by Craig Weatherby
As we've reported, the search has since narrowed to the family of powerfully anti-inflammatory chemicals that makes turmeric bright yellow and gives curry spice blends—which usually contain lots of turmeric—their rich yellow colors.
The polyphenol family encompasses vitamin E, flavonoids, flavanols, and lesser-known stilbene-class compounds such as resveratrol: the grape-derived compound that made headlines last week by seeming to protect obese mice from the ravages of high-fat diets (See “Antioxidant might extend life- and health-spans”).
How did scientists come to scrutinize curcumin?
Inflammation is both an effect and promoter of Alzheimer's disease, which is why regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen seems to reduce the risk of developing AD and reduce its severity or progression (Lim GP et al 2000).
Aspirin and other NSAIDs inhibit inflammation by blocking a multi-purpose enzyme called cyclooxygenase-1 (COX-1) that can play a pro-inflammatory role. But COX-1 has key metabolic uses in addition to inducing inflammation, so chronic use of NSAIDs can cause gastrointestinal, liver, and kidney damage.
Thanks to earlier animal and human research on arthritis, scientists knew that curcuminexerts strong antioxidant and anti-inflammatory effects, in part by blocking excessive pro-inflammatory activation of the COX-2 enzyme.
This is why curcumin appears to offers strong anti-cancer, anti-Alzheimer's, anti-arthritis potential. See “Colorful Spice Seen to Combat Cancer" and “Curry Spices versus Colorectal Cancer.”
(Note: The omega-3 fatty acids in fish exert their anti-inflammatory effects in similar ways, which would explain the benefits they've demonstrated in Alzheimer's and arthritis; see “Fighting Internal Fires with Fish Fats.”)
The COX-2 enzyme is also inhibited by the now-discredited drugs Vioxx and Celebrex, which block it indiscriminately, with unhealthful implications.
Unlike these synthetic COX-2-inhibiting drugs, curcumin only blocks the COX-series enzymes conditionally. Curcumin also inhibits excessive activation of pro-inflammatory genetic switches—nuclear transcription factors such as Nf-kappaB and AP-1—which also promote premature tissue aging and cancer.
Because turmeric's yellow pigment targets Alzheimer's disease in multiple ways, curcumin can approximate or even exceed the potent anti-inflammatory power of common NSAIDs, without eliciting their adverse effects.
In fact, lab studies indicate that curcumin prevents formation of the beta-amyloid plaques that characterize Alzheimer's disease much more effectively, compared with NSAIDs like aspirin and ibuprofen.
The new studies: curcumin versus Alzheimer's and arthritis
The past month witnessed publication of three studies that served to confirm the value of curcumin in preventive health, and suggest strong therapeutic potential as well.
Study #1: Curry lovers enjoy lower risks of Alzheimer's
Researchers at the National University of Singapore recruited 1,010 elderly Asians (average age 68.9), questioned them about their curry intake, and placed them into one of three curry-consumption categories:
- “often or very often” (once a month to daily; 43 percent of participants)
- “occasionally” (41 percent of participants)
- “never or rarely” (16 percent of participants)
|Dementia rates rise worldwide as lifestyles shift to Western model|
An estimate published in 2005 (Ferri CP et al 2005) suggests that some 24 million people have Alzheimer's disease or another form of dementia, with one new case every 7 seconds (4.6 million new cases every year). Worse, the number of people affected may double every 20 years.
The authors said that in 2001, some 60 percent of dementia cases occurred in developing countries, and that this proportion may rise to 71 percent by 2040.
Sadly, as diets and lifestyles in developed countries shift toward the Western model, the number of cases occurring in their populations is forecast to increase by 100 percent by 2040, and to increase by more than 300 percent in India, China, and their immediate neighbors.
While lengthened life-spans play a major role in this phenomenon, many observers attribute the rapid worldwide rise in dementia rates to the increasing dominance of the standard Western diet, which is high in fat, sugar, and calories but low in protective dietary factors (fish-derived omega-3 fatty acids and plant-derived antioxidants).
Mini-Mental State Examination (MMSE), and compared the participants' test performance with their curry consumption.
