Higher dietary choline intake is associated with increased risk of all-cause and cause-specific mortality: A systematic review and dose-response meta-analysis of cohort studies

Evidence indicates that choline and betaine intakes are associated with mortality. Based on the available evidence, we hypothesized that dietary choline and betaine do not increase mortality risk. This meta-analysis was conducted to investigate the association of dietary choline and betaine with mortality from all causes, cardiovascular diseases, and stroke. Online databases including PubMed, Scopus, Web of Science, Embase, and Google Scholar were searched up to 9 March 2024. Six cohort studies comprising 482,778 total participants, 57,235 all-cause, 9351 cardiovascular disease, and 4,400 stroke deaths were included in this study. The linear dose-response analysis showed that each 100 mg/day increase in choline intake was significantly associated with 6% and 11% increases in risk of all-cause (RR = 1.06, 95% CI: 1.03, 1.10, I² =83.7%, P < .001) and cardiovascular diseases mortality (RR = 1.11, 95% CI: 1.06, 1.16, I² = 54.3%, P = .02) respectively. However, dietary betaine, was not associated with the risk of mortality. Furthermore, the result of the nonlinear dose-response analysis showed a significant relationship between betaine intake and stroke mortality at the dosages of 50 to 250 mg/day (P_{non-linearity}= .0017). This study showed that each 100 mg/day increment in choline consumption was significantly associated with a 6% and 11% higher risk of all-cause and cardiovascular disease mortality respectively. In addition, a significant positive relationship between betaine intake and stroke mortality at doses of 50 to 250 mg/day was observed. Due to the small number of the included studies and heterogeneity among them more well-designed prospective observational studies considering potential confounding variables are required.