| Study ID | |
| RefID (DistillerSR) | 4355 |
| Reference (authors, year, title, other info) | Teysseire, F., Bordier, V., Budzinska, A., Weltens, N., Rehfeld, J. F., Holst, J. J., Hartmann, B., Beglinger, C., Van Oudenhove, L., Wölnerhanssen, B. K. and Meyer‐Gerspach, A. C. (2022). 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. The Journal of Nutrition, 152(5), 1228–1238. https://doi.org/10.1093/jn/nxac026 |
| Source (published/unpublished) | Published |
| Study design | |
| Study type | HCT – Cross‐over trial – Randomised – Placebo‐controlled |
| Type of blinding | Double‐blind |
| Duration of the study and length of follow‐up | 1 day per test material |
| Subjects | |
| Number of participants in the study | 21 participants |
| Number of exposed/non‐exposed subjects or number of cases/controls (if applicable) | 18 exposed |
| Sex (male/female) | 5 Males and 13 Females |
| Age (mean or range as reported) | 19–39 |
| Geography (country) | Switzerland |
| Ethnicity | Not reported |
| Confounders and other variables as reported | Not reported |
| Special health condition of participants | Healthy |
| Inclusion and exclusion criteria in the study | Exclusion criteria included substance and alcohol abuse, acute infections, chronic medical illness or illnesses affecting the GI system |
| Other information | |
| Intervention/exposure | |
| Test material | Erythritol |
| Description of the intervention and estimated dietary exposure | On 6 separate test sessions, at least 3 days apart and after a 10‐h overnight fast, after taking blood samples (t = −10 and − 1 min) and breath samples (t = −10 min) as well as recording of appetite‐related sensations and GI symptoms, participants received one of the following test solutions (at t = 0 min) via intragastric administration over 2 min in a randomised order:
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| Co‐exposure description (if applicable) | Not applicable |
| Endpoint measured, measurement time points and methods |
After the administration of the test solution, blood samples (at t = 15, 30, 45, 60, 90, 120 and 180 min), for analysis of plasma CCK, GLP‐1 and PYY, and end‐expiratory breath samples (at t = 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 and 240 min), for analysis of gastric emptying rates, were taken Appetite‐related sensations (hunger, prospective food consumption, satiety and fullness) were assessed at t = 15, 30, 45, 60, 90, 120 and 180 min using visual analog scales (VASs) as previously described Participants were also asked to rate GI symptoms (no symptoms [0 points], mild [1 point] or severe symptoms [2 points]) at t = 30, 60, 90, 120, 150, 180 and 240 min after the administration of the test solutions The list included the following symptoms: abdominal pain, nausea, vomiting, diarrhoea, borborygmus, abdominal bloating, eructation and flatulence Vital signs (blood pressure, heart rate) were measured at the beginning and at the end of each study day |
| Were sub‐groups analyses predefined? (yes/no, including justification) | Not applicable |
| Results | |
| Findings reported by the study author/s |
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) |
| Statistical analysis | |
| Statistical methods (including power analyses, multiple comparison, potential sources of bias, adjustment for confounders, test for interactions) |
A 2‐tailed p‐value ≤ 0.05 was considered significant and Cohen's dz for paired t‐tests was reported as a measure of effect size For all analyses, if the assumption of normally distributed residuals was violated (based on a significant p‐value of the Shapiro–Wilk test), natural logarithmic transformations of the dependent variables were used to normalise this distribution. Analysis was performed on transformed data. Logarithmic transformation of the dependent variables adequately normalised the residual distribution. Visit number was included to control for putative order effects in all models. All outcome variables were analysed using (generalised) linear mixed models on changes from baseline (average of pre‐infusion time point[s]). ‘Test solution’ (intragastric d‐allulose, d‐allulose + lactisole, erythritol, erythritol + lactisole, tap water and tap water + lactisole) and ‘time’ were included as within‐subject independent variables in the models (including their main effects and the interaction). All the models were controlled for baseline values. To follow‐up