Meta-analysisindependent cross-checkabstract checked I-EGG-114 standard review
High TMAO in blood is linked to heart events
Gut microbe-generated metabolite trimethylamine-N-oxide as cardiovascular risk biomarker: a systematic review and dose-response meta-analysis.
Overview
Schiattarella GG et al.. Eur Heart J 2017 · PMID 29020409 · DOI 10.1093/eurheartj/ehx342
People with high TMAO had more cardiovascular events (HR 1.67) and deaths (HR 1.91).
Does the study support the specific claim? Partly · Methodological quality: moderate
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Pool studies of TMAO and outcomes.
- How was the study done?
Meta-analysis.
- How many people, animals or samples were studied?
26,167.
- What was actually found?
Positive association.
- How large was the observed effect?
MACCE HR 1.67 (1.33-2.11).
- What do the results mean in everyday life?
TMAO is a risk marker, but this does not show eggs raise it.
- What are the study's limitations?
Heterogeneous; confounding by kidney disease.
- What does it say about Elawady's specific claim?
Supports the biomarker link only.
- Do the results apply to Germany and Europe?
Universal.
- What can explicitly not be concluded from this study?
It cannot show TMAO causes disease or that eggs matter.
Scientific in-depth review
1. Full reference
- Authors
- Schiattarella GG et al.
- Journal
- Eur Heart J
- Year
- 2017
- Identifier
- PMID 29020409 DOI 10.1093/eurheartj/ehx342
- Verification
- verified – PubMed efetch 2026-10-26; Crossref works API 2026-10-26
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
not stated in abstract
2. Research question
Are plasma TMAO levels associated with mortality and major adverse cardio- and cerebrovascular events?
3. Study design and population
- Study design
- Meta-analysis – Systematic review and dose-response meta-analysis of clinical studies
- Population
17 clinical studies, 26,167 subjects
- Country
Multinational
- Period
Search to April 2017
- Sample size
26,167
- Inclusion and exclusion criteria
not detailed in abstract
4. Methods and endpoints
- Exposure / intervention
High plasma TMAO
- Comparator
Low plasma TMAO
- Endpoints
All-cause mortality; MACCE
- Statistical methods
Random-effects; dose-response
5. Actual results
- Results
High TMAO: all-cause mortality HR 1.91 (1.40-2.61; I2 94%); MACCE HR 1.67 (1.33-2.11; I2 46%). Per 10 umol/L TMAO: mortality RR 1.07 (1.04-1.11).
- Absolute risks
not reported
- Authors' conclusion
Positive dose-dependent association between TMAO plasma levels and increased cardiovascular risk and mortality.
6. Strengths
- Dose-response analysis
7. Weaknesses
- Very high heterogeneity for mortality
- Mostly patient cohorts; confounding by kidney function
- Association, not causation
8. Risk of bias
- Orienting tool
- AMSTAR 2
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- some concerns
- Rationale
Biomarker association; reverse causation possible.
9. Assessment of the statistical interpretation
The association is with blood TMAO, not with egg intake; per 10 umol/L only 7% mortality increase.
10. Relevance to the specific claim
Supports the part of the claim that high blood TMAO is associated with cardiovascular events; does not link eggs to TMAO or events.
11. Independent contrary findings
Mendelian randomization (I-EGG-115) suggests confounding/reverse causation.
12. Transferability to Germany and Europe
Universal.
13. Overall methodological judgement
Real biomarker association, causality uncertain.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | moderate |
| Risk of bias | some concerns |
| Precision of results | moderate |
| Directness | indirect |
| Reproducibility | replicated |
| Consistency with the overall evidence | mixed |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | not applicable |
14. Open questions
Is TMAO a cause or a marker of kidney/metabolic disease?