Obesity is a worldwide growing public health concern. The causes of obesity are complex and the health consequences significant. They not only include an increased risk of non-communicable diseases (NCDs), such as type two diabetes mellitus (T2DM) or cardiovascular disease (CVD), but also a number of psychosocial issues, such as low self-esteem, depression, and discrimination. The availability and affordability of high-caloric foods, especially sugar-sweetened beverages (SSBs) and their overconsumption, contribute to its development. Currently, pharmacotherapy or surgery are the main management tools applied to treat obesity and associated NCDs. These interventions have, however, a significant impact on quality of life, and are associated with a financial burden. In 2015, the World Health Organisation (WHO) published a guideline to limit sugar intake worldwide as a simple, effective, and low-cost strategy that can be used both preventively and therapeutically. A possible way to implement this guideline is to substitute sugar with artificial low-caloric sweeteners (LCS) to meet the desire for sweet taste with minimal or no caloric intake. However, the potential health impacts of artificial LCS ingestion remain a topic of ongoing debate, with no definitive consensus regarding their overall benefits or harms. Therefore, two other alternative sweetener classes, low-caloric bulk sweeteners and rare sugars, are emerging. Representatives include the non-caloric bulk sweetener erythritol and the rare sugar D-allulose. The focus of this thesis was to study the effects of substituting sugar with erythritol and D allulose in healthy humans. These aims were pursued in two clinical studies. In part I of the first study, we investigated the involvement of the gut sweet taste receptor T1R2/T1R3 in the release of gastrointestinal (GI) satiation hormones, such as cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and peptide tyrosine tyrosine (PYY) in response to erythritol and D-allulose. Participants received an ...