Gut-level Antiinflammatory Activities of Green Tea in Metabolic Syndrome

Sponsor

Ohio State University (Other)

Overall Status

Completed

CT.gov ID

NCT03973996

Collaborator

USDA Beltsville Human Nutrition Research Center (U.S. Fed)

Enrollment

Location

Arms

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study evaluates dietary green tea extract to improve gut health and inflammation in persons with metabolic syndrome and healthy adults. Participants will complete two phases of intervention in random order in which they will consume green tea extract or placebo for one month and then switch to the opposite treatment for an additional month.

Condition or Disease	Intervention/Treatment	Phase
Dysbiosis Endotoxemia Metabolic Syndrome Inflammation	Dietary Supplement: Green Tea Extract Dietary Supplement: Placebo	N/A

Detailed Description

Tea is the most abundantly consumed prepared beverage in the world. Green tea, containing catechins, exerts antiinflammatory activities. However, a fundamental gap exists concerning its intestinal-level targets that can prevent metabolic syndrome (MetS) development and progression. Studies in obese rodents indicate that green tea inhibits nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) activation by limiting gut-derived endotoxin translocation to the portal circulation and decreasing hepatic Toll-like receptor-4 (TLR4) pro-inflammatory signaling. The objective of this clinical investigation is to establish evidence-based recommendations for green tea, based on improvements in endotoxemia and restored gut barrier function, that promote optimal health. The hypothesis is that green tea catechins function to limit metabolic endotoxemia by ameliorating gut dysbiosis-mediated inflammation that otherwise provokes intestinal permeability. This will be tested by conducting a double-blind, placebo-controlled, randomized-order, crossover trial in MetS and healthy persons to examine the efficacy of green tea on metabolic endotoxemia. Each treatment will be one-month in duration and separated by a washout period. The anticipated outcomes are expected to be of significance, because they will advance a dietary strategy to help avert MetS complications attributed to metabolic endotoxemia by establishing antiinflammatory prebiotic and antimicrobial bioactivities of catechins that promote intestinal health.

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Prevention

Official Title:

Gut-level Antiinflammatory Activities of Green Tea in Metabolic Syndrome

Actual Study Start Date :

Jul 1, 2019

Actual Primary Completion Date :

Mar 1, 2021

Actual Study Completion Date :

Mar 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Green Tea Participants consuming gummy confections with catechin-rich green tea extract daily for 4 weeks	Dietary Supplement: Green Tea Extract A gummy confection with catechin-rich green tea extract (1 g/d) Other Names: Camellia sinesis plant extract
Placebo Comparator: Placebo Participants consuming matched gummy confections formulated without green tea extract daily for 4 weeks	Dietary Supplement: Placebo A matched gummy confection formulated without green tea extract

Arm

Intervention/Treatment

Experimental: Green Tea

Participants consuming gummy confections with catechin-rich green tea extract daily for 4 weeks

Dietary Supplement: Green Tea Extract

A gummy confection with catechin-rich green tea extract (1 g/d)

Other Names:

Camellia sinesis plant extract

Placebo Comparator: Placebo

Participants consuming matched gummy confections formulated without green tea extract daily for 4 weeks

Dietary Supplement: Placebo

A matched gummy confection formulated without green tea extract

Outcome Measures

Primary Outcome Measures

Change in metabolic endotoxemia [Day 0, 14, and 28 of the 28-day intervention]
Serum endotoxin concentration (EU/mL) will be measured at the beginning, in the middle, and at the end of each treatment. Time-dependent changes relative to baseline (day 0) in each treatment and between-treatment differences will be measured in MetS vs. healthy individuals.

