The Effect of Sweet Orange and Pomegranate Extract Supplementation on Exercise Capacity in Middle-aged Adults (Actiful2)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Exercise Capacity
• Intervention / Treatment: Dietary supplement: Sweet orange and pomegranate extract; Other: Maltodextrin control

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 52
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Freddy Troost, dr.; Phone Number: +31(0)43 3884296; Email: f.troost@maastrichtuniversity.nl

Study Locations

• Netherlands
  • Maastricht, Netherlands
    • Recruiting
    • Maastricht University
    • Contact: Freddy Troost, dr.; Phone Number: +31(0)43 3884296; Email: f.troost@maastrichtuniversity.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sweet orange and pomegranate extract; Supplementation	Dietary supplement: Sweet orange and pomegranate extract; 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.
Placebo Comparator: Maltodextrin; Supplementation	Other: Maltodextrin control; Supplementation with 760 mg maltodextrin

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Maastricht University
• Collaborators: BioActor B.V.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2021
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: October 26, 2021
• First Submitted That Met QC Criteria: November 15, 2021
• First Posted (Actual): November 24, 2021

Study Record Updates

• Last Update Posted (Actual): November 24, 2021
• Last Update Submitted That Met QC Criteria: November 15, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Pomegranate; Polyphenols; Exercise capacity; Sweet orange; Ekblom-bak
• Other Study ID Numbers: Actiful2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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