Serum metabolomic markers of artificially sweetened beverage consumption.

Abstract

The consumption of artificially sweetened beverages is on the rise. Use of artificial sweeteners has been associated with adverse health outcomes. There is a need to identify novel objective biomarkers of artificially sweetened beverages in order to improve dietary assessment and to provide insight into their metabolic impact. We aim to identify serum metabolites that are associated with artificially sweetened beverage consumption. In the Atherosclerosis Risk in Communities (ARIC) study, consumption of artificially sweetened beverages was assessed using a food frequency questionnaire and fasting serum samples were collected during the first study visit (1987-1989). Participants were categorized as "non-users" if they reported almost never consumption of artificially sweetened beverages, "moderate users" for 1 glass/month to 6 glasses/week, and "heavy users" for ≥1 glasses/day. Untargeted metabolomic profiling was conducted in two subgroups (subgroup 1: n=1,866, profiled in 2010; subgroup 2 profiled in 2014: n=2,072) and 360 metabolites were analyzed. In this secondary data analysis, multivariable linear regression models were used, adjusting for demographics, health behaviors, health status, and dietary factors. Analyses were conducted in each subgroup and results were meta-analyzed. In a meta-analysis of 3,938 generally healthy participants (mean age 54 years, 60% women, 62% Black participants) from ARIC study visit 1, 11 serum metabolites were significantly associated with artificially sweetened beverage consumption. Heavier consumption of artificially sweetened beverages was associated with higher levels of 10 metabolites (saccharin, threonate, erythronate, glycerate, gluconate, mannitol, glucose, tryptophan betaine, trehalose, and N6-acetyllysine) and lower levels of glycocholenate sulfate. We found 11 serum metabolites related to artificially sweetened beverage intake, that consisted of known sugar substitutes, processed food additives, glucose-related compounds, and gut microbiome-related metabolites. These findings enhance our knowledge of the metabolic activity of artificial sweeteners and suggests new biomarkers for monitoring intake.