Life Extension Magazine August 2014
How Green Tea Protects Against Alzheimer’s Disease
By Michael Downey
Live Images Reveal Immediate Memory Enhancement
Data about the consumption of black, oolong, or green tea and cognitive function was obtained and examined for over 1,000 Japanese subjects age 70 or over during a period of four months. Analysis of the data revealed that consumption of 2 or more cups per day of green tea reduced the odds of cognitive impairment by 54%, whereas those that consumed equal amounts of black or oolong tea had an odds reduction of only 13%.20
However, this was a cross-sectional study that did not provide hard scientific evidence of effectiveness. To achieve more definitive results, scientists use double-blind, placebo-controlled studies. Unfortunately, it is extremely difficult to conduct intervention studies that would continually monitor human volunteers for adherence and allow for the time required to sufficiently establish, through memory tests, whether green tea enhances memory and recall.
But in a recent study published in the European Journal of Clinical Nutrition, scientists performed the first neuroimaging study allowing them to see the real-time effects of green tea extract inside the human brain’s working-memory area!19
On four separate occasions, with a one-week interval between sessions, healthy volunteers between 21 and 28 years old consumed either a placebo drink, a 250 mL, or a 500 mL combination drink containing green tea extract. The researchers used a feeding tube to rule out taste as a factor.
After consuming the drink, the subjects then performed a memory-stimulating task while researchers simultaneously monitored their brain function using functional magnetic resonance imaging, or fMRI, to zero-in on the working-memory region.
Thanks to this imaging technique, rather than relying on possibly imperceptible differences in performance on a brief memory test following a single dose or even a week of supplementation—scientists could watch the volunteers’ working memories in action on a second-by-second basis.
Compared to placebo, the beverages containing green tea extract significantly boosted activity in the dorsolateral prefrontal cortex—the area of the brain used for working-memory processing.19,59 This small region allows the brain to simultaneously store and process information, and it facilitates complex cognitive tasks, such as language comprehension, reasoning, and learning.
Activity in this memory area was increased even further by the higher dose drink.19 This dose-related response backs up the cause-and-effect connection between green tea and improved memory processing.
Not only did this finding confirm green tea extract’s immediate and significant enhancement of working-memory activity, the researchers noted that it also established for the first time the effectiveness of neuroimaging in observing green tea’s instant impact on the human brain.19
Taken together, all of these findings indicate green tea extract’s marked protection of brain neurons by inhibiting the formation of amyloid-beta fibrils and other processes associated with Alzheimer’s disease and, possibly, by triggering the production of new brain neurons.
Amyloid-beta plaques slowly form in the brain and interfere with nerve cells, often killing them. The tragic result too often is Alzheimer’s disease—the sixth leading cause of American deaths.
Accumulating evidence demonstrates that green tea extract may reduce the risk of Alzheimer’s disease and other forms of cognitive decline by 54%.
Studies show that the powerful green tea compound EGCG prevents formation of amyloid plaques, breaks down existing amyloid plaques,and promotes production of new neurons in the adult hippocampus.
In an exciting development, scientists used MRI scanning for the first time in a human clinical setting to watch the immediate boost in working-memory activity that green tea extract produces—illustrating in real-time the potent neuroprotection of green tea compounds.
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.
- Lin JK, Lin-Shiau SY. Mechanisms of hypolipidemic and anti-obesity effects of tea and tea polyphenols. Mol Nutr Food Res. 2006 Feb; 50(2):211-7.
- Riemersma RA, Rice-Evans CA, Tyrrell RM, Clifford MN, Lean ME. Tea flavonoids and cardiovascular health. QJM. 2001 May; 94(5):277-82.
- Kuriyama S, Shimazu T, Ohmori K, et al. Green tea consumption and mortality due to cardiovascular disease, cancer, and all causes in Japan: the Ohsaki study. JAMA. 2006 Sep 13; 296(10):1255-65.
- Wu LY, Juan CC, Hwang LS, Hsu YP, Ho PH, Ho LT. Green tea supplementation ameliorates insulin resistance and increases glucose transporter IV content in a fructose-fed rat model. Eur J Nutr. 2004 Apr; 43(2):116-24.
