Usual choline and betaine dietary intake and incident coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Stu

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Low dietary intake of the essential nutrient choline and its metabolite betaine may increase atherogenesis both through effects on homocysteine methylation pathways as well as through choline's antioxidants properties. Nutrient values for many common foods for choline and betaine have recently become available in the U.S. nutrient composition database. Our objective was to assess the association of dietary intake of choline and betaine with incident coronary heart disease (CHD), adjusting for dietary intake measurement error.


We conducted a prospective investigation of the relation between usual intake of choline and betaine with the risk of CHD in 14,430 middle-aged men and women of the biethnic Atherosclerosis Risk in Communities study. A semi-quantitative food frequency questionnaire was used to assess nutrient intake. Proportional hazard regression models were used to calculate the risk of incident CHD. A regression calibration method was used to adjust for measurement error.

Results During an average 14 years of follow-up (1987├óÔé¼ÔÇ£2002), 1,072 incident CHD events were documented. Compared with the lowest quartile of intake, incident CHD risk was slightly and non-significantly higher in the highest quartile of choline and choline plus betaine, HR = 1.22 (0.91, 1.64) and HR = 1.14 (0.85, 1.53), controlling for age, sex, education, total energy intake, dietary intakes of folate, methionine and vitamin B6. No association was found between dietary choline intake and incident CHD when correcting for measurement error.

Higher intakes of choline and betaine were not protective for incident CHD. Similar investigations in other populations are of interest.

The essential nutrient choline, its metabolite betaine, as well as folate and methionine are all metabolically interrelated by transmethylation pathways [1-4]. Through under-methylation of DNA, low dietary intakes of choline and betaine alter the epigenetic regulation for a series of genes reported to accelerate the atherogenic process [5,6]. Like folate, choline is involved in the methylation of homocysteine (a putative cardiovascular risk factor) to methionine through a betaine-dependent pathway. When folate availability diminishes there is an increased demand for betaine as a methyl donor [7]. Conversely, when choline availability is decreased the demand for folate is increased [8]. Because of the interrelationship of folate and choline pathways, both nutrients should be considered in epidemiological studies assessing the relationship between dietary intake of these compounds and cardiovascular disease.


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