Non-nutritive sweeteners and their association with the metabolic syndrome and non-alcoholic fatty liver disease: a review of the literature.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is increasing in incidence worldwide, paralleling epidemics in obesity and metabolic syndrome. Widely considered the hepatic manifestation of the metabolic syndrome, NAFLD is associated with significant morbidity, mortality, and increased healthcare costs. There is an abundance of data linking sugar-sweetened beverages, and fructose, in particular, to the metabolic syndrome and NAFLD. As a result, non-nutritive sweeteners (NNSs) are frequently substituted for sugar in drinks and a variety of foods. However, despite the widespread consumption of NNSs, there is growing concern about their impact on metabolic health. This review examines the experimental and clinical evidence on non-nutritive sweetener (NNS) consumption and features of the metabolic syndrome, including NAFLD. Experimental animal studies show that NNS consumption can induce glucose intolerance, increased food consumption, and weight gain, with proposed mechanisms including altered gut microbiome, inhibition of protective intestinal enzymes, and increased appetite. The evidence from clinical studies is more controversial. Observational studies overwhelmingly show an association between NNS consumption and features of the metabolic syndrome, and this includes NAFLD when analyses are not adjusted for obesity. The evidence from randomized-controlled trials in humans is sparse and conflicting, and primarily evaluates weight-related outcomes. Further research is urgently needed to evaluate NNS consumption and its relationship with NAFLD and the gut microbiome in humans.