Fall Skin Care Sale

Life Extension Magazine

LE Magazine December 2004
image
Can Curcumin Prevent Alzheimer's Disease?
By John C. Martin

The Curcumin Advantage
Even if NSAIDs are proven as effective as curcumin as a prophylaxis for Alzheimer’s disease, researchers are not heralding these anti-inflammatory drugs in the long-term struggle against Alzheimer’s. The reason for their reticence is simple: NSAIDs have potentially lethal side effects. According to the UCLA research team, “A principal limitation precluding widespread NSAID use for prevention of Alzheimer’s disease is gastrointestinal and occasional liver and kidney toxicity caused by inhibiting cyclooxygenase-1 [an enzyme that protects the stomach lining]. Side-effect issues could be overcome using alternative anti-inflammatory drugs directed against different inflammatory targets.”21

One such anti-inflammatory agent, they postulated, is curcumin, which may offer powerful protection for humans as well as mice. Curcumin’s antioxidant effects are central to its promise, as scientists have determined that the pathology of Alzheimer’s involves oxidative damage that correlates directly with the beta amyloid deposits that typically characterize the disease.22 In this vicious cycle, oxidative stress promotes the production of beta amyloid in the brain, and increasing levels of beta amyloid inflict greater levels of oxidative damage.

Mystery Waiting to Be Solved
Although curcumin shows great promise as an agent for preventing Alzheimer’s disease, many questions remain to be answered. Scientists still are not completely certain of curcumin’s mechanism of action against neuronal plaques, though they do know that it inhibits many of the body’s inflammatory mediators. In fact, studies have found that curcumin retards the action of molecules such as phospholipase, lipooxygenase, cyclooxygenase-2 (COX-2), leukotrienes, thromboxane, prostaglandins, nitric oxide, collagenase, elastase, hyalur-onidase, monocyte chemoattractant protein-1 (MCP-1), interferon-inducible protein, tumor necrosis factor, and interleukin-12.23

Recent research suggests that oxidation caused by free radicals in the brain sparks neuronal toxicity, not only in Alzheimer’s disease but possibly in other neurodegenerative disorders such as Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis.24 These disorders likewise have been associated at the molecular level with free-radical-induced mutation, oxidative enzyme impairment, and mitochondrial dysfunction.24

Some experts believe an antioxidant molecule known as glutathione plays a central role in the evolutionary events in the brain that lead to oxidation. “[Glutathione] plays multiple roles in the nervous system, including free radical scavenger, redox modulator of ionotropic receptor activity, and possible neurotransmitter,” wrote investigators from the University of British Columbia in 1997.25

Other experts have noted that brain cell abnormalities, specifically in the cells’ mitochondria, may contribute to the abnormal production of free radicals in the brain.25 Abnormal mitochondrial function leads to dysfunction of cytochrome-c oxidase, a necessary mitochondrial enzyme that in turn may contribute to the abnormal production of free radicals, thus causing levels of beta amyloid to increase. As the vicious cycle continues, beta amyloid attracts even more free radicals.

“The free radical hypothesis can account for the vastly heterogeneous nature of Alzheimer’s disease and the fact that both genetic and nongenetic causes are involved,” wrote one expert. “Such general considerations suggest that free radicals are involved in many age-related pathologies, specifically in Alzheimer’s disease and all neurodegenerative diseases.”26

The inflammation and destructive oxidation inherent in Alzheimer’s are why antioxidants like curcumin may be so effective in preventing progression of the disease. By its very nature, curcumin fends off free radicals, preventing their destructive effects in the illness’s very earliest stages. Antioxidants not only target free radicals in the brain, but also possess powerful anti-inflammatory mechanisms, another reason why curcumin may be efficacious against Alzheimer’s disease.27 These dual mechanisms of protection against inflammation and oxidative damage make curcumin a particularly promising natural agent in fighting the ravages of aging and degenerative diseases.

References

1. Graeber MB, Kosel S, Grasbon-Frodl E, Moller HJ, Mehraein P. Histopathology and APOE genotype of the first Alzheimer disease patient, Auguste D. Neurogenetics. 1998 Mar;1(3):223-8.

