Impact of short-term flavanol supplementation on fasting plasma trimethylamine N-oxide concentrations in obese adults

Authors: ANGILETTA, CHRIS - Virginia Polytechnic Institution & State University; GRIFFIN, LAURA - Virginia Polytechnic Institution & State University; STEELE, CORTEY - Virginia Polytechnic Institution & State University; Baer, David; Novotny, Janet; DAVY, KEVIN - Virginia Polytechnic Institution & State University; NEILSON, ANDREW - Virginia Polytechnic Institution & State University

Submitted to: Food & Function
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/23/2018
Publication Date: 9/25/2018
Citation: Angiletta, C.J., Griffin, L.E., Steele, C.N., Baer, D.J., Novotny, J., Davy, K.P., Neilson, A.P. 2018. Impact of short-term flavanol supplementation on fasting plasma trimethylamine N-oxide concentrations in obese adults. Food & Function. 9:5350-5361. https://doi.org/10.1039/C8FO00962G.
DOI: https://doi.org/10.1039/C8FO00962G

Interpretive Summary: In the past decade, there has been increasing appreciation for an association between the gut microbiota and heart disease. The gut microbiome metabolizes choline and carnitine (both provided by the diet), and produces trimethylamine (TMA), which is then converted in the liver to trimethylamine N-oxide (TMAO). Higher concentration of TMAO is associated with cardiovascular disease and all-cause mortality risk. Dietary flavanols modulate the composition and function of the gut microbiome. Therefore, the possibility exists that these compounds could change microbial production of TMA and therefore reduce circulating TMAO. To determine if dietary flavanols reduce TMA and TMAO concentrations, a secondary analysis was performed on blood samples from a clinical study in which obese subjects at risk for insulin resistance consumed tea or cocoa flavanols (three levels of cacoa flavanols) in a randomized crossover design while consuming a controlled diet. None of the dietary interventions (tea or any level of cocoa) significantly altered TMAO levels. Individual variability for choline and carnitine was relatively low. However, TMAO exhibited somewhat greater inter-individual variability. No differences in mean TMAO concentrations observed across interventions were seen based on separating subjects by glycemic status, body mass index (BMI), race, age, or gender. However, subject minimum and maximum values observed across the interventions appeared to be more strongly associated with glycemic status and age than mean values across interventions, suggesting that average TMAO values over time may be less useful than maximum or minimum values as markers of disease risk. The present results suggest that a short-term flavanol intervention does not reduce fasting TMAO levels in subjects with elevated circulating TMAO.

Technical Abstract: The gut microbiome metabolizes choline and carnitine to release trimethylamine (TMA), which subsequently undergoes hepatic conversion to trimethylamine N-oxide (TMAO). Elevated TMAO levels are associated with cardiovascular disease and all-cause mortality risk. Dietary flavanols modulate the composition and function of the gut microbiome. Therefore, the possibility exists that these compounds could reduce intestinal TMA production and lower circulating TMAO. However, this hypothesis has never been tested in humans. A secondary analysis was performed on blood samples from a clinical study in which obese subjects at risk for insulin resistance consumed tea or cocoa flavanols in a randomized crossover design while consuming a controlled diet. These subjects generally had elevated TMAO levels (~5 µM) compared to levels previously measured in healthy subjects (~1 µM). None of the interventions significantly altered TMAO levels. Individual variability for choline and carnitine was relatively low. However, TMAO exhibited somewhat greater inter-individual variability. No differences in mean TMAO concentrations observed across interventions were seen based on separating subjects by glycemic status, body mass index (BMI), race, age, or gender. However, subject minimum and maximum values observed across the interventions appeared to be more strongly associated with glycemic status and age than mean values across interventions, suggesting that average TMAO values over time may be less useful than maximum or minimum values as markers of disease risk. Traditional physiological characteristics do not appear to predict TMAO responsiveness to flavanol interventions. However, African-American subjects appeared less responsive compared to non-Hispanic white subjects for both green tea and high cocoa treatments, and female subjects appeared less responsive than males for the high cocoa treatment. The present results suggest that a short-term flavanol intervention does not generally reduce fasting TMAO levels in subjects with elevated circulating TMAO.