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A Double-Blind, Randomized Controlled, Acute Feeding Equivalence Trial of Small, Catalytic Doses of Fructose and Allulose on Postprandial Blood Glucose Metabolism in Healthy Participants: The Fructose and Allulose Catalytic Effects (FACE) Trial.

ABSTRACT: Recent literature suggests that catalytic doses (≤10 g/meal or 36 g/day) of D-fructose and D-allulose may reduce postprandial blood glucose responses to carbohydrate loads in people with and without type 2 diabetes by inducing glycogen synthesis. To assess the effect of small single doses of fructose and allulose on postprandial blood glucose regulation in response to a 75 g-oral glucose tolerance test (75 g-OGTT) in healthy individuals, we conducted an acute randomized, crossover, equivalence trial in healthy adults. Each participant randomly received six treatments, separated by a minimum one-week washout. Treatments consisted of a 75 g-OGTT with the addition of fructose or allulose at 0 g (control), 5 g or 10 g. A standard 75 g-OGTT protocol was followed with blood samples at −30, 0, 30, 60, 90, 120 min. The primary outcome was the difference in plasma glucose incremental area under the curve (iAUC). A total of 27 participants underwent randomization with data available from 25 participants. Small doses of fructose or allulose did not show a significant effect on plasma glucose iAUC or other secondary markers of postprandial blood glucose regulation in response to a 75 g-OGTT in healthy individuals. These results were limited by the low power to detect a significant difference, owing to greater than expected intra-individual coefficient of variation (CV) in plasma glucose iAUC. Overall, we failed to confirm the catalytic effects of small doses of fructose and allulose in healthy individuals. Future trials may consider recruiting larger sample sizes of healthy individuals. TRIAL REGISTRATION:clinicaltrials.gov identifier, NCT02459834.

SUBMITTER: Braunstein CR

PROVIDER: S-EPMC6024645 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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A Double-Blind, Randomized Controlled, Acute Feeding Equivalence Trial of Small, Catalytic Doses of Fructose and Allulose on Postprandial Blood Glucose Metabolism in Healthy Participants: The Fructose and Allulose Catalytic Effects (FACE) Trial.

Braunstein Catherine R CR Noronha Jarvis C JC Glenn Andrea J AJ Viguiliouk Effie E Noseworthy Rebecca R Khan Tauseef A TA Au-Yeung Fei F Blanco Mejia Sonia S Wolever Thomas M S TMS Josse Robert G RG Kendall Cyril W C CWC Sievenpiper John L JL

Nutrients 20180609 6

Recent literature suggests that catalytic doses (≤10 g/meal or 36 g/day) of D-fructose and D-allulose may reduce postprandial blood glucose responses to carbohydrate loads in people with and without type 2 diabetes by inducing glycogen synthesis. To assess the effect of small single doses of fructose and allulose on postprandial blood glucose regulation in response to a 75 g-oral glucose tolerance test (75 g-OGTT) in healthy individuals, we conducted an acute randomized, crossover, equivalenc ...[more]

PMID: 29890724

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Project description:Abstract Objectives Fructose providing excess calories has been shown to increase postprandial triglycerides (TAG). Whether this effect holds for different food sources of fructose-containing sugars is unclear. We conducted a systematic review and meta-analysis of controlled feeding trials on the effect of different food sources of fructose-containing sugars at different levels of energy control on postprandial blood lipids (NCT02716870). Methods MEDLINE, EMBASE, and Cochrane Library were searched through June 1st, 2020 for controlled feeding trials ≥7-days assessing the effect of food sources of fructose-containing sugars on postprandial lipids. Trial designs were prespecified based on energy control: substitution (energy matched replacement of sugars by other macronutrients); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced by other macronutrients) trials. Independent reviewers extracted data and assessed risk of bias. Outcomes were postprandial TAG and apoB48. Certainty of evidence was assessed using GRADE. Results We included 29 trials (60 trial comparisons, N = 943) assessing 5 food sources (SSBs, fruit, sweets and desserts, added caloric sweetener and mixed sources) across 4 levels of energy control. Total fructose-containing sugars increased postprandial TAG in substitution (MD: 0.17 mmol/L [95% CI: 0.05, 0.30], P = 0.007), addition (0.38 mmol/L [0.13, 0.62], P = 0.003), and ad libitum (0.17 mmol/L [0.02, 0.31], P = 0.024) trials and increased apoB48 in addition trials (0.12 g/L [0.07, 0.18], P < 0.001).There was evidence of interaction by food source with SSBs increasing postprandial TAG and apoB48 in addition trials and mixed sources increasing postprandial TAG in ad libitum trials. The certainty of the evidence was “moderate” for SSBs increasing TAG in addition trials and mixed sources increasing TAG in ad libitum trials and “low” for all other comparisons. Conclusions Food source more than energy control appears to mediate fructose-containing sugars on postprandial lipids. Good evidence suggests that SSBs and mixed sources increase postprandial lipids while evidence is less certain for the lack of effect of other food sources. More high-quality trials of different food sources are needed. Funding Sources Primary: Diabetes Canada.

Project description:BACKGROUND/OBJECTIVES:To investigate the effect of dried fruit in modifying postprandial glycemia, we assessed the ability of 4 dried fruits (dates, apricots, raisins, sultanas) to decrease postprandial glycemia through three mechanisms: a glycemic index (GI) effect, displacement effect, or 'catalytic' fructose effect. SUBJECTS/METHODS:We conducted an acute randomized, multiple-crossover trial in an outpatient setting in 10 healthy adults. Participants received 3 white bread control meals and 12 dried fruit test meals in random order. The test meals included each of 4 dried fruits (dates, apricots, raisins, sultanas) alone (GI effect), 4 of the dried fruits displacing half the available carbohydrate in white bread (displacement effect), or 4 of the dried fruits providing a small 'catalytic' dose (7.5?g) of fructose added to white bread ('catalytic' fructose effect). The protocol followed the ISO method for the determination of GI (ISO 26642:2010). The primary outcome was mean?±?SEM GI (glucose scale) for ease of comparison across the three mechanisms. RESULTS:Ten healthy participants (7 men, 3 women; mean?±?SD age and BMI: 39?±?12 years and 25?±?2?kg/m2) were recruited and completed the trial. All dried fruit had a GI below that of white bread (GI?=?71); however, only dried apricots (GI?=?42?±?5), raisins (GI?=?55?±?5), and sultanas (51?±?4) showed a significant GI effect (P?<?0.05). When displacing half the available carbohydrate in white bread, all dried fruit lowered the GI; however, only dried apricots (GI?=?57?±?5) showed a significant displacement effect (P?=?0.025). None of the dried fruits showed a beneficial 'catalytic' fructose effect. CONCLUSIONS:In conclusion, dried fruits have a lower GI and reduce the glycemic response of white bread through displacement of half of the available carbohydrate. Longer-term randomized trials are needed to confirm whether dried fruit can contribute to sustainable improvements in glycemic control. TRIAL REGISTRATION:ClinicalTrials.gov identifier, NCT02960373.

Project description:Objective: Contrary to the concerns that fructose may have adverse metabolic effects, an emerging literature has shown that small doses (?10 g/meal) of fructose and its low-caloric epimers (allulose, tagatose, and sorbose) decrease the glycemic response to high glycemic index meals. Whether these acute reductions manifest as sustainable improvements in glycemic control is unclear. Our objective was to synthesize the evidence from controlled feeding trials that assessed the effect of small doses of fructose and its low-caloric epimers on glycemic control. Methods: We searched MEDLINE, EMBASE, and the Cochrane Library through April 18, 2018. We included controlled feeding trials of ?1 week that investigated the effect of small doses (?50 g/day or ?10% of total energy intake/day) of fructose and its low-caloric epimers on HbA1c, fasting glucose, and fasting insulin. Two independent reviewers extracted data and assessed risk of bias. Data were pooled using the generic inverse variance method and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed using the Cochran Q statistic and quantified using the I² statistic. Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessed the certainty of the evidence. Results: We identified 14 trial comparisons (N = 337) of the effect of fructose in individuals with and without diabetes, 3 trial comparisons (N = 138) of the effect of allulose in individuals without diabetes, 3 trial comparisons (N = 376) of the effect of tagatose mainly in individuals with type 2 diabetes, and 0 trial comparisons of the effect of sorbose. Small doses of fructose and tagatose significantly reduced HbA1c (MD = -0.38% (95% CI: -0.64%, -0.13%); MD = -0.20% (95% CI: -0.34%, -0.06%)) and fasting glucose (MD = -0.13 mmol/L (95% CI: -0.24 mmol/L, -0.03 mmol/L)); MD = -0.30 mmol/L (95% CI: -0.57 mmol/L, -0.04 mmol/L)) without affecting fasting insulin (p > 0.05). Small doses of allulose did not have a significant effect on HbA1c and fasting insulin (p > 0.05), while the reduction in fasting glucose was of borderline significance (p = 0.05). The certainty of the evidence of the effect of small doses of fructose and allulose on HbA1c, fasting glucose, and fasting insulin was graded as low. The certainty of the evidence of the effect of tagatose on HbA1c, fasting glucose, and fasting insulin was graded as moderate. Conclusions: Our results indicate that small doses of fructose and tagatose may improve glycemic control over the long term. There is a need for long-term randomized controlled trials for all four sugars to improve our certainty in the estimates.

Dataset Information

A Double-Blind, Randomized Controlled, Acute Feeding Equivalence Trial of Small, Catalytic Doses of Fructose and Allulose on Postprandial Blood Glucose Metabolism in Healthy Participants: The Fructose and Allulose Catalytic Effects (FACE) Trial.

Publications

A Double-Blind, Randomized Controlled, Acute Feeding Equivalence Trial of Small, Catalytic Doses of Fructose and Allulose on Postprandial Blood Glucose Metabolism in Healthy Participants: The Fructose and Allulose Catalytic Effects (FACE) Trial.

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