Background: The effects of non-nutritive sweeteners (NNS) on glucose metabolism and appetite regulating hormones are not clear. There is an ongoing debate concerning NNS use and deleterious changes in metabolism. Objectives: The aim of this review is to analyze the scientific available evidence regarding the effects of NNS on glucose metabolism and appetite regulating hormones. Data Sources and Study Eligibility Criteria: We identified human observational studies evaluating the relation between NNS consumption and obesity, diabetes, and metabolic syndrome, in addition to clinical trials evaluating the effects of NNS in glucose metabolism and appetite regulating hormones. Results: Fourteen observational studies evaluating the association between NNS consumption and the development of metabolic diseases and twenty-eight clinical trials studying the effects of NNS on metabolism were included. Finally, two meta-analyses evaluating the association between the consumption of NNS-containing beverages and the development of type 2 diabetes were identified. Conclusions: Some observational studies suggest an association between NNS consumption and development of metabolic diseases; however, adiposity is a confounder frequently found in observational studies. The effects of the NNS on glucose metabolism are not clear. The results of the identified clinical trials are contradictory and are not comparable because of the major existing differences between them. Studies evaluating specific NNS, with an adequate sample size, including a homogeneous study group, identifying significant comorbidities, with an appropriate control group, with an appropriate exposure time, and considering adjustment for confounder variables such as adiposity are needed.
Summarising the results, the majority of the observational studies (11 out of 14) have found significant associations between LCS consumption and the development of metabolic diseases, however, in most of these studies, this association was lost after adjustments for adiposity, body mass index (BMI) and/ or energy intake. This actually implies that the link between low calorie sweeteners (or LCS beverages) and metabolic diseases which is found in some observational studies may be due to reverse causality. Furthermore, out of the twenty-eight (28) clinical trials identified, eighteen (18) studies found no effect of LCS on glucose metabolism, and ten (10) out of these showing statistical significant effects on some or all of the studies variables. However, the results are contradictory and there is no possible comparison between the trials due to heterogeneity in the population included (e.g. study by Suez et al included only 7 participants, Pepino et al study was conducted on subjects with a big degree of obesity etc), the type of LCS studied, placebo use, different exposure time, study design etc. Based on the available evidence, an effect of low calorie sweeteners on glucose metabolism cannot be established, which actually is consistent with what we already knew about low calorie sweeteners that they do not affect glucose and insulin levels.