Effects Of A Lifestyle Intervention On Trimethylamine N-oxide (tmao) Concentrations In Overweight And Obese Adults

Abstract

PURPOSE: Trimethylamine N-Oxide (TMAO), a metabolite produced by gut microbiota and flavin-containing monooxygenase-3 (FMO3) of the liver, is found in foods high in carnitine, choline, and lecithin (e.g., egg yolks and full-fat dairy). The oxidation of choline that leads to betaine production also contributes to increased TMAO levels. Epidemiological studies have related TMAO concentrations to obesity and cardiovascular disease, yet few data exist on the effects of combined diet and exercise interventions on TMAO. METHODS: Twenty-six sedentary, overweight or obese adults (Age: 47.4 ± 10.7 yrs.; Weight: 95.1 ± 13.1 kg; BMI: 34.1 ± 3.2 kg/m2) completed a 10-week exercise and hypocaloric diet intervention to obtain clinically significant weight loss of ≥7%. Aerobic exercise volume began at 300 MET min per week and increased 50 MET min weekly until 700 MET min per week was reached. For 8 weeks, the OPTIFAST program included full meal replacement (~800 daily kcal). The last 2 weeks participants could replace 2 products with whole foods and increase intake (~1400 daily kcal). Weekly classes on behavior modification were also offered. Plasma blood samples were collected at baseline and follow-up and analyzed via nuclear magnetic resonance. RESULTS: At baseline, TMAO correlated with body weight (r = 0.40, p = 0.046), waist circumference (r = 0.40, p = 0.044), and RMR (r = 0.50, p = 0.009). Waist circumference (-7.6 cm), BMI (-3.1 kg/m2), body weight (-8.5 kg, -9.0%), total body fat (-1.7%), and triglycerides (-31.7 mg/dL) (all ps < 0.001) decreased following the intervention, however, there were no changes in TMAO (-0.3 μM, p = 0.292) or betaine (0.3 μM, p = 0.838) levels. Changes in TMAO were correlated with waist circumference (r = 0.50, p = 0.010), but not with change in body weight, body composition (lean mass, visceral mass, total fat mass), fitness, or cardiometabolic risk factors (all ps > 0.05), while changes in betaine were correlated with average RMR changes (r = -0.42, p = 0.037). CONCLUSIONS: Weight loss from a hypocaloric diet with aerobic exercise did not decrease TMAO, however, improvements in TMAO were associated with reductions in waist circumferenc in previously sedentary overweight and obese adults. Future studies should evaluate predictors of changes in TMAO during weight maintenance.