Background Consumption of trimethylamine N ‐oxide (TMAO) precursors, such as carnitine found in lean beef, raises circulating TMAO concentrations; however, a healthy dietary pattern may attenuate these effects. Methods This randomized, 4‐period crossover, controlled‐feeding study investigated the effects of Mediterranean‐style (MED) diets (carbohydrate 42%, protein 17%, fat 41%) with 14 (MED0.5; 0.5 oz), 71 (MED2.5; 2.5 oz), and 156 (MED5.5; 5.5 oz) g/day/2000 kcal of lean beef, compared with an average American diet (AAD; carbohydrate 52%, protein 15%, fat 33%; 71 g/day/2000 kcal beef), on gut microbiota composition and plasma, urinary, and fecal metabolites including TMAO and precursor molecules. Thirty generally healthy individuals consumed each diet for 4 weeks with a ≥1‐week washout. Fasting blood samples, 24‐hour urine samples, and fecal samples were collected at baseline and at the end of each 4‐week diet period. Metabolites were measured by proton nuclear magnetic resonance and liquid chromatography/mass spectrometry. Gut microbiota composition was measured using amplicon sequencing of the 16S rRNA gene. Results The 3 MED diets increased gut microbiota diversity compared with the AAD. Plasma TMAO was higher following the AAD compared with the MED0.5 (mean fold difference, 1.78 95% CI, 1.05–3.06) and MED2.5 (2.04 95% CI, 1.18–3.52). Urinary TMAO was higher following the AAD compared with the MED0.5 (1.88 95% CI, 1.19–2.97), MED2.5 (2.15 95% CI, 1.37– 3.39), and MED5.5 (1.76 95% CI, 1.12–2.77). Conclusions Compared with an AAD, inclusion of up to 71 g/day of lean beef in a Mediterranean‐style diet increased gut microbiota diversity and lowered TMAO concentrations in healthy adults. REGISTRATION URL: https://clinicaltrials.gov ; Unique identifier: NCT02723617.
DiMattia et al. (2025) studied this question.