It turned out that those who consumed curry “often or very often” were 49 percent less likely to display cognitive impairment, compared to those who never or rarely consumed, while eating curry “occasionally” was associated with a 38 percent lower risk (Ng TP et al 2006).
According to Dr. Ng, “These findings present the first epidemiological evidence supporting a link between curry consumption and cognitive performance that was suggested by a large number of earlier experimental evidence.”
The study had limitations, since it did not take into account other possible risk-reducing or -promoting factors in the curry dishes, such as vegetables and fats, while the accuracy of self-reported curry consumption is not certain.
Despite these limitations, the researchers point at turmeric as an obvious explanation for the observed differences between curry-lovers and those who rarely consume it.
As Dr. Ng noted, “Interestingly, it has also been purported that the prevalence of Alzheimer's disease in India among elderly between 70 and 79 years of age is four-fold less than that of the United States. The results reported here are therefore significant, as they point to a significant beneficial effect on cognitive functioning with even low-to-moderate levels of curry consumption.”
We should note that the high levels of omega-6 fats in commercial curry sauces, which stem from use of soy, corn, and conventional sunflower or safflower oils, may make them less beneficial. Recipes containing turmeric or turmeric-rich curry blends should be more beneficial if they employ oils low in these pro-inflammatory fatty acids, such as extra virgin olive oil, macadamia nut oil, or hi-oleic versions of sunflower or safflower oils.
Study #2: Turmeric pigment clears plaques from Alzheimer's patients' brains
In a first, researchers from the University of California Los Angeles (UCLA) School of Medicine report that curcumin enhances the ability of immune-system cells to remove plaque from brain tissues taken from Alzheimer's disease patients (Zhang L et al 2006).
Blood-borne immune-system cells called macrophages participate in clearance of amyloid-beta a rogue protein that forms the brain-damaging plaques characteristic of Alzheimer's. Last year, the UCLA team showed that this process is defective in many patients: a deficiency that could elicit compensatory responses by the immune system, including the brain-damaging inflammation characteristic of Alzheimer's (Fiala M et al 2005).
In this new study, they drew blood taken from six Alzheimer's disease patients and three healthy controls, and isolated macrophage cells that target beta-amyloid.
|Turmeric outweighs curry as a practical curcumin source|
As we would expect, new research proves that pure turmeric powder is a much more reliable source of curcumin compared with commercial curry products, whether bottled sauces or dry mixes.
Earlier this year, researchers analyzed 28 turmeric or curry powders and found that pure turmeric powder had the highest curcumin concentration (3.14 percent by weight on average) by far.
Most of the curry powder samples contained much less curcumin, and the amounts varied widely (Tayyem RF et al 2006).
Isolated macrophage cells from the volunteers were exposed to a curcumin-rich turmeric extract for 24 hours, and the researchers then added amyloid-beta material to the culture.
The treated macrophage cells were better able to ingest amyloid-beta, compared with untreated cells. Macrophages from the healthy controls, which were already able to clear amyloid-beta quite effectively, did not benefit from exposure to the curcumin product.
According to lead UCLA researcher Milan Fiala, M.D., “These initial findings may lead to a new approach in treating Alzheimer's disease by enhancing the natural function of the immune system using curcumin, thus increasing the body's ability to remove plaques that may cause Alzheimer's disease and other forms of dementia.”
Study #3: Curcumin aids against arthritis damage in animals
It's long been known that the curcumin fraction of turmeric can alleviate the symptoms of arthritis in animals, and it has even displayed strong therapeutic benefit in preliminary clinical trials:
- Indian scientists tested curcumin in 49 patients with rheumatoid arthritis. Half were given 1,200 mg of curcumin per day, and the rest received a standard dose of the potent synthetic NSAID phenylbutazone. At the end of six weeks, both groups enjoyed similar improvement in morning stiffness and physical endurance (Deodhar SD, et al 1980).
- The anti-inflammatory potency of curcumin was tested in hospital patients who had either undergone surgery or suffered some kind of physical trauma. One-third received curcumin (1,200 mg/day), one-third received a placebo and one-third took phenylbutazone (300 mg/day), for three to five days. Curcumin was judged to be as effective as phenylbutazone (Satsokar RR, et al 1986).
