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December 02, 2014; 83 (23) Article

Results of 2-year vitamin B treatment on cognitive performance

Secondary data from an RCT

Nikita L. van der Zwaluw, Rosalie A.M. Dhonukshe-Rutten, Janneke P. van Wijngaarden, Elske M. Brouwer-Brolsma, Ondine van de Rest, Paulette H. In 't Veld, Anke W. Enneman, Suzanne C. van Dijk, Annelies C. Ham, Karin M.A. Swart, Nathalie van der Velde, Natasja M. van Schoor, Tischa J.M. van der Cammen, André G. Uitterlinden, Paul Lips, Roy P.C. Kessels, Lisette C.P.G.M. de Groot
First published November 12, 2014, DOI: https://doi.org/10.1212/WNL.0000000000001050
Nikita L. van der Zwaluw
From the Division of Human Nutrition (N.L.v.d.Z., R.A.M.D.-R., J.P.v.W., E.M.B.-B., O.v.d.R., P.H.I.t.V., L.C.P.G.M.d.G.), Wageningen University; Department of Internal Medicine (A.W.E., S.C.v.D., A.C.H., N.v.d.V., T.J.M.v.d.C., A.G.U.), Erasmus University Medical Center, Rotterdam; Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research (K.M.A.S., N.M.v.S., P.L.), and Department of Internal Medicine, Endocrine Section (P.L.), VU University Medical Center, Amsterdam; Radboud Alzheimer Center (R.P.C.K.) and Department of Medical Psychology (R.P.C.K.), Radboud University Medical Center, Nijmegen; and Donders Institute for Brain, Cognition and Behavior (R.P.C.K.), Radboud University Nijmegen, the Netherlands.
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Rosalie A.M. Dhonukshe-Rutten
From the Division of Human Nutrition (N.L.v.d.Z., R.A.M.D.-R., J.P.v.W., E.M.B.-B., O.v.d.R., P.H.I.t.V., L.C.P.G.M.d.G.), Wageningen University; Department of Internal Medicine (A.W.E., S.C.v.D., A.C.H., N.v.d.V., T.J.M.v.d.C., A.G.U.), Erasmus University Medical Center, Rotterdam; Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research (K.M.A.S., N.M.v.S., P.L.), and Department of Internal Medicine, Endocrine Section (P.L.), VU University Medical Center, Amsterdam; Radboud Alzheimer Center (R.P.C.K.) and Department of Medical Psychology (R.P.C.K.), Radboud University Medical Center, Nijmegen; and Donders Institute for Brain, Cognition and Behavior (R.P.C.K.), Radboud University Nijmegen, the Netherlands.
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Janneke P. van Wijngaarden
From the Division of Human Nutrition (N.L.v.d.Z., R.A.M.D.-R., J.P.v.W., E.M.B.-B., O.v.d.R., P.H.I.t.V., L.C.P.G.M.d.G.), Wageningen University; Department of Internal Medicine (A.W.E., S.C.v.D., A.C.H., N.v.d.V., T.J.M.v.d.C., A.G.U.), Erasmus University Medical Center, Rotterdam; Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research (K.M.A.S., N.M.v.S., P.L.), and Department of Internal Medicine, Endocrine Section (P.L.), VU University Medical Center, Amsterdam; Radboud Alzheimer Center (R.P.C.K.) and Department of Medical Psychology (R.P.C.K.), Radboud University Medical Center, Nijmegen; and Donders Institute for Brain, Cognition and Behavior (R.P.C.K.), Radboud University Nijmegen, the Netherlands.
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Elske M. Brouwer-Brolsma
From the Division of Human Nutrition (N.L.v.d.Z., R.A.M.D.-R., J.P.v.W., E.M.B.-B., O.v.d.R., P.H.I.t.V., L.C.P.G.M.d.G.), Wageningen University; Department of Internal Medicine (A.W.E., S.C.v.D., A.C.H., N.v.d.V., T.J.M.v.d.C., A.G.U.), Erasmus University Medical Center, Rotterdam; Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research (K.M.A.S., N.M.v.S., P.L.), and Department of Internal Medicine, Endocrine Section (P.L.), VU University Medical Center, Amsterdam; Radboud Alzheimer Center (R.P.C.K.) and Department of Medical Psychology (R.P.C.K.), Radboud University Medical Center, Nijmegen; and Donders Institute for Brain, Cognition and Behavior (R.P.C.K.), Radboud University Nijmegen, the Netherlands.
