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Vitamin supplementation in the treatment of schizophrenia.

ABSTRACT: This article reviews the current literature addressing the treatment of schizophrenia with vitamin supplementation. It describes the important roles that vitamins play in normal metabolism, and reviews the evidence pertaining to vitamin deficiency and supplementation in patients with schizophrenia. There is mounting evidence suggesting that vitamin supplementation, in particular with folic acid, vitamin B12 and vitamin D, may be important in treatment within certain subgroups of patients. There is a need for larger randomized controlled trials, and further studies examining the incidence of schizophrenia in countries with poor prenatal care and malnutrition, as well as in countries that have adopted mandatory folic acid fortification of grain products, are recommended.

SUBMITTER: Brown HE

PROVIDER: S-EPMC4083629 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Vitamin supplementation in the treatment of schizophrenia.

Brown Hannah E HE Roffman Joshua L JL

CNS drugs 20140701 7

This article reviews the current literature addressing the treatment of schizophrenia with vitamin supplementation. It describes the important roles that vitamins play in normal metabolism, and reviews the evidence pertaining to vitamin deficiency and supplementation in patients with schizophrenia. There is mounting evidence suggesting that vitamin supplementation, in particular with folic acid, vitamin B12 and vitamin D, may be important in treatment within certain subgroups of patients. There ...[more]

PMID: 24846474

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Project description:More effective treatments are needed for negative symptoms of schizophrenia, which are typically chronic, disabling, and costly. Negative symptoms have previously been associated with reduced blood folate levels, especially among patients with low-functioning variants in genes that regulate folate metabolism, suggesting the potential utility of folate supplementation.To determine whether folic acid plus vitamin B12 supplementation reduces negative symptoms of schizophrenia and whether functional variants in folate-related genes influence treatment response.Parallel-group, randomized, double-blind, placebo-controlled clinical trial of 16 weeks of treatment with 2 mg of folic acid and 400 ?g of vitamin B12.Three community mental health centers affiliated with academic medical centers in the United States.Outpatients with chronic schizophrenia who were psychiatrically stable but displayed persistent symptoms despite antipsychotic treatment. Eligible patients were 18 to 68 years old, were treated with an antipsychotic agent for 6 months or more at a stable dose for 6 weeks or more, and scored 60 or more on the Positive and Negative Syndrome Scale.One hundred forty subjects were randomized to receive daily oral folic acid plus vitamin B12 or placebo.Change in negative symptoms (Scale for the Assessment of Negative Symptoms [SANS]), as well as positive and total symptoms (Positive and Negative Syndrome Scale).Folate plus vitamin B12 improved negative symptoms significantly compared with placebo (group difference, -0.33 change in SANS score per week; 95% CI, -0.62 to -0.05) when genotype was taken into account but not when genotype was excluded. An interaction of the 484C>T variant of FOLH1 (rs202676) with treatment was observed (P = .02), where only patients homozygous for the 484T allele demonstrated significantly greater benefit with active treatment (-0.59 change in SANS score per week; 95% CI, -0.99 to -0.18). In parallel, we observed an inverse relationship between red blood cell folate concentration at baseline and 484C allele load (P = .03), which persisted until 8 weeks of treatment. Change in positive and total symptoms did not differ between treatment groups.Folate plus vitamin B12 supplementation can improve negative symptoms of schizophrenia, but treatment response is influenced by genetic variation in folate absorption. These findings support a personalized medicine approach for the treatment of negative symptoms.clinicaltrials.gov Identifier: NCT00611806.

Project description:BACKGROUND:Patients with haematological malignancies are often vitamin C deficient, and vitamin C is essential for the TET-induced conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), the first step in active DNA demethylation. Here, we investigate whether oral vitamin C supplementation can correct vitamin C deficiency and affect the 5hmC/5mC ratio in patients with myeloid cancers treated with DNA methyltransferase inhibitors (DNMTis). RESULTS:We conducted a randomized, double-blinded, placebo-controlled pilot trial (NCT02877277) in Danish patients with myeloid cancers performed during 3?cycles of DNMTi-treatment (5-azacytidine, 100?mg/m2/d for 5?days in 28-day?cycles) supplemented by oral dose of 500?mg vitamin C (n?=?10) or placebo (n?=?10) daily during the last 2?cycles. Fourteen patients (70%) were deficient in plasma vitamin C (<?23??M) and four of the remaining six patients were taking vitamin supplements at inclusion. Global DNA methylation was significantly higher in patients with severe vitamin C deficiency (<?11.4??M; 4.997 vs 4.656% 5mC relative to deoxyguanosine, 95% CI [0.126, 0.556], P?=?0.004). Oral supplementation restored plasma vitamin C levels to the normal range in all patients in the vitamin C arm (mean increase 34.85?±?7.94??M, P?=?0.0004). We show for the first time that global 5hmC/5mC levels were significantly increased in mononuclear myeloid cells from patients receiving oral vitamin C compared to placebo (0.037% vs -?0.029%, 95% CI [-?0.129, -?0.003], P?=?0.041). CONCLUSIONS:Normalization of plasma vitamin C by oral supplementation leads to an increase in the 5hmC/5mC ratio compared to placebo-treated patients and may enhance the biological effects of DNMTis. The clinical efficacy of oral vitamin C supplementation to DNMTis should be investigated in a large randomized, placebo-controlled clinical trial. TRIAL REGISTRATION:ClinicalTrials.gov, NCT02877277 . Registered on 9 August 2016, retrospectively registered.

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Vitamin supplementation in the treatment of schizophrenia.

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Vitamin supplementation in the treatment of schizophrenia.

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