- Wolfram S, Wang Y, Thielecke F. Anti-obesity effects of green tea: from bedside to bench. Mol Nutr Food Res. 2006 Feb; 50(2):176-87.
- Dulloo AG, Duret C, Rohrer D, et al. Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. Am J Clin Nutr. 1999 Dec; 70(6):1040-5.
- Chantre P, Lairon D. Recent findings of green tea extract AR25 (Exolise) and its activity for the treatment of obesity. Phytomedicine. 2002 Jan; 9(1):3-8.
- Hsu S, Dickinson D. A new approach to managing oral manifestations of Sjogren’s syndrome and skin manifestations of lupus. J Biochem Mol Biol. 2006 May 31; 39(3):229-39.
- Hsu S, Dickinson DP, Qin H, et al. Inhibition of autoantigen expression by (-)-epigallocatechin-3-gallate (the major constituent of green tea) in normal human cells. J Pharmacol Exp Ther. 2005 Nov; 315(2):805-11.
- Siddiqui IA, Shukla Y, Adhami VM, et al. Suppression of NFkappaB and its regulated gene products by oral administration of green tea polyphenols in an autochthonous mouse prostate cancer model. Pharm Res. 2008 Sep; 25(9):2135-42.
- Amin AR, Khuri FR, Chen ZG, Shin DM. Synergistic growth inhibition of squamous cell carcinoma of the head and neck by erlotinib and epigallocatechin-3-gallate: the role of p53-dependent inhibition of nuclear factor-kappaB. Cancer Prev Res (Phila). 2009 Jun; 2(6):538-45.
- Nihal M, Ahsan H, Siddiqui IA, Mukhtar H, Ahmad N, Wood GS. (-)-Epigallocatechin-3-gallate (EGCG) sensitizes melanoma cells to interferon induced growth inhibition in a mouse model of human melanoma. Cell Cycle. 2009 Jul 1; 8(13):2057-63.
- Sen T, Moulik S, Dutta A, et al. Multifunctional effect of epigallocatechin-3-gallate (EGCG) in downregulation of gelatinase-A (MMP-2) in human breast cancer cell line MCF-7. Life Sci. 2009 Feb 13; 84(7-8):194-204.
- Roy P, Nigam N, Singh M, et al. Tea polyphenols inhibit cyclooxygenase-2 expression and block activation of nuclear factor-kappa B and Akt in diethylnitrosoamine induced lung tumors in Swiss mice. Invest New Drugs. 2010 Aug; 28(4):466-71.
- Hyung SJ, DeToma AS, Brender JR, et al. Insights into antiamyloidogenic properties of the green tea extract (-)-epigallocatechin-3-gallate toward metal-associated amyloid-beta species. Proc Natl Acad Sci USA. 2013 Mar 5; 110(10):3743-8.
- Rushworth JV, Griffiths HH, Watt NT, Hooper NM. Prion protein-mediated toxicity of amyloid-beta oligomers requires lipid rafts and the transmembrane LRP1. J Biol Chem. 2013 Mar 29; 288(13):8935-51.
- Wang Y, Li M, Xu X, Song M, Tao H, Bai Y. Green tea epigallocatechin-3-gallate (EGCG) promotes neural progenitor cell proliferation and sonic hedgehog pathway activation during adult hippocampal neurogenesis. Mol Nutr Food Res. 2012 Aug;56(8):1292-303.
- Tomata Y, Kakizaki M, Nakaya N, et al. Green tea consumption and the risk of incident functional disability in elderly Japanese: the Ohsaki Cohort 2006 Study. Am J Clin Nutr. 2012 Mar; 95(3):732-9.
- Borgwardt S, Hammann F, Scheffler K, Kreuter M, Drewe J, Beglinger C. Neural effects of green tea extract on dorsolateral prefrontal cortex. Eur J Clin Nutr. 2012 Nov;66(11):1187-92.
- Kuriyama S, Hozawa A, Ohmori K, Shimazu T, Matsui T, Ebihara S, Awata S, Nagatomi R, Arai H, Tsuji I. Green tea consumption and cognitive function: a cross-sectional study from the Tsurugaya Project 1. Am J Clin Nutr. 2006 Feb;83(2):355-61.
