Serum Erythritol and Risk of Overall and Cause-Specific Mortality in a Cohort of Men

Erythritol occurs naturally in some fruits and fermented foods, and has also been used as an artificial sweetener since the 1990s. Although there have been questions and some studies regarding its potential adverse health effects, the association between serum erythritol and long-term mortality has not been evaluated. To examine the association between serum erythritol's biochemical status and risk of overall and cause-specific mortality, a prospective cohort analysis was conducted using participants in the ATBC Study (1985-1993) previously selected for metabolomic sub-studies. The analysis included 4468 participants, among whom 3377 deaths occurred during an average of 19.1 years of follow-up. Serum erythritol was assayed using an untargeted, global, high-resolution, accurate-mass platform of ultra-high-performance liquid and gas chromatography. Cause-specific deaths were identified through Statistics Finland and defined by the International Classification of Diseases. After adjustment for potential confounders, serum erythritol was associated with increased risk of overall mortality (HR = 1.50 [95% CI = 1.17-1.92]). We found a positive association between serum erythritol and cardiovascular disease mortality risk (HR = 1.86 [95% CI = 1.18-2.94]), which was stronger for heart disease mortality than for stroke mortality risk (HR = 3.03 [95% CI = 1.00-9.17] and HR = 2.06 [95% CI = 0.72-5.90], respectively). Cancer mortality risk was also positively associated with erythritol (HR = 1.54 [95% CI = 1.09-2.19]). The serum erythritol-overall mortality risk association was stronger in men ≥ 55 years of age and those with diastolic blood pressure ≥ 88 mm Hg (<i>p</i> for interactions 0.045 and 0.01, respectively). Our study suggests that elevated serum erythritol is associated with increased risk of overall, cardiovascular disease, and cancer mortality. Additional studies clarifying the role of endogenous production and dietary/beverage intake of erythritol in human health and mortality are warranted.