Also see commercial Turmeric Curcumin
Curcumin & Alzheimer's Disease
Excerpts from "Can Curcumin Prevent Alzheimer's Disease?" LE Magazine,
December 2004 By John C. Martin
In recent studies, curcumin’s ability to scavenge free radicals and suppress
inflammatory cytokines has impressed scientists who are seeking ways to
prevent and treat Alzheimer’s disease and other neurodegenerative disorders.
Alzheimer’s disease was discovered in 1907 by Dr. Alois Alzheimer, a German
medical researcher who described a unique and destructive pathology in his
patients’ brains.1 Today as then, Alzheimer’s is a ravaging illness that
robs its victims not only of their health, but also of their relationships
with family and friends. Alzheimer’s is also a burgeoning disease that
affects more than 4 million Americans, a number that has doubled in the past
25 years. The disease is expected to continue its devastating surge over the
next several decades.2
No cure exists for Alzheimer’s, and the drugs currently available to treat
the disease address only its symptoms, and with only limited effectiveness.
Medical experts believe that therapeutic intervention that could postpone
the onset or progression of Alzheimer’s—even by as little as two years—would
dramatically reduce the number of cases over the next 50 years.3 A growing
body of evidence suggests that a promising therapeutic modality may already
be available. This remedy is most commonly found not in a biochemical
laboratory, but rather in the kitchen spice rack: the perennial herb known
around the world as turmeric.
Curcumin is the active compound in turmeric powder.
From Ancient Healing to Modern Medicine
A plant cultivated mostly in Asia, turmeric (Curcuma longa) is a member
of the ginger family.4 Its root and rhizome, or underground stem, are ground
into a powder and used as a spice in various food preparations. Turmeric is
the seasoning that gives curry powder its yellow color.
In addition to its uses as a spice, turmeric has been used therapeutically
over the centuries in different parts of the world. Turmeric is rich in its
active compound, curcumin, which is widely prescribed in Indian medicine as
a potent remedy for liver disorders, rheumatism, diabetic wounds, runny
nose, cough, and sinusitis.5 Traditional Chinese medicine uses curcumin as a
treatment for diseases associated with abdominal pain, and it is used in
ancient Hindu medicine as a treatment for sprains and swelling.5
While the therapeutic use of this treasured spice has been commonplace
throughout history, emerging medical research has begun to elucidate
curcumin’s beneficial effects for a range of diseases and conditions. Much
of the recent science has focused on its effects against cancer, both
therapeutically and prophylactically.6 Curcumin’s potential apparently stems
from its ability to suppress the proliferation of a wide variety of tumor
cells and to inhibit harmful molecules and enzymes, as well as its
antioxidant and anti-inflammatory properties. Some studies have even
suggested that curcumin can inhibit cancer metastasis.6
In research studies, curcumin has shown potential activity against cataract
formation,7 liver injury,8 and the resultant damage from heart attack9 and
stroke.10 More important, curcumin’s anti-inflammatory effects and apparent
effectiveness in keeping Alzheimer’s disease at bay are attracting the
notice of more and more medical researchers.
Alzheimer’s and Its Risk Factors
Alzheimer’s disease is considered a form of dementia, a brain disorder
that seriously affects a person’s ability to carry out daily activities.
Alzheimer’s is the most common form of dementia in people over the age of
65.11 Symptoms typically appear after age 60, with some early-onset forms of
the disease linked to a specific genetic defect.
Alzheimer’s disease primarily involves the parts of the brain that control
thought, memory, and language. Its causes are still essentially unknown, and
no cure exists. Alzheimer’s evolves slowly. At first, its only symptom may
be mild forgetfulness. As the disease progresses, more serious symptoms
arise, such as forgetting how to carry out simple tasks like combing one’s
hair or brushing one’s teeth. People with Alzheimer’s disease eventually
require comprehensive care.11
There is probably no one specific cause of Alzheimer’s disease; instead,
several factors are likely to affect each person differently. Age is a
common denominator in the disease, with the incidence of Alzheimer’s
doubling every five years in people over age 65. Family history also plays
an important role, as Alzheimer’s disease with a familial component can
occur between the ages of 30 and 60. In older people, however, no obvious
family pattern has been noted.11 Other genes that may be centrally involved
in the onset and progression of Alzheimer’s remain to be discovered.
