In summary, curcumin has following activities:

• a cancer preventative
• the greatest antioxidant
• an anti-inflammatory agent in the management of osteoarthritis and rheumatoid arthritis
• endurance increasing
• cholesterol lowering
• liver protecting

It can be used in the following conditions:

• Altzheimer disease
• Crohn's disease and ulcerative colitis
• Alcoholic liver disease
• Prevention of cancer

Altzheimer Disease

Experiments on mice genetically engineered to express human amyloid-beta protein (and that develop a condition resembling Alzheimer's) show a delayed onset with curcumin supplementation, but an accelerated onset if they take too much. Curcumin, like most antioxidants, becomes a pro-oxidant if taken at excessive levels.

Crohn's and ulcerative colitis

The National Institutes of Health estimates that some two million Americans suffer from IBD, which is of unknown origin, but thought to be caused by a combination of genetic, environmental, and immunologic factors. The two debilitating illnesses are characterised by chronic recurrent ulceration of the bowel, abdominal pain, digestive problems, diarrhoea or constipation.

Curcumin's anti-inflammatory properties have already been recognised, while its role in the reduction of colonic cancer in animal models has also been established.

Although effective, current available agents are expensive and not without side effects, say the researchers, led by B. Salh, at the Jack Bell Research Centre at the Vancouver General Hospital, in Vancouver, British Columbia, Canada. Consequently, they suggest there is a need for alternative agents that may be equally or more effective as well as being cheaper.

The researchers used the dinitrobenzene sulfuric acid (DNB) murine model of colitis, which has been previously validated. Seven-week-old mice had inflammation induced with instillation of 100 ¦Ìl of DNB (60 mg/ml) in 50 per cent ethanol with control animals receiving 100 ¦Ìl of 50 per cent ethanol alone. After this, they were kept in position for 30 seconds before being returned to their cages.

On day 5, post-induction was conducted for evaluation of the colitis. Test groups of five mice had curcumin added to their diet at a concentration of 0.25 per cent beginning five days before the DNB instillation. Animals were weighed daily after induction of colitis.

The study results revealed a clear reduction in the amount of weight loss in the animals pre-treated with curcumin, according to Salh. Curcumin was found to improve intestinal cell function in DNB-induced colitis, while mucosal ulceration, thickening of the wall, and significant infiltration with inflammatory cells in the DNB- treated animals were all reduced in those animals pre-treated with curcumin.

The team also noted that when animals were pre-treated with curcumin, there was a clear reduction in DNA binding, thus proving that curcumin does indeed inhibit NF-kappa B activation in the colon in vivo. These findings indicate for the first time that curcumin is able to impact on an important transcriptional mechanism in the gastrointestinal tract, they added.

However Sal adds that the team is not entirely certain how curcumin achieves its effects. He therefore concludes that as it has been shown to possess free radical scavenging - antioxidant - properties in addition to its effects on the activation of NF-kappa B, its in vivo effects may well rely on a complementation of these two and other activities.

Finally, although curcumin has been shown to be safe up to levels as high as 10 per cent (100,000 ppm), the researchers said it showed effectiveness at a concentration as low as 0.25 per cent, a dose that was well tolerated with no reduction in dietary intake.

The team's findings 'Curcumin Attenuates DNB- Induced Murine Colitis' appeared in the July 2003 edition of the American Journal of Physiology-Gastrointestinal and Liver Physiology.

Alcoholic liver disease

Now a study published in the February 2003 edition of the American Journal of Physiology D Gastrointestinal and Liver Physiology provides evidence that curcumin can halt the development of alcohol-induced liver disease (ALD, or cirrhosis)(3)! The transcription factor, NF-kappa-B (a transcription factor is a protein required to activate RNA information transfers - "transcription"), has previously been shown to stimulate Kuppfer cells (cells in the liver that remove particulate matter) to produce toxins that result in cirrhosis. Curcumin has already been discovered to inhibit NF-kappa-B activation, so the link between curcumin and the possible prevention of cirrhosis was provided by previous studies. The current study (conducted on rats) has essentially confirmed the suspicion that cirrhosis can be controlled or prevented through the suppression of NF-kappa-B. The researchers also discovered that the curcumin can halt lipid peroxidation. What remains to be shown is whether cirrhosis can be reversed through the same mechanism.

