# Acute Effects of Polyphenol-Rich Fruit Juice on Exercise Capacity and Vessels Dilatation in Healthy Humans: A Randomized, Controlled, Crossover Study

Olivier Rouyer, Anne-Laure Charles, Cyril Auger, Samy Talha, Emmanuel Andres, Anne Charloux, Valerie Schini-Kerth, Bernard Geny

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Olivier Rouyer, Anne-Laure Charles, Cyril Auger, Samy Talha, Emmanuel Andres, et al.. Acute Effects of Polyphenol-Rich Fruit Juice on Exercise Capacity and Vessels Dilatation in Healthy Humans: A Randomized, Controlled, Crossover Study. Applied Sciences, 2025, 15 (21), pp.11553. 10.3390/app152111553. hal-05449964

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Article

# Acute Effects of Polyphenol-Rich Fruit Juice on Exercise Capacity and Vessels Dilatation in Healthy Humans: A Randomized, Controlled, Crossover Study

Olivier Rouyer <fnref n="1" />,<fnref n="2" /> ID, Anne-Laure Charles <fnref n="1" /> ID, Cyril Auger <fnref n="3" /> ID, Samy Talha <fnref n="1" />,<fnref n="2" /> ID, Emmanuel Andres <fnref n="1" />,<fnref n="4" /> ID, Anne Charloux <fnref n="1" />,<fnref n="2" />, Valerie Schini-Kerth <fnref n="3" /> ID and Bernard Geny <fnref n="1" />,<fnref n="2" />,* ID

<figure><img src="image_2.png" /></figure>

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updates

Academic Editors: Alessandra Biancolillo and Chiara Cavaliere

Received: 20 August 2025

Revised: 26 September 2025

Accepted: 22 October 2025

Published: 29 October 2025

**Citation:** Rouyer, O.; Charles, A.-L.; Auger, C.; Talha, S.; Andres, E.; Charloux, A.; Schini-Kerth, V.; Geny, B. Acute Effects of Polyphenol-Rich Fruit Juice on Exercise Capacity and Vessels Dilatation in Healthy Humans: A Randomized, Controlled, Crossover Study. *Appl. Sci.* **2025**, *15*, 11553. https://doi.org/10.3390/app152111553

**Copyright:** © 2025 by the authors. License MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

## Abstract

This study examined the acute effects of polyphenol (PP)-rich fruit juice supplementation on the exercise capacity of healthy humans. Thirty-five healthy, sedentary volunteers participated in this randomized, controlled, crossover study. They performed a 6 min walk test two hours after consuming 200 mL of a PP-rich fruit juice (fruit juice) or a PP-poor control juice (apple), separated by a one-week washout. In addition to monitoring the heart rate during exercise, we determined the reactive hyperemia index (RHI), an indicator of vascular dilatation that contributes to exercise capacity. The distance walked during the 6 min test tended to be greater after the consumption of the PP-rich juice, compared to the PP-poor juice (588 ± 15 vs. 561 ± 14 m, respectively). The increase in heart rate was similar in both situations. The RHI increases were similar after both juices' intake at 1 h, but after 2 h, the RHI increase was significant only after the PP-rich juice intake (from 6.78 ± 0.46 to 8.47 ± 0.47, *p* < 0.001). In conclusion, acute consumption of PP-rich juice increases vessel dilatation and tends to improve exercise capacity. These data support further studies to determine whether greater consumption of PP-rich fruit juices could improve exercise capacity in healthy subjects.

**Keywords:** exercise; 6 min walking test; polyphenols; reactive hyperemia index (RHI); vascular dilatation

## 1. Introduction

Exercise capacity relies on both central (cardio-respiratory) and peripheral (vessels, skeletal muscles and blood composition) parameters that might be limited by numerous situations and diseases. In patients, for instance, inappropriate vessels dilatation may reduce muscle perfusion and therefore favor exercise-induced ischemia. This results in a limited walking distance, with the patients needing to rest when leg pain occurs [1]. This is confirmed by experimental and clinical studies which support that reduced exercise

