Modulation of Circulating Trimethylamine N-Oxide Concentrations by Dietary Supplements and Pharmacological Agents: A Systematic Review

Discovery of the association of plasma/serum trimethylamine N-oxide (TMAO) concentrations with atherosclerosis has sparked immense interest in exploring TMAO as a predictor of cardiovascular disease risk. A spectrum of antibiotics and other therapeutic strategies have been employed to test their potential to modulate TMAO concentrations, assuming the gut microbiome to be the key source of TMAO. The aim of this systematic review was to determine whether dietary supplements or pharmacological agents affect TMAO concentrations in adults. Six databases were searched (Medline, EMBASE, CINAHL, Scopus, ProQuest, and PubMed) for randomized and nonrandomized controlled trials. Searches were limited to the English language and to studies in adults. Thirteen eligible trials were identified, including 6 studies on dietary supplements and 7 on pharmacological agents. Whereas intervention studies involving dietary supplements were mostly randomized controlled trials, those involving pharmacological agents appeared opportunistic and varied greatly in study design and duration. Different interventional products were tested, and the studies lacked the consistency to reliably synthesize any evidence for the modifiability of TMAO concentrations by dietary supplements or pharmacological agents. Choline and l-carnitine are conditionally essential nutrients, and carefully designed placebo-controlled randomized trials specifically aimed at reducing the synthesis of microflora-dependent TMAO production from choline-containing precursors by pro- and/or prebiotics, antibiotics, or other pharmaceutical agents may be the way forward for future research.