Turmeric Is “The Spice of Life”

Turmeric—Ancient Wisdom in a Bottle

Turmeric Is “The Spice of Life”
An old kid on the block demonstrates new capabilities in combating Alzheimer’s disease
By Will Block

ome colors, like the late Rodney Dangerfield, don’t get no respect. Take yellow, which has somehow acquired a bad reputation in some quarters. Yellow journalism is the pits (are you listening, C-BS?). Being yellow-bellied or having a yellow stripe down your back is shameful, although perhaps not as bad as having a yellow sheet (for you innocents, that’s slang for a criminal record). Either way, you surely wouldn’t want to come down with yellow fever or develop the blurry, yellowed vision characteristic of cataracts.

On the other hand, many good things are yellow, such as the sun, and daffodils and canaries and bananas. And gold. And blondes! Yellow highlighters are nifty, the Yellow Pages are useful, and yellow tennis balls are fun, especially if you have a yellow Labrador retriever who plays tennis. Yellowknife is a great town (it’s the capital of Canada’s Northwest Territories—remember that in case you ever get on Jeopardy). And yellow mustard is yummy—it gets its color from turmeric. Which is very yellow.

How Much Curry Do You Eat?

If you lived in India or in some other countries of Southeast Asia, you would probably eat turmeric (Curcuma longa) almost every day, because it’s one of the principal spices found in the curries that are such an important part of the diet in that part of the world. (Turmeric is also a well-known remedy in the ancient Indian tradition of Ayurvedic medicine.) You might also become part of an interesting statistic: the elderly (aged 70–79) residents of rural India, who eat large amounts of curry, appear to have the lowest incidence of Alzheimer’s disease in the world—significantly lower than that of Americans. 1

Does that prove that curry helps prevent Alzheimer’s? No, but there is good reason to think that it might, mainly because of the turmeric it contains. This yellow spice, a member of the ginger family, contains a class of polyphenolic compounds called curcuminoids. Research on these compounds has focused primarily on the one for which the group is named: curcumin, which is known to be a very potent antioxidant (as are several other curcuminoids as well). Curcumin is also a potent anti-inflammatory agent—it’s widely used in the treatment of arthritis—and for that reason it is described as an NSAID, a nonsteroidal anti-inflammatory drug (it’s a “drug” only in the same sense in which countless other nonprescription remedies sold in the drugstore are called drugs).

These two well-established properties of curcumin—antioxidant and anti-inflammatory—are believed to account in large measure for its demonstrated ability to help prevent the neurodegenerative changes seen in Alzheimer’s disease and Parkinson’s disease.* Particularly noteworthy is curcumin’s ability to inhibit both the formation of amyloid-beta (also called beta-amyloid) and the neurotoxicity of amyloid-beta that has already been formed. Amyloid-beta, a protein, is the principal constituent of senile plaque, the yellowish (there’s that color again!) gunk that destroys the brain cells of Alzheimer’s victims.


*See “Turmeric May Help Prevent Alzheimer’s and Parkinson’s Diseases” (February 2002) and “Turmeric Protects Your Brain Cells” (July 2004). It’s worth noting that curcumin is also believed to have significant anticholesterol and antitumor effects, which may or may not be related to its antioxidant and anti-inflammatory effects.2 And here’s an odd fact: although curcumin is bright yellow, it has no flavor—turmeric’s flavor comes from other components.


Heat! Shock! Proteins! Good!

It turns out, though, that there may be additional ways in which curcumin and its chemical cousins help protect our brains from the ravages of dementia. For example, in addition to being a direct antioxidant, i.e., a molecule that can neutralize harmful free radicals through direct chemical reaction, it turns out that curcumin may also be an indirect antioxidant by stimulating other chemical processes that tend to reduce oxidative stress. One such process, discussed in a recent review paper, is the generation of heat-shock proteins.3 These proteins are so named because our bodies produce larger-than-normal amounts of them in response to excessive heat, which the exquisitely tuned biochemical machinery of our cells cannot long tolerate without suffering irreversible damage. (Heat-shock proteins, of which there are many varieties, are also called stress proteins.)

The primary role of the ubiquitous, tough, and amazingly versatile heat-shock proteins is to try to control and repair the damage done to other proteins (including countless different kinds of enzymes that are vital for all life processes), which are notoriously vulnerable to the effects of heat and other forms of stress. Think of the heat-shock proteins as army medics, rushing onto the battlefield to tend to the wounded and save as many as they can. They do this not just when the “enemy” is heat, but also when it is various other forms of attack, such as infection, inflammation, oxidative stress, exposure to environmental toxins or cytotoxic drugs (drugs that are toxic to cells), tissue trauma, oxygen deprivation, or other processes that threaten to damage or even kill the cells. Such processes can be life-threatening, depending on which cells are affected.