<footnote n="1">¹ Biomedicine Research Center of Strasbourg (CRBS), UR 3072, Mitochondria, Oxidative Stress and Muscle Plasticity, Faculty of Medicine, University of Strasbourg, 67081 Strasbourg, France; orouyer@chu-clermontferrand.fr (O.R.); anne.laure.charles@unistra.fr (A.-L.C.); samy.talha@chru-strasbourg.fr (S.T.); emmanuel.andres@chru-strasbourg.fr (E.A.); anne.charloux@chru-strasbourg.fr (A.C.)</footnote>

<footnote n="2">² Department of Physiology and Functional Explorations, University Hospital of Strasbourg, 67000 Strasbourg, France</footnote>

<footnote n="3">³ Biomedicine Research Center of Strasbourg, UR 3074 Translational Cardiovascular Medicine, Faculty of Medicine, University of Strasbourg, 67081 Strasbourg, France; cyril.auger@unistra.fr (C.A.); valerie.schini-kerth@unistra.fr (V.S.-K.)</footnote>

<footnote n="4">⁴ Department of Internal Medicine, University Hospital of Strasbourg, 67091 Strasbourg, France</footnote>

<footnote>* Correspondence: bernard.geny@chru-strasbourg.fr</footnote>
capacity can be associated with endothelial dysfunction and reduced nitric oxide (NO) production [2–6].

Interestingly, diet adaptation and, particularly, polyphenols (PP) consumption, can potentially increase exercise capacity by improving vascular dilatation and by enhancing muscle metabolism [7–10]. Accordingly, chronic supplementation with *Euterpe oleracea* Mart seed, rich in PP, was demonstrated to increase the aerobic physical performance of rats by improving the vascular function [11]. Although under debate, some polyphenols may also be beneficial in the process of injury, inflammation, and muscle regeneration during and after exercise [12].

In healthy sedentary young humans, data spars. However, interestingly, young athletes present with enhanced microvascular function as compared to age-matched untrained healthy subjects, supporting that even normal flow-mediated dilatation could be improved [10,13–16]. In this way, the ingestion of several beverages demonstrated vascular protective effects. In healthy volunteers, ingestion of a drink rich in cocoa improved the endothelial function 1 to 4 h later and increased plasma NO and polyphenols. Similar beneficial effects were obtained with other products rich in PP [17–23]. In terms of the kinetic, Hashimoto et al. [24] demonstrated that a single ingestion of red wine improved flow-mediated vasodilatation in healthy subjects as early as after 30 min, with the vasodilation persisting for 120 min. Agewall et al. [25] also reported improved vasodilation 30 and 60 min after single consumption of de-alcoholic red wine (250 mL). Accordingly, and recently, Tucci et al. reported that blueberries improved peripheral vascular function in older subjects, potentially in relation to increased anthocyanins levels [26].

Our hypothesis is that fruit juice rich in PP might enhance vessel dilatation and thereby exercise capacity. However, there is little data on the effects of commonly consumed fruit juices, and the concomitant effects of fruit juices on endothelial function and exercise capacity in healthy volunteers is largely unknown.

The aim of the study was to address these specific knowledge gaps (effects of commonly consumed juices and their relationship with exercise capacity) and, therefore, to investigate, in a randomized, controlled, crossover study, whether acute PP-rich fruit juice intake might enhance the exercise capacity in healthy humans, potentially through a beneficial effect on their vascular function. We determined the exercise capacity in 35 healthy volunteers after PP-rich or -poor juice consumption, together with their reactive hyperemia index (RHI), which is a marker of vessels dilatation.

## 2. Methods

### 2.1. *Population*

Thirty-five healthy volunteers participated in the study after signing an informed consent form. The public call for participation in the study was carried out through the distribution of flyers in the university elevators of Strasbourg and by a written proposal on our hospital's intranet. After approval by the Institutional Review Board (Person Committee Protection EST IV, protocol code 080103), the study was conducted according to the guidelines of the Declaration of Helsinki.

