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Blueberry Polyphenols Protect the Brain from the Degenerative Processes Associated with Brain Aging and Alzheimer’s Diseas

Posted Feb 03 2011 2:09am

By Ralph Sanchez, L.Ac.,CNS,D.Hom

The study of plant and fruit polyphenols, a rich source of dietary antioxidants, represents one of the most promising areas of research in the field of anti-aging, and the prevention of degenerative disorders such as Alzheimer’s disease. Recent and ongoing research indicates that polyphenols present in berries and other fruits and vegetables provide protective and supportive nourishment to critical structures (i.e. hippocampus) in the brain responsible for learning, and memory formation and retention. (1)


Polyphenols are a class of phytochemicals found in fruits and vegetables. Their inherent evolutionary role in plants served to protect against the detrimental effects of sun rays (radiation), and from harmful pests and herbivores. It is also theorized that polyphenols “play a role in the fluxes of inorganic and organic soil nutrient cycling and retention”. (2)

The most extensively researched polyphenols are flavonoids. Flavonoids constitute a large sub-class of polyphenols with considerable research demonstrating their brain protective and optimizing benefits. Flavonoid-rich foods such as red wine, tea, blueberries and chocolate, are gathering increasing interest and study for their neuroprotective benefits, including neutralizing the effects of neurotoxins on the brain, suppressing inflammation, and boosting memory and cognition. (3)

A subset of flavonoids termed anthocyanins has been found to have significant research associated with benefits in brain health, and to hippocampal function in particular. Anthocyanins, found in brightly colored fruits such as berries and other foods, provide antioxidant/anti-inflammatory mediated benefits, enhance cell signaling dynamics and neuronal communication, improves plasticity, * and support neurogenesis in hippocampal tissue. (4) ( Please read: Brain-Derived Neurotrophic Factor – Growth Factor Demonstrates Promise in the Protection Against Alzheimer’s Disease Progression ). In a nutshell, blueberries protect your brain cells, optimize the communication dynamics between neurons, and promote the generation of new brain cells (neurons).

Blue Blueberries-Horizontal

The role of flavonoids as neuroprotective and neurogenic compounds, is an area of intense interest, and promises to be one of the most fruitful fields of investigation in the quest for strategies for the prevention of age related decline and neurodegenerative diseases.

The Research

Perhaps the first study that brought to bear the significance of fruit and vegetable polyphenols in the prevention of Alzheimer’s disease was the Kame Project-a collaborative effort by of Washington, and thy Japanese American community in Seattle WA. In this population-based study, 1836 participants that were dementia-free at the start of the study (1992-1994) were interviewed for their dietary habits and followed through the year 2001.

The study found a 76% lower risk for developing Alzheimer’s disease in the study group who drank fruit and vegetable juices at least 3 times in a week, versus the group who drank less than once per week. Individuals who drank juices 1 to 2 times per week had a 16% lower risk. (5)

In a more recent study, various dietary supplements consisting of vegetable and fruit extracts with equal ORAC values were tested for their effect on age-related changes to cognitive and motor performance in rats. Diets rich in polyphenol containing extracts such as spinach, strawberries and blueberries were all effective in reversing decline in cognitive behavior, while only a diet rich in blueberries was effective in improving motor functions such as balance and coordination. Moreover, cognitive and neuronal functions were sensitive to greater variety of diets, while only diets of blueberry, strawberry and Concord grape extract resulted in reversing the decline of age related motor defects. (4)

The researchers noted that the foods with equivalent ORAC scores used in the study were not equally effective in retarding the senescence related changes in the brain. This has led scientists to believe that the polyphenols in the dietary supplements may have distinct actions on varying regions of the brain, and a wider scope of action apart from preventing oxidative stress ** and inflammation (see section on microglia below). (4)

Note that the antioxidant activity of a substance is measured in terms of the oxygen radical absorbance capacity assay (ORAC). The higher the ORAC value, the more potent the antioxidant is believed to be. However, scientists now caution against the use of ORAC value as a predictor of antioxidant mediated potency, as the activity of a dietary supplement in a test tube may be very different from its functional benefit inside the body. (4)

Blueberries, Microglia & beta-Amyloid

While polyphenols in certain foods inherently provide antioxidative and anti-inflammatory benefits to vital structures in the brain responsible for memory and learning, recent evidence reveals that they also interact with the brain’s microglial cells-a class of innate immune cells.

Microglia are considered to act as the first and main immune defense in the central nervous system. In the early stages of AD, microglia fulfill a vital role in the clearance (phagocytosis) of beta-Amyloid-the toxic protein aggregates that cause oxidative stress, stimulate inflammation, and eventually form amyloid plaque (see article: Plaques and Tangles in the Alzheimer’s Brain-Which One Is Most To Blame For Alzheimer’s Disease? ). However, as immune cells and mediators of inflammatory molecules (cytokines) associated with immune system activation, microglia are also linked to the neuroinflammatory insult associated with the progression of AD.

Aging, and the neurodegenerative processes associated with AD, eventually render the microglial dysfunctional. Microglia lose their beta-amyloid clearing ability, but their production of proinflammatory cytokines continues. This scenario is theorized to be a component central to the inflammatory driven accumulation of beta-Amyloid aggregates, and the ensuing formation of amyloid plaque. (5) Enter polyphenols…polyphenol interactions with microglia appear to both support microglial clean up of beta-Amyloid, and inhibit their very formation.

