Replacing sugars with the alternative sweeteners rrythritol and D-allulose

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 intragastric administration of erythritol, D allulose, or tap water, with or without lactisole (a T1R2/T1R3 receptor antagonist), respectively, in six sessions. Erythritol and D-allulose induced a significant release of CCK, GLP-1 ,and PYY compared to tap water. Lactisole did not affect the erythritol- and D-allulose-induced release of these GI satiation hormones. The lack of effect of lactisole suggests that erythritol- and D-allulose-induced GI satiation hormone release is not mediated via T1R2/T1R3 in the gut and that other receptor/transporters are responsible.
In part II of the first study, we assessed different metabolic parameters and safety aspects of acute intragastric administration of erythritol and D-allulose. We found that both alternative sweeteners show beneficial physiological effects regarding glycemic control and the release of ghrelin, and have no effects on blood lipids, uric acid and high-sensitive C-reactive protein (hsCRP). This indicates that erythritol and D-allulose are, at least in the short-term, effective as sugar alternatives and have a positive safety profile.
In the second study, we compared the effect of oral administration of erythritol to sucrose, sucralose, or tap water on energy intake during a subsequent ad libitum test meal and examined the release of CCK in response to these substances. We found that (total) energy intake was significantly lower after erythritol compared to sucrose, sucralose, or tap water. Before the start of the ad libitum test meal, erythritol led to a significant increase in CCK compared to the other substances. These findings document once more the potential role for erythritol as a useful sugar alternative. Moreover, our results challenge the existing paradigm that only nutrients with calories are able to induce a satiating effect and decrease subsequent energy intake.
In summary, the results of both studies demonstrate that alternative sweeteners have unique physiological effects and should be evaluated independently and not as a homogenous group. Additionally, the acute findings of erythritol but also D-allulose indicate that they are simple and effective sugar alternatives that can be used by healthy individuals, but also by people with obesity and other NCDs, as a preventative or therapeutic approach. Whether these acute effects sustain in more long-term studies needs to be investigated.