All volunteers followed the inclusion and exclusion criteria presented in Table 1.
<table><caption>**Table 1.** Inclusion and exclusion criteria.</caption><thead><tr><th></th><th></th></tr></thead><tbody><tr><td><strong>Inclusion Criteria</strong></td><td></td></tr><tr><td>- Men and women between 30 and 60 years of age</td><td></td></tr><tr><td>- Sedentary according to the Baecke questionnaire</td><td></td></tr><tr><td>- Non-smoker or smoker of less than 5 cigarettes per day</td><td></td></tr><tr><td>- Subject not taking medication or whose medication can be safely stopped for 24 h</td><td></td></tr><tr><td>- Subject affiliated with a social security scheme</td><td></td></tr><tr><td>- Subject having signed informed consent</td><td></td></tr><tr><td>- Subject having been informed of the results of the prior medical examination</td><td></td></tr><tr><td><strong>Exclusion Criteria</strong></td><td></td></tr><tr><td>- Diabetic subjects</td><td></td></tr><tr><td>- Subject taking nitrates</td><td></td></tr><tr><td>- Inability to provide informed information to the subject (subject in an emergency situation, difficult understanding by the subject, etc.)</td><td></td></tr><tr><td>- Subject under legal protection</td><td></td></tr><tr><td>- Subject under guardianship or curatorship</td><td></td></tr><tr><td>- Known pregnancy (interview)</td><td></td></tr><tr><td>- Breastfeeding</td><td></td></tr></tbody></table>

## 2.2. *Experimental Design*

During this randomized, controlled, crossover study, each healthy volunteer was their own control, and we compared the acute effect of a PP-rich fruit juice (fruit juice) with a control product poor in PP (apple). The washout period lasted one week, which allowed enough time for the effects of the first juice to dissipate before the second juice intake.

Participants were selected based on their ability and commitment to follow study guidelines, and their compliance with dietary restrictions was assessed by their oral confirmation of adherence to the criteria.

Each participant received three visits. The first was for informational purposes. Informed consent and randomization took place during the second visit. The randomization to each study arm was performed independently, in blocks of five. Neither the participants nor the team implementing the protocol were aware of the juices being tested, and, more specifically, their composition.

The explorations detailed below were carried out according to the same protocol during the second and third visits. Subjects abstained from tobacco, chocolate, caffeine, and alcohol for at least 12 h before the investigation, which began at 8 a.m.

We determined vessel dilatation using digital arterial tonometry, as inferred from the reactive hyperemia index (RHI), at baseline and at 1 and 2 h after juice intake (200 mL of fruit juice rich or poor in polyphenols). The baseline corresponds to the first RHI determination, before any juice intake, and serves as a reference. Thereafter, the effects of juices were compared to baseline values. Indeed, in healthy subjects, like in diseased patients, the endothelial function can be assessed non-invasively using reactive hyperemia index (RHI) analysis, proposed to discern the ability of vessels to dilate in response to acute ischemia [26,27].

Then, the healthy volunteers performed the exercise, completing the 6 min walking test as described below in detail.

## 2.3. *Control (Apple) and Fruit Juices Compositions*

The control juice was a PP-poor apple juice (PP < 0.4 g/L), selected for its specificity to be light in polyphenols. Rather than water, we chose to use apple juice because the subjects,
given its potential beneficial effects, often consume it. This pragmatic choice means that the control is not a bioactively neutral beverage.

The PP-rich fruit juice (PP > 3 g/L) was enriched in anthocyanins and consisted of juices or purées of the following fruits: acerola (3.5%), apple (10%), grape (63%), aronia (3.5%), blueberry (10%), and strawberry (10%). The fruit juice was selected by a panel of 80 consumers for its acceptability in terms of flavor. Its characteristics have been previously reported [28]. The volume ingested was 200 mL. Such a dose might modify vessel function, and therefore exercise capacity, and is commonly ingested during or around exercise periods, depending on the duration and intensity of the training or competition performed.

The juices' compositions are shown in Tables 2 and 3. The total phenolic content of the fruit juice was determined in triplicate and expressed as mg of gallic acid equivalents (GAE) using the Folin–Ciocalteu method, and the flavanols content was measured using HPLC with the direct injection onto HyperClone C18 column with post-column derivatization (Table 2).

