Dataset Information

Effects of Lifestyle Intervention on Plasma Trimethylamine N-Oxide in Obese Adults.

ABSTRACT: Accumulating evidence linking trimethylamine N-oxide (TMAO) to cardiovascular disease (CVD) risk has prompted interest in developing therapeutic strategies to reduce its production. We compared two lifestyle intervention approaches: hypocaloric versus eucaloric diet, combined with exercise, on TMAO levels in relation to CVD risk factors. Sixteen obese adults (66.1 ± 4.4 years, BMI (body mass index): 35.9 ± 5.3 kg/m², fasting glucose: 106 ± 16 mg/dL, 2-h PPG (postprandial glucose): 168 ± 37 mg/dL) were randomly assigned to 12 weeks of exercise (5 days/week, 80?85% HR_max (maximal heart rate)) plus either a hypocaloric (HYPO) (-500 kcal) or a eucaloric (EU) diet. Outcomes included plasma TMAO, glucose metabolism (oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamps for glucose disposal rates (GDR)), exercise capacity (VO_2max, maximal oxygen consumption), abdominal adiposity (computed tomography scans), cholesterol, and triglycerides. Results showed that body composition (body weight, subcutaneous adiposity), insulin sensitivity, VO_2max, and cholesterol all improved (p < 0.05). HYPO decreased the percentage change in TMAO compared to an increase after EU (HYPO: -31 ± 0.4% vs. EU: 32 ± 0.6%, p = 0.04). Absolute TMAO levels were not impacted (HYPO: p = 0.09 or EU: p = 0.53 group). The change in TMAO after intervention was inversely correlated with baseline visceral adipose tissue (r = -0.63, p = 0.009) and GDR (r = 0.58, p = 0.002). A hypocaloric diet and exercise approach appears to be effective in reducing TMAO. Larger trials are needed to support this observation.

SUBMITTER: Erickson ML

PROVIDER: S-EPMC6356515 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Effects of Lifestyle Intervention on Plasma Trimethylamine N-Oxide in Obese Adults.

Erickson Melissa L ML Malin Steven K SK Wang Zeneng Z Brown J Mark JM Hazen Stanley L SL Kirwan John P JP

Nutrients 20190116 1

Accumulating evidence linking trimethylamine N-oxide (TMAO) to cardiovascular disease (CVD) risk has prompted interest in developing therapeutic strategies to reduce its production. We compared two lifestyle intervention approaches: hypocaloric versus eucaloric diet, combined with exercise, on TMAO levels in relation to CVD risk factors. Sixteen obese adults (66.1 ± 4.4 years, BMI (body mass index): 35.9 ± 5.3 kg/m², fasting glucose: 106 ± 16 mg/dL, 2-h PPG (postprandial glucose): 168 ± 37 mg/dL ...[more]

