Acute and two-week effects of neotame, stevia rebaudioside M and sucrose-sweetened biscuits on postprandial appetite and endocrine response in adults with overweight/obesity-a randomised crossover trial from the SWEET consortium.

BACKGROUND: Sweeteners and sweetness enhancers (S&SE) are used to replace energy yielding sugars and maintain sweet taste in a wide range of products, but controversy exists about their effects on appetite and endocrine responses in reduced or no added sugar solid foods. The aim of the current study was to evaluate the acute (1 day) and repeated (two-week daily) ingestive effects of 2 S&SE vs. sucrose formulations of biscuit with fruit filling on appetite and endocrine responses in adults with overweight and obesity. METHODS: In a randomised crossover trial, 53 healthy adults (33 female, 20 male) with overweight/obesity in England and France consumed biscuits with fruit filling containing 1) sucrose, or reformulated with either 2) Stevia Rebaudioside M (StRebM) or 3) Neotame daily during three, two-week intervention periods with a two-week washout. The primary outcome was composite appetite score defined as [desire to eat + hunger + (100 - fullness) + prospective consumption]/4. FINDINGS: Each formulation elicited a similar reduction in appetite sensations (3-h postprandial net iAUC). Postprandial insulin (2-h iAUC) was lower after Neotame (95% CI (0.093, 0.166); p < 0.001; d = -0.71) and StRebM (95% CI (0.133, 0.205); p < 0.001; d = -1.01) compared to sucrose, and glucose was lower after StRebM (95% CI (0.023, 0.171); p < 0.05; d = -0.39) but not after Neotame (95% CI (-0.007, 0.145); p = 0.074; d = -0.25) compared to sucrose. There were no differences between S&SE or sucrose formulations on ghrelin, glucagon-like peptide 1 or pancreatic polypeptide iAUCs. No clinically meaningful differences between acute vs. two-weeks of daily consumption were found. INTERPRETATION: In conclusion, biscuits reformulated to replace sugar using StRebM or Neotame showed no differences in appetite or endocrine responses, acutely or after a two-week exposure, but can reduce postprandial insulin and glucose response in adults with overweight or obesity. FUNDING: The present study was funded by the Horizon 2020 program: Sweeteners and sweetness enhancers: Impact on health, obesity, safety and sustainability (acronym: SWEET, grant no: 774293).

Impact of acute consumption of beverages containing plant-based or alternative sweetener blends on postprandial appetite, food intake, metabolism, and gastro-intestinal symptoms: Results of the SWEET beverages trial.

Project SWEET examined the barriers and facilitators to the use of non-nutritive sweeteners and sweetness enhancers (hereafter "S&SE") alongside potential risks/benefits for health and sustainability. The Beverages trial was a double-blind multi-centre, randomised crossover trial within SWEET evaluating the acute impact of three S&SE blends (plant-based and alternatives) vs. a sucrose control on glycaemic response, food intake, appetite sensations and safety after a carbohydrate-rich breakfast meal. The blends were: mogroside V and stevia RebM; stevia RebA and thaumatin; and sucralose and acesulfame-potassium (ace-K). At each 4 h visit, 60 healthy volunteers (53% male; all with overweight/obesity) consumed a 330 mL beverage with either an S&SE blend (0 kJ) or 8% sucrose (26 g, 442 kJ), shortly followed by a standardised breakfast (∼2600 or 1800 kJ with 77 or 51 g carbohydrates, depending on sex). All blends reduced the 2-h incremental area-under-the-curve (iAUC) for blood insulin (p < 0.001 in mixed-effects models), while the stevia RebA and sucralose blends reduced the glucose iAUC (p < 0.05) compared with sucrose. Post-prandial levels of triglycerides plus hepatic transaminases did not differ across conditions (p > 0.05 for all). Compared with sucrose, there was a 3% increase in LDL-cholesterol after stevia RebA-thaumatin (p < 0.001 in adjusted models); and a 2% decrease in HDL-cholesterol after sucralose-ace-K (p < 0.01). There was an impact of blend on fullness and desire to eat ratings (both p < 0.05) and sucralose-acesulfame K induced higher prospective intake vs sucrose (p < 0.001 in adjusted models), but changes were of a small magnitude and did not translate into energy intake differences over the next 24 h. Gastro-intestinal symptoms for all beverages were mostly mild. In general, responses to a carbohydrate-rich meal following consumption of S&SE blends with stevia or sucralose were similar to sucrose.