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Ondine van de Rest
From the Division of Human Nutrition (N.L.v.d.Z., R.A.M.D.-R., J.P.v.W., E.M.B.-B., O.v.d.R., P.H.I.t.V., L.C.P.G.M.d.G.), Wageningen University; Department of Internal Medicine (A.W.E., S.C.v.D., A.C.H., N.v.d.V., T.J.M.v.d.C., A.G.U.), Erasmus University Medical Center, Rotterdam; Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research (K.M.A.S., N.M.v.S., P.L.), and Department of Internal Medicine, Endocrine Section (P.L.), VU University Medical Center, Amsterdam; Radboud Alzheimer Center (R.P.C.K.) and Department of Medical Psychology (R.P.C.K.), Radboud University Medical Center, Nijmegen; and Donders Institute for Brain, Cognition and Behavior (R.P.C.K.), Radboud University Nijmegen, the Netherlands.
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Paulette H. In 't Veld
From the Division of Human Nutrition (N.L.v.d.Z., R.A.M.D.-R., J.P.v.W., E.M.B.-B., O.v.d.R., P.H.I.t.V., L.C.P.G.M.d.G.), Wageningen University; Department of Internal Medicine (A.W.E., S.C.v.D., A.C.H., N.v.d.V., T.J.M.v.d.C., A.G.U.), Erasmus University Medical Center, Rotterdam; Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research (K.M.A.S., N.M.v.S., P.L.), and Department of Internal Medicine, Endocrine Section (P.L.), VU University Medical Center, Amsterdam; Radboud Alzheimer Center (R.P.C.K.) and Department of Medical Psychology (R.P.C.K.), Radboud University Medical Center, Nijmegen; and Donders Institute for Brain, Cognition and Behavior (R.P.C.K.), Radboud University Nijmegen, the Netherlands.
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Anke W. Enneman
From the Division of Human Nutrition (N.L.v.d.Z., R.A.M.D.-R., J.P.v.W., E.M.B.-B., O.v.d.R., P.H.I.t.V., L.C.P.G.M.d.G.), Wageningen University; Department of Internal Medicine (A.W.E., S.C.v.D., A.C.H., N.v.d.V., T.J.M.v.d.C., A.G.U.), Erasmus University Medical Center, Rotterdam; Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research (K.M.A.S., N.M.v.S., P.L.), and Department of Internal Medicine, Endocrine Section (P.L.), VU University Medical Center, Amsterdam; Radboud Alzheimer Center (R.P.C.K.) and Department of Medical Psychology (R.P.C.K.), Radboud University Medical Center, Nijmegen; and Donders Institute for Brain, Cognition and Behavior (R.P.C.K.), Radboud University Nijmegen, the Netherlands.
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Suzanne C. van Dijk
From the Division of Human Nutrition (N.L.v.d.Z., R.A.M.D.-R., J.P.v.W., E.M.B.-B., O.v.d.R., P.H.I.t.V., L.C.P.G.M.d.G.), Wageningen University; Department of Internal Medicine (A.W.E., S.C.v.D., A.C.H., N.v.d.V., T.J.M.v.d.C., A.G.U.), Erasmus University Medical Center, Rotterdam; Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research (K.M.A.S., N.M.v.S., P.L.), and Department of Internal Medicine, Endocrine Section (P.L.), VU University Medical Center, Amsterdam; Radboud Alzheimer Center (R.P.C.K.) and Department of Medical Psychology (R.P.C.K.), Radboud University Medical Center, Nijmegen; and Donders Institute for Brain, Cognition and Behavior (R.P.C.K.), Radboud University Nijmegen, the Netherlands.
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Annelies C. Ham