Secondary Outcome Measures

Gastrointestinal permeability [Day 28 of the 28-day intervention]
Lactulose/mannitol ratio will be measured in urine collected 0-5 h post-ingestion to assess small intestinal permeability. Sucralose (%) will be measured in urine collected 0-24 h post-ingestion to assess colonic permeability. Between-treatment differences will be measured in MetS vs. healthy individuals.
Plasma inflammatory biomarker: C-reactive protein [Day 28 of the 28-day intervention]
Plasma concentration (mg/L) of C-reactive protein will be measured at the end of each treatment. Between-treatment differences will be measured in MetS vs. healthy individuals.
Plasma inflammatory biomarkers: interleukin-6, interleukin-8, and tumor necrosis factor alpha [Day 28 of the 28-day intervention]
Plasma concentrations (pg/mL) of interleukin-6, interleukin-8, and tumor necrosis factor alpha will be measured individually at the end of each treatment. Between-treatment differences will be measured in MetS vs. healthy individuals.
Plasma inflammatory biomarker: myeloperoxidase [Day 28 of the 28-day intervention]
Plasma concentration (ng/mL) of myeloperoxidase will be measured at the end of each treatment. Between-treatment differences will be measured in MetS vs. healthy individuals.
Pro-inflammatory gene expression from peripheral blood mononuclear cells [Day 28 of the 28-day intervention]
Relative expression of toll-like receptor 4, myeloid differentiation factor 88, p65 subunit of NF-kappa B, interleukin-6, interleukin-8, tumor necrosis factor alpha, and monocyte chemoattractant protein-1 will be measured individually at the end of each treatment. Between-treatment differences will be measured in MetS vs. healthy individuals.
Intestinal inflammatory biomarker: calprotectin [Days 25-27 of the 28-day intervention]
Fecal concentration (μg/g) of calprotectin will be measured in samples collected over 3 consecutive days and pooled prior to analysis. Between-treatment differences will be measured in MetS vs. healthy individuals.
Intestinal inflammatory biomarker: myeloperoxidase [Days 25-27 of the 28-day intervention]
Fecal concentration (ng/g) of myeloperoxidase will be measured in samples collected over 3 consecutive days and pooled prior to analysis. Between-treatment differences will be measured in MetS vs. healthy individuals.
Changes in plasma catechins and their metabolites [Day 0, 14, and 28 of the 28-day intervention]
Plasma concentrations (nmol/L) of epigallocatechin gallate, epicatechin gallate, epigallocatechin, epicatechin, gamma-valerolactones, and catechin-derivates will be measured individually at the beginning, in the middle, and at the end of each treatment. Time-dependent changes relative to baseline (day 0) in each treatment and between-treatment differences will be measured in MetS vs. healthy individuals.
Fecal catechins and their metabolites [Days 25-27 of the 28-day intervention]
Fecal concentrations (μmol/kg) of epigallocatechin gallate, epicatechin gallate, epigallocatechin, epicatechin, gamma-valerolactones, and catechin-derivates will be measured individually in samples collected over 3 consecutive days and pooled prior to analysis. Between-treatment differences will be measured in MetS vs. healthy individuals.
Fecal short-chain fatty acids [Days 25-27 of the 28-day intervention]
Fecal concentrations (mmol/kg) of butyrate, acetate, propionate, isobutyric acid, and isovaleric acid will be measured individually in samples collected over 3 consecutive days and pooled prior to analysis. Between-treatment differences will be measured in MetS vs. healthy individuals.
Gut microbiota diversity indices [Days 25-27 of the 28-day intervention]
Gut microbiota diversity indices (Shannon species and Chao1) will be measured in fecal samples collected over 3 consecutive days and pooled prior to analysis. Between-treatment differences will be measured in MetS vs. healthy individuals.
Gut microbiota Firmicutes/Bacteroidetes ratio [Days 25-27 of the 28-day intervention]
Gut microbiota Firmicutes/Bacteroidetes ratio will be measured in fecal samples collected over 3 consecutive days and pooled prior to analysis. Between-treatment differences will be measured in MetS vs. healthy individuals.
Gut microbiota relative abundance [Days 25-27 of the 28-day intervention]
Gut microbiota relative abundance (% order, genus, and species level) will be measured in fecal samples collected over 3 consecutive days and pooled prior to analysis. Between-treatment differences will be measured in MetS vs. healthy individuals.
Gut microbiota function proportions [Days 25-27 of the 28-day intervention]
Gut microbiota function proportions (%) based on microbial genome analysis will be measured in fecal samples collected over 3 consecutive days and pooled prior to analysis. Between-treatment differences will be measured in MetS vs. healthy individuals.
Change in plasma glucose [Day 0, 14, and 28 of the 28-day intervention]
Plasma concentration (mg/dL) of glucose will be measured at the beginning, in the middle, and at the end of each treatment. Time-dependent changes relative to baseline (day 0) in each treatment and between-treatment differences will be measured in MetS vs. healthy individuals.
Change in plasma insulin [Day 0, 14, and 28 of the 28-day intervention]
Plasma concentration (μIU/mL) of insulin will be measured at the beginning, in the middle, and at the end of each treatment. Time-dependent changes relative to baseline (day 0) in each treatment and between-treatment differences will be measured in MetS vs. healthy individuals.
Change in plasma lipids [Day 0, 14, and 28 of the 28-day intervention]
Plasma concentrations (mg/dL) of triglyceride and HDL-cholesterol will be measured at the beginning, in the middle, and at the end of each treatment. Time-dependent changes relative to baseline (day 0) in each treatment and between-treatment differences will be measured in MetS vs. healthy individuals.
Changes in serum alanine transaminase and aspartate transaminase [Day 0, 14, and 28 of the 28-day intervention]
Serum concentrations (U/L) of alanine transaminase and aspartate transaminase will be measured at the beginning, in the middle, and at the end of each treatment. Time-dependent changes relative to baseline (day 0) in each treatment and between-treatment differences will be measured in MetS vs. healthy individuals.
Changes in serum creatinine and blood urea nitrogen [Day 0, 14, and 28 of the 28-day intervention]
Serum concentrations (U/L) of creatinine and blood urea nitrogen will be measured at the beginning, in the middle, and at the end of each treatment. Time-dependent changes relative to baseline (day 0) in each treatment and between-treatment differences will be measured in MetS vs. healthy individuals.
Change in blood hematocrit [Day 0, 14, and 28 of the 28-day intervention]
Blood hematocrit (%) will be measured at the beginning, in the middle, and at the end of each treatment. Time-dependent changes relative to baseline (day 0) in each treatment and between-treatment differences will be measured in MetS vs. healthy individuals.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion criteria:

Individuals with ≥3 of the following established criteria for metabolic syndrome:

Fasting glucose 100-126 mg/dL
Waist circumference >89/>102 cm for females/males
HDL-C <50/<40 mg/dL for females/males
Triglyceride >150 mg/dL
Blood pressure >130/85 mmHg

Healthy adults:

Body weight 19-25 kg/m2
Fasting glucose <100 mg/dL
HDL-C >50/>40 mg/dL for females/males
Triglyceride <150 mg/dL
Blood pressure <120/80 mmHg

Exclusion criteria:

Concurrent tea consumption
Use of dietary supplements, prebiotics, or probiotics
Use of antibiotics or antiinflammatory agents
History of liver disease, cardiovascular disease, hypertension (blood pressure >140/90 mmHg), or cancer
History of gastrointestinal disorders, chronic diarrhea, or surgeries
Hemochromatosis
Parkinson's disease
Use of medications to manage diabetes, hypertension, or hyperlipidemia
Use of antipsychotic medications [Clozapine, lithium, Diazepam]
Use of blood thinning medications [Warfarin]
Use of high blood pressure medications [nadolol]
Use of monoamine oxidase inhibitors [selegiline]
Alcohol consumption >2 drinks/d
Smoking tobacco
Vegetarian
Pregnancy, lactation, or recent changes in birth control use for women