Original Article

European Journal of Clinical Nutrition (2008) 62, 386–394; doi:10.1038/sj.ejcn.1602725; published online 21 March 2007

Prospective study on dietary intakes of folate, betaine, and choline and cardiovascular disease risk in women

Contributors: GWD carried out the data analyses and wrote the manuscript. MRO, PV and YtvdS assisted and provided advice during all the stages of the work. All authors contributed in the discussion and interpretation of the results, and in drafting and editing the manuscript. No conflicts of interest are declared.

G W Dalmeijer1,3, M R Olthof1,2, P Verhoef1,2, M L Bots3 and Y T van der Schouw3

  1. 1Wageningen University, Wageningen, The Netherlands
  2. 2Wageningen Centre for Food Sciences, Wageningen, The Netherlands
  3. 3Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands

Correspondence: Dr YT van der Schouw, University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, STR 6.131, PO Box 85500, 3508 GA Utrecht, The Netherlands. E-mail: y.t.vanderschouw@umcutrecht.nl

Received 4 December 2005; Revised 17 August 2006; Accepted 13 February 2007; Published online 21 March 2007.





To investigate the association between dietary intakes of folate, betaine and choline and the risk of cardiovascular disease (CVD).



Prospective cohort study.



A total of 16165 women aged 49–70 years without prior CVD. Subjects were breast cancer screening participants in the PROSPECT–EPIC cohort, which is 1 of the 2 Dutch contributions to the European Prospective Investigation into Cancer and Nutrition (EPIC).



Each participant completed a validated food frequency questionnaire. Folate intake was calculated with the Dutch National Food Database. Betaine and choline intakes were calculated with the USDA database containing choline and betaine contents of common US foods. Data on coronary heart disease (CHD) events and cerebrovascular accident (CVA) events morbidity data were obtained from the Dutch Centre for Health Care Information.



During a median follow-up period of 97 months, 717 women were diagnosed with CVD. After adjustment, neither folate, nor betaine, nor choline intakes were associated with CVD (hazard ratios for highest versus lowest quartile were 1.23 (95% confidence interval 0.75; 2.01), 0.90 (0.69; 1.17), 1.04 (0.71; 1.53), respectively). In a subsample of the population, high folate and choline intakes were statistically significantly associated with lower homocysteine levels. High betaine intake was associated with slightly lower high-density lipoprotein (HDL)-cholesterol concentrations.



Regular dietary intakes of folate, betaine and choline were not associated with CVD risk in post-menopausal Dutch women. However, the effect of doses of betaine and choline beyond regular dietary intake – for example, via supplementation or fortification – remains unknown.


betaine, choline, folate, homocysteine, cholesterol, cardiovascular disease



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