The effect of blueberry interventions on cognitive performance and mood: A systematic review of randomized controlled trials
Introduction
Polyphenols – bioactive plant compounds abundant in foods such as fruits, vegetables, spices, and teas – are a group of diverse compounds that are characterised by their phenolic structural features. Polyphenol-rich dietary patterns such as the Mediterranean diet, as well as specific polyphenol-rich foods, including berries, green tea, and cacao, have been reported in clinical and observational studies to improve measures of cognition and mood (Bell et al., 2015a, Chang et al., 2016, Donnelly et al., 2015, Hardman et al., 2016, Jacka et al., 2017, Kent et al., 2017a, Lassale et al., 2018).
Blueberries (Vaccinium corybosum L.) are a rich source of polyphenolic compounds, particularly anthocyanins, a sub-class of polyphenols that are responsible for the fruit’s deep purple and blue colour (Li et al., 2017). These blueberry-derived polyphenols possess multiple properties that may mediate cognitive performance and neurodegeneration. In a preclinical animal model, anthocyanins have been identified in specific cerebral sites of 19-month-old male F344 rats after 8–10 weeks of receiving a blueberry-enriched diet, including the hippocampus and neocortex, regions essential for cognitive performance (Andres-Lacueva et al., 2005). Preclinical studies have also demonstrated decreased excitotoxicity relating to oxidative stress following blueberry supplementation, with its direct scavenging activity reducing the production of reactive oxygen species (ROS) (Shukitt-Hale, 2012). This antioxidant capacity may be driven via hormesis, whereby initial increases in total ROS are followed by an increased antioxidant defence (Elks et al., 2011). Blueberries have also been shown to protect against the neurodegenerative effects of beta-amyloid and tau proteins in rats through the downregulation of inflammatory responses and inhibition of pro-inflammatory molecules such as cytokines (Ebenezer et al., 2016). This is achieved via a reduction in nuclear factor kappa B (NF-κB) signalling (Goyarzu et al., 2004) and suppression of microglial activation (Zhu et al., 2008). Following blueberry consumption, neuroplasticity has been reported in structures such as the hippocampus and frontal cortex through the stimulation of trophic factors including brain-derived neurotrophic factor (BDNF) (Rendeiro et al., 2013) and Insulin-like growth factor 1 (IGF-1) (Shukitt-Hale et al., 2008). In an animal model of post-traumatic stress disorder, a blueberry-enriched diet significantly increased production of neurotransmitters such as serotonin and its precursor enzymes, tyrosine hydroxylase and tryptophan hydroxylase (Ebenezer et al., 2016). As a result, blueberries appeared to enhance resiliency as indicated by reduced anxiety levels when exploring new surroundings in the elevated plus-maze. Additional modes of action include reduced lipid peroxidation and acetylcholinesterase activity (Papandreou et al., 2009), neuroprotective activity against glutamatergic excitotoxicity (Vyas et al., 2013) and suppressed expression of neuronal apoptosis (Shin et al., 2006). Furthermore, blueberries have reported to possess a range of beneficial cardiovascular properties such as antihypertension (Shaughnessy et al., 2009), hypoglycaemic (Erlund et al., 2008), and anticoagulant actions (Martineau et al., 2006) which may improve cardiovascular outcomes and provide indirect benefits to cognition by improving cerebrovascular flow, (Bowtell et al., 2017) a marker of cognitive impairment (Kalaria Raj, 2012).
Recently, there have been numerous clinical trials that have evaluated the effect of blueberries and blueberry products (including juices, whole blueberries, and freeze-dried powders preparations) on cognition in various populations using randomized, double blind controlled study designs. However, the results of these studies have not been systematically evaluated. Therefore, this systematic review aims to examine the current evidence from randomized controlled trials to evaluate the potential effects of blueberries on cognitive performance and mood in humans.
Section snippets
Methods
This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines as a methodological template (Moher et al., 2009), and was prospectively registered in an international registry of systematic reviews (PROSPERO registration no. CRD42018100888). The systematic review strategy was guided by the PICOS (population, intervention, comparator, outcomes and setting) approach. The criteria within each of these categories were as follows:
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Population: Human
Results
In total, 504 articles were identified during the initial search, with 186 omitted as duplicates. A further 296 were excluded during initial screening of the inclusion criteria, with an additional 12 excluded for reasons noted in the PRISMA flow chart (Fig. 1), leaving eleven articles for inclusion in the final review. The manuscript by Khalid et al. (2017) reported results from two separate studies. Furthermore, Khalid et al., 2017, Barfoot et al., 2018 reported on separate outcomes from the
Discussion
The results of this systematic review suggest that various formulations of blueberry interventions can improve some aspects of cognition and mood. Eight studies reported blueberry consumption or supplementation at various doses and time lengths to improve some measures of cognitive performance, particularly short- and long- term memory and one study reported improvements in positive affect. However, as shown in Table 1, two studies did not show improvements in cognition and four studies did not
Conclusion
The results of this review provide preliminary evidence for the potential efficacy of blueberries as an intervention to promote cognitive performance and mood. However, due to the limited number of current trials in the area, with heterogenous age groups, large variation in cognitive tests between trials, relatively small sample sizes, and differing anthocyanin content in the blueberry interventions, further investigation is needed. A number of suggestions, including the use of standardized
Competing interest statement
The authors declare no conflicts of interest.