<table><caption>**Table 2.** Total phenolic and flavanols contents in the fruit juice.</caption><thead><tr><th>Fruits and Berries</th><th>Total Phenolic Content (g/L GAE)</th></tr></thead><tbody><tr><td>Acerola</td><td>3.12</td></tr><tr><td>Apple</td><td>1.70</td></tr><tr><td>Aronia</td><td>7.15</td></tr><tr><td>Blueberry</td><td>5.94</td></tr><tr><td>Grape</td><td>1.99</td></tr><tr><td>Strawberry</td><td>2.03</td></tr></tbody><thead><tr><th colspan="2">Flavanols Content (mg/L)</th></tr></thead><tbody><tr><td>Flavan-3-ols</td><td>13.1</td></tr><tr><td>Procyanidin B1</td><td>11.8</td></tr><tr><td>Procyanidin B2</td><td>15.3</td></tr><tr><td>Epicatechin</td><td>12.8</td></tr><tr><td>Gallocatechin-3-O-gallate</td><td>0.8</td></tr></tbody></table>

<table><caption>**Table 3.** Concentration of fat, sugar, protein, salt, and vitamin C in apple and fruit juices.</caption><thead><tr><th></th><th>Apple Juice (g/L)</th><th>Fruit Juice (g/L)</th></tr></thead><tbody><tr><td>Fat</td><td>0</td><td>0</td></tr><tr><td>Sugar</td><td>98</td><td>122.4</td></tr><tr><td>Protein</td><td>0</td><td>0</td></tr><tr><td>Salt</td><td>0</td><td>0</td></tr><tr><td>Vitamin C</td><td>0</td><td>0.40</td></tr></tbody></table>

Table 3 allows comparison between both juices of their main other components. As shown, there was more sugar and more vitamin C in the fruit juice compared to the apple juice. Both juices were free of fat, protein, and salt.

## 2.4. Parameters Determined

### 2.4.1. Six-Minute Walking Test

The six-minutes walking test is a validated submaximal exercise test, easy to perform and commonly used by our team in our clinical department of Physiology and Functional Exploration. In detail, the healthy volunteers walked as fast as possible (without running), on flat ground for a period of 6 min. A nurse or doctor quoted the distance traveled and recorded the heart rate throughout the test.

This test is the most frequently used submaximal exercise test and reflects better daily life activities than maximal exercise tests. The distance attained can predict functional
changes resulting from disease progression or therapeutic intervention and allows the
assessment of functional exercise performance across various populations [29,30].

2.4.2. Heart Rate and Systemic Blood Pressure

Heart rate (HR) in beats per minute (b/min), and systolic (PAS) and diastolic (PAD) systemic arterial pressures in millimeters of mercury (mmHg) were determined using an automatic cuff Dynamap®. Body weight was measured using a scale to the nearest 0.1 kg (Seca 878 Dr, Seca, Hamburg, Germany) and height was measured to the nearest 1 cm.

2.4.3. Reactive Hyperemia Index

The Reactive Hyperemia Index (RHI) is an index of vascular reactivity determined at the fingertip level using Endo-PAT2000 (Itamar Medical Ltd., Caesarea, Israel), an operator independent and non-invasive devices based on plethysmographic probes. It allows for determination of the amplitude of reactive hyperemia by measuring the changes in the pulsations in finger pressure (ratio of post-ischemia to baseline pulse amplitude in the hyperemic finger, divided by the ratio in the contralateral finger) that occur for some minutes following the induction of a reactive hyperemic response. This flow-mediated dilatation response is induced by occluding for five minutes and then releasing the brachial artery with a cuff inflated between 200 and 220 mmHg. More precisely, as previously described, one peripheral arterial tonometry (PAT) finger probe was placed on the index finger of the hand undergoing hyperemia testing. The second PAT probe was placed on the contralateral index finger. To decrease the confounding variables, including the potential systemic effects of unilateral arm ischemia, this ratio was normalized to the concurrent signal from the contralateral, nonischemic hand. PAT measurements were analyzed with a computerized, automated algorithm [26,31–33].