Researchers at Tufts University Human Nutrition Research Center on Aging (Massachusetts, USA) have found that polyphenol antioxidants present in berries help microglia to scavenge beta-Amyloid. (6) Similar research demonstrates the suppression of microglial-mediated inflammation, and the inhibition of beta-Amyloid aggregation by blueberries. (7) Polyphenols present in other foods provide similar protective benefits.

In animal studies, the polyphenol stilbene found in Resveratrol, also inhibits the aggregation of beta-Amyloid. (8) Grape Seed extract reduces microglial-mediated inflammation, and the deposition of amyloid and neufribrillary tangles. (9, 10) Polyphenols in green tea (EGCg) suppress the formation of beta-Amyloid, and inhibits the beta-Amyloid induced cell death of neurons. (11) Curcumin inhibits the accumulation of beta-Amyloid, binds and reduces amyloid plaque, and buffers its toxicity. (12)

Neuronutrition is a burgeoning field of fertile strategies within the landscape of Alzheimer’s disease prevention. A brain friendly diet loaded with polyphenolic compounds from a variety of foods not only modify inflammatory and oxidative stress induced damage to the brain, they improve neuronal communication, stimulate regeneration (neurogenesis) and strengthen existing neuronal connections (synaptic plasticity). The science dictates that both dietary and supplemental intake of polyphenol rich foods and nutraceuticals, must be a center point to any dementia and Alzheimer’s disease prevention or care program.

* Brain plasticity refers to the brain’s malleability-its capacity for adaptive change.
** Oxidative Stress: Oxidative stress is a physiological condition whereby there is an imbalance between protective antioxidants and oxidative free radicals and other oxidants. The “oxidative balance” between antioxidants and the free radicals and oxidants that they quench, is a key element in optimizing health and buffering against the aging process, and the degenerative diseases associated with it.


1. Impact of diet on adult hippocampal neurogenesis.
Stangl D and Thuret S.
Genes Nutr (2009) 4:271–282.

2. The role of polyphenols in terrestrial ecosystem nutrient cycling Stephan Hättenschwiler and Peter M.Vitousek.
Trends in Ecology & Evolution, Volume 15, Issue 6, 238-243, 1 June 2000

3. The neuroprotective potential of flavonoids: a multiplicity of effects
Vauzour D, Vafeiadou K. Rodriguez-Mateos A. Spencer J.
Genes Nutr. 2008 December; 3(3-4): 115-126

4. Berry Fruit Supplementation and the Aging Brain.
Shukitt-Hale B, Lau FC and Joseph JA.
J Agric Food Chem. 2008 Feb 13;56(3):636-41.

5. Fruit and vegetable juices and Alzheimer’s disease: the Kame Project. Dai Q, Borenstein AR, Wu Y, Jackson JC, Larson EB.
Am J Med. 2006 September; 119(9): 751–759.

6. Microglial Dysfunction and Defective β-Amyloid Clearance Pathways in Aging Alzheimer’s Disease
Suzanne E. Hickman, Elizabeth K. Allison, and Joseph El Khoury.
The Journal of Neuroscience, August 13, 2008,28(33):8354-83

7. Berry extracts and brain aging: Clearance of toxic protein accumulation in brain via induction of autophagy.
Shibu M Poulose, Donna F Bielinski, Barbara Shukitt-Hale, Derek R Fisher,  James A. Joseph.
(Abstract #60), presented at The 240th American Chemical Society National Meeting & Exposition, August 23, 2010.

8. Blueberry Opposes β-Amyloid Peptide-Induced Microglial Activation Via   of  p44/42 Mitogen-Activation Protein Kinase
Yuyan Zhu, Paula C. Bickford, Paul Sanberg, Brian Giunta, Jun Tan.
Rejuvenation Research. October 2008, 11(5): 891-901.

9. Inhibitory activity of stilbenes on Alzheimer’s beta-amyloid fibrils in vitro.
Rivière C, Richard T, Quentin L, Krisa S, Mérillon JM, Monti JP.
Bioorg Med Chem. 2007 Jan 15;15(2):1160-7. Epub 2006 Oct 1.

10. Consumption of Grape Seed Extract Prevents Amyloid-β Deposition and Attenuates Inflammation in Brain of an Alzheimer’s Disease Mouse
Yan-Jiang Wang, Philip Thomas, Jin-Hua Zhong, Fang-Fang Bi, Shantha Kosaraju, Anthony Pollard, Michael Fenech and Xin-Fu Zhou
Neurotoxicity Research. Volume 15, Number 1, 3-14,

11. Grape derived polyphenols attenuate tau neuropathology in a mouse model of Alzheimer’s disease.
Wang J, Santa-Maria I, Ho L, Ksiezak-Reding H, Ono K, Teplow DB, Pasinetti GM.
J Alzheimers Dis. 2010;22(2):653-61.

12. Green tea (-)-epigallocatechin-3-gallate inhibits beta-amyloid-induced cognitive dysfunction through modification of secretase activity via inhibition of ERK and NF-kappaB pathways in mice.
Lee JW, Lee YK, Ban JO, Ha TY, Yun YP, Han SB, Oh KW, Hong JT. J Nutr. 2009 Oct;139(10):1987-93. Epub 2009 Aug 5.

13. Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo.
Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, Chen PP, Kayed R, Glabe CG, Frautschy SA, Cole GM.
J Biol Chem. 2005 Feb 18;280(7):5892-901. Epub 2004 Dec 7.

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