Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies.

BACKGROUND: Nonnutritive sweeteners, such as aspartame, sucralose and stevioside, are widely consumed, yet their long-term health impact is uncertain. We synthesized evidence from prospective studies to determine whether routine consumption of non-nutritive sweeteners was associated with long-term adverse cardiometabolic effects. METHODS: We searched MEDLINE, Embase and Cochrane Library (inception to January 2016) for randomized controlled trials (RCTs) that evaluated interventions for nonnutritive sweeteners and prospective cohort studies that reported on consumption of non-nutritive sweeteners among adults and adolescents. The primary outcome was body mass index (BMI). Secondary outcomes included weight, obesity and other cardiometabolic end points. RESULTS: From 11 774 citations, we included 7 trials (1003 participants; median follow-up 6 mo) and 30 cohort studies (405 907 participants; median follow-up 10 yr). In the included RCTs, nonnutritive sweeteners had no significant effect on BMI (mean difference -0.37 kg/m2; 95% confidence interval [CI] -1.10 to 0.36; I2 9%; 242 participants). In the included cohort studies, consumption of nonnutritive sweeteners was associated with a modest increase in BMI (mean correlation 0.05, 95% CI 0.03 to 0.06; I2 0%; 21 256 participants). Data from RCTs showed no consistent effects of nonnutritive sweeteners on other measures of body composition and reported no further secondary outcomes. In the cohort studies, consumption of nonnutritive sweeteners was associated with increases in weight and waist circumference, and higher incidence of obesity, hypertension, metabolic syndrome, type 2 diabetes and cardiovascular events. Publication bias was indicated for studies with diabetes as an outcome. 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. Further research is needed to fully characterize the long-term risks and benefits of nonnutritive sweeteners. Protocol registration: PROSPERO-CRD42015019749.

Early Exposure to Nonnutritive Sweeteners and Long-term Metabolic Health: A Systematic Review.

CONTEXT: Nonnutritive sweetener (NNS) consumption is increasing among children, yet its long-term health impact is unclear, particularly when exposure occurs during early life. OBJECTIVE: To synthesize evidence from prospective studies evaluating the association of early-life NNS exposure and long-term metabolic health. DATA SOURCES: Medline, Embase, and Cochrane Library (inception to July 2015). STUDY SELECTION: We aimed to include randomized controlled trials (RCTs) evaluating NNS-based interventions and prospective cohort studies reporting NNS exposure among pregnant women, infants, or children (<12 years of age), with a minimum study duration of 6 months. DATA EXTRACTION: The primary outcome was BMI; secondary outcomes included growth velocity, overweight/obesity, adiposity, and adverse metabolic effects. Study quality and risk of bias were evaluated using validated assessment tools. RESULTS: We identified 6 eligible cohort studies and 2 RCTs (n = 15,641 children). Half of the cohorts reported increasing weight gain or fat mass accumulation with increasing NNS intake, and pooled data from 2 cohorts showed a significant correlation with BMI gain (weighted mean correlation 0.023, 95% confidence interval 0.006 to 0.041). RCTs reported contradictory effects on weight change in children receiving NNSs. No eligible studies evaluated prenatal or infant NNS exposure. LIMITATIONS: Meta-analysis was limited because of the small number of eligible studies and heterogeneity of populations and outcomes. CONCLUSIONS: There is limited and inconsistent evidence of the long-term metabolic effects of NNS exposure during gestation, infancy, and childhood. Further research is needed to inform recommendations for the use of NNSs in this sensitive population.