Objective: The objective of this review was to critically review findings from recent studies evaluating the effects of nonnutritive sweeteners (NNSs) on metabolism, weight, and obesity-related chronic diseases. Biologic mechanisms that may explain NNS effects will also be addressed.
Methods: A comprehensive review of the relevant scientific literature was conducted.
Results: Most cross-sectional and prospective cohort studies report positive associations between NNS consumption, body weight, and health conditions, including type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease. Although findings in cellular and rodent models suggest that NNSs have harmful effects on metabolic health, most randomized controlled trials in humans demonstrate marginal benefits of NNS use on body weight, with little data available on other metabolic outcomes.
Conclusions: NNS consumption is associated with higher body weight and metabolic disease in observational studies. In contrast, randomized controlled trials demonstrate that NNSs may support weight loss, particularly when used alongside behavioral weight loss support. Additional long-term, well-con- trolled intervention studies in humans are needed to determine the effects of NNSs on weight, adiposity, and chronic disease under free-living conditions.
This review study compares evidence regarding the role of low calorie sweeteners in weight management between observational studies and randomised clinical trials (RCTs) and concludes that RCTs demonstrate that low calorie sweeteners may support weight loss, particularly when used alongside behavioral weight loss support. In contrast, some observational studies suggest a positive association between low calorie sweeteners and higher body weight and metabolic disease, however, observational studies, by nature, are studies unable to establish cause and effect and they are subject to inherently flawed dietary assessments or can be biased by reverse causality and residual confounding. The authors also call for further research to explore the discrepancies between controlled clinical trials’ findings and observational data.
The paper also discusses proposed physiological mechanisms that have been examined in in-vitro or animal studies to explore how would be possible for low calorie sweeteners, which provide no calories, to affect body weight. In discussing potential mechanisms (for example: LCS effects on sweet taste receptors, alterations in gut microbiota, impact in taste preferences, disturbance of relationship between sweetness and calories), the authors state that it is unclear whether the same potential mechanisms would be expected in humans and that these mechanisms warrant further investigation. Other review papers addressing the mechanisms by which low calorie sweeteners may hypothetically promote energy intake, reveals that none are substantiated by the available evidence (Mattes & Popkin, 2009; Bryant & McLaughlin, 2016; Rogers, 2017) Indeed, no mechanism has been validated at more than a descriptive level, so they should be viewed as speculative.