De-stressing the Brain: Can Eating Grapes During Periods of Mental Stress Protect Brain and Vascular Health in Young Adults

A Placebo-controlled, Randomized, Double-masked, Cross-over Acute Intervention Study Investigating the Effects of Grape Polyphenols on Cerebral Oxygenation, Cognitive and Vascular Function in the Context of Mental Stress in Young Adults

The main aim of the current study is to investigate whether consuming grapes rich in flavonoids just before mental stress can protect cerebrovascular and peripheral vascular function, mood and cognition, from the negative effects of mental stress in young healthy adults. A second, exploratory aim, will further address whether quality of habitual diet, microbiome health (composition; metabolites production e.g. Short-chain fatty acids) and levels of cardiorespiratory fitness play a role on the beneficial effects of grapes during mental stress. All participants will receive a high-flavonoid grape intervention (60 g freeze-dried grape powder, equivalent to 300 g fresh grapes) and a low-flavonoid grape intervention (60 g powdere isocaloric-matched control). It is hypothesized that the high-flavonoid grape intervention will improve cortical oxygenation and cognitive function in the context of mental stress, and prevent the stress-induced decline in peripheral endothelial function following stress. Furthermore, it is hypothesized that individuals with poorer diets, cardiorespiratory fitness and a poorer gut microbiome will benefit more from the grape intervention in the context of mental stress.

Study Overview

• Status: Recruiting
• Conditions: Healthy
• Intervention / Treatment: Dietary supplement: High-flavonoid grape intervention; Dietary supplement: Low-flavonoid grape intervention

Detailed Description

Psychological stress is widespread in our societies, and has been extensively shown to have negative consequences for human health. Specifically, psychological stress induces significant declines in human vascular function, as measured by brachial Flow-mediated Dilatation (FMD). We have demonstrated that flavonoid interventions can prevent the harmful effects of stress on the vascular system. Indeed, flavonoid-rich interventions have also been extensively shown to improve peripheral and cerebrovascular function in the absence of stress. However, the effect of flavonoids on cerebrovascular function and cognition in the context of mental stress is unknown. In the proposed project, our key objectives are to investigate whether grape intake prior to a mental stress task results in better brain oxygenation and vascular function, which leads to improved cognitive performance and mood in young healthy adults. These data will establish whether grapes can be effective as a 'stress snack' to optimize cognitive and brain function in the context of psychological stress. Furthermore, we will explore whether there are certain participant characteristics that mediate the impact of grape flavonoids on cerebrovascular function and cognition in the context of mental stress. Such as, physical fitness (assessed by a VO2 max test), composition of gut microbiome (assessed by faecal sample), habitual diet (assessed by 3-day food diary and the food frequency questionnaire), and eating behaviour and chronic stress (assessed by the eating behaviour questionnaire and perceived stress scale). This work will be important to guide future dietary recommendations around stress and might ultimately result in increased intake of flavonoid-rich grapes and other flavonoid-rich fruits/vegetables overall.

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B15 2TT
      • Recruiting
      • School of Sport, Exercise & Rehabilitation Sciences
      • Contact: Catarina Rendeiro; Phone Number: +44 7389190669; Email: c.rendeiro@bham.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Males and females
• 18 - 40 years old

Exclusion Criteria:

