Curry Power

Imagine that you’re living 3,000 years ago in a village in what’s now southern India. When you get sick or injured, you visit the healer, who most likely is a practitioner of the herbal medicine called ayurveda. For whatever ails you, you’ll probably get a treatment that includes a bit of bright, yellow-orange powder, the spice turmeric.

If you have a scrape, the healer will put turmeric on it. Indigestion? Turmeric. Jaundice? Turmeric. “Nervous weakness”? That’s right—turmeric.

The powder comes from a broad-leafed plant that thrives in the hot, rainy climates of southern Asia. Its pinecone-shaped stalks of white, pink, and yellow flowers smell faintly of mango, and its bulbous roots resemble those of the ginger plant, to which it is closely related. Cut a root open, however, and you’ll find its fleshy interior is that vivid yellow-orange.

People in the region long ago discovered that boiling, drying, and grinding these roots produces a fragrant powder with a nutty, slightly bitter taste. People ascribed healing properties to the powder, particularly for ailments involving inflammation. Meanwhile, the substance became pervasive in regional diets as the color-giving component of most yellow curries. The widespread use of turmeric continues today in both Indian cuisine and in ayurvedic medicine.

Western medical doctors are often skeptical about traditional and herbal cures. In the case of turmeric, however, a surge of scientific research in recent years has supported at least some of the claims made for turmeric’s active ingredient, a compound called curcumin. This research has shown that curcumin—available commercially as an extract—acts as both a powerful antioxidant and an anti-inflammatory agent.

It was this anti-inflammatory property that led University of California, Los Angeles researchers Greg Cole and Sally Frautschy to wonder in the mid-1990s whether curcumin might be effective against a condition that ayurvedic practitioners might not have considered: Alzheimer’s disease.

An estimated 24 million people worldwide have Alzheimer’s. The U.S. Food and Drug Administration has approved five drugs to mitigate its symptoms, but no FDA-approved drug exists to combat the causes of the disease.

Alzheimer’s disease involves the steady deterioration of nerve cells in the brain, leading to dementia. A leading theory holds that the disease arises when a small protein in the brain gathers into toxic clumps called plaques. In this scenario, these plaques kill brain cells in part by triggering inflammation, a state of heightened immune system activity that can damage the body’s own cells. The plaques also produce free radicals, which cause oxidative damage to nerve cells.

“We looked at [curcumin] and said, ‘You know, here’s something which is anti-inflammatory,'” says Cole. “When we saw that curcumin was also a better antioxidant than even vitamin E, we said, ‘This thing has got all these properties that look good, so we’ll test it,'” against Alzheimer’s.

Those experiments and subsequent work by other scientists have shown that, in addition to its anti-inflammatory and antioxidant properties, curcumin has several effects that may work in tandem to protect the brain from plaques in other ways. “If curcumin had a single [molecular] target, it probably would not be as good a drug,” says Bharat Aggarwal, who studies curcumin at the M.D. Anderson Cancer Center in Houston. “But because it has multiple targets, [it’s] very attractive.”

Counting the ways

In the late 1990s, Cole’s team screened curcumin and 11 other candidate compounds that have antioxidant and anti-inflammatory properties. The scientists tested the substances in mice that had an Alzheimer’s-like condition created by infusing the plaque-forming protein, called amyloid-beta, into the mice’s brains. The results were surprising, Cole says. “Amyloid-beta was reduced by the curcumin but not by these other [compounds].” Compared with mice that were fed normal diets, the animals treated with curcumin had up to 80 percent fewer plaques.

The reasons for this decrease in amyloid-beta plaques began to emerge in 2002, when Cole’s team showed that, in lab dishes, curcumin inhibits amyloid-beta proteins from clumping into plaques. Two years later, a team of researchers in Japan led by Kenjiro Ono of the Kanazawa University Graduate School of Medical Science found that curcumin not only blocks plaque formation but also weakens existing plaques in the lab and triggers their disintegration. Ono’s group didn’t figure out the physical mechanism by which curcumin disrupted the plaques, however.

A clue to that mechanism came from an unexpected source. It turned out that curcumin resembles molecules that scientists had been using in medical imaging to make plaques more visible in brain scans. Because of that structural similarity, curcumin also has a strong affinity for binding to amyloid-beta.

Using mice engineered to have a mutated human gene known to cause plaque, Cole’s group showed in 2005 that curcumin’s direct binding to the amyloid-beta protein accounts for the chemical’s ability to interfere with plaque formation and to degrade existing plaques.

Ingesting curcumin can also lower a person’s cholesterol. In a study by researchers at the Amala Cancer Hospital and Research Center in Amalanagar, India, people who took 500 milligrams of curcumin daily for 7 days had a 29 percent higher concentration of beneficial high-density lipoprotein cholesterol than they’d initially had, and their total blood-cholesterol concentration was an encouraging 11 percent lower.

