Submitted to: American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/3/2010
Publication Date: 3/10/2010
Citation: Lee, J.E., Jacques, P.F., Dougherty, L., Selhub, J., Giovannucci, E., Zeisel, S.H., Cho, E. 2010. Are dietary choline and betaine intakes determinants of total homocysteine concentration? American Journal of Clinical Nutrition. 91(5):1303-1310. Interpretive Summary: Methyl (one carbon) groups are essential for a number of metabolic processes, including, but not limited to, protein metabolism, modulation of gene expression and regulation of chromosomal stability. There are several nutrients including methionine, folate, and choline are involved in a very integrated manner in methyl group metabolism. It has been estimated that approximately 60% of methyl groups are derived from choline, 20% from dietary methionine, and 10-20% from folate, supporting the central role of choline as a methyl donor. Elevated homocysteine concentrations, a risk factor for stroke, heart disease and dementia, indicate a disturbance in one-carbon metabolism. Given the importance of folate in methyl group metabolism, it is important to consider the impact of folic acid fortification of the American diet on the relation of choline intake and one carbon metabolism. Therefore, in our current study we examined the association between homocysteine concentrations and choline intake and sought to determine whether the associations were affected by folic acid fortification. We assessed the association between choline and homocysteine in 1,325 male and 1,407 female participants in the sixth examination (1995-1998) of the Framingham Offspring Study. This examination began prior to the initiation of FDA-mandated enriched cereal grain fortification with folic acid and extended through the period of implementation of folic acid fortification, allowing us to study participants who were and were not exposed to fortification. Choline and intakes were associated with homocysteine concentrations, but only among participants with low folate status. The inverse association between choline intake and homocysteine concentrations was no longer present in the post-fortification period, possibly due to the low prevalence of individuals with inadequate folate after implementation of fortification. Methyl group metabolism would appear to be less dependent on choline intake in the presence of folic acid fortification.
Technical Abstract: Elevated homocysteine concentrations are associated with an increased risk of cardiovascular disease and a decline in cognitive function. Intakes of choline and betaine, as methyl donors, may affect homocysteine concentrations. The objective was to examine whether choline and betaine intakes, assessed from food-frequency questionnaires, are associated with total plasma homocysteine concentrations under both fasting and post–methionine-load conditions in both pre– and post– folic acid fortification periods in the United States. We assessed the association between choline and betaine intakes with fasting and post–methionine-load homocysteine concentrations using the United States Department of Agriculture (USDA)-revised food composition tables. We then evaluated whether the associations varied by folic acid fortification periods in 1,325 male and 1,407 female participants in the sixth examination (1995–1998) of the Framingham Offspring Study. A higher choline-plus-betaine intake was associated with lower concentrations of post–methionine-load homocysteine; the multivariate geometric means were 24.1 lmol/L (95% CI: 23.4, 24.9 lmol/L) in the top quintile of intake and 25.0 lmol/L (95% CI: 24.2, 25.7 lmol/L) in the bottom quintile (P for trend = 0.01). We found an inverse association between choline-plus-betaine intake and fasting homocysteine concentrations; the multivariate geometric mean fasting homocysteine concentrations were 9.6 lmol/L (95% CI: 9.3, 9.9 lmol/L) in the top quintile and 10.1 lmol/L (95% CI: 9.8, 10.4 lmol/L) in the bottom quintile (P for trend , 0.001). When we stratified by plasma folate and vitamin B-12 concentrations, the inverse association was limited to participants with low plasma folate or vitamin B-12 concentrations. In the postfortification period, the inverse association between choline-plus-betaine intake and either fasting or post–methionine-load homocysteine was no longer present. Choline and betaine intakes were associated with both fasting and post–methionine-load total homocysteine concentrations, especially in participants with low folate and vitamin B-12 status. The inverse association between choline and betaine intakes and homocysteine concentrations was no longer present in the postfortification period.