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
N1 - Publisher Copyright:
© 2021 The Author(s). Published by Oxford University Press on behalf of the American Society for Nutrition.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - Background: Choline is an essential nutrient; however, the associations of choline and its related metabolites with cardiometabolic risk remain unclear. Objective: We examined the associations of circulating choline, betaine, carnitine, and dimethylglycine (DMG) with cardiometabolic biomarkers and their potential dietary and nondietary determinants. Methods: The 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. Results: We 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. Conclusions: Circulating 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 - Background: Choline is an essential nutrient; however, the associations of choline and its related metabolites with cardiometabolic risk remain unclear. Objective: We examined the associations of circulating choline, betaine, carnitine, and dimethylglycine (DMG) with cardiometabolic biomarkers and their potential dietary and nondietary determinants. Methods: The 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. Results: We 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. Conclusions: Circulating 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.
KW - betaine
KW - biomarkers
KW - cardiometabolic disease
KW - carnitine
KW - choline
KW - dimethylglycine
UR - http://www.scopus.com/inward/record.url?scp=85115444105&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85115444105&partnerID=8YFLogxK
U2 - 10.1093/ajcn/nqab152
DO - 10.1093/ajcn/nqab152
M3 - Article
C2 - 34020444
AN - SCOPUS:85115444105
SN - 0002-9165
VL - 114
SP - 893
EP - 906
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
IS - 3
ER -