The Effect of Citric Flavonoid on Endothelial Function

Study Overview
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Brief Summary
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This randomized, double-blind, placebo-controlled, parallel study aims to determine the 6-week and acute effects of daily administration of a citrus flavonoid on cardiovascular and intestinal health as assessed by investigation of endothelial function, blood pressure and heart rate, glucose/insulin metabolism, lipid profile and gut barrier function in overweigh subjects. Futhermore we aim to relate the specific intestinal (microbial) metabolism with final serum levels of specific metabolites of the study product.

Official Title
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The Effect of Citric Flavonoid Administration on Endothelial Function and Gut Barrier Function

Conditions
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Obesity, Overweight

Intervention / Treatment
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* Dietary Supplement: Capsule containing citrus flavonoid
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Overweight men/women (BMI 25-35 kg/m2) Healthy individuals Age between 18 and 70 years Fasting glucose < 7.0 mmol/L Normal HbA1c (4.4 to 6.2%) Exclusion Criteria: Type 2 diabetes mellitus (defined as fasting plasma glucose ≥ 7.0 mmol/L) Gastroenterological diseases or abdominal surgery Cardiovascular diseases, cancer, liver or kidney malfunction, thyroid disorders, disease with a life expectancy shorter than 5 years Self-admitted HIV-positive status Abuse of products; alcohol (> 20 alcoholic consumptions per week) and drugs Smoking Plans to lose weight or following a hypocaloric diet during the study period Weight gain or loss > 3 kg in previous 3 months Use of medication interfering with endpoints Intake of antihypertensive medication, statins, corticosteroids, NSAIDs, ciclosporin A, rifampicin are strictly forbidden Use of antioxidants, minerals and vitamin supplements available in pharmacies, drugstores, food markets or in alternative medicine Hormone replacement therapy (women) Use of antibiotics in the 90 days prior to the start of study Administration of investigational drugs or participation in any scientific intervention study which may interfere with this study (to be decided by the principle investigator) in the 180 days prior to the study Known pregnancy (assessed by a pregnancy test before start of study), lactation Blood donation within 3 months before study period Failure to comply prohibited intake of hesperidin containing food products during study period and prohibited intake of food products that are able to influence the FMD measurements one day prior to test days. History of any side effects towards the intake of flavonoids or citrus fruits

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Cellulose | Dietary Supplement: Placebo<br> <br> |
| Experimental: Citric flavonoid<br>Citric flavonoid | Dietary Supplement: Capsule containing citrus flavonoid<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial function | The primary objective of this study is to evaluate the efficacy on endothelial function, as assessed by flow mediated dilatation (FMD) measurements, after 6 weeks of administration of study product. | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial function | The second secondary objective of this study is to determine the 6-week effect on plasma biomarkers of endothelial dysfunction and low-grade inflammation. | 6 weeks | 
| Blood pressure & heart rate | The third objective of this study is to assess the 6-week effect on blood pressure and heart rate by measuring systolic and diastolic blood pressure and heart rate. | 6 weeks | 
| Glucose / insulin metabolism | The fourth secondary objective of this study is to determine the 6-week effect on glucose / insulin metabolism by blood measurements. | 6 weeks | 
| Lipid profile | The fourth secondary objective of this study is to determine the 6-week effect on lipid profile by blood measurements. | 6 weeks | 
| Gut barrier function | The fifth secondary objective of this study is to assess the acute and 6-week effect on gut barrier function by measuring plasma and fecal endotoxin (LPS) and zonulin. | 6 weeks | 
| Gut barrier function | The sixth secondary objective of this study is to assess the 6-week effect of on gut barrier function by performing a gut sugar permeability test. | 6 weeks | 
| Colonic inflammation | The seventh secondary objective of this study is to assess the 6-week effect on colonic inflammation, by measuring fecal calprotectin. | 6 weeks | 
| Bioavailability and metabolism | The eight secondary objective of this study is to enlarge the understanding of the bioavailability and metabolism of this study product in human beings, by relating specific intestinal (microbial) metabolism with serum levels of its metabolites. | 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polyphenols, Endothelial function, Gut barrier function