2.5. Statistical Analysis

All data were expressed as mean ± standard error of the mean (SEM). The statistical analyses were performed using Prism software (GraphPad Prism 8.4.3, GraphPad Software, San Diego, CA, USA). After checking normality using the Shapiro-Wilk test, it was found that the overall population did not follow a normal distribution, and the tests used were also non-parametric tests. The comparison of the two-paired groups was performed using the Wilcoxon test. One-way ANOVA (Friedman test, for paired values) was performed with the Dunnett post hoc test to analyze the kinetic, and a Kruskal-Wallis test was used to compare the curves between groups. A *p*-value < 0.05 was considered statistically significant. The area under the curve (AUC) was calculated in GraphPad Prism. The baseline was the minimum value for each group.

The calculation for the number of volunteers to include was based on the results of
a similar study [34]. In this study, the peripheral arterial tonometry index of 10 healthy
subjects was measured before and after taking a drink enriched with flavanols. Starting
from a basal value of 1.9 ± 0.1, this index shows a significant increase of 68.9 ± 10.3%
after taking the drink enriched with polyphenols. Expecting an increase in the same
magnitude and retaining alpha and beta risks of 5%, this meant we needed to include at
least 15 subjects per group.

3. Results

Thirty-five subjects participated in the study. No participants reported significant side effects. During the intake of polyphenol-poor juice, 33 completed the entire procedure. One subject did not undergo the analysis at 1 h after the juice intake, and another did not undergo the analysis at 2 h after the juice intake. Regarding the intake of polyphenol-rich juice, 34 completed the entire procedure. The corresponding flowchart is shown below (Figure 1).
<figure><img src="image_3.png" /><figcaption>**Figure 1.** Flowchart of the study.</figcaption></figure>

### 3.1. Clinical Characteristics of the Subjects

The clinical characteristics of the healthy volunteers are presented in Table 4. Twenty-four women and eleven men were included in the study. They were healthy and sedentary, as indicated by their normal BMI and cardiovascular parameters and by a Baecke index of 7.45 ± 0.21.

<table><caption>**Table 4.** Baseline clinical characteristics of the subjects. Results are expressed as mean [95% confidence intervals]. BMI: body mass index. BP: blood pressure. Bpm: beats per minute.</caption><thead><tr><th>n</th><th>Total<br>35</th><th>Women<br>24</th><th>Men<br>11</th></tr></thead><tbody><tr><td>Age (years)</td><td>48.9 ± 1.50</td><td>49.1 [45.36; 52.83]</td><td>48.48 [42.23; 54.74]</td></tr><tr><td>BMI (kg/m²)</td><td>25.96 ± 0.94</td><td>25.83 [23.39; 28.26]</td><td>26.25 [22.69; 29.82]</td></tr><tr><td>Systolic BP (mm Hg)</td><td>129.1 ± 3.57</td><td>121.2 [113.2; 129.1]</td><td>146.3 [136.3; 156.3]</td></tr><tr><td>Diastolic BP (mm Hg)</td><td>81.03 ± 3.84</td><td>78.08 [67.01; 89.16]</td><td>87.45 [80.41; 94.50]</td></tr><tr><td>Heart rate (bpm)</td><td>68.34 ± 1.66</td><td>69.83 [66.26; 73.40]</td><td>65.09 [56.96; 73.22]</td></tr><tr><td>Baecke index</td><td>7.45 ± 0.21</td><td>7.27 [6.68; 7.86]</td><td>7.85 [7.46; 8.24]</td></tr></tbody></table>

### 3.2. Effects of Both Juices on Subject's Exercise Capacity

To evaluate their exercise capacity, all healthy volunteers performed a 6 min walking test, which is well known to correspond to individuals' everyday fitness.

As shown in Figure 2a, whatever the ingestion of fruit juice, rich or poor in PP, the walking distance (561 ± 13.8 vs. 588 ± 15.4 m) remained in a normal range. However, a trend toward a greater walking distance was observed after the PP-rich juice intake (*p* = 0.08).
a

<figure><img src="image_4.png" /></figure>

b

<figure><img src="image_5.png" /><figcaption>**Figure 2.** Effect of juices on exercise capacity. Distance (a) and HR (b) measured during exercise. Values are means ± SEM. n = 35. Bpm: Beats per minute.</figcaption></figure>

To go into further detail, we assessed cardiovascular work by precisely determining the heart rate response during the walking test (Figure 2b). As expected, the exercise induced a significant (*p* < 0.0001) increase in heart rate, which was similar after the PP-rich and -poor juices.