Curcumin Induces Heat-Shock Proteins

This generalized stress response of the human body, like various other stress responses, has a hidden benefit beyond the immediate results of the intervention: it results in a certain amount of stress tolerance by conditioning us to cope with the daily barrage of biochemical “insults” upon our cells. Although prolonged exposure to severe stress will inevitably lead to cell damage or death, it is believed that lower, more benign levels of stress are actually good for us by keeping the biochemical machinery of cell repair in good working order. The net result is a cytoprotective effect against stress-induced molecular damage, such as that which leads to the formation of two of the hallmarks of Alzheimer’s disease: senile plaque (amyloid-beta) and its evil twin, neurofibrillary tangles.

In the brains of Alzheimer’s victims, researchers have found significant associations between plaques and tangles and the presence of a particular heat-shock protein called heme oxygenase-1 (HO-1).3 This enzyme (all enzymes are proteins, but not all proteins are enzymes) is apparently released in an effort to control a particular aspect of the damage associated with neurodegeneration, and its action results in the formation of antioxidant molecules called biliverdin and bilirubin. We know that HO-1 is triggered by the presence of free radicals as well as by depletion of glutathione, the body’s most important antioxidant. Thus it has become a matter of interest to determine whether any nutritional supplements might also induce the production of HO-1, for an added boost to the cytoprotective effect afforded by this enzyme.

You can see it coming, can’t you? Yup, it turns out that curcumin is a good candidate for this role, because studies have shown that it is a potent inducer of HO-1 in vascular endothelial cells (the cells that form the inside lining of blood vessels).4,5 Other evidence suggests that curcumin probably has this effect in the central nervous system as well, and it may therefore be able to help forestall the development of Alzheimer’s disease.3,6

Metal Ions! Good! Bad! (It Depends)

Yet another way in which curcumin and the related curcuminoids may help protect our brains is through the process of metal chelation (see the sidebar), in which curcumin reduces the levels of certain metal ions by chemically scavenging them.* Metal ions of many kinds—mostly light metals, i.e., those of low atomic weight—are ubiquitous in the human body. (Fortunately, this is not true of heavy metals, most of which are toxic.) At one extreme of the “freedom scale,” the metal ions are dissolved, as free ions, in all of our bodily fluids, including the aqueous interiors of our cells; at the other extreme, they are chemically bound in large, complex molecules, such as metalloproteins (e.g., hemoglobin).


*A metal ion is a metal atom that has lost one or more of its electrons and thus carries a positive electric charge. Calcium atoms, e.g., characteristically lose two electrons and thus have a charge of +2. Iron ions can be either +2 or +3. In metal-containing chemical compounds, the metal atoms are always ionized.


How Does Chelation Work?

Claw. Quick—what does that make you think of? Chances are, you thought first of a lion or tiger, or maybe your own sweet little kitty. Or perhaps you thought of a bear (especially if you have a sweet tooth for pastries). If you like seafood, maybe you thought of lobster or crab—and now we’re getting somewhere (you’ll see in a moment). Unless you’re a terminally nerdy chemist, however, it’s a cinch that you didn’t think of a chelating agent, such as EDTA (a synthetic diamino acid) or curcumin (a polyphenolic alpha,beta-unsaturated diketone).

A chelating agent is a kind of molecular claw (the word comes from the Greek khele, claw), in which two similar groups of atoms within the same molecule, acting like tiny pincers, “grab” a metal ion by forming chemical bonds to it (think of a crab seizing and holding a prey item between its claws). When this occurs, the metal ion becomes a chemical link between the pincer atoms, and a stable, ringlike molecular structure is formed. In this example, the chelating agent is said to be bidentate, because the pincer action consists of two “teeth” (yes, the metaphor is hopelessly mixed, but that’s the way the terminology evolved). Many other chelating agents have more than two teeth; EDTA, e.g., has six, so it’s hexadentate and can grab a metal ion with six bonds coming from six different directions.

The secret to chelation is in the nature of the individual atoms that constitute the teeth, in the juxtaposition of these atoms within the larger molecular structure, and in their ability to form a special kind of bond, called a coordinate covalent bond, with the ions of certain metals. If all the requirements are met, then bingo—the metal ion is grabbed and “locked up” in the chelator’s clawlike embrace. The resulting molecular entity, called a coordination complex, is typically very stable and will not easily yield back the metal ion. Thus, if this complex is excreted in the natural course of things, the metal ion goes with it.

Coordination complexes formed from chelated metal ions are common in living organisms. Three examples are heme (the iron-containing nonprotein portion of the hemoglobin molecule), chlorophyll (the magnesium-containing green pigment that plays a central role in photosynthesis), and cyanocobalamin (vitamin B12, which contains a cobalt ion).

