Orange Juice, Hesperidin and Their Role in Vascular Health Benefit

N/ACompletedNCT04731987

University Hospital, Clermont-Ferrand50 enrolled

Overview

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.

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

QUADRUPLE

Enrollment

Interventions

Beverage consumptionBEHAVIORAL

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.

Eligibility

Sex: ALLMin age: 40 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

University Hospital, Clermont Ferrand

Clermont-Ferrand, AURA, France

Outcomes

Primary Outcomes

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

Time frame: Day 1

Brachial artery Flow Mediated Dilation (FMD)

Time frame: Day 42

Brachial artery Flow Mediated Dilation (FMD)

Time frame: Day 70

Brachial artery Flow Mediated Dilation (FMD)

Time frame: Day 111

Brachial artery Flow Mediated Dilation (FMD)

Time frame: Day 139

Brachial artery Flow Mediated Dilation (FMD)

Time frame: Day 180

Secondary Outcomes

Sex

Participant sex (man/women) will be requested.

Time frame: Day -14

Age

Participant age (years) will be requested.

Time frame: Day 34

Basal Systolic Blood Pressure

Blood pressure measure (mm Hg) with monitor.

Time frame: Day -14

Basal Heart Rate

Heart rate measure (beat/min) with monitor.

Time frame: Day -14

D-3 visit systolic Blood Pressure (BP)

Self-monitored blood pressure (mmHg) at home with tensiometer, at home the morning, 3 days before the visit, in fasted state.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

D-3 visit diastolic BP

Self-monitored blood pressure (mmHg) at home with tensiometer, at home the morning, 3 days before the visit, in fasted state.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

D-3 visit Heart Rate

Self-monitored heart rate (beat/min) at home with tensiometer,at home the morning, 3 days before the visit, in fasted state.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

FMD post prandial endothelial response 3h after a challenge meal

Assessment of the postprandial endothelial response to a challenge meal (900kcal, fresh cream, sucrose and milk proteins) by measuring FMD (percent) using ultrasound technique, 3h after intake of the full daily dose of study products concomitantly with challenge meal.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Data from ClinicalTrials.gov

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FMD post prandial endothelial response 6h after a challenge meal

Assessment of the postprandial endothelial response to a challenge meal by measuring FMD (percent) using ultrasound technique, 6h after intake of the full daily dose of study products concomitantly with challenge meal.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Arterial compliance assessment

Noninvasive measure with Sphygmocor (AtCor Medical Pty. Ltd) of pulse transit time between carotid artery and femoral artery. The carotid-femoral Pulse Wave Velocity (PWV) (m/sec) is an established index of arterial stiffness,in fasted state.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Rest flow by Flowmetry Laser Doppler (FLD) in fasted state

Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the rest flow using laser-Doppler system at the level of the skin of the hand, in fasted state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Occlusion area by FLD in fasted state

Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the occlusion area using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement) in fasted state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Hyperaemia area by FLD in fasted state

Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the hyperaemia area using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement) in fasted state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Hyperaemia area / occlusion area ratio by FLD in fasted state

Vascular endothelial function in the micro-vascular compartment will be assessed using the ratio hyperaemia area / occlusion area determined by FLD.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Maximal flow by FLD in fasted state

Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the maximal flow using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), in fasted state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Hyperaemia half time by FLD in fasted state

Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the hyperaemia half time using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), in fasted state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Rest flow by FLD 3h after a challenge meal

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Occlusion area by FLD 3h after a challenge meal

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Hyperaemia area by FLD 3h after a challenge meal

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Hyperaemia area / occlusion area ratio by FLD 3h after a challenge meal

Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the ratio hyperaemia area/ occlusion area determined by FLD, 3h after intake of the full daily dose of study products concomitantly with challenge meal

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Maximal flow by FLD 3h after a challenge meal

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Hyperaemia half time by FLD 3h after a challenge meal

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Rest flow by FLD 6h after a challenge meal

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Occlusion area by FLD 6h after a challenge meal

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Hyperaemia area by FLD 6h after a challenge meal

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Hyperaemia area / occlusion area ratio by FLD 6h after a challenge meal

Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the ratio hyperaemia area / occlusion area ratio determined by FLD, 6h after intake of the full daily dose of study products concomitantly with challenge meal

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Maximal flow by FLD 6h after a challenge meal

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Hyperaemia half time by FLD 6h after a challenge meal

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Hesperetin concentration in 24h urine

Concentration of hesperetin in urine (nM) will be measured.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Hesperetin concentration in plasma on fasted state