Acute and repeated impact of sweeteners and sweetness enhancers in solid and semi-solid foods on appetite: protocol for a multicentre, cross-over, RCT in people with overweight/obesity - the SWEET Project.

INTRODUCTION: Intake of free sugars in European countries is high and attempts to reduce sugar intake have been mostly ineffective. Non-nutritive sweeteners and sweetness enhancers (S&SEs) can maintain sweet taste in the absence of energy, but little is known about the impact of acute and repeated consumption of S&SE in foods on appetite. This study aims to evaluate the effect of acute and repeated consumption of two individual S&SEs and two S&SE blends in semisolid and solid foods on appetite and related behavioural, metabolic and health outcomes. METHODS AND ANALYSIS: A work package of the SWEET Project; this study consists of five double-blind randomised cross-over trials which will be carried out at five sites across four European countries, aiming to have n=213. Five food matrices will be tested across three formulations (sucrose-sweetened control vs two reformulated products with S&SE blends and no added sugar). Participants (body mass index 25-35 kg/m2; aged 18-60 years) will consume each formulation for 14 days. The primary endpoint is composite appetite score (hunger, inverse of fullness, desire to eat and prospective food consumption) over a 3-hour postprandial incremental area under the curve during clinical investigation days on days 1 and 14. ETHICS AND DISSEMINATION: The trial has been approved by national ethical committees and will be conducted in accordance with the Declaration of Helsinki. Results will be published in international peer-reviewed open-access scientific journals. Research data from the trial will be deposited in an open-access online research data archive. TRIAL REGISTRATION NUMBER: NCT04633681.

Protocol for a multicentre, parallel, randomised, controlled trial on the effect of sweeteners and sweetness enhancers on health, obesity and safety in overweight adults and children: the SWEET project.

INTRODUCTION: The aim of this randomised controlled trial (RCT) is to investigate whether prolonged consumption of sweeteners and sweetness enhancers (S&SEs) within a healthy diet will improve weight loss maintenance and obesity-related risk factors and affect safety markers compared with sugar. METHODS AND ANALYSIS: SWEET (S&SEs: prolonged effects on health, obesity and safety) is a 1-year multicentre RCT including at least 330 adults with overweight (18-65 years, body mass index (BMI) >25 kg/m2) and 40 children (6-12 years, BMI-for-age >85th percentile). In an initial 2-month period, adults will consume a low-energy diet with the aim to achieve ≥5% weight loss. Children are advised to consume a generally healthy diet to maintain body weight, thus reducing their BMI-for-age z-score. In the following 10 months, participants will be randomised to follow a healthy ad libitum diet with or without S&SE products. Clinical investigations are scheduled at baseline, after 2, 6 and 12 months. The primary outcomes are body weight for efficacy and gut microbiota composition (in relation to metabolic health) for safety, both in adults. Secondary outcomes include anthropometry, risk markers for type-2 diabetes and cardiovascular diseases, questionnaires including, for example, food preferences, craving and appetite and tests for allergenicity. ETHICS AND DISSEMINATION: The trial protocol has been approved by the following national ethical committees; The research ethics committees of the capital region (Denmark), approval code: H-19040679, The medical ethics committee of the University Hospital Maastricht and Maastricht University (the Netherlands), approval code: NL70977.068.19/METC19-056s, Research Ethics Committee of the University of Navarra (Spain), approval code: 2019.146 mod1, Research Ethics Committee of Harokopio University (Greece), approval code: 1810/18-06-2019. The trial will be conducted in accordance with the Declaration of Helsinki. Results will be published in international peer-reviewed scientific journals regardless of whether the findings are positive, negative or inconclusive. TRIAL REGISTRATION NUMBER: NCT04226911 (Clinicaltrials.gov).