For many years, people around the world have been preparing their meals with an Indian spice called curry. Although most people who eat curry probably do so simply because of its pleasant taste, some current research suggests that the spice may actually have another important characteristic: it may be helpful in combating the effects of some neurodegenerative diseases. According to research on Alzheimer’s disease (AD), the disease-fighting effects of curry come from a compound called curcumin, which is a component of turmeric, the yellow spice that is used in most traditional curries. This chapter gives an overview of curcumin’s beneficial effects on AD and suggests possibilities for how curcumin may affect Huntington’s disease.
Table of Contents
- How Curry Relates to the Epidemiology of Alzheimer’s in Humans
- The Effects of Curcumin On the Cells of Rodents with Alzheimer’s
- How this Alzheimer’s Research May Affect Huntington’s Disease
- Uncertainties in How the Animal Research Relates to Humans
- For further reading
How Curry Relates to the Epidemiology of Alzheimer’s in Humans^
Scientists first became interested in studying curcumin when they looked into some statistics about the prevalence of AD in India, where curry is eaten in large quantities. In India, a relatively small proportion (1%) of people age 65 and older have AD. Additionally, in comparison to their American counterparts (who eat significantly less curry), Indians aged 70-79 develop AD one-fourth as often.
Although these data indicate that there is something special about Indian people with regard to AD, the many factors involved in the disease (which may involve a variety of things like genetics, exposure to certain toxins, eating things besides curry, etc.) make it inaccurate to state that curcumin is definitely the cause of India’s low prevalence of AD. However, the fact that curry (and thus, curcumin) is much more common in the Indian diet than the American diet does demonstrate what is called an inverse correlation between the use of curry and the prevalence of AD; that is to say, higher average amounts of curry intake are associated with lower prevalences of AD.
Having recognized this inverse correlation between curry and AD, scientists were able to take the research one step further. Interested in finding out whether or not curcumin might have a causal effect on combating AD, researchers turned to rodents (mice) as experimental animals in which to study the effect of curcumin on nerve cells. What they found in this research is discussed in the next section.
The Effects of Curcumin On the Cells of Rodents with Alzheimer’s^
The process through which Alzheimer’s disease degrades nerve cells is believed to involve three things: inflammation, oxidative damage, and most notably, the formation of beta-amyloid plaques. In order to understand how curcumin combats AD, we will look at its effects on each of these three phenomena.
On a short-term scale, inflammation is a very helpful event: it is the body’s way of protecting itself from foreign invaders. However, over an extended period of time, inflammation can actually be quite harmful. (For more info about inflammation, click here.) One of the ways that AD degrades nerve cells (and thus results in the manifestation of the disease’s symptoms) is by causing chronic inflammation in the central nervous system. For this reason, populations that exhibit prolonged use of certain nonsteroidal anti-inflammatory (NSAID) drugs like ibuprofen have been shown to have a reduced risk of developing the symptoms of AD. However, while ibuprofen significantly reduces the amount of inflammation in the central nervous system, its prolonged use has dangerous side effects like gastrointestinal, liver, and kidney damage.
Curcumin is a natural NSAID. For this reason, in mice models of AD, it was shown to reduce the levels of inflammation in the brain by about 60% (as measured by the reduced presence of a certain indicator of inflammation). An added benefit of curcumin is that it appears to be far less toxic than most drug NSAIDs. If further research confirms the safety of the substance, its use may become an alternative to drug NSAIDs for combating AD.
Like Huntington’s disease, AD can also increase the number of free radicals that nerve cells produce. Over time, this increased number of free radicals leads to oxidative damage, which can degrade nerve cells. In comparison to untreated mice with AD, mice with AD that were treated with curcumin had significantly reduced levels of free radicals. Thus, the oxidative damage that AD caused to the nerve cells of the curcumin mice was far less than the damage to the untreated mice.
The most prominent characteristic in the brains of people with Alzheimer’s disease is the presence of beta-amyloid plaques. These plaques are basically an accumulation of small fibers called beta-amyloid fibrils. The plaques can be found in the spaces between nerve cells, and in addition to being a tell-tale sign of the disease, their presence is believed to contribute greatly to the neurodegenerative process of AD.
The levels of beta-amyloid in AD mice that were given low doses of curcumin were decreased by around 40% in comparison to those AD mice that were not treated with curcumin. In addition, low doses of curcumin also caused a 43% decrease in the so-called “plaque burden” that these beta-amyloids have on the brains of AD mice. Surprisingly, those AD mice that received high doses of curcumin did not show any decreases in beta-amyloid levels or plaque burden in comparison with untreated mice. While the exact reason for this finding is not yet clear, the results of it are intriguing: low doses of curcumin were actually more effective than high doses in combating the neurodegenerative process of AD.
How this Alzheimer’s Research May Affect Huntington’s Disease^
Although research to confirm such a notion is just now getting underway, the results of the Alzheimer’s study suggest that curcumin might well be helpful in combating other neurodegenerative diseases like HD. Despite the differences in the fundamental “cause” of each disease – HD is believed to be a purely genetic disorder, while AD is believed to have both genetic and environmental components – the damage to nerve cells in each disorder is strikingly similar. Thus, because curcumin combats the phenomena that contribute to neurodegeneration in AD, it is fair to suggest that the substance may possibly be capable of combating similar phenomena in HD.