3.3. Effects of Juices Intake on Reactive Hyperemia-Index (RHI)

The RHI was measured to allow precise kinetic analysis. Since changes between
groups might otherwise have been missed, we also determined the area under the curve
before, and 1 and 2 h after the juices intake.
### 3.3.1. RHI Kinetic After Control Juice Intake, with a Low Polyphenol Content (Apple Juice)

Before taking the juice, as expected, the baseline RHI showed a significant increase from 0.94 ± 0.08 to a maximal value of 1.84 ± 0.16 at 1 min 30 s after artery occlusion release, *p* < 0.0001 (Figure 3a). To assess a specific effect of the juice, we also determined the RHI kinetic 1 and 2 h after the juice intake. One hour after the apple juice intake, the RHI increased significantly from 1.22 ± 0.09 to a maximal value of 2.43 ± 0.17 at 1 min 30 s, *p* < 0.0001. Two hours after the apple juice intake, the RHI increased significantly from 1.14 ± 0.07 to a maximal value of 2.26 ± 0.15 at 1 min 30 s, *p* < 0.0001.

a

<figure><img src="image_6.png" /></figure>

b

<figure><img src="image_7.png" /></figure>

**Figure 3.** Kinetic (a) and area under the curve (AUC) (b) of reactive hyperemia index (RHI) before and after intake of apple juice, poor in polyphenols. Values are means ± SEM. n = 35. RHI kinetic: \* *p* < 0.05, \*\* *p* < 0.01, \*\*\* \*p* < 0.0001 vs. baseline. Comparison between groups: \$ between before juice and after 1 h. \$ \*p* < 0.05, \$\$ \*p* < 0.01. Comparison between groups: \£ between before juice and after 2 h. \£ \*p* < 0.05. Area under the curve (AUC): before juice intake (before), 1 h and 2 h after juice intake (1H, 2H). \* \*p* < 0.05 vs. before.

To analyze further the apple juice effect on RHI, we compared the area under the curve (AUC) in the following three situations: before, and at 1 and at 2 h after taking the juice. After the apple juice intake, the RHI AUC increased significantly at 1 h (from 2.70 ± 0.75 to 3.20 ± 0.78, *p* < 0.05). The increase was no longer significant at 2 h after the juice intake (3.01 ± 0.76) (Figure 3b).
3.3.2. RHI Kinetic After Polyphenol Rich Juice Intake (Fruit Juice)

Before the fruit juice intake, the baseline RHI increased significantly from 0.89 ± 0.06 to a maximal value of 1.67 ± 0.13 at 1 min 30 s after the transient ischemia, *p* < 0.0001 (Figure 4a). One hour after the fruit juice intake, the RHI increased significantly from 1.12 ± 0.05 to a maximal value of 2.23 ± 0.13, at 1 min 30 s, *p* < 0.0001. Two hours after the fruit juice intake, the RHI increased significantly from 1.15 ± 0.06 to a maximal value of 2.39 ± 0.14 at 1 min 30 s, *p* < 0.0001.

<figure><img src="image_8.png" /></figure>

<figure><img src="image_9.png" /></figure>

**Figure 4.** Kinetic (a) and area under the curve (AUC) (b) of reactive hyperemia index (RHI) before and after intake of fruit juice, rich in polyphenols. Values are means ± SEM. n = 35. RHI kinetic: * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001 vs. baseline. Comparison between groups: $ between before juice and after 1 h. $ p < 0.05, $$ p < 0.01, $$$ p < 0.001. Comparison between groups: £ between before juice and after 2 h. ££ p < 0.01, £££ p < 0.001, ££££ p < 0.0001. (b) Area under the curve (AUC): before juice intake (before), 1 h and 2 h after juice intake (1H, 2H). **** p < 0.0001 vs. before.

