MedPath

Orange Juice, Hesperidin and Their Role in Vascular Health Benefit

Not Applicable
Completed
Conditions
Vascular Compliance
Predisposition to Cardiovascular Disease
Metabolic Syndrome
Interventions
Behavioral: Beverage consumption
Registration Number
NCT04731987
Lead Sponsor
University Hospital, Clermont-Ferrand
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

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
50
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Orange juice (A)Beverage consumption42 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
Control beverage (B)Beverage consumption42 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
Control beverage supplemented with hesperidin formulation (B+HESP)Beverage consumption42 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
Primary Outcome Measures
NameTimeMethod
Brachial artery Flow Mediated Dilation (FMD)Day 180

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

Secondary Outcome Measures
NameTimeMethod
Basal Heart RateDay -14

Heart rate measure (beat/min) with monitor.

D-3 visit diastolic BPDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

D-3 visit Heart RateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

FMD post prandial endothelial response 6h after a challenge mealDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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.

Rest flow by Flowmetry Laser Doppler (FLD) in fasted stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Hyperaemia area / occlusion area ratio by FLD in fasted stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

D-3 visit systolic Blood Pressure (BP)Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

FMD post prandial endothelial response 3h after a challenge mealDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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.

Arterial compliance assessmentDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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.

SexDay -14

Participant sex (man/women) will be requested.

AgeDay 34

Participant age (years) will be requested.

Occlusion area by FLD in fasted stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Hyperaemia area by FLD in fasted stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Occlusion area by FLD 3h after a challenge mealDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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), 3h after intake of the full daily dose of study products concomitantly with challenge meal

Hyperaemia area by FLD 3h after a challenge mealDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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), 3h after intake of the full daily dose of study products concomitantly with challenge meal

Hesperetin catabolites concentration in plasma on fasted stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Basal Systolic Blood PressureDay -14

Blood pressure measure (mm Hg) with monitor.

Hyperaemia half time by FLD in fasted stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Rest flow by FLD 3h after a challenge mealDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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,3h after intake of the full daily dose of study products concomitantly with challenge meal

Hyperaemia area / occlusion area ratio by FLD 6h after a challenge mealDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Hyperaemia half time by FLD 6h after a challenge mealDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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), 6h after intake of the full daily dose of study products concomitantly with challenge meal

Hesperetin concentration in 24h urineDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Hesperetin concentration in plasma on fasted stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Naringenin catabolites concentration in 24h urineDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Naringenin concentration in plasma on fasted stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Maximal flow by FLD in fasted stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Hyperaemia half time by FLD 3h after a challenge mealDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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), 3h after intake of the full daily dose of study products concomitantly with challenge meal

Hyperaemia area / occlusion area ratio by FLD 3h after a challenge mealDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Maximal flow by FLD 3h after a challenge mealDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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), 3h after intake of the full daily dose of study products concomitantly with challenge meal

Rest flow by FLD 6h after a challenge mealDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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, 6h after intake of the full daily dose of study products concomitantly with challenge meal

Hyperaemia area by FLD 6h after a challenge mealDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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), 6h after intake of the full daily dose of study products concomitantly with challenge meal

Naringenin catabolites concentration in plasma on 3h post prandial testDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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.

Naringenin concentration in plasma on 6h post prandial testDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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.

Flavanone catabolites concentration in plasma on 6h post prandial testDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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.

Plasma nitrites dosageDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Plasma Vascular-CAM (VCAM) dosage on fasted stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Occlusion area by FLD 6h after a challenge mealDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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), 6h after intake of the full daily dose of study products concomitantly with challenge meal

Maximal flow by FLD 6h after a challenge mealDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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), 6h after intake of the full daily dose of study products concomitantly with challenge meal

Hesperetin concentration in plasma on 3h post prandial testDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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.

Hesperetin catabolites concentration in plasma on 3h post prandial testDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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.

Hesperetin concentration in plasma on 6h post prandial testDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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.

