TY - JOUR

T1 - Associations of circulating choline and its related metabolites with cardiometabolic biomarkers

T2 - an international pooled analysis

AU - Pan, Xiong-Fei

AU - Yang, Jae Jeong

AU - Shu, Xiao-Ou

AU - Moore, Steven C

AU - Palmer, Nicholette D

AU - Guasch-Ferré, Marta

AU - Herrington, David M

AU - Harada, Sei

AU - Eliassen, Heather

AU - Wang, Thomas J

AU - Gerszten, Robert E

AU - Albanes, Demetrius

AU - Tzoulaki, Ioanna

AU - Karaman, Ibrahim

AU - Elliott, Paul

AU - Zhu, Huilian

AU - Wagenknecht, Lynne E

AU - Zheng, Wei

AU - Cai, Hui

AU - Cai, Qiuyin

AU - Matthews, Charles E

AU - Menni, Cristina

AU - Meyer, Katie A

AU - Lipworth, Loren P

AU - Ose, Jennifer

AU - Fornage, Myriam

AU - Ulrich, Cornelia M

AU - Yu, Danxia

PY - 2021

Y1 - 2021

N2 - BackgroundCholine is an essential nutrient; however, the associations of choline and its related metabolites with cardiometabolic risk remain unclear.ObjectiveWe examined the associations of circulating choline, betaine, carnitine, and dimethylglycine (DMG) with cardiometabolic biomarkers and their potential dietary and nondietary determinants.MethodsThe cross-sectional analyses included 32,853 participants from 17 studies, who were free of cancer, cardiovascular diseases, chronic kidney diseases, and inflammatory bowel disease. In each study, metabolites and biomarkers were log-transformed and standardized by means and SDs, and linear regression coefficients (β) and 95% CIs were estimated with adjustments for potential confounders. Study-specific results were combined by random-effects meta-analyses. A false discovery rate <0.05 was considered significant.ResultsWe observed moderate positive associations of circulating choline, carnitine, and DMG with creatinine [β (95% CI): 0.136 (0.084, 0.188), 0.106 (0.045, 0.168), and 0.128 (0.087, 0.169), respectively, for each SD increase in biomarkers on the log scale], carnitine with triglycerides (β = 0.076; 95% CI: 0.042, 0.109), homocysteine (β = 0.064; 95% CI: 0.033, 0.095), and LDL cholesterol (β = 0.055; 95% CI: 0.013, 0.096), DMG with homocysteine (β = 0.068; 95% CI: 0.023, 0.114), insulin (β = 0.068; 95% CI: 0.043, 0.093), and IL-6 (β = 0.060; 95% CI: 0.027, 0.094), but moderate inverse associations of betaine with triglycerides (β = −0.146; 95% CI: −0.188, −0.104), insulin (β = −0.106; 95% CI: −0.130, −0.082), homocysteine (β = −0.097; 95% CI: −0.149, −0.045), and total cholesterol (β = −0.074; 95% CI: −0.102, −0.047). In the whole pooled population, no dietary factor was associated with circulating choline; red meat intake was associated with circulating carnitine [β = 0.092 (0.042, 0.142) for a 1 serving/d increase], whereas plant protein was associated with circulating betaine [β = 0.249 (0.110, 0.388) for a 5% energy increase]. Demographics, lifestyle, and metabolic disease history showed differential associations with these metabolites.ConclusionsCirculating choline, carnitine, and DMG were associated with unfavorable cardiometabolic risk profiles, whereas circulating betaine was associated with a favorable cardiometabolic risk profile. Future prospective studies are needed to examine the associations of these metabolites with incident cardiovascular events.

AB - BackgroundCholine is an essential nutrient; however, the associations of choline and its related metabolites with cardiometabolic risk remain unclear.ObjectiveWe examined the associations of circulating choline, betaine, carnitine, and dimethylglycine (DMG) with cardiometabolic biomarkers and their potential dietary and nondietary determinants.MethodsThe cross-sectional analyses included 32,853 participants from 17 studies, who were free of cancer, cardiovascular diseases, chronic kidney diseases, and inflammatory bowel disease. In each study, metabolites and biomarkers were log-transformed and standardized by means and SDs, and linear regression coefficients (β) and 95% CIs were estimated with adjustments for potential confounders. Study-specific results were combined by random-effects meta-analyses. A false discovery rate <0.05 was considered significant.ResultsWe observed moderate positive associations of circulating choline, carnitine, and DMG with creatinine [β (95% CI): 0.136 (0.084, 0.188), 0.106 (0.045, 0.168), and 0.128 (0.087, 0.169), respectively, for each SD increase in biomarkers on the log scale], carnitine with triglycerides (β = 0.076; 95% CI: 0.042, 0.109), homocysteine (β = 0.064; 95% CI: 0.033, 0.095), and LDL cholesterol (β = 0.055; 95% CI: 0.013, 0.096), DMG with homocysteine (β = 0.068; 95% CI: 0.023, 0.114), insulin (β = 0.068; 95% CI: 0.043, 0.093), and IL-6 (β = 0.060; 95% CI: 0.027, 0.094), but moderate inverse associations of betaine with triglycerides (β = −0.146; 95% CI: −0.188, −0.104), insulin (β = −0.106; 95% CI: −0.130, −0.082), homocysteine (β = −0.097; 95% CI: −0.149, −0.045), and total cholesterol (β = −0.074; 95% CI: −0.102, −0.047). In the whole pooled population, no dietary factor was associated with circulating choline; red meat intake was associated with circulating carnitine [β = 0.092 (0.042, 0.142) for a 1 serving/d increase], whereas plant protein was associated with circulating betaine [β = 0.249 (0.110, 0.388) for a 5% energy increase]. Demographics, lifestyle, and metabolic disease history showed differential associations with these metabolites.ConclusionsCirculating choline, carnitine, and DMG were associated with unfavorable cardiometabolic risk profiles, whereas circulating betaine was associated with a favorable cardiometabolic risk profile. Future prospective studies are needed to examine the associations of these metabolites with incident cardiovascular events.

U2 - 10.1093/ajcn/nqab152

DO - 10.1093/ajcn/nqab152

M3 - Journal article

VL - 114

SP - 893

EP - 906

JO - American Journal of Clinical Nutrition

JF - American Journal of Clinical Nutrition

SN - 0002-9165

IS - 3

ER -