Several studies during the 1990s found that people with unhealthy cholesterol profiles had a greater risk of developing Alzheimer’s disease than did people with normal cholesterol readings. A team led by Takashi Mori of the Saitama Medical University in Japan found in 2001 that cholesterol accumulates within plaques and may help amyloid-beta proteins bundle together, suggesting that reducing cholesterol might also inhibit plaque formation in the brain.

More recently, some scientists have suggested that a person’s immune system may also be involved in Alzheimer’s. “Everybody is always producing amyloid-beta, but not everybody is developing the disease,” says Milan Fiala of the Greater Los Angeles Veterans’ Affairs Medical Center. The reason, he argues, is that immune system cells called macrophages normally patrol the brain and gobble up budding plaques. Fiala suspects that, in people who develop Alzheimer’s, these macrophages aren’t performing their cleanup duty properly.

That’s just what he found when he tested macrophages taken from Alzheimer’s patients. When placed in lab dishes with amyloid-beta plaques, these cells had almost no ability to devour the plaques, largely because of reduced activity of a gene called MGAT3. Adding curcumin to the dish restored the plaque-clearing prowess of about half of these macrophages and returned MGAT3 to its normal activity, Fiala and his colleagues report in the July 31 Proceedings of the National Academy of Sciences (SN: 7/21/07, p. 37).

“The list of [curcumin’s] effects goes on and on, and they’re all in your favor,” Aggarwal says.

Down to the roots

If curcumin really does fight the plaques that lead to Alzheimer’s, shouldn’t populations in which people eat a lot of turmeric-containing curry have a lower incidence of the disease?

In fact, studies in India seem to show a much lower rate of Alzheimer’s disease than exists in Western, industrialized countries. For example, a 2001 comparison of sample populations of people 65 and older in Ballabgarh, India, and in Monongahela Valley, Pa., found that only 4.7 cases of probable Alzheimer’s disease were diagnosed per year among every 1,000 people in India, while the comparable rate in the Pennsylvania sample was 17.5 cases—almost four times as high. The researchers, led by Vijay Chandra of the University of Pittsburgh Graduate School of Public Health, wrote that, “These are the first [Alzheimer’s disease] incidence rates to be reported from the Indian subcontinent, and they appear to be among the lowest ever reported.”

Of course, a curry-consuming tradition is not the only difference between India and other countries. Some other physical or cultural trait, such as genetic differences or a relatively short life expectancy there, could account for India’s low rate of Alzheimer’s disease.

Some evidence suggests that a diet rich in yellow curry may indeed play a role. In 2003, Tze-Pin Ng of the National University of Singapore and his colleagues tested the mental performance of 1,010 Singaporeans between the ages of 60 and 93, none of whom had been diagnosed with any form of dementia. The researchers also surveyed the volunteers about their eating habits and found that those who reported that they ate curry “occasionally” or “often or very often” gave significantly better cognitive performances than did people who claimed to eat curry only rarely, Ng’s team reported in the Nov. 1, 2006 American Journal of Epidemiology (SN: 11/11/06, p. 316). The researchers noted that the curry typically used in Singapore is yellow curry, which is rich in curcumin-containing turmeric, rather than green or red curry.

Such studies of dementia in curry-consuming cultures are not conclusive, scientists agree, but some researchers believe that these data suggest that a link may exist between frequent consumption of yellow curry and reduced risk of mental decline from Alzheimer’s.

Cupboard cure?

If it does prove effective against the disease, curcumin would have an important advantage over other Alzheimer’s treatments under development. People can get it at the grocery store, in turmeric powder shelved in the spice aisle.

The fact that turmeric root is already sold all over the world was one of the reasons for researchers’ original interest. “If we’re going to have a treatment which has worldwide impact, it would need to be cheap,” says Jeffrey Cummings of the University of California, Los Angeles. “So the economics of curcumin are very fortuitous in that it is a cheap, widely available compound.”

However, Cummings and others caution that the ready availability of curcumin is also one of its dangers. In the United States, the 1994 Dietary Supplement Health and Education Act allows companies to sell dietary-supplement pills containing concentrated plant extracts such as curcumin without approval from the FDA. The quality of such pills is essentially unregulated—each company is responsible for ensuring that its pills’ ingredients are safe and that they contain what the company claims them to be. Although bills pending in Congress would increase FDA oversight of the supplement industry, it’s currently a buyer-beware market.

Fortunately, millennia of use in food, as well as recent scientific tests, have left curcumin with an excellent safety record. Neither history nor recent research has turned up adverse health effects in people consuming reasonable amounts of curcumin, Aggarwal says.

The final word on whether curcumin actually helps prevent and treat Alzheimer’s disease can come only from the gold standard of medical research: a placebo-controlled trial on people. Such data for curcumin are not yet available, but University of California, Los Angeles neurologist John Ringman is conducting a trial of curcumin in about 40 Alzheimer’s patients. The trial is in its final stages, and the researchers expect to have their results prepared for publication by early next year.

In the meantime, if you want to remember to check back later on Ringman’s study, it certainly couldn’t hurt to add some yellow curry to your diet.