The Effect of Sweet Orange and Pomegranate Extract Supplementation on Exercise Capacity in Middle-aged Adults

Study Overview
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Brief Summary
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The aim of the present study is to investigate the effect of 12-week long daily administration of a sweet orange and pomegranate extract on exercise capacity in healthy adults.

Detailed Description
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Background of the study: Polyphenols have been studied for their protective effect against the development of ROS-related diseases like cancers, cardiovascular diseases, diabetes, osteoporosis, and neurodegenerative diseases. The combined supplementation of pomegranate and sweet orange polyphenols could be an effective strategy to improve exercise performance, due to their antioxidant character and ability to stimulate NO production, to stimulate mitochondrial biogenesis and to accelerate muscle repair and decrease muscle tissue damage. The study aims to assess the effect of a combined supplementation of pomegranate and sweet orange extract on exercise capacity, physical activity, muscle strength and quality of life in healthy adults. Objective of the study: The aim of the present study is to investigate the effect of 12-week long daily administration of a sweet orange and pomegranate extract on exercise capacity in healthy adults (40 - 65 y). Study design: Randomized, double-blind, placebo-controlled parallel trial Study population: Healthy, overweight, sedentary adults between 40 and 65 years old. Intervention: 12-week supplementation with 650 mg sweet orange and pomegranate extract (2 capsules per day) compared to placebo (760 mg maltodextrin). Primary outcome of the study: Change in aerobic capacity (VO2max), assessed with an Ekblom-Bak submaximal cycling test. Secondary study parameters/outcome of the study: Daily physical activity as determined by accelerometer Dietary intake as measured by a 3-day food record Handgrip strength Muscle cell proliferation and differentiation and mitochondrial biogenesis assessed in skeletal muscle biopsies Quality of Life as measured by the WHO-QOL-100 questionnaire General health as measured by SF-36 questionnaire Vitality as measured by the Dutch Vitality Questionnaire (Vita-16) Cardiometabolic health biomarkers, cortisol, C-reactive protein determined with ELISA Antioxidative capacity measured with a Trolox equivalent antioxidant capacity (TEAC) assay

Official Title
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The Effect of Sweet Orange and Pomegranate Extract Supplementation on Exercise Capacity: a Randomized Controlled Parallel Intervention Study in Healthy Overweight Individuals

Conditions
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Exercise Capacity

Intervention / Treatment
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* Dietary Supplement: Sweet orange and pomegranate extract
* Other: Maltodextrin control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male/female (based on medical history provided during a general health questionnaire) Age between 40 - 65 yrs Overweight (BMI ≥25 to ≤29.9 kg/m2) Sedentary subjects (Low Level [<600 MET-minutes/week] as assessed by the Physical Activity Questionnaire (IPAQ)) Exclusion Criteria: Allergy to test product/control or citrus fruits and pomegranate Medical conditions that might interfere with endpoints or compromise participant safety during testing (e.g. Cardiovascular diseases, cancer, Parkinson's disease, Gastrointestinal diseases or abdominal surgery) to be decided by the principal investigator Use of medication that might interfere with endpoints (i.e.: β-blockers, antioxidant, antidepressants) High fasting blood glucose (FBG ≥100 mg/dL) Recent skeletal muscle injury in less than one month before the start of the study Use of antibiotics within 3 months prior to Visit 2 Use of probiotics or supplements containing vitamins, minerals or antioxidants four weeks prior to Visit 2 Regular smoking (including use of e-cigarettes) Inability to correctly perform the PA test during screening/familiarization Abuse of alcohol (alcohol consumption >20 units/week) and/or drugs Plans to change diet or medication for the duration of the study Treatment with an investigational drug (phase 1-3) 180 days before the start of the study Inability to understand study information and/or communicate with staff

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind, placebo-controlled parallel trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sweet orange and pomegranate extract<br>Supplementation | Dietary Supplement: Sweet orange and pomegranate extract<br>* From the daily 650mg total supplementation of the investigational product, 250 mg will be of pomegranate extract containing 100mg of punicalagin. The remaining 400 mg will consist of sweet orange peel extract containing 360 mg of hesperidin.<br>|
| Placebo Comparator: Maltodextrin<br>Supplementation | Other: Maltodextrin control<br>* Supplementation with 760 mg maltodextrin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in endurance capacity | An Ekblom-bak cycling test is used to estimate the maximal oxygen consumption | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Daily physical activity | Measured with an accelerometer | 12 weeks | 
| Change in Handgrip strength | Measured with a dynamometer | 12 weeks | 
| Change in Self reported quality of life | Measured with the World Health Organization Quality of Life (WHO-QOL-100) questionnaire. For 6 domains (including physical, psychological, level of independence, social relationships, environment and religion/personal beliefs), a score will be calculated between 2 - 40 in which a higher score indicates better quality of life. | 12 weeks | 
| Change in General health | Measured with the 36-Item Short Form Health Survey. For 4 domains (including functional status, wellbeing, general health and change in health), a score will be calculated between 0 - 100 in which a higher score indicates better health. | 12 weeks | 
| Change in Vitality | Measured with the vita-16 questionnaire. For 4 domains (including energy, motivation, resilience and overall vitality), a score will be calculated between 1 - 7 in which a higher score indicates higher vitality. | 12 weeks | 
| Change in Glucose levels | Measured in blood samples | 12 weeks | 
| Change in Cholesterol levels | Measured in blood samples | 12 weeks | 
| Change in Triglyceride levels | Measured in blood samples | 12 weeks | 
| Change in Insulin levels | Measured in blood samples | 12 weeks | 
| Change in Cortisol levels | Measured in blood samples | 12 weeks | 
| Change in C-reactive protein levels | Measured in blood samples | 12 weeks | 
| Change in Antioxidative capacity | Measured with a TEAC assay in blood | 12 weeks | 
| Change in Cell elongation index | Measured with immunohistochemistry in muscle tissue samples | 12 weeks | 
| Change in Muscle proliferation (marker Pax7) | Measured with qPCR in muscle tissue samples | 12 weeks | 
| Change in Muscle differentiation (marker MyoD) | Measured with qPCR in muscle tissue samples | 12 weeks | 
| Change in Muscle differentiation (marker Myogenin) | Measured with qPCR in muscle tissue samples | 12 weeks | 
| Change in Muscle differentiation (marker Myosin Heavy Chain) | Measured with qPCR in muscle tissue samples | 12 weeks | 
| Change in Muscle mitochondrial biogenesis (marker PGC1alpha) | Measured with qPCR in muscle tissue samples | 12 weeks | 
| Change in Muscle metabolism (marker Glut4) | Measured with qPCR in muscle tissue samples | 12 weeks | 
| Change in Muscle redox biology (marker GCLC) | Measured with qPCR in muscle tissue samples | 12 weeks | 
| Change in Muscle redox biology (marker Hmox1) | Measured with qPCR in muscle tissue samples | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sweet orange, Pomegranate, Polyphenols, Exercise capacity, Ekblom-bak