With nothing but folklore and casual observation to speak for it, turmeric has come to be recognized over the ages and across the continents as "the spice of life" and not just due to its unique taste and food-preserving qualities. Turmeric is the bright yellow spice that is a principal ingredient in curry powder. Long a staple of South Asian cuisine, it also has a long history in the ancient Indian tradition of Ayurvedic medicine, for, among other qualities, its ability to preserve cognition long into old age. It´s probably no coincidence, then, that the curry-eating people of rural India have the lowest incidence of Alzheimer´s disease of any comparable population in the world.
Long ignored by Western medicine, medical science is beginning to take its closest look ever at turmeric and it likes what it sees. Turmeric contains a class of compounds called curcuminoids. Of these, curcumin, the one for which the group is named, is a very potent antioxidant. In many studies, curcumin extract from turmeric is used. The evidence is becoming unmistakable that this remarkable spice may help prevent and even reverse Alzheimer´s disease,1 Parkinson´s disease,2 gastric ulcers,3 and even coronary heart disease.4 While its mechanism of action appears to be quite complex, it appears to be quite safe, even at very high doses. This is in sharp contrast to the only pharmaceutical drugs that act in a similar manner, the nonsteroidal anti-inflammatory drugs (NSAIDs), such as, naproxen, ketoprofen, indomethacin, and ibuprofen.
Alzheimer´s disease results from the slow deposition among brain cells of an insoluble protein known as amyloid-ß. Amyloid-ß deposits eventually turn the brain´s complex neural microplumbing system into a desolate landscape of plaques and tangles of useless nerves and disruptive fibers. Recent studies have convincingly shown that some NSAIDs, such as naproxen (Naprosyn®, Aleve®), may slow the progression of Alzheimer´s by inhibiting the production and accumulation of amyloid-ß.5-11
Like a Natural — and Safe — NSAID
Turmeric/curcumin is well known for its anti-inflammatory activity and is an important natural treatment for arthritis pain and inflammation, functioning, in effect, as a natural NSAID. Like the other NSAIDs, turmeric also reduces the accumulation of amyloid-ß, but it works much better.12, 13 And best of all, turmeric has none of the serious and even fatal side effects of pharmaceutical NSAIDs.
Figures 1 through 3 show the results of a recent in-vitro (test-tube) study comparing the relative abilities of curcumin, naproxen, and ibuprofen to inhibit the formation of amyloid-ß deposits.1 Curcumin was significantly more effective than either drug and at far lower concentrations.
|Figure 1. Curcumin begins preventing amyloid-ß deposits even at its lowest concentrations and shows a clear “dose-response” effect as the concentration increases.
|Figure 2. Naproxen was comparably effective only at concentrations four times higher than those of curcumin. Doses high enough to produce this concentration are potentially very toxic.
|Figure 3. The NSAID ibuprofen (Motrin®, Advil®) is only barely effective at blocking formation of amyloid-ß deposits, even at its highest concentrations.
Translated into real-life dosing, this means that you would need to take much higher doses of naproxen and ibuprofen compared to curcumin to produce a given therapeutic effect. This is important, because heavy use of NSAID drugs kills thousands of people each year, usually due to gastric ulcer, perforation, gastric outlet obstruction, or gastric bleeding. Potentially fatal kidney toxicity is also an important concern with these drugs.14, 15
No such worries are necessary with turmeric. You can consume turmeric all day every day with no adverse effects. Turmeric has been given long term to cancer patients at daily doses of 4 to 8 grams with no sign of toxicity.16
Reversing Alzheimer´s Brain Damage
Not only does turmeric inhibit amyloid-ß aggregation at extremely low doses (note the effective concentration ranges for curcumin versus the two other drugs in Figs. 1-3), higher doses can actually disassemble amyloid-ß aggregates that have already formed.1
These results suggest that turmeric might not only help prevent the onset of Alzheimer´s disease, it might also help reverse the disease´s principal degenerative process. Since brain damage in Alzheimer´s can go on for years before cognitive deficits begin to appear, this means that turmeric may ward off Alzheimer´s symptoms for a lifetime, especially if the disease is caught early, before too much permanent brain damage has occurred. Unfortunately, no well-controlled studies have tested the efficacy and safety of turmeric in people with Alzheimer´s disease. Of course, there are those people in India!
Just how turmeric works to break up amyloid-ß deposits is unclear, but according to one line of evidence, it may work, at least in part, as a chelator of metals, such as copper and iron. These metals – in extremely low concentrations – stimulate the production of amyloid-ß deposits in the brain.17, 18 In one small placebo-controlled study, clioquinol, a drug that keeps zinc and copper ions from binding to amyloid-ß, significantly slowed cognitive decline in Alzheimer´s patients.19 In a related way, turmeric binds copper and iron at very low brain concentrations that could be easily reached by turmeric ingestion.20
Several other mechanisms of action for turmeric have also been suggested. For example, consuming turmeric reduces brain levels of iNOS (inducible nitric oxide synthase), inflammatory cytokines, and lipid peroxidation, all of which may contribute to brain pathology.21 In fact, curcumin inhibits lipid peroxidation better than vitamin E, and it´s also a more potent antioxidant.22
Real World Support
The results of test-tube studies can be very suggestive, but there´s always a chance they will bear no relation to what goes on in the real – in vivo – world of animal experiments and especially human trials. Such research is just starting to get under way as the therapeutic possibilities of turmeric become ever harder to ignore. One study in middle-aged rats compared ibuprofen and curcumin for protecting rats against damage induced by an injection of human amyloid-ß peptides directly into their brains. Both ibuprofen and curcumin prevented some forms of damage, but only curcumin blocked oxidative damage and bound closest to amyloid-ß deposits. Most exciting, though, was a second group of amyloid-ß-treated rats, in which curcumin treatment prevented the occurrence of spatial memory deficits (tested in a water maze).12
These results demonstrate that turmeric/curcumin has many of the properties it needs to prevent and even reverse Alzheimer´s disease:
- It readily crosses the blood-brain barrier, so that ingesting it gets it to the brain tissue where it is needed at the concentrations needed.
