PLoS ONE: Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial

Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial

Controlled-Trials.com ISRCTN94410159

A. David Smith1,2#*, Stephen M. Smith3, Celeste A. de Jager1, Philippa Whitbread1, Carole Johnston1,2, Grzegorz Agacinski1, Abderrahim Oulhaj1, Kevin M. Bradley4, Robin Jacoby5, Helga Refsum1,2,6#

1 Oxford Project to Investigate Memory and Ageing (OPTIMA), University of Oxford, Oxford, United Kingdom, 2 University Department of Pharmacology and Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, United Kingdom, 3 Department of Clinical Neurology, Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, Oxford, United Kingdom, 4 Department of Radiology and Nuclear Medicine, Oxford Radcliffe Hospitals NHS Trust, Oxford, United Kingdom, 5 University Department of Psychiatry, University of Oxford, Oxford, United Kingdom, 6 Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

Abstract
Background
An increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins.

Objective
To determine whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial (VITACOG, ISRCTN 94410159).

Methods and Findings
Single-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B6 and B12 in 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment. A subset (187) volunteered to have cranial MRI scans at the start and finish of the study. Participants were randomly assigned to two groups of equal size, one treated with folic acid (0.8 mg/d), vitamin B12 (0.5 mg/d) and vitamin B6 (20 mg/d), the other with placebo; treatment was for 24 months. The main outcome measure was the change in the rate of atrophy of the whole brain assessed by serial volumetric MRI scans.

Results
A total of 168 participants (85 in active treatment group; 83 receiving placebo) completed the MRI section of the trial. The mean rate of brain atrophy per year was 0.76% [95% CI, 0.63–0.90] in the active treatment group and 1.08% [0.94–1.22] in the placebo group (P = 0.001). The treatment response was related to baseline homocysteine levels: the rate of atrophy in participants with homocysteine >13 µmol/L was 53% lower in the active treatment group (P = 0.001). A greater rate of atrophy was associated with a lower final cognitive test scores. There was no difference in serious adverse events according to treatment category.

Conclusions and Significance
The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. Sixteen percent of those over 70 y old have mild cognitive impairment and half of these develop Alzheimer's disease. Since accelerated brain atrophy is a characteristic of subjects with mild cognitive impairment who convert to Alzheimer's disease, trials are needed to see if the same treatment will delay the development of Alzheimer's disease.

Trial Registration
Controlled-Trials.com ISRCTN94410159

Citation: Smith AD, Smith SM, de Jager CA, Whitbread P, Johnston C, et al. (2010) Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial. PLoS ONE 5(9): e12244. doi:10.1371/journal.pone.0012244

Editor: Ashley I. Bush, Mental Health Research Institute of Victoria, Australia


Received: May 27, 2010; Accepted: July 22, 2010; Published: September 8, 2010

Copyright: © 2010 Smith et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This work was supported by grants from the Charles Wolfson Charitable Trust, Medical Research Council, Alzheimer's Research Trust, Henry Smith Charity, John Coates Charitable Trust, Thames Valley Dementias and Neurodegenerative Diseases Research Network of the National Institute for Health Research, UK, and the Sidney and Elizabeth Corob Charitable Trust, and Meda AB/Recip AB, Solna, Sweden. None of the funders or the sponsor (University of Oxford) played any role in the design and conduct of the study, collection, management, analysis, and interpretation of the data; nor in the preparation, review, or approval of the manuscript.

Competing interests: Dr. A. D. Smith is named as an inventor on two patents held by the University of Oxford on the use of folic acid to treat Alzheimer's disease (US6008221; US6127370); under the University's rules he could benefit financially if the patent is exploited. Drs. Refsum and A. D. Smith report having in the past received speaking honoraria from Recip AB, the company that donated the vitamin tablets, and from Axis-Shield, who make the equipment used to assay homocysteine. These competing interests do not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. None of the other authors have any financial disclosures.

* E-mail: david.smith@pharm.ox.ac.uk

# These authors contributed equally to this work.


PLoS ONE: Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial



NEUROLOGÍA
Actualidad Ultimas noticias - JANOes -
La vitamina B podría ayudar a frenar la demencia en personas mayores
JANO.es · 13 Septiembre 2010 10:04

El consumo de altas dosis de esta vitamina demora el avance del deterioro cognitivo leve, un importante factor de riesgo en la enfermedad de Alzheimer, según un estudio de la Universidad de Oxford.


Consumir dosis altas de vitaminas B en tabletas diarias puede reducir a la mitad la tasa a la que se hace más pequeño el cerebro en personas mayores con problemas de memoria y desaceleraría el avance hacia la demencia, según datos de un estudio británico publicado en la revista PLoS One.

El deterioro cognitivo leve (DCL) afecta a alrededor del 16% de los mayores de 70 años y se caracteriza por problemas leves de pérdida de memoria, lenguaje y otras funciones mentales. Aunque no suele interferir con la vida diaria, cerca del 50% de las personas diagnosticadas avanzan hacia la enfermedad de Alzheimer en unos cinco años.

Científicos de la Universidad de Oxford estudiaron a 168 voluntarios con DCL, que recibieron una píldora con altas dosis de ácido fólico, vitamina B6 y B12, o una pastilla placebo.

Estas vitaminas B son conocidas por controlar los niveles en sangre de un aminoácido denominado homocisteína, sustancia que, en cantidades elevadas en la sangre, se vincula con un aumento del riesgo de desarrollar enfermedad de Alzheimer.

Las píldoras, llamadas TrioBe Plus, contenían unas 300 veces más de la ingesta diaria recomendada de B12, cuatro veces más de los niveles aconsejados de ácido fólico por día y 15 veces más de la cantidad pautada como límite diario para la vitamina B6. "Se trata de una intervención farmacológica, no vitamínica", destacó Helga Refsum, una de las científicas que trabajó en el estudio.

Los resultados mostraron que, en promedio, los cerebros de quienes tomaron las vitaminas encogieron a una tasa del 0,76% anual, mientras que entre quienes consumieron placebo, el promedio de reducción cerebral fue del 1,08%.

Las personas con los mayores niveles de homocisteína al comienzo del estudio fueron las más beneficiadas con el tratamiento, ya que sus cerebros se redujeron a la mitad de la tasa de lo que lo hicieron quienes tomaron las píldoras falsas.

El mayor estudio sobre vitaminas
"Este es un resultado muy drástico (...) Es mucho más de lo que podríamos haber predicho", dijo David Smith, del departamento de farmacología de Oxford, que co-dirigió el ensayo. "Esperamos que este tratamiento simple y seguro demore el desarrollo del Alzheimer en muchas personas que tiene problemas de memoria leves", agregó Smith.

Los investigadores aseguran que su ensayo clínico, de dos años de duración, es el mayor realizado hasta la fecha sobre el efecto de las vitaminas B en el "deterioro cognitivo leve", un importante factor de riesgo de la enfermedad de Alzheimer y otras formas de demencia.

Otros expertos calificaron de importantes los resultados del estudio e instaron a que se efectúen más ensayos a gran escala para ver si puede confirmarse la seguridad y efectividad de las vitaminas B en la prevención de condiciones neurodegenerativas.


PLoS ONE 5(9): e12244. doi:10.1371/journal.pone.0012244
PLoS ONE: Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial


PLoS ONE
PLoS ONE : accelerating the publication of peer-reviewed science

Universidad de Oxford
Homepage - University of Oxford

Actualidad Ultimas noticias - JANOes - La vitamina B podria ayudar a frenar la demencia en personas mayores - JANO.es - ELSEVIER