on significant main or interaction effects, planned contrast analyses were performed to test our specific hypotheses, with stepdown Bonferroni (Holm) correction for multiple testing. To test the hypothesis that d‐allulose or erythritol induces an increase in GI satiation hormones and retards gastric emptying compared with tap water, were compared post‐infusion GI satiation hormone concentrations and gastric emptying (change from baseline) between tap water, on one hand, and d‐allulose or erythritol, on the other hand. To test the hypothesis that d‐allulose or erythritol increases satiety/fullness and decreases hunger/prospective food consumption compared with tap water, respectively, were compared post‐infusion appetite‐related sensations between tap water, on one hand, and d‐allulose or erythritol, on the other hand. To test the hypothesis that addition of lactisole does (not) decrease GI satiation hormones, retard gastric emptying or change appetite‐related sensations in response to d‐allulose or erythritol, were compared post‐infusion GI satiation hormone concentrations and gastric emptying (change from baseline) to each of the substances with and without added lactisole For the associations, the difference between the test solutions of the significant planned contrasts at each time point was calculated and used as a dependent variable in the model with the same difference at each time point for the GI satiation hormones as an independent variable in addition to time |
| Further information | |
| 21 participants were recruited for the study. There were three dropouts (one participant had to withdraw due to a knee surgery and two withdrew for personal reasons). Therefore, 18 participants completed the 6 treatments. Complete data from all 18 participants were available for analysis | |
| Study ID | |
| RefID (DistillerSR) | 1242 |
| Reference (authors, year, title, other info) | Kim, Y., Park, S.C., Wolf, B.W., & Hertzler, S.R. (2011). Combination of erythritol and fructose increases gastrointestinal symptoms in healthy adults. Nutrition Research, 31, 836–841. https:\\doi.org\ 10.1016/j.nutres.2011.09.025 |
| Source (published/unpublished) | Published |
| Study design | |
| Study type | HCT – randomised, cross‐over study |
| Type of blinding | Double‐blinded |
| Duration of the study and length of follow‐up | 1 day per test material |
| Subjects | |
| Number of participants in the study | Participants were enrolled (n = 62) until at least 36 completed the study. Subjects were recruited from The Ohio State University community (Columbus, Ohio, USA) |
| Number of exposed/non‐exposed subjects or number of cases/controls (if applicable) | 37 exposed |
| Sex (male/female) | 13 males and 24 females |
| Age (mean or range as reported) | 23 ± 0.5 years old |
| Geography (country) | US |
| Ethnicity | 73% White, 5% African American, 19% Asian or Pacific Islander and 3% Hispanic |
| Confounders and other variables as reported | Not reported |
| Special health condition of participants | Healthy |
| Inclusion and exclusion criteria in the study | Inclusion criteria: 18–75 years old, male or non‐pregnant, non‐lactating female greater than 6 weeks postpartum, body mass index (BMI) 18–28 kg/m2 or up to 30 kg/m2 if waist circumference < 88.9 cm for females or < 101.6 cm for males, no tobacco use, fasting plasma glucose ≤ 5.56 mmol/L, no previous diagnosis of diabetes mellitus or other metabolic or GI diseases, no infection, surgery or corticosteroid treatment within past 3 months or antibiotic therapy within past 3 weeks, and breath hydrogen excretion (> 10 ppm above baseline) after oral lactulose challenge and greater hydrogen than methane excretion. |
| Other information | |
| Intervention/exposure | |
| Test material | Erythritol |
| Description of the intervention and estimated dietary exposure |
