autistic children (77%) had levels that were more than 2 standard deviations above the median value of the controls. The autistic girls (n = 5) also had elevated levels (mean of 54.6 ng/mL, median of 60 ng/mL). Discussion: These results are consistent with previous studies that found that: (1) pyridoxal kinase had a very low activity in children with autism and (2) pyridoxal 5 phosphate (PLP) levels are unusually low in children with autism. Thus, it appears that the low conversion of pyridoxal and pyridoxine to PLP results in low levels of PLP, which is the active cofactor for 113 known enymatic reactions, including the formation of many key neurotransmitters. Conclusions: Total vitamin B-6 is abnormally high in autism, consistent with previous reports of an impaired pyridoxal kinase for the conversion of pyridoxine and pyridoxal to PLP. This may explain the many published studies of benefits of high-dose vitamin B-6 supplementation in some children and adults with autism.