Causal relationship from coffee consumption to diseases and mortality: a review of observational and Mendelian randomization studies including cardiometabolic diseases, cancer, gallstones and other diseases

PURPOSE: High coffee consumption is associated with low risk of mortality and morbidity, but the causality remains unclear. This review aims to discuss findings from observational studies on coffee consumption in context of Mendelian randomization studies.

METHODS: The PubMed database was searched for all Mendelian randomization studies on coffee consumption and corresponding observational studies.

RESULTS: High coffee consumption is associated with low risk of all-cause and cardiovascular mortality in observational studies (HRs of 0.85-0.90 vs. no/low consumers), with no support of causality in Mendelian randomization studies. Moderate/high consumption is associated with low risk of cardiometabolic diseases, including ischemic heart disease (HRs of 0.85-0.90 vs. no/low consumption), stroke (HRs of approximately 0.80 vs. no/low consumption), type 2 diabetes (HRs of approximately 0.70 vs. no/low consumption) and obesity in observational studies, but not in Mendelian randomization studies. High consumption is associated with low risk of endometrial cancer and melanoma and high risk of lung cancer in observational studies, but with high risk of colorectal cancer in Mendelian randomization studies. In observational and Mendelian randomization studies, high coffee consumption is associated with low risk of gallstones (HRs of 0.55-0.70 for high vs. no/low self-reported and 0.81 (0.69-0.96) for highest vs. lowest genetic consumption).

CONCLUSION: High coffee consumption is associated with low risk of mortality, cardiometabolic diseases, some cancers and gallstones in observational studies, with no evidence to support causality from Mendelian randomization studies for most diseases except gallstones.