Curcumin: A Powerful Brain Protection Supplement, © 2005-2008 by John Smart
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Overview

Curcumin is an inexpensive dietary supplement that offers powerful protection for aging brains. It has been used as a food additive for thousands of years in the East as the active ingredient in turmeric, or yellow curry spice. Since 2000, curcumin's many memory and brain benefits are being slowly uncovered by scientists, clinicians and gerontologists (researchers who study the aging process). Curcumin has many, many mild physiologic effects when we eat it as a nutritional supplement, but one of the more important ones is that it reduces the buildup of Alzheimer's-related amyloid in our brains as we age (for details, see this nice 2008 overview by Mishra of USC[1]).

This impressive effect and its mental benefits have been well documented in animal models, but it will be several more years before the more definitive long-term human studies are completed and its use can and very likely will be recommended to the general public. Fortunately, hundreds of millions of Asian Indians eat it daily, and once you understand its benefits, you can too.

Amyloid buildup is a degenerative process that affects all of us, without exception as we age, steadily gunking up our brains with protein deposits and decreasing our brain's memory and learning abilities. It is one of those things we all die "with," and an unlucky few of us die "of." Fortunately, because we all have "cognitive reserve" (redundant ways to learn everything important that we do), this steady loss of our brain's function isn't necessarily noticable to others around us, but it means our minds have to work harder and harder and harder over time to do things that were previously easy. If we pay attention (many of us don't, perhaps because it is an unpleasant realization), almost all of us will typically begin to notice creeping recall, learning, and awareness ("brain fog") issues beginning in our 30's (or even late 20's for some) and steadily becoming worse with advancing years. Eventually, with enough damage, even your reserve capacity begins to fail and significantly reduced mental ability, forgetfulness, and in your later years, even full-blown Alzhiemer's can emerge.

If you care about protecting your mind and learning capacity throughout your long future life, we hope you will take this article to your physician for further evaluation. As outlined in my companion article, "A Basic Brain Protection Plan," 2008, you may significantly improve your future mental performance by following some version of this very affordable supplementation plan under the advice of your physician.

Disclaimer

This article is not medical advice. Take this information to your physician. You should always seek expert medical advice before starting any new drug or supplement regimen.

Article

As medical science keeps us alive longer than ever before, age-associated diseases have become a prime health concern for us all. Alzheimer's Disease (AD) is presently the fourth leading cause of death among elderly in the developed nations, after heart disease, cancer, and stroke. Preventing it is the subject of this article.

Just like progressive atherosclerosis (arterial plaques), which everyone begins to collect to varying degrees in their circulatory system even in their teens, we all die with the buildup of varying degrees of amyloid plaque deposits in our brain. New research has shown that it is primarily these amyloid plaques and their associated effects that create Alzheimer's when they have sufficiently advanced in size and scope within the brain.

While most of us won't die from Alzheimer's, all of us will die with insoluble toxic amyloid buildup in our brains, which increasingly impairs our memory and learning capacities as we age. Amyloid accumulates in different brains at different rates, depending on our diet, genetics, and lifetime stress-immune histories. The more we have, the more we will notice mild-to-significant progessive cognitive impairment, particularly after the age of 50. Our 50's and beyond is the time of our lives when we finally have enough experience, connections, capital, and collective wisdom to do some of our most important work. But we need healthy brains to do so. Fortunately, this handout relays important new therapeutic information which, with your doctor's approval, might significantly improve your mental prime in your later years.

Greg Cole, Ph.D[2] is professor of medicine and neurology at the UCLA David Geffen School of Medicine, associate director of the UCLA Alzheimer's Disease Research Center, and associate director of the Geriatric Research, Education, and Clinical Center at the LA Sepulveda VA. For over twenty years Dr. Cole has systematically explored potential Alzheimer's prevention drugs including supplements like DHA, NSAIDs, vitamin E, and many others, as well as the etiology and pathophysiology of neurodegeneration.

After learning of his fascinating work, we invited Dr. Cole to speak at our July 2005 Los Angeles Future Salon. The following is my unauthorized summary of his fascinating presentation, see his PowerPoint [3] below, in my own attempt to publicize the breakthroughs that he and his colleagues have recently made.

