Coffee and health outcomes: a systematic review of Mendelian randomisation studies

Coffee is a widely consumed beverage, which has been extensively studied for its potential effects on health. We aimed to map genetic evidence for the effect of habitual coffee consumption on health. We searched PubMed, Embase, Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature and two preprint repositories from inception to 30 September 2022, and included fifty-nine studies, spanning 160 disease or biomarker associations. We evaluated the articles for certainty of evidence using a modified GRADE tool and robustness of the associations by comparing Mendelian randomisation (MR) sensitivity analyses. Coffee consumption was associated with smaller grey matter brain volume in one study, and there was probable evidence for an increased risk of Alzheimer’s disease and younger age of onset of Huntington’s disease. MR studies provided probable evidence for an association with increased risk of oesophageal and digestive cancers, but protective effects for hepatocellular carcinomas and ovarian cancer. We found probable evidence for increased risk of type 2 diabetes mellitus, osteoarthritis, rheumatoid arthritis, menopausal disorders, glaucoma, higher total cholesterol, LDL-cholesterol and ApoB, and lowered risk of migraines, kidney disease and gallstone disease. Future studies should aim to understand underlying mechanisms of disease, expand knowledge in non-European cohorts and develop quality assessment tools for systematic reviews of MR studies.<b>Systematic review registration:</b> PROSPERO registration number CRD42021295323.