There is a growing body of research from preclinical and adult human trials indicating that both chronic and acute interventions with flavonoids can lead to cognitive improvements (1-4) with berries (the main source of anthocyanins, a particular class of flavonoids, in the human diet) being known to protect against neuronal stress (5) and positively mediate signalling pathways in the brain (6). Indeed, preclinical work has found that 7–12 weeks of supplementation with blueberry anthocyanins produces significant improvements in visuo-spatial memory (7,8).
Similarly, following one-off interventions in adults, improvements have been reported following acute flavonol interventions on memory-related areas such as spatial working memory (9) and attention-related executive function tasks (10), and immediate verbal memory following 12-week supplementation with blueberry and grape anthocyanins (11,12).
Neuroprotection
The mechanisms by which flavonoids exert these actions on cognitive performance are still being elaborated, including evidence which suggests that they may increase cerebral blood flow (CBF) (13-15) as well as modulate the activation status of neuronal receptors, signalling proteins and gene expression (15). Alternatively, the blueberry-derived flavonoids may act to enhance the efficiency of spatial memory indirectly by acting on the dentate gyrus (DG)-the hippocampal sub-region most sensitive to the effects of ageing (16-18). Blueberry supplementation has been shown to significantly increase the proliferation of precursor cells in the DG (19). This link between DG neurogenesis, cognitive performance and ageing is well documented (20) and may represent another mechanism by which fruits rich in flavonoids may improve memory by acting on the hippocampus.
Blueberry poly¬phenols are also potent intracellular antioxidants even at low concentrations, and their action can be direct or mediated by the enhancement of cell endogenous antioxi¬dants (21). In human beings, blueberry anthocyanins are absorbed unchanged in their glycosylated form and are detectable in serum after their consumption (22,23).
Memory
Barros et al., (24) demonstrated an enhancement of long-term memory and an improvement of anxiety-related behaviour (anxiolytic effect) in addition to decreased oxidative damage in the DNA of the hippocampus. An association between berry polyphenol supplementa¬tion and beneficial effects in verbal memory emerged in acute and chronic conditions (25). Furthermore, according to an epidemiological long-scale study performed on older women (26), an increased long-term intake of blueberries is associated with a slower rate of cognitive decline, evaluated through tests on overall cognition and verbal memory; this slowing down is seen to correspond to a delay of aging signs by up to 2.5 years. In elderly subjects with an early age-related memory impairment, a 12-week administration of blueberry juice was shown to improve memory per¬formance, assessed through verbal memory tests relying upon hippocampal function (26). The administration of a formulation of antioxidants including blueberries, was observed to improve processing speed, an aspect of cognition, in elderly adults with no evidence of cognitive impairment (mini-mental state >24) across eight weeks of testing with a good safety profile (27).
A placebo controlled double-blind cross-over study assessed the effect of blueberry powder using repeated tests of verbal memory, word recognition, response interference, response inhibition and levels of processing. Significant blueberry improvements included final immediate recall, delayed word recognition sustained over each period, and accuracy on cognitively demanding incongruent trials in the interference task. Across all measures, cognitive performance improved. The beneficial effects seemed to be particularly sensitive to the cognitive demand of task (28).
Retinal Protection
Blueberry polyphenols have also been shown to confer a retinal protective activity against light-induced retinal injury in vivo and inhibiting lipid peroxidation of unsaturated fatty acids in the retina was proposed to be another important function to protect the eyes (29). The same authors again demonstrated Blueberry anthocyanins protected against ageing and light-induced damage in retinal pigment epithelial cells (30).
References
1 Lamport DJ, et al (2012) The effects of flavonoid and other polyphenol consumption on cognitive performance: a systematic research review of human studies. Nutr Aging 1:5–25.
2 Macready AL, et al (2009) Flavonoids and cognitive function: a review of human randomized controlled trial studies and recommendations for future studies. Genes Nutr 4:227–242.
3 Spencer JP (2008) Food for thought: the role of dietary flavonoids in enhancing human memory, learning and neuro-cognitive performance. Proc Nutr Soc 67:238–252.
4 Spencer JP (2010) The impact of fruit flavonoids on memory and cognition. Brit J Nutr 104:S40–S47.
5 Shukitt-Hale B (2012) Blueberries and neuronal aging. Gerontology 58:518–523.
6 Miller MG, Shukitt-Hale B (2012) Berry fruit enhances beneficial signaling in the brain. J Agric Food Chem 60:5709–5715.
