Reference
Cheng N, Barfoot KL, Le Cozannet R, Fança-Berthon P, Lamport DJ, Williams CM. Wild blueberry extract intervention in healthy older adults: a multi-study, randomised, controlled investigation of acute cognitive and cardiovascular effects. Nutrients. 2024;16(8):1180.
Study Objective
To determine the acute effects of wild blueberry extract on executive functioning, episodic memory, and cardiovascular health
Key Takeaway
Acute use of wild blueberry extract is a well-tolerated intervention that may be effective in improving cognitive function in healthy aging adults.
Design
Investigators undertook 2 studies; each 1 was a randomized, double-blind, crossover, placebo-controlled design.
Study 1, ROAB, investigated if wild blueberry extract could impact executive function, episodic memory, and cardiovascular outcomes at varying doses.
Study 2, BEAT, was designed to replicate the results of ROAB, using a specified dose to determine the effects of wild blueberry extract compared to placebo on cognitive and cardiovascular outcomes, which included episodic memory, executive function, blood pressure, and heart rate in adults aged 68 to 75 years.
Investigators provided doses of 111 mg, 222 mg, 444 mg, 888 mg, or placebo to identify the ideal dose related to positive cognitive and cardiovascular effects.
They also investigated cardiovascular outcomes, and subjects received 222 mg of wild blueberry extract vs placebo.
Participants
Participants across both ROAB and BEAT trials were healthy adults ranging between the ages of 68 to 75 years.
Exclusion criteria for each trial included the following: history of metabolic disorder, diabetes, substance abuse, diagnosis of psychiatric or neurological condition, smokers, vegetarians, body mass index (BMI) greater than or equal to 30, allergy to compounds in the investigational product, more than 2 alcoholic beverages per day on average in a week, use of complementary or alternative medicine for memory or cognitive performance within 1 month prior to study enrollment, participation in other clinical trials within the previous month or other cognitive trial within the previous 6 months.
ROAB Study: There were 40 volunteers initially, but 12 withdrew from the study due to the demands of the task battery and length of the initial assessment, leaving a total of 28 participants (11 male and 17 female). The mean age at enrollment was 70.71 years.
BEAT Study: Forty-eight subjects enrolled, and 3 withdrew before the assessment process, leaving a total of 45 volunteers. The initial goal was to build a larger sample size based on ROAB trial data, but this was not possible due to Covid-related restrictions during the recruitment period. The mean age at enrollment was 71.02 years, with 18 men and 27 women.
Interventions
Participants in the ROAB study received five treatments of wild blueberry extract, with each treatment varying in dosage (111 mg, 222 mg, 444 mg, 888 mg, or placebo). They received each treatment on a single day over a 5-week period, with the treatments separated by a 1-week washout.
Investigators measured outcomes beginning with a low-polyphenol breakfast as the start (0 hour). Then the tests were repeated at 2 hours, 4 hours, and 6 hours postintervention.
In the BEAT study, 45 participants received a single treatment of 222 mg of wild blueberry extract or placebo. Investigators measured outcomes at the 0 hour and at 6 hours (14:00) when a postlunch dip was anticipated.
Wild blueberry extract capsules consisted of wild blueberry powder extract (89%), L-cysteine (10%), and L-glutathione (1%). The wild blueberry extract was obtained from the Vaccinium angustifolium cultivar using a proprietary process. The formulation was standardized to a minimum of 35% polyphenols and contained at least 5% anthocyanins. The placebo capsules contained inert components of the wild blueberry formulation—specifically, artificially colored maltodextrin.
Study Parameters Assessed
ROAB collected cognitive data regarding executive functioning and episodic memory. Tests used for cognitive evaluation included the Rey Auditory Verbal Learning Test (RAVLT), Corsi block-tapping task, Task Switch Task (TST), Trail Making Test Parts A and B, and the Choice Reaction Time task.
Investigators measured blood pressure and heart rate. They recorded the mean of 3 consecutive heart-rate readings separated by 2-minute intervals.
