Turmeric and its derivatives have a great deal of pharmacologic activity. Although a number of components demonstrate activity, the volatile oil components and curcumin are believed to be the most active components. Turmeric has been described as follows:

HEALTH BENEFITS OF TURMERIC OR CURCUMIN

Antioxidant Effects

Turmeric extracts exert significant antioxidant activity. Although both water- and fat-soluble extracts have been shown to be effective antioxidants in various in vitro and in vivo models, curcumin is the most potent component. The antioxidant activity of curcumin is comparable to standard antioxidants like vitamins C and E and butylated hydroxyanisole and butylated hydroxytoluene.

Because of its bright yellow color and antioxidant properties against lipid peroxidation, curcumin is used in butter, margarine, cheese, and other food products.

For active oxygen species, curcumin is slightly weaker than vitamin C but stronger than vitamin E and superoxide dismutase.

Against hydroxyl radicals, curcumin offers greater effectiveness than these vitamins. Not all of the antioxidant properties of turmeric are due to curcumin alone, since the aqueous extract of turmeric is more effective against superoxide than curcumin and is much stronger in inhibiting oxidative damage to DNA. The antioxidant activities of curcumin may in part explain the anticarcinogenic and cardioprotective capacity of this spice. In vitro and in vivo studies have also shown this antioxidant action to be neuroprotective as well.

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Anticarcinogenic Effects

The antineoplastic effects of turmeric and curcumin have been demonstrated at all steps of carcinogenesis: initiation, promotion, and progression. In addition to inhibiting the development of cancer, several studies suggest that curcumin can also promote cancer regression.

Turmeric and curcumin are nonmutagenic and have been shown to suppress the mutagenicity of several common mutagens (e.g., cigarette smoke condensates, benzopyrene, dimethylbenz[a] anthracene), as do chili and capsaicin. Turmeric and curcumin compounds have been found to induce apoptosis in lung and colon tumor cell lines. Turmeric and curcumin have also demonstrated impressive anticancer effects against a number of chemical carcinogens on a wide range of cell types in both in vitro and in vivo studies. Curcumin has demonstrated an impressive ability to reduce the levels of urinary mutagens.

The protective effects of turmeric and its derivatives are only partially explained by its direct antioxidant and free radical–scavenging effects. It also inhibits nitrosamine formation, enhances the body’s natural antioxidant system, increases the levels of glutathione and other nonprotein sulfhydryls, and acts directly on several enzymes and gene loci.

Curcumin’s ability to protect against damage to DNA was demonstrated in a study in a community with a high content of groundwater arsenic. Arsenic is extremely carcinogenic because it causes severe oxidative damage to DNA. Blood samples before curcumin supplementation showed severe DNA damage, with increased levels of free radicals and lipid peroxidation. Three months of curcumin intervention reduced the DNA damage, retarded free radical formation and lipid peroxidation, and raised the level of antioxidant activity. In another study, cigarette smokers receiving turmeric demonstrated a significant reduction in the level of urinary-excreted mutagens—an indication of the ability of the body to rid cancer-causing compounds via detoxification mechanisms. For many reasons, curcumin is emerging as a very important agent in the battle against cancer.

Data also suggest that curcumin causes cancer to regress. Some of curcumin’s benefits come from its antioxidant activity, but it also:

• Inhibits the formation of cancer-causing nitrosamines

• Enhances the body’s production of cancer-fighting compounds, such as glutathione

• Promotes the liver’s proper detoxification of cancer-causing compounds

• Prevents overproduction of cyclooxygenase-2, an enzyme that may contribute to the development of tumors

In addition to these preventative actions, curcumin has also been shown to inhibit tumor growth in several ways by:

• Inhibiting epidermal growth factor (EGF) receptor sites: EGF stimulates cells to proliferate by connecting to a receptor on the cell surface. About two thirds of all cancers produce an abundance of these receptors, which makes them highly sensitive to EGF. By reducing the number of EGF receptors, curcumin decreases the cell’s tendency to proliferate.

• Inhibiting angiogenesis: Fibroblast growth factor is a protein that promotes the formation of new blood vessels to feed the growing tumor. Curcumin inhibits production of this growth factor.

• Inhibiting nuclear factor-κβ: This is a protein that many cancer cells produce to block the signals commanding them to stop proliferating.

• Increasing the expression of the nuclear p53 protein: This protein is essential for apoptosis, the normal process of cell “suicide.”

• Inhibiting enzymes that promote cancer cell growth.

 

Antiinflammatory Effects

The volatile oil fraction of C. longa has been demonstrated to possess antiinflammatory activity in various experimental models. Its effects in these studies were comparable to cortisone and phenylbutazone.