PMID: 30654453

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Project description:Abstract Objectives To determine the effect of adopting a Mediterranean-style eating pattern with different quantities of lean unprocessed red meat on the plasma concentration of Trimethylamine N-Oxide (TMAO), an emerging potential cardiovascular disease risk factor, in middle-aged adults classified as overweight or obese. Methods Thirty-nine adults (12 males and 27 females; age 46 ±10 years, BMI 30.6 ± 3.6 kg/m2; mean ± SD) participated in a randomized, crossover and controlled feeding trial. Each participant consumed a Mediterranean-style eating pattern for two 5-week intervention periods separated by ?4 weeks of consuming their unrestricted, self-selected diet (washout). The Mediterranean-style eating pattern contained either a commonly recommended amount of red meat (?200 g/wk, Med-200) or the average amount consumed in the U.S. (?500 g/wk, Med-500). Plasma samples were collected before (baseline) and at the end (post) of the two intervention periods and TMAO was measured by stable isotope dilution chromatography tandem mass spectrometry. Geometric means were compared with mixed model tests in SAS. Results Baseline TMAO concentrations were not different between interventions (Med-200 = 4.4 ± 2.7 and Med-500 = 5.2 ± 4.5 ?M, P = 0.476). These concentrations are similar to values reported in healthy adults. Post-intervention, TMAO was lower in Med-200 vs. Med-500 (3.1 ± 1.2 and 5.0 ± 2.6 ?M, P = 0.001). Conclusions The 2015–2020 Dietary Guidelines for Americans encourages adopting a Mediterranean-style eating pattern to promote cardiovascular health, including reduced blood pressure and improved lipid-lipoprotein profile. The current results suggest that adopting a Mediterranean-study eating pattern may also reduce the cardiovascular disease risk factor TMAO, but only when it contains a lower, recommended, amount of lean unprocessed red meat. The influences of animal- and plant-based foods consumed with a Mediterranean-style and other healthy eating patterns on emerging cardiovascular disease risk factors remain to be determined. This trial was registered at clinicaltrials.gov as NCT02573129. Funding Sources Supported by theBeef Checkoff, the Pork Checkoff, the NIH pre-doctoral training grant 5T32DK076540-08, the NIH-supported Indiana Clinical and Translational Sciences Institute and the USDA-ARS-Western Human Nutrition Research Center.

Project description:Background Trimethylamine N-oxide (TMAO) is a gut microbiota-dependent metabolite of dietary choline, L-carnitine, and phosphatidylcholine-rich foods. On the basis of experimental studies and patients with prevalent disease, elevated plasma TMAO may increase risk of atherosclerotic cardiovascular disease (ASCVD). TMAO is also renally cleared and may interact with and causally contribute to renal dysfunction. Yet, how serial TMAO levels relate to incident and recurrent ASCVD in community-based populations and the potential mediating or modifying role of renal function are not established. Methods and Results We investigated associations of serial measures of plasma TMAO, assessed at baseline and 7 years, with incident and recurrent ASCVD in a community-based cohort of 4131 (incident) and 1449 (recurrent) older US adults. TMAO was measured using stable isotope dilution liquid chromatography-tandem mass spectrometry (laboratory coefficient of variation, <6%). Incident ASCVD (myocardial infarction, fatal coronary heart disease, stroke, sudden cardiac death, or other atherosclerotic death) was centrally adjudicated using medical records. Risk was assessed by multivariable Cox proportional hazards regression, including time-varying demographics, lifestyle factors, medical history, laboratory measures, and dietary habits. Potential mediating effects and interaction by estimated glomerular filtration rate (eGFR) were assessed. During prospective follow-up, 1766 incident and 897 recurrent ASCVD events occurred. After multivariable adjustment, higher levels of TMAO were associated with a higher risk of incident ASCVD, with extreme quintile hazard ratio (HR) compared with the lowest quintile=1.21 (95% CI, 1.02-1.42; P-trend=0.029). This relationship appeared mediated or confounded by eGFR (eGFR-adjusted HR, 1.07; 95% CI, 0.90-1.27), as well as modified by eGFR (P-interaction <0.001). High levels of TMAO were associated with higher incidence of ASCVD in the presence of impaired renal function (eGFR <60 mL/min per 1.73 m2: HR, 1.56 [95% CI, 1.13-2.14]; P-trend=0.007), but not normal or mildly reduced renal function (eGFR ≥60 mL/min per 1.73 m2: HR, 1.03 [95% CI, 0.85-1.25]; P-trend=0.668). Among individuals with prior ASCVD, TMAO associated with higher risk of recurrent ASCVD (HR, 1.25 [95% CI, 1.01-1.56]; P-trend=0.009), without significant modification by eGFR. Conclusions In this large community-based cohort of older US adults, serial measures of TMAO were associated with higher risk of incident ASCVD, with apparent modification by presence of impaired renal function and with higher risk of recurrent ASCVD.