• Smokers
• Consumes > 21 units of alcohol per week
• History of cardiovascular, respiratory, metabolic, liver or inflammatory diseases
• Suffers from blood-clotting disorders
• Allergies or intolerances to foods
• On a weight reducing dietary regiment
• Currently taking dietary supplements, including fatty acids and vitamins
• On long-term medication or have been on antibiotics in the last 3 months
• Has an infection at present (e.g. cold) or viral infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-flavonoid grape intervention; 60 g freeze-dried grape powder, equivalent to 300 g fresh grapes (Total polyphenols: 437 mg/100g)	Dietary supplement: High-flavonoid grape intervention; High-flavonoid grape powder: 60 g, equivalent to 300 g fresh grapes. Total polyphenols: 437 mg/100g).
Placebo Comparator: Low-flavonoid grape intervention; 60 g powder isocaloric-matched control (Total polyphenols: < 60 mg)	Dietary supplement: Low-flavonoid grape intervention; 60 g powder isocaloric-matched control (Total polyphenols: < 60 mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pre-frontal cortical Tissue Oxygenation Index (NIRS) - TOI	Pre-frontal levels of Tissue Oxygenation Index (% TOI) will be assessed by functional Near-Infrared Spectroscopy (fNIRS). The NIRS device measures changes in chromophore concentrations of oxyhaemoglobin (O2Hb) and deoxyhaemoglobin (HHb), providing depth-resolved measures of total tissue oxygen saturation.	Change from pre-intervention baseline to 1 hour post-intervention (during mental stress) and 1 hour 15 minutes post-intervention (during cognitive tasks, 10 minutes post-stress)
Pre-frontal cortical Tissue Oxygenation Index (NIRS) - O2Hb	Pre-frontal levels of oxygenated (O2Hb) haemoglobin concentration (μmol) will be assessed by functional Near-Infrared Spectroscopy (fNIRS).	Change from pre-intervention baseline to 1 hour post-intervention (during mental stress) and 1 hour 15 minutes post-intervention (during cognitive tasks, 10 minutes post-stress).
Pre-frontal cortical Tissue Oxygenation Index (NIRS) - HHb	Pre-frontal levels of deoxygenated (HHb) haemoglobin concentration (μmol) will be assessed by functional Near-Infrared Spectroscopy (fNIRS).	Change from pre-intervention baseline to 1 hour post-intervention (during mental stress) and 1 hour 15 minutes post-intervention (during cognitive tasks, 10 minutes post-stress).
Pre-frontal cortical Tissue Oxygenation Index (NIRS) - nTHI	Pre-frontal levels of normalised haemoglobin index (relative value of total haemoglobin normalised to the initial value, nTHI) content (a.u.) will be assessed by functional Near-Infrared Spectroscopy (fNIRS).	Change from pre-intervention baseline to 1 hour post-intervention (during mental stress) and 1 hour 15 minutes post-intervention (during cognitive tasks, 10 minutes post-stress).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Flow-mediated dilatation (FMD) of the brachial artery	FMD of the brachial artery. Expressed as % FMD: change in brachial diameter from baseline to peak dilation following 5 minutes of arterial occlusion. Brachial artery diameter and blood flow will be measured using Doppler ultrasonography (uSmart 3300, Terason).	Change from pre-intervention baseline to 2 hours and 2 hours 45 minutes post-intervention (45-90 minutes post-stress).
Common Carotid Artery (CCA) - Blood flow	Common Carotid Artery (CCA) blood flow velocity (ml min-1) will be measured using Doppler ultrasonography (uSmart 3300, Terason) interfaced with the Quipu analysis software. CCA blood flow is calculated using CCA blood velocity and diameter across 2 minutes of recording.	Change from pre-intervention baseline to 2 hours and 2 hours 45 minutes post-intervention (45-90 minutes post-stress).
Common Carotid Artery (CCA) - Shear rate	Common Carotid Artery (CCA) shear rate (s-1) will be measured using Doppler ultrasonography (uSmart 3300, Terason) interfaced with the Quipu analysis software.	Change from pre-intervention baseline to 2 hours and 2 hours 45 minutes post-intervention (45-90 minutes post-stress).
Executive Function (MANT) - Accuracy	Executive function accuracy will be measured using the Modified Attention Network Task (MANT) which measures response to cognitive load	Change from pre-intervention baseline to 1 hour 15 minutes post-intervention (10 minutes post-stress).
Executive Function (Switch) - Accuracy	Executive function accuracy will be measured using the Switch Task which considers cognitive flexibility.	Change from pre-intervention baseline to 1 hour 15 minutes post-intervention (10 minutes post-stress).
Executive Function (MANT) - Reaction time	Executive function reaction time will be measured using Modified Attention Network Task (MANT) which measures response to cognitive load.	Change from pre-intervention baseline to 1 hour 15 minutes post-intervention (10 minutes post-stress).
Executive Function (Switch) - Reaction time	Executive function reaction time will be measured using the Switch Task which considers cognitive flexibility.	Change from pre-intervention baseline to 1 hour 15 minutes post-intervention (10 minutes post-stress).
Executive Function (MANT) - Inverse Efficiency Score	Executive function inverse efficiency will be measured using the Modified Attention Network Task (MANT), calculated by dividing task reaction time by task accuracy.	Change from pre-intervention baseline to 1 hour 15 minutes post-intervention (10 minutes post-stress).
Executive Function (Switch) - Inverse Efficiency Score	Executive function inverse efficiency will be measured using the Switch Task, calculated by dividing task reaction time by task accuracy.	Change from pre-intervention baseline to 1 hour 15 minutes post-intervention (10 minutes post-stress).
Mood (POMS)	Mood (total mood disturbance, TMD) will be assessed by the questionnaire Profile-of-Mood-States (POMS).	Change from pre-intervention baseline to 1 hour post-intervention (immediately following stress), 2 hours and 2 hours 45 minutes post-intervention (45-90 minutes post-stress).