Concerning the area under the curve, after 1 h of juice intake, the AUC increased significantly from 2.47 ± 0.11 to 3.34 ± 0.15, *p* < 0.0001. Interestingly, after 2 h, the increase was still significant as compared to the baseline (3.37 ± 0.14, *p* < 0.0001) (Figure 4b).
To go further, we investigated whether gender might modulate the RHI responses to the intake of the juices (Figure 5). Interestingly, gender had no effect on RHI kinetics before juice intake, but women presented with a greater RHI than men 1 h after the PP-poor juice intake. At 2 h, the difference between genders was not significant. A similar pattern was observed considering the PP-rich juice intake.

<figure><img src="image_10.png" /><figcaption>**Figure 5.** Gender specific responses of reactive hyperemia index (RHI) before and after intake of fruit juice rich in polyphenols. Area under the curve (AUC) of reactive hyperemia index (RHI) before and after intake of apple juice or fruit juice. (a): after intake of apple juice and (b): after intake of fruit juice. Values are means ± SEM. n = 11 men, and n = 24 women. \* *p* < 0.05, \*\* *p* < 0.01, \*\*\* *p* < 0.001, \*\*\*\* *p* < 0.0001 vs. baseline.</figcaption></figure>

**4. Discussion**

This study aimed to determine, using a randomized, controlled, crossover design, whether acute PP-rich fruit juice intake might enhance exercise capacity through increased
vascular reactive hyperemia. The main results are that the distance walked by healthy humans tended to be greater after PP-rich juice consumption, together with enhanced vessel dilatation, as compared to after PP-poor juice intake. Thus, PP-rich juice intake can acutely improve the reactive hyperemia index and our data support that improved RHI might be associated with improved exercise capacity in healthy humans.

## 4.1. *Effect of Increased Reactive Hyperemia on Exercise Capacity*

In addition to cardiorespiratory functions, exercise capacity depends on peripheral factors, such as muscles and vessels, including vascular endothelial function [5,6,10,13–16,35]. Indeed, during exercise, vascular dilatation allows for an increase in blood supply in activated muscles, and, therefore, an increase in exercise capacity.

During this study, healthy volunteers performed a 6 min walking test, well corresponding to daily activities. The distance covered, around 580 m during these 6 min, confirms that the volunteers were healthy [36,37]. Interestingly, the intake of the PP-rich juice tended to increase the distance walked. However, such increase was not statistically significant. To approach exercise qualitatively, we determined whether the heart rate change during exercise was different after taking fruit juice rich or poor in polyphenols. As expected, the heart rate increased significantly during exercise. Such an increase was nevertheless the same in both groups.

Thus, the fruit juice-induced RHI enhancement only tended to increase healthy volunteer's submaximal exercise capacity. This is consistent with a previous study showing that acute epicatechin supplementation did not increase exercise performance in healthy humans [38]. Taken together, these results suggest, nevertheless, that the beneficial effect on RHI might have been too small to significantly improve exercise capacity in healthy people with quite well adapted vascular responses to both resting and exercise situations.

## 4.2. *PP-Rich-Fruit-Juice-Induced Enhancement in Reactive Hyperemia Index Lasted Longer*

In this study, ischemia induced reactive hyperemia with a significant increase in RHI, peaking 1 min 30 s after cuff release and returning toward baseline value at the fifth minute post-ischemia. These results are in accordance with the literature and correspond to a normal flow dilatation, as expected in healthy subjects.

The intake of fruit juices, whether rich or poor in polyphenols, induced an improvement in the ischemia-dependent flow dilatation. Thus, the RHI area under the curve significantly increased as compared to baseline, providing evidence to support the beneficial effect of acute juice intake, even in healthy volunteers. Although the authors did not always observe an acute flow improvement, this result is consistent with a large portion of the scientific literature. Indeed, previous studies using acute chocolate, red wine, champagne or tea and more generally foodstuff rich in PP demonstrated acute improvement in vessels dilatation [23,33,39–44].

Interestingly, the fruit juice rich in PP enhanced the RHI longer, as compared to the juice poor in PP. Thus, considering the PP-rich fruit juice, the increase in RHI was significant both after 1 and 2 h. Such increase was only significant after 1 h considering the PP-poor juice. This is consistent with previous data supporting that a significant increase in RHI was observed 2 h after blueberry ingestion as compared to water [26].

