Prospective study on dietary intakes of folate, betaine, and choline and cardiovascular disease risk in women
To investigate the association between dietary intakes of folate, betaine and choline and the risk of cardiovascular disease (CVD). Prospective cohort study. Subjects: A total of 16 165 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.
Get notified about updates to this publicationFollow publication
[Show abstract] [Hide abstract] ABSTRACT: α-Glycerophosphocholine (GPC) is a putative acetylcholine precursor that potentially increases growth hormone secretion through the action of acetylcholine-stimulated catecholamine. The aim of this study was to investigate acute physiologic responses to a single intake of GPC. Eight healthy male subjects (25 ± 1 y old) ingested GPC 1000 mg or a placebo in a double-blind randomized crossover study. Fasting blood samples were obtained before the administration of GPC (baseline) and 60 and 120 min after administration. All subjects repeated the identical protocol using the placebo. Plasma free choline levels significantly increased at 60 and 120 min after GPC administration. Plasma growth hormone secretion was increased significantly 60 min after taking GPC, whereas no significant change was observed with the placebo. In addition, the serum free fatty acid was increased 120 min after GPC ingestion, but no changes were seen with the placebo. Moreover, serum acetoacetate and 3-hydroxybutyrate levels, which are indices of hepatic fat oxidation, were increased at 120 min after taking GPC, whereas the placebo had no effect. These findings suggest that a single dose of GPC increases growth hormone secretion and hepatic fat oxidation, with concomitant increases in choline levels, in young adults.0Comments 5Citations
- "However, the sample in the present study was small; therefore, further investigation is needed to confirm these results. There is a strong potential for GPC supplements to improve health; for example, choline supplementation may acutely decrease the risk of cardiovascular diseases [24,25] and increase learning and memory performance . These findings bolster the need for an improved understanding of the mechanism of the action of GPC in healthy subjects. "
[Show abstract] [Hide abstract] ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is the most common liver condition in the developed world and may progress to more severe forms of disease such as cirrhosis or liver cancer. Thus, steps taken to reduce its prevalence through preventative nutritional approaches such as functional foods and nutraceuticals (FFN) should be pursued. It is well known that certain lipotropic nutrients such as choline and metabolites betaine and phosphatidylcholine (PC; lecithin) could prevent or alleviate fatty liver through a variety of mechanisms, including increased hepatic VLDL secretion. Animal and human studies have demonstrated clear protective effects of choline, betaine and PC for NAFLD as well as possible roles in CVD prevention from epidemiological data. Currently, choline consumption is below dietary recommendations due in large part to a general lack of understanding regarding the importance of this nutrient for human health. As lecithin is commonly added (in small amounts) in many processed foods due to its functional capabilities, it is projected that increasing its abundance in the food supply and increasing consumer education and acceptance of lecithin-based functional foods and nutraceuticals may represent a progressive step towards preventing liver and whole-body metabolic pathologies in many areas of the world.0Comments 4Citations
- "Because inflammation plays such a key role in atherogenesis, or the development of plaque build-up in arteries, the authors concluded that high intake of these nutrients may protect against CVD. However, two large prospective studies conducted in 2007 based on the subjects in the Dutch PROSPECT-EPIC cohort  and the Atherosclerosis Risk in Communities (ARIC) study  demonstrated no association between choline and betaine consumption and CVD. It has been noted, however, that these null findings may be due to the large measurement error of intake estimates for choline and betaine . "
[Show abstract] [Hide abstract] ABSTRACT: Betaine is an essential osmolyte and source of methyl groups and comes from either the diet or by the oxidation of choline. Its metabolism methylates homocysteine to methionine, also producing N,N-dimethylglycine. Betaine insufficiency is associated with the metabolic syndrome, lipid disorders and diabetes, and may have a role in vascular and other diseases. Betaine is important in development, from the pre-implantation embryo to infancy. Betaine supplementation improves animal and poultry health, but the effect of long-term supplementation on humans is not known, though reports that it improves athletic performance will stimulate further studies. Subsets of the population that may benefit from betaine supplementation could be identified by the laboratory, in particular those who excessively lose betaine through the urine.Plasma betaine is highly individual, in women typically 20–60 μmol/L and in men 25–75 μmol/L. Plasma dimethylglycine is typically < 10 μmol/L. Urine betaine excretion is minimal, even following a large betaine dose. It is constant, highly individual and normally < 35 mmol/mole creatinine. The preferred method of betaine measurement is by LC-MS/MS, which is rapid and capable of automation. Slower HPLC methods give comparable results. Proton NMR spectrometry is another option but caution is needed to avoid confusion with trimethylamine-N-oxide.0Comments 118Citations
- "However, there are few studies that directly test a connection between betaine supply and vascular disease. In healthy subjects, short-or medium-term betaine supplementation does not improve flow-mediated vasodilation, a marker of endothelial function, despite reduced homocysteine , and prospective general population studies in Holland  and the United States  failed to detect an association between the intake of choline and betaine and cardiovascular disease. Thus, the claims made that the nutritional supplement " TMG " will protect against vascular disease have not been substantiated , though the effects of long-term use of supplemental betaine have not been tested, and it would be particularly interesting to see the results of studies on at-risk sections of the population (for example, those with the metabolic syndrome or those who are losing excessive betaine) that should benefit from an increased betaine intake. "
Discover cutting-edge research
ResearchGate is where you can find and access the latest publications from your field of research.Discover more