The Effect of Blueberry Supplementation on Cognitive Functioning in Older Adults (BrainBerries)

In this randomized placebo controlled intervention study, the effect of 12 weeks of supplementation with either 150g whole blueberries, freeze-dried blueberry powder (dose equivalent to 150g berries) versus placebo on cognitive functioning will be investigated in older adults.

Study Overview

• Status: Withdrawn
• Conditions: Aging; Cognitive Decline; Cognition Disorders in Old Age
• Intervention / Treatment: Other: Blueberry; Dietary supplement: Freeze-dried blueberry powder; Dietary supplement: Placebo powder

Detailed Description

Dementia is a public health priority. The prevalence of dementia is rapidly increasing due to population ageing, posing a great social and economic impact on caregivers, families and society. This, in combination with the lack of effective treatment options, demonstrates the urgent need for better understanding on how to prevent and slow down progression of this condition. As ageing and dementia are associated with increased levels of inflammation, nutritional compounds that exhibit anti-inflammatory properties may propose a solution. Blueberries, a good source of anthocyanins, have shown anti-inflammatory properties in several human trials. Therefore, in this randomized placebo controlled intervention study, we aim to investigate the effect of 12 weeks of supplementation with either 150g whole blueberries or freeze-dried blueberry powder (dose equivalent to 150g berries) versus placebo on cognitive functioning in overweight older adults with mild memory complaints. Secondary objectives include the assessment of whole blueberry and freeze-dried blueberry powder supplementation on inflammatory markers, oxidative stress, intestinal health markers, vascular and metabolic health markers, mental well-being, and levels of neurotransmitters.

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥65y
• Overweight, body mass index ≥25 kg/m2
• Mild memory complaints, i.e. ≥22 points on the Cognitive Failure Questionnaire (CFQ) and reporting to have memory complaints and being hampered by these complaints
• No mild cognitive impairment, i.e. ≥26 points on the Montreal Cognitive Assessment (MoCA)
• Able to understand and perform the study procedures

Exclusion Criteria:

• Body Mass Index (BMI) ≥35 kg/m2
• Current use of >500 mg/day of acetylsalicylic acid
• Current use of antidepressants
• Current use of medication that affects inflammation (anti-inflammatory medication)
• Current or recent (<1 month) use of berry supplements
• Current or recent (<1 month) use of anti-inflammatory dietary supplements such as fish oil, quercetin, curcumin, resveratrol, and/or other flavonoids
• Current or recent (<3 month) use of antibiotics.
• Berry consumption of more than 1 serving (150g) per week
• Not willing to quit anthocyanin-rich product consumption during the study period
• Allergy to berries/salicylates
• Having a current disease which interferes with the effect of berries/ freeze-dried berry powder and/or with the outcome measure (cognitive functioning), including diagnosis of dementia, psychiatric disorders, gastro-intestinal disease, diabetes, and cancer, as judged by a medical doctor
• Excessive alcohol consumption (on average >21 glasses/week for men and >14 glasses/week for women)
• Current participation in other scientific research

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Whole blueberries; Participants will consume a daily dose of 150g of whole blueberries	Other: Blueberry; Daily consumption of blueberries
Experimental: Freeze-dried blueberry powder; Participants will consume a daily dose of 24g freeze-dried blueberry powder, equivalent to 150g whole blueberries	Dietary supplement: Freeze-dried blueberry powder; Daily consumption of a freeze-dried blueberry powder
Placebo Comparator: Placebo powder; Participants will consume a daily dose of 24g colour- and flavour-matched maltodextrin powder	Dietary supplement: Placebo powder; Daily consumption of a placebo powder

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Verbal fluency	Performance on verbal fluency	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive functioning	Rey Auditory Verbal Learning Test (RAVLT)	12 weeks
Cognitive function	Wechsler Digit Span Task (forward, backward, sequencing) WAIS-IV	12 weeks
Cognition	Symbol digit modalities test	12 weeks
Cognition	Trail Making Test (TMT) version A and B	12 weeks
Cognition	Stroop Color-Word test	12 weeks
Inflammation - CRP	Inflammatory blood marker: C-reactive protein	12 weeks
Inflammation - TNFalpha	tumor necrosis factor-alpha	12 weeks
Inflammation - IL6	interleukin-6	12 weeks
Oxidative stress	total plasma nitric oxide (NO)	12 weeks
Oxidative stress	serum superoxide dismutase (SOD)	12 weeks
Intestinal health	Intestinal health markers as measured in blood and feces (microbiota composition, inflammatory fecal markers, microbiota-derived bioactive compounds, intestinal integrity markers	12 weeks
Metabolic health	Blood markers of metabolic health: plasma fasting glucose,	12 weeks
Metabolic health	Blood markers of metabolic health (plasma fasting glucose, Hb1Ac, triglyceride, adiponectin)	12 weeks
Metabolic health	Blood markers of metabolic health: Hb1Ac,	12 weeks
Metabolic health	Blood markers of metabolic health: triglyceride	12 weeks
Metabolic health	Blood markers of metabolic health: adiponectin	12 weeks
Mental well-being	Score on 12-item short form health survey	12 weeks
Mental well-being	profiles of mood states-short form (POMS)	12 weeks
Neurotransmitters	Levels of plasma neurotransmitters (dopamine, serotonin, (nor)adrenaline, and their metabolites)	12 weeks
Vascular health	Markers of vascular health (systolic blood pressure, diastolic blood pressure)	12 weeks

Collaborators and Investigators

• Sponsor: Wageningen University
• Investigators: Principal Investigator: Lisette de Groot, prof, Division of Human Nutrition and Health, Wageningen University and Research, The Netherlands

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2021
• Primary Completion (Estimated): October 1, 2022
• Study Completion (Estimated): October 1, 2022

Study Registration Dates

• First Submitted: August 26, 2021
• First Submitted That Met QC Criteria: September 5, 2025
• First Posted (Estimated): September 12, 2025

Study Record Updates

• Last Update Posted (Estimated): September 12, 2025
• Last Update Submitted That Met QC Criteria: September 5, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Ageing; Cognition; Blueberry; Anthocyanins
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; blueberry extract
• Other Study ID Numbers: NL77025.091.21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Starting 12 months after article publication. Sharing only upon reasonable request in consultation with the study team.
• IPD Sharing Time Frame: Starting 12 months after article publication.
• IPD Sharing Access Criteria: Upon reasonable request. Sharing will be done in consultation with the study team

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