Besides PP, other parameters might have been involved in the results observed. Hyperglycaemia is thought to modulate flow-mediated dilatation [45] and the concentration of sugar was greater in the PP-rich fruit juice, as compared to the apple juice. However, an acute increase in plasma glucose is usually associated with either no effect or rapid and transient reduction in endothelium-mediated vasodilation [46–48]. Thus, if any, an eventual effect of hyperglycaemia might have reduced the RHI, further supporting a ben-
eficial effect of PP-rich juice on RHI, particularly if hyperglycaemia is avoided. Another
difference between juices is increased vitamin C in the PP-rich fruit juice, as compared to
the apple juice. An impact on RHI is unlikely since no difference in RHI was observed in a
randomized double-blind crossover study comparing the effects of beetroot juice, with or
without 1000 mg of vitamin C [49].

Interestingly, gender might also modulate the effects of juices intake. Indeed, women
may have better endothelial dilation due to estrogens, a more favorable metabolism of
polyphenols, and greater vascular elasticity. Accordingly, as compared to men, women
demonstrated a greater RHI 1 h after juices intakes. Such enhancement was not significant at
the second hour. This result is consistent with the fact that vascular function enhancement is
more marked in women than in men after both endurance and resistance exercise. Estrogens
likely participate in such gender difference [50].

This study has several limitations. Firstly, we aimed to use apple juice as a control
since it is largely consumed. Although this is particularly interesting since the juices
evaluated here correspond to common drinks, such a choice might have reduced the
difference observed between study arms, and the RHI increase might likely have been
more significant if compared to water. Secondly, although neither the participants nor the
team performing the protocol were aware of the juice tested and, specifically, did not know
the composition of the juices, apple and fruit juices taste different. This is a potential bias.
Whether participants may have been psychologically influenced by the different taste of
the juices cannot be totally excluded but it is unlikely considering RHI and we believed
that exercise responses should also not have been modified based on this parameter.

**5. Conclusions and Perspectives**

The present randomized, controlled, crossover study indicates that acute intake of polyphenol-rich juice increased RHI in healthy volunteers but did not result in a statistically significant improvement in exercise capacity. Longer-term supplementation studies may demonstrate more consistent effects. Indeed, our data and the literature suggest that greater beneficial effects in healthy volunteers should be observed after longer PP-rich juice supplementation. Furthermore, as a perspective, although not investigated in this study, patients presenting with mild vascular dysfunction and reduced exercise capacities might also benefit from PP-rich functional supplementation. Indeed, the acute addition of *Euterpe oleracea* Mart seed failed to improve aerobic physical performance in rats, and chronic supplementation increased exercise capacity [11]. In humans, beetroot juice improved both RHI and exercise capacity in chronic pulmonary obstructive disease patients [51]. Further studies will be useful to challenge these hypotheses [52]. Indeed, improving the health of the general population and of patients is an important goal that could be achieved by prioritizing beneficial foods and drinks.

**Author Contributions:** Conceptualization, O.R., A.-L.C., C.A., V.S.-K. and B.G.; Format Analysis, O.R., A.-L.C. and C.A.; Investigation, O.R., A.-L.C. and C.A.; Methodology, O.R., V.S.-K. and B.G.; Supervision, V.S.-K. and B.G.; Validation, All; Visualization, All; Writing—original drafts, A.-L.C. and B.G.; Writing—review and editing, All. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was supported in part by Strasbourg's clinical research directory team of the University Hospital (PRI HUS N° 4125) and by Eckes-Granini Group GmbH.

**Informed Consent Statement:** All subjects signed an informed consent form, and the ethical committee (Comité de Protection des Personnes EST IV number 080103) approved the study.

**Data Availability Statement:** Data contained within the article.
**Acknowledgments:** We are very grateful to Anne-Marie Kasprowicz for her skillful secretarial assistance, to François Piquard and Amelia Arpel and to the clinical research and innovation team of University Hospital of Strasbourg for help in performing the study.

**Conflicts of Interest:** The authors declare no conflict of interest.

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