Suggested Use
Take one softgel twice daily with food, or as directed by a qualified health care practitioner.

Main Applications
• Cancer
• Inflammation
• Antioxidant
• Lipid metabolism
• Gastrointestinal health

Source
Curcuma longa Linn.

Pregnancy / Nursing
No Studies. Best to avoid

Cautions
None Known

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

There are few natural health supplements whose reputation for effectiveness matches that of curcumin, the principle polyphenol found in the Indian spice turmeric. It has even been dubbed "curecumin" by certain scientists and all but revered as a panacea by many in the preventative health community. It has long been established as one of the most effective antioxidants and anti-inflammatories in the natural world, and modern science is further revealing an ever-proliferative list of capabilities. These include its use as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and even as an anti-angiogenic and chemopreventive agent. Its axiomatic anti-inflammatory function also enables it to be of potentially therapeutic value in the myriad of conditions for which inflammation is an underlying factor, including arthritis, inflammatory bowel disease and psoriasis.

Ayurveda, The Natural World and Curcumin
During the period between 1981 and 2002, 61% of the 877 new molecular drugs developed were originally extracted from natural sources. It is therefore easy to appreciate ancient medicinal paradigms such as Ayurveda and traditional Chinese medicine which are so deeply rooted in such natural sources, and these paradigms have no staple more renowned, more widely utilized, and in the case of Ayurveda more revered, than curcumin.

Curcumin (i.e. Curcuma Longa) is a perennial herb - commonly known as turmeric, especially in its powdered form - that belongs to the ginger family. The active constituents of curcumin are curcuminoids, of which there are three principal types, namely curcumin I (diferuloylmethane), curcumin II (demethoxycurcumin) and curcumin III (bisdemethoxycurcumin). There is also a fourth category encompassing ‘other' curcuminoids, but these comprise roughly 4-5% of the curcuminoid complex, with curcumin I (diferuloylmethane) usually forming more than three-quarters of this complex.

Traditional and Modern Roles of Curcumin
Most people will likely be familiar with curcumin as a food spice used to provide curry with its distinctive flavour and colour. Practitioners of Ayurvedic medicine will refer to it as a treatment for ailments ranging from respiratory conditions such as asthma, bronchial hyperactivity, and allergies, to liver disorders, anorexia, rheumatism, diabetes, runny nose, cough, and sinusitis. In traditional Chinese medicine it is most often used to treat conditions associated with abdominal pain and as an anti-inflammatory. The latter has also been the focus of a great deal of modern research into the mechanism(s) of action for curcumin, particularly since such research has also isolated inflammation as the greatest common denominator behind a number of terminal conditions. The following table lists the range of inflammation mediators (cytokines) that are inhibited by curcumin supplementation:

Table 1: List of Inflammatory Cytokines and Transcription Factors Inhibited by Curcumin

Modern scientific research has also identified some very potent anti-carcinogenic, anti-microbial, thrombosuppressive, cardiovascular, hypoglycemic and anti-arthritic capabilities within curcumin. Curcumin's anti-carcinogenic and anti-tumour capabilities are heavily based on extensive laboratory animal (murine) studies, and a partial synopsis of those studies is provided in Table 2.

Table 2: Volume and Types of Murine Cancer Studies Successfully Demonstrating the Chemopreventive Capacity of Curcumin

The Real World: Clinical Trials
Curcumin's success is of course not exclusively based on trials with laboratory animals. Curcumin's status as an anti-inflammatory has produced a series of successful human trials involving conditions where inflammation is an underlying factor. In one study involving patients with post-operative inflammation, curcumin's effects were comparable to the drug phenylbutazone. In another study among patients of type II diabetes, curcumin was found to reduce inflammatory markers such as Interleukin-6 (IL-6) and Tumour Necrosis Factor (TNFα) in a manner comparable to the drug atorvastatin. However, Table 3 offers an exhaustive (but still not conclusive) list of clinical studies involving curcumin, a list by no means limited to inflammation.

Table 3: Curcumin Clinical Trial Summary

References:

Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as "Curecumin": from kitchen to clinic. Biochem Pharmacol. 2008 Feb 15;75(4):787-809.

Newman DJ, Cragg GM, Snader KM. Natural products as sources of new drugs over the period 1981-2002. J Nat Prod 2003;66:1022-37.

Usharani P, Mateen AA, Naidu MU, Raju YS, Chandra N. Effect of NCB-02, atorvastatin and placebo on endothelial function, oxidative stress and inflammatory markers in patients with type 2 diabetes mellitus: a randomized, parallel-group, placebo-controlled, 8-week study. Drugs R D. 2008;9(4):243-50.

Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.

Curcumin as "Curecumin": from kitchen to clinic.
Goel A, Kunnumakkara AB, Aggarwal BB.
Biochem Pharmacol. 2008 Feb 15;75(4):787-809.

Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be "Curecumin".

Phase I Clinical Trial of Oral Curcumin
Clinical Cancer Research 2004;10:6847-6854.
Sharmal RA, Euden SA, Platton SL, Cooke DN, Shafayat A, Hewitt R, Marczylol TH, Morgan B, Hemingway D, Plummer SM, Pirmohamed M, Gescher AJ and Steward WP.