Concentration of hesperetin in plasma (nM) will be measured.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Hesperetin catabolites concentration in plasma on fasted state

Concentration of hesperetin microbial catabolites in plasma (nM) will be measured, on fasted state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Hesperetin concentration in plasma on 3h post prandial test

Concentration of hesperetin in plasma (mM) will be measured, in post prandial state 3h after the concomitant consumption of the study drink and challenge meal.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Hesperetin catabolites concentration in plasma on 3h post prandial test

Concentration of hesperetin microbial catabolites in plasma (mM) will be measured, in post prandial state 3h after the concomitant consumption of the study drink and challenge meal.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Hesperetin concentration in plasma on 6h post prandial test

Concentration of hesperetin in plasma (mM) will be measured, in post prandial state 6h after the concomitant consumption of the study drink and challenge meal.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Hesperetin catabolites concentration in plasma on 6h post prandial test

Concentration of hesperetin microbial catabolites in plasma (mM) will be measured, in post prandial state 6h after the concomitant consumption of the study drink and challenge meal.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Naringenin concentration in 24h urine

Concentration of naringenin in urine (nM) will be measured.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Naringenin catabolites concentration in 24h urine

Concentration of naringenin microbial catabolites in urine (nM) will be measured.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Naringenin concentration in plasma on fasted state

Concentration of naringenin in plasma (nM) will be measured, on fasted state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Naringenin catabolites concentration in plasma on fasted state

Concentration of naringenin microbial catabolites in plasma (nM) will be measured, on fasted state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Naringenin concentration in plasma on 3h post prandial test

Concentration of naringenin in plasma (mM) will be measured, in post prandial state 3h after the concomitant consumption of the study drink and challenge meal.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Naringenin catabolites concentration in plasma on 3h post prandial test

Concentration of naringenin microbial catabolites in plasma (mM) will be measured, in post prandial state 3h after the concomitant consumption of the study drink and challenge meal.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Naringenin concentration in plasma on 6h post prandial test

Concentration of naringenin in plasma (mM) will be measure, in post prandial state 6h after the concomitant consumption of the study drink and challenge meal.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Naringenin catabolites concentration in plasma on 6h post prandial test

Concentration of naringenin microbial catabolites in plasma (mM) will be measured, in post prandial state 6h after the concomitant consumption of the study drink and challenge meal.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Flavanone concentration in 24h urine

Concentration of flavanone in urine (nM) will be measured.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Flavanone catabolites concentration in 24h urine

Concentration of flavanone microbial catabolites in urine (nM) will be measured.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Flavanone concentration in plasma on fasted state

Concentration of flavanone in plasma (nM) will be measured, on fasted state.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Flavanone catabolites concentration in plasma on fasted state

Concentration of flavanone microbial catabolites in plasma (nM) will be measured, on fasted state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Flavanone concentration in plasma on 3h post prandial test

Concentration of flavanone in plasma (mM) will be measured, in post prandial state 3h after the concomitant consumption of the study drink and challenge meal.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Flavanone catabolites concentration in plasma on 3h post prandial test

Concentration of flavanone microbial catabolites in plasma (mM) will be measured,in post prandial state 3h after the concomitant consumption of the study drink and challenge meal.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Flavanone concentration in plasma on 6h post prandial test

Concentration of flavanone in urine (nM) will be measured, in post prandial state 6h after the concomitant consumption of the study drink and challenge meal.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Flavanone catabolites concentration in plasma on 6h post prandial test

Concentration of flavanone microbial catabolites in plasma (mM) will be measured, in post prandial state 6h after the concomitant consumption of the study drink and challenge meal.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma nitrites dosage

Determination of nitrite plasma concentration (nM) (a biomarker of endothelial activation), on fasted state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma nitroso-thiols dosage

Determination of nitroso-thiols plasma concentration (nM) (a biomarker of endothelial activation), on fasted state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma Inter-Cellular Adhesion Molecules (ICAM) dosage on fasted state

Determination of ICAM plasma concentration (ng/ml) (a biomarker of endothelial activation), on fasted state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma ICAM dosage on 6h post prandial state

Determination of ICAM plasma concentration (ng/ml) (a biomarker of endothelial activation), on 6h post prandial state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma Vascular-CAM (VCAM) dosage on fasted state

Determination of VCAM plasma concentration (ng/ml) (a biomarker of endothelial activation), on fasted state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma VCAM dosage on 6h post prandial state

