Curcumin

In addition to its use as a spice and a pigment, turmeric has been used in India for medicinal purposes for centuries. More recently, evidence that curcumin may have anti-inflammatory and anticancer activities has renewed scientific interest in its potential to prevent and treat disease.

For the last few decades, extensive work has been done to establish the biological activities and pharmacological actions of curcumin. Its anticancer effects stem from its ability to induce apoptosis in cancer cells without cytotoxic effects on healthy cells. Curcumin can interfere with the activity of the transcription factor NF-kB , which is often highly overexpressed in many cancer cells, according to a talk given by Dr. Dennis Liotta at Davidson College in January 2006.

Extensive scientific research on curcumin has demonstrated its potent antioxidant properties. Through its antioxidant mechanisms, curcumin supports colon health, exerts neuroprotective activity and helps maintain a healthy cardiovascular system.

Curcumin acts as a free radical scavenger and antioxidant, inhibiting lipid peroxidation and oxidative DNA damage. Curcuminoids induce glutathione S-transferase and are potent inhibitors of cytochrome (COX-2 inhibitors).

Curcumin is known for its powwerful antitumor, antioxidant, anti-amyloid and anti-inflammatory properties.

Curcumin's Anti-inflammatory action may be due to leukotriene inhibition.

New research shows that turmeric and its main bioactive compound, curcumin have the power to block inflammation, stop cancer, kill infectious microbes, and improve heart health.

Turmeric powder also is a popular remedy for stomach complaints throughout Asia. In Hawaii, it is reportedly used to treat swimmer's ear (infection) and sinus infections. Perhaps one of its most important applications is as an anti-inflammatory for the treatment of arthritis; it has been used as such in China and India for thousands of years.

Modern scientists have examined these largely faith-based claims and have subjected them to rigorous testing over the last 50 years. Although few large-scale human trials have been completed, hundreds of experiments conducted by researchers around the globe have demonstrated curcumin's ability to halt or prevent certain types of cancer, stop inflammation, improve cardiovascular health, prevent cataracts, kill or inhibit the toxic effects of certain microbes including fungi and dangerous parasites, and protect, at least in the laboratory, against the damaging effects of heterocyclic amines (potentially carcinogenic compounds found in some cooked foods). As one investigative team declared: "Curcumin has been proven to exhibit remarkable anticarcinogenic, anti-inflammatory, and antioxidant properties."

As if that were not enough, this hard-working spice shows promise as a potential treatment for multiple sclerosis, and may ameliorate the damaging effects of long-term diabetes. It is even being investigated as a topical treatment to speed diabetic wound healing. Some researchers also have noted an exciting link between turmeric consumption and a dramatically decreased incidence of Alzheimer's disease, an effect that may well be related to curcumin's ability to block signaling pathways that lead to inflammation.

Cancer-Fighting Capabilities Documented

Numerous studies published in peer-reviewed medical journals detail curcumin's ability to protect against cancer. In addition to its capacity to intervene in the initiation and growth of cancer cells and tumors . . . and to prevent their subsequent spread throughout the body by metastasis . . . curcumin also has been shown to increase cancer cells' sensitivity to certain drugs commonly used to combat cancer, rendering chemotherapy more effective in some cases Much research has focused on curcumin's anti-inflammatory properties, and some new research suggests that curcumin may protect the heart and circulatory system, and prevent the onset of Alzheimer's disease. Still other studies have examined curcumin's potential ability to counteract the effects of fungal toxins in the food supply, and to protect the eyes from cataracts and uveitis, an inflammation of a portion of the eye that may result in glaucoma.

As an anticancer agent, curcumin is promising enough to warrant serious attention from the National Cancer Institute (NCI). In its 2002 annual report, the Chemopreventive Agent Development Research Group, a subset of the NCI's Division of Cancer Prevention, details its efforts to encourage and support research on curcumin's utility in cancer prevention and treatment. Because curcumin is a non-patentable product (see sidebar), such support is crucial, especially for research involving all-important human trials, as other sources of funding are virtually nonexistent. At least one human trial, focusing on dosing, bioavailability, and pharmacokinetics (how curcumin is used, metabolized, and eliminated by the body), is under way at the University of Michigan Comprehensive Cancer Center. Other curcumin studies have been proposed to the NIC and are awaiting approval.

Test-tube and animal-model studies have demonstrated that curcumin exhibits significant anti-cancer activity. Numerous experiments have shown that curcumin inhibits the progression of chemically induced colon and skin cancers. In colon cancer, in particular, curcumin seems to significantly inhibit both the promotional and progression stages of the disease. Various studies have reported that curcumin reduces the number and size of existing tumors, and decreases the incidence of new tumor formation.

Much discussion lately has focused on the use of cyclooxygenase-2 (COX-2) inhibitors . . . such as the prescription medications Celebrex® and Vioxx® . . as potential colon cancer preventive agents. This new approach arose from the observation that people who routinely take anti-inflammatory non-steroidal drugs (NSAIDs) are statistically less likely to develop cancer than those who do not. Unfortunately, NSAIDs are poorly tolerated by some and can even cause bleeding in the gastrointestinal tract. Regarding curcumin's potential benefits for the prevention and treatment of colon cancer, one research team commented: "Naturally occurring COX-2 inhibitors such as curcumin and certain phytosterols have been proven to be effective as chemopreventive agents against colon carcinogenesis with minimal gastrointestinal toxicity."

Additionally, other studies using cancer cells grown in the laboratory in vitro have demonstrated curcumin's ability to prompt apoptosis, or programmed cell death, among leukemia, B lymphoma, and other cancerous cells. Curcumin has been used as a topical application to successfully induce apoptosis in skin cancer cells both in vitro and in animal models. Curcumin is under investigation as a preventive agent for increasingly common non-melanoma skin cancers, and as a potential preventive or treatment agent in breast, prostate, oral, pancreatic, and gastric cancers, among others. One researcher understated the matter, noting, " . . . curcumin . . . should be considered for further development as a cancer preventive agent."

Curcumin also has been shown to enhance the effectiveness of certain anti-cancer drugs, and, amazingly, to potentially improve the effectiveness of anti-cancer radiation treatment by preventing tumor cells from developing radiation resistance. Protein kinase C (PKC) has been suggested as a possible mechanism by which tumor cells develop resistance to radiation therapy. Curcumin's helpful effect may be due to its ability to inhibit radiation-induced PKC activity. Additionally, one study found that curcumin protected study animals from the tumor-producing effects of deadly gamma radiation, while another found that it protects against damaging ultraviolet light, which is known to play a role in the development of skin cancer.

Among the Reactive Oxygen Species (ROS) whose levels or activities were reduced by curcumin were xanthine oxidase, superoxide anion, malondialdehyde, glutathionine peroxidase, superoxide dismutase, and lactate dehydrogenase. As most readers already know, scientists attribute many of the undesirable effects of aging to the rogue activities of damaging free radicals, and antioxidants are crucial for their control. As noted previously, curcumin is a powerful antioxidant and many of its beneficial effects may be directly related to its ability to scavenge and neutralize these ROS.

Antioxidant Activity

Curcumin is an effective scavenger of reactive oxygen species and reactive nitrogen species in the test tube (in vitro). However, it is not clear whether curcumin acts directly as an antioxidant in vivo. Due to its limited oral bioavailability in humans (see Metabolism and Bioavailability above), plasma and tissue curcumin concentrations are likely to be much lower than that of other fat-soluble antioxidants, such as alpha-tocopherol (vitamin E). However, the finding that 7 days of oral curcumin supplementation (3.6 g/day) decreased the number of oxidative DNA adducts in malignant colorectal tissue suggests that curcumin taken orally may reach sufficient concentrations in the gastrointestinal tract to inhibit oxidative DNA damage. In addition to direct antioxidant activity, curcumin may function indirectly as an antioxidant by inhibiting the activity of inflammatory enzymes or by enhancing the synthesis of glutathione, an important intracellular antioxidant (see below).

Anti-inflammatory Activity

The metabolism of arachidonic acid in cell membranes plays an important role in the inflammatory response by generating potent chemical messengers known as eicosanoids. Membrane phospholipids are hydrolyzed by phospholipase A2 (PLA2), releasing arachidonic acid, which may be metabolized by cyclooxygenases (COX) to form prostaglandins and thromboxanes, or lipoxygenases (LOX) to form leukotrienes. Curcumin has been found to inhibit PLA2, COX-2 and 5-LOX activity in cultured cells (12). Although curcumin inhibited the catalytic activity of 5-LOX directly, it inhibited PLA2 by preventing its phosphorylation and COX-2 mainly by inhibiting its transcription. Nuclear factor-kappa B (NF-kB) is a transcription factor that binds DNA and enhances the transcription of the COX-2 gene and other pro-inflammatory genes, such as inducible nitric oxide synthase (iNOS). In inflammatory cells, such as macrophages, iNOS catalyzes the synthesis of nitric oxide, which can react with superoxide to form peroxynitrite, a reactive nitrogen species that can damage proteins and DNA. Curcumin has been found to inhibit NF-kB-dependent gene transcription, and to inhibit the induction of COX-2 and iNOS in cell culture and animal studies

Inflammatory Diseases

Although the anti-inflammatory activity of curcumin has been demonstrated in cell culture and animal studies, few controlled clinical trials have examined the efficacy of curcumin in the treatment of inflammatory conditions. A preliminary intervention trial that compared curcumin with a nonsteroidal anti-inflammatory drug (NSAID) in 18 rheumatoid arthritis patients found that improvements in morning stiffness, walking time and joint swelling after 2 weeks of curcumin supplementation (1200 mg/day) were comparable to those experienced after 2 weeks of phenylbutazone (NSAID) therapy (300 mg/day). A placebo-controlled trial in 40 men who had surgery to repair an inguinal hernia or hydrocele found that 5 days of oral curcumin supplementation (1200 mg/day) was more effective than placebo in reducing post surgical edema, tenderness and pain, and was comparable to phenylbutazone therapy (300 mg/day)