In recent years Dr. Cole has been studying curcumin, the active ingredient in Indian yellow curry spice, which is made from turmeric root (left). Indians consume large quantities of yellow curry turmeric in their diet, and it has long been a component of their Ayurvedic medicine. We in the West are only now coming to understand the value of this dietary supplement.

It is a little known fact of epidemiology that Asian Indians have age-adjusted Alzheimer's and other senile dementia rates that are only half to a quarter of ours in the developed world. See this 2001 study [4] for one example. On learning this fact, Dr. Cole and colleagues postulated that curcumin may be a natural neuroprotectant against Alzheimer's Disease, an decided to study it in greater depth.

As medical researcher and gerontologist Steve Harris, M.D. notes, "India, where turmeric is consumed daily, has a vastly lower age-specific dementia rate [than the developed world], despite heart disease rates which vary widely across the country and in some cases surpass the West. All this suggests a specific brain-sparing minor component of the Indian diet. We can guess what this may be."

Curcumin is a lipophilic (fat-soluble) yellow-orange pigment that has long been known as a powerful antioxidant and anti-inflammatory agent. It was first significantly studied by U.S. researchers in the 1980's and 1990's for its mild anticancer effects. They discovered curcumin wasn' t particularly effective against cancer, but in the process documented that it has great safety profile. One would expect it to, because hundreds of millions have eaten it for generations in India, with no associated medical problems.

As noted in this Chemical and Engineering News article [5], Dr. Cole first suspected curcumin might be a beta-amyloid plaque binder in the brain when he noticed that the curcumin molecule was structurally very similar to two dyes, Congo Red and RS-0406, dyes commonly used by medical researchers to stain amyloid plaques in brains. This insight, combined with the epidemiological data, motivated his group to a study curcumin in greater detail.

In 2001 he and his colleagues showed that curcumin crosses the blood-brain barrier from the diet into the mouse brain, due to its low molecular weight, central lipophilicity, and polar groups at the ends. Around the same time they also fed curcumin to an Alzheimer's-prone transgenic mouse, a mouse engineered to create rapid amyloid buildup and mental problems. They discovered it had a powerful protective effect against the emergence of mental problems. Then they proved that curcumin also slows brain aging in ordinary Sprague-Dawley rats, by testing age-related decline in their ability to run water mazes [6]. Then in 2005 they uncovered some of the molecular ways in which curcumin binds to amyloid plaques and allows the immune system to break them down in living mouse brains [7].

The slide to the right indicates a number of beneficial inhibitory pathways (-), due to curcumin's ability to protect against oxidative damage and inflammation in the brain, and its apparent inhibition of cholesterol buildup as well (it is already well known that people who take statins to lower their cholesterol have half of the normal Alzheimer's risk). The slide also indictes a beneficial catalytic pathway (+), due to amyloid breakdown and clearance from the brain by the neuroimmune system, once curcumin binds to existing plaques.

Like any natural biomolecule, curcumin is a "dirty" drug with a number of different effects (antioxidant, antiinflammatory, amyloid binder, etc.), but fortunately in this case all of its effects seem to push in the same direction: neuroprotection. Such natural drugs are often much better than synthetic molecules designed by pharmaceutical companies, because the latter are usually designed for one specific biochemical purpose, but as a result often have other unanticipated side effects when used long term. Unanticipated side effects, like unanticipated mutations, are usually negative. There are no perfect drugs, only better and worse ones, and curcumin appears to be as good as they come.

Another interesting fact about curcumin is that it is also the only known therapy other than caloric restriction that reliably will reliably extend lifespan (about 10-12%) in laboratory mice. It seems most reasonable to suspect that curcumin's life extension effect is due to improved total body immunity (mediated, as with most things, through the brain) in old age. There's no reason at present to suspect that benefit wouldn't also operate in humans.