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forearm blood flow (FBF)	Venous occlusion plethysmography will assess the forearm vasodilatory response (ml/100ml/min) to mental stress.	Change from pre-intervention baseline to 1 hour post-intervention (during 8 minutes rest and 8 minutes of mental stress).
Forearm vascular conductance (FVC)	Forearm vascular conductance (FVC) will be calculated by dividing FBF by beat-to-beat mean arterial pressure (MAP).	Change from pre-intervention baseline to 1 hour post-intervention (during 8 minutes rest and 8 minutes of mental stress).
Cardiovascular activity - Heart rate (HR)	Heart rate (HR, bpm) is assessed using an electrocardiogram.	Change from pre-intervention baseline to 1 hour post-intervention (during 8 minutes rest and 8 minutes of mental stress).
Cardiovascular activity - R-wave to pulse interval (RPI)	R-wave to pulse interval (RPI, ms) is assessed using an electrocardiogram, to provide an indication of sympathetic activity.	Change from pre-intervention baseline to 1 hour post-intervention (during 8 minutes rest and 8 minutes of mental stress).
Cardiovascular activity - Heart rate variability (HRV)	Heart rate variability (HRV, ms) is assessed using an electrocardiogram, to provide an indication of parasympathetic activity.	Change from pre-intervention baseline to 1 hour post-intervention (during 8 minutes rest and 8 minutes of mental stress).
Cardiovascular activity - beat-to-beat systolic blood pressure (SBP)	Beat-to-beat systolic blood pressure (SBP) will be measured using a Finometer (mmHg).	Change from pre-intervention baseline to 1 hour post-intervention (during 8 minutes rest and 8 minutes of mental stress).
Cardiovascular activity - beat-to-beat diastolic blood pressure (DBP)	Beat-to-beat diastolic blood pressure (SBP) will be measured using a Finometer (mmHg).	Change from pre-intervention baseline to 1 hour post-intervention (during 8 minutes rest and 8 minutes of mental stress).
Cardiovascular activity - beat-to-beat mean arterial pressure (MAP)	Beat-to-beat mean arterial pressure (MAP) will be measured using a Finometer (mmHg).	Change from pre-intervention baseline to 1 hour post-intervention (during 8 minutes rest and 8 minutes of mental stress).
Brachial Systolic Blood Pressure (SBP)	Resting systolic blood pressure (mmHg) will be measured using an automated oscillometric blood pressure monitor, with a cuff attached to the right upper arm, following at least 10 minutes rest.	Change from pre-intervention baseline to 1 hour 15 minutes post-intervention (10 minutes post-stress), 2 hours post-intervention (45 minutes post-stress) and 2 hour 45 minutes post-intervention (90 minutes post-stress).
Brachial Diastolic Blood Pressure (DBP)	Resting diastolic blood pressure (mmHg) will be measured using an automated oscillometric blood pressure monitor, with a cuff attached to the right upper arm, following at least 10 minutes rest.	Change from pre-intervention baseline to 1 hour 15 minutes post-intervention (10 minutes post-stress), 2 hours post-intervention (45 minutes post-stress) and 2 hour 45 minutes post-intervention (90 minutes post-stress).

Collaborators and Investigators

• Sponsor: University of Birmingham
• Collaborators: California Table Grape Commission

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2025
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: March 27, 2025
• First Submitted That Met QC Criteria: April 10, 2025
• First Posted (Actual): April 11, 2025

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: December 3, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: cognition; flavonoids; vascular function; executive function; cerebral oxygenation; Functional Near-Infrared Spectroscopy; Flow-mediated dilatation; mental stress; grape
• Additional Relevant MeSH Terms: Behavioral Symptoms; Behavior; Stress, Psychological
• Other Study ID Numbers: ERN_17-1755H; 3155902 (Other Grant/Funding Number: California Table Grape Comission)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No