Protection from Inflammation/Oxidative Stress

Maintain Your Brain: Take a multifaceted approach to protect your brain from degenerative diseases like Alzheimer’s

A mind is a terrible thing to waste. These words have never rung more true than when it comes to Alzheimer’s disease. One of the most debilitating degenerative diseases of our time, Alzheimer’s robs a person of his or her mind, destroying brain cells and leading to extreme memory loss and behavior problems. As many as 5.3 million Americans are living with Alzheimer’s and it is predicted that healthcare costs for the disease will exceed one trillion dollars by 2050.[1]  However, researchers calculate that delaying Alzheimer’s disease onset by one or two years could significantly decrease the disease burden by 2050 by 9.5 million or 23 million cases, respectively.[2] With this sort of information in mind, much research is shifting from finding a cure to prevention and searching for ways to delay onset and slow progression.

Alzheimer’s is a neurological disease in which brain nerve cells (neurons) deteriorate and die. Researchers have found two abnormal structures–plaques and tangles–that are the prime suspects in damaging and killing brain cells in Alzheimer’s. Plaques build up between nerve cells and contain deposits of a protein called beta amyloid. Tangles are twisted fibers of another protein called tau proteins. The plaques and tangles tend to form in a predictable pattern, beginning in areas important in learning and memory and then spreading to other regions.[3]

It is believed that long-term oxidative stress and inflammation may be factors in the development of Alzheimer’s; therefore, much of the current research is investigating how diet and particular nutrients like antioxidants and essential fatty acids (EFAs) may play a role in protecting the brain from oxidative damage, inflammation, and amyloid plaque.

Lifestyle habits, including diet and exercise, may have a profound affect in protecting the brain from Alzheimer’s. A study conducted at the Columbia University Medical Center in NYC and published last summer in the Journal of the American Medical Association, found that those subjects who consumed the most foods found in the Mediterranean diet–vegetables, fruit, fish, olive oil, nuts, and legumes–and who were physically active, had a lower risk of developing the disease.[4]

The Mediterranean diet combines several foods and nutrients that are potentially neuroprotective, including fish, monounsaturated fatty acids, vitamins B12 and folate, and antioxidants (vitamin E, carotenoids, flavonoids).

It is known that certain phytonutrients protect cells (including brain cells) from oxidative damage and inflammation; some of them also seem to protect the brain from the buildup of the amyloid plaques associated with Alzheimer’s. Curcumin, epigallocatechin (EGCG), and resveratrol, phytonutrients that are known to have potent antioxidant and anti-inflammatory properties, are a few that have been researched.

Curcumin

It is well known that curcumin exhibits significant antioxidant and anti-inflammatory properties, and now, a number of in-vitro and animal models of Alzheimer’s disease studies have indicated that curcumin has a direct effect in decreasing amyloid plaque buildup, helping to break it apart[5] and possibly preventing it from forming in the first place.[6] [7] [8] [9] Research published in Food and Chemical Toxicology found that curcumin also protected cells from damage from amyloid plaques by decreasing oxidative and DNA damage to the brain cells.[10] Human clinical trials are currently underway, but population studies have shown that populations who consume a large amount of curcumin (in the form of turmeric) have a significantly lower risk of developing Alzheimer’s compared to those populations who consume little to no curcumin.[11] [12]

Green tea

Another phytonutrient showing promise in Alzheimer’s research is epigallocatechin (EGCG), found in green tea. A 2005 paper reported that the EGCG in green tea reduced amyloid plaque formation in Alzheimer mice.[13] Later, in 2008, the same researchers reported that they gave mice that were engineered to develop Alzheimer’s disease green tea extracts in water for six months. Drinking their daily green tea halved the amyloid plaque deposited in the brains of the mice.[14] That same year, a team of German researchers found that EGCG appears to change potentially harmful amyloid proteins into proteins that are nontoxic to brain cells.[15] A 2009 study found that EGCG reduced amyloid-induced memory dysfunction, and actually enhanced memory function, as well as reducing amyloid plaque levels and inhibiting amyloid-induced neuron cell death in the brain.[16]

Resveratrol

Several epidemiological studies indicate that moderate consumption of red wine is associated with a lower incidence of dementia and Alzheimer’s disease. Red wine is a source of resveratrol, an antioxidant with potential neuroprotective effects. A number of studies have indicated that like curcumin and EGCG, resveratrol also promotes the break down of amyloid plaque.[17] [18] [19] [20] Additionally, a Chinese study indicated that resveratrol could improve cognitive ability in Alzheimer mice.[21]

