The Association Between Lifestyle Interventions and Trimethylamine N-Oxide: A Systematic-Narrative Hybrid Literature Review

Abstract

Background: Trimethylamine N-oxide (TMAO) is a gut- and food-derived molecule. Elevated TMAO concentrations have been associated with an increased risk of cardiovascular disease (CVD) and all-cause mortality, highlighting its significance as a potential biomarker for adverse health outcomes. Given these associations, it is hypothesized that lifestyle interventions, such as healthy dietary patterns and exercise, could reduce TMAO concentrations. The aim of this systematic-narrative hybrid literature review was to evaluate the relationship between various lifestyle interventions and TMAO.

Methods: MEDLINE (via PubMed^®), Scopus^®, and grey literature were searched until July 2024 for eligible clinical trials. Case reports, case series, case studies and observational studies were excluded, as well as studies that investigated food products, nutraceuticals, dietary supplements or have been conducted in the pediatric population.

Results: In total, 27 studies were included in this review. While some dietary interventions, such as plant-based, high-dairy, very low-calorie ketogenic diet or the Mediterranean diet, were associated with lower TMAO concentrations, others-including high-protein and high-fat diets-were linked to an increase in TMAO concentrations. Studies that incorporated a combination of nutrition and exercise-based intervention presented neutral results.

Conclusions: The relationship between dietary interventions and TMAO concentration remains controversial. While certain interventions show promise in reducing TMAO levels, others yield mixed or contradictory outcomes. Further research, including well-structured RCTs, is needed to investigate the aforementioned associations.

Keywords: dietary interventions; gut microbiome; physical activity; trimethylamine N-oxide.