Authors
Rima Obeid, Lorenz Mohr, Bryan A White, Gunnar H Heine, Insa Emrich, Juergen Geisel, R Colin Carter
Published in
Nutrition & metabolism. Volume 23. Issue 1. Sep 23, 2026. Epub Sep 23, 2026.
Abstract
Circulating trimethylamine N-oxide (TMAO) may be a causal factor or marker for major adverse cardiac and cerebrovascular events (MACE), but evidence in humans is limited to observational studies with inherent uncertainties.
We conducted an umbrella systematic review and meta-analysis of human studies. The search in MEDLINE, Web of Science, Cochrane Library and PROSPERO (last updated in February 2025) identified 120 publications that met our inclusion criteria.
The pooled hazard ratio (HR) and 95% confidence intervals (95%CIs) from 34 cohort studies on TMAO and MACE = 1.20 (1.12-1.27), the prediction interval (PI) was 0.93-1.54, and I2 = 73.3%. After correction for publication bias (p < 0.001 Egger's test), the pooled HR (95%CIs) was 1.10 (1.03-1.17). The pooled odds ratio (95%CIs) from 18 case-control studies after accounting for publication bias was 1.05 (0.94-1.18). As a diagnostic test, the estimated pooled area under the curve (95%CIs) for TMAO was 72.8 (68.8-77.1)%, PI = 54.7%-97.1%, I2 = 93.8%, n = 24 studies. The mean (95%CIs) sensitivity and specificity of TMAO were 65.3 (56.1-74.5)% and 79.0 (65.4-92.6)%, respectively. The data did not suggest a threshold for elevated TMAO concentrations.
Previously reported association estimates between TMAO and MACE in human studies are systematically overestimated. The results do not support TMAO being a causal factor or marker of MACE and related conditions. Harmonisation of TMAO measurements between labs and cohort studies in healthy people that address confounding factors remain critically needed.
PMID:
42778937
Bibliographic data and abstract were imported from PubMed on 24 Sep 2026.
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