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Folate and Vitamin B12-Related Biomarkers in Relation to Brain Volumes.

ABSTRACT: We investigated cross-sectional associations between circulating homocysteine, folate, biomarkers of vitamin B12 status and brain volumes. We furthermore compared brain volumes of participants who received daily folic acid and vitamin B12 supplementation with participants who did not.Participants of the B-PROOF study (n = 2919) were assigned to 400 µg folic acid and 500 µg vitamin B12, or a placebo. After two years of intervention, T?-weighted magnetic resonance imaging (MRI) scans were made in a random subsample (n = 218) to obtain grey and white matter volume, and total brain volume (TBV). Plasma homocysteine, serum folate, vitamin B12, holotranscobalamin, and methylmalonic acid concentrations were measured.Multiple linear regression analyses showed inverse associations between plasma homocysteine with TBV (? = -0.91, 95% CI -1.85-0.03; p = 0.06) and between serum folate and TBV (? = -0.20, 95% CI -0.38, -0.02; p = 0.03). No significant associations were observed for serum vitamin B12 and holotranscobalamin. Fully adjusted ANCOVA models showed that the group that received B-vitamins had a lower TBV (adjusted mean 1064, 95% CI 1058-1069 mL) than the non-supplemented group (1072, 95% CI 1067-1078 mL, p = 0.03).Results were contradictory, with higher Hcy levels associated with lower TBV, but also with higher folate levels associated with lower TBV. In addition, the lack of a baseline measurement withholds us from giving recommendations on whether folic acid and vitamin B12 supplementation will be beneficial above and beyond normal dietary intake for brain health.

SUBMITTER: van der Zwaluw NL

PROVIDER: S-EPMC5295052 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Folate and Vitamin B<sub>12</sub>-Related Biomarkers in Relation to Brain Volumes.

van der Zwaluw Nikita L NL Brouwer-Brolsma Elske M EM van de Rest Ondine O van Wijngaarden Janneke P JP In 't Veld Paulette H PH Kourie Daniella I DI Swart Karin M A KM Enneman Anke W AW van Dijk Suzanne C SC van der Velde Nathalie N Kessels Roy P C RP Smeets Paul A M PA Kok Frans J FJ Dhonukshe-Rutten Rosalie A M RA de Groot Lisette C P G M LC

Nutrients 20161224 1

<h4>Aim</h4>We investigated cross-sectional associations between circulating homocysteine, folate, biomarkers of vitamin B<sub>12</sub> status and brain volumes. We furthermore compared brain volumes of participants who received daily folic acid and vitamin B<sub>12</sub> supplementation with participants who did not.<h4>Methods</h4>Participants of the B-PROOF study (<i>n</i> = 2919) were assigned to 400 µg folic acid and 500 µg vitamin B<sub>12</sub>, or a placebo. After two years of interventi ...[more]

PMID: 28029114

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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.

Dataset Information

Folate and Vitamin B12-Related Biomarkers in Relation to Brain Volumes.

Publications

Folate and Vitamin B<sub>12</sub>-Related Biomarkers in Relation to Brain Volumes.

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