- Available at: http://www.alz.org/alzheimers_disease_facts_and_figures.asp. Accessed May 23, 2014.
- Available at: http://www.alz.co.uk/research/world-report-2013. Alzheimer’s Disease International. World Alzheimer Report 2013. Journey of Caring: An analysis of long-term care for dementia. Accessed May 23, 2014.
- Available at: http://www.medicaldaily.com/dementia-cases-triple-2050-how-medical-advancements-boost-risk-demographics-developing-countries . Accessed May 23, 2014.
- Ho L, Sharma N, Blackman L, Festa E, Reddy G, Pasinetti GM. From proteomics to biomarker discovery in Alzheimer’s disease. Brain Res Brain Res Rev . 2005 Apr;48(2):360-9.
- Hardy J, Allsop D. Amyloid deposition as the central event in the aetiology of Alzheimer’s Disease. Trends Pharmacol Sci. 1991;12(10):383-88.
- Ibegbu AO, McBean D, Fyfe L, Mullaney I. Morphological changes induced by opioid receptor agonist treatment of B50 neuronal cells cultured in hypoxia. Journal of Morphological Sciences.2013; 30(4), 219-227.
- Ferris SH, Farlow M. Language impairment in Alzheimer’s disease and benefits of acetylcholinesterase inhibitors. Clin Interv Aging. 2013;8:1007-14.
- Zidan M, Arcoverde C, Bom de Araujo N, Vasques P, Rios A, Laks J, Deslandes A. Motor and functional changes in different stages of Alzheimer’s disease. Rev Psiq Clín. 2012;39(5):161-5
- Cotman CW, Su JH. Mechanisms of neuronal death in Alzheimer’s disease. Brain Pathol. 1996 Oct;6(4):493-506.
- Lemkul JA, Bevan DR. Assessing the stability of Alzheimer’s amyloid protofibrils using molecular dynamics. J Phys Chem B. 2010 Feb 4;114(4):1652-60.
- Citron M. Alzheimer’s disease: strategies for disease modification. Nat Rev Drug Discov. 2010 May 9:387-98.
- Available at: http://www.alz.org/research/science/alzheimers_disease_treatments.asp. Accessed May 23, 2014.
- Casey DA, Antimisiaris D, O’Brien J. Drugs for Alzheimer’s disease: Are they effective? P&T. 2010;35(4):208-11.
- Rezai-Zadeh K, Shytle D, Sun N, Mori T, Hou H, Jeanniton D, Ehrhart J, Townsend K, Zeng J, Morgan D, Hardy J, Town T, Tan J. Green tea epigallocatechin-3-gallate (EGCG) modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice. J Neurosci. 2005 Sep 21;25(38):8807-14.
- Preston AR, Shohamy D, Tamminga CA, Wagner AD. Hippocampal function, declarative memory, and schizophrenia: anatomic and functional neuroimaging considerations. Curr Neuro Neurosci Rep. 2005;5:249–56.
- Commenges D, Scotet V, Renaud S, Jacqmin-Gadda H, Barberger-Gateau P, Dartigues JF. Intake of flavonoids and risk of dementia. Eur J Epidemiol. 2000;16:357-63.
- Kakuda T. Neuroprotective effects of the green tea components theanine and catechins. Biol Pharm Bull. 2002 Dec;25(12):1513-8.
- Chen WQ, Zhao XL, Wang DL, et al. Effects of epigallocatechin-3-gallate on behavioral impairments induced by psychological stress in rats. Exp Biol Med (Maywood). 2010;12(5):577-83.
- Lee SY, Kim CY, Lee JJ, et al. Effects of delayed administration of (-)-epigallocatechin gallate, a green tea polyphenol on the changes in polyamine levels and neuronal damage after transient forebrain ischemia in gerbils. Brain Res Bull 2003;61:399-406.
- Suganuma M, Okabe S, Oniyama M, Tada Y, Ito H, Fujiki H. Wide distribution of [3H](-)-epigallocatechin gallate, a cancer preventive tea polyphenol, in mouse tissue. Carcinogenesis. 1998;19:1771-6.