From the Division of Human Nutrition (N.L.v.d.Z., R.A.M.D.-R., J.P.v.W., E.M.B.-B., O.v.d.R., P.H.I.t.V., L.C.P.G.M.d.G.), Wageningen University; Department of Internal Medicine (A.W.E., S.C.v.D., A.C.H., N.v.d.V., T.J.M.v.d.C., A.G.U.), Erasmus University Medical Center, Rotterdam; Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research (K.M.A.S., N.M.v.S., P.L.), and Department of Internal Medicine, Endocrine Section (P.L.), VU University Medical Center, Amsterdam; Radboud Alzheimer Center (R.P.C.K.) and Department of Medical Psychology (R.P.C.K.), Radboud University Medical Center, Nijmegen; and Donders Institute for Brain, Cognition and Behavior (R.P.C.K.), Radboud University Nijmegen, the Netherlands.
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Karin M.A. Swart
From the Division of Human Nutrition (N.L.v.d.Z., R.A.M.D.-R., J.P.v.W., E.M.B.-B., O.v.d.R., P.H.I.t.V., L.C.P.G.M.d.G.), Wageningen University; Department of Internal Medicine (A.W.E., S.C.v.D., A.C.H., N.v.d.V., T.J.M.v.d.C., A.G.U.), Erasmus University Medical Center, Rotterdam; Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research (K.M.A.S., N.M.v.S., P.L.), and Department of Internal Medicine, Endocrine Section (P.L.), VU University Medical Center, Amsterdam; Radboud Alzheimer Center (R.P.C.K.) and Department of Medical Psychology (R.P.C.K.), Radboud University Medical Center, Nijmegen; and Donders Institute for Brain, Cognition and Behavior (R.P.C.K.), Radboud University Nijmegen, the Netherlands.
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Nathalie van der Velde
From the Division of Human Nutrition (N.L.v.d.Z., R.A.M.D.-R., J.P.v.W., E.M.B.-B., O.v.d.R., P.H.I.t.V., L.C.P.G.M.d.G.), Wageningen University; Department of Internal Medicine (A.W.E., S.C.v.D., A.C.H., N.v.d.V., T.J.M.v.d.C., A.G.U.), Erasmus University Medical Center, Rotterdam; Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research (K.M.A.S., N.M.v.S., P.L.), and Department of Internal Medicine, Endocrine Section (P.L.), VU University Medical Center, Amsterdam; Radboud Alzheimer Center (R.P.C.K.) and Department of Medical Psychology (R.P.C.K.), Radboud University Medical Center, Nijmegen; and Donders Institute for Brain, Cognition and Behavior (R.P.C.K.), Radboud University Nijmegen, the Netherlands.
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Natasja M. van Schoor
From the Division of Human Nutrition (N.L.v.d.Z., R.A.M.D.-R., J.P.v.W., E.M.B.-B., O.v.d.R., P.H.I.t.V., L.C.P.G.M.d.G.), Wageningen University; Department of Internal Medicine (A.W.E., S.C.v.D., A.C.H., N.v.d.V., T.J.M.v.d.C., A.G.U.), Erasmus University Medical Center, Rotterdam; Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research (K.M.A.S., N.M.v.S., P.L.), and Department of Internal Medicine, Endocrine Section (P.L.), VU University Medical Center, Amsterdam; Radboud Alzheimer Center (R.P.C.K.) and Department of Medical Psychology (R.P.C.K.), Radboud University Medical Center, Nijmegen; and Donders Institute for Brain, Cognition and Behavior (R.P.C.K.), Radboud University Nijmegen, the Netherlands.
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Tischa J.M. van der Cammen
From the Division of Human Nutrition (N.L.v.d.Z., R.A.M.D.-R., J.P.v.W., E.M.B.-B., O.v.d.R., P.H.I.t.V., L.C.P.G.M.d.G.), Wageningen University; Department of Internal Medicine (A.W.E., S.C.v.D., A.C.H., N.v.d.V., T.J.M.v.d.C., A.G.U.), Erasmus University Medical Center, Rotterdam; Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research (K.M.A.S., N.M.v.S., P.L.), and Department of Internal Medicine, Endocrine Section (P.L.), VU University Medical Center, Amsterdam; Radboud Alzheimer Center (R.P.C.K.) and Department of Medical Psychology (R.P.C.K.), Radboud University Medical Center, Nijmegen; and Donders Institute for Brain, Cognition and Behavior (R.P.C.K.), Radboud University Nijmegen, the Netherlands.
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André G. Uitterlinden
