Orange Juice, Hesperidin and Their Role in Vascular Health Benefit

NCT ID: NCT04731987

Last Updated: 2024-07-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-24
• Study Completion Date: 2023-06-20

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.

Detailed Description

This human dietary intervention study is a double blind, randomized, placebo controlled, cross over trial with 3 arms, carried out on subjects with predisposition to cardiovascular diseases (CVD) based on age and overweight. This study aims to demonstrate the vascular protective effects (with Flow Mediated Dilatation (FMD) as main criteria) of the consumption of a flavanone rich orange juice or of orange flavanones by comparison with a control sugary drink alone.

The 42 recruited participants will receive the 3 drinks in a random order. For each subject, the study is divided into 3 identical experimental periods of 45 days (period 1,2,3): including 3 days prior to the beginning of the product intake, during which specific dietary guidelines, samplings and measures will be asked to be performed at home followed by a 6 weeks period of consumption of each of the 3 beverages). A period of 4 to 6 weeks of wash-out is planned between each experimental period.

To summarize: Visit 1 (D-14) = inclusion, Visit 2 (D1: baseline) to 3 (D42) = period 1, Visit 3 (D42) to 4 (D70) = wash out 1, Visit 4 (D70) to 5 (D111) = period 2, Visit 5 (D111) to 6 (D139) = wash out 2, Visit 6 (D139) to 7 (D180) = period 3. The wash-out periods (minimum duration: 4 weeks) may be extended until 6 weeks for the convenience of participants.

The protocol includes a total of 7 visits to PIC/CIC Inserm 1405 of the Clermont-Fd University Hospital.

The total duration of the study will be between 28 and 34 weeks

Conditions

Metabolic Syndrome; Vascular Compliance; Predisposition to Cardiovascular Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Orange juice (A)

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

Group Type: EXPERIMENTAL

Beverage consumption

Intervention Type: 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)

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

Group Type: PLACEBO_COMPARATOR

Beverage consumption

Intervention Type: 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 supplemented with hesperidin formulation (B+HESP)

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

Group Type: EXPERIMENTAL

Beverage consumption

Intervention Type: 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.

Interventions

Beverage consumption

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.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Man or post-menopausal woman ;
• 40-65 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.

Exclusion Criteria

• 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 ;
• Anyone who in the opinion of the investigator is unlikely to be able to comply with the protocol ;
• Subjects involved in another clinical trial or being in the exclusion period of another study or having received a total compensation greater than 4,500 euros over the 12 months preceding the start of the trial ;
• Subject benefiting from a legal protection measure (curatorship, guardianship, safeguard of justice) ;
• Refusal to participate.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

UMR 1019, Unité de Nutrition Humaine, INRAE, Auvergne-Rhône Alpes Center

UNKNOWN

Sponsor Role: collaborator

Department of Beverage Research, Chair of analysis and technology of plant-based foods, Geisenheim University

UNKNOWN

Sponsor Role: collaborator

European Fruit Juice Association (AIJN)

UNKNOWN

Sponsor Role: collaborator

University Hospital, Clermont-Ferrand

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University Hospital, Clermont Ferrand

Clermont-Ferrand, AURA, France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 34848522 (View on PubMed)

Other Identifiers

RBHP 2020 PICKERING 2

Identifier Type: -

Identifier Source: org_study_id