Browsing by Author "Steele, Cortney N."

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    Fasting and postprandial trimethylamine N-oxide in sedentary and endurance-trained males following a short-term high-fat diet
    Steele, Cortney N.; Baugh, Mary Elizabeth; Griffin, Laura E.; Neilson, Andrew P.; Davy, Brenda M.; Hulver, Matthew W.; Davy, Kevin P. (Wiley, 2021-08-01)
    Gut bacteria release trimethylamine (TMA) from dietary substrates. TMA is absorbed and is subsequently oxidized in the liver to produce trimethylamine N-oxide (TMAO). Plasma TMAO levels are positively correlated with risk for type 2 diabetes (T2D) and cardiovascular disease (CVD). High-fat diet (HFD) consumption has been reported to increase fasting and postprandial TMAO in sedentary individuals. However, whether the increase in TMAO with consumption of an HFD is observed in endurance-trained males is unknown. Healthy, sedentary (n = 17), and endurance-trained (n = 7) males consumed a 10-day eucaloric diet comprised of 55% carbohydrate, 30% total fat, and <10% saturated fat prior to baseline testing. Blood samples were obtained in a fasted state and for a 4-hour high-fat challenge (HFC) meal at baseline and then again following 5-day HFD (30% carbohydrate, 55% total fat, and 25% saturated fat). Plasma TMAO and TMA-moiety (choline, betaine, L-carnitine) concentrations were measured using isocratic ultraperformance liquid chromatography-tandem mass spectrometry. Age (23 ±3 vs. 22 ± 2 years) and body mass index (23.0 ± 3.0 vs. 23.5 ± 2.1 kg/m2) were similar (both p > 0.05) in the sedentary and endurance-trained group, respectively. VO2max was significantly higher in the endurance-trained compared with sedentary males (56.7 ± 8.2 vs. 39.9 ± 6.0 ml/kg/min). Neither the HFC nor the HFD evoked a detectable change in plasma TMAO (p > 0.05) in either group. Future studies are needed to identify the effects of endurance training on TMAO production.
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    Gut Microbiota-Generated Trimethylamine N-Oxide and Cardiometabolic Health in Humans
    Steele, Cortney N. (Virginia Tech, 2021-01-29)
    There is an association between the human microbiome and disease. Gut microbes metabolize dietary sources to release trimethylamine (TMA). TMA is absorbed and then oxidized by flavin monooxygenase 3 (FMO3) to form trimethylamine N-oxide (TMAO). Elevated TMAO is associated with increased risk of cardiovascular disease and type 2 diabetes; however, the causal nature is unclear. There is also limited evidence supporting the efficacy of strategies to reduce accumulation of TMAO. Therefore, the purpose of these studies is to determine the effects of increases in TMAO on cardiometabolic health. In study 1, healthy sedentary and endurance trained males consumed a high fat diet. Blood samples were obtained in a fasted state and every hour during a 4-hour high fat challenge. We hypothesized sedentary individuals would produce higher TMAO concentrations. In study 2, healthy sedentary individuals consumed an acute 1000 mg dose of choline (CHOL) and placebo (PLC). Fasted blood samples were collected, flow-mediated dilation (FMD) and oral glucose tolerance (OGT) were measured. In study 3, healthy sedentary individuals consumed 4-wks of CHOL and PLC. Fasted blood samples were collected, FMD and OGT were measured. We hypothesized acute and 4-wk choline supplementation would impair FMD and OGT. In study 1, neither fasting (1.49± 1.2 µM vs. 2.25 ± 1.4 µM, p>0.05) or postprandial TMAO changed significantly with the HFD in sedentary or endurance trained individuals even with the endurance group consuming more TMA dietary precursors. Study 2 found increased plasma TMAO concentrations after choline supplementation on day 1(PLC; 4.14 ± 2.6 μM vs. CHOL; 23.6 ± 33.8 μM, p=0.018) and day 2 (PLC; 5.13±4.9 μM vs. CHOL; 32.6±37.5 μM, p=0.082) however, there were no differences in OGT or FMD. Study 3 found no differences in FMD or OGT following 4-wks of choline consumption. In summary, there were no differences between sedentary and endurance trained individuals fasting or post-prandial TMAO. There was also no effect on acute or 4-wk supplementation of choline on FMD and OGT. More research is needed to understand effects of elevated TMAO on cardiometabolic health.
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    Impact of short-term flavanol supplementation on fasting plasma trimethylamine N- oxide concentrations in obese adults
    Angiletta, Chris J.; Griffin, Laura E.; Steele, Cortney N.; Baer, David J.; Novotny, Janet A.; Davy, Kevin P.; Neilson, Andrew P. (2018-10-01)
    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 (approximate to 5 M) compared to levels previously measured in healthy subjects (approximate to 1 M). 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.
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    Inulin Supplementation Does Not Reduce Plasma Trimethylamine N-Oxide Concentrations in Individuals at Risk for Type 2 Diabetes
    Baugh, Mary Elizabeth; Steele, Cortney N.; Angiletta, Christopher J.; Mitchell, Cassie M.; Neilson, Andrew P.; Davy, Brenda M.; Hulver, Matthew W.; Davy, Kevin P. (MDPI, 2018-06-20)
    Trimethylamine N-oxide (TMAO) is associated with type 2 diabetes (T2DM) and increased risk of adverse cardiovascular events. Prebiotic supplementation has been purported to reduce TMAO production, but whether prebiotics reduce fasting or postprandial TMAO levels is unclear. Sedentary, overweight/obese adults at risk for T2DM (n = 18) were randomized to consume a standardized diet (55% carbohydrate, 30% fat) with 10 g/day of either an inulin supplement or maltodextrin placebo for 6 weeks. Blood samples were obtained in the fasting state and hourly during a 4-h high-fat challenge meal (820 kcal; 25% carbohydrate, 63% fat; 317.4 mg choline, 62.5 mg betaine, 8.1 mg l-carnitine) before and after the diet. Plasma TMAO and trimethylamine (TMA) moieties (choline, l-carnitine, betaine, and γ-butyrobetaine) were measured using isocratic ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). There were no differences in fasting or postprandial TMAO or TMA moieties between the inulin and placebo groups at baseline (all p > 0.05). There were no significant changes in fasting or postprandial plasma TMAO or TMA moiety concentrations following inulin or placebo. These findings suggest that inulin supplementation for 6 weeks did not reduce fasting or postprandial TMAO in individuals at risk for T2DM. Future studies are needed to identify efficacious interventions that reduce plasma TMAO concentrations.