Metal ions are vital for many life processes (our hearts and brains, e.g., could not possibly function without them), but sometimes they can be harmful, as when calcium ions become incorporated into atherosclerotic plaque, a process called calcification (for more on this serious cardiovascular problem, see the article on page 28 of this issue.)

Another way in which metal ions can be harmful is when they catalyze unwanted chemical reactions, such as some of the oxidative reactions that are responsible for the formation of amyloid-beta in the brains of Alzheimer’s victims, or subsequent reactions that are responsible for the oxidative damage caused by amyloid-beta (it’s curious that oxidative stress is both a cause of, and an effect of, amyloid-beta). Certain metal ions, notably copper, iron, and zinc, are known to induce the aggregation of amyloid-beta molecules into senile plaques, and they are found in much greater concentrations in the vicinity of the plaques than elsewhere. (Bear in mind that senile plaque is totally different from atherosclerotic plaque. And then there’s dental plaque …)

Curcumin Chelates Alzheimer’s Metals

Intrigued by the “metal connection” and the fact that curcumin, a known anti-Alzheimer’s agent, is also known to be a chelating agent for some metals, researchers at the Chinese University of Hong Kong decided to investigate whether the former property might result, at least in part, from the latter property, i.e., they wanted to know whether curcumin could slow the development or progression of Alzheimer’s disease by chelating some of the metals believed to play a role in it.7

In laboratory experiments, they established that curcumin is an effective chelator of copper and iron, but not of zinc. Actually, they used a turmeric extract of curcuminoids, consisting of a typical mixture: about 80% curcumin, 15% desmethoxycurcumin, and 5% bisdesmethoxycurcumin. The concentrations of the metals that could be chelated were lower than those in Alzheimer’s brains, and lower even than those in normal brains, which means that chelation of the actual (higher) concentrations would also occur. The ability of curcumin to be an effective chelator in a human being would then depend on whether its own concentration in brain tissue could be made high enough, through supplementation with turmeric, to provide effective chelation—and that remains an open question.

Turmeric Is Unburied Treasure

Not open to question, however, is the indisputable fact of turmeric’s beneficial effects, through its curcuminoid content, on human health. One of life’s best yellow things, turmeric (often called “the spice of life”) also serves as a reminder that the natural world holds medicinal treasures galore. Many have already been revealed to us through the wisdom of the ancients, but many others are surely still undiscovered—waiting, like buried gold, to be unearthed by us or by generations yet unborn. Let us hope that we will have the collective wisdom to preserve and protect our priceless natural heritage forever.

References

  1. 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;21:8370-7.
  2. PDR for Nutritional Supplements. Medical Economics Company, Montvale, NJ, 2001.
  3. Calabrese V, Scapagnini G, Colombrita C, Ravagna A, Pennisi G, Giuffrida Stella AM, Galli F, Butterfield DA. Redox regulation of heat shock protein expression in aging and neurodegenerative disorders associated with oxidative stress: a nutritional approach. Amino Acids 2003 Dec;25(3-4):437-44.
  4. Motterlini R, Foresti R, Bassi R, Green CJ. Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress. Free Rad Biol Med 2000;28:1303-12.
  5. Motterlini R, Foresti R, Bassi R, Calabrese V, Clark JE, Green CJ. Endothelial heme oxygenase-1 induction by hypoxia: modulation by inducible nitric oxide synthase (iNOS) and S-nitrosothiols. J Biol Chem 2000;275:13613-20.
  6. Calabrese V, Butterfield DA, Stella G. Nutritional antioxidants and the heme oxygenase pathway of stress tolerance: novel targets for neuroprotection in Alzheimer’s disease. Ital J Biochem 2003;52(4):177-81.
  7. Baum L, Ng A. Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer’s disease animal models. J Alzheimer’s Dis 2004;6:367-77.

Dual-Action Galantamine

Galantamine provides a heralded dual-mode action for boosting cholinergic function: it inhibits the enzyme acetylcholinesterase, thereby boosting brain levels of acetylcholine, and it modulates the brain's nicotinic receptors so as to maintain their function. The recommended daily serving ranges from a low of 4 to 8 mg of galantamine to begin with to a maximum of 24 mg, depending on the individual's response.

For an added measure of benefit, it is a good idea to take choline, the precursor molecule to acetylcholine, as well as pantothenic acid (vitamin B5), an important cofactor for choline. Thus it is possible to cover all bases in providing the means to enhance the levels and effectiveness of your acetylcholine.


Will Block is the publisher and editorial director of Life Enhancement magazine.

FREE Subscription

  • You're just getting started! We have published thousands of scientific health articles. Stay updated and maintain your health.

    It's free to your e-mail inbox and you can unsubscribe at any time.
    Loading Indicator