The Effect of Red Meat Consumption on Circulating, Urinary, and Fecal Trimethylamine-N-Oxide: A Systematic Review and Narrative Synthesis of Randomized Controlled Trials

Cardiovascular concerns exist about the effect of red meat on circulating concentrations of trimethylamine N-oxide (TMAO), an emerging cardiovascular disease risk factor. The aim was to conduct a systematic review of randomized controlled trials (RCTs) to evaluate the effect of higher red meat intake, compared with lower intake, on circulating, urinary, and fecal TMAO concentrations in generally healthy adults and/or adults with stable chronic diseases. A systematic literature search was conducted using PubMed, the Cochrane Collaboration Library, and Web of Science. RCTs examining the effect of a ≥7-d dietary intervention featuring red meat on urinary, fecal, and/or circulating (plasma or serum) concentrations of TMAO in adults (≥18 y) were included. Eligible trials had a comparator group/condition that was exposed to a dietary intervention for ≥ 7 d lower in red meat and featuring white meat, fish, eggs, dairy, or plant-based protein sources. In total, 375 publications were identified. Fifteen publications reporting the results of 13 RCTs (n = 553; median duration 28 d), including 15 diet comparisons, were eligible. In 6 comparisons, higher circulating or urinary TMAO concentrations were observed after higher red meat intake (∼71-420 g/d) compared with comparator conditions lower in red meat. In 7 comparisons, no differences in serum/plasma TMAO concentrations were observed with higher red meat-containing diets (∼60-156 g/d) compared with diets lower in red meat. Two comparisons showed that consuming higher red meat diets lowered TMAO concentrations after 28 d compared with lower red meat diets containing seafood. In short-term studies (median duration of 28 d), higher red meat intake had inconsistent effects on circulating and urinary TMAO concentrations. Further high-quality research on red meat-related TMAO modulation, including effect magnitude and clinical relevance, is needed. This study was registered at Prospective Register of Systematic Reviews (PROSPERO) as CRD42023396799.