One recently discovered risk factor is the presence of a protein known as
apolipoprotein E, which normally helps carry cholesterol in the blood. This
molecule has three forms, and while one form helps protect people from
Alzheimer’s disease, scientists have found another form that can do just the
Alzheimer’s disease is characterized by two key abnormalities in the brain:
amyloid plaques and neurofibrillary tangles. Amyloid plaques are clumps of a
protein known as beta amyloid. They are found in the tissue between nerve
cells in the brain, along with degenerating bits of neurons and other
Neurofibrillary tangles, largely comprising a protein called tau, are
bundles of twisted filaments found within neurons. In healthy individuals,
the tau protein augments the function of microtubules (part of the cell’s
structural support) and delivers various substances throughout them. In
Alzheimer’s sufferers, tau’s function is transformed abnormally so that it
twists into pairs of helical filaments that collect in tangles. When this
occurs, the microtubules do not function correctly and disintegrate. The
resulting collapse of the neurons’ transport system eventually impairs
communication between nerve cells, and causes them to die.13
Targeting Destructive Plaques and Cells
Studies suggest curcumin helps to avert the insidious evolution of
amyloid beta plaques in the brain. Building on previous research examining
the inhibitory effects of certain compounds on beta amyloid formation,
investigators have studied the effects of curcumin and rosmarinic acid, a
phenolic compound that has been shown to possess anti-inflammatory and
antioxidant properties. In one study, researchers compared the effects of
curcumin and rosmarinic acid on the formation, extension, and
destabilization of beta amyloid fibrils.14 They found that both curcumin and
rosmarinic acid inhibited the formation and extension of beta amyloid
fibrils, and also destabilized beta amyloid plaques that had already
formed.14 Although the mechanism by which curcumin exerted these effects is
not known, the Japanese study team notes that curcumin “could be a key
molecule for the development of therapeutics for Alzheimer’s disease.”14
In another in-vitro study, researchers studied the action of curcumin
against the abnormal growth and proliferation of neuroglial cells, which
provide mechanical and physical support for, as well as electrical
insulation between, neurons in the brain.15 In Alzheimer’s disease, a
condition known as gliosis can occur, characterized by the rapid
proliferation of neuroglia. Alzheimer’s disease is also marked by
astrocytosis, an abnormal proliferation of astrocytes near neurodegenerative
lesions. Astrocytes are the largest and most numerous neuroglial cells in
the central nervous system.
In this study, researchers at the University of California, Berkeley,
infused various doses of curcumin into rat glioma cells, which are malignant
tumors of neuroglial origin. The researchers concluded: “Curcumin inhibited
neuroglial proliferation, with the degree of inhibition correlated directly
with the curcumin concentration.”15
Amyloid plaques are known to cause oxidative damage in the brains of
Alzheimer’s sufferers. Free radicals generated by beta amyloid and other
factors, such as mitochondrial abnormalities in cells, inadequate energy
supply, inflammation, or abnormal changes in natural antioxidant defenses,
may play a role in the pathophysiology of Alzheimer’s disease. Substances
with antioxidant properties, such as curcumin, may therefore offer
biochemical support in this condition.
“Treatment with antioxidants is a promising approach for slowing disease
progression to the extent that oxidative damage may be responsible for the
cognitive and functional decline observed in Alzheimer’s disease,” wrote
researchers at the University of California, San Diego.16
In another theory of how curcumin provides its advantageous effects against
oxidative damage, medical experts speculate that curcumin induces a
heat-shock response in the brain.17 Heat-shock proteins serve as a
prophylaxis against stress exerted on cells.
Impressive Pre-clinical Research Evidence of Curcumin on Alzheimer's
Observation of curcumin’s benefits is not limited to in-vitro studies.
Promising studies in animals have also been published. Scientists tested the
effects of curcumin against damage induced by beta amyloid in rats, and
compared the results with the protective effects of ibuprofen, a common
non-steroidal anti-inflammatory drug (NSAID).18 Some clinical trials have
indicated that NSAIDs may help prevent the onset of Alzheimer’s disease as a
result of their anti-inflammatory properties.19,20
In a pre-clinical trial involving 22 rodents, researchers gave the rats a
beta amyloid amino acid, which resulted in oxidative damage, loss of
synaptophysin (a protein involved in brain synapses), and widespread amyloid
deposits. When both ibuprofen and curcumin were then introduced into the
rats’ diets after this cerebral damage had occurred, only curcumin
suppressed both the oxidative damage and continual synaptophysin loss.18
Both interventions reduced levels of microglia—small glial cells in that
brain that serve as support structures for neurons—in the cortical layers.18
In a second group of rats infused with beta amyloid, dietary curcumin
prevented spatial memory problems as shown in the Morris Water Maze
exercise, a sensitive test used to assess spatial memory, in which rats must
locate a hidden escape platform. These rats also showed lower levels of beta
amyloid after curcumin was introduced in their diet. “Because of its low
side-effect profile and long history of safe use, curcumin may find clinical
application for Alzheimer’s disease prevention,” the study team concluded.18
Additional pre-clinical studies echo these findings.21 In a 2001 study, UCLA
researchers fed groups of mice one of two different doses of curcumin (160
or 5,000 parts per million) as part of their normal diet. The researchers
wanted to determine how each dose affected inflammation, oxidative damage,
and cerebral plaque levels. Both doses of the spice were effective. Curcumin
lowered levels of oxidized proteins and the proinflammatory cytokine known
as interleukin-1 beta, which were previously elevated in the brains of the
mice. Interestingly, only low-dose curcumin lowered levels of an
inflammatory biological marker, glial fibrillary acidic protein, by as much
as 16%. Amyloid plaques were also reduced in the rodents’ brains by up to
50%. Microgliosis was also suppressed when rats were fed curcumin, though
only in neuronal layers and not in proximity to plaques.21
The researchers concluded that curcumin “is a promising agent” as a
prophylactic therapy against Alzheimer’s and possibly other brain disorders
such as Parkinson’s disease.21
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
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
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
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
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
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
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
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
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
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
23. Chainani-Wu N. Safety and anti-inflammatory activity of curcumin: a
component of tumeric (Curcuma longa). J Altern Complement Med. 2003
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
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.
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