In a new study involving 140 patients with schizophrenia, researchers found that adding folic acid and vitamin B12 supplements to treatment with standard antipsychotic medication improved a core symptom component of schizophrenia .
Folate is required for the synthesis of DNA and neurotransmitters and plays a role in the control of gene expression. Sufficient prenatal folate intake can reduce the risk of birth defects--in particular neural tube defects--and studies have suggested that folate deficiency during pregnancy significantly increases the risk of schizophrenia among offspring.
Earlier research found low blood folate levels were associated with more severe negative symptoms in patients with schizophrenia, and a pilot study in 2011 found symptom improvement only among patients carrying a variant in a folate-pathway gene called MTHFR that reduced the gene's activity.
To get a clearer picture of folate's effect on negative symptoms, the current study enrolled patients with schizophrenia and took blood samples to determine the genetic variants in 4 specific genes related to folate metabolism--MTHFR, FOLH1, MTR, and COMT--all of which are genes previously associated with the severity of negative symptoms of schizophrenia.
When the analysis accounted for the variants in the genes of interest, intake of the two nutrients provided significant improvement in negative symptoms, mainly in those with specific variants in MTHFR and FOLH1 (variants in the other two genes studied did not appear to have an effect on treatment outcome).
What's really interesting to me, however, was that the form of folate administered was folic acid (the inactive, synthetic form of the nutrient that the body must convert into the metabolically active form called L-methylfolate). It's even more shocking when you consider that the study specifically focused on the genes involved in folate metabolism. Why they didn't just use L-methylfolate in this study is a mystery to me. Perhaps they have extra money to waste on running basically the same study twice.
"We are now conducting a clinical trial of L-methylfolate, which bypasses some of these folate-pathway enzymes and might have greater efficiency among individuals with low-functioning variants," explains the lead author of the study.
Source: Randomized Multicenter Investigation of Folate Plus Vitamin B12 Supplementation in Schizophrenia
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