Circulating trimethylamine N-oxide and cardiovascular, cerebral, and renal diseases including mortality: Umbrella review of published systematic reviews and meta-analyses.
Level 3 - non-randomized controlled study
Umbrella review synthesizing systematic reviews and meta-analyses of observational studies
PubMed 40118729 · doi:10.1016/j.numecd.2025.103908
What was done
Researchers conducted an umbrella review and critical evaluation of published systematic reviews and meta-analyses examining associations between circulating trimethylamine N-oxide (TMAO) and cardiovascular disease, stroke, renal disease, and mortality. The review was registered on PROSPERO (CRD42024534940) and identified 27 systematic reviews/meta-analyses (7 on stroke, 14 on cardiovascular disease/mortality, and 6 on other related outcomes).
What was found
The abstract reports no specific numerical effect estimates, odds ratios, or hazard ratios. It states that the majority of included meta-analyses reported higher circulating TMAO concentrations in patients with adverse outcomes. However, the authors identified widespread and serious methodological, conduct, and reporting flaws across the included reviews, resulting in critically low confidence in their pooled conclusions.
Why it matters
Elevated TMAO is frequently cited as a potential cardiovascular risk factor or therapeutic target, but this umbrella review demonstrates that current secondary evidence rests on low-quality meta-analyses with unproven causality.
Limits
The underlying primary studies were conducted almost exclusively in populations with pre-existing risk factors and failed to adequately control for major confounders. No prospective cohort studies evaluated baseline TMAO in healthy populations, and clinical trial evidence testing TMAO-lowering interventions is absent. The abstract lacks quantitative effect sizes and formal quality assessment scores.
Cited by
- supports High circulating levels of TMAO over time carry cardiovascular risk.