Artificial and Other Non-Nutritive Sweeteners, the Microbiome, and Cardiometabolic Health.

purpose of reviewIn this narrative review complemented by a novel meta-analysis, we critically analyzed current scientific evidence from RCTs and cohort studies regarding the impact of non-nutritive sweeteners (NNS) on cardiometabolic health, and assessed the interplay with the gut microbiome as a potential mechanistic pathway. We focused on the question of direct physiological effects of NNS, rather than the additional effects of energy displacement by NNS, to inform future research and the development of dietary and clinical guidelines. RECENT

findingsCohort studies assessing NNS from all dietary sources suggest that total NNS and each commonly used NNS are associated with higher risk of type 2 diabetes, and that total intake and specific agents are associated with certain cardiovascular disease outcomes. These findings are consistent with prior evidence from cohorts focusing on NNS in beverages. Such observational evidence may be confounded by reverse causation: people at higher cardiometabolic risk choosing to use NNS. However, our new meta-analysis of RCTs with non-caloric comparators and a recent RCT on glycemia outcomes with human-to-mice microbiota transplant suggest that NNS have harmful effects on glucose-insulin homeostasis including fasting insulin, HbA1c, and glucose area under the curve during oral glucose tolerance test (OGTT), potentially mediated by effects on the composition and functional potential of the gut microbiome. The summed evidence supports potential long-term risk of cardiometabolic diseases associated with NNS intake and short-term harmful effects of NNS on glycemia. Future clinical trials of physiologic effects and molecular mechanisms will strengthen interpretations and causal inference. Given potential for harm, caution is warranted for the use of NNS.