Other nutrients

In addition to the protective antioxidant phytonutrients mentioned above, other nutrients are gaining support for use in protecting the brain from Alzheimer’s disease. In a small human study of nine Alzheimer’s patients, vitamin D, in combination with curcumin, was shown to strongly stimulate the uptake and absorption of amyloid beta by macrophages in a majority of patients. Macrophages act as the immune system’s clean-up crew, traveling through the brain and body, mopping up waste products, including amyloid plaque.[22]

Another powerful antioxidant, alpha lipoic acid (ALA), has been shown to have a variety of properties that can interfere with the development or progression of Alzheimer’s disease, including down regulating the expression of pro-inflammatory proteins and increasing production of acetylcholine, an important neurotransmitter; a deficiency of acetylcholine has been linked to the development of Alzheimer’s.[23] Researchers say that “data from cell culture and animal models suggest that ALA could be combined with curcumin, EGCG, and DHA from fish oil to synergistically decrease oxidative stress, inflammation, amyloid levels and amyloid plaque load associated with Alzheimer’s disease.” [24]

Epidemiological studies suggest that increased intake of the omega-3 fatty acids found in fish oil, particularly DHA, is associated with a reduced risk of developing Alzheimer’s. It is believed that DHA suppresses neuro-inflammation and oxidative damage that contribute to neuronal dysfunction.[25] DHA also appears to slow the development of Alzheimer’s by reducing amyloid plaque buildup. A mouse model showed that a DHA-enriched diet significantly reduced overall plaque burden by 40.3 percent. The researchers concluded that “the results suggest that dietary DHA could be protective against beta amyloid production, accumulation, and potential downstream toxicity.”[26] In addition to having its own neuro-protective effects, fish oil has also been shown to enhance bioavailability of other protective phytonutrients, including EGCG and curcumin, while also working synergistically with these antioxidants to inhibit amyloid deposits.[27] [28]

A multifaceted approach

Alzheimer’s is a complex disease, and it is important to note that there is no magic bullet to prevent or cure it. Additionally, researchers have found that the disease is often already far progressed before any noticeable symptoms appear, which makes it difficult to treat. It is also important to note that much of the research has been done in vitro and on animal models, though a few human clinical trials are currently underway. However, we do know that like in most degenerative diseases, chronic inflammation and oxidative damage play a role. We also know that there is a number of phytonutrients and other nutrients that work together to protect the health of the brain by reducing inflammation, oxidative stress, and amyloid plaque buildup. Lifestyle habits, including diet and exercise, also play an important role in the prevention of developing a disease like Alzheimer’s. Take a multifaceted approach in maintaining the health of your brain, because remember… a mind is a terrible thing to waste.


References

[1] http://alz.org/documents_custom/report_alzfactsfigures2010.pdf

[2] Roses AD, Lutz MW, Amrine-Madsen H, Saunders AM, Crenshaw DG, Sundseth SS, et al. A TOMM40 variable-length polymorphism predicts the age of late-onset Alzheimer’s disease.  Pharmacogenomics J. 2009 Dec 22.

[3] http://alz.org/alzheimers_disease_what_is_alzheimers.asp

[4] JAMA and Archives Journals (2009, August 13). Mediterranean Diet, Physical Activity Linked With Lower Risk Of Alzheimer Disease. ScienceDaily. Retrieved June 16, 2010, from http://www.sciencedaily.com­ /releases/2009/08/090811161306.htm

[5] Ono K, Hasegawa K, Naiki H, Yamada M. Curcumin has potent anti-amyloidogenic effects for Alzheimer’s beta-amyloid fibrils in vitro. J Neurosci Res. 2004 Mar 15;75(6):742-50.

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

[7] Ringman JM, Frautschy SA, Cole GM, Masterman DL, Cummings JL. A potential role of the curry spice curcumin in Alzheimer’s disease. Curr Alzheimer Res. 2005 Apr;2(2):131-6.

[8] Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci. 2001 Nov 1;21(21):8370-7.

[9] Frautschy SA, Hu W, Kim P, Miller SA, Chu T, Harris-White ME, Cole GM. Phenolic anti-inflammatory antioxidant reversal of Abeta-induced cognitive deficits and neuropathology.  Neurobiol Aging. 2001 Nov-Dec;22(6):993-1005.

[10] Park SY, Kim HS, Cho EK, Kwon BY, Phark S, Hwang KW, Sul D. Curcumin protected PC12 cells against beta-amyloid-induced toxicity through the inhibition of oxidative damage and tau hyperphosphorylation. Food Chem Toxicol. 2008 Aug;46(8):2881-7. Epub 2008 Jun 4.