Determination of VCAM plasma concentration (ng/ml) (a biomarker of endothelial activation), on 6h post prandial state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma e-selectin dosage on fasted state

Determination of e-selectin plasma concentration (ng/ml) (a biomarker of endothelial activation), on fasted state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma e-selectin dosage on 6h post prandial state

Determination of e-selectin plasma concentration (ng/ml) (a biomarker of endothelial activation), on 6h post prandial state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma Extracellular Vesicles analyses (EVs) on fasted state

EVs (a biomarker of endothelial activation) will be isolated from platelet-poor plasma samples and analyzed, on fasted state

Time frame: Day 42, Day 111, Day 180

EVs analyses on 3h post prandial state

EVs (a biomarker of endothelial activation) will be isolated from platelet-poor plasma samples and analyzed, on post prandial state 3h after the concomitant consumption of the study drink and challenge meal.

Time frame: Day 42, Day 111, Day 180

Plasma oxylipins identification on fasted state

Determination of oxylipins present in plasma (a biomarker of inflammation and oxidative stress) using a method of profiling, on fasted state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma oxylipin concentration on fasted state

Determination of oxylipin plasma concentration (a biomarker of inflammation and oxidative stress), on fasted state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma oxylipins identification on 6h post prandial state

Determination of oxylipins present in plasma (a biomarker of inflammation and oxidative stress) using a method of profiling, on post-prandial state 6h after the concomitant consumption of the study drink and challenge meal.

Time frame: Day 42, Day 111, Day 180

Plasma oxylipin concentration on 6h post prandial state

Determination of oxylipin plasma concentration (a biomarker of inflammation and oxidative stress), on post-prandial state 6h after the concomitant consumption of the study drink and challenge meal.

Time frame: Day 42, Day 111, Day 180

Plasma Interleukin 6 (IL-6) dosage

Determination of IL-6 plasma concentration (pg/ml) (a biomarker of inflammation and oxidative stress), on fasted state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma Tumor Necrosis Factor α (TNFα) dosage

Determination of TNFα plasma concentration (pg/ml) (a biomarker of inflammation and oxidative stress), on fasted state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma high-sensitivity C-reactive protein (hs-CRP) dosage

Determination of hs-CRP plasma concentration (mg/L) (a biomarker of inflammation and oxidative stress), on fasted state

Time frame: Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma glucose dosage on fasted state

Determination of glucose plasma concentration (mM) (a metabolic parameter), on fasted state

Time frame: Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma glucose dosage on 3h post prandial state

Determination of glucose plasma concentration (mM) (a metabolic parameter), on post-prandial state 3h after the concomitant consumption of the study drink and challenge meal.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma glucose dosage on 6h post prandial state

Determination of glucose plasma concentration (mM) (a metabolic parameter), on post-prandial state 6h after the concomitant consumption of the study drink and challenge meal.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

-Plasma Triacylglycerol (TAG) dosage on fasted state

Determination of TAG plasma concentration (g/L) (a metabolic parameter), on fasted state

Time frame: Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma TAG dosage on 3h post prandial state

Determination of TAG plasma concentration (g/L) (a metabolic parameter), on post-prandial state 3h after the concomitant consumption of the study drink and challenge meal, on post-prandial state 3h after the concomitant consumption of the study drink and challenge meal.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma TAG dosage on 6h post prandial state

Determination of TAG plasma concentration (g/L) (a metabolic parameter), on post-prandial state 6h after the concomitant consumption of the study drink and challenge meal.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma uric acid dosage on fasted state

Determination of uric acid plasma concentration (mM) (a metabolic parameter) method, on fasted state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma uric acid on 3h post prandial state

Determination of uric acid plasma concentration (mM) (metabolic parameter), on post-prandial state 3h after the concomitant consumption of the study drink and challenge meal.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma uric acid on 6h post prandial state

Determination of uric acid plasma concentration (mM) (metabolic parameter) will be determined, on post-prandial state 6h after the concomitant consumption of the study drink and challenge meal.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma total cholesterol dosage

Determination of total cholesterol plasma concentration (mM) (a metabolic parameter), on fasted state

Time frame: Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma High Density Lipoprotein cholesterol (HDL-chol) dosage

Determination of HDL-chol plasma concentration (mM) (a metabolic parameter), on fasted state

Time frame: Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma High Density Lipoprotein cholesterol (LDL-chol) calculation

Determination of LDL-chol plasma concentration (mM) (metabolic parameter), on fasted state

Time frame: Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma Total Fatty Acids (FA) dosage

Determination of total FA plasma concentration (mM) (a metabolic parameter), on fasted state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Serum Insulin dosage

Determination of insulin serum concentration (mU/L or pM) (a metabolic parameter), on fasted state

Time frame: Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Weight measure

the body weight (kg) will be recorded with a bathroom scale, on fasted state

Time frame: Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Height measure

the body height (cm) will be measured with a stadiometer.