2. Available at: http://www.alz.org/AboutAD/Statistics.asp. Accessed September 22, 2004.

3. Brookmeyer R, Gray S, Kawas C. Projections of Alzheimer’s disease in the United States and the public health impact of delaying disease onset. Am J Pub Health. 1998;88(9):1337-42.

4. Van Erk MJ, Teuling E, Staal YCM et al. Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells. J Carcinog. 2004 May 12;3(1):8.

5. Araujo CC, Leon LL. Biological activities of Curcuma longa L. Mem Inst Oswaldo Cruz. 2001 Jul;96(5):723-8.

6. Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res. 2003 Jan-Feb;23(1A):363-98.

7. Padmaja S, Raju TN. Antioxidant effect of curcumin in selenium induced cataract of Wistar rats. Indian J Exp Biol. 2004 Jun;42(6):601-3.

8. Liu YG, Chen HC, Jiang YP. Protective effect of curcumin on experimental liver injury in mice. Zhongguo Zhong Yaho Za Zhi. 2003 Aug;28(8):756-8, 93.

9. Nirmala C, Puvanakrisnan R. Protective role of curcumin against isoproterenol induced myocardial infarction. Mol Cell Biochem. 1996 Jun 21;159(2):85-93.

10. Thiyagarajan M, Sharma SS. Neuroprotective effect of curcumin in middle cerebral artery occlusion induced focal cerebral ischemia in rats. Life Sci. 2004 Jan 9;74(8):969-85.

11. National Institute on Aging. National Institutes of Health (NIH).

12. Sambamurti K, Granholm AC, Kindy MS, et al. Cholesterol and Alzheimer’s disease: clinical and experimental models suggest interactions of different genetic, dietary and environmental risk factors. Curr Drug Targets. 2004 Aug;5(6):517-28.

13. National Institute of Neurological Disorders and Stroke. National Institutes of Health (NIH).

14. Ono K, Hasegawa K, Naiki H, Yamanda 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.

15. Ambegaokar SS, Wu L, Alamshahi K, et al. Curcumin inhibits dose-dependently and time-dependently neuroglial cell proliferation and growth. Neuro Endocrinol Lett. 2003 Dec;24(6):469-73.

16. Grundman M, Grundman M, Delaney P. Antioxidant strategies for Alzheimer’s disease. Proc Nutr Soc. 2002 May;61(2):191-202.

17. Calabrese V, Butterfield DA, Stella AM. Nutritional antioxidants and the heme oxygenase pathway of stress tolerance: novel targets for neuroprotection in Alzheimer’s disease. Ital J Biochem. 2003 Dec;52(4):177-81.

18. Frautschy SA, Hu W, Kim P, et al. Phenolic anti-inflammatory antioxidant reversal of Abeta-induced cognitive deficits and neuropathology. Neurobiol Aging. 2001 Nov;22(6):993-1005.

19. in t’Veld BA, Ruitenberg A, Hofman A, et al. Nonsteroidal antiinflammatory drugs and risk of Alzheimer’s disease. N Engl J Med. 2001 Nov 22;345(21):1515-21.

20. Etminan M, Gill S, Samii A. Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer’s disease: systematic review and meta-analysis of observational studies. BMJ. 2003 Jul 19;327(7407):128.

21. 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.

22. Smith MA, Hirai K, Hsiao K, et al. Amyloid-beta deposition in Alzheimer transgenic mice is associated with oxidative stress. J Neurochem. 1998 May;70(5):2212-5.

23. Chainani-Wu N. Safety and anti-inflammatory activity of curcumin: a component of turmeric (Curcuma longa). J Altern Complement Med. 2003 Feb;9(1):161-8.

24. Rao AV, Balachandran B. Role of oxidative stress and antioxidants in neurodegenerative diseases. Nutr Neurosci. 2002 Oct;5(5):291-309.

25. Bains JS, Shaw CA. Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death. Brain Res Brain Res Rev. 1997 Dec;25(3):335-58.

26 Christen Y. Oxidative stress and Alzheimer disease. Am J Clin Nutr. 2000 Feb;71(2):621S-9S.

27. Miquel J, Bernd A, Sempere JM, Diaz-Alperi J, Ramirez A. The curcuma antioxidants: pharmalogical effects and prospects for future clinical use. A review. Arch Gerontol Geriatr. 2002 Feb;34(1):37-46.