- It binds tightly with amyloid-ß plaques.
- It inhibits the aggregation of amyloid-ß protein so that plaques cannot form.
- At high enough (but still safe) levels, it promotes the dissolution of already formed amyloid-ß deposits.
- It has no known toxicity, even at extremely high blood levels.
- It is readily available and inexpensive.
Thus, it seems we may be able to consume all the turmeric we like for the better part of our lives and prevent the occurrence or progression of Alzheimer´s, and probably other serious diseases. Although systematic studies in humans are still on the drawing board, right now we can simply ask the people of rural India.
We all enjoy a curry-flavored meal, but it isn´t necessary to change our diet to gain the potential benefits to turmeric/curcumin, because it is available in a variety of nutritional supplements.
- Yang F, Lim GP, Begum AN, et al. Curcumin inhibits formation of Abeta oligomers and fibrils and binds plaques and reduces amyloid in vivo. J Biol Chem Dec 2004; 10.1074/jbc.M404751200..
- Glasson B, Dude J, Murray I, et al. Oxidative damage linked to neurodegeration by selective alpha-synuclein nitration in synucleinopathy lesions. Science 2000;290:985-9.
- Swarnakar S, Ganguly K, Kundu P, Banerjee A, Maity P, Sharma AV. Curcumin regulates expression and activity of matrix metalloproteinases-9 and -2 during prevention and healing of indomethacin-induced gastric ulcer. J Biol Chem Dec 2004; 10.1074/jbc.M413398200..
- Ramaswami G, Chai H, Yao Q, Lin PH, Lumsden AB, Chen C. Curcumin blocks homocysteine-induced endothelial dysfunction in porcine coronary arteries. J Vasc Surg 2004;40:1216-22.
- Anthony JC, Breitner JC, Zandi PP, et al. Reduced prevalence of AD in users of NSAIDs and H2 receptor antagonists: the Cache County study. Neurology 2000;54:2066-71.
- in 't Veld BA, Launer LJ, Hoes AW, et al. NSAIDs and incident Alzheimer's disease. The Rotterdam Study. Neurobiol Aging 1998;19:607-11.
- in t' Veld BA, Ruitenberg A, Hofman A, et al. Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease. N Engl J Med 2001;345:1515-21.
- 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;327:128.
- Launer LJ. Nonsteroidal anti-inflammatory drugs and Alzheimer disease: what's next? JAMA 2003;289:2865-67.
- Landi F, Cesari M, Onder G, Russo A, Torre S, Bernabei R. Non-steroidal anti-inflammatory drug (NSAID) use and Alzheimer disease in community-dwelling elderly patients. Am J Geriatr Psychiatr 2003;11:179-85.
- Zandi PP, Anthony JC, Hayden KM, Mehta K, Mayer L, Breitner JC. Reduced incidence of AD with NSAID but not H2 receptor antagonists: the Cache County Study. Neurology 2002;59:880-6.
- Frautschy SA, Hu W, Kim P, et al. Phenolic anti-inflammatory antioxidant reversal of Abeta-induced cognitive deficits and neuropathology. Neurobiol Aging 2001;22:993-1005.
- Shoghi-Jadid K, Small GW, Agdeppa ED, et al. Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease. Am J Geriatr Psychiatry 2002;10:24-35.
- Fries JF. Assessing and understanding patient risk. Scand J Rheumatol Suppl 1992;92:21-4.
- U.S. Food and Drug Administration. Safety concerns associated with over-the-counter drug products containing analgesic/antipyretic active ingredients for internal use. Bethesda, MD: www.fda.gov/cder/drug/analgesics/SciencePaper.htm; Accessed January 16, 2005 2004.
- Cheng AL, Hsu CH, Lin JK, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 2001;21:2895-2900.
- Perry G, Taddeo MA, Petersen RB, et al. Adventiously-bound redox active iron and copper are at the center of oxidative damage in Alzheimer disease. Biometals 2003;16:77-81.
- Castellani RJ, Honda K, Zhu X, et al. Contribution of redox-active iron and copper to oxidative damage in Alzheimer disease. Ageing Res Rev 2004;3:319-26.
- Ritchie CW, Bush AI, Mackinnon A, et al. Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer disease: a pilot phase 2 clinical trial. Arch Neurol 2003;60:1685-91.
- Baum L, Ng A. Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer's disease animal models. J Alzheimers Dis 2004;6:367-377; discussion 443-9.
- Cole G, Yang F, Lim G, Cummings J, Masterman D, Frautschy SA. Curr Med Chem-Immun, Endoc, & Metab Agents 2003;3:15-25.
- Zhao BL, Li XJ, He RG, Cheng SJ, Xin WJ. Scavenging effect of extracts of green tea and natural antioxidants on active oxygen radicals. Cell Biophys 1989;14:175-85.