From the Division of Human Nutrition (N.L.v.d.Z., R.A.M.D.-R., J.P.v.W., E.M.B.-B., O.v.d.R., P.H.I.t.V., L.C.P.G.M.d.G.), Wageningen University; Department of Internal Medicine (A.W.E., S.C.v.D., A.C.H., N.v.d.V., T.J.M.v.d.C., A.G.U.), Erasmus University Medical Center, Rotterdam; Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research (K.M.A.S., N.M.v.S., P.L.), and Department of Internal Medicine, Endocrine Section (P.L.), VU University Medical Center, Amsterdam; Radboud Alzheimer Center (R.P.C.K.) and Department of Medical Psychology (R.P.C.K.), Radboud University Medical Center, Nijmegen; and Donders Institute for Brain, Cognition and Behavior (R.P.C.K.), Radboud University Nijmegen, the Netherlands.
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Paul Lips
From the Division of Human Nutrition (N.L.v.d.Z., R.A.M.D.-R., J.P.v.W., E.M.B.-B., O.v.d.R., P.H.I.t.V., L.C.P.G.M.d.G.), Wageningen University; Department of Internal Medicine (A.W.E., S.C.v.D., A.C.H., N.v.d.V., T.J.M.v.d.C., A.G.U.), Erasmus University Medical Center, Rotterdam; Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research (K.M.A.S., N.M.v.S., P.L.), and Department of Internal Medicine, Endocrine Section (P.L.), VU University Medical Center, Amsterdam; Radboud Alzheimer Center (R.P.C.K.) and Department of Medical Psychology (R.P.C.K.), Radboud University Medical Center, Nijmegen; and Donders Institute for Brain, Cognition and Behavior (R.P.C.K.), Radboud University Nijmegen, the Netherlands.
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Roy P.C. Kessels
From the Division of Human Nutrition (N.L.v.d.Z., R.A.M.D.-R., J.P.v.W., E.M.B.-B., O.v.d.R., P.H.I.t.V., L.C.P.G.M.d.G.), Wageningen University; Department of Internal Medicine (A.W.E., S.C.v.D., A.C.H., N.v.d.V., T.J.M.v.d.C., A.G.U.), Erasmus University Medical Center, Rotterdam; Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research (K.M.A.S., N.M.v.S., P.L.), and Department of Internal Medicine, Endocrine Section (P.L.), VU University Medical Center, Amsterdam; Radboud Alzheimer Center (R.P.C.K.) and Department of Medical Psychology (R.P.C.K.), Radboud University Medical Center, Nijmegen; and Donders Institute for Brain, Cognition and Behavior (R.P.C.K.), Radboud University Nijmegen, the Netherlands.
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Lisette C.P.G.M. de Groot
From the Division of Human Nutrition (N.L.v.d.Z., R.A.M.D.-R., J.P.v.W., E.M.B.-B., O.v.d.R., P.H.I.t.V., L.C.P.G.M.d.G.), Wageningen University; Department of Internal Medicine (A.W.E., S.C.v.D., A.C.H., N.v.d.V., T.J.M.v.d.C., A.G.U.), Erasmus University Medical Center, Rotterdam; Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research (K.M.A.S., N.M.v.S., P.L.), and Department of Internal Medicine, Endocrine Section (P.L.), VU University Medical Center, Amsterdam; Radboud Alzheimer Center (R.P.C.K.) and Department of Medical Psychology (R.P.C.K.), Radboud University Medical Center, Nijmegen; and Donders Institute for Brain, Cognition and Behavior (R.P.C.K.), Radboud University Nijmegen, the Netherlands.
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Full PDF
Citation
Results of 2-year vitamin B treatment on cognitive performance
Secondary data from an RCT
Nikita L. van der Zwaluw, Rosalie A.M. Dhonukshe-Rutten, Janneke P. van Wijngaarden, Elske M. Brouwer-Brolsma, Ondine van de Rest, Paulette H. In 't Veld, Anke W. Enneman, Suzanne C. van Dijk, Annelies C. Ham, Karin M.A. Swart, Nathalie van der Velde, Natasja M. van Schoor, Tischa J.M. van der Cammen, André G. Uitterlinden, Paul Lips, Roy P.C. Kessels, Lisette C.P.G.M. de Groot
Neurology Dec 2014, 83 (23) 2158-2166; DOI: 10.1212/WNL.0000000000001050

