{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T08:20:22Z","timestamp":1788337222172,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EU Horizon 2020","award":["774293"],"award-info":[{"award-number":["774293"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Sweeteners and sweetness enhancers (S&amp;SEs) have been proposed to impair energy metabolism acutely and over time. Methods: This sub-study investigated the acute effects of a mixture of acesulfame potassium and cyclamate (Ace-K\/Cyc) versus water on postprandial substrate oxidation, energy expenditure, and glucose and insulin concentrations at baseline, after a 2-month weight loss period, and after a 4-month weight loss maintenance period including or excluding S&amp;SEs in the diet. In both groups, allowed added sugar intake was &lt;10 energy-%. A total of 26 participants (18\u201365 years; BMI \u2265 25.0 kg\/m2) were recruited from the 1-year randomized controlled SWEET trial, and 16 completed the final test day. Fasting measurements were taken (ventilated hood; blood samples) before a standardized breakfast. Hereafter, postprandial measurements were taken until time point 250 min. At time point 120 min, a test drink containing either Ace-K\/Cyc or water was served. Result: There were no differences between the two groups in fasting or postprandial fat oxidation (primary outcome), carbohydrate oxidation, energy expenditure, glucose, or insulin (secondary outcomes) on or across the three test days (p &gt; 0.05). Conclusions: There were no statistically significant differences between Ace-K\/Cyc and water in postprandial fat oxidation, carbohydrate oxidation, energy expenditure, or glucose or insulin either acutely, after a weight loss period, or after a 4-month period including or excluding S&amp;SEs in the diet. The low number of participants should, however, be considered a limitation of our conclusions.<\/jats:p>","DOI":"10.3390\/nu18172863","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T07:53:11Z","timestamp":1788335591000},"page":"2863","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Acute and Prolonged Effects of Sweeteners and Sweetness Enhancers on Postprandial Substrate Oxidation, Energy Expenditure, Glucose, and Insulin in Humans\u2014A SWEET Sub-Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0336-3785","authenticated-orcid":false,"given":"Sabina S. H.","family":"Andersen","sequence":"first","affiliation":[{"name":"Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, 1958 Frederiksberg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4310-9332","authenticated-orcid":false,"given":"Louise","family":"Kj\u00f8lb\u00e6k","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, 1958 Frederiksberg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1629-3189","authenticated-orcid":false,"given":"Jason C. G.","family":"Halford","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Leeds, Leeds LS2 9JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Joanne A.","family":"Harrold","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Liverpool, Liverpool L69 7ZX, UK"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5229-4491","authenticated-orcid":false,"given":"Anne","family":"Raben","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, 1958 Frederiksberg, Denmark"},{"name":"Clinical Prevention Research, Copenhagen University Hospital\u2013Steno Diabetes Center Copenhagen, 2730 Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1007\/s13197-011-0571-1","article-title":"Artificial Sweeteners\u2014A Review","volume":"51","author":"Chattopadhyay","year":"2014","journal-title":"J. Food Sci. Technol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1093\/nutrit\/nuw032","article-title":"Biological Fate of Low-Calorie Sweeteners","volume":"74","author":"Magnuson","year":"2016","journal-title":"Nutr. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.1080\/10408398.2019.1625859","article-title":"A Review of Polyols\u2013Biotechnological Production, Food Applications, Regulation, Labeling and Health Effects","volume":"60","author":"Rice","year":"2020","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00217-015-2437-7","article-title":"Sugar Alcohols-Their Role in the Modern World of Sweeteners: A Review","volume":"241","author":"Grembecka","year":"2015","journal-title":"Eur. Food Res. Technol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.38212\/2224-6614.3107","article-title":"Suitability of Sugar Alcohols as Antidiabetic Supplements: A Review","volume":"29","author":"Msomi","year":"2021","journal-title":"J. Food Drug Anal."},{"key":"ref_6","first-page":"425","article-title":"An Update on Alternative Sweeteners","volume":"110","author":"Funes","year":"2008","journal-title":"Int. Sugar J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1079\/NRR200371","article-title":"Health Potential of Polyols as Sugar Replacers, with Emphasis on Low Glycaemic Properties","volume":"16","author":"Livesey","year":"2003","journal-title":"Nutr. Res. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1039\/D0FO02424D","article-title":"A Rational Review on the Effects of Sweeteners and Sweetness Enhancers on Appetite, Food Reward and Metabolic\/Adiposity Outcomes in Adults","volume":"12","author":"Pang","year":"2021","journal-title":"Food Funct."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Pang, M.D., Goossens, G.H., and Blaak, E.E. (2021). The Impact of Artificial Sweeteners on Body Weight Control and Glucose Homeostasis. Front. Nutr., 7.","DOI":"10.3389\/fnut.2020.598340"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1007\/s11894-017-0602-9","article-title":"The Association Between Artificial Sweeteners and Obesity","volume":"19","author":"Pearlman","year":"2017","journal-title":"Curr. Gastroenterol. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1111\/j.1467-789X.2012.01009.x","article-title":"Gut Microbial Adaptation to Dietary Consumption of Fructose, Artificial Sweeteners and Sugar Alcohols: Implications for Host-Microbe Interactions Contributing to Obesity","volume":"13","author":"Payne","year":"2012","journal-title":"Obes. Rev."},{"key":"ref_12","first-page":"1289","article-title":"Physiological Mechanisms by Which Non-Nutritive Sweeteners May Impact Body Weight and Metabolism","volume":"30","author":"Burke","year":"2015","journal-title":"Physiol. Behav."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.physbeh.2016.04.029","article-title":"Reshaping the Gut Microbiota: Impact of Low Calorie Sweeteners and the Link to Insulin Resistance?","volume":"164","author":"Nettleton","year":"2016","journal-title":"Physiol. Behav."},{"key":"ref_14","first-page":"129","article-title":"Non-Nutritive Sweeteners: Evidence on Their Association with Metabolic Diseases and Potential Effects on Glucose Metabolism and Appetite","volume":"69","year":"2017","journal-title":"Rev. Investig. Clin."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3945\/ajcn.2008.26792","article-title":"Nonnutritive Sweetener Consumption in Humans: Effects on Appetite and Food Intake and Their Putative Mechanisms","volume":"89","author":"Mattes","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_16","unstructured":"World Health Organization (WHO) (2023). Guideline: Use of Non-Sugar Sweeteners, World Health Organization (WHO)."},{"key":"ref_17","unstructured":"World Health Organization (WHO) (2022). Health Effects of the Use of Non-Sugar Sweeteners: A Systematic Review and Meta-Analysis, World Health Organization (WHO)."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1017\/S0954422419000283","article-title":"Expert Consensus on Low-Calorie Sweeteners: Facts, Research Gaps and Suggested Actions","volume":"33","author":"Ashwell","year":"2020","journal-title":"Nutr. Res. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1111\/j.1742-1241.2009.02056.x","article-title":"Observational Studies: A Review of Study Designs, Challenges and Strategies to Reduce Confounding","volume":"63","author":"Lu","year":"2009","journal-title":"Int. J. Clin. Pract."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e222092","DOI":"10.1001\/jamanetworkopen.2022.2092","article-title":"Association of Low- and No-Calorie Sweetened Beverages as a Replacement for Sugar-Sweetened Beverages with Body Weight and Cardiometabolic Risk: A Systematic Review and Meta-Analysis","volume":"5","author":"McGlynn","year":"2022","journal-title":"JAMA Netw. Open"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zhang, R., Noronha, J.C., Khan, T.A., Mcglynn, N., Back, S., Grant, S.M., Kendall, C.W.C., and Sievenpiper, J.L. (2023). The Effect of Non-Nutritive Sweetened Beverages on Postprandial Glycemic and Endocrine Responses: A Systematic Review and Network Meta-Analysis. Nutrients, 15.","DOI":"10.3390\/nu15041050"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/s41366-020-00704-2","article-title":"The Effects of Low-Calorie Sweeteners on Energy Intake and Body Weight: A Systematic Review and Meta-Analyses of Sustained Intervention Studies","volume":"45","author":"Rogers","year":"2021","journal-title":"Int. J. Obes."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/ijo.2015.177","article-title":"Does Low-Energy Sweetener Consumption Affect Energy Intake and Body Weight? A Systematic Review, Including Meta-Analyses, of the Evidence from Human and Animal Studies","volume":"40","author":"Rogers","year":"2016","journal-title":"Int. J. Obes."