Association of Sugar-Sweetened, Artificially Sweetened, and Unsweetened Coffee Consumption with Chronic Liver Disease and Liver-Related Events: A Large Prospective Cohort Study

Background: Previous observational studies have not reached an agreement on the association between coffee consumption and risk of liver diseases. Also, none of these studies took sweetener added in coffee into consideration. Objectives: We aim to explore the associations of consumption of sweetened and unsweetened coffee with chronic liver disease (CLD) and liver-related events (LREs), and evaluate the degree to which sweetener added counteracted the effect of coffee. Methods: We performed a longitudinal cohort study of 170,044 participants without liver diseases or cancer at baseline investigation (2006–2010) and followed until 2022. Consumption of coffee and sweetener was assessed by 24-h dietary recall questionnaire. Cox proportional hazards models and restricted cubic splines were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: During a median follow-up of 12.4 y, we identified 4152 incident of CLD and 853 LREs. Compared with nonconsumers, unsweetened coffee consumers of various amount had lower risk of CLD (HR: 0.75; 95% CI: 0.67, 0.83 for 1.5∼2.5 drinks/d) and LREs (HR: 0.60; 95% CI: 0.46, 0.80 for 2.5∼3.5 drinks/d) in the multivariable Cox models. U-shaped associations of unsweetened coffee with CLD and LREs were observed. The results for sweetened coffee were less consistent and conclusive in both CLD and LREs. We detected positive associations between sweetener and CLD and LREs. Compared with unsweetened coffee consumers, consumers of different amount of sugar added to coffee had higher risk of CLD in the multivariable Cox model. For artificial sweetener, a significant higher risk of CLD (HR: 1.61; 95% CI: 1.25, 2.05)and LREs (HR: 1.82; 95% CI: 1.11, 2.98) was only found in those who added ≥2 teaspoons/drink. We detected significant interaction between artificial sweetener and coffee intake on the risk of CLD (HR for product term: 0.76; 95% CI: 0.60, 0.96; P = 0.018; relative excess risk due to interaction: −0.32; 95% CI: −0.58, −0.06). Conclusions: Moderate consumption of unsweetened coffee was associated with lower risk of CLD and LREs. Adding sweetener into coffee could bring additional risk of liver diseases in coffee consumers.