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Research Article

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

  • A. David Smith equal contributor mail,

    equal contributor Contributed equally to this work with: A. David Smith, Helga Refsum

    david.smith@pharm.ox.ac.uk

    Affiliations: Oxford Project to Investigate Memory and Ageing (OPTIMA), University of Oxford, Oxford, United Kingdom, University Department of Pharmacology and Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, United Kingdom

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  • Stephen M. Smith,

    Affiliation: Department of Clinical Neurology, Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, Oxford, United Kingdom

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  • Celeste A. de Jager,

    Affiliation: Oxford Project to Investigate Memory and Ageing (OPTIMA), University of Oxford, Oxford, United Kingdom

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  • Philippa Whitbread,

    Affiliation: Oxford Project to Investigate Memory and Ageing (OPTIMA), University of Oxford, Oxford, United Kingdom

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  • Carole Johnston,

    Affiliations: Oxford Project to Investigate Memory and Ageing (OPTIMA), University of Oxford, Oxford, United Kingdom, University Department of Pharmacology and Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, United Kingdom

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  • Grzegorz Agacinski,

    Affiliation: Oxford Project to Investigate Memory and Ageing (OPTIMA), University of Oxford, Oxford, United Kingdom

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  • Abderrahim Oulhaj,

    Affiliation: Oxford Project to Investigate Memory and Ageing (OPTIMA), University of Oxford, Oxford, United Kingdom

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  • Kevin M. Bradley,

    Affiliation: Department of Radiology and Nuclear Medicine, Oxford Radcliffe Hospitals NHS Trust, Oxford, United Kingdom

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  • Robin Jacoby,

    Affiliation: University Department of Psychiatry, University of Oxford, Oxford, United Kingdom

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  • Helga Refsum equal contributor

    equal contributor Contributed equally to this work with: A. David Smith, Helga Refsum

    Affiliations: Oxford Project to Investigate Memory and Ageing (OPTIMA), University of Oxford, Oxford, United Kingdom, University Department of Pharmacology and Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, United Kingdom, Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

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  • Published: September 08, 2010
  • DOI: 10.1371/journal.pone.0012244

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B12 and folate supplements increase cancer and mortality

Posted by weed01 on 01 Oct 2010 at 14:40 GMT

Cancer Incidence and Mortality After Treatment With Folic Acid and Vitamin B12
Marta Ebbing, MD; Kaare Harald Bønaa, MD, PhD; Ottar Nygård, MD, PhD; Egil Arnesen, MD; Per Magne Ueland, MD, PhD; Jan Erik Nordrehaug, MD, PhD; Knut Rasmussen, MD, PhD; Inger Njølstad, MD, PhD; Helga Refsum, MD, PhD; Dennis W. Nilsen, MD, PhD; Aage Tverdal, PhD; Klaus Meyer, PhD; Stein Emil Vollset, MD, DrPH


JAMA. 2009;302(19):2119-2126.

Context Recently, concern has been raised about the safety of folic acid, particularly in relation to cancer risk.

Objective To evaluate effects of treatment with B vitamins on cancer outcomes and all-cause mortality in 2 randomized controlled trials.

Design, Setting, and Participants Combined analysis and extended follow-up of participants from 2 randomized, double-blind, placebo-controlled clinical trials (Norwegian Vitamin Trial and Western Norway B Vitamin Intervention Trial). A total of 6837 patients with ischemic heart disease were treated with B vitamins or placebo between 1998 and 2005, and were followed up through December 31, 2007.

Interventions Oral treatment with folic acid (0.8 mg/d) plus vitamin B12 (0.4 mg/d) and vitamin B6 (40 mg/d) (n = 1708); folic acid (0.8 mg/d) plus vitamin B12 (0.4 mg/d) (n = 1703); vitamin B6 alone (40 mg/d) (n = 1705); or placebo (n = 1721).

Main Outcome Measures Cancer incidence, cancer mortality, and all-cause mortality.

Results During study treatment, median serum folate concentration increased more than 6-fold among participants given folic acid. After a median 39 months of treatment and an additional 38 months of posttrial observational follow-up, 341 participants (10.0%) who received folic acid plus vitamin B12 vs 288 participants (8.4%) who did not receive such treatment were diagnosed with cancer (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03-1.41; P = .02). A total of 136 (4.0%) who received folic acid plus vitamin B12 vs 100 (2.9%) who did not receive such treatment died from cancer (HR, 1.38; 95% CI, 1.07-1.79; P = .01). A total of 548 patients (16.1%) who received folic acid plus vitamin B12 vs 473 (13.8%) who did not receive such treatment died from any cause (HR, 1.18; 95% CI, 1.04-1.33; P = .01). Results were mainly driven by increased lung cancer incidence in participants who received folic acid plus vitamin B12. Vitamin B6 treatment was not associated with any significant effects.

Conclusion Treatment with folic acid plus vitamin B12 was associated with increased cancer outcomes and all-cause mortality in patients with ischemic heart disease in Norway, where there is no folic acid fortification of foods.

Trial Registration clinicaltrials.gov Identifier: NCT00671346

No competing interests declared.