Impact of Poplar Propolis on Metabolic Disturbances of Insulin Resistance

Impact of Poplar Propolis on Insulin Homeostasis and Pancreatic Cell Function in Insulin Resistant Subjects

Propolis, a natural resinous mixture rich in polyphenols, produced by bees from a variety of plant sources, has shown significant therapeutic effects and may prevent the development of certain chronic diseases. Current evidence supports the beneficial effect of these bioactive phytochemicals on the management of type 2 diabetes mellitus (T2DM) and other chronic diseases. The objective of this study is to evaluate the effect of poplar propolis extract powder (PPEP) on glucose homeostasis and other clinical parameters in insulin-resistant patients (diagnosed by HOMA-IR index > 1.85 for men and > 2.07 for women).

Study Overview

• Status: Completed
• Conditions: Insulin Resistance
• Intervention / Treatment: Dietary supplement: Propolis; Dietary supplement: Placebo

Detailed Description

Backgroud: Propolis, a natural resinous mixture rich in polyphenols, produced by bees from a variety of plant sources, has shown significant therapeutic effects and may prevent the development of certain chronic diseases. Current evidence supports the beneficial effect of these bioactive phytochemicals on the management of type 2 diabetes mellitus (T2DM) and other chronic diseases. The objective of this study is to evaluate the effect of poplar propolis extract powder (PPEP) on glucose homeostasis and other clinical parameters in insulin-resistant patients (diagnosed by HOMA-IR index > 1.85 for men and > 2.07 for women).

Methods: The trial was a randomized, controlled, crossover, intervention study. Insulin-resistant patients (n=9) (8 women, 1 man), with a mean ± SD age 49 ± 7, were subjected to two periods of supplementation (propolis and placebo) for 3-months, separated by a 2-week washout period. The quantity of propolis administered was determined individually to reach 6 mg of polyphenols/kg. Fasting blood test and oral glucose tolerance test (OGTT) were performed before and after each treatment.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Marseille, France
    • CIC La conception

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Body mass index (BMI) ≥ 30 kg/m2
• Insulin resistance defined as a HOMA-IR index > 1.85 for men and > 2.07 for women

Exclusion Criteria:

• Presence of diabetes
• Recent weight change (≥ 5% in the last 3 months)
• Documented allergy to bee products and/or fish products
• Positive serology for human immunodeficiency virus or hepatitis
• High blood pressure
• Elevated transaminases (AST > 40 IU/L ; ALT > 45 IU/L)
• Low creatine clearance (estimated glomerular filtration rate < 90 ml/min)
• Interfering treatment (cholesterol-lowering treatment, intestinal absorption modulating treatment, absorption modulating treatment and/or insulin sensitivity)
• Gastrointestinal tract surgery
• Pregnancy and / or lactation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Propolis; Propolis supplements were packaged in marine capsules and consisted of poplar propolis powder (propolis concentrate, carob powder, magnesium stearate and silicon dioxide), concentrated to 30% total polyphenols. Each supplementation period lasted 3 months, with a 2-week wash-out period, to allow total excretion of polyphenols by the body and do not interfere with the new supplementation phase. The subjects in this study were submitted to five visits, allowing the tracking of biological parameters (clinical examination, fasting blood samples, HGPO) during the study. During the supplementation phases, follow-up by telephone call was performed.	Dietary supplement: Propolis; Propolis supplements were packaged in marine capsules and consisted of poplar propolis powder (propolis concentrate, carob powder, magnesium stearate and silicon dioxide), concentrated to 30% total polyphenols. Each supplementation period lasted 3 months, with a 2-week wash-out period, to allow total excretion of polyphenols by the body and do not interfere with the new supplementation phase. The subjects in this study were submitted to five visits, allowing the tracking of biological parameters (clinical examination, fasting blood samples, HGPO) during the study. During the supplementation phases, follow-up by telephone call was performed.
PLACEBO_COMPARATOR: Placebo; Placebo powder capsules (maltodextrin, fatty acids, magnesium salts and silicon dioxide) are presented in the same packaging to have an identical appearance and taste. Patients in the propolis group were dosed with propolis to reach 6 mg total polyphenols/kg body weight, based on the results of a previous preclinical study in mice. Each supplementation period lasted 3 months, with a 2-week wash-out period, to allow total excretion of polyphenols by the body and do not interfere with the new supplementation phase. The subjects in this study were submitted to five visits, allowing the tracking of biological parameters (clinical examination, fasting blood samples, HGPO) during the study. During the supplementation phases, follow-up by telephone call was performed.	Dietary supplement: Placebo; Placebo powder capsules (maltodextrin, fatty acids, magnesium salts and silicon dioxide) are presented in the same packaging to have an identical appearance and taste. Patients in the propolis group were dosed with propolis to reach 6 mg total polyphenols/kg body weight, based on the results of a previous preclinical study in mice. Each supplementation period lasted 3 months, with a 2-week wash-out period, to allow total excretion of polyphenols by the body and do not interfere with the new supplementation phase. The subjects in this study were submitted to five visits, allowing the tracking of biological parameters (clinical examination, fasting blood samples, HGPO) during the study. During the supplementation phases, follow-up by telephone call was performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Matsuda-DeFronzo Insulin Sensitivity Index (ISI-M)	The primary outcome was change in the Matsuda-DeFronzo Insulin Sensitivity Index (ISI-M) at the end of supplementation. The ISI-M is calculated by the following formula: 10,000 / square root [(Glu0 × Ins0) × (Glumean OGTT × Insmean OGTT)], where Glux and Insx represent plasma glucose (mg/dL) and insulin values (UI/L), respectively, at time x min during. The ISI-M index, proposed by Matsuda and Defronzo, makes it possible to estimate insulin sensitivity derived from the OGTT	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in glucose homeostasis	Glycaemia at T0, T30, T60, T90 and T120 (mmol/L) mesured after after an oral glucose tolerance test (OGTT).	3 months
Change in insulin homeostasis	Insulinemia at T0, T30, T60, T90 and T120 (mUI/L) mesured after after an oral glucose tolerance test (OGTT).	3 months
Change in triglyceride levels	Enzymatic assay by spectrophotometry of triglycerides (mmol/L).	3 months
Change in cholesterol levels	Enzymatic assay by spectrophotometry of cholesterol (mmol/L).	3 months
Change in high density lipoprotein (HDL) cholesterol levels	Enzymatic assay by spectrophotometry of HDL cholesterol (mmol/L).	3 months
Change in low density lipoprotein (LDL) cholesterol levels	Friedewald formula : LDL=cholesterol-HDL-(triglyceride/2,2) expressed in mmol/L.	3 months
Change in glycated hemoglobin A1c (HbA1c) levels	HbA1c mass spectrometry assay (%).	3 months
Change in weight	Weight measurement by scale (kg).	3 months
Change in body mass index (BMI)	BMI calculated by weight (kg) / size (m) squared.	3 months
Change in body fat rate	Fat mass rate estimated by impedancemetry (DEXA) (%).	3 months
Change in body lean rate	Lean mass rate estimated by impedancemetry (DEXA) (%).	3 months
Change in C-reactive protein	Enzymatic determination of CRP (mg/L).	3 months
Change in transaminases levels	Enzymatic determination of alanine aminotransferase (ALAT) and aspartate aminotransférase (ASAT) (UI/L).	3 months
Change in gamma glutamyl transferases (GGT)	Enzymatic determination of gamma glutamyl transferases (GGT) (UI/L).	3 months
Change in 8-iso-prostaglandin F2α levels	Enzymatic determination of 8-iso-prostaglandin F2α (8-iso-PGF 2α) (pg/mL).	3 months
Change in creatinine levels	Enzymatic determination of creatinine (mg/L).	3 months
Change in creatinine clearance	Estimation of creatinine clearance (mL/min) by formula : 1,23 (for men) or 1,04 (for women) x weight (kg) x (140 - age)/creatinine (mg/L).	3 months
Change in leptin levels	Enzymatic determination of leptin (pg/mL).	3 months
Change in adiponectin levels	Enzymatic determination of adiponectin (ng/mL).	3 months

Collaborators and Investigators

• Sponsor: Aix Marseille Université
• Collaborators: Assistance Publique Hopitaux De Marseille
• Investigators: Principal Investigator: Jean Francois Landrier, PhD, Aix Marseille Université

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 2, 2020
• Primary Completion (ACTUAL): September 30, 2020
• Study Completion (ACTUAL): September 10, 2021

Study Registration Dates

• First Submitted: January 27, 2023
• First Submitted That Met QC Criteria: February 6, 2023
• First Posted (ACTUAL): February 8, 2023

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 6, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Propolis
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance; Anti-Infective Agents; Propolis
• Other Study ID Numbers: 1

Drug and device information, study documents

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