Time frame: Day -14

Body Mass Index (BMI) calculation

the BMI (kg/m²) will be calculated, on fasted state

Time frame: Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Waist circumference measure

the waist circumference (cm) will be recorded with a measuring tape, on fasted state

Time frame: Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Fat mass ratio determination

The percentage of fat mass (percent) (body composition) will be determined on each participant using a multi-frequency bioelectrical Impedance Analyzer, on fasted state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Lean mass ratio determination

The percentage of lean mass (percent) (body composition) will be determined on each participant using a multi-frequency bioelectrical Impedance Analyzer, on fasted state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Water mass ratio determination

The percentage of water (percent) (body composition) will be determined using a multi-frequency bioelectrical Impedance Analyzer, on fasted state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

RNA profiling on fasted state

Nutrigenomic analysis will be performed from total Ribo Nucleic Acid (RNA) isolated blood collected in PAXgene Blood RNA Tube. The isolated RNA will be used to perform microarray analyses that allow identification of expression of all genes of the genome, on fasted state

Time frame: Day 42, Day 111, Day 180

RNA profiling on 6h post prandial state

Analysis will be performed from total RNA isolated blood collected in PAXgene Blood RNA Tube. The isolated RNA will be used to perform microarray analyses that allow identification of expression of all genes of the genome, on post-prandial state 6h after the concomitant consumption of the study drink and challenge meal.

Time frame: Day 42, Day 111, Day 180

Gut microbiota profiling

Identification of the microbiota composition of feces samples (collected by subjects) by performing a genetic sequencing analysis of bacterial DNA.

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma carotenoids dosage

Carotenoids will be quantitated from plasma (nM), on fasted state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Plasma vitamine C dosage

Vitamin C status will be quantified in deproteinized plasma (mg/L), on fasted state

Time frame: Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Treatment compliance

Treatment compliance (percent) will be determined using counting of empty orange drinks brought back by volunteers after the consumption periods

Time frame: Day 42, Day 111, Day 180

Polyphenol intake

Polyphenol intake (ml/day) in basal and during treatment consumption periods will be determined by a dietician using food report completed by volunteers.

Time frame: Day 1, Day 42, Day 111, Day 180

Low-polyphenol diet compliance

Respect (y/n) of a low-polyphenol diet in basal (between Visit 1 - Visit 2) and during treatment consumption periods (between Visit 2 - Visit 3, Visit 4 - Visit 5, Visit 6 - Visit 7) will be determined by a dietician using 3 days food reports completed by volunteers.

Time frame: Day 1, Day 42, Day 111, Day 180

Calorie intake

Calorie (kcal/day) intake in basal and during treatment consumption periods will be determined by a dietician using food report completed by volunteers.

Time frame: Day 1, Day 42, Day 111, Day 180

Protein intake

Protein (g/day) intake in basal and during treatment consumption periods will be determined by a dietician using food report completed by volunteers.

Time frame: Day 1, Day 42, Day 111, Day 180

Lipid intake

Lipid intake (g/day) in basal and during treatment consumption periods will be determined by a dietician using food report completed by volunteers.

Time frame: Day 1, Day 42, Day 111, Day 180

Carbohydrate intake

Carbohydrate intake (g/day) in basal and during treatment consumption periods will be determined by a dietician using food report completed by volunteers.

Time frame: Day 1, Day 42, Day 111, Day 180

Diet division of protein/lipid/carbohydrate intakes

The overall distribution of the protein/lipid/carbohydrate food intakes (%) will be determined by a dietician using food report completed by volunteers.

Time frame: Day 1, Day 42, Day 111, Day 180

Diet stability

Diet stability (y/n) in terms of polyphenols, calories, proteins, carbohydrates and lipids intakes during the whole study will be determined by a dietician using the 4 food reports completed by volunteers.

Time frame: Day 180

Biobank for food metabolome

Urine samples will be stored for further assessment of food metabolome to potentially identify new bioactive compounds present in the juice that could contribute to the biological response after orange juice/HESP intake.

Time frame: Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

Orange Juice, Hesperidin and Their Role in Vascular Health Benefit

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes