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

BACKGROUND: Despite substantial research highlighting the importance of exogenous dietary cholesterol intake and endogenous serum cholesterol level in human health, a thorough evaluation of the associations is lacking. Our study objective was to examine overall and cause-specific mortality in relation to dietary and serum cholesterol, as well as egg consumption, and conduct an updated meta-regression analysis of cohort studies. METHODS: We conducted a prospective analysis of 27 078 men in the ATBC Study (Alpha-Tocopherol, Beta-Carotene Cancer Prevention). Multivariable-controlled cause-specific Cox proportional hazards regression models were used to calculate hazard ratios and 31-year absolute mortality risk differences. A systematic review and meta-analysis of cohort studies was also performed (PROSPERO [URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42021272756]). RESULTS: Based on 482 316 person-years of follow-up, we identified 22 035 deaths, including 9110 deaths from cardiovascular disease (CVD). Greater dietary cholesterol and egg consumption were associated with increased risk of overall and CVD-related mortality. Hazard ratios for each additional 300 mg cholesterol intake per day were 1.10 and 1.13 for overall and CVD-related mortality, respectively; for each additional 50-g egg consumed daily, hazard ratios were 1.06 and 1.09, respectively, for overall and CVD-related mortality (all P values<0.0001). After multivariable adjustment, higher serum total cholesterol concentrations were associated with increased risk of CVD-related mortality (hazard ratios per 1 SD increment, 1.14; P<0.0001). The observed associations were generally similar across cohort subgroups. The updated meta-analysis of cohort studies on the basis of 49 risk estimates, 3 601 401 participants, and 255 479 events showed consumption of 1 additional 50-g egg daily was associated with significantly increased CVD risk (pooled relative risk, 1.04 [95% CI, 1.00-1.08]; I-2=80.1%). In the subgroup analysis of geographic regions (P-interaction=0.02), an increase of 50-g egg consumed daily was associated with a higher risk of CVD in US cohorts (pooled relative risk, 1.08 [95% CI, 1.02-1.14]) and appeared related to a higher CVD risk in European cohorts with borderline significance (pooled relative risk, 1.05), but was not associated with CVD risk in Asian cohorts. CONCLUSIONS: In this prospective cohort study and updated meta-analysis, greater dietary cholesterol and egg consumption were associated with increased risk of overall and CVD-related mortality. Our findings support restricted consumption of dietary cholesterol as a means to improve long-term health and longevity.