Curcumin Eased Alzheimer's in Animals
Curry spice aided memory and reduced a key disease marker in rats with Alzheimer’s
Curry spice aided memory and reduced a key disease marker in rats with Alzheimer’s
Alzheimer's disease is characterized by formation of a “plaque” made of inflammation-inducing proteins called beta-amyloid, which also form wiry tangles.
It remains uncertain whether amyloid plaque and tangles cause or result from the still-mysterious process that leads to Alzheimer's disease (AD).
Drugs and nutrients that inhibit inflammation, oxidation, and formation of amyloid plaque and tangles also reduce AD symptoms.
The other key characteristic of AD is the accumulation of a mishaped protein called tau. And last year, new studies in mice showed that Alzheimer's disease spreads from brain cell to brain cell, with tau acting as the carrier.
Interestingly, recent clinical trials suggested that drugs targeting "infectious" tau proteins may be more effective than drugs that target plaque- and tangle-forming beta-amyloid proteins.
No current drugs target tau proteins effectively.
Fortunately, polyphenol-type “antioxidants” from plant foods – particularly curcumin, the orange-yellow pigment in turmeric root – hold promise as anti-tau agents.
These findings may explain the encouraging results of large, long-term epidemiological studies ... such as one from 2006, which suggested that the polyphenols in colorful fruits and vegetables may reduce the risk of Alzheimer's disease fairly dramatically (see “Alzheimer's Risk Curbed by Antioxidants in Fruit and Vegetable Juice”).
Curcumin vs. Alzheimer's: The story so far
Studies show that supplemental curcumin significantly lowers levels of beta-amyloid, inflammation, and tau protein in mice with AD ... as do certain other polyphenols from plant foods, such as OPCs and resveratrol from grapes.
Back in 2005, UCLA researchers conducted a successful study of the effects of supplemental curcumin in the brain cells of rodents with AD (Yang F, 2005).
As the UCLA team wrote, “The phenolic yellow curry pigment curcumin has potent anti-inflammatory and antioxidant activities and can suppress oxidative damage, inflammation, cognitive deficits, and amyloid accumulation.”
Their results showed dietary curcumin substantially reduced formation of amyloid plaques and fibrils, and dissolved existing plaques and fibrils in AD-afflicted mice.
Those indications received subsequent support from studies in cells and animals, which also show that curcumin is far more effective against amyloid plaque, compared with anti-inflammatory drugs like aspirin and ibuprofen (Thomas P et al. 2009; Wang YJ et al. 2009; Davinelli S et al. 2012; Jayasena T et al. 2013).
This is probably because, as the UCLA team put it in 2005, “the yellow pigment in turmeric … [targets] multiple AD pathogenic [disease-causing] cascades.” (See “Turmeric Power, Part II: Curry Spice May Curb Alzheimer's”.)
Subsequent studies from the UCLA group suggested that vitamin D3 and omega-3s enhance the body's ability to remove amyloid plaque from the brain.
And they show that curcumin and vitamin D3 – both shown to help clear amyloid plaque from the brain – do that job better together than separately (see “Brain-Killing Plaque Cleared by Omega-3s, Vitamin D”).
A new animal study from China bolsters the idea that diets rich in turmeric and/or supplemental curcumin may help prevent and/or treat Alzheimer's … and possibly other tau-related degenerative brain diseases, like Parkinson's.
Curcumin eased Alzheimer's symptoms and signs in rodents
The curcumin study was led by researchers from Shandong, China, and involved rats suffering a disease similar to Alzheimer's.
They divided the animals into curcumin-supplemented and control (no curcumin) groups, and then looked for two things: Changes in the rats' spatial memory (e.g., ability to remember a maze path).
Changes in levels of a certain protein (GFAP) found in brain cells called astrocytes.
Astrocytes are the most abundant cells in the human brain, and facilitate regeneration of damaged brain cells.
The Chinese team examined changes in the genetic “expression” of a protein found in astrocytes, called GFAP (glial fibrillary acidic).
GFAP builds up in damaged, degenerating astrocytes, and rising GFAP levels in the brain's astrocytes signal the onset of Alzheimer's' disease.
In Alzheimer's patients, astrocytes located near amyloid plaques and its degenerating neurons swing into action and slow progression of the disease (Kraft AW et al. 2013).
The results show that rats fed supplemental curcumin showed improved spatial memory and lower levels of GFAP.
Numerous studies find curcumin a safe supplement, even at doses of up to 12 grams per day, though the usual doses range from one to four grams per day.
However, curcumin is not well-absorbed when extracted from turmeric ... unless it is accompanied by turmeric volatile oils ... also known as essential oils.
Accordingly, clinical studies show that the curcumin in such extracts is absorbed six to seven times better than the curcumin in conventional 95%-curcumin dietary supplements (Antony B et al. 2012).
Recent research shows that these essential oils also enhance the benefits of curcumin and provide their own ... yet other curcumin supplements rarely include any.
- Aggarwal BB, Harikumar KB. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol. 2009 Jan;41(1):40-59. Epub 2008 Jul 9. Review.
- Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm. 2007 Nov-Dec;4(6):807-18. Epub 2007 Nov 14. Review.
- Antony B, Merina B, Iyer VS, Judy N, Lennertz K, Joyal S. A pilot cross-over study to evaluate human oral bioavailability of BCM-95CG (Biocurcumax), A novel bioenhanced preparation of curcumin. Indian J Pharm Sci. 2008 Jul-Aug;70(4):445-9.
- Antony B, Merina B, Rao SB. Enhancing the absorption of curcuminoids. Spice Board of India. July 2005, 23-26.
- Antony B, Merina B. Bioavailability of Curcumax (BCM – 095™). Little Flower Medical Research Center, Angamaly, India (Research Center of Mahatma Gandhi University). September 2006. Spice Board of India.
- Bar-Sela G, Epelbaum R, Schaffer M. Curcumin as an anti-cancer agent: review of the gap between basic and clinical applications. Curr Med Chem. 2010;17(3):190-7. Review.
- Davinelli S, Sapere N, Zella D, Bracale R, Intrieri M, Scapagnini G. Pleiotropic protective effects of phytochemicals in Alzheimer's disease. Oxid Med Cell Longev. 2012;2012:386527. doi: 10.1155/2012/386527. Epub 2012 May 28. Review.
- Gupta SC, Sung B, Kim JH, Prasad S, Li S, Aggarwal BB. Multitargeting by turmeric, the golden spice: From kitchen to clinic. Mol Nutr Food Res. 2012 Aug 13. doi: 10.1002/mnfr.201100741. [Epub ahead of print]
- Hatcher H, Planalp R, Cho J, Torti FM, Torti SV. Curcumin: from ancient medicine to current clinical trials. Cell Mol Life Sci. 2008 Jun;65(11):1631-52. Review.
- Jayasena T, Poljak A, Smythe G, Braidy N, Münch G, Sachdev P. The role of polyphenols in the modulation of sirtuins and other pathways involved in Alzheimer's disease. Ageing Res Rev. 2013 Jul 5;12(4):867-883. doi: 10.1016/j.arr.2013.06.003. [Epub ahead of print]
- Jurenka JS Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern Med Rev. 2009 Jun;14(2):141-53. Review. Erratum in: Altern Med Rev. 2009 Sep;14(3):277.
- Kraft AW, Hu X, Yoon H, Yan P, Xiao Q, Wang Y, Gil SC, Brown J, Wilhelmsson U, Restivo JL, Cirrito JR, Holtzman DM, Kim J, Pekny M, Lee JM. Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice. FASEB J. 2013 Jan;27(1):187-98. doi: 10.1096/fj.12-208660. Epub 2012 Oct 4.
- Martin RC, Aiyer HS, Malik D, Li Y Effect on pro-inflammatory and antioxidant genes and bioavailable distribution of whole turmeric vs curcumin: Similar root but different effects. Food Chem Toxicol. 2012 Feb;50(2):227-31. Epub 2011 Nov 4.