[11] Chandra V, Pandav R, Dodge HH, Johnston JM, Belle SH, DeKosky ST, Ganguli M. Incidence of Alzheimer’s disease in a rural community in India: the Indo-US study.Neurology. 2001 Sep 25;57(6):985-9.

[12] Ng TP, Chiam PC, Lee T, Chua HC, Lim L, Kua EH. Am J Epidemiol. 2006 Nov 1;164(9):898-906. 26. Curry consumption and cognitive function in the elderly.

[13] 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.

[14] Rezai-Zadeh K, Arendash GW, Hou H, Fernandez F, Jensen M, Runfeldt M, Shytle RD, Tan J. Green tea epigallocatechin-3-gallate (EGCG) reduces beta-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice. Brain Res. 2008 Jun 12;1214:177-87. Epub 2008 Apr 7.

[15] Erich Wanker, Ph.D., Max Delbrueck Center for Molecular Medicine, Berlin, Germany. EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers. Nature Structural & Molecular Biology; May 30, 2008

[16] Lee JW, Lee YK, Ban JO, Ha TY, Yun YP, Han SB, Oh KW, Hong JT. 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. J Nutr. 2009 Oct;139(10):1987-93. Epub 2009 Aug 5.

[17] Marambaud, P, Zhao Haitian, Davies Peter. Resveratrol Promotes Clearance of Alzheimer’s Disease Amyloid Peptides. Journal of Biological Chemistry. 2005 Nov 11.

[18] Vingtdeux V, Giliberto L, Zhao H, Chandakkar P, Wu Q, Simon JE, Janle EM, Lobo J, Ferruzzi MG, Davies P, Marambaud P. AMP-activated protein kinase signaling activation by resveratrol modulates amyloid-beta peptide metabolism. J Biol Chem. 2010 Mar 19;285(12):9100-13. Epub 2010 Jan 14.

[19] Vingtdeux V, Dreses-Werringloer U, Zhao H, Davies P, Marambaud P. Therapeutic potential of resveratrol in Alzheimer’s disease. BMC Neurosci. 2008 Dec 3;9 Suppl 2:S6.

[20] Karuppagounder SS, Pinto JT, Xu H, Chen HL, Beal MF, Gibson GE. Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer’s disease. Neurochem Int. 2009 Feb;54(2):111-8. Epub 2008 Nov 8.

[21] Zhong Nan Da Xue Xue Bao Yi Xue Ban. Effect of resveratrol on the cognitive ability of Alzheimeros mice 2006 Aug;31(4):566-9. Department of Nutrition and Food Hygiene, School of Public Health, Central South University, Changsha 410078, China.

[22] University of California – Los Angeles (2009, July 16). Vitamin D, Curcumin May Help Clear Amyloid Plaques Found In Alzheimer’s Disease. ScienceDaily. Retrieved June 16, 2010, from http://www.sciencedaily.com­ /releases/2009/07/090715131558.htm

[23] Whitehouse, P.J. The cholinergic deficit in Alzheimer’s disease. Journal of Clinical Psychiatry. 1998; volume 59 (supplement 13): pages 19-22.

[24] Maczurek A, Hager K, Kenklies M, Sharman M, Martins R, Engel J, Carlson DA, Münch G. Lipoic acid as an anti-inflammatory and neuroprotective treatment for Alzheimer’s disease. Adv Drug Deliv Rev. 2008 Oct-Nov;60(13-14):1463-70. Epub 2008 Jul 4.

[25] Cole GM, Frautschy SA. DHA may prevent age-related dementia. J Nutr. 2010 Apr;140(4):869-74. Epub 2010 Feb 24.

[26] Lim GP, Calon F, Morihara T, Yang F, Teter B, Ubeda O, Salem N Jr, Frautschy SA, Cole GM. A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. J Neurosci. 2005 Mar 23;25(12):3032-40.

[27] Giunta B, Hou H, Zhu Y, Salemi J, Ruscin A, Shytle RD, Tan J. Fish oil enhances anti-amyloidogenic properties of green tea EGCG in Tg2576 mice. Neurosci Lett. 2010 Mar 8;471(3):134-8. Epub 2010 Jan 22.

[28] Ma QL, Yang F, Rosario ER, Ubeda OJ, Beech W, Gant DJ, Chen PP, Hudspeth B, Chen C, Zhao Y, Vinters HV, Frautschy SA, Cole GM. Beta-amyloid oligomers induce phosphorylation of tau and inactivation of insulin receptor substrate via c-Jun N-terminal kinase signaling: suppression by omega-3 fatty acids and curcumin. J Neurosci. 2009 Jul 15;29(28):9078-89.