- Bastianetto S, Yao ZX, Papadopoulos V, Quirion R. Neuroprotective effects of green and black teas and their catechin gallate esters against beta-amyloid-induced toxicity. Eur J Neurosci. 2006;23:55-64.
- Mandel SA, Avramovich-Tirosh Y, Reznichenko L, et al. Multifunctional activities of green tea catechins in neuroprotection. Modulation of cell survival genes, iron-dependent oxidative stress and PKC signaling pathway. Neurosignals. 2005;14:46-60.
- Weinreb O, Mandel S, Amit T, Youdim MB. Neurological mechanisms of green tea polyphenols in Alzheimer’s and Parkinson’s diseases. J Nutr Biochem. 2004 Sep;15(9):506-16.
- Khan SG, Katiyar SK, Agarwal R, Mukhtar H. Enhancement of antioxidant and phase II enzymes by oral feeding of green tea polyphenols in drinking water to SKH-1 hairless mice: possible role in cancer chemoprevention. Cancer Res. 1992;52:4050-2.
- Chou FP, Chu YC, Hsu JD, et al. Specific induction of glutathione S-transferase GSTM2 subunit expression by epigallocatechin gallate in rat liver. Biochem Pharmacol. 2000;60:643-50.
- Luo H, Tang L, Tang M, et al. Phase IIa chemoprevention trial of green tea polyphenols in high-risk individuals of liver cancer: modulation of urinary excretion of green tea polyphenols and 8-hydroxydeoxyguanosine. Carcinogenesis. 2006;27:262-8.
- Selkoe DJ. Review Toward a comprehensive theory for Alzheimer’s disease. Hypothesis: Alzheimer’s disease is caused by the cerebral accumulation and cytotoxicity of amyloid beta-protein. Ann N Y Acad Sci. 2000; 924:17-25.
- Tougu V, Karafin A, Palumaa P. Binding of zinc(II) and copper(II) to the full-length Alzheimer’s amyloid-beta peptide. J. Neurochem. 2008, 104, 1249–59.
- Faller, P. Copper and zinc binding to amyloid-beta: coordination, dynamics, aggregation, reactivity and metal-ion transfer. Chembiochem. 2009 Dec 14;10(18):2837-45.
- Bieschke J, Russ J, Friedrich RP, Ehrnhoefer DE, Wobst H, Neugebauer K. EGCG remodels mature alpha-synuclein and amyloid-beta fibrils and reduces cellular toxicity. Proc Natl Acad Sci. 2010; USA 107:7710–15
- Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, Brett FM, et al. Amyloid-β protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory. Nature Med.2008;14:837–42.
- Chin J. Selecting a mouse model of Alzheimer’s disease. Methods Mol Biol. 2011;670:169-89.
- He M, Zhao L, Wei MJ, Yao WF, Zhao HS, Chen FJ. Neuroprotective effects of (-)-epigallocatechin-3-gallate on aging mice induced by D-galactose. Biol Pharm Bull. 2009 Jan;32(1):55-60.
- Cui X, Zuo P, Zhang Q, et al. Chronic systemic D-galactose exposure induces memory loss, neurodegeneration, and oxidative damage in mice: protective effects of R-alpha-lipoic acid. J Neuroscience Res. 2006;84(3):647-54.
- Liu M, Chen F, Sha L, et al. (-)-Epigallocatechin-3-Gallate ameliorates learning and memory deficits by adjusting the balance of TrkA/p75NTR signaling in APP/PS1 transgenic mice. Mol Neurobiol. Epub 2013 Dec 20.
- Dong Z, Gong B, Li H, Bai Y, Wu X, Huang Y, He W, Li T, Wang YT. Mechanisms of hippocampal long-term depression are required for memory enhancement by novelty exploration. J Neurosci. 2012 Aug 29;32(35):11980-90.
- Jin K, Peel AL, Mao XO, Xie L, Cottrell BA, Henshall DC, Greenberg DA. Increased hippocampal neurogenesis in Alzheimer’s disease. Proc. Natl. Acad. Sci.2004;101:343–47.