Cole's group also found curcumin is an even better inhibitor of amyloid buildup in the Alzheimer's mouse brain than nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen. Such drugs have have long been known to have significant risk reduction effect in Alzheimer's by slowing inflammation-mediated amyloid buildup in the brain, but they are hard on the gastrointestinal tract (some people can't take them orally without getting upset stomachs and nausea), and they have recently come under suspicion of causing cardiovascular problems [8].

Dr. Cole had one bit of fascinating anecdotal data to relate as well. He noted that he had been present at autopsies of very old Asian Indian and British individuals, and that the Indian brains were often stained faint yellow from years of curry eating (remember that curcumin crosses the blood-brain barrier, so this should be expected) but by his inspection these brains had youthful cell densities in the cortex.

The British brains, by contrast, having suffered through many decades of damaging high-fat diets, and without the protection of curcumin, were normal colored but appeared to have about half the cell densities of the Indian brains. I'm sure there's a very interesting paper waiting to be published here. In the meantime I will take a yellow brain, thanks!

Dr. Cole and colleagues are now testing curcumin on human Alzheimer's patients in clinical trials, but it will take several more years before this data becomes available. Meanwhile, if you are noticing age-related decline in memory or learning ability, I suggest you try curcumin empirically, under the supervision of your physician, to see if you notice any improvement. If you are like me I predict it will have a substantial positive effect.

If you are going to take curcumin in doses beyond the occasional curry dinner, you will want to take supplements. According to Sally Frautschy, Ph.D. a 900mg curcumin capsule is the rough equivalent of five regular turmeric curry dinners. The only well known problem with curcumin, besides its low absorption into the bloodstream, is that you can't repeatedly take it without food or you will tend to get an upset stomach. Taking it with some fatty food, or ideally with your daily fish oil supplements at the same time, will maximize absorption. As curcumin also has well known in vitro anticancer effects, many of which operate by direct antioxidant effect, and as very little curcumin is absorbed from the gut each time you take it, it is also very likely that you are also significantly preventing colon cancer with a lifetime of curcumin supplementation. As this 2007 study [9] shows, many in vitro studies show curcumin's anticancer effects, and Phase II studies in humans for colorectal cancer prevention are now underway and are very likely to show positive effects in a few years time.

Let me conclude by relaying Dr. Cole's comments on curcumin dosage, safety, and efficacy when I asked him by email in August 2005. Dr. Cole reminded me that he is not a physician, and is not dispensing medical advice, so be sure to take this information to your physician.

"We have a small pilot clinical trial at UCLA which is testing two fairly high doses of 2,000 and 4,000 mgs of curcumin manufactured as an extract by Sabinsa. Long term trials have not shown side effects at ~1200 mg for three years while short term (3 mos) trials in cancer patients report no problems up to 8 grams a day, but other studies suggest some patients get diarrhea at 3 or 4 grams [3,000 - 4,000 mg/day]. As I said in my talk, one reason the doses are so high is poor absorption. Curcumin is poorly soluble and poorly absorbed because of glucuronidation and high first pass metabolism[, a problem that] that the addition of piperine [in the Life Extension Foundation and Sabinsa formulations] is supposed to limit a bit. For now, curcumin should be taken with a fatty meal—milk products, plant or animal fat sources are all handled the same way. I would suggest people who want to try it start on around 500-1,000 mg a day, which seems to have useful effects in small trials in people and if they have no tolerance problems and have say mild Alzheimer's Disease or are on the cusp of getting it maybe go up to 2,000 mg, but not higher. I have never heard of a problem with people taking less than 2,000 mg/day, but it could happen because large scale human trials with high doses still have not been done. Small trials for cancer claim no adverse effects up to 8 grams/day, but I definitely wouldn't go there.

We believe that curcumin synergizes with omega-3 fatty acids in [preventing] Alzheimer's Disease and probably other neurodegenerative conditions and would suggest taking it with fish oil or algal DHA, based on our animal data. The American Heart Association recommends 2 or 3 fish oil capsules (1 gram each) a day and they have clinical trial and safety data backing this up. DHA will soon go into large multicenter trials. Unfortunately, all of my current thoughts about dose and efficacy are just guesstimates since we have no trial data on curcumin or omega-3 fatty acids. We are currently seeking grant support to address the issue of curcumin bioavailability which is a problem that we think we can solve. At least we have some reasonable things to test. All we have now are anecdotal reports suggesting some efficacy and of course our animal model data. Without trial data we cannot formally recommend anything, so Caveat Emptor!"