To ensure similar glycogen stores on test days, participants were instructed to consume at least 150 g carbohydrates per day for 3 days before each visit (verified by food records) and to refrain from exercise the day before each visit Also, participants were provided a low‐residue, low‐fibre (≤ 5 g) standard dinner for consumption between 4 and 7 pm on the day before each visit. The standard dinner consisted of 240 mL Ensure Plus and variable quantities of Ensure Nutrition and Energy Bars (Abbott Nutrition, Abbott Laboratories, Columbus, OH, USA) calculated to provide total energy equal to one third of each participant's estimated daily energy requirement (based on the Harris‐Benedict equation multiplied by a light activity factor of 1.3 a ) At each visit, participants consumed one of the three test beverages consisting of 500 mL water plus one of the following: 50 g fructose (control product, 0.56 mol/L), 50 g fructose and 50 g glucose (positive control, 1.11 mol/L), and 50 g fructose and 33.3 g erythritol (experimental product, 1.11 mol/L). Treatment sequence was randomly assigned Participants were instructed to consume the test beverage within 10 min after the first sip and then allowed to drink up to 240 mL water during the 3 h tolerance test Drinks were administered 3–14 days apart |
| Co‐exposure description (if applicable) | Erythritol and fructose (33.3 g and 50 g, respectively) |
| Endpoint measured, measurement time points and methods |
Breath hydrogen samples were collected in sealed evacuated tubes (Exetainer, Labco International Inc., Houston, TX, USA) using an AlveoSampler mouthpiece (Quintron Instrument Company, Milwaukee, Wis., USA) at baseline and hourly during the 3 h tolerance test on site and for an additional 5 h off site. At 4 h postprandial, participants were allowed to consume up to two cans (240 mL per can) of Ensure Plus and then resumed fasting until the 8 h postprandial study product administration breath sample was collected. Samples were analysed for hydrogen, methane and carbon dioxide concentrations by gas chromatography (Quintron Microanalyzer Model SC, Quintron Instrument Company). Participants were identified as having carbohydrate malabsorption if their breath hydrogen concentrations increased more than 10 ppm for 8 h compared with the basal nadir value (i.e. the lowest breath hydrogen value at baseline, 1 or 2 h postprandial). Participants recorded the total number of rectal gas passages using a portable counting device (VWR International, West Chester, PA, USA) during the 3 h tolerance test on site and for an additional 5 h off site. The number of bowel movements for the first 3 h after study product administration was recorded when the participants were on site, and also for an additional 5 h off site. Stool consistency for each bowel movement was rated using a 5‐point visual analog scale (VAS). Participants recorded frequency and intensity of nausea, abdominal cramping, distension and flatulence for 0–24 h after study product consumption using a VAS (0 = usual or absent; 10 = more than usual or severe) |
| Were sub‐groups analyses predefined? (yes/no, including justification) | Not applicable |
| Results | |
| Findings reported by the study author/s |
The breath hydrogen AUC for the fructose and erythritol beverage was 2× the AUC of the fructose beverage and 8.75× the AUC of the fructose and glucose beverage (p < 0.001, respectively). Compared with the fructose and glucose beverage and fructose alone, when participants consumed fructose and erythritol combined, the frequency of watery stools increased (p < 0.05) and GI tolerance worsened (p < 0.05). The data suggested that co‐ingestion of equimolar concentrations of fructose and erythritol increased carbohydrate malabsorption A study limitation was the lack of an erythritol‐only test beverage, which would have allowed a more complete evaluation of serum erythritol levels and breath hydrogen concentrations. Data for this beverage would help to identify which carbohydrate, either erythritol or fructose, was not well absorbed |
| Statistical analysis | |
| Statistical methods (including power analyses, multiple comparison, potential sources of bias, adjustment for confounders, test for interactions) |
After examination for normality, data were analysed using ANOVA with a randomised block design to test for global significant differences; the Tukey–Kramer post hoc test was then used for pairwise comparisons. The NCSS 2000 software package (NCSS computing, Kayesville, Utah, USA) was used for statistical analysis Power analysis on data from a previous study b indicated that 36 participants would be required to detect a 47% difference in the incremental AUC for breath hydrogen with 84% power |
| Further information | |
Harris, J. A., & Benedict, F. G. (1919). A biometric study of basal metabolism in man. Carnegie Institute. pp. 227.
Ravich, W. J., Bayless, T. M., & Thomas, M. (1983). Fructose: Incomplete intestinal absorption in humans. Gastroenterology, 84, 26–29.