British Journal of Nutrition

Human and Clinical Nutrition

Choline supplementation and measures of choline and betaine status: a randomised, controlled trial in postmenopausal women

Julie M. W. Wallacea1 c1, Jacqueline M. McCormacka1, Helene McNultya1, Paula M. Walsha1, Paula J. Robsona2, Maxine P. Bonhama3, Maresa E. Duffya1, Mary Warda1, Anne M. Molloya4, John M. Scotta4, Per M. Uelanda5 and J. J. Straina1

a1 Northern Ireland Centre for Food and Health (NICHE), University of Ulster, Coleraine, County Londonderry BT52 1SA, UK

a2 Division of Population Health and Information, Alberta Cancer Board, Edmonton, AB, Canada

a3 Department of Nutrition and Dietetics, Monash University, Clayton, VIC, Australia

a4 Department of Clinical Medicine and School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Republic of Ireland

a5 Section for Pharmacology, Institute of Medicine, University of Bergen, and Haukeland University Hospital, Bergen, Norway


Choline is an essential nutrient and can also be obtained by de novo synthesis via an oestrogen responsive pathway. Choline can be oxidised to the methyl donor betaine, with short-term supplementation reported to lower plasma total homocysteine (tHcy); however, the effects of longer-term choline supplementation are less clear. We investigated the effect of choline supplementation on plasma concentrations of free choline, betaine and tHcy and B-vitamin status in postmenopausal women, a group more susceptible to low choline status. We also assessed whether supplementation altered plasma lipid profiles. In this randomised, double-blinded, placebo-controlled study, forty-two healthy postmenopausal women received 1 g choline per d (as choline bitartrate), or an identical placebo supplement with their habitual diet. Fasting blood samples were collected at baseline, week 6 and week 12. Administration of choline increased median choline and betaine concentrations in plasma, with significant effects evident after 6 weeks of supplementation (P < 0·001) and remaining significant at 12 weeks (P < 0·001); no effect was observed on folate status or on plasma lipids. Choline supplementation induced a median (25th, 75th percentile) change in plasma tHcy concentration at week 6 of − 0·9 ( − 1·6, 0·2) μmol, a change which, when compared to that observed in the placebo group 0·6 ( − 0·4, 1·9) μmol, approached statistical significance (P = 0·058). Choline supplementation at a dose of 1 g/d significantly increases the circulating concentration of free choline, and can also significantly increase the concentration of the methyl donor, betaine, thereby potentially enhancing the betaine–homocysteine methyltransferase-mediated remethylation of tHcy. This trial was registered at

(Received June 30 2011)

(Revised November 01 2011)

(Accepted November 08 2011)

(Online publication December 15 2011)


c1 Corresponding author: Dr J. M. W. Wallace, fax +44 28 7012 3023, email


Abbreviations: AI, adequate intake; BHMT, betaine–homocysteine methyltransferase; DMG, dimethylglycine; EGRac, erythrocyte glutathione reductase activation coefficient; HRT, hormone replacement therapy; tHcy, total homocysteine