Meta-analysisindependent cross-checkfull text checked★ key study I-EGG-109 in-depth review

Large review links eggs to slightly higher heart risk, mainly in the USA

Associations of Dietary Cholesterol, Serum Cholesterol, and Egg Consumption With Overall and Cause-Specific Mortality: Systematic Review and Updated Meta-Analysis.

Overview

Zhao B et al.. Circulation 2022 · PMID 35360933 · DOI 10.1161/CIRCULATIONAHA.121.057642

Each extra egg per day: 4% higher CVD risk overall (RR 1.04), 8% in US studies, none in Asian studies.

Does the study support the specific claim? Partly · Methodological quality: moderate

Original publication

Plain-language summary

Study explained simply
What did the researchers want to find out?

Combine all cohort data on eggs, cholesterol and death.

How was the study done?

Finnish cohort plus meta-analysis of 3.6 million people.

How many people, animals or samples were studied?

27,078 men; 49 estimates.

What was actually found?

Small positive association, strongest in US studies.

How large was the observed effect?

RR 1.04 (1.00-1.08) per 50 g egg/day.

What do the results mean in everyday life?

Very high egg intake might slightly increase heart risk in some populations; moderate intake is a small issue at most.

What are the study's limitations?

Observational; big differences between studies.

What does it say about Elawady's specific claim?

Partly supports the archive's direction but with a much smaller and region-dependent effect.

Do the results apply to Germany and Europe?

Borderline in Europe.

What can explicitly not be concluded from this study?

It cannot prove that eggs cause heart disease.

Scientific in-depth review

1. Full reference

Authors
Zhao B et al.
Journal
Circulation
Year
2022
Identifier
PMID 35360933 DOI 10.1161/CIRCULATIONAHA.121.057642
Verification
verified – PubMed efetch 2026-10-26; Crossref works API 2026-10-26
Retracted
no
Corrections
none
Extent checked
full text
Conflicts of interest and funding

ATBC supported by the US National Cancer Institute intramural programme; authors declared no competing interests (full text).

2. Research question

Are dietary cholesterol, serum cholesterol and egg consumption associated with overall and cause-specific mortality?

3. Study design and population

Study design
Meta-analysis – Prospective cohort analysis (ATBC Study, Finnish male smokers) plus systematic review and dose-response meta-analysis of cohort studies (PROSPERO CRD42021272756)
Population

ATBC: 27,078 Finnish male smokers aged 50-69; meta-analysis: 49 risk estimates, 3,601,401 participants

Country

Finland (cohort); USA, Europe, Asia (meta-analysis)

Period

ATBC recruited 1985-1988, follow-up up to 31 years

Sample size

ATBC 27,078 (22,035 deaths); meta-analysis 3.6 million participants, 255,479 events

Inclusion and exclusion criteria

not detailed in abstract

4. Methods and endpoints

Exposure / intervention

Dietary cholesterol, egg intake (per 50 g/day), serum total cholesterol

Comparator

Lower intake

Endpoints

All-cause, CVD and cause-specific mortality; CVD (meta-analysis)

Statistical methods

Cox models with absolute risk differences; random-effects dose-response meta-analysis; Egger tests; Newcastle-Ottawa scale

5. Actual results

Results

ATBC: per 300 mg/day cholesterol HR 1.10 (overall) and 1.13 (CVD mortality); per 50 g egg/day HR 1.06 and 1.09 (all P<0.0001); egg-mortality associations diminished after adjustment for dietary cholesterol. Meta-analysis: per 50 g egg/day CVD RR 1.04 (1.00-1.08), I2 80.1%; US 1.08 (1.02-1.14); Europe 1.05 (0.98-1.14); Asia 0.96 (0.87-1.06); P-interaction 0.02.

Absolute risks

31-year absolute risk differences were computed in the cohort (values not extracted here).

Authors' conclusion

Greater dietary cholesterol and egg consumption were associated with increased overall and CVD mortality; findings support restricted dietary cholesterol intake.

6. Strengths

  • Very large updated meta-analysis
  • Long follow-up cohort with absolute risk differences
  • Explores regional heterogeneity

7. Weaknesses

  • Cohort limited to male smokers
  • High heterogeneity (I2 80%)
  • Single baseline FFQ
  • Observational, residual confounding possible

8. Risk of bias

Orienting tool
ROBINS-E
Type of assessment
simplified assessment (abstract only)
Full formal assessment
no
Overall risk of bias
some concerns
Rationale

Observational evidence; heterogeneity largely by region; simplified judgement.

9. Assessment of the statistical interpretation

Recomputed US vs Asia difference z = 2.04, p = 0.04 (stats/C-EGG-04_regional_heterogeneity.py). The pooled RR of 1.04 per egg/day is small and the association is confined to US (and borderline European) cohorts.

10. Relevance to the specific claim

Strongest recent support for a modest positive egg-CVD association; also shows the association is absent in Asian cohorts.

11. Independent contrary findings

Drouin-Chartier 2020 (I-EGG-01), Krittanawong 2021 (I-EGG-110), PURE (I-EGG-02) found no association at moderate intake.

12. Transferability to Germany and Europe

Europe borderline (RR 1.05, 0.98-1.14). Egypt: no direct data; Middle East cohort (Isfahan, I-EGG-111) null.

13. Overall methodological judgement

Credible but modest positive association concentrated in US data; it supports caution with high intakes, not a general egg ban.

Multidimensional assessment
Multidimensional assessment
Authenticity of the sourceverified
Methodological qualitymoderate
Risk of biassome concerns
Precision of resultshigh
Directnessdirect
Reproducibilitypartly replicated
Consistency with the overall evidenceinconsistent
Regional transferabilitymoderate
Adequacy of the interpretation (by the archive)not applicable

14. Open questions

Why regional differences exist (accompanying foods, cooking, baseline diet).

15. Linked fact checks