Tumeric (Curcuma Longa)
CURCUMIN IN CANCER RISK REDUCTION AND THERAPY
Curcumin (diferuloylmethane) is a polyphenol derived from the rhizome of the plant curcuma longa, a perennial herb of the ginger family (Zingiberaceae). Also known as turmeric, Indian yellow root or Indian saffron, curcuma longa is cultivated throughout Asia and used extensively as a culinary spice and is a principal ingredient in curry. Curcumin also has a long history of use as a botanical medicine in both traditional Chinese and Indian (Ayurvedic) medicines to treat a wide variety of conditions.
Curcumin appears to 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. Curcumin has been described as follows:
- An effective antioxidant
- A cardiovascular protectant
- A gastrointestinal carminative and protectant
- An antimicrobial agent
There is an impressive amount of peer-reviewed literature on curcumin. A Pubmed search in 2017 yielded more than 11,000 articles on curcumin, over 4,000 of which are specifically related to its impact on cancer. Curcumin has been shown to exhibit multiple anticancer effects in a wide variety of cancer types. The mechanisms through which curcumin is believed to interfere with carcinogenesis are many. They include inhibition of inflammation via NF-kB inhibition, promotion of programmed cell death (apoptosis), interference with new blood vessel growth to tumors (angiogenesis), decreased activation of multiple kinase pathways with resultant decreased cellular proliferation, reduction in cancer cell motility and possibly synergistic effects with some chemotherapeutic agents and radiotherapy. Oral administration of curcumin in doses up to 8 to 10 g per day without dose-limiting toxicity further marks curcumin as a promising therapy for both the prevention and treatment of cancer
These beneficial effects of curcumin, however, are largely based upon in vitro or experimental models. There are significant pharmacokinetic issues with curcumin, as it is poorly absorbed and rapidly metabolized and eliminated from the body. Pharmacokinetic studies in animals showed that 40% to 85% of an oral dose of curcumin passes through the gastrointestinal tract unchanged. 3,4 In humans, doses as high as 12 g of curcumin failed to significantly raise blood levels. New curcumin products with much greater bioavailability are now on the market, but more clinical research is required to validate the promise of turmeric and curcumin to be to medicine what curry is to Asian cuisine.
The mechanisms through which curcumin is believed to interfere with carcinogenesis are many and include: 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, 7,12-dimethylbenz[ a] anthracene), as do chili and capsaicin. Turmeric and curcumin compounds have been found to induce apoptosis (programmed cell death) 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.
On the basis of the evidence presented, consideration should be given for turmeric to 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 (black pepper) 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).
Toxicity has not been reported at standard dosage levels. The oral mean lethal dose levels for turmeric, its alcohol extracts, and curcumin have not been determined, because 2.5 g/ kg fed to mice, rats, guinea pigs, and monkeys, and 3 g/ kg sodium curcuminate fed to rats resulted in neither mortality nor chromosomal aberrations in teratology tests. At high doses, curcumin or turmeric may damage the gastrointestinal system, since curcumin, with doses of 100 mg/ kg body weight, was ulcerogenic in rats. Some studies found sensitivity of mice to turmeric that resulted in hepatotoxicity. Curcumin toxicity has not been found in rats or other mammals, even at very high doses (5% to 10% by weight of diet). Human studies suggest that curcumin is nontoxic to humans up to 8000 mg/ day when taken by mouth for 3 months.