British Journal of Nutrition

Full Papers

The association of betaine, homocysteine and related metabolites with cognitive function in Dutch elderly people

Simone J. P. M. Eussena1 c1, Per M. Uelanda2, Robert Clarkea3, Henk J. Bloma4, Willibrord H. L. Hoefnagelsa5, Wija A. van Staverena1 and Lisette C. P. G. M. de Groota1

a1 Division of Human Nutrition, Wageningen University, P.O. Box 8129 6700 EV Wageningen, The Netherlands

a2 Section for Pharmacology, Institute of Medicine, University of Bergen and Haukeland University Hospital, Armauer Hanssen Hus (Building), 5021 Bergen, Norway

a3 Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford OX3 7LF, UK

a4 Department of Clinical Chemistry, VU University Medical Center, PO Box 7057 1007 MB Amsterdam, The Netherlands

a5 Department of Geriatrics, University Medical Center Nijmegen, PO Box 9101 6500 HB Nijmegen, The Netherlands


The importance of the one-carbon metabolites, choline and homocysteine, to brain function is well known. However, the associations between the one-carbon metabolites choline, betaine, methionine and dimethylglycine with cognition in elderly are unclear. We therefore examined the associations of these metabolites with cognition in a double-blind, placebo-controlled trial. Individuals (n 195) were randomized to receive daily oral capsules with either 1000 μg cobalamin (vitamin B12), or 1000 μg cobalamin plus 400 μg folic acid, or placebo for 24 weeks. Concentrations of homocysteine, methionine, choline, betaine and dimethylglycine were assessed before and after 12 and 24 weeks of treatment. Cognitive function, including domains of attention, construction, sensomotor speed, memory and executive function, was assessed before and after 24 weeks of treatment. At baseline, elevated plasma homocysteine was associated with lower performance of attention, construction, sensomotor speed and executive function. In addition, betaine was positively associated with better performance of construction, sensomotor speed and executive function, whereas elevated concentrations of methionine were positively associated with sensomotor speed. Daily combined supplementation with cobalamin plus folic acid decreased total homocysteine concentrations by 36 %, and increased betaine concentrations by 38 %. Participants with the largest increases in betaine concentrations showed a borderline significant (P = 0·07) higher memory performance compared to those without it. Although this trial observed associations of homocysteine and betaine with cognitive domains prior to supplementation, decreased concentrations of homocysteine were not related to improved cognitive performance. There was a tendency of participants with the largest increases in betaine concentrations to show the greatest improvement in memory function.

(Received August 14 2006)

(Revised March 29 2007)

(Accepted April 03 2007)


c1 Corresponding author: Dr Simone Eussen, fax +47 31 317 482 782, email


Abbreviations: DMG, dimethylglycine; MMSE, Mini-Mental State Examination; tHcy, total homocysteine