Turmeric and Alzheimer 's disease
Jacob Schor, ND
October 2, 2007
We usually think of curcumin in terms of cancer treatment yet it may play an equally valuable role in the prevention and treatment of Alzheimer's disease. A fascinating story of theory, research and clinical trials has quietly unfolded over the last ten years. Turmeric and curcumin are about to hit the public's awareness in a big way.
Those of us in practice in the early 1990s, who can still remember anything that far back, will recall there was a lot of talk about ibuprofen and other NSAIDs protecting against Alzheimer's disease (AD). There were about 20 studies showing that people who took NSAIDs (non-steroidal anti-inflammatory drugs) long term for whatever their reason lowered their risk of developing AD. Of course, the problem with ibuprofen is that you can't suggest that people take it long term because of the potential side effects, especially liver and kidney damage. Looking for a safer and better ‘drug', Greg Cole and Sally Frautschy at UCLA tried curcumin. Curcumin, concentrated from the spice turmeric, is well known for its anti-inflammatory properties and is safe even in huge amounts. Unlike NSAIDs, curcumin also acts as an antioxidant; it stops damage caused by free radicals. Reactive oxygen damage is a main contributor to Alzheimer's disease.
In 2001, writing in the Journal of Neuroscience, these UCLA scientists reported on their first experiments. They tested curcumin on mice forced to develop amyloid plaques in their brains like those seen in Alzheimer's disease. The mice eating food spiced with turmeric developed about half the amount of brain plaque as mice not eating turmeric. (Lim 2001)
Though drawn to experiment with curcumin thinking it was safer than ibuprofen, Frautschy et al reported in the November 2001 issue of Neurobiology and Aging that it was also more effective at protecting experimental mice than ibuprofen. (Frautschy 2001)
The leading theory these days is that small bits of protein called amyloid that clump together in the brain into toxic lumps called plaques cause AD. These plaques kill brain cells because they trigger inflammation that damages the cells. The plaques also produce free radicals that cause oxidative damage to nerve cells. Ibuprofen apparently slows this process by slowing the inflammatory reactions. Curcumin acts as both an anti-inflammatory but also as a very potent antioxidant. A ‘dual action' as future advertisements will probably say.
If curcumin were protective against Alzheimer's disease, one would think that in parts of the world where people eat a lot of turmeric there would be a lower incidence of AD. When Cole and Frautschy started their research, no one had published data on AD rates in India , where just about everyone eats turmeric in their food. The first data was published in 2001; people in India have the lowest incidence of AD in the world.
Chandra et al. reported in a 2001 issue of Neurology that of people 65 and older in Ballabgarh , India , only 4.7 per 1,000 show signs of Alzheimer's disease. They compared this incidence to that of people of the same age living in Monongahela Valley , Pennsylvania . In the Pennsylvania group, 17.5 people per 1,000 showed signs of Alzheimer's. That puts the Indian turmeric eaters at about one-fourth the risk of the Americans. The Indians in this study had the lowest incidence of Alzheimer's seen anywhere in the world. (Chandra 2001)
Eating curry also seems to be protective. In 2006, Tze-Pin Ng of the National University of Singapore tested 1,010 Singaporeans between 60 and 93 years old. He also surveyed these people about their eating habits. Those who ate curry "occasionally" or "often or very often" scored better on cognitive performance tests than did people who ate curry only rarely. Curry powder is a blend of spices; the curry powder used in Singapore contains a lot of turmeric. (Ng 2006)
A February 2005 paper by Yang et al., says that curcumin does more than act as an anti-inflammatory and antioxidant in the brain. It doesn't just prevent the amyloid clumps from causing damage, it actually prevents them from forming into plaques in the first place. (Yang 2005)
Wait, there is more;
In 2004, Ono et al. reported that curcumin triggers amyloid plaques to break apart. (Ono 2004) Structurally, curcumin resembles the chemicals used as contrast material in CT brain scant to make plaques more visible. Because of this similarity, curcumin apparently binds to amyloid. This binding ability may explain why curcumin interferes with plaque formation and degrades existing plaques.
There's still more to this story.
