Food Sources of Animal Protein in Relation to Overall and Cause-Specific Mortality-Causal Associations or Confounding? An Analysis of the EPIC-Heidelberg Cohort.

While prior prospective iso-caloric substitution studies show a robust association between higher intake of animal protein and risk of mortality, associations observed for mortality risk in relation to major food sources of animal protein have been generally more diverse. We used the EPIC-Heidelberg cohort to examine if confounding, notably, by smoking, adiposity, or alcohol intake, could cause inconsistencies in estimated mortality hazard ratios (HR) related to intake levels of different types of meat and dairy products. Higher intakes of red or processed meats, and lower intakes of milk or cheese, were observed among current heavy smokers, participants with obesity, or heavy alcohol drinkers. Adjusting for age, sex, and total energy intake, risk models showed increased all-cause, cardiovascular, and cancer-related mortality with higher red or processed meat intakes (HR ranging from 1.25 [95% confidence interval = 1.15-1.36] to 1.76 [1.46-2.12] comparing highest to lowest tertiles), but reduced risks for poultry, milk, or cheese (HR ranging from 0.55 [0.43-0.72] to 0.88 [0.81-0.95]). Adjusting further for smoking history, adiposity indices, alcohol consumption, and physical activity levels, the statistical significance of all these observed was erased, except for the association of processed meat intake with cardiovascular mortality (HR = 1.36 [CI = 1.13-1.64]) and cheese intake with cancer mortality (HR = 0.86 [0.76-0.98]), which, however, were substantially attenuated. These findings suggest heavy confounding and provide little support for the hypothesis that animal protein, as a nutrient, is a major determinant of mortality risk.