7 Rendeiro C, Vazour D, Rattray M et al (2013) Dietary levels of pure flavonoids improve spatial memory performance and increase hippocampal brain derived neurotrophic factor. PLoS One 8:e63535.
8 Williams CM, et all (2008) Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and (BDNF) levels. Free Radic Biol Med 45:295–305.
9 Field DT, Williams CM, Butler LT (2011) Consumption of cocoa flavanols results in an acute improvement in visual and cognitive functions. Physiol Behav 103:255–260.
10 Scholey AB, et al (2010) Consumption of cocoa flavanols results in acute improvements in mood and cognitive performance during sustained mental effort. J Psychopharmacol 24:1505–1514.
11 Krikorian R, et al (2010) Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. Brit J Nutr 103:730–734.
12 Krikorian R, Shidler MD, Nash TA et al (2010) Blueberry supplementation improves memory in older adults. J Agric Food Chem 58:3996–4000.
13 Francis ST, Head K, Morris PG, Macdonals IA (2006) The effect of flavanol-rich cocoa on the fMRI response to a cognitive task in healthy young people. J Cardiovasc Pharm 47:S215–S220
14 Lamport DJ, et al The effect of flavanol-rich cocoa on cerebral perfusion in healthy older adults during conscious resting state. Psychopharmacology232:3227–3234.
15 Dodd FD (2012) The acute effects of flavonoid-rich blueberries on cognitive function in healthy younger and older adults. Dissertation. University or Reading
16 Rendeiro C, et al (2012) Blueberry supplementation induces spatial memory improvements and region specific regulation of hippocampal BDNF mRNA expression. Psychopharmacology 223:319–330.
17 Burke SN & Barnes CA (2006) Neural plasticity in the ageing brain. Nat Rev Neurosci 7, 30–40.
18 Small SA, Tsai WY, DeLaPaz R, et al. (2002) Imaging hippocampal function across the human life span: is memory decline normal or not? Ann Neurol 51, 290–295.
19 Small SA, et al. (2004) Imaging correlates of brain function in monkeys and rats isolates a hippocampal subregion differentially vulnerable to aging. Proc Natl Acad Sci U S A 101, 7181–7186.
20 Casadesus G, et al (2004) Modulation of hippocampal plasticity and cognitive behaviour by short-term blueberry supplementation. Nutr Neurosci 7, 309–316.
21 Stangl D & Thuret S (2009) Impact of diet on adult hippocampal= neurogenesis. Genes Nutr 4, 271–282.
22 Bornsek, S.M., et al 2012. Bilberry and blueberry anthocya¬nins act as powerful intracellular antioxidants in mammalian cells. Food Chem. 134, 1878–1884.
23 Mazza, G., Kay, C.D., Cottrell, T., Holub, B.J., 2002. Absorption of anthocyanins from blueberries and serum antioxidant status in human subjects. J. Agric. Food Chem. 50, 7731–7737.
24 Barros, D et al, 2006. Behavioral and genoprotective effects of Vaccinium berries intake in mice. Pharmacol. Biochem. Behav. 84, 229–234.
25 Lamport, D.J., et al, 2012. The effects of flavonoid and other polyphenol consumption on cognitive per¬formance: a systematic research review of human studies. Nutr. Aging. 1, 5–25.
26 Devore EE, Kang JH, Breteler M, Grodstein F. Dietary intakes of berries and flavonoids in relation to cognitive decline. Annals of neurology. 2012 Jul 1;72(1):135-43.
27 Krikorian, et al, 2010. Blueberry supplementa¬tion improves memory in older adults. J. Agric. Food Chem. 58, 3996–4000.
28 Small, B., et al., 2013. Nutraceutical intervention improves older adults’ cognitive functioning. Rejuve¬nation. Res. In press.
29 Whyte AR, Schafer G, Williams CM. Cognitive effects following acute wild blueberry supplementation in 7-to 10-year-old children. European journal of nutrition. 2016 Sep 1;55(6):2151-62.
30 Lui Y et al. Visible Light-Induced Lipid Peroxidation of Unsaturated Fatty Acids in the Retina and the Inhibitory Effects of Blueberry Polyphenols J. Agric. Food Chem. 2015, 63, 9295−9305