Even more potent in acute inflammation is curcumin.30-33 Curcumin is as effective as cortisone or phenylbutazone in models of acute inflammation but only half as effective in chronic models.

However, although phenylbutazone and cortisone are associated with significant toxicity, curcumin displays virtually no toxicity.

The rank in order of potency of curcumin analogs, cortisone, and phenylbutazone in carrageenan-induced paw edema is as follows:

Sodium curcuminate can be produced by mixing turmeric with slaked lime. This mixture, applied as a poultice, is an

·        O

·        C CH3

·        H3CO

·        HO CH CH CH

·        OCH3

·        OH

sodium curcuminate > tetrahydrocurcumin > curcumin > cortisone > phenylbutazone > triethylcurcumin

Curcumin’s counterirritant effect may also be a major factor in its topical antiinflammatory action. Capsaicin, a similar pungent principle from Capsicum frutescens (cayenne pepper), has been shown to be quite effective as a topical pain reliever in cases of postherpetic neuralgia and arthritis. Both capsaicin and curcumin deplete nerve endings of the neurotransmitter of pain.

Based upon in vitro studies, curcumin exhibits many direct antiinflammatory effects including:

• Inhibition of leukotriene formation

• Inhibition of platelet aggregation

• Promotion of fibrinolysis

• Inhibition of neutrophil response to various stimuli involved in the inflammatory process

• Stabilization of lysosomal membranes

In addition to its direct antiinflammatory effects, curcumin also appears to exert some indirect effects. In models of chronic inflammation, curcumin was much less active in adrenalectomized animals. Possible mechanisms of action include the following:

• Stimulation of the release of adrenal corticosteroids

• “Sensitizing” or priming cortisol receptor sites, thereby potentiating cortisol action

• Increasing the half-life of endogenous cortisol through alteration of hepatic degradation

 

Cardiovascular Effects

The effects of turmeric and curcumin on the cardiovascular system include prevention of oxidative damage to low-density lipoprotein cholesterol, inhibiting platelet aggregation, and reducing fibrinogen levels. These effects are of great significance in preventing atherosclerosis and its complications.

In animal studies, adding as little as 0.1% curcumin to a high cholesterol rat diet decreased cholesterol levels to one half of those found in rats fed cholesterol but no curcumin.38 Curcumin’s cholesterol-lowering actions include interfering with intestinal cholesterol uptake; increasing the conversion of cholesterol into bile acids by increasing the activity of hepatic cholesterol-7-α-hydroxylase, the rate-limiting enzyme of bile acid synthesis; and increasing the excretion of bile acids via its choleretic effects.

Effects on blood lipids from human studies are equivocable. In one small study, 10 healthy volunteers received 500 mg/day of curcumin for 7 days.40 A significant decrease in the level of serum lipid peroxides of 33%, an increase in high-density lipoprotein cholesterol of 29%, and a decrease in total serum cholesterol of 11.63% were observed. However, two other studies failed to show any effect on blood lipids.

Curcumin’s effect on fibrinogen and platelet aggregation, which are known predictors of future coronary heart disease, may be more significant than its effects on cholesterol.47 In a preliminary study of 30 apparently healthy volunteers, baseline levels of fibrinogen were recorded, and 8 subjects were found to have high plasma fibrinogen (above 350 ng/mL).48 These subjects were given a hydroalcoholic extract of C. longa containing 20 mg of curcumin for 15 days. Impressively, curcumin administration decreased the fibrinogen levels to the 240 to 290 mg/dL range.

Turmeric’s and curcumin’s action on inhibiting platelet aggregation appears to be mediated by inhibiting the formation of thromboxanes (a promoter of aggregation) while simultaneously increasing prostacyclin (an inhibitor of aggregation).

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Hepatic Effects

Curcumin exhibited hepatoprotection similar to that of glycyrrhizin and silymarin against carbon tetrachloride and galactosamine-induced liver injury.2,49 This protection was largely a result of its potent antioxidant activity. Similar results were seen with Javanese turmeric (Curcuma xanthorrhiza). Mice given intraperitoneal injections of the hepatoxic drugs carbon tetrachloride (32 mg/kg) and acetaminophen (600 mg/kg) experienced significantly decreased liver damage, as measured by serum glutamate oxaloacetate and serum glutamate pyruvate transaminase when treated with 100 mg/kg of turmeric.

The antioxidant and hepatoprotective effects alone support turmeric’s historical use in liver disorders; however, turmeric and curcumin also exert antiinflammatory and choleretic effects. The increases of serum glutamate oxaloacetate and serum glutamate pyruvate transaminase commonly seen in experimental models of inflammation were prevented by curcumin.