Prevention of cancer (Phase I Clinical Trial)

A 2001 paper1 reported on the results of a phase I clinical trial of curcumin to reduce the risk of or prevent cancer in patients with high-risk conditions, including: (1) recently resected urinary bladder cancer; (2) arsenic Bowen's disease of the skin; (3) uterine cervical intraepithelial neoplasm; (4) oral leukoplakia; and (5) intestinal metaplasia of the stomach. Thus, this was not a trial of the ability of curcumin to prevent cancer in healthy individuals, but in those who have already had cancer (and are at risk of recurrence) or have premalignant lesions.

Evidence suggests that curcumin acts on stages of initiation, promotion, and progression of carcinogenesis.¹

A total of 25 patients were enrolled in this study. The subjects took curcumin once in the morning on an empty stomach. Since a previous small-series human study used 500 mg/day for 7 days without observing any toxicity, and a commonly consumed diet in India may contain as much as 100 mg/day of curcumin, the authors chose 500 mg/day as the starting dose. The patients were then moved up into the next dose level (1000, 2000, 4000, 8000, and 12,000 mg/day) as soon as at least two patients at a given level had completed the 3-month treatment and no more than one patient had experienced any equal to or greater than grade II toxicity. Tissue samples were taken from the indicator lesions before and at completion of the 3-month treatment with curcumin.

No toxicity was observed up to 8000 mg/day. However, it was not possible to increase patients to the next level (12,000 mg/day) because the bulky volume of the tablets was unacceptable.

The authors found that curcumin was not well absorbed from the GI tract. The peak serum concentration was only 1.77 ¦ÌM even at the 8000-mg/day dose. However, these researchers had earlier found in an animal study that curcumin was rapidly biotransformed to dihydrocurcumin and tetrahydrocurcumin and that these compounds were later converted to monoglucuronide conjugates. They suggest that some of the metabolites may retain the pharmacologic properties of curcumin, so the relatively low serum concentrations in the patients in this trial may not reflect the entire beneficial activity of the oral curcumin.

After 3 months in this study, they found histologic improvement in 7 out of 25 patients with these various high-risk and premalignant lesions. They note the need for further phase IIb studies with placebo control for individual lesions to confirm the findings of this study. The authors recommend an oral dose of 6000-8000 mg/day of curcumin in the phase II study. However, since this would be a study of high-risk individuals, 6000-8000 mg/day of curcumin would be an excessive dose for a healthy individual taking curcumin as a supplement; we suggest 200 mg/day.

1. Cheng et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or premalignant lesions. Anticancer Res 21:2895-2900 (2001).

Curcumin blocks estrogen mimicking chemicals

Banned Pesticide Could Be In Your Food

Chlordane is a pesticide composed of over 50 different chemicals. A chlorine chemical that mimics estrogen, chlordane was banned in the U.S. over 50 years ago. Nonetheless, it continued to be manufactured in the U.S. and shipped to Mexico where it was sprayed on food crops exported back to the U.S. According to the Agency for Toxic Substances and Disease Registry, almost every human on earth has chlordane in their fat. There is no way to get it out of the body. Losing weight simply concentrates the chemical in the remaining fat.

Besides being sprayed on America's corn, millions of tons of chlordane were put into the ground around house foundations to kill termites before it was banned. The half life of chlordane in soil is 22 years (which means it doesn't degrade for at least 40 years). That means that if you plant a vegetable garden next to your house, you might end up with a big dose of chlordane on your dinner plate.

Researchers in Connecticut testing random samples of U.S. produce found chlordane in vegetables grown on soil that hadn't been treated with chlordane for 20 years. So they decided to do an experiment. They grew vegetables on soil previously treated with chlordane to see what would happen. The soil they used was under the lawn of their own institution that had been sprayed with chlordane in 1960 to see how well it worked.

In May, 2000, they published their findings in the Journal of Agricultural and Food Chemistry (the journal of the American Chemical Society). All 12 vegetables they grew on soil sprayed decades earlier contained chlordane. Potatoes, carrots and beets absorbed chlordane systemically-it was in the flesh. Zucchini acted like a sponge for it. It also ended up in beans, eggplant, lettuce, dandelion and spinach.

