Aspartame (Asp) and acesulfame-K (Ace-K) are nonnutritive sweeteners (NNSs) commonly used in combination to replace added sugars in reduced- or low-calorie foods and beverages. Despite Asp/Ace-K blends having negligible calories, their effects on appetite have not been reviewed systematically. We therefore undertook a systematic review and meta-analysis of the metabolic effects of Asp/Ace-K blends on energy intake (EI), subjective appetite scores, blood glucose, and the incretin hormones glucose-dependent insulinotropic peptide and glucagon-like peptide. MEDLINE, Web of Science, and Cochrane CENTRAL databases (Embase, PubMed, and CINAHL) were searched (May 2021) for randomized controlled trials (RCTs). Human RCTs using Asp/Ace-K blends compared with sugar and water controls were included, whereas isolated cell and animal studies were excluded. An overall 4829 publications were identified and 8 studies, including 274 participants, were retrieved for review. The Asp/Ace-K group's EI was significantly reduced compared with sugar [mean difference (MD): –196.56 kcal/meal; 95% CI: –332.01, –61.11 kcal/meal; P = 0.004] and water (MD: –213.42 kcal/meal; 95% CI: –345.4, –81.44 kcal/meal; P = 0.002). Meta-analysis of subjective appetite scores and incretins could not be undertaken due to inconsistencies in data reporting and insufficient data, respectively, but of the 4 studies identified, no differences were observed between Asp/Ace-K blends and controls. The Asp/Ace-K group's blood glucose was nonsignificantly reduced compared with sugar (MD: –1.48 mmol/L; 95% CI: –3.26, 0.3 mmol/L; P = 0.1) and water (MD: –0.08 mmol/L; 95% CI: –0.62, 0.47 mmol/L; P = 0.78). Lower EI in participants who were predominantly healthy and assigned to Asp/Ace-K blends could not be reliably attributed to changes in subjective appetite scores. Blood glucose and incretins were also generally not affected by Asp/Ace-K blends when compared with controls. Additional short- and long-term RCTs using NNSs and sugars at dietarily relevant levels are needed. This trial was registered at the International Prospective Register of Systematic Reviews (PROSPERO: CRD42017061015).

Due to the rise in diabetes rates across the world, the enteroendocrine cells (EEC) of the small intestine have gathered much interest in recent years because of their roles in secreting the incretin hormones, glucagon‐like peptide 1 (GLP‐1) and glucose‐dependent insulinotropic peptide (GIP) in response to ingested carbohydrates. Both GLP‐1 and GIP promote insulin synthesis and secretion and therefore play an important role in controlling blood glucose levels. While glucose induced incretin secretion by EEC cells has been well established, the response of EEC cells to other dietary carbohydrates, such as the dissacharides, and non‐nutritive sweeteners, such as artificial sweeteners (AS), is less well understood. Thus, to investigate the effects of the AS, aspartame, acesfulfame‐K and Canderel® (1.4% aspartame;0.95% acesulfame‐k) and the disaccharides, maltose, sucrose, trehalose and lactose on GLP‐1 secretion, we used the mouse EEC line, GLUTag, a well established model of the L cell, which is predominantly found in the distal regions of the small intestine. GLUTag cells were incubated with the AS (at 0, 0.25, 0.4 and 5mM), and the disaccharides and glucose (at 0, 0.25, 0.5, 2.5, 5, 12.5, 25 and 50mM) for 2 hours at 37° C and the supernatant collected. GLP‐1 was measured from the supernatant using a GLP‐1 (Active) ELISA assay (EMD Millipore®, UK). Our results showed that at dietary relevant doses (0.25–5mM) the individual AS, aspartame and acesulfame‐k, and the AS mixture, Canderel® significantly induced GLP‐1 secretion in GLUTag cells when compared to baseline (except for 0.25mM acesulfame‐k) and values were similar to glucose‐induced GLP‐1 secretion. Cells incubated in a combination of Canderel® and glucose (0.4mM and 5mM) showed the highest secretion of GLP‐1; indicating a potential synergistic effect of AS and other nutrients in EEC function. Of the disaccharides tested, maltose showed a significant dose‐responsive increase in GLP‐1 secretion from 0–5mM with values nearly similar to glucose induced secretion over the same concentration range. Gene expression studies by RT‐PCR showed the sweet taste receptors (T1R3) and maltase‐glucoamylase (MGAM) gene to be expressed in the cell line; suggesting the potential mechanism behind AS and maltose sensing in EEC. These in vitro results indicate a possible role for AS and the disaccharide maltose in promoting incretin hormone secretion and having an impact on glycaemia.Support or Funding InformationSelf‐funded projectThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The effects of artificial sweeteners (AS) on the peptide hormone-producing enteroendocrine cells (EEC) of the gastrointestinal tract are controversial (contradictory studies in humans, animals and cells) (1). Recently, sucralose, a highly potent AS, has been shown to induce secretion of the insulin regulating and blood glucose lowering hormone, glucagon-like peptide 1 (GLP-1), from intestinal in vitro models (2). It is suggested that it may be interacting with the sweet taste-receptors found on EECs (3). However the effects of other commonly used AS in the UK, such as aspartame, acesulfame-k and Canderel ® (1.4 % aspartame; 0.95 % acesulfame-k) have not been investigated. The aim of the present study was to assess the effects of these AS on GLP-1 secretion in GLUTag cells (mouse EEC line). GLUTag cells were incubated with test reagents for 2 hours at 37 o C and the supernatant collected. GLP-1 was measured from the supernatant using a GLP-1 (Active) ELISA assay (EMD Millipore ® , UK). Data is presented as means and standard deviation. At dietary relevant doses (0.25-5 mM) the individual AS, aspartame and acesulfame-k, and the AS mixture, Canderel ® significantly induced GLP-1 secretion in GLUTag cells when compared to baseline (except for 0.25 mM acesulfame-k) and values were similar to glucose-induced GLP-1 secretion (table 1). Cells incubated in a combination of Canderel ® and glucose (0.4 mM and 5 mM) showed the highest secretion of GLP-1 (table 1); indicating a potential synergistic effect of AS and other nutrients in EEC function. In conclusion, our in vitro data suggests certain AS given alone and in combination with glucose may result in a GLP-1 response.