Project description:BackgroundThe microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) has been reported as a novel and independent risk factor for the development of cardiovascular and metabolic diseases, but the association with gestational diabetes mellitus (GDM) remains unclear.ObjectiveThe aim of this study was to investigate the association between plasma TMAO concentration and GDM in a 2-phase study.DesignA 2-phase design was used in the current study. An initial phase included 866 participants (433 GDM cases and 433 matched controls) with fasting blood samples collected at the time of GDM screening (24-32 wk of gestation). An independent-phase study, with 276 GDM cases and 552 matched controls who provided fasting blood samples before 20 wk of gestation and who had GDM screened during 24-32 wk of gestation, was nested within a prospective cohort study. These 2 studies were both conducted in Wuhan, China, and the incidence of GDM in the cohort study was 10.8%. Plasma TMAO concentrations were determined by stable isotope dilution liquid chromatography-tandem mass spectrometry. GDM was diagnosed according to the American Diabetes Association criteria by using an oral-glucose-tolerance test.ResultsIn the initial case-control study, the adjusted OR of GDM comparing the highest TMAO quartile with the lowest quartile was 1.94 (95% CI: 1.28, 2.93). Each SD increment of ln-transformed plasma TMAO was associated with 22% (95% CI: 5%, 41%) higher odds of GDM. In the nested case-control study, women in the highest quartile also had increased odds of GDM (adjusted OR: 2.06; 95% CI: 1.28, 3.31) compared with women in the lowest quartile, and the adjusted OR for GDM per SD increment of ln-transformed plasma TMAO was 1.26 (95% CI: 1.08, 1.47).ConclusionsConsistent findings from this 2-phase study indicate a positive association between plasma TMAO concentrations and GDM. Future studies are warranted to elucidate the underlying mechanisms. This trial was registered at www.clinicaltrials.gov as NCT03415295.

Project description:BackgroundGut microbiota profiles are closely related to cardiovascular diseases through mechanisms that include the reported deleterious effects of metabolites, such as trimethylamine N-oxide (TMAO), which have been studied as diagnostic and therapeutic targets. Moderate red wine (RW) consumption is reportedly cardioprotective, possibly by affecting the gut microbiota.ObjectivesTo investigate the effects of RW consumption on the gut microbiota, plasma TMAO, and the plasma metabolome in men with documented coronary artery disease (CAD) using a multiomics assessment in a crossover trial.MethodsWe conducted a randomized, crossover, controlled trial involving 42 men (average age, 60 y) with documented CAD comparing 3-wk RW consumption (250 mL/d, 5 d/wk) with an equal period of alcohol abstention, both preceded by a 2-wk washout period. The gut microbiota was analyzed via 16S rRNA high-throughput sequencing. Plasma TMAO was evaluated by LC-MS/MS. The plasma metabolome of 20 randomly selected participants was evaluated by ultra-high-performance LC-MS/MS. The effect of RW consumption was assessed by individual comparisons using paired tests during the abstention and RW periods.ResultsPlasma TMAO did not differ between RW intervention and alcohol abstention, and TMAO concentrations showed low intraindividual concordance over time, with an intraclass correlation coefficient of 0.049 during the control period. After RW consumption, there was significant remodeling of the gut microbiota, with a difference in β diversity and predominance of Parasutterella, Ruminococcaceae, several Bacteroides species, and Prevotella. Plasma metabolomic analysis revealed significant changes in metabolites after RW consumption, consistent with improved redox homeostasis.ConclusionsModulation of the gut microbiota may contribute to the putative cardiovascular benefits of moderate RW consumption. The low intraindividual concordance of TMAO presents challenges regarding its role as a cardiovascular risk biomarker at the individual level. This study was registered at clinical trials.gov as NCT03232099.

Dataset Information

Effects of Lifestyle Intervention on Plasma Trimethylamine N-Oxide in Obese Adults.

Publications

Effects of Lifestyle Intervention on Plasma Trimethylamine N-Oxide in Obese Adults.

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