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

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.