Curcumin lowers cholesterol. In 1992, researchers in Amalanagar , India , gave people 500 milligrams of curcumin a day for just one week and measured a 29% increase in HDL cholesterol, and 11% drop in total cholesterol. (Soni 1992) In these modern times, I am hesitant to reference a paper now fifteen years old. Luckily, a 2007 paper explains that this effect is because curcumin changes the expression of certain genes that make cholesterol. (Peschel 2007) Certainly, this is relevant to cardiovascular disease, but this cholesterol lowering effect is also important with Alzheimer's.
Studies during the 1990s linked high cholesterol with increased risk of Alzheimer's disease. Cholesterol accumulates within the brain plaques and may aid amyloid proteins to bind together. This explains the current push by the pharmaceutical companies to convince us that Alzheimer's is just a symptom of statin deficiency. (Kuller 2007) The research, though it links cholesterol with Alzheimer's, has not shown that statins provide protection.
The immune system also plays a role in AD. Macrophages normally cruise through the brain and swallow up the amyloid plaques as they form. In people who develop Alzheimer's, these macrophages are not doing their jobs properly. Milan Fiala from the Los Angeles VA hospital took macrophages from Alzheimer's patients and mixed them with amyloid plaques. Published just this past July in the Proceedings of the National Academy of Sciences, Fiala's team report that the macrophages were total slackers, exhibiting anthropomorphic leukocytic shrugs of, “whatever.” They ignored the plaques and showed no tendency to consume them. Fiala attributes this lack of response as due to decreased expression of the gene MGAT3.
Exposing the macrophages to curcumin returned MGAT3 to its normal state and restored the macrophage's interest in destroying plaque, at least in about 50% of the cells. (Fiala 2007)
Turmeric's ability to fight cancer has overshadowed its use in treating Alzheimer's disease. As of October 1 2007 , PubMed lists 765 papers related to turmeric, of which 218 are to do with cancer but only 24 to do with Alzheimer's disease.
All of these studies added up to enough evidence in support of using curcumin, that in April 2005, John Ringman with Cole, Frautschy and few other associates at UCLA announced the start of a clinical trial using curcumin in Alzheimer's patients. (Ringman 2005) Ringman is comparing two doses, 2000 and 4000 mg per day in a double blinded placebo controlled trial with 33 patients. His data should tell us if curcumin does for people what it does for rodents. Their results are expected early next year.
These doses are similar to those already shown safe and well tolerated in phase I trials for cancer. It will not hurt to give curcumin to people showing signs and symptoms of Alzheimer's disease while we await Ringman's report.
It might help.
References and Links:
Chandra V, et al. Incidence of Alzheimer's disease in a rural community in India : the Indo-US study. Neurology. 2001 Sep 25;57(6):985-9.
Fiala M, et al. Innate immunity and transcription of MGAT-III and Toll-like receptors in Alzheimer's disease patients are improved by bisdemethoxycurcumin. Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12849-54.
Frautschy SA, et al. Phenolic anti-inflammatory antioxidant reversal of Abeta-induced cognitive deficits and neuropathology. Neurobiol Aging. 2001 Nov-Dec;22(6):993-1005
Kuller LH. Statins and dementia. Curr Atheroscler Rep. 2007 Aug;9(2):154-61
Lim GP, et al. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci. 2001 Nov 1;21(21):8370-7
Ng TP, et al. Curry consumption and cognitive function in the elderly. Am J Epidemiol. 2006 Nov 1;164(9):898-906. 26.
Ono K, et al. Curcumin has potent anti-amyloidogenic effects for Alzheimer's beta-amyloid fibrils in vitro. J Neurosci Res. 2004 Mar 15;75(6):742-50.
Peschel D, et al. Curcumin induces changes in expression of genes involved in cholesterol homeostasis. J Nutr Biochem. 2007 Feb;18(2):113-9.
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.
Soni KB, and Kuttan R. Effect of oral curcumin administration on serum peroxides and cholesterol levels in human volunteers. Indian J Physiol Pharmacol. 1992 Oct;36(4):273-5.
Yang F, et al. 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.