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"k4718","DOI":"10.1136\/bmj.k4718","article-title":"Association between Intake of Non-Sugar Sweeteners and Health Outcomes: Systematic Review and Meta-Analyses of Randomised and Non-Randomised Controlled Trials and Observational Studies","volume":"364","author":"Toews","year":"2019","journal-title":"BMJ"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Andersen, S.S.H., Zhu, R., Kj\u00f8lb\u00e6k, L., and Raben, A. (2023). Effect of Non- and Low-Caloric Sweeteners on Substrate Oxidation, Energy Expenditure, and Catecholamines in Humans\u2014A Systematic Review. Nutrients, 15.","DOI":"10.3390\/nu15122711"},{"key":"ref_26","unstructured":"Hunt, F., Bopp, B.A., and Price, P. (2016). Cyclamate. Alternative Sweeteners, CRC Press. [4th ed.]."},{"key":"ref_27","first-page":"379","article-title":"Functional Roles of the Sweet Taste Receptor in Oral and Extraoral Tissues","volume":"17","author":"Laffitte","year":"2014","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"32475","DOI":"10.1074\/jbc.M113.514034","article-title":"Artificial Sweeteners Stimulate Adipogenesis and Suppress Lipolysis Independently of Sweet Taste Receptors","volume":"288","author":"Simon","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e061075","DOI":"10.1136\/bmjopen-2022-061075","article-title":"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","volume":"12","author":"Manios","year":"2022","journal-title":"BMJ Open"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1038\/s42255-025-01381-z","article-title":"Effect of sweeteners and sweetness enhancers on weight management and gut microbiota composition in individuals with overweight or obesity: The SWEET study","volume":"7","author":"Pang","year":"2025","journal-title":"Nat. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Andersen, S.S.H., Kj\u00f8lb\u00e6k, L., Halford, J.C.G., Harrold, J.A., and Raben, A. (2026). Acute and Prolonged Effects of Sweeteners and Sweetness Enhancers on Postprandial Appetite Sensations, Palatability, and Ad Libitum Energy Intake in Humans: A SWEET Sub-Study. Nutrients, 18.","DOI":"10.20944\/preprints202601.2326.v1"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1159\/000421672","article-title":"Energy Expenditure and Fuel Selection in Biological Systems: The Theory and Practice of Calculations Based on Indirect Calorimetry and Tracer Methods","volume":"70","author":"Elia","year":"1992","journal-title":"World Rev. Nutr. Diet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1177\/02601060211057415","article-title":"Comparison of Aspartame- and Sugar-Sweetened Soft Drinks on Postprandial Metabolism","volume":"29","author":"Pearson","year":"2023","journal-title":"Nutr. Health"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Chern, C., and Tan, S.-Y. (2019). Energy Expenditure, Carbohydrate Oxidation and Appetitive Responses to Sucrose or Sucralose in Humans: A Pilot Study. Nutrients, 11.","DOI":"10.3390\/nu11081782"},{"key":"ref_35","first-page":"47","article-title":"Effect of Sucrose and Sweetener on Appetite Sensation and Energy Expenditure in Normal Weight and Overweight Subjects","volume":"19","author":"Mourao","year":"2004","journal-title":"Rev. Bras. Nutr. Clin."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"36","DOI":"10.3945\/ajcn.113.081554","article-title":"Sucrose Compared with Artificial Sweeteners: A Clinical Intervention Study of Effects on Energy Intake, Appetite, and Energy Expenditure after 10 Wk of Supplementation in Overweight Subjects","volume":"100","author":"Vasilaras","year":"2014","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1743-7075-1-5","article-title":"Diet Induced Thermogenesis","volume":"1","author":"Westerterp","year":"2004","journal-title":"Nutr. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1006\/appe.1999.0310","article-title":"Sweet Taste of Aspartame and Sucrose: Effects on Diet-Induced Thermogenesis","volume":"34","author":"Oppert","year":"2000","journal-title":"Appetite"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/17\/2863\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T07:57:14Z","timestamp":1788335834000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/17\/2863"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,2]]},"references-count":38,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["nu18172863"],"URL":"https:\/\/doi.org\/10.3390\/nu18172863","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,2]]}}}