In summary, curcumin appears to be an amazing natural neuroprotectant, at least as good for your brain as DHA/fish oils, and perhaps even better. It is a substance that people may only learn slowly about for the time being because, as Dr. Cole points out, drug companies cannot patent it, so it falls in the realm of nutritional supplements. Supplements are a crowded field full of lots of hype and misinformation, and an area where multimillion dollar studies proving efficacy are slow to fund and emerge. Fortunately, armed with the information you can find here and on the web, you may not have to wait.

Let me close with my personal story: As outlined in "A Basic Brain Protection Plan," 2006, I take two 900 mg capsules of Super Curcumin with Bioperine, from LEF.org. I also take 3,000 mg/day of Omega-3 fatty acids from fish oils (ten regular strength capules/day). I've been on this curcumin and fish oils regimen for six months as of this writing, long enough for any placebo effect to have worn off, and journaling my impressions.

After noticing increasing difficulty over the last several years recalling things both recently and distantly learned, and having to speak sentences that aren't what I want to say because I have a word on the tip of my tongue but can't immediately remember the name for it, I have seen a clear improvement in my working, verbal, and long term memory and learning ability. I've also noticed I can do more activities than I did before on the computer and in other complex mental tasks.

One final tip: Before you begin these supplements you should think about taking a formal before test and after test of your memory (make sure it is six months after starting curcumin, so there is no longer any placebo effect), to better validate your own subjective impressions of their benefit. A quick $20 online memory assessment designed for individuals betweeen 45 and 86 years of age can be found at Cognicheck.com. Free online tests may also available, but I haven't found any good ones yet. I was too busy at the time of starting curcumin to search out and take a formal test, but you don't have to make the same mistake.

In April 2006 Nintendo released a memory game, Brain Age, for their DS portable game player. I've played it and while not perfect I found it reasonably fun to play and a good first effort at keeping track of changes in your "mental age" over time, as well as a nice way to regularly exercise your short term memory. I'm looking forward to seeing more of these "serious games" for mental assessment and development in coming years.

Best of luck and thank you for passing on this information to those who may benefit from it. I wish you and yours many future years of healthy mind!

Feedback? Reach me at johnsmart{at}accelerating{dot}org.

References
[1] Mishra S, Palanivelu K. The effect of curcumin (turmeric) on Alzheimer's disease: An overview. Ann Indian Acad Neurol [serial online] 2008 [cited 2008 Jul 30];11:13-9. Available from: http://www.annalsofian.org/text.asp?2008/11/1/13/40220
[2] Dr. Cole's home page: http://www.neurology.ucla.edu/faculty/ColeG.htm
[3] Dr. Cole's PowerPoint slides from his LA Future Salon talk: http://accelerating.org/ftp/Alzheimers(GregCole05).ppt
[4] Vas CJ et. al. Prevalence of dementia in an urban Indian population. Int Psychogeriatr, 2001 Dec;13(4):439-50. Available from: http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=12003250
[5] Rovner, S.L. (2005). "Untangling Alzheimer's," Chemical and Engineering News, 83(8), 38-45.
[6] Frautschy SA, Cole GM, etc (2001).,"Phenolic anti-inflammatory antioxidant reversal of Abeta-induced cognitive deficits and neuropathology," , Neurobiol Aging, 22(6):993-1005 (http://nootropics.com/curcumin/)
[7] Yang F, Cole GM, etc (2005)., "Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo.," J Biol Chem, 280(7):5892-5901
[8] Marx, V (2005). "Doubts escalate over painkillers," Chemical and Engineering News, 82(31), 7.
[9] Johnson, JJ, Mukhtar H. Curcumin for chemoprevention of colon cancer. Cancer Letters, 2007 Oct 8;255(2):170-81. Epub 2007 Apr 19.