Researchers at the University of Arizona in Tucson compared the effects in arthritic mice of a turmeric extract containing 34 per cent curcuminoids and the spice's natural essential oils, versus an extract with 41 per cent curcuminoids and no essential oils.
(The majority of curcumin supplements are free of essential oils and their curcuminoid contents ranges from 35 to 95 percent.)
Lead author Janet Funk, M.D. and her colleagues reported used female rats to test the efficacy of the extracts. The animals were injected with either a saline solution or an arthritis-inducing solution, and also with one of the turmeric extracts or a control (placebo) solution.
They then measured tissue damage and markers of joint inflammation. The version of turmeric extract that was free of essential oils—which therefore matched the composition of commercially available supplements most closely—had the greatest positive impact.
- Destruction of cartilage n the tibia of the rats was reduced by 66 percent, compared to the rats that got the placebo solution.
- Loss of bone mineral density (BMD) in the animals' thighs was reduced by 57 percent, compared to the rats that got the placebo solution.
Unsurprisingly, a companion study by Dr. Funk's team showed that the turmeric extracts inhibited NF-kappaB: the nuclear transcription factor (genetic switch) mentioned above, which promotes inflammation via several pathways, including activation of the pro-inflammatory COX-enzyme we discussed at the outset (Funk JL et al Arthritis Rheum 2006).
As Dr. Funk's team wrote, “Given the critical role of NK-kappaB as the ‘master switch' in innate immunity, these in vivo experiments… provide proof-of-concept for the use of this botanical [extract] in other [inflammatory] diseases… including inflammatory bowel disease, asthma, and multiple sclerosis.”
- Cole GM, Morihara T, Lim GP, Yang F, Begum A, Frautschy SA. NSAID and antioxidant prevention of Alzheimer's disease: lessons from in vitro and animal models. Ann N Y Acad Sci. 2004 Dec;1035:68-84. Review.
- Deodhar SD, et al. Preliminary studies on anti-rheumatic activity of curcumin (diferuloyl methane). Ind J Med Res 1980;71:632.
- Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M; Alzheimer's Disease International. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005 Dec 17;366(9503):2112-7.
- Fiala M, Lin J, Ringman J, Kermani-Arab V, Tsao G, Patel A, Lossinsky AS, Graves MC, Gustavson A, Sayre J, Sofroni E, Suarez T, Chiappelli F, Bernard G. Ineffective phagocytosis of amyloid-beta by macrophages of Alzheimer's disease patients. J Alzheimers Dis. 2005 Jun;7(3):221-32; discussion 255-62.
- Funk JL, Frye JB, Oyarzo JN, Kuscuoglu N, Wilson J, McCaffrey G, Stafford G, Chen G, Lantz RC, Jolad SD, Solyom AM, Kiela PR, Timmermann BN. Efficacy and mechanism of action of turmeric supplements in the treatment of experimental arthritis. Arthritis Rheum. 2006 Oct 30;54(11):3452-3464 [Epub ahead of print]
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- 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.
- Lim GP, Yang F, Chu T, Chen P, Beech W, Teter B, Tran T, Ubeda O, Ashe KH, Frautschy SA, Cole GM. Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer's disease. J Neurosci. 2000 Aug 1;20(15):5709-14.
- Ng TP, Chiam PC, Lee T, Chua HC, Lim L, Kua EH. Curry consumption and cognitive function in the elderly. Am J Epidemiol. 2006 Nov 1;164(9):898-906. Epub 2006 Jul 26.
- Satsokar RR, et al. Evaluation of antiinflammatory property of curcumin in patients with post-operative inflammation. Int J clin Pharmacol Toxicol 1986;24:651.
- Tayyem RF, Heath DD, Al-Delaimy WK, Rock CL. Curcumin content of turmeric and curry powders. Nutr Cancer. 2006;55(2):126-31.
- 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. Epub 2004 Dec 7.
- Zhang L, Fiala M, Cashman J, Sayre J, Espinosa A, Mahanian M, Zaghi J, Badmaev V, Graves MC, Bernard G, Rosenthal M. Curcuminoids enhance amyloid-beta uptake by macrophages of Alzheimer's disease patients. J Alzheimers Dis. 2006 Nov;10(1):1-7.