Science Update

Vitamin B6 Deficiency Increases Noradrenergic Activity, Inducing Behavioral and Cognitive Impairments Associated with Schizophrenia

According to a recent study published in Translational Psychology, vitamin B6 deficiency may lead to social and behavioral deficits associated with schizophrenia. This is a debilitating heterogenous psychiatric condition that affects approximately 20 million people worldwide, according to the World Health Organization. The disorder is characterized by hallucinations, delusions, and distorted thinking, perception, emotions, language, behavior, and a sense of self, often resulting in considerable disability, social stigma, and increased risk for early death from physical illnesses.  

The current study reported that more than 35% of patients who have schizophrenia also have significantly lower blood levels of vitamin B6. Previous research demonstrated vitamin B6 status was inversely proportional to the Positive and Negative Syndrome Scale (PANSS) score for measuring symptom severity, suggesting that vitamin B6 deficiency or insufficiency may increase the risk of developing schizophrenic symptoms. Vitamin B6-dependent enzymes are involved in the metabolism of many neurotransmitters, including dopamine (DA), noradrenaline, serotonin (5-hydroxytryptamine [5-HT]), gamma-aminobutyric acid (GABA), and histamine.

To clarify the potential relationship between vitamin B6 status and schizophrenia, a team of researchers in Tokyo, Japan produced a mouse model of a schizophrenic subpopulation by randomly assigning mice to a vitamin B6-deficient diet or a vitamin B6-enriched normal diet for 4 weeks. Then they compared the behavior and monoamine levels of these mice. After 4 weeks, vitamin B6-deficient mice showed remarkable decreases in serum vitamin B6 concentrations, dropping to 2.9% of the levels in control mice. Furthermore, there were behavioral abnormalities of sociability and cognitive memory in vitamin B6-deficient mice when they performed a social interaction and novel object recognition test. The mice that were fed a diet lacking in vitamin B6 also had stunted body growth. Vitamin B6-deficient mice exhibited a significant increase in noradrenaline release in the prefrontal cortex and striatum, which has been shown in previous clinical studies to play a pathophysiological role in schizophrenia. There were no changes in DA, 5-HT, or GABA between the two groups.

To assess whether vitamin B6 supplementation could help reverse the behavioral deficits and noradrenergic hyperactivation, vitamin B6-deficient mice were treated with pyridoxal-5-phosphate (the metabolically active form of vitamin B6) into the brain for 3 weeks. Vitamin B6 supplementation improved social and cognitive deficits and suppressed the enhanced noradrenergic activity and turnover, but it could not rescue reduced body growth.  

The results from this animal model shows vitamin B6 deficiency overactivated noradrenergic signaling in some brain regions, leading to behavioral and cognitive impairments, suggesting that vitamin B6 repletion may help ameliorate behavioral deficits and cognitive impairments in schizophrenic patients by inhibiting excessive release of noradrenaline. It is important to consider the degree and duration of vitamin B6 deficiency before supplementing at high doses. Further long-term human clinical trials are warranted to fully understand the relationship between VB6 deficiency and schizophrenia.

Previous research has shown that schizophrenia is associated with an upregulation in proinflammatory mediators and oxidative stress within the central nervous system. It is suggested that supplementation with antioxidants, omega-3 fatty acids from fish oil, and micronutrients that possess anti-inflammatory properties may provide some benefit to patients with severe schizophrenic symptoms. Additional research suggests that the bioactive compound found in cruciferous vegetables — sulforaphane — may promote healthy glutamate and glutathione status in the brains of those who have psychosis.   

Promoting a whole-food diet rich in vitamins and minerals is necessary for optimal brain function and nervous system health. Patients who suffer from schizophrenia may require additional vitamin B6 to support healthy neurotransmitter metabolism and function and to help reduce symptom severity as part of their multidimensional treatment plan. 

By Caitlin Higgins, MS, CNS