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Abstract

Objective: We investigated the effects of 2-year folic acid and vitamin B12 supplementation on cognitive performance in elderly people with elevated homocysteine (Hcy) levels.

Methods: This multicenter, double-blind, randomized, placebo-controlled trial included 2,919 elderly participants (65 years and older) with Hcy levels between 12 and 50 µmol/L. Participants received daily either a tablet with 400 µg folic acid and 500 µg vitamin B12 (B-vitamin group) or a placebo tablet. Both tablets contained 15 µg vitamin D3. Data were available for global cognitive functioning assessed by Mini-Mental State Examination (n = 2,556), episodic memory (n = 2,467), attention and working memory (n = 759), information processing speed (n = 731), and executive function (n = 721).

Results: Mean age was 74.1 (SD 6.5) years. Hcy concentrations decreased 5.0 (95% confidence interval −5.3 to −4.7) µmol/L in the B-vitamin group and 1.3 (−1.6 to −0.9) µmol/L in the placebo group. Cognitive domain scores did not differ over time between the 2 groups, as determined by analysis of covariance. Mini-Mental State Examination score decreased with 0.1 (−0.2 to 0.0) in the B-vitamin group and 0.3 (−0.4 to −0.2) in the placebo group (p = 0.05), as determined by an independent t test.

Conclusions: Two-year folic acid and vitamin B12 supplementation did not beneficially affect performance on 4 cognitive domains in elderly people with elevated Hcy levels. It may slightly slow the rate of decline of global cognition, but the reported small difference may be attributable to chance.

Classification of evidence: This study provides Class I evidence that 2-year supplementation with folic acid and vitamin B12 in hyperhomocysteinemic elderly people does not affect cognitive performance.

GLOSSARY

B-PROOF=
B-Vitamins for the Prevention of Osteoporotic Fractures;
CI=
confidence interval;
Hcy=
homocysteine;
holoTC=
holotranscobalamin;
IQR=
interquartile range;
MCI=
mild cognitive impairment;
MMSE=
Mini-Mental State Examination;
MTHFR=
methylenetetrahydrofolate reductase;
RAVLT=
Rey Auditory Verbal Learning Test;
RCT=
randomized controlled trial;
TMT=
Trail Making Test;
WU=
Wageningen University

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Received March 26, 2014.
  • Accepted in final form September 2, 2014.
  • © 2014 American Academy of Neurology
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Letters: Rapid online correspondence

  • B-vitamins and cognition - food for thought
    • Zoe R. Yates, University Lecturer, University of Newcastlezoe.yates@newcastle.edu.au
    • Mark Lucock, Newcastle, Australia; Emma Beckett, Newcastle, Australia; Martin Veysey, Newcastle, Australia
    Submitted December 26, 2014
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