Differences in the sweetness transduction cascade, and neuronal signalling may result in incretin hormone release upon activation of the sweet taste receptor from some sweeteners, but not others.

Due to the rise in diabetes rates across the world, the enteroendocrine cells (EEC) of the small intestine have gathered much interest in recent years because of their roles in secreting the incretin hormones, glucagon‐like peptide 1 (GLP‐1) and glucose‐dependent insulinotropic peptide (GIP) in response to ingested carbohydrates. Both GLP‐1 and GIP promote insulin synthesis and secretion and therefore play an important role in controlling blood glucose levels. While glucose induced incretin secretion by EEC cells has been well established, the response of EEC cells to other dietary carbohydrates, such as the dissacharides, and non‐nutritive sweeteners, such as artificial sweeteners (AS), is less well understood. Thus, to investigate the effects of the AS, aspartame, acesfulfame‐K and Canderel® (1.4% aspartame;0.95% acesulfame‐k) and the disaccharides, maltose, sucrose, trehalose and lactose on GLP‐1 secretion, we used the mouse EEC line, GLUTag, a well established model of the L cell, which is predominantly found in the distal regions of the small intestine. GLUTag cells were incubated with the AS (at 0, 0.25, 0.4 and 5mM), and the disaccharides and glucose (at 0, 0.25, 0.5, 2.5, 5, 12.5, 25 and 50mM) for 2 hours at 37° C and the supernatant collected. GLP‐1 was measured from the supernatant using a GLP‐1 (Active) ELISA assay (EMD Millipore®, UK). Our results showed that at dietary relevant doses (0.25–5mM) the individual AS, aspartame and acesulfame‐k, and the AS mixture, Canderel® significantly induced GLP‐1 secretion in GLUTag cells when compared to baseline (except for 0.25mM acesulfame‐k) and values were similar to glucose‐induced GLP‐1 secretion. Cells incubated in a combination of Canderel® and glucose (0.4mM and 5mM) showed the highest secretion of GLP‐1; indicating a potential synergistic effect of AS and other nutrients in EEC function. Of the disaccharides tested, maltose showed a significant dose‐responsive increase in GLP‐1 secretion from 0–5mM with values nearly similar to glucose induced secretion over the same concentration range. Gene expression studies by RT‐PCR showed the sweet taste receptors (T1R3) and maltase‐glucoamylase (MGAM) gene to be expressed in the cell line; suggesting the potential mechanism behind AS and maltose sensing in EEC. These in vitro results indicate a possible role for AS and the disaccharide maltose in promoting incretin hormone secretion and having an impact on glycaemia. Support or Funding Information Self‐funded project This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.