Hesperetin catabolites concentration in plasma on 6h post prandial testDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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.

Naringenin concentration in 24h urineDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Naringenin concentration in plasma on 3h post prandial testDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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.

Naringenin catabolites concentration in plasma on fasted stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Flavanone catabolites concentration in 24h urineDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Naringenin catabolites concentration in plasma on 6h post prandial testDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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.

Flavanone concentration in 24h urineDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Flavanone catabolites concentration in plasma on fasted stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Flavanone concentration in plasma on 3h post prandial testDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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.

Plasma Inter-Cellular Adhesion Molecules (ICAM) dosage on fasted stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Plasma ICAM dosage on 6h post prandial stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Flavanone catabolites concentration in plasma on 3h post prandial testDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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.

Plasma Extracellular Vesicles analyses (EVs) on fasted stateDay 42, Day 111, Day 180

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

Flavanone concentration in plasma on fasted stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Plasma nitroso-thiols dosageDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Flavanone concentration in plasma on 6h post prandial testDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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.

Plasma e-selectin dosage on fasted stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Plasma e-selectin dosage on 6h post prandial stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Plasma VCAM dosage on 6h post prandial stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

EVs analyses on 3h post prandial stateDay 42, Day 111, Day 180

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.

Plasma oxylipins identification on fasted stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Plasma oxylipin concentration on fasted stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Plasma oxylipin concentration on 6h post prandial stateDay 42, Day 111, Day 180

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.

Plasma Tumor Necrosis Factor α (TNFα) dosageDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Plasma high-sensitivity C-reactive protein (hs-CRP) dosageDay -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Plasma glucose dosage on 3h post prandial stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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.

Plasma glucose dosage on 6h post prandial stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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.

Plasma TAG dosage on 3h post prandial stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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.

Plasma TAG dosage on 6h post prandial stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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.

Plasma uric acid dosage on fasted stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Plasma uric acid on 3h post prandial stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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.

Plasma Total Fatty Acids (FA) dosageDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Serum Insulin dosageDay -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Plasma oxylipins identification on 6h post prandial stateDay 42, Day 111, Day 180

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.

Plasma Interleukin 6 (IL-6) dosageDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Plasma glucose dosage on fasted stateDay -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

-Plasma Triacylglycerol (TAG) dosage on fasted stateDay -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Plasma uric acid on 6h post prandial stateDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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.

Height measureDay -14

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

RNA profiling on fasted stateDay 42, Day 111, Day 180

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

RNA profiling on 6h post prandial stateDay 42, Day 111, Day 180

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.

Gut microbiota profilingDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Plasma carotenoids dosageDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Plasma total cholesterol dosageDay -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Plasma High Density Lipoprotein cholesterol (HDL-chol) dosageDay -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Plasma High Density Lipoprotein cholesterol (LDL-chol) calculationDay -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Weight measureDay -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Waist circumference measureDay -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Lean mass ratio determinationDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Body Mass Index (BMI) calculationDay -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Fat mass ratio determinationDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Water mass ratio determinationDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Plasma vitamine C dosageDay 1, Day 42, Day 70, Day 111, Day 139, Day 180

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

Biobank for food metabolomeDay -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180

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.

Treatment complianceDay 42, Day 111, Day 180

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

Polyphenol intakeDay 1, Day 42, Day 111, Day 180

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

Carbohydrate intakeDay 1, Day 42, Day 111, Day 180

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

Diet division of protein/lipid/carbohydrate intakesDay 1, Day 42, Day 111, Day 180

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

Diet stabilityDay 180

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.

Calorie intakeDay 1, Day 42, Day 111, Day 180

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

Protein intakeDay 1, Day 42, Day 111, Day 180

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

Low-polyphenol diet complianceDay 1, Day 42, Day 111, Day 180

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.

Lipid intakeDay 1, Day 42, Day 111, Day 180

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

Trial Locations

Locations (1)

University Hospital, Clermont Ferrand

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Clermont-Ferrand, Aura, France

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