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1.
Metabolic Effects of Selected Conventional and Alternative Sweeteners: A Narrative Review.
Teysseire, F, Bordier, V, Beglinger, C, Wölnerhanssen, BK, Meyer-Gerspach, AC
Nutrients. 2024;(5)
Abstract
Sugar consumption is known to be associated with a whole range of adverse health effects, including overweight status and type II diabetes mellitus. In 2015, the World Health Organization issued a guideline recommending the reduction of sugar intake. In this context, alternative sweeteners have gained interest as sugar substitutes to achieve this goal without loss of the sweet taste. This review aims to provide an overview of the scientific literature and establish a reference tool for selected conventional sweeteners (sucrose, glucose, and fructose) and alternative sweeteners (sucralose, xylitol, erythritol, and D-allulose), specifically focusing on their important metabolic effects. The results show that alternative sweeteners constitute a diverse group, and each substance exhibits one or more metabolic effects. Therefore, no sweetener can be considered to be inert. Additionally, xylitol, erythritol, and D-allulose seem promising as alternative sweeteners due to favorable metabolic outcomes. These alternative sweeteners replicate the benefits of sugars (e.g., sweetness and gastrointestinal hormone release) while circumventing the detrimental effects of these substances on human health.
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2.
Metabolic Effects and Safety Aspects of Acute D-allulose and Erythritol Administration in Healthy Subjects.
Teysseire, F, Bordier, V, Budzinska, A, Van Oudenhove, L, Weltens, N, Beglinger, C, Wölnerhanssen, BK, Meyer-Gerspach, AC
Nutrients. 2023;(2)
Abstract
The rapid increase in sugar consumption is associated with various negative metabolic and inflammatory effects; therefore, alternative sweeteners become of interest. The aim of this study was to investigate the metabolic effects and safety aspects of acute D-allulose and erythritol on glucose, insulin, ghrelin, blood lipids, uric acid, and high-sensitive C-reactive protein (hsCRP). In three study visits, 18 healthy subjects received an intragastric administration of 25 g D-allulose or 50 g erythritol, or 300 mL tap water (placebo) in a randomized, double-blind and crossover order. To measure the aforementioned parameters, blood samples were drawn at fixed time intervals. Glucose and insulin concentrations were lower after D-allulose compared to tap water (p = 0.001, dz = 0.91 and p = 0.005, dz = 0.58, respectively); however, Bayesian models show no difference for insulin in response to D-allulose compared to tap water, and there was no effect after erythritol. An exploratory analysis showed that ghrelin concentrations were reduced after erythritol compared to tap water (p = 0.026, dz = 0.59), with no effect after D-allulose; in addition, both sweeteners had no effect on blood lipids, uric acid and hsCRP. This combination of properties identifies both sweeteners as excellent candidates for effective and safe sugar alternatives.
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3.
The Role of D-allulose and Erythritol on the Activity of the Gut Sweet Taste Receptor and Gastrointestinal Satiation Hormone Release in Humans: A Randomized, Controlled Trial.
Teysseire, F, Bordier, V, Budzinska, A, Weltens, N, Rehfeld, JF, Holst, JJ, Hartmann, B, Beglinger, C, Van Oudenhove, L, Wölnerhanssen, BK, et al
The Journal of nutrition. 2022;(5):1228-1238
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Abstract
BACKGROUND Glucose induces the release of gastrointestinal (GI) satiation hormones, such as glucagon-like peptide 1 (GLP-1) and peptide tyrosine tyrosine (PYY), in part via the activation of the gut sweet taste receptor (T1R2/T1R3). OBJECTIVES The primary objective was to investigate the importance of T1R2/T1R3 for the release of cholecystokinin (CCK), GLP-1, and PYY in response to D-allulose and erythritol by assessing the effect of the T1R2/T1R3 antagonist lactisole on these responses and as secondary objectives to study the effect of the T1R2/T1R3 blockade on gastric emptying, appetite-related sensations, and GI symptoms. METHODS In this randomized, controlled, double-blind, crossover study, 18 participants (5 men) with a mean ± SD BMI (in kg/m2) of 21.9 ± 1.7 and aged 24 ± 4 y received an intragastric administration of 25 g D-allulose, 50 g erythritol, or tap water, with or without 450 parts per million (ppm) lactisole, respectively, in 6 different sessions. 13C-sodium acetate was added to all solutions to determine gastric emptying. At fixed time intervals, blood and breath samples were collected, and appetite-related sensations and GI symptoms were assessed. Data were analyzed with linear mixed-model analysis. RESULTS D-allulose and erythritol induced a significant release of CCK, GLP-1, and PYY compared with tap water (all PHolm < 0.0001, dz >1). Lactisole did not affect the D-allulose- and erythritol-induced release of CCK, GLP-1, and PYY (all PHolm > 0.1). Erythritol significantly delayed gastric emptying, increased fullness, and decreased prospective food consumption compared with tap water (PHolm = 0.0002, dz = -1.05; PHolm = 0.0190, dz = 0.69; and PHolm = 0.0442, dz = -0.62, respectively). CONCLUSIONS D-allulose and erythritol stimulate the secretion of GI satiation hormones in humans. Lactisole had no effect on CCK, GLP-1, and PYY release, indicating that D-allulose- and erythritol-induced GI satiation hormone release is not mediated via T1R2/T1R3 in the gut.