Investigators assessed mood at the end of each cognitive test using the Positive and Negative Affect Schedule (PANAS).
BEAT collected cognitive data regarding executive functioning and episodic memory and used similar testing, including RAVLT, the Corsi block-tapping task, and the TST. It also collected blood pressure and heart-rate measurements.
Primary Outcome
The primary outcome of the ROAB Study (study 1) was to investigate the efficacy of wild blueberry extract in maintaining episodic memory throughout the day in adults aged 68 to 75 years.
The primary outcome of the BEAT Study (study 2) was to determine the time point indicative of postlunch cognitive performance dip.
Key Findings
ROAB Study Findings
Placebo participants had significantly poorer executive functioning at 4 hours compared to 2 hours and 6 hours (P<0.05; dose x session interaction, F (8, 206)=2.057, P=0.04). This suggests a postprandial dip at 4 hours for placebo treatment, which did not occur following wild blueberry extract treatment.
Wild blueberry extract at 222 mg was associated with a significantly lower systolic blood pressure (P=0.038) and diastolic blood pressure (P=0.027) compared to placebo. Diastolic blood pressure was also significantly lower with 222 mg of wild blueberry extract compared to 888 mg (P=0.025).
Investigators also observed benefits in episodic memory with 444 mg of wild blueberry extract.
BEAT Study Findings
TST reaction time was significantly faster following wild blueberry extract treatment (222 mg) compared to placebo (F(1, 303)=6.4, P=0.01), which relates to executive functioning. Investigators did not observe other significant cognitive benefits or cardiovascular outcomes with this wild blueberry extract dosage.
Transparency
The study was funded by a grant to coauthor CMW from Givaudan France Naturals. Two of the authors were employed by Givaudan France Naturals. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; or in the decision to publish the results.
Practice Implications & Limitations
The ROAB and BEAT studies aimed to evaluate the benefit of wild blueberry extract on cognitive function and cardiovascular health.
These studies showed that wild blueberry extract may help to inhibit cognitive decline throughout the day, particularly the decline associated with a postprandial dip. Some studies have shown that lunch leads to potential impairment of some aspects of cognitive functioning in the early afternoon.1
There were greater cognitive and cardiovascular benefits demonstrated in the ROAB Study compared to the BEAT Study. This may be due to increased demand based on more extensive testing and greater time requirement in the ROAB Study (as implied by the high dropout rate). The authors speculate that there may have been an enhanced cognitive benefit displayed in the BEAT Study if there were a greater level of cognitive fatigue.
Investigators may have observed greater benefit in the ROAB and BEAT studies if participants took the supplement over a longer period of time.
There was a reduction in systolic and diastolic blood pressure observed in the ROAB Study with wild blueberry extract dosed at 222 mg. This was not observed in the BEAT Study with the identical dosage. This may be related to the higher diastolic blood pressures taken at baseline in the BEAT Study compared to the ROAB Study. Elevated blood pressure has been shown to contribute significantly to endothelial dysfunction.2 Acute flavonoid action from wild blueberry may be most efficient in those with better baseline endothelial function.3
It is well-known that the risk of developing both cardiovascular and neurodegenerative diseases increases with aging.4 Previous randomized, controlled trials have shown beneficial effects of daily blueberry consumption on executive functioning and episodic memory following at least 6 weeks of daily consumption in healthy older adults. Investigators may have observed greater benefit in the ROAB and BEAT studies if participants took the supplement over a longer period of time.
Practitioners can take away from these studies that healthy adults can safely use acute dosing of wild blueberry extract to improve cognitive health, especially with supporting executive function throughout the afternoon hours when there is typically a postprandial dip. In addition, wild blueberry extract may work to reduce systolic and diastolic blood pressure, which was particularly demonstrated in the ROAB study.
Further research should be done to study the potential benefit of wild blueberry extract in adults with existing cognitive impairment.
Conflict of Interest Disclosure
The author declares no conflict of interest.