- Masoumi A, Goldenson B, Ghirmai S, Avagyan H, Zaghi J, Abel K, Zheng X, Espinosa-Jeffrey A, Mahanian M, Liu PT, Hewison M, Mizwickie M, Cashman J, Fiala M. 1alpha,25-dihydroxyvitamin D3 interacts with curcuminoids to stimulate amyloid-beta clearance by macrophages of Alzheimer's disease patients. J Alzheimers Dis. 2009;17(3):703-17. doi: 10.3233/JAD-2009-1080.
- Memorial Sloan-Kettering Cancer Center - Turmeric/Curcumin Monograph. Accessed at http://www.mskcc.org/cancer-care/herb/turmeric.
- Mizwicki MT et al. 1α,25-Dihydroxyvitamin D3 and Resolvin D1 Retune the Balance between Amyloid-β Phagocytosis and Inflammation in Alzheimer's Disease Patients. Journal of Alzheimer's Disease. Volume 34, Number 1 / 2013. DOI: 10.3233/JAD-121735. Accessed at http://iospress.metapress.com/content/m73252850m04g801/
- Mizwicki MT, Liu G, Fiala M, Magpantay L, Sayre J, Siani A, Mahanian M, Weitzman R, Hayden EY, Rosenthal MJ, Nemere I, Ringman J, Teplow DB. 1α,25-Dihydroxyvitamin D3 and Resolvin D1 Retune the Balance between Amyloid-β Phagocytosis and Inflammation in Alzheimer's Disease Patients. J Alzheimers Dis. 2013 Jan 1;34(1):155-70. doi: 10.3233/JAD-121735.
- Mizwicki MT, Menegaz D, Zhang J, Barrientos-Durán A, Tse S, Cashman JR, Griffin PR, Fiala M. Genomic and nongenomic signaling induced by 1α,25(OH)2-vitamin D3 promotes the recovery of amyloid-β phagocytosis by Alzheimer's disease macrophages. J Alzheimers Dis. 2012;29(1):51-62. doi: 10.3233/JAD-2012-110560.
- Mukkadan JK et al. Bioavailability of BCM-95TM SG. A human study. Department of Bio-Chemistry
- Padhye S, Chavan D, Pandey S, Deshpande J, Swamy KV, Sarkar FH. Perspectives on chemopreventive and therapeutic potential of curcumin analogs in medicinal chemistry. Mini Rev Med Chem. 2010 May;10(5):372-87. Review.
- Shishodia S. Molecular mechanisms of curcumin action: Gene expression. Biofactors. 2012 Sep 20. doi: 10.1002/biof.1041. [Epub ahead of print]
- Thomas P, Wang YJ, Zhong JH, Kosaraju S, O'Callaghan NJ, Zhou XF, Fenech M. Grape seed polyphenols and curcumin reduce genomic instability events in a transgenic mouse model for Alzheimer's disease. Mutat Res. 2009 Feb 10;661(1-2):25-34. doi: 10.1016/j.mrfmmm.2008.10.016. Epub 2008 Nov 6
- UCLA. Vitamin D, omega-3 may help clear plaques found in Alzheimer's. February 12, 2013. Accessed at http://www.ift.org/food-technology/daily-news/2013/february/12/vitamin-d-omega3-may-help-clear-plaques-found-in-alzheimers.aspx
- Verkhratsky A, Olabarria M, Noristani HN, Yeh CY, Rodriguez JJ. Astrocytes in Alzheimer's disease. Neurotherapeutics. 2010 Oct;7(4):399-412. doi: 10.1016/j.nurt.2010.05.017. Review.
- Wang Y, Yin H, Wang L, Shuboy A, Lou J, Han B, Zhang X, Li J. Curcumin as a potential treatment for Alzheimer's disease: a study of the effects of curcumin on hippocampal expression of glial fibrillary acidic protein. Am J Chin Med. 2013;41(1):59-70. doi: 10.1142/S0192415X13500055.
- Wang YJ, Thomas P, Zhong JH, Bi FF, Kosaraju S, Pollard A, Fenech M, Zhou XF. Consumption of grape seed extract prevents amyloid-beta deposition and attenuates inflammation in brain of an Alzheimer's disease mouse. Neurotox Res. 2009 Jan;15(1):3-14. doi: 10.1007/s12640-009-9000-x. Epub 2009 Feb 10.