TY - JOUR

T1 - Circulating trimethylamine N-oxide in association with diet and cardiometabolic biomarkers

T2 - An international pooled analysis

AU - Yang, Jae Jeong

AU - Shu, Xiao Ou

AU - Herrington, David M.

AU - Moore, Steven C.

AU - Meyer, Katie A.

AU - Ose, Jennifer

AU - Menni, Cristina

AU - Palmer, Nicholette D.

AU - Eliassen, Heather

AU - Harada, Sei

AU - Tzoulaki, Ioanna

AU - Zhu, Huilian

AU - Albanes, Demetrius

AU - Wang, Thomas J.

AU - Zheng, Wei

AU - Cai, Hui

AU - Ulrich, Cornelia M.

AU - Guasch-Ferré, Marta

AU - Karaman, Ibrahim

AU - Fornage, Myriam

AU - Cai, Qiuyin

AU - Matthews, Charles E.

AU - Wagenknecht, Lynne E.

AU - Elliott, Paul

AU - Gerszten, Robert E.

AU - Yu, Danxia

N1 - Publisher Copyright: © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.

PY - 2021

Y1 - 2021

N2 - Background: Trimethylamine N-oxide (TMAO), a diet-derived, gut microbial-host cometabolite, has been linked to cardiometabolic diseases. However, the relations remain unclear between diet, TMAO, and cardiometabolic health in general populations from different regions and ethnicities. Objectives: To examine associations of circulating TMAO with dietary and cardiometabolic factors in a pooled analysis of 16 population-based studies from the United States, Europe, and Asia. Methods: Included were 32,166 adults (16,269 white, 13,293 Asian, 1247 Hispanic/Latino, 1236 black, and 121 others) without cardiovascular disease, cancer, chronic kidney disease, or inflammatory bowel disease. Linear regression coefficients (β) were computed for standardized TMAO with harmonized variables. Study-specific results were combined by random-effects meta-analysis. A false discovery rate <0.10 was considered significant. Results: After adjustment for potential confounders, circulating TMAO was associated with intakes of animal protein and saturated fat (β = 0.124 and 0.058, respectively, for a 5% energy increase) and with shellfish, total fish, eggs, and red meat (β = 0.370, 0.151, 0.081, and 0.056, respectively, for a 1 serving/d increase). Plant protein and nuts showed inverse associations (β = -0.126 for a 5% energy increase from plant protein and -0.123 for a 1 serving/d increase of nuts). Although the animal protein-TMAO association was consistent across populations, fish and shellfish associations were stronger in Asians (β = 0.285 and 0.578), and egg and red meat associations were more prominent in Americans (β = 0.153 and 0.093). Besides, circulating TMAO was positively associated with creatinine (β = 0.131 SD increase in log-TMAO), homocysteine (β = 0.065), insulin (β = 0.048), glycated hemoglobin (β = 0.048), and glucose (β = 0.023), whereas it was inversely associated with HDL cholesterol (β = -0.047) and blood pressure (β = -0.030). Each TMAO-biomarker association remained significant after further adjusting for creatinine and was robust in subgroup/sensitivity analyses. Conclusions: In an international, consortium-based study, animal protein was consistently associated with increased circulating TMAO, whereas TMAO associations with fish, shellfish, eggs, and red meat varied among populations. The adverse associations of TMAO with certain cardiometabolic biomarkers, independent of renal function, warrant further investigation.

AB - Background: Trimethylamine N-oxide (TMAO), a diet-derived, gut microbial-host cometabolite, has been linked to cardiometabolic diseases. However, the relations remain unclear between diet, TMAO, and cardiometabolic health in general populations from different regions and ethnicities. Objectives: To examine associations of circulating TMAO with dietary and cardiometabolic factors in a pooled analysis of 16 population-based studies from the United States, Europe, and Asia. Methods: Included were 32,166 adults (16,269 white, 13,293 Asian, 1247 Hispanic/Latino, 1236 black, and 121 others) without cardiovascular disease, cancer, chronic kidney disease, or inflammatory bowel disease. Linear regression coefficients (β) were computed for standardized TMAO with harmonized variables. Study-specific results were combined by random-effects meta-analysis. A false discovery rate <0.10 was considered significant. Results: After adjustment for potential confounders, circulating TMAO was associated with intakes of animal protein and saturated fat (β = 0.124 and 0.058, respectively, for a 5% energy increase) and with shellfish, total fish, eggs, and red meat (β = 0.370, 0.151, 0.081, and 0.056, respectively, for a 1 serving/d increase). Plant protein and nuts showed inverse associations (β = -0.126 for a 5% energy increase from plant protein and -0.123 for a 1 serving/d increase of nuts). Although the animal protein-TMAO association was consistent across populations, fish and shellfish associations were stronger in Asians (β = 0.285 and 0.578), and egg and red meat associations were more prominent in Americans (β = 0.153 and 0.093). Besides, circulating TMAO was positively associated with creatinine (β = 0.131 SD increase in log-TMAO), homocysteine (β = 0.065), insulin (β = 0.048), glycated hemoglobin (β = 0.048), and glucose (β = 0.023), whereas it was inversely associated with HDL cholesterol (β = -0.047) and blood pressure (β = -0.030). Each TMAO-biomarker association remained significant after further adjusting for creatinine and was robust in subgroup/sensitivity analyses. Conclusions: In an international, consortium-based study, animal protein was consistently associated with increased circulating TMAO, whereas TMAO associations with fish, shellfish, eggs, and red meat varied among populations. The adverse associations of TMAO with certain cardiometabolic biomarkers, independent of renal function, warrant further investigation.

KW - biomarker

KW - cardiovascular disease

KW - Consortium of Metabolomics Studies

KW - diet

KW - trimethylamine N-oxide

U2 - 10.1093/ajcn/nqaa430

DO - 10.1093/ajcn/nqaa430

M3 - Journal article

C2 - 33826706

AN - SCOPUS:85106538129

VL - 113

SP - 1145

EP - 1156

JO - American Journal of Clinical Nutrition

JF - American Journal of Clinical Nutrition

SN - 0002-9165

IS - 5

ER -