References (59)
- et al.
Recommendations on reporting requirements for flavonoids in research
Am. J. Clin. Nutr.
(2015) - et al.
Dietary flavonoid intake and risk of incident depression in midlife and older women
Am. J. Clin. Nutr.
(2016) - et al.
Favorable effects of berry consumption on platelet function, blood pressure, and HDL cholesterol–
Am. J. Clin. Nutr.
(2008) - et al.
Polyphenols, anthocyanins, and flavonoids contents and the antioxidant capacity of various cultivars of highbush and half-high blueberries
J. Food Compost. Anal.
(2017) - et al.
Regulation of adult neurogenesis by stress, sleep disruption, exercise and inflammation: implications for depression and antidepressant action
Eur. Neuropsychopharmacol.
(2010) - et al.
Anti-diabetic properties of the Canadian lowbush blueberry Vaccinium angustifolium Ait
Phytomedicine
(2006) - et al.
Cognitive response to fish oil, blueberry, and combined supplementation in older adults with subjective cognitive impairment
Neurobiol. Aging
(2018) - et al.
Effect of a polyphenol-rich wild blueberry extract on cognitive performance of mice, brain antioxidant markers and acetylcholinesterase activity
Behav. Brain Res.
(2009) - et al.
Cognitive demand and blood glucose
Physiol. Behav.
(2001) - et al.
Diets containing blueberry extract lower blood pressure in spontaneously hypertensive stroke-prone rats
Nutr. Res.
(2009)
Protective effect of anthocyanins in middle cerebral artery occlusion and reperfusion model of cerebral ischemia in rats
Life Sci.
Effects of a single dose of a flavonoid-rich blueberry drink on memory in 8 to 10 y old children
Nutrition (Burbank, Los Angeles County, Calif.)
Effects of cortisol on cognition in major depressive disorder, posttraumatic stress disorder and borderline personality disorder-2014 Curt Richter Award Winner
Psychoneuroendocrinology
Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory
Nutr. Neurosci.
The effects of acute wild blueberry supplementation on the cognition of 7–10-year-old schoolchildren
Eur. J. Nutr.
A review of the cognitive effects observed in humans following acute supplementation with flavonoids, and their associated mechanisms of action
Nutrients
A review of the cognitive effects observed in humans following acute supplementation with flavonoids, and their associated mechanisms of action
Nutrients
Enhanced neural activation with blueberry supplementation in mild cognitive impairment
Nutr. Neurosci.
Enhanced task-related brain activation and resting perfusion in healthy older adults after chronic blueberry supplementation
Appl. Physiol. Nutr. Metab.
Bioavailability of the polyphenols: status and controversies
Int. J. Mol. Sci.
The Acute Effects of Flavonoid-rich Blueberries on Cognitive Function in Healthy Younger and Older Adults
The acute and sub-chronic effects of cocoa flavanols on mood, cognitive and cardiovascular health in young healthy adults: a randomized, controlled trial
Front. Pharmacol.
The anti-inflammatory effects of blueberries in an animal model of post-traumatic stress disorder (PTSD)
PLoS One
Arterial pulse wave velocity and cognition with advancing age
Hypertension
A blueberry-enriched diet attenuates nephropathy in a rat model of hypertension via reduction in oxidative stress
PLoS One
Impact of flavonoids on cellular and molecular mechanisms underlying age-related cognitive decline and neurodegeneration
Curr. Nutr. Rep.
Protective effects of foods containing flavonoids on age-related cognitive decline
Curr. Nutr. Rep.
Blueberry supplemented diet: effects on object recognition memory and nuclear factor-kappa B levels in aged rats
Nutr. Neurosci.
Adherence to a mediterranean-style diet and effects on cognition in adults: a qualitative evaluation and systematic review of longitudinal and prospective trials
Front. Nutr.
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Both authors contributed to this manuscript equally (co-first authors).