Effects of Cranberry Powder Supplements on Gut Microbiota Diversity and Metabolic Syndrome (MICA)

Evaluation of the Effect of Cranberry Whole Fruit Powder on Gut Microbiota Diversity, Intestinal Health and Metabolic Syndrome in Overweight Individuals: a Proof-of-concept Study

It is of major importance to refine prevention strategies in order to alleviate inflammation, insulin resistance and metabolic syndrome and it appear that improving gut health and microbiota represent a promising strategy. Cranberry-enriched diets may help prevent metabolic syndrome and its associated chronic diseases by a protective effect of gut health and microbiota. It is therefore highly relevant to test the hypothesis that a whole cranberry powder supplements (which include a mixture of polyphenols, free and fiber-associated proanthocyanidins, and fruits fibers) is associated with changes on the gut health and microbiota playing a major role in alleviating inflammation and obesity-associated metabolic disorders.

Study Overview

• Status: Completed
• Conditions: Overweight; Metabolic Syndrome; Insulin Resistance; Endotoxemia; Microbiota
• Intervention / Treatment: Dietary supplement: Cranberry powder; Dietary supplement: Placebo

Detailed Description

Over the past decade it has become clear that the gut microbiota is a key determinant of obesity and that its perturbations by nutritional insults play a significant role in the development of metabolic complications such as insulin resistance, type 2 diabetes, cardiovascular diseases and non-alcoholic fatty liver disease. Indeed, there is growing amounts of studies that have shown that dysbiosis of the intestinal microbiota promotes obesity-linked chronic inflammation, and is causally related to diet-induced type 2 diabetes. Our group recently published that a polyphenol-rich cranberry extract exert striking effect on the gut microbiota of high-fat and high-sucrose fed mice, which was associated with prevention of diet-induced weight gain, visceral obesity, insulin resistance and hepatic steatosis. Notably, metagenomic analyses of feces of the cranberry extract-treated mice suggested that these metabolic effects were associated with a dramatic increase in the proportion of Akkermansia muciniphila, a dominant commensal bacterium in the intestinal mucus layer which has received particular attention in the last few years since its abundance is associated with improved metabolic health and beneficial responses to various interventions in both mice and humans with obesity and diabetes. Polyphenols are now recognized as potent molecules capable to protect against obesity-linked metabolic diseases and dysbiosis. Among polyphenols, there is increasing evidence supporting the beneficial impact of dietary proanthocyanidins. Cranberries being rich in proanthocyanidins, we believe that these phyto-elements could be associated to their beneficial effects. On the other hand, apart from the recognized beneficial effects of fibers on gut health, their association with high molecular proanthocyanidins could also contribute to their health benefits.

The main objective of this study is to investigate in a cross-over randomized placebo-controlled clinical trial the beneficial properties of a whole cranberry powder on gut microbiota, intestinal health and metabolic syndrome parameters in overweight men.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada, G1V 0A6
    • Institut sur la nutrition et les aliments fonctionnels

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• overweight
• fasting insulin > 42 pmol/L
• non smoking
• Stable weight in the past 3 months

Exclusion Criteria:

• chronic diseases
• Taking drugs that could affect glucose or lipid metabolism
• Taking anti-inflammatory, immunosuppressant or anticoagulant drugs
• Inflammatory bowel disease
• vegetarians, vegan or following any restrictive dietary pattern or if they are big consumers of berries (>1 portion/day)
• taking pre- and probiotics
• antibiotics in the past 3 months or change in their regular medication
• Major surgery in the past 3 months
• taste aversion for cranberries or cranberry allergy or allergies to other ingredients used in the placebo

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	Dietary supplement: Placebo; 3 capsules/day of a placebo comparator
Experimental: Cranberry; Whole Cranberry Powder Supplements	Dietary supplement: Cranberry powder; 3 capsules /day of whole cranberry powder (500mg/each)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Gut Microbiota Diversity	Global variation of the fecal microbiota	At the beginning and the end of each treatment (4 weeks each)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Endotoxemia	Plasma Lipopolysaccharides (LPS) and Lipopolysaccharide Binding Protein (LBP)	At the beginning and the end of each treatment (4 weeks each)
Change in Intestinal permeability	Plasma zonulin	At the beginning and the end of each treatment (4 weeks each)
Change in Inflammation state of the tissue	Fecal calprotectin and chromogranin	At the beginning and the end of each treatment (4 weeks each)
Change in Short chain fatty acids in the feces	Measure short chain fatty acids in the feces	At the beginning and the end of each treatment (4 weeks each)
Change in Gut health and stool consistency	Evaluation of gastrointestinal symptoms and stool consistency using standardized questionnaires	At the beginning and the end of each treatment (4 weeks each)
Change in Lipid profile	Evaluation of plasma triglycerides (TG), Total cholesterol, LDL, HDL and Apolipoprotein B from the beginning to the end of two dietary treatment	At the beginning and the end of each treatment (4 weeks each)
Change in chronic inflammation	Evaluation of plasma high sensitive C-Reactive Protein (hs-CRP)	At the beginning and the end of each treatment (4 weeks each)
Change in Glucose homeostasis	Evaluation of plasma fasting glucose and insulin concentration	At the beginning and the end of each treatment (4 weeks each)

Collaborators and Investigators

• Sponsor: Laval University
• Collaborators: Naturex
• Investigators: Principal Investigator: André Marette, Ph.D, Institute of nutrition and functional foods, Laval University

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2018
• Primary Completion (Actual): March 1, 2020
• Study Completion (Actual): March 1, 2020

Study Registration Dates

• First Submitted: November 19, 2018
• First Submitted That Met QC Criteria: November 21, 2018
• First Posted (Actual): November 27, 2018

Study Record Updates

• Last Update Posted (Actual): March 30, 2020
• Last Update Submitted That Met QC Criteria: March 26, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Disease; Body Weight; Sepsis; Hyperinsulinism; Bacteremia; Toxemia; Syndrome; Metabolic Syndrome; Insulin Resistance; Endotoxemia; Overweight
• Other Study ID Numbers: MICA 2018-146

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes