High Serum Vitamin B12 in Children, Adolescents and Adults with Neurodevelopmental Disorders.

Background: The disease mechanisms underlying Neurdodevelopmental Disorders (ND) imply both heriditable and environmental factors. Vitamin B12 is a factor which is essential for proper neurodevelopment, and serum levels are influenced by diet as well as by genetic variants. Lack of vitamin B12 during pregnancy and in childhood pertubs neurodevelopment and adequate vitamin B12 status is necessary for neurocognitive function in adults. The last years it has become clear that not only lack of vitamin B12 confers a health hazard, but that also too high serum levels have negative implications. Vitamin B12 is solemnly present in animal products and a high plasma level is a common finding in a western country as Norway were diets are rich in meat. Elevated serum levels of vitamin B12 associate with poor outcome and mortality of diseases, as cancer, liver and kidney failure. Importantly, it was recently reported that elevated serum levels in pregnant women increased the risk of autism in the child.

Objectives: We hypothesized that high vitamin B12 would be frequent in patients with ND and that their mean vitamin B12 levels would be equal as in healthy controls (HC). We also hypothesized that vitamin B12 levels would be equal as in schizophrenia, a clinical group that shares some genetic and sociodemographic characteristics with autistic patients, and were previous studies indicate adequate vitamin B12 status.

Methods: Patients with ND conferred to specialist services were asked to participate. Altogether 217 children, adolescents and adults with a diagnose of pervasive ND, specific NDs or intellectual disability were included. Their vitamin B12 serum levels were compared with 498 HC and 414 schizophrenia patients. In addition, 117.000 primary care patients from a catchment area were used as reference population. Levels in ND were also compared with a clinical control group consisting of 414 schizophrenia patients that had been conferred to specialist health services. We controlled the results for possible confounders. In Norway, available vitamin B12 supplements also contain folic acid, and thus we controlled for levels of folic acid as a proxy for supplement intake. We also controlled for indicators of general nutrition, liver disease, kidney function and inflammation.

Results:

19% of the patients with ND had elevated levels (above the current reference range of 650 mmol/l) of vitamin B12 and mean vitamin B12 levels (age and gender adjusted) were higher than among HC (p=0.004) and among schizophrenia patients (p=0.0003). We controlled the results for differences in age, gender, levels of folic acid, hemoglobin, creatinine, Alanine transaminase and leukocyte count. Serum vitamin B12 was still significantly higher in ND than in HC (p=0.015). Vitamin B12 was not associated with scores on the Social Responsiveness Scale, but was higher in patients who had experienced a loss of previous abilities (p<0.05).

Conclusions: Patients with ND have higher serum vitamin B12 than HC and schizophrenia patients. This result is supported by a previous finding of high levels in pregnancy increasing the risk of autism and warrants further research for possible underlying mechanisms.