![]() ![]() We did not limit the search by using terms related to outcomes of interest. We included the following terms, among others: nonnutritive sweeteners, aspartame, saccharin, sucralose, xylitol, stevia, carbonated beverages, calories and food frequency. ![]() Our MEDLINE strategy (Appendix 1, available at Table S1) was peer reviewed and also translated for searches in Embase and The Cochrane Central Register of Controlled Trials. The search strategy was developed by an information specialist (M.F.) to overcome the limitations 13 of previous reviews. Our objective was to synthesize evidence addressing this question: Is routine consumption of nonnutritive sweeteners by adults and adolescents associated with adverse long-term cardiometabolic effects in RCTs and prospective cohort studies? 13 Several studies involving more than 100 000 new participants and representing several new geographic settings have since been published. However, the review did not evaluate outcomes beyond body composition. ![]() 7, 11 A previous meta-analysis 12 reported conflicting evidence: randomized controlled trials (RCTs) showed potential benefits (modest weight loss), whereas observational studies showed a small but significant association with increased body mass index (BMI). 10 However, consumption of nonnutritive sweeteners has been paradoxically associated with weight gain and incident obesity. The position of the Academy of Nutrition and Dietetics is that nonnutritive sweeteners can help limit energy intake as a strategy to manage weight or blood glucose. 7, 8 Moreover, studies involving animals have reported that chronic exposure to nonnutritive sweeteners leads to increased food consumption, weight gain and adiposity. 6 Researchers have suggested that nonnutritive sweeteners may have adverse effects on glucose metabolism, gut microbiota and appetite control. In 2008, more than 30% of Americans reported daily intake of non-nutritive sweeteners, and this proportion is increasing. 1 Evidence that sugar consumption is fuelling this epidemic 2 – 4 has stimulated the increasing popularity of nonnutritive sweeteners, 5 including aspartame, sucralose and stevioside. Obesity is a major public health challenge that contributes to type 2 diabetes and cardiovascular disease. Protocol registration: PROSPERO-CRD42015019749 Further research is needed to fully characterize the long-term risks and benefits of nonnutritive sweeteners. INTERPRETATION Evidence from RCTs does not clearly support the intended benefits of nonnutritive sweeteners for weight management, and observational data suggest that routine intake of nonnutritive sweeteners may be associated with increased BMI and cardiometabolic risk. ![]()
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