Curcumin, a polyphenolic antioxidant derived from a dietary spice, exhibits anticancer activity in rodents and in humans. Its efficacy appears to be related to induction of glutathione S-transferase enzymes, inhibition of prostaglandin E2 (PGE2) production, or suppression of oxidative DNA adduct (M1G) formation. We designed a dose-escalation study to explore the pharmacology of curcumin in humans. Fifteen patients with advanced colorectal cancer refractory to standard chemotherapies consumed capsules compatible with curcumin doses between 0.45 and 3.6 g daily for up to 4 months. Levels of curcumin and its metabolites in plasma, urine, and feces were analyzed by high-pressure liquid chromatography and mass spectrometry. Three biomarkers of the potential activity of curcumin were translated from preclinical models and measured in patient blood leukocytes: glutathione S-transferase activity, levels of M1G, and PGE2 production induced ex vivo. Dose-limiting toxicity was not observed. Curcumin and its glucuronide and sulfate metabolites were detected in plasma in the 10 nmol/L range and in urine. A daily dose of 3.6 g curcumin engendered 62% and 57% decreases in inducible PGE2 production in blood samples taken 1 hour after dose on days 1 and 29, respectively, of treatment compared with levels observed immediately predose (P < 0.05). A daily oral dose of 3.6 g of curcumin is advocated for Phase II evaluation in the prevention or treatment of cancers outside the gastrointestinal tract. PGE2 production in blood and target tissue may indicate biological activity. Levels of curcumin and its metabolites in the urine can be used to assess general compliance.

Mechanism of antiinflammatory actions of curcumine and boswellic acids.
J Ethnopharmacol 1993 Mar; 38(2-3): 113-9.
Ammon HP, Safayhi H, Mack T, Sabieraj J.

Curcumine from Curcuma longa and the gum resin of Boswellia serrata, which were demonstrated to act as anti-inflammatories in in vivo animal models, were studied in a set of in vitro experiments in order to elucidate the mechanism of their beneficial effects. Curcumine inhibited the 5-lipoxygenase activity in rat peritoneal neutrophils as well as the 12-lipoxygenase and the cyclooxygenase activities in human platelets. In a cell free peroxidation system curcumine exerted strong antioxidative activity. Thus, its effects on the dioxygenases are probably due to its reducing capacity. Boswellic acids were isolated from the gum resin of Boswellia serrata and identified as the active principles. Boswellic acids inhibited the leukotriene synthesis via 5-lipoxygenase, but did not affect the 12-lipoxygenase and the cyclooxygenase activities. Additionally, boswellic acids did not impair the peroxidation of arachidonic acid by iron and ascorbate. The data suggest that boswellic acids are specific, non-redox inhibitors of leukotriene synthesis either interacting directly with 5-lipoxygenase or blocking its translocation.


Inhibitory effect of dietary curcumin on skin carcinogenesis in mice.
Cancer Lett 1997 Jun 24; 116(2): 197-203.
Limtrakul P, Lipigorngoson S, Namwong O, Apisariyakul A, Dunn FW.

Laboratory animal model studies have suggested that curcumin may play an important role in inhibiting the process of carcinogenesis. Curcumin, the yellow pigment that is obtained from rhizomes of the plant Curcuma longa Linn (Family Zingiberaceae), is commonly used as a spice and food coloring agent. The present study was designed to investigate the chemopreventive action of dietary curcumin on 7,12-dimethylbenz[a]anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumor formation in male Swiss ablino mice. At 6 weeks of age, groups of animals were fed the standard (modified AIN-76 A) diet or a diet containing 1% curcumin. At 8 weeks of age, all animals, except those in the vehicle (acetone)-treated groups, received 100 microg of DMBA dissolved in 100 microl of acetone in a single application to the skin of the back. From 1 week after DMBA application, tumor promoter (2.5 microg of TPA dissolved in 100 microl of acetone) was applied to the same areas on mouse skin twice a week for 26 weeks. All groups continued on their respective dietary regimen until the termination of the experiment. The results indicate that dietary administration of curcumin significantly inhibited the number of tumors per mouse (P < 0.05) and the tumor volume (P < 0.01). The percentage of tumor-bearing mice tended to be lower in the mice on the curcumin diet than those on the standard diet. There was no difference in growth between mice of the standard and 1% curcumin groups. The results indicate the safety and the anti-carcinogenic effect of curcumin in mice.

Turmeric: A Brief Review of Medicinal Properties
Fitoterapia 1997; 68(6): 483-493.
Srimal RC

Turmeric has been attributed a number of medicinal properties in the traditional system of medicine and its internal as well local use has been advocated. The major claims have been for use as antiseptic, cure for poisoning, eliminating body waste products, for dyspesia, respiratory disorders and cure for a number of skin diseases including promotion of wound healing. Recent studies have confirmed some of the older claims and brought out several new useful properties. Curcumin, curcuminoids and essential oils are the major active constituents. The main activities have been found to be anti-inflammatory, hepatoprotective, antimicrobial, wound healing, anticancer, antitumor and antiviral. Discovery of antiviral properties in curcumin, particularly against HIV, is interesting and needs proper evaluation. The review highlights some of the newer researchers, which may explain the multifaceted activity of this natural product. Different extracts of turmeric and also curcumin have been tried clinically in several diseased conditions with gratifying results.