Orange Juice, Hesperidin and Their Role in Vascular Health Benefit

NCT04731987 | Completed

• 1 other identifier: RBHP 2020 PICKERING 2
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Although epidemiological studies have associated the consumption of sugary beverages with adverse health effects, experimental studies have demonstrated that the metabolic response of the human body to fruit juice as compared to artificial beverages is substantially different. Fruit juices do not just provide sugars and related calories, but they are rich sources of bioactive compounds especially of flavonoids. Flavanones constitute a class of flavonoids that are specifically and abundantly found in citrus fruits, with hesperidin being the major compound in orange. From prospective cohort studies, higher intakes of flavanones are associated with a lower incidence of mortality by cardiovascular disease (CVD). This relation is supported by results from a number of animal studies demonstrating a slowdown in atherosclerosis development and vascular protective effects in dietary interventions with flavanones. Randomized, controlled clinical trials to corroborate the suggested vasculo-protective effects of orange juice presumably mediated by the flavanones are scarce and available data do not allow to draw firm conclusions about their efficacy. To fill this gap, the "HESPER-HEALTH study" conducted in humans will assess the vascular protective effects of 100% orange juice consumption and evaluate the contribution of hesperidin in these effects.

Conditions

Metabolic Syndrome; Vascular Compliance; Predisposition to Cardiovascular Disease

Keywords

Cardiovascular disease prevention; Endothelial dysfunction; Orange juice; Flavanone; Hesperidin; Nutrition Assessment; Nutritional Physiological Phenomena

Outcome Measures

Primary Outcomes (6)

• Brachial artery Flow Mediated Dilation (FMD)

  The endothelial function will be assessed using the non-invasive ultrasound technique of flow mediated dilatation of the brachial artery. FMD measure is the percentage of dilation of brachial artery in response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery in fasted state

  Day 1

• Brachial artery Flow Mediated Dilation (FMD)

  The endothelial function will be assessed using the non-invasive ultrasound technique of flow mediated dilatation of the brachial artery. FMD measure is the percentage of dilation of brachial artery in response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery in fasted state

  Day 42

• Brachial artery Flow Mediated Dilation (FMD)

  The endothelial function will be assessed using the non-invasive ultrasound technique of flow mediated dilatation of the brachial artery. FMD measure is the percentage of dilation of brachial artery in response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery in fasted state

  Day 70

• Brachial artery Flow Mediated Dilation (FMD)

  The endothelial function will be assessed using the non-invasive ultrasound technique of flow mediated dilatation of the brachial artery. FMD measure is the percentage of dilation of brachial artery in response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery in fasted state

  Day 111

• Brachial artery Flow Mediated Dilation (FMD)

  The endothelial function will be assessed using the non-invasive ultrasound technique of flow mediated dilatation of the brachial artery. FMD measure is the percentage of dilation of brachial artery in response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery in fasted state

  Day 139

• Brachial artery Flow Mediated Dilation (FMD)

  The endothelial function will be assessed using the non-invasive ultrasound technique of flow mediated dilatation of the brachial artery. FMD measure is the percentage of dilation of brachial artery in response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery in fasted state

  Day 180

Secondary Outcomes (104)

• Sex

  Day -14

• Age

  Day 34

• Basal Systolic Blood Pressure

  Day -14

• Basal Heart Rate

  Day -14

• D-3 visit systolic Blood Pressure (BP)

  Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Study Arms (3)

Orange juice (A)

EXPERIMENTAL

42 subjects between 40 and 65 years old with predisposition to cardiovascular disease will consume daily 330 ml of orange juice naturally rich in hesperidin (drink A) during 6 weeks

Behavioral: Beverage consumption

Control beverage (B)

PLACEBO COMPARATOR

42 subjects between 40 and 65 years old with predisposition to cardiovascular disease will consume daily 330 ml of control beverage (drink B)- a soft drink with sugar concentration identical to drink A - during 6 weeks

Behavioral: Beverage consumption

Control beverage supplemented with hesperidin formulation (B+HESP)

EXPERIMENTAL

42 subjects between 40 and 65 years old with predisposition to cardiovascular disease will consume daily 330 ml of control beverage (identical to drink B but supplemented with hesperidin to reach level of drink A) during 6 weeks

Behavioral: Beverage consumption

Interventions

Beverage consumption BEHAVIORAL

Volunteers will consume, in random order, daily 330 ml of 1 experimental beverage per period (Orange Juice, Control Beverage, Control Beverage supplemented with hesperidin) for 6 weeks in each period. At the beginning and the end of each period, exploration will be conducted at fasted state and at post-prandial state after the administration of a high-fat high-sugar meal.

Control beverage (B); Control beverage supplemented with hesperidin formulation (B+HESP); Orange juice (A)

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Man or post-menopausal woman ;
• years old (inclusive) ;
• Body Mass Index (BMI)≤ 30 ;
• Waist circumference ≥80 cm for women, and ≥94 cm for men ;
• Weight \> 46 kg
• Normal biological balance sheet or considered normal by the investigator
• No aversion or intolerance to citrus foods ;
• Accept to limit their total intake of flavonoid rich beverages (tea, coffee, cocoa, wine, fruit juice) to 250 mL/day ;
• Ability to give informed consent to participate in research ;
• Willingness to accept randomization and undergo the testing and intervention procedures and deliver stool, blood and urine samples for testing ;
• Affiliation to Social Security.

You may not qualify if:

• Treated pre-diabetic or diabetic ;
• Treated for hypertension ;
• Use of statins or other medications for lowering cholesterol ;
• Treated with antibiotics, antifungals, probiotics or prebiotics in the 3 months before the enrolment ;
• Menopausal hormone replacement therapy ;
• Diagnosed gastrointestinal illness in the judgement of the investigator ;
• Any serious medical condition that precludes safe participation in the study, such as coronary artery disease, peripheral vascular disease, stroke, congestive heart failure, chronic obstructive pulmonary disease, insulin-dependent diabetes, psychiatric disease, renal disease, liver disease, active cancer and anemia ;
• History of eating disorders such as bulimia nervosa, anorexia nervosa and severe binge eating disorder in the last 5 years ;
• Digestive disorders with diarrhea during the 3 months preceding the beginning of the study ;
• Self-declared vegetarian, vegetalian, vegan ;
• History of substance abuse or alcohol abuse ;
• Involvement in a weight loss intervention program (including anti-obesity medication) within the past 3 months or who have had bariatric surgery ;
• Current smokers (within the last 30 days) ;
• Use of dietary supplements (vitamins, antioxidants) currently or in the past one month ;
• Strenuous exercise greater than 6 hours per week ;

Sponsors & Collaborators

• University Hospital, Clermont-Ferrand: lead
• UMR 1019, Unité de Nutrition Humaine, INRAE, Auvergne-Rhône Alpes Center: collaborator
• Department of Beverage Research, Chair of analysis and technology of plant-based foods, Geisenheim University: collaborator
• European Fruit Juice Association (AIJN): collaborator

Study Sites (1)

University Hospital, Clermont Ferrand

Clermont-Ferrand, AURA, 63000, France

Location

Related Publications (1)

• Verny MA, Milenkovic D, Macian N, Pereira B, Evrard R, Gilcher C, Steingass CB, Mosoni P, Gladine C, Monfoulet LE, Schweiggert R, Pickering G, Morand C. Evaluating the role of orange juice, HESPERidin in vascular HEALTH benefits (HESPER-HEALTH study): protocol for a randomised controlled trial. BMJ Open. 2021 Nov 30;11(11):e053321. doi: 10.1136/bmjopen-2021-053321.

  PMID: 34848522 DERIVED

MeSH Terms

Conditions

Metabolic Syndrome

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: drinks kits will be labelled and packaged according to the pre-established randomization plane by the pharmacy department of University Hospital of Clermont-Ferrand, France. Kits will be distributed in a blind fashion for each cross over period on the basis of the randomization schedule.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2021
• First Posted: February 1, 2021
• Study Start: February 24, 2021
• Primary Completion: June 20, 2023
• Study Completion: June 20, 2023
• Last Updated: July 19, 2024

Record last verified: 2024-07

Locations

FR (1)