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Erythritol and xylitol differentially impact brain networks involved in appetite regulation in healthy volunteers.
Meyer-Gerspach, AC, Wingrove, JO, Beglinger, C, Rehfeld, JF, Le Roux, CW, Peterli, R, Dupont, P, O'Daly, O, Van Oudenhove, L, Wölnerhanssen, BK
Nutritional neuroscience. 2022;(11):2344-2358
Abstract
BACKGROUND There is a growing consensus that sugar consumption should be reduced and the naturally occurring, low-calorie sweeteners xylitol and erythritol are gaining popularity as substitutes, but their effect on brain circuitry regulating appetite is unknown. AIM: The study's objective was to examine the effects of the two sweeteners on cerebral blood flow (rCBF) and resting functional connectivity in brain networks involved in appetite regulation, and test whether these effects are related to gut hormone release. METHODS The study was performed as a randomized, double-blind, placebo-controlled, cross-over trial. Twenty volunteers received intragastric (ig) loads of 50g xylitol, 75g erythritol, 75g glucose dissolved in 300mL tap water or 300mL tap water. Resting perfusion and blood oxygenation level-dependent data were acquired to assess rCBF and functional connectivity. Blood samples were collected for determination of CCK, PYY, insulin and glucose. RESULTS We found: (i) xylitol, but not erythritol, increased rCBF in the hypothalamus, whereas glucose had the opposite effect; (ii) graph analysis of resting functional connectivity revealed a complex pattern of similarities and differences in brain network properties following xylitol, erythritol, and glucose; (iii) erythritol and xylitol induced a rise in CCK and PYY, (iv) erythritol had no and xylitol only minimal effects on glucose and insulin. CONCLUSION Xylitol and erythritol have a unique combination of properties: no calories, virtually no effect on glucose and insulin while promoting the release of gut hormones, and impacting appetite-regulating neurocircuitry consisting of both similarities and differences with glucose.
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Absorption and Metabolism of the Natural Sweeteners Erythritol and Xylitol in Humans: A Dose-Ranging Study.
Bordier, V, Teysseire, F, Senner, F, Schlotterbeck, G, Drewe, J, Beglinger, C, Wölnerhanssen, BK, Meyer-Gerspach, AC
International journal of molecular sciences. 2022;(17)
Abstract
The natural sweeteners erythritol and xylitol might be helpful to reduce sugar consumption and therefore prevent obesity and diabetes. The aim of the present study was to determine the absorption and metabolization into erythronate of different concentrations of erythritol and xylitol. Seventeen healthy lean participants received intragastric solutions of 10, 25, or 50 g erythritol or 7, 17, or 35 g xylitol on three study days in a randomized order. The study was double blinded with respect to the doses administered. We assessed plasma concentrations of erythritol, xylitol, and erythronate at fixed time intervals after administration with gas chromatography-mass spectrometry. We found: (i) a dose-dependent and saturable absorption of erythritol, (ii) a very low absorption of xylitol, (iii) a dose-dependent metabolization of erythritol into erythronate, and (iv) no metabolization of xylitol into erythronate. The implications of the metabolization of erythritol into erythronate for human health remain to be determined and more research in this area is needed.
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Oral Erythritol Reduces Energy Intake during a Subsequent ad libitum Test Meal: A Randomized, Controlled, Crossover Trial in Healthy Humans.