Just as in Alzheimer’s, inflammation and oxidative damage play a strong role in the neurodegenerative process of HD: oxidative damage (also known as “oxidative stress”) helps to degrade nerve cells in the basal ganglia and cerebral cortex; chronic inflammation in the brains of people with HD is believed to play a significant role in the progression of the disease. ( For more info about inflammation, click here.) As shown previously, curcumin was able to reduce inflammation and oxidative damage in mouse models of AD. Although it is possible that the pattern of inflammation in the brain and the severity of oxidative damage may be different between AD and HD, if they are even slightly similar in the two disorders, then one would expect curcumin to also have a positive effect on combating HD.
Despite the harmful effects of inflammation and oxidative damage, beta-amyloid fibrils (which make up beta-amyloid plaques) have won the most attention among researchers and the general public with regard to AD. Similarly, despite the harmful effects of other phenomena that contribute to neurodegeneration, the most attention among researchers and the general public with regard to Huntington’s disease is devoted to huntingtin protein aggregation. The attention paid to beta-amyloid fibrils and huntingtin protein aggregation is not unjustified: in addition to being telltale signs of their respective disorders, these two phenomena may be key players in the neurodegenerative process. For instance, some researchers believe that substances which inhibit huntingtin protein aggregation will also be found to inhibit the initial structural alteration of the huntingtin protein, an alteration that is believed to start the entire disease process in HD. But there is another discovery that could have potentially profound effects on the research underway for both of these diseases: based on their ribbon-like structure and the mechanism by which they are created, huntingtin protein aggregates are quite similar to beta-amyloid fibrils. Given this discovery, it is possible that substances that decrease the presence of beta-amyloid fibrils may do the same with huntingtin protein aggregates, and vice-versa.
As of this writing (June 2004), research on the effectiveness of curcumin in combating huntingtin protein aggregation has just gotten underway. Should curcumin prove to decrease huntingtin protein aggregates as well as it did beta-amyloid plaques, this would be a true triumph in HD research. However, while this possibility is certainly a source of intrigue, it is important to note that not all substances that are proven to decrease beta-amyloid levels have shown the same effectiveness with huntingtin protein aggregation. For instance, the compounds thioflavine T, gossypol, melatonin, and rifampicin, all of which are believed to decrease the presence of beta-amyloid, had little or no success in inhibiting huntingtin protein aggregation. On the other hand, Congo Red and thioflavine S, which are also believed to decrease beta-amyloid, did effectively decrease huntingtin protein aggregation. Thus, while the similarities between beta-amyloid fibrils and huntingtin protein aggregates make us hopeful that curcumin can decrease the aggregates, current research on curcumin and HD will have the final say.
A closing remark: This section lacks definitive answers about how curcumin affects HD for one reason: the research simply has not yet been done. As the studies that are currently underway produce results, and as potentially more studies are begun, we will learn a great deal about how curcumin affects HD.
Uncertainties in How the Animal Research Relates to Humans^
The AD mice study mentioned in the above sections prompts us to offer some cautionary notes about directly applying results from mice to humans:
First, the AD study tested curcumin by splitting the mice into three groups: one group received a low dose of curcumin, another group received a high dose, and the third group received no curcumin at all. Curiously, comparing the low-dose group and high-dose group, low doses of curcumin actually appeared to combat neurodegeneration in AD better than high doses. While the reason for this finding is not yet fully understood, the results do tell us something important: just because a substance is helpful does not mean its helpfulness is increased with every increase in dosage. In fact, increased or prolonged dosages of an initially helpful substance can actually be harmful. In the ibuprofen study mentioned above, for example, gastrointestinal, liver, and kidney damage resulted from the prolonged use of otherwise helpful ibuprofen.
Second, it is also important to keep in mind that mice, of course, have significantly smaller bodies than humans and may metabolize substances differently than we do. Thus, despite its apparent safety in animal studies (for example, one study on mice used 83 times the normal amount of curcumin, and still produced no mortalities), one should always exercise caution when using a new substance (medicinal or natural) to treat a disorder. And as always, for advice about treating disease, it is important to consult a physician.
Clinical trials should soon be underway in order to establish the safety of using curcumin to combat AD in humans. If future laboratory and animal studies suggest that curcumin holds promise for combating Huntington’s disease as well, then clinical trials to test its safety and effectiveness in HD would also be needed.
For further reading^
- Heiser V, Scherzinger E, Boeddrich A, Nordhoff E, Lurz R, Schugardt N, Lehrach H, Wanker EE. Inhibition of huntingtin fibrillogenesis by specific antibodies and small molecules: implications for Huntington’s disease therapy. Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6739-44. PMID: 10829068 [PubMed - indexed for MEDLINE]
A technical paper that describes the effectiveness of certain compounds in decreasing the amount of huntingtin protein aggregation in HD.
- 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. PMID: 11606625 [PubMed - indexed for MEDLINE]
A technical paper that discusses how curcumin affects the nerve cells of Alzheimer’s mice. This is the paper on which the majority of the chapter was based.
- Scherzinger E, Sittler A, Schweiger K, Heiser V, Lurz R, Hasenbank R, Bates GP, Lehrach H, Wanker EE. Self-assembly of polyglutamine-containing huntingtin fragments into amyloid-like fibrils: implications for Huntington’s disease pathology. Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4604-9. PMID: 10200309 [PubMed - indexed for MEDLINE]
A technical paper that discusses the similarities between huntingtin protein aggregates and beta-amyloid fibrils.
-M. Stenerson, 6-28-04