Trimethylamine N-oxide (TMAO) is linked to cardiovascular disease (CVD) through partly altered central hemodynamics. We sought to examine if a low-calorie diet plus interval exercise (LCD+INT) intervention reduces TMAO more than a low-calorie diet (LCD) program alone in relation to hemodynamics, prior to clinically meaningful weight loss. Women with obesity were randomized to 2 weeks of LCD (n = 12, ~1200 kcal/d) or LCD+INT (n = 11; 60 min/d, 3 min at 90% and 50% HRpeak, respectively). A 180 min 75 g OGTT was performed to assess fasting TMAO and precursors (carnitine, choline, betaine, and trimethylamine (TMA)) as well as insulin sensitivity. Pulse wave analysis (applanation tonometry) including augmentation index (AIx75), pulse pressure amplification (PPA), forward (Pf) and backward pressure (Pb) waveforms, and reflection magnitude (RM) at 0, 60, 120, and 180 min was also analyzed. LCD and LCD+INT comparably reduced weight (p < 0.01), fasting glucose (p = 0.05), insulin tAUC_180min (p < 0.01), choline (p < 0.01), and Pf (p = 0.04). Only LCD+INT increased VO₂peak (p = 0.03). Despite no overall treatment effect, a high baseline TMAO was associated with decreased TMAO (r = -0.45, p = 0.03). Reduced TMAO was related to increased fasting PPA (r = -0.48, p = 0.03). Lowered TMA and carnitine correlated with higher fasting RM (r = -0.64 and r = -0.59, both p < 0.01) and reduced 120 min Pf (both, r = 0.68, p < 0.01). Overall, treatments did not lower TMAO. Yet, people with high TMAO pre-treatment reduced TMAO after LCD, with and without INT, in relation to aortic waveforms.

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