Effects of Maple Syrup on Gut Microbiota Diversity and Metabolic Syndrome

Impact of Free Sugar Replacement by Maple Syrup on Prevention of Metabolic Disorders Associated With Overweight in Humans : Role of Gut Microbiota

It has been suggested that the actual obesity epidemy is related to chronic overconsumption of added or free sugars. The increasing popularity of artificial sweeteners attest the population willingness to reduce added sugars intake and to use alternatives to alleviate health impact of free sugar overconsumption. However, recent findings suggest that artificial sweeteners may rather contribute to obesity epidemy and its associated adverse health effects, potentially via a negative impact on gut microbiota. It has been shown in various studies that, for the same amount of sucrose, unrefined sugars (such as maple syrup) are associated with favorable metabolic effects. The polyphenols contained in maple syrup, especially lignans, could contribute to these positive effects. Indeed, the strong impact of those biomolecules on the modulation of gut microbiota and on gastro-intestinal and metabolic health has been demonstrated in several studies. It is therefore highly relevant to test the hypothesis that the substitution of refined sugar by an equivalent amount of maple syrup (5% of daily energy intake) result in a lesser metabolic deterioration, by the modulation of maple syrup on gut microbiota, than the one observed with refined sugar.

Study Overview

• Status: Completed
• Conditions: Overweight; Metabolic Syndrome; Insulin Resistance; Endotoxemia; Non-Alcoholic Fatty Liver Disease; Microbiota
• Intervention / Treatment: Other: Maple syrup; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada, G1V 0A6
    • INAF, Université Laval

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• BMI between 23 and 40 kg/m2
• At least one of the following: Fasting triglyceride > 1,35 mmol/L, Fasting insulinemia > 42 pmol/L, fasting glycemia between 5,5 and 6,9 mmol/L and glycated haemoglobin (HbA1c) between 5.7 and 6.4 %
• Understanding of spoken and written french
• Accept to follow study instructions
• If there is natural health product consumption, the dose and frequency of consumption must be stable since 3 months or more

Exclusion Criteria:

• Smoking
• Any metabolic disorder requiring medication or affecting glucose or lipid metabolism
• Aversion for maple taste
• Allergy or intolerance for maple syrup or for an ingredient of the placebo syrup
• Alcohol consumption of > 2 drinks / day
• Weight change > 5% of body weight in the last 3 months
• Being in a weight loss attempt
• Antibiotics intake in the last 3 months
• Regular probiotics intake in the last 3 months
• Major surgical operation in the last 3 months or planned in the next months
• Gastrointestinal malabsorption
• Cirrhosis
• Chronic kidney disease
• Pregnant or breastfeeding women or women planning pregnancy in the next months
• Participation in another clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Substitution of refined sugar by an equivalent quantity of maple-flavored sucrose syrup (5% of daily energy intake) in the participant diet. A dietitian will help study subjects to target added sugar sources in their usual diet and suggest ways to substitute it with the placebo (sucrose syrup).
Experimental: Maple	Other: Maple syrup; Substitution of refined sugar by an equivalent quantity of maple syrup (5% of daily energy intake) in the participant diet. A dietitian will help study subjects to target added sugar sources in their usual diet and suggest ways to substitute it with maple syrup.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Glucose homeostasis	Evaluation of plasma glucose, insulin and c-peptide concentration using a 3-hour oral glucose tolerance test	Change between the beginning and the end of each treatment (8 weeks each)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Endotoxemia	Plasma Lipopolysaccharides (LPS) and Lipopolysaccharide Binding Protein (LBP)	Change between the beginning and the end of each treatment (8 weeks each)
Change in Intestinal permeability	Plasma zonulin	Change between the beginning and the end of each treatment (8 weeks each)
Change in Inflammation state of the tissue	Fecal calprotectin and chromogranin	Change between the beginning and the end of each treatment (8 weeks each)
Change in Short chain fatty acids in the feces	Measure short chain fatty acids in the feces	Change between the beginning and the end of each treatment (8 weeks each)
Change in Gut health and stool consistency	Evaluation of gastrointestinal symptoms and stool consistency using standardized questionnaires (the gastrointestinal symptom rating scale (GSRS) and Bristol stool chart)	Change between the beginning and the end of each treatment (8 weeks each)
Change in fat accumulation in the liver	Evaluation of fat accumulation by magnetic resonance imaging (MRI)	Change between the beginning and the end of each treatment (8 weeks each)
Change in Glucose homeostasis	Evaluation of glycated haemoglobin	Change between the beginning and the end of each treatment (8 weeks each)
Change in Lipid profile	Evaluation of plasma triglycerides (TG), Total cholesterol, LDL, HDL, Apolipoprotein B and free fatty acids end of two dietary treatment	Change between the beginning and the end of each treatment (8 weeks each)
Change in anthropometric measurements	Evaluation of bmi with weight and height measurements	Change between the beginning and the end of each treatment (8 weeks each)
Change in anthropometric measurements	Evaluation of waist circumference	Change between the beginning and the end of each treatment (8 weeks each)
Change in body composition	Evaluation of body composition by osteodensitometry	Change between the beginning and the end of each treatment (8 weeks each)
Change in chronic inflammation	Evaluation of plasma high sensitive C-Reactive Protein (hs-CRP)	Change between the beginning and the end of each treatment (8 weeks each)
Change in gene expression levels	Transcriptomic analyses to investigate underlying mechanisms of action	Change between the beginning and the end of each treatment (8 weeks each)
Change in circulating levels of plasma metabolites	Metabolomic analyses to investigate underlying mechanisms of action	Change between the beginning and the end of each treatment (8 weeks each)
Change in maple-derived metabolites present in stool	Evaluation of metabolome: camu-camu derived metabolites, short chain fatty acids, branched chain fatty acids, bile acids, phenolic compounds	Change between the beginning and the end of each treatment (8 weeks each)
Change in blood pressure	Evaluation of systolic and diastolic blood pressure	Change between the beginning and the end of each treatment (8 weeks each)
Change in Gut Microbiota Composition	Gut microbiota composition will be evaluated by 16S rRNA amplicon sequencing (V3-V4 region)	Change between the beginning and the end of each treatment (8 weeks each)
Change in Gut Microbiota Composition	Gut microbiota composition will also be evaluated by whole genome sequencing	Change between the beginning and the end of maple syrup treatment (8 weeks)
Change in Gut Microbiota alpha Diversity	To quantify bacterial alpha diversity, Shannon's reciprocal index will be calculated	Change between the beginning and the end of each treatment (8 weeks each)
Change in Gut Microbiota alpha Diversity	To quantify bacterial alpha diversity, Simpson's reciprocal index will be calculated	Change between the beginning and the end of each treatment (8 weeks each)
Change in Gut Microbiota beta Diversity	Principal component analysis (PCA) will be performed on the Aitchison distance matrix to measure beta diversity.	Change between the beginning and the end of each treatment (8 weeks each)

Collaborators and Investigators

• Sponsor: Laval University

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2019
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): December 1, 2021

Study Registration Dates

• First Submitted: September 30, 2019
• First Submitted That Met QC Criteria: October 3, 2019
• First Posted (Actual): October 7, 2019

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Disease; Overnutrition; Nutrition Disorders; Body Weight; Sepsis; Hyperinsulinism; Bacteremia; Toxemia; Liver Diseases; Syndrome; Fatty Liver; Metabolic Syndrome; Insulin Resistance; Endotoxemia; Overweight; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: ERABLE-21793

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No