Teysseire, F, Flad, E, Bordier, V, Budzinska, A, Weltens, N, Rehfeld, JF, Beglinger, C, Van Oudenhove, L, Wölnerhanssen, BK, Meyer-Gerspach, AC
Nutrients. 2022;(19)
Abstract
The impact of oral erythritol on subsequent energy intake is unknown. The aim was to assess the effect of oral erythritol compared to sucrose, sucralose, or tap water on energy intake during a subsequent ad libitum test meal and to examine the release of cholecystokinin (CCK) in response to these substances. In this randomized, crossover trial, 20 healthy volunteers received 50 g erythritol, 33.5 g sucrose, or 0.0558 g sucralose dissolved in tap water, or tap water as an oral preload in four different sessions. Fifteen minutes later, a test meal was served and energy intake was assessed. At set time points, blood samples were collected to quantify CCK concentrations. The energy intake (ad libitum test meal) was significantly lower after erythritol compared to sucrose, sucralose, or tap water (p < 0.05). Before the start of the ad libitum test meal, erythritol led to a significant increase in CCK compared to sucrose, sucralose, or tap water (p < 0.001). Oral erythritol given alone induced the release of CCK before the start of the ad libitum test meal and reduced subsequent energy intake compared to sucrose, sucralose, or tap water. These properties make erythritol a useful sugar alternative.
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Effect of a Chronic Intake of the Natural Sweeteners Xylitol and Erythritol on Glucose Absorption in Humans with Obesity.
Bordier, V, Teysseire, F, Schlotterbeck, G, Senner, F, Beglinger, C, Meyer-Gerspach, AC, Wölnerhanssen, BK
Nutrients. 2021;(11)
Abstract
In patients with obesity, accelerated nutrients absorption is observed. Xylitol and erythritol are of interest as alternative sweeteners, and it has been shown in rodent models that their acute ingestion reduces intestinal glucose absorption. This study aims to investigate whether a chronic intake of xylitol and erythritol impacts glucose absorption in humans with obesity. Forty-six participants were randomized to take either 8 g of xylitol or 12 g of erythritol three times a day for five to seven weeks, or to be part of the control group (no substance). Before and after the intervention, intestinal glucose absorption was assessed during an oral glucose tolerance test with 3-Ortho-methyl-glucose (3-OMG). The effect of xylitol or erythritol intake on the area under the curve for 3-OMG concentration was not significant. Neither the time (pre or post intervention), nor the group (control, xylitol, or erythritol), nor the time-by-group interaction effects were significant (p = 0.829, p = 0.821, and p = 0.572, respectively). Therefore, our results show that a chronic intake of the natural sweeteners xylitol and erythritol does not affect intestinal glucose absorption in humans with obesity.
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Gastric emptying of solutions containing the natural sweetener erythritol and effects on gut hormone secretion in humans: A pilot dose-ranging study.
Wölnerhanssen, BK, Drewe, J, Verbeure, W, le Roux, CW, Dellatorre-Teixeira, L, Rehfeld, JF, Holst, JJ, Hartmann, B, Tack, J, Peterli, R, et al
Diabetes, obesity & metabolism. 2021;23(6):1311-1321
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Plain language summary
In recent years, erythritol, a non-calorie sweetener, has gained popularity due to the rise in obesity and Type 2 diabetes worldwide. The purpose of this randomised, placebo-controlled, double-blind, cross-over trial was to assess the effects of erythritol on the release of gut hormones, speed of gastric emptying, and the release of glucagon, motilin, and glucose-dependent insulinotropic polypeptide after erythritol administration. Erythritol in doses of ten, twenty-five, and fifty grams was well tolerated by the participants. The administration of erythritol induced a statistically significant dose-dependent stimulation of gut hormones such as plasma cholecystokinin, active glucagon‐like peptide‐1 and peptide tyrosine. Compared to the placebo, participants had slower gastric emptying with erythritol. Erythritol had no effect on the levels of motilin, glucose-dependent insulinotropic polypeptide, blood glucose, insulin, glucagon, blood lipids, or uric acid. Erythritol should be evaluated in larger, robust studies to determine whether it improves glycaemic control. However, healthcare professionals can use the results of this study to understand the potential uses of erythritol in the management of obesity and type 2 diabetes.
