Sweeteners and Sweetness Enhancers’ Acute and Prolonged Effects on Substrate Oxidation, Energy Expenditure, and Appetite

PhD defence by 

Sabina Stoffer Hjorth Andersen

About the PhD thesis

Non- and low-caloric sweeteners (NCS/LCS) have been proposed to promote impaired energy metabolism acutely and over time. As a group, NCS and LCS can be defined as sweeteners and sweetness enhancers (S&SEs).

Previous randomized controlled trials (RCTs) in humans have overall not found adverse effects on appetite and glucose regulation. Their impact on substrate oxidation and energy expenditure is less explored. This PhD project aimed to investigate how S&SEs affect substrate oxidation, energy expenditure, and appetite.

The PhD thesis is built on 4 papers; Paper I systematically reviewed the existing literature assessing the impact of NCS and LCS on substrate oxidation, energy expenditure, and catecholamines compared to caloric sweeteners, water, and various doses and types of NCS and LCS.

Paper II presented a 1-year European multicenter RCT assessing prolonged effects of S&SEs on health, obesity, and safety – the SWEET WP3 study.

Paper III and IV presented the design and results of an RCT sub-study including participants from SWEET WP3. The aim of this sub-study was to investigate the acute effects of a mixture of acesulfame potassium and cyclamate versus water on postprandial substrate oxidation and energy expenditure, glucose and insulin concentrations, and appetite at baseline, after a 2-month weight loss period, and after a 4–month weight loss maintenance period with either S&SEs or sugar in the diet.

Overall, data from the papers included in this thesis find evidence to suggest that NCS have similar effects as water on substrate oxidation and energy expenditure both acutely and in the longer-term. Regarding appetite, Paper IV suggests that acesulfame potassium and cyclamate may induce sensory-specific satiety acutely both at baseline and after regular exposure to S&SEs.

For LCS, less data are in general available. However, based on the findings in Paper I, it can be concluded that compared to caloric sweeteners, LCS do not seem do exert any effect on substrate oxidation beyond what can be expected based on their energy load and metabolism. However, more long-term studies are warranted for both NCS and LCS across all outcomes. The studies should include a range of S&SEs and include isoenergetic comparators.

2024, 134 pages.

Download Publications; Summary; Sammendrag (Danish summary); Table of contents.


5 March 2024, 13:00


Aud. A2-70.04, Thorvaldsensvej 40, st., Frederiksberg


Professor Inge Tetens (chair), Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark. 

Emeritus Professor Peter John Rogers, School of Psychological Science, University of Bristol, United Kingdom.

Associate Professor Per Bendix Jeppesen, Department of Clinical Medicine, Faculty of Health, University of Aarhus, Denmark.

Principal supervisor

Professor Anne Raben, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark.


Assistant professor Louise Kjølbæk, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark.