Zeneng Wang1, W H Wilson Tang1,2, Thomas O'Connell3,4, Erwin Garcia3,5, Elias J Jeyarajah3, Xinmin S Li1, Xun Jia1, Taylor L Weeks1, Stanley L Hazen6,7. 1. Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Mail Code NC10, Cleveland, OH, 44195, USA. 2. Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH, USA. 3. LipoScience, Laboratory Corporation of America® Holdings, Raleigh, NC, 27616, USA. 4. Department of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. 5. Laboratory Corporation of America Holdings (Labcorp), Morrisville, NC, 27560, USA. 6. Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Mail Code NC10, Cleveland, OH, 44195, USA. hazens@ccf.org. 7. Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH, USA. hazens@ccf.org.
Abstract
PURPOSE: Some species of fish and seafood are high in trimethylamine N-oxide (TMAO), which accumulates in muscle where it protects against pressure and cold. Trimethylamine (TMA), the metabolic precursor to TMAO, is formed in fish during bacterial spoilage. Fish intake is promoted for its potential cardioprotective effects. However, numerous studies show TMAO has pro-atherothrombotic properties. Here, we determined the effects of fish or seafood consumption on circulating TMAO levels in participants with normal renal function. METHODS: TMAO and omega-3 fatty acid content were quantified across multiple different fish or seafood species by mass spectrometry. Healthy volunteers (n = 50) were recruited for three studies. Participants in the first study consented to 5 consecutive weekly blood draws and provided dietary recall for the 24 h preceding each draw. In the second study, TMAO levels were determined following defined low and high TMAO diets. Finally, participants consumed test meals containing shrimp, tuna, fish sticks, salmon or cod. TMAO levels were quantified by mass spectrometry in blood collected before and after dietary challenge. RESULTS: TMAO + TMA content varied widely across fish and seafood species. Consumption of fish sticks, cod, and to a lesser extent salmon led to significant increases in circulating TMAO levels. Within 1 day, circulating TMAO concentrations in all participants returned to baseline levels. CONCLUSIONS: We conclude that some fish and seafood contain high levels of TMAO, and may induce a transient elevation in TMAO levels in some individuals. Selection of low TMAO content fish is prudent for subjects with elevated TMAO, cardiovascular disease or impaired renal function.
PURPOSE: Some species of fish and seafood are high in trimethylamine N-oxide (TMAO), which accumulates in muscle where it protects against pressure and cold. Trimethylamine (TMA), the metabolic precursor to TMAO, is formed in fish during bacterial spoilage. Fish intake is promoted for its potential cardioprotective effects. However, numerous studies show TMAO has pro-atherothrombotic properties. Here, we determined the effects of fish or seafood consumption on circulating TMAO levels in participants with normal renal function. METHODS: TMAO and omega-3 fatty acid content were quantified across multiple different fish or seafood species by mass spectrometry. Healthy volunteers (n = 50) were recruited for three studies. Participants in the first study consented to 5 consecutive weekly blood draws and provided dietary recall for the 24 h preceding each draw. In the second study, TMAO levels were determined following defined low and high TMAO diets. Finally, participants consumed test meals containing shrimp, tuna, fish sticks, salmon or cod. TMAO levels were quantified by mass spectrometry in blood collected before and after dietary challenge. RESULTS: TMAO + TMA content varied widely across fish and seafood species. Consumption of fish sticks, cod, and to a lesser extent salmon led to significant increases in circulating TMAO levels. Within 1 day, circulating TMAO concentrations in all participants returned to baseline levels. CONCLUSIONS: We conclude that some fish and seafood contain high levels of TMAO, and may induce a transient elevation in TMAO levels in some individuals. Selection of low TMAO content fish is prudent for subjects with elevated TMAO, cardiovascular disease or impaired renal function.
Authors: Zeneng Wang; Adam B Roberts; Jennifer A Buffa; Bruce S Levison; Weifei Zhu; Elin Org; Xiaodong Gu; Ying Huang; Maryam Zamanian-Daryoush; Miranda K Culley; Anthony J DiDonato; Xiaoming Fu; Jennie E Hazen; Daniel Krajcik; Joseph A DiDonato; Aldons J Lusis; Stanley L Hazen Journal: Cell Date: 2015-12-17 Impact factor: 41.582
Authors: Chrysi Bogiatzi; Gregory Gloor; Emma Allen-Vercoe; Gregor Reid; Ruth G Wong; Bradley L Urquhart; Vincent Dinculescu; Kelsey N Ruetz; Thomas J Velenosi; Michael Pignanelli; J David Spence Journal: Atherosclerosis Date: 2018-04-17 Impact factor: 5.162
Authors: W H Wilson Tang; Zeneng Wang; Bruce S Levison; Robert A Koeth; Earl B Britt; Xiaoming Fu; Yuping Wu; Stanley L Hazen Journal: N Engl J Med Date: 2013-04-25 Impact factor: 91.245
Authors: Weifei Zhu; Jill C Gregory; Elin Org; Jennifer A Buffa; Nilaksh Gupta; Zeneng Wang; Lin Li; Xiaoming Fu; Yuping Wu; Margarete Mehrabian; R Balfour Sartor; Thomas M McIntyre; Roy L Silverstein; W H Wilson Tang; Joseph A DiDonato; J Mark Brown; Aldons J Lusis; Stanley L Hazen Journal: Cell Date: 2016-03-10 Impact factor: 41.582
Authors: Zeneng Wang; Elizabeth Klipfell; Brian J Bennett; Robert Koeth; Bruce S Levison; Brandon Dugar; Ariel E Feldstein; Earl B Britt; Xiaoming Fu; Yoon-Mi Chung; Yuping Wu; Phil Schauer; Jonathan D Smith; Hooman Allayee; W H Wilson Tang; Joseph A DiDonato; Aldons J Lusis; Stanley L Hazen Journal: Nature Date: 2011-04-07 Impact factor: 49.962
Authors: Gabriele Giacomo Schiattarella; Anna Sannino; Evelina Toscano; Giuseppe Giugliano; Giuseppe Gargiulo; Anna Franzone; Bruno Trimarco; Giovanni Esposito; Cinzia Perrino Journal: Eur Heart J Date: 2017-10-14 Impact factor: 29.983
Authors: Robert A Koeth; Zeneng Wang; Bruce S Levison; Jennifer A Buffa; Elin Org; Brendan T Sheehy; Earl B Britt; Xiaoming Fu; Yuping Wu; Lin Li; Jonathan D Smith; Joseph A DiDonato; Jun Chen; Hongzhe Li; Gary D Wu; James D Lewis; Manya Warrier; J Mark Brown; Ronald M Krauss; W H Wilson Tang; Frederic D Bushman; Aldons J Lusis; Stanley L Hazen Journal: Nat Med Date: 2013-04-07 Impact factor: 53.440