Curcumin is an active choleretic, increasing bile acid output by more than 100%.2 In addition to increasing biliary excretion of bile salts, cholesterol, and bilirubin, curcumin also increases the solubility of bile.44 This suggests a benefit in the prevention and treatment of cholelithiasis.

Gastrointestinal Effects

Turmeric and its components exert a number of beneficial effects on the gastrointestinal system. Turmeric’s long use as a carminative has significant research support.2 Specifically, curcumin was shown to inhibit gas formation by Clostridium perfringens and in rats given diets rich in flatulence-producing foods. In addition, sodium curcuminate was shown to inhibit intestinal spasm, and another compound from turmeric, p-tolymethylcarbinol, was shown to increase the secretion of secretin, gastrin, bicarbonate, and pancreatic enzymes.2

As a component of curries and spicy foods, there is some concern that turmeric may be irritating to the stomach. However, several studies showed turmeric to be beneficial to gastric integrity.

Turmeric and curcumin were shown to increase the mucin content of the stomach and exert gastroprotective effects against ulcer formation induced by stress, alcohol, indomethacin, pyloric ligation, and reserpine.2,51 However, at high doses, curcumin or turmeric may be ulcerogenic.

 

Antiaging and Neuroprotective Effects

As far as slowing down the aging process, in addition to the effects discussed previously, there is considerable evidence that curcumin protects against age-related brain damage and in particular, Alzheimer’s disease. Researchers began exploring this effect after noting that elderly (aged 70 to 79) residents of rural India, who eat large amounts of turmeric, were shown to have the lowest incidence of Alzheimer’s disease in the world, 4.4 times lower than that of Americans. In addition, researchers also demonstrated that curcumin was able to prevent the development of amyloid plaque and the neurofibrillary tangles that are the hallmark features of the brain lesions in mice specifically bred to develop the disease.

Studies also suggested a neuroprotective role of curcumin in stroke models. Curcumin was shown to reduce plaque burden in models of Alzheimer’s disease. Curcumin was also shown to decrease naphthalene and 4-hydroxy-2-nonenal–induced cataract formation on the lens by decreasing the rate of apoptosis and subsequent opacification resistance of the lens.54,55 The authors postulated that induction of the enzyme glutathione S-transferase, which acts to decrease lipid peroxidation, was probably responsible for the cataractogenesis-inhibiting effects.

 

Antimicrobial Effects

Alcohol extracts and the essential oil of C. longa were shown in one study to inhibit the growth of most organisms occurring in cholecystitis (i.e., Sarcina, Gaffkya, Corynebacterium, and Clostridium).

2 Other microorganisms that were inhibited include Staphylococcus, Streptococcus, Bacillus, Entamoeba histolytica, and several pathogenic fungi.

 The concentrations used in these studies were relatively high: 0.5 to 5 mg/mL of the alcohol extract and essential oil, and 5 to 100 mg/mL of curcumin.

DOSAGE

On the basis of the evidence presented earlier, turmeric should be consumed liberally in the diet. When specific medicinal effects are desired, higher doses of turmeric can be given or extracts of C. longa or curcumin can be used. Because curcumin is so poorly absorbed, its clinical use should include something that may increase its absorption. Historically, this suggestion has meant using it in a lipid base, such as lecithin, fish oils, or essential fatty acids (with meals), or formulated in conjunction with piperine or bromelain (on an empty stomach).

A number of new methods now exist to enhance the absorption of curcumin. Of these, Meriva is establishing itself as a leading form of curcumin as a result of a growing body of clinical research at doses of 1000 to 1200 mg providing 200 to 240 mg of curcumin.

Another preparation, Theracurmin, is a surface controlled particle dispersion, with an average particle size of curcumin of 0.19 μm compared with an average particle size of 22.75 μm in curcumin powder. This represents a reduction of over 100 times, and its absorption rate is 27 times greater than regular curcumin.

This is a superior absorption compared with all other commercial forms tested, including other enhanced forms of curcumin, including phosphatidylcholine-bound curcumin (Meriva).

Based upon a limited number of clinical studies, the dosage of Theracurmin is 300 mg/day (providing 30 mg of curcumin).

DRUG INTERACTIONS

Curcumin has several possible drug interactions, only a few of which have been confirmed. In one human study, 300 mg of curcumin reduced the absorption of the β-blocker talinolol by roughly 35%.

In rabbits, pretreatment with curcumin resulted in increased plasma elimination half-life, thereby reducing the dosage of norfloxacin.

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