Rikuta Hamaya1,2,3, Kerry L Ivey1,4,5, Dong H Lee1, Molin Wang6, Jun Li1, Adrian Franke7, Qi Sun1,8, Eric B Rimm1,8,9. 1. Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA. 2. Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. 3. Department of Cardiology, Tokyo Medical and Dental University, Tokyo, Japan. 4. Microbiome and Host Health Programme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia. 5. Department of Nutrition and Dietetics, College of Nursing and Health Sciences, Flinders University, Adelaide, South Australia, Australia. 6. Department of Biostatistics, Harvard TH Chan School of Public Health, Boston, MA, USA. 7. University of Hawaii Cancer Center, Honolulu, HI, USA. 8. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. 9. Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA.
Abstract
BACKGROUND: Trimethylamine-N-oxide (TMAO) is a compound that is present in seafood and produced through human gut microbial metabolism of its precursors. Previous studies have suggested that elevated TMAO concentrations are associated with an increased risk of cardiovascular events. However, the association between diet and TMAO concentrations in free-living adult populations has not been adequately described. OBJECTIVES: The objective of this study was to identify dietary predictors of plasma TMAO concentrations. METHODS: TMAO concentrations were assessed in 2 fasting plasma samples collected 6 mo apart among 620 healthy men. Short-term and long-term dietary intakes were assessed during the same time-frame of blood collections via repeated 7-d dietary records (7DDRs) and a semiquantitative food-frequency questionnaire (SFFQ), respectively. We grouped individual food items into 21 groups and regressed against averaged TMAO concentrations. We also assessed the association between dietary scores and TMAO concentrations. RESULTS: In models adjusted for demographic characteristics and mutually adjusted for food groups, SFFQ-assessments of fish and egg intakes were significantly associated with increased TMAO concentration (β = 0.082; 95% CI: 0.021, 0.14; P = 0.009 for fish; β = 0.065; 95% CI: 0.004, 0.13; P = 0.039 for egg). The positive association between fish consumption and TMAO concentration was replicated in the 7DDR-assessments (β = 0.12; 95% CI: 0.060, 0.18; P < 0.001). There was no association between red meat intake and TMAO concentrations. The unhealthful plant-based diet index (uPDI) was inversely associated (β = -0.013; 95% CI: -0.021, -0.005; P = 0.001) and healthy dietary scores were positively correlated with TMAO concentration. CONCLUSIONS: TMAO concentration was significantly associated with fish intake, but not with red meat consumption. uPDI, an unhealthy dietary pattern, was inversely related to TMAO concentration. As such, this study suggests that in free-living populations, higher circulating concentrations of TMAO cannot simply be interpreted as a marker of unhealthy food intake or an unhealthy dietary pattern.
BACKGROUND:Trimethylamine-N-oxide (TMAO) is a compound that is present in seafood and produced through human gut microbial metabolism of its precursors. Previous studies have suggested that elevated TMAO concentrations are associated with an increased risk of cardiovascular events. However, the association between diet and TMAO concentrations in free-living adult populations has not been adequately described. OBJECTIVES: The objective of this study was to identify dietary predictors of plasma TMAO concentrations. METHODS:TMAO concentrations were assessed in 2 fasting plasma samples collected 6 mo apart among 620 healthy men. Short-term and long-term dietary intakes were assessed during the same time-frame of blood collections via repeated 7-d dietary records (7DDRs) and a semiquantitative food-frequency questionnaire (SFFQ), respectively. We grouped individual food items into 21 groups and regressed against averaged TMAO concentrations. We also assessed the association between dietary scores and TMAO concentrations. RESULTS: In models adjusted for demographic characteristics and mutually adjusted for food groups, SFFQ-assessments of fish and egg intakes were significantly associated with increased TMAO concentration (β = 0.082; 95% CI: 0.021, 0.14; P = 0.009 for fish; β = 0.065; 95% CI: 0.004, 0.13; P = 0.039 for egg). The positive association between fish consumption and TMAO concentration was replicated in the 7DDR-assessments (β = 0.12; 95% CI: 0.060, 0.18; P < 0.001). There was no association between red meat intake and TMAO concentrations. The unhealthful plant-based diet index (uPDI) was inversely associated (β = -0.013; 95% CI: -0.021, -0.005; P = 0.001) and healthy dietary scores were positively correlated with TMAO concentration. CONCLUSIONS:TMAO concentration was significantly associated with fish intake, but not with red meat consumption. uPDI, an unhealthy dietary pattern, was inversely related to TMAO concentration. As such, this study suggests that in free-living populations, higher circulating concentrations of TMAO cannot simply be interpreted as a marker of unhealthy food intake or an unhealthy dietary pattern.
Authors: Changzheng Yuan; Donna Spiegelman; Eric B Rimm; Bernard A Rosner; Meir J Stampfer; Junaidah B Barnett; Jorge E Chavarro; Amy F Subar; Laura K Sampson; Walter C Willett Journal: Am J Epidemiol Date: 2017-04-01 Impact factor: 4.897
Authors: Megu Y Baden; Gang Liu; Ambika Satija; Yanping Li; Qi Sun; Teresa T Fung; Eric B Rimm; Walter C Willett; Frank B Hu; Shilpa N Bhupathiraju Journal: Circulation Date: 2019-08-12 Impact factor: 29.690
Authors: Zeneng Wang; Bruce S Levison; Jennie E Hazen; Lillian Donahue; Xin-Min Li; Stanley L Hazen Journal: Anal Biochem Date: 2014-04-01 Impact factor: 3.365
Authors: Zeneng Wang; Nathalie Bergeron; Bruce S Levison; Xinmin S Li; Sally Chiu; Xun Jia; Robert A Koeth; Lin Li; Yuping Wu; W H Wilson Tang; Ronald M Krauss; Stanley L Hazen Journal: Eur Heart J Date: 2019-02-14 Impact factor: 35.855
Authors: Rachel Gibson; Chung-Ho E Lau; Ruey Leng Loo; Timothy M D Ebbels; Elena Chekmeneva; Alan R Dyer; Katsuyuki Miura; Hirotsugu Ueshima; Liancheng Zhao; Martha L Daviglus; Jeremiah Stamler; Linda Van Horn; Paul Elliott; Elaine Holmes; Queenie Chan Journal: Am J Clin Nutr Date: 2020-02-01 Impact factor: 7.045
Authors: Meng Wang; Zeneng Wang; Stanley L Hazen; Dariush Mozaffarian; Yujin Lee; Heidi T M Lai; Marcia C de Oliveira Otto; Rozenn N Lemaitre; Amanda Fretts; Nona Sotoodehnia; Matthew Budoff; Joseph A DiDonato; Barbara McKnight; W H Wilson Tang; Bruce M Psaty; David S Siscovick Journal: Arterioscler Thromb Vasc Biol Date: 2022-08-01 Impact factor: 10.514
Authors: Mauro Lombardo; Giovanni Aulisa; Daniele Marcon; Gianluca Rizzo; Maria Grazia Tarsisano; Laura Di Renzo; Massimo Federici; Massimiliano Caprio; Antonino De Lorenzo Journal: Nutrients Date: 2021-04-23 Impact factor: 5.717
Authors: Vienna E Brunt; Abigail G Casso; Rachel A Gioscia-Ryan; Zachary J Sapinsley; Brian P Ziemba; Zachary S Clayton; Amy E Bazzoni; Nicholas S VanDongen; James J Richey; David A Hutton; Melanie C Zigler; Andrew P Neilson; Kevin P Davy; Douglas R Seals Journal: Hypertension Date: 2021-05-10 Impact factor: 9.897
Authors: Kristen L McArthur; Mingyu Zhang; Xiumei Hong; Guoying Wang; Jessie P Buckley; Xiaobin Wang; Noel T Mueller Journal: Curr Dev Nutr Date: 2022-06-21
Authors: Hannah Craven; Dagmara McGuinness; Sarah Buchanan; Norman Galbraith; David H McGuinness; Brian Jones; Emilie Combet; Denise Mafra; Peter Bergman; Anne Ellaway; Peter Stenvinkel; Umer Z Ijaz; Paul G Shiels Journal: Sci Rep Date: 2021-06-16 Impact factor: 4.996
Authors: Harold E Bays; Pam R Taub; Elizabeth Epstein; Erin D Michos; Richard A Ferraro; Alison L Bailey; Heval M Kelli; Keith C Ferdinand; Melvin R Echols; Howard Weintraub; John Bostrom; Heather M Johnson; Kara K Hoppe; Michael D Shapiro; Charles A German; Salim S Virani; Aliza Hussain; Christie M Ballantyne; Ali M Agha; Peter P Toth Journal: Am J Prev Cardiol Date: 2021-01-23