Effect of Cranberry and Agaves Extract on Microbiota and Intestinal Health (Phenulin)

Prebiotic Supplementation and Metabolic Endotoxemia and Modulation of the Gut Microbiota: Double-blind and Randomized Parallel Clinical Study of the Efficacy and Synergistical Effect of Cranberry Polyphenols and Inulin From Agaves

The growing prevalence of obesity and type 2 diabetes (T2D) is a major public health problem. Recent studies have clearly established that the gut microbiota plays a key role in the investigator's propensity to develop obesity and associated metabolic health disorders. The gut microbiota compositions plays a decisive role in glucose metabolism and the chronic inflammatory state associated with insulin resistance. Consuming prebiotic rich diet, including polyphenol and inulin rich food could help modulate favorably the gut microbiota which could lead to a reduction of endotoxemia and beneficial metabolic health effects.

Study Overview

• Status: Completed
• Conditions: Glucose Metabolism Disorders; Metabolic Syndrome; Insulin Resistance; Endotoxemia
• Intervention / Treatment: Dietary supplement: Cranberry; Dietary supplement: Agaves; Dietary supplement: Placebo

Detailed Description

It is now recognized that overweight individuals have altered microbiota which could lead to intestinal barrier defects and chronic inflammation disorders. Polyphenols such as Proanthocyanidins may modulate the gut microbiota thereby providing beneficial effects on metabolic health. Inulin is a well known prebiotic that could stimulate growth of favorable bacteria in the gut.

The overall goal is to determine the efficacy and synergy of a supplement of polyphenols from cranberry extract with or without a supplement of inulin from agaves to reduce chronic inflammation and endotoxemia and to improve glucose metabolism and insulin sensitivity by modulating microbiota of overweight human subjects with metabolic syndrome symptoms.

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Québec, Quebec, Canada, G1V 0A6
      • Institute of nutrition and functional foods, Laval University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• overweight (BMI 25-39.9 kg/m2) or waist circumference ≥ 80 cm (women) and ≥94 cm (men)
• fasting insulin over 60 pmol/L or fasting glucose 5.6 - 6.9 mmol/L
• at least one of the following criteria: Tg ≥ 1.7 mmol/L; blood pressure ≥ 130/85 mmHg; HDL < 0,9 mmol/L; hsCRP 1-10 mg/L
• non-smoking
• eating fruits and vegetables less then 5 portions/day

Exclusion Criteria:

• chronic disease
• taking drugs or natural health products that could affect glucose or lipid metabolism
• taking anti-inflammatory, antiacids
• taking pre or probiotics
• inflammatory bowel disease
• antibiotics in the past 3 months
• allergy or intolerance to cranberries or agaves
• Major surgery in the past 3 months

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cranberry and Agaves; Cranberry extract (2 capsules) + Agaves powder (1 single-dose packet)	Dietary supplement: Cranberry; Supplementation of polyphenols from cranberry extract; Dietary supplement: Agaves; Supplementation of inulin from Agaves powder
Experimental: Cranberry and placebo; Cranberry extract (2 capsules) + Placebo powder (1 single-dose packet)	Dietary supplement: Cranberry; Supplementation of polyphenols from cranberry extract; Dietary supplement: Placebo; Supplementation with placebo
Experimental: Placebo and Agaves; Placebo (2 capsules) + Agaves powder (1 single-dose packet)	Dietary supplement: Agaves; Supplementation of inulin from Agaves powder; Dietary supplement: Placebo; Supplementation with placebo
Placebo Comparator: Placebo and placebo; Placebo (2 capsules) + Placebo powder (1 single-dose packet)	Dietary supplement: Placebo; Supplementation with placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in metabolic endotoxemia: Measure concentration of Lipopolysaccharides (LPS) and Lipopolysaccharide Binding Protein (LBP) in plasma	effect of the supplements on variation in plasma concentration of LPS and LBP	At the beginning and the end of treatment (10 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in intestinal permeability: Measure concentration of zonulin in plasma	effect of the supplements on plasma concentration of zonulin	At the beginning and the end of treatment (10 weeks)
Change in inflammation state of the tissue: Measure concentration of calprotectin and lactoferrin in feces	effect of the supplements on fecal calprotectin and lactoferrin	At the beginning and the end of treatment (10 weeks)
Change in systemic inflammation: Measure concentration of inflammation biomarkers in the serum	effect of the supplements on chronic inflammation (serum concentration of hsCRP, Il-6, TNF-alpha, IL-1 beta, IL-23)	At the beginning and the end of treatment (10 weeks)
Change in glucose serum concentration	effect of the supplements on serum concentration of glucose	At the beginning and the end of treatment (10 weeks)
Change in insulin and C-peptide serum concentration	effect of the supplements on serum concentration of insulin and C-peptide	At the beginning and the end of treatment (10 weeks)
Change in microbiota diversity: growth of Akkermancia muciniphila, Lactobacillus, Prevotella, Bifdobacterium and inhibition of Clostridium perfringens, C. difficile, Bacteroides spp.)	Global variation of the fecal microbiota and gut microbiota profiling	At the beginning and the end of treatment (10 weeks)

Collaborators and Investigators

• Sponsor: Laval University
• Collaborators: Atrium Innovations; Ministry of Agriculture, Fisheries and Food, Quebec; Ministry of economic development, innovation and export trade, Quebec; Diana Food, Symrise; NutriAgaves, Mexico; Société des Produits Nestlé (SPN)
• Investigators: Principal Investigator: Hélène Jacques, PhD, Institute of nutrition and functional foods, Laval University; Study Director: Yves Desjardins, PhD, Institute of nutrition and functional foods, Laval University

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2018
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: December 6, 2018
• First Submitted That Met QC Criteria: January 8, 2019
• First Posted (Actual): January 11, 2019

Study Record Updates

• Last Update Posted (Actual): March 21, 2023
• Last Update Submitted That Met QC Criteria: March 17, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Hyperinsulinism; Bacteremia; Toxemia; Metabolic Syndrome; Insulin Resistance; Endotoxemia; Metabolic Diseases; Glucose Metabolism Disorders
• Other Study ID Numbers: GASTRO-Phenulin (2016-317)

Drug and device information, study documents

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