Dietary Polyphenols and Insulin Sensitivity in Overweight and Obese Humans

NCT02381145 | Completed

• 1 other identifier: NL31421.068.10
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

In this double-blind, randomized, placebo-controlled study, we aim to investigate the effects of a long-term supplementation on insulin sensitivity, mitochondrial function and substrate metabolism in healthy overweight men and women. In each group, 21 subjects consume 100mg Resveratrol (RSV) and 150mg Epigallocatechin-gallate (EGCG), respectively Placebo capsules, twice daily over a period of 12 weeks. The subjects receive the capsules after the last pre-measurement and continue to take them throughout the post-measurements. Before and after the supplementation period, we perform a hyperinsulinemic-euglycemic clamp with a glucose-tracer infusion to assess hepatic and systemic insulin sensitivity. Simultaneously, substrate oxidation is measured throughout the clamp by indirect calorimetry. Furthermore, we perform a high-fat mixed meal test, in which we collect blood and measure substrate oxidation during fasted and postprandial conditions. During the meal tests, extra plasma is collected at the start (t=-30) and the end (t=240), of which the supernatant is stored in light-protected tubes (EGCG is mixed 1:1 with an EGCG buffer) for analyzing polyphenol concentrations in the blood. In the male subgroup (21 men), we additionally place each 2 microdialysis probes in the subcutaneous adipose tissue and the gastrocnemius in order to assess local lipolysis and blood flow by means of ethanol infusion. Furthermore, a dexa-scan is performed to assess body composition and biopsies are taken under fasted conditions from the subcutaneous adipose tissue and the quadriceps femoralis muscle. These samples are stored at -80C. Part of the adipose tissue samples is collected to measure adipocyte size. Of the skeletal muscle biopsy, one part is directly buffered and used for the oxygraph to measure mitochondrial function. At last, feces samples are collected before and after the intervention in order to assess energy content, microbial composition and short-chain fatty acid content. Based on previous human studies in our and other departments, we hypothesize that after 12 weeks of the combined polyphenol supplementation, insulin sensitivity and mitochondrial function improve. Furthermore, based on results of a short-term study performed by our group, that demonstrated an increase in energy expenditure, a positive effect on the regulation of body composition might be expected.

Conditions

Healthy

Keywords

Polyphenols; Resveratrol; Epigallocatechin-gallate; Insulin sensitivity; mitochondrial function; lipid oxidation; tissue lipolysis

Outcome Measures

Primary Outcomes (1)

• Systemic insulin sensitivity

  hyperinsulinemic euglycemic clamp with glucose-tracer

  change from week 0 to week 12 after supplementation

Secondary Outcomes (1)

• skeletal muscle mitochondrial function

  change from week 0 to week 12 after supplementation

Other Outcomes (2)

• lipid oxidation

  change from week 0 to week 12 after supplementation

• skeletal muscle and adipose tissue lipolysis

  change from week 0 to week 12 after supplementation

Study Arms (2)

Placebo

PLACEBO COMPARATOR

micro-cellulose-filled Placebo

Dietary Supplement: Placebo

EGCG+RSV-supplementation

ACTIVE COMPARATOR

EGCG+RSV: 300mg/d + 80mg/d

Dietary Supplement: EGCG+RSV-supplementation

Interventions

EGCG+RSV-supplementation DIETARY_SUPPLEMENT

Teavigo (\~300mg/d) Resveratrol (\~80mg/d)

Also known as: Teavigo, Pure Encapsulations Inc. (Massachusetts, USA), Resveratrol, Pure Encapsulations Inc. (Massachusetts, USA)

EGCG+RSV-supplementation

Placebo DIETARY_SUPPLEMENT

Placebo

Eligibility Criteria

• Age: 20 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Overweight men and women (BMI≥25kg/m2-39.9kg/m2),
• Aged 20-35 and 35-50 years
• Caucasian
• Normal fasting glucose (\< 6.1 mmol/L) and normal postprandial glucose (2h-glucose \<7.8 mm)
• Normal blood pressure (systolic blood pressure 100-140 mmHg, diastolic blood pressure 60-90 mmHg)
• Weight stable in last 3 months (± 2kg)

You may not qualify if:

• Women lactating, pregnant or (post) menopausal
• Regular smokers
• People with intensive fitness training, eg. athletes (≥ 3 per week ≥ 1 hour training)
• Habitual consumption of green tea (more than 1 cup per day) or products containing green tea extract
• Total caffeine consumption \> 300 mg/day (1 can of cola or 2 cups of regular coffee or 2 cups of black tea or 1 cup of coffee and 1 cup of black tea or other combinations)
• Alcohol intake \>20 g/day (2 glasses of beer or wine)
• Any dietary vitamins or dietary supplements
• Diabetes mellitus (defined as FPG ≥ 7.0 mmol/l and/or 2hPG ≥ 11.1 mmol/l)
• Serious pulmonary, cardiovascular, hepatic or renal disease
• History of cardiovascular disease
• All other relevant medical disorders that potentially interfere with this trial (e.g. history of gastro-intestinal, liver or thyroid disorders)
• Current use of medication interfering with study intervention or interfering with study endpoints/hypotheses (e.g. medication containing caffeine like analgesics, anorectics and analeptics)
• Not to be able to understand the study information
• Subjects on a special diet or vegetarian
• Blood donation 2 months prior to the study and during the study

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (1)

Maastricht University

Maastricht, 6229 ER, Netherlands

Location

Related Publications (3)

• Fazelzadeh P, Hoefsloot HCJ, Hankemeier T, Most J, Kersten S, Blaak EE, Boekschoten M, van Duynhoven J. Global testing of shifts in metabolic phenotype. Metabolomics. 2018 Oct 4;14(10):139. doi: 10.1007/s11306-018-1435-8.

  PMID: 30830386 DERIVED

• Most J, Goossens GH, Reijnders D, Canfora EE, Penders J, Blaak EE. Gut microbiota composition strongly correlates to peripheral insulin sensitivity in obese men but not in women. Benef Microbes. 2017 Aug 24;8(4):557-562. doi: 10.3920/BM2016.0189. Epub 2017 Jun 16.

  PMID: 28618864 DERIVED

• Most J, Timmers S, Warnke I, Jocken JW, van Boekschoten M, de Groot P, Bendik I, Schrauwen P, Goossens GH, Blaak EE. Combined epigallocatechin-3-gallate and resveratrol supplementation for 12 wk increases mitochondrial capacity and fat oxidation, but not insulin sensitivity, in obese humans: a randomized controlled trial. Am J Clin Nutr. 2016 Jul;104(1):215-27. doi: 10.3945/ajcn.115.122937. Epub 2016 May 18.

  PMID: 27194304 DERIVED

MeSH Terms

Conditions

Insulin Resistance

Interventions

Resveratrol

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Stilbestrols; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polyphenols; Phenols

Study Officials

• Ellen E Blaak, Prof.

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2013
• First Posted: March 6, 2015
• Study Start: August 1, 2012
• Primary Completion: May 1, 2014
• Study Completion: September 1, 2014
• Last Updated: September 5, 2018

Record last verified: 2018-09

Locations

NL (1)