Effects of Maple Syrup on Gut Microbiota Diversity and Metabolic Syndrome

Study Overview
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Brief Summary
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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.

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

Conditions
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Overweight, Microbiota, Endotoxemia, Metabolic Syndrome, Non-Alcoholic Fatty Liver Disease, Insulin Resistance

Intervention / Treatment
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* Other: Maple syrup
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Maple<br> | Other: Maple syrup<br>* 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.<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Gut Microbiota Composition and Diversity | Global variation of the fecal microbiota | 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 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) | 
| 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) |