Vitamin D may have direct effect on brain development, social behaviour and autism
Writing in The FASEB Journal, the study suggests that adequate levels of vitamin D may be required to produce serotonin in the brain - where it shapes the structure and wiring of the brain, acts as a neurotransmitter, and affects social behaviour.
Led by Professor Bruce Ames of Children's Hospital Oakland Research Institute (CHORI) in the US, the study demonstrates that serotonin, oxytocin, and vasopressin - three brain hormones that affect social behaviour - are all activated by vitamin D.
“We present evidence that vitamin D hormone (calcitriol) activates the transcription of the serotonin-synthesizing gene tryptophan hydroxylase 2 (TPH2) in the brain at a vitamin D response element (VDRE) and represses the transcription of TPH1 in tissues outside the blood-brain barrier at a distinct VDRE suggesting a causal link between the sunshine vitamin, serotonin and autism,” wrote Ames and his colleagues.
They noted that autism, which is characterized by abnormal social behaviour, has previously been linked to low levels of serotonin in the brain and to low vitamin D levels, but no mechanism has linked the two until now.
Indeed, Ames and his team suggested that their study sheds light on, and offers a mechanism to explain many of the known, but previously not understood facts about autism.
“This mechanism ex- plains how low vitamin D hormone levels result in aberrant serotonin synthesis, subsequently leading to abnormal brain development,” wrote the research team. “Low vitamin D hormone levels during foetal and neonatal development could result in poor TPH2 expression and subsequently reduced serotonin concentrations in the developing brain.”
They added that such a suggestion may mean that adequate vitamin D hormone levels during pregnancy, as well as nutritional intake of tryptophan and vitamin D during early childhood, “may have a critical influence on brain serotonin levels and, thus, on the structure and neural wiring of the brain.”
As part of the study, Ames and his team show that vitamin D activates the gene that makes the enzyme tryptophan hydroxylase 2 (TPH2), which in turn converts the essential amino acid tryptophan to serotonin in the brain.
They also point to evidence that the gene that makes the enzyme tryptophan hydroxylase 1 (TPH1) is inhibited by vitamin D, which subsequently halts the production of serotonin in the gut and other tissues, where it is known to promote inflammation when found in excess.
“The differential regulation of TPH1 and TPH2 by vitamin D hormone can explain some of the most prevalent phenotypes of ASD,” said the research team.
“Vitamin D-mediated differential regulation of TPH1 and TPH2 may also be an important clue in understanding the inverse relation- ship between serotonin concentrations in blood com- pared with the brain in children with autism,” they added.
Ames and his colleagues suggested that dietary intervention with vitamin D, tryptophan and omega 3 fatty acids could boost brain serotonin concentrations and help prevent and possibly ameliorate some of the symptoms associated with ASD without side effects – adding that clinical trials are now needed.
They also noted that current guidelines for vitamin D sufficiency are based on serum concentrations of 25(OH)D3 required to maintain bone health, which is considered to be 30 ng/ml (45).
“It is unclear whether these guidelines are sufficient to maintain non-classical functions of vitamin D hormone in other tissues,” they said.
Source: The FASEB Journal
Published online ahead of print, doi: 10.1096/fj.13-246546
“Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism”
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