Vitamin D may have direct effect on brain development, social behaviour and autism

By Nathan Gray contact

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Vitamin D may have direct effect on brain development, social behaviour and autism
Vitamin D could have a 'critical influence' levels of serotonin in the brain and may directly effect social behaviours associated with Autism Spectrum Disorder (ASD), according to new research.

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.”

Research details

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”
Authors: Rhonda P. Patrick, Bruce N. Ames

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