After the findings were made public, the lead author, Dr. Mary Jane Incorvia Mattina was quoted as saying, "The main recommendation is to wash the foods you are going to eat, and not to plant near a house foundation that could have been treated with chlordane. If you take these precautions, you shouldn't have any cause for concern." When asked by us how one washes chlordane out of a vegetable, she admitted that it's impossible.

Mexico was still importing 45 tons of chlordane from the U.S. in 1997, when it instituted a program to gradually quit using the pesticide (it also plans to phase out DDT by the year 2007). The only official use of chlordane in Mexico (which grows vegetables for the U.S. market) is for killing termites in urban areas.

One of the things that sets curcumin apart from most other anti-cancer supplements (I3C being an exception), is that this phenolic can actually block chemicals from getting inside cells. Importantly, curcumin can interfere with pesticides that mimic estrogen. These include DDT and dioxin, two extremely toxic chemicals that contaminate America's water and food. (Dioxin is so toxic that a few ounces of it could wipe out the entire population of New York City). Curcumin has the unique ability to fit through a cellular doorway known as the aryl hydrocarbon receptor. This is a feat it shares with estrogen and estrogen-mimicking chemicals. Because it can compete for the same doorway, curcumin has the power to block access to the cell and protect against estrogen mimickers.

Like estrogen, estrogen-mimicking chemicals promote the growth of breast cancer. In a study on human breast cancer cells, curcumin reversed growth caused by 17b-estradiol by 98%. DDT's growth-enhancing effects on breast cancer were blocked about 75% by curcumin.

Two other estrogen mimickers were tested for their ability to enhance breast cancer. Chlordane and endosulfane together make breast cancer cells grow about as much as17b-estradiol. Curcumin can reverse that growth about 90%. Adding the soy phytochemical, genistein, causes a 100% growth arrest.

Curcumin's ability to block other chemicals have been documented. It has been tested against paraquat (weed killer), nitrosamines (in cooked meat and "lunch" meats) and carbon tetrachloride (a solvent in varnish and other products). In all cases, curcumin is able to block the chemical's effect. The beneficial effects are evident in a study where mice were treated with diethylnitrosamine. All mice treated with this chemical would usually develop liver cancer. However, when treated with curcumin, the percentage of animals developing cancer went from 100% to 38%, and the number of tumors dropped by 81%.

Curcumin inhibits kinases

Drug companies rush to make synthetic versions

One of the hottest areas of oncology drug development is in the area of kinase inhibitors. Kinases are the equivalent of phone lines into cancer cells. There are over 2000 known protein kinases, or phone lines. These lines run from the outside of a cell into the DNA command center. They carry messages. Cut these lines, and you can effectively stop the growth of some types of cancer cells.

Curcumin effectively blocks some of the lines. In cells treated with curcumin, certain "grow" signals are blocked from reaching the cell.

The most well-studied growth factor blocked by curcumin is nuclear factor-k B. NF-kB is activated by chemical messengers known as cytokines. Cytokines help the immune system, but they also activate signals that tell cells to multiply, grow. By interfering with those signals, curcumin effectively stops the growth of cancer cells by kinase pathways. It has been demonstrated, for example, that curcumin can prevent the bug that causes ulcers (Helicobacter pylori) from causing cancer. H. pylori increases levels of a cytokine (IL-8) that activates NF-kB. Curcumin blocks the process.

Drug companies are rushing to patent chemicals that do what curcumin does-inhibit kinases. AstraZeneca has gotten one off the ground called "Iressa". Iressa inhibits protein kinase C (PKC), a kinase that plays a significant role in cancer. PKC transmits signals from the "epidermal growth factor (EGF) receptor." Cutting off signal transmission through EGF significantly slows the growth of any cancer that uses this factor to grow-glioma, breast, prostate, skin and lung cancers.

Curcumin has long been known for its ability to prevent skin cancer. In 1993, researchers in Taiwan reported that curcumin inhibits PKC. The next year it was reported that curcumin blocks EGF signals up to 90% and stops growth.

It turns out that the structure of curcumin enables it to inhibit multiple kinases. This ability is shared with other phytochemicals including silymarin, apigenin and hypericin. While drug companies rush to try to recreate safe, patentable, chemical versions of this structure, curcumin sits ready and available for use. Blocking kinases, however, is only one of curcumin's anti-cancer effects.

