Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women
Wang Z, Bergeron N, Levison BS, Li XS, Chiu S, Jia X, Koeth RA, Li L, Wu Y, Tang WHW, Krauss RM, Hazen SL
European heart journal · 389 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- Randomized controlled trial (indexed by PubMed)
- Studied in
- People
- Main outcome
- Mechanisms only
- Intake measured by
- Food provided by researchers
Who paid for it
- Funding
- Independent funding
- Government
- Office of Dietary Supplements
- Nonprofit
- Fondation Leducq
- Government
- National Institutes of Health
- University or hospital
- University of California, San Francisco
- Government
- National Heart, Lung, and Blood Institute
- Government
- National Institute of Diabetes and Digestive and Kidney Diseases
- Government
- NIDDK NIH HHS
- University or hospital
- Clinical and Translational Science Unit
- Government
- NHLBI NIH HHS
- Nonprofit
- Leducq Foundation
- Grants
- National Heart, Lung, and Blood Institute (R01HL126827); National Institute of Diabetes and Digestive and Kidney Diseases (R01DK106000); Office of Dietary Supplements (R01 HL103866); Office of Dietary Supplements (HL126827); National Heart, Lung, and Blood Institute (R01HL130819); National Heart, Lung, and Blood Institute (R01HL103866); Office of Dietary Supplements (DK106000); Office of Dietary Supplements (HL103866); National Heart, Lung, and Blood Institute (R01 HL106003); National Institutes of Health (R01HL130819); National Institutes of Health (R01 DK106000); National Institutes of Health (RO1 HL106003); National Institutes of Health (HL103866); National Institutes of Health (R01HL126827)
Based on 10 listed funder(s).
Publication
- Published
- 2018-11-19 · Eur Heart J · vol. 40 · issue 7 · pp. 583–594
- Publisher
- Oxford University Press
- Cited
- 500 citations · more than 100% of similar papers · 24.7× the field average
- Impact
- Top 10% most cited in its field
- References
- 40 works
- Access
- Free to read
- Research areas
- Metabolism and Genetic Disorders · Gut microbiota and health · Folate and B Vitamins Research
- Keywords
- Medicine, White meat, Trimethylamine N-oxide, Red meat, Excretion, Food science, Cooked meat, Trimethylamine, Internal medicine, Biochemistry, Pathology
- MeSH
- animals, poultry, humans, methylamines, dietary proteins, diet, cross-over studies, feeding behavior, reference values, adult, aged, middle aged, female, male, young adult, renal elimination, red meat
12 authors
From US
- Zeneng WangCleveland Clinic Lerner College of Medicine
- Nathalie BergeronTouro University California
- Bruce S. LevisonCleveland Clinic Lerner College of Medicine
- Xinmin S. LiCleveland Clinic Lerner College of Medicine
- Sally Chiu
- Xun JiaCleveland Clinic Lerner College of Medicine
Abstract
Aims
Carnitine and choline are major nutrient precursors for gut microbiota-dependent generation of the atherogenic metabolite, trimethylamine N-oxide (TMAO). We performed randomized-controlled dietary intervention studies to explore the impact of chronic dietary patterns on TMAO levels, metabolism and renal excretion.
Methods and results
Volunteers (N = 113) were enrolled in a randomized 2-arm (high- or low-saturated fat) crossover design study. Within each arm, three 4-week isocaloric diets (with washout period between each) were evaluated (all meals prepared in metabolic kitchen with 25% calories from protein) to examine the effects of red meat, white meat, or non-meat protein on TMAO metabolism. Trimethylamine N-oxide and other trimethylamine (TMA) related metabolites were quantified at the end of each diet period. A random subset (N = 13) of subjects also participated in heavy isotope tracer studies. Chronic red meat, but not white meat or non-meat ingestion, increased plasma and urine TMAO (each >two-fold; P < 0.0001). Red meat ingestion also significantly reduced fractional renal excretion of TMAO (P < 0.05), but conversely, increased fractional renal excretion of carnitine, and two alternative gut microbiota-generated metabolites of carnitine, γ-butyrobetaine, and crotonobetaine (P < 0.05). Oral isotope challenge revealed red meat or white meat (vs. non-meat) increased TMA and TMAO production from carnitine (P < 0.05 each) but not choline. Dietary-saturated fat failed to impact TMAO or its metabolites.
Conclusion
Chronic dietary red meat increases systemic TMAO levels through: (i) enhanced dietary precursors; (ii) increased microbial TMA/TMAO production from carnitine, but not choline; and (iii) reduced renal TMAO excretion. Discontinuation of dietary red meat reduces plasma TMAO within 4 weeks.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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