Abstract
AIM: To determine whether a dose-dependent effect in the stimulation of gut hormone release (plasma cholecystokinin [CCK], active glucagon-like peptide-1 [aGLP-1] and peptide tyrosine tyrosine [PYY]) is found for the natural sweetener erythritol. MATERIALS AND METHODS Twelve healthy, lean volunteers received solutions with 10, 25 or 50 g erythritol, or tap water enriched with 13 C-sodium acetate on four study days via a nasogastric tube in this randomized (active treatments), placebo-controlled, double-blind, cross-over trial. Blood samples and breath samples (13 C-sodium acetate method for measurement of gastric emptying [GE]) were taken at regular intervals, and sensations of appetite and gastrointestinal symptoms were rated. RESULTS We found (a) a dose-dependent stimulation of CCK, aGLP-1 and PYY, and slowing of GE, (b) no effect on blood glucose, insulin, motilin, glucagon or glucose-dependent insulinotropic polypeptide, (c) no effect on blood lipids and uric acid, and (d) no abdominal pain, nausea or vomiting. CONCLUSIONS Solutions with 10 and 50 g of erythritol stimulated gut hormone release. Emptying of erythritol-containing solutions from the stomach was slower compared with placebo. There was no effect on plasma glucose, insulin, glucagon, blood lipids or uric acid. All doses were well tolerated.
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Effect of the Natural Sweetener Xylitol on Gut Hormone Secretion and Gastric Emptying in Humans: A Pilot Dose-Ranging Study.
Meyer-Gerspach, AC, Drewe, J, Verbeure, W, Roux, CWL, Dellatorre-Teixeira, L, Rehfeld, JF, Holst, JJ, Hartmann, B, Tack, J, Peterli, R, et al
Nutrients. 2021;(1)
Abstract
Sugar consumption is associated with a whole range of negative health effects and should be reduced and the natural sweetener xylitol might be helpful in achieving this goal. The present study was conducted as a randomized, placebo-controlled, double-blind, cross-over trial. Twelve healthy, lean volunteers received intragastric solutions with 7, 17 or 35 g xylitol or tap water on four separate days. We examined effects on: gut hormones, glucose, insulin, glucagon, uric acid, lipid profile, as well as gastric emptying rates, appetite-related sensations and gastrointestinal symptoms. We found: (i) a dose-dependent stimulation of cholecystokinin (CCK), active glucagon-like peptide-1 (aGLP-1), peptide tyrosine tyrosine (PYY)-release, and decelerated gastric emptying rates, (ii) a dose-dependent increase in blood glucose and insulin, (iii) no effect on motilin, glucagon, or glucose-dependent insulinotropic peptide (GIP)-release, (iv) no effect on blood lipids, but a rise in uric acid, and (v) increased bowel sounds as only side effects. In conclusion, low doses of xylitol stimulate the secretion of gut hormones and induce a deceleration in gastric emptying rates. There is no effect on blood lipids and only little effect on plasma glucose and insulin. This combination of properties (low-glycemic sweetener which stimulates satiation hormone release) makes xylitol an attractive candidate for sugar replacement.
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First-Phase Insulin and Amylin after Bariatric Surgery: A Prospective Randomized Trial on Patients with Insulin Resistance or Diabetes after Gastric Bypass or Sleeve Gastrectomy.
Nussbaumer, R, Meyer-Gerspach, AC, Peterli, R, Peters, T, Beglinger, C, Chiappetta, S, Drewe, J, Wölnerhanssen, B
Obesity facts. 2020;(6):584-595
Abstract
BACKGROUND Most patients with severe obesity show glucose intolerance. Early after sleeve gastrectomy (LSG) or gastric bypass (LRYGB), a marked amelioration in glycemic control occurs. The underlying mechanism is not yet clear. OBJECTIVE To determine whether the improvement in glycemic control on the level of endocrine pancreatic function is due to an increased first-phase insulin secretion comparing LRYGB to LSG. SETTING University of Basel Hospital and St. Clara Research Ltd., Basel, Switzerland. METHODS Sixteen morbidly obese patients with severe obesity and different degrees of insulin resistance were randomized to LSG or LRYGB, and islet cell functions were tested by intravenous glucose and intravenous arginine administration before and 4 weeks after surgery. RESULTS Fasting insulin and glucose levels and homeostasis model assessment insulin resistance were significantly lower in both groups after surgery compared to baseline, while no change was seen in fasting C-peptide, amylin, and glucagon. After intravenous glucose stimulation, no statistically significant pre- to postoperative change in area under the curve (AUC 0-60 min) was seen for insulin, glucagon, amylin, and C-peptide. No statistically significant pre- to postoperative change in incremental AUC for first-phase insulin release (AUC 0-10 min), second-phase insulin secretion (AUC 10-60 min), and insulin/glucose ratio could be shown in either group. Arginine-stimulated insulin and glucagon release showed no pre- to postoperative change. CONCLUSION Intravenous glucose and arginine administrations show no pre- to postoperative changes of insulin release, amylin, glucagon, or C-peptide concentrations, and no differences between LRYGB and LSG were found. The postoperative improvement in glycemic control is not caused by changes in endocrine pancreatic hormone secretion.