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Vitamin B6 and schizophrenia

Vitamin B6 deficiency may cause schizophrenia-like symptoms in an animal model by altering noradrenaline metabolism

A study of vitamin B6 deficiency in mice found that the deficiency stimulates the noradrenergic system, altering behaviour and damaging cognition in ways similar to that seen in schizophrenia. The study suggests that supplementation with vitamin B6 could help some schizophrenia patients.

The link between vitamin B6 and schizophrenia
Low levels of B6 in the blood are found in about 35% of schizophrenia patients, reports the study led by scientists at the Tokyo Metropolitan Institute of Medical Science. Previous work by this research group discovered that levels of vitamin B6 correlated with patients’ symptom severity suggesting it could contribute to symptoms. The group has also shown that supplements of vitamin B6 can alleviate psychotic symptoms in some schizophrenics. How this happens is not clear however, and this study set out to find some answers.

What this study found
This study aimed to deliberately create vitamin B6 deficiency in an animal model and examine the effects on cognition, behaviour and monoamine neurotransmitter levels and turnover in the brain. The researchers also aimed to discover if replacing vitamin B6 in deficient mice caused the brain and behaviour to return to normal.

The researchers randomised 8-week old C57BL/6J mice to a diet containing 5 micrograms vitamin B6 per 100 g or one containing 1.4 mg vitamin B6 per 100 g for 4 weeks. After that time the mice on the low vitamin B6 diet had levels of vitamin B6 in their blood that were about 3% that of control mice. At 12 weeks a social interaction test showed the deficient mice were less likely than the controls to interact with unfamiliar mice. They also scored worse on a novel object recognition test that assessed memory compared with controls. In their brains increases in levels of a marker of noradrenaline metabolism (3-methoxy-4-hydroxyphenylglycol) suggested that the deficient mice were producing more noradrenaline than usual. There were no changes in dopamine or serotonin levels. Giving mice vitamin B6 directly into the brain or a drug that blocks noradrenaline action, improved these symptoms.

The study concludes: “These findings suggest that the behavioral deficits shown in VB6(−) mice are caused by enhancement of the noradrenergic (NAergic) system.” They are now focusing on developing a treatment strategy based on the vitamin.

The study was a collaboration between Tokyo Metropolitan Institute of Medical ScienceOsaka University and Kowa company. No conflicts of interest were declared.

Vitamin B6
Vitamin B6, is found in a variety of foods, the best sources being fish, organ meats, starchy vegetables and non-citrus fruits. It is also added to fortified cereals. It has a wide range of functions in the body as a coenzyme including production of neurotransmitters.

In the US population between 10 and 20% of people may have low levels of the vitamin B6 metabolite PLP, according to the NIH Office of Dietary Supplements (ODS). A number of conditions including those affecting absorption are associated with deficiency - for example, heavy drinking, autoimmune disorders, inflammatory bowel disease, impaired kidney function, and certain antiepileptic medications. Obesity and pregnancy may also predispose to deficiency, according to the ODS.

Schizophrenia and nutritional research
WHO figures suggest 20 million people worldwide have schizophrenia, a severe mental illness. Those with the illness experience hallucinations and delusions, and disorganised behaviour and speech as well as emotional disturbances. Treatment includes drugs and talking therapies. Nutritional research into schizophrenia has included studies of anti-inflammatory diets, the gut microbiome, probiotic supplements, vitamin D and omega- fatty acids. See ‘Further reading’ for details.

Find out more

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(“vitamin B6” or pyridoxal or pyridoxine)


Toriumi, K., Miyashita, M., Suzuki, K. et al. Vitamin B6 deficiency hyperactivates the noradrenergic system, leading to social deficits and cognitive impairment. Transl Psychiatry 11, 262 (2021).


Article details

  • Author(s)
  • I. Hoskins
  • Date
  • 27 May 2021
  • Subject(s)
  • Nutrition physiology