Choline consumption in Norway : Dietary sources, association with one-carbon and lipid metabolism and cardiovascular disease risk

Abstract

Background: Choline is an essential nutrient involved in a wide variety of physiological functions. Through its metabolite betaine, it is closely connected to the one-carbon metabolism, and phosphatidylcholine (PC) is essential for the formation and secretion of very-low-density-lipoprotein in the liver, connecting choline to lipid metabolism. Choline is found in foods and in the body in different forms. Food products of animal origin contain higher amounts of total choline, and mainly fat-soluble forms, per unit weight compared to plant-derived products. An adequate intake (AI) has been set in the US and Europe, however, not yet in the Nordic countries.

Both the one-carbon and lipid metabolism are closely related to the risk of chronic diseases. However, few studies have investigated the association between dietary choline intake and cardiovascular disease, and findings are contradictory. In Paper I and II the association between dietary choline intake and the risk of acute myocardial infarction (AMI) in patients with pre-existing coronary heart disease was addressed. Further, dietary intake of total choline and individual choline forms and their dietary contributors have not been investigated, which was the objective of Paper III and IV. Additionally, in Paper IV, the association between choline intake and plasma concentrations of one-carbon and lipid metabolites was explored in healthy community-dwelling adults.

Methods: Western Norway B-vitamin Intervention Trial (WENBIT): Patients with stable angina pectoris from WENBIT (n=1981 and 1929, for Paper I and Paper II respectively) were included. Dietary data was derived from a food frequency questionnaire (FFQ) and choline content of food items was quantified using the U.S. Department of Agriculture (USDA) Database for Choline Content of Common Foods, release 2. Cox regression models were used to estimate the association between total choline intake or intake of individual choline forms and risk of AMI. Effect modification was investigated for trimethylamine N-oxide (TMAO) and trimethyllysine (TML) and mediation analysis was applied considering TMAO as a mediator.

Hordaland Health Study 1997-1999 (HUSK): HUSK included community-dwelling adults, and 5746 of these were included in the current analysis. Dietary data were derived from the same FFQ used in the WENBIT cohort and choline intake was estimated using the USDA choline database. To explore the relationship between one-carbon and lipid metabolites and total dietary choline intake, choline intake was modeled as a polynomial spline.

Results: The geometric mean (95% prediction interval) total energy-adjusted choline intake was 287 (182, 437) mg/d and 260 (170, 389) mg/d in the WENBIT and HUSK populations, respectively. PC was the main consumed form in both study populations and eggs contributed most to total choline intake (12.6% and 15.3% in WENBIT and HUSK respectively). Other main dietary contributors were milk, vegetables, potatoes, and lean fish. Most of the individual choline forms were primarily obtained from animal-based food sources, apart from free choline. In patients with SAP, increased intakes of energy-adjusted total choline (Hazard ratio (HR) [95% confidence interval] 1.10 [1.02, 1.19]), PC (1.23 [1.07, 1.41]), and sphingomyelin (1.15 [1.03, 1.30]) were associated with higher AMI risk. We did not observe any effect modification by plasma TMAO and TML, nor any mediation by TMAO. In community-dwelling adults, dietary choline consumption showed clear associations with plasma concentration of one-carbon metabolites and to a lesser extent with serum lipid metabolites.

Conclusion: Choline was mainly consumed in the form of PC and mostly obtained from animal food sources. The self-reported choline intake was below the established AI for most of the participants. Further, total dietary choline, PC, and sphingomyelin were positively associated with AMI risk. Also, dietary choline was associated with the plasma concentration of metabolites of the one-carbon and lipid metabolism.