- Reubinoff BE, Itsykson P, Turetsky T, Pera MF, Reinhartz E, Itzik A, Ben-Hur T. Neural progenitors from human embryonic stem cells. Nat Biotechnol . 2001 Dec;19(12):1134-40.
- Barr MS, Farzan F, Rajji TK, Voineskos AN, Blumberger DM, Arenovich T, Fitzgerald PB, Daskalakis ZJ. Can repetitive magnetic stimulation improve cognition in schizophrenia? Pilot data from a randomized controlled trial. Biol Psychiatry. 2013 Mar 15;73(6):510-7.
- Sutherland BA, Rahman RMA, Appleton I. Mechanisms of action of green tea catechins, with a focus on ischemia-induced neurodegeneration. The Journal of Nutritional Biochemistry.2006;17, 291–306.
- Rahman I, Biswas SK, Kirkham PA. Regulation of inflammation and redox signaling by dietary polyphenols. Biochem Pharmacol. 2006 Nov 30;72(11):1439-52.
- Curin Y, Andriantsitohaina R. Polyphenols as potential therapeutical agents against cardiovascular diseases. Pharmacol Rep. 2005;57 Suppl:97-107.
- Meeran SM, Mantena SK, Elmets CA, Katiyar SK. (-)-Epigallocatechin-3-gallate prevents photocarcinogenesis in mice through interleukin-12-dependent DNA repair. Cancer Res. 2006 May 15;66(10):5512-20.
- Yang CS, Wang X. Green tea and cancer prevention. Nutr Cancer. 2010;62(7):931-7.
- Frank B, Gupta S. A review of antioxidants and Alzheimer’s disease. Ann Clin Psychiatry. 2005 Oct;17(4):269-86.
- Levites Y, Amit T, Youdim MB, Mandel S. Involvement of protein kinase C activation and cell survival/cell cycle genes in green tea polyphenol (-)-epigallocatechin 3-gallate neuroprotective action. J Biol Chem. 2002;277:30574-80.
- Sinha S, Du Z, Maiti P, et al. Comparison of three amyloid assembly inhibitors: the sugar scyllo-inositol, the polyphenol epigallocatechin gallate, and the molecular tweezer CLR01. ACS Chem Neurosci. 2012 Jun 20;3(6):451-8.
- Bieschke J. Natural compounds may open new routes to treatment of amyloid diseases. Neurotherapeutics. 2013 Jul;10(3):429-39.
- Okello EJ, McDougall GJ, Kumar S, Seal CJ. In vitro protective effects of colon-available extract of Camellia sinensis (tea) against hydrogen peroxide and beta-amyloid (Aβ (1-42)) induced cytotoxicity in differentiated PC12 cells. Phytomedicine. 2011 Jun 15;18(8-9):691-6.
- Choi YT, Jung CH, Lee SR, et al. The green tea polyphenol (-)-epigallocatechin gallate attenuates beta-amyloid-induced neurotoxicity in cultured hippocampal neurons. Life Sci. 2001 Dec 21; 70(5):603-14.
- Bastianetto S, Brouillette J, Quirion R. Neuroprotective effects of natural products: interaction with intracellular kinases, amyloid peptides and a possible role for transthyretin. Neurochem Res. 2007 Oct;32(10):1720-5.
- Haque AM, Hashimoto M, Katakura M, Hara Y, Shido O. Green tea catechins prevent cognitive deficits caused by Abeta1-40 in rats. J Nutr Biochem. 2008 Sep; 19(9):619-26.
- Dragicevic N, Smith A, Lin X, et al. Green tea epigallocatechin-3-gallate (EGCG) and other flavonoids reduce Alzheimer’s amyloid-induced mitochondrial dysfunction. J Alzheimers Dis. 2011;26(3):507-21.
- He Y, Cui J, Lee JC, et al. Prolonged exposure of cortical neurons to oligomeric amyloid-beta impairs NMDA receptor function via NADPH oxidase-mediated ROS production: protective effect of green tea (-)-epigallocatechin-3-gallate. ASN Neuro. 2011;3(1):e00050.