Inflammation: Curcumin suppresses LOX and COX

Squamous cell carcinoma can affect the bronchial tubes, mouth or skin. When researchers at the University of Missouri treated oral squamous cell carcinoma cells with curcumin, it caused significant growth inhibition.

Curcumin is also notably effective against colon cancer. Inflammation appears to play a significant role in promoting this type of cancer. Curcumin has long been known for its anti-inflammatory action. More recently, it has been shown that curcumin inhibits cyclooxygenase (COX) and lipoxygenase (LOX), two enzymes that promote inflammation. Inflammation is in the limelight these days because of the discovery that people who take nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, have stunning protection against colon cancer. Inflammation, it turns out, plays significant and diverse roles in the initiation and promotion of cancer. Oxidative stress helps activate PKC, for example. Part of curcumin's ability to block PKC signals is due to its powerful antioxidant activity.

Curcumin acts as an antioxidant and maintains DNA Methylation

Curcumin possesses several other anti-cancer benefits that make it useful for cancer prevention. One of its most recognized features is its antioxidant action. Turmeric is a spice that contains curcumin. It has traditionally been used as a food preservative for a good reason: it keeps food from going rancid-oxidizing. And just as it keeps oxygen from turning meat rancid, it protects our own bodies from damaging free radicals. Free radicals promote cancer by damaging DNA and activating genes.

Radiation damages DNA partially through free radicals. In a recent study, it was demonstrated that under laboratory conditions, curcumin could protect bacteria from a lethal dose of radiation almost perfectly. Bacterial DNA emerged virtually intact.

Methylation of DNA is critical for maintaining a cancer-free state. More specifically, certain patterns of methylated and non-methylated DNA keep cancer genes turned off, and tumor suppressor genes turned on. Dr. Khing Lertratanangkoon has done research showing that chemicals which deplete glutathione in the liver, cause DNA methylation disruption. In other words, maintaining glutathione is important for maintaining DNA methylation.

Glutathione is the liver's natural antioxidant. Chemicals (which are all processed by the liver) deplete glutathione. Curcumin protects glutathione in the presence of chemicals (including alcohol).

Dr. Lertratanangkoon has shown that a glutathione-depleting chemical can disrupt DNA methylation. But if curcumin is given at the same time, both methylation and glutathione are maintained. Bottom line: curcumin may also save DNA methylation patterns, another anti-cancer benefit.

Curcumin prevents multiplying and induces apoptosis of cancer cells

Curcumin can stop cancer in its earliest stages, long before it's detectable. It works at the level of the cell. One of the things it does is to tell damaged cells to self-destruct so they won't keep multiplying. The process is called "apoptosis" and it's the body's way of destroying abnormal cells that can become cancerous. Cancer cells can circumvent the process, but curcumin can override them and send "self-destruct" signals to many different types of cancer cells. Curcumin does not induce apoptosis of healthy cells, only cancerous ones. It identifies cancer cells by their abnormal chemistry. Unfortunately, it doesn't work in all types of cancer, but Indian researchers may have figured out why. Their findings, published in the Journal of Biological Chemistry, may lead to ways of making most types of cancer susceptible to curcumin's effects.

Before apoptosis is induced, curcumin stops cancer cells from multiplying. In cancer research, this is known as "interrupting the cell cycle." The cell cycle can be interrupted at several different points. This is the rationale behind using various chemotherapy treatments in one person. One drug stops the cells when they are in one stage of growth; another stops them at another stage. Using a variety of drugs that stop growth at different stages increases the chances of killing all the cancer cells. Curcumin arrests the growth of cancer cells in the G2 stage.

Other phytochemicals stop the cell cycle at other stages. Genistein, a soy phytochemical, arrests growth at G2, like curcumin. But epigallocatechin-3-gallate (EGCG) from green tea, arrests cancer cell growth at the G1 phase. Combining EGCG with curcumin increases the odds of killing more cells. Researchers at Sloan-Kettering Cancer Center have suggested that EGCG and curcumin be used together for cancer prevention.

Curcumin enhances immunity

Curcumin can also help the body fight off cancer should some cells escape apoptosis. When researchers looked at the lining of the intestine after ingestion of curcumin, they found that CD4+ T-helper and B type immune cells were greater in number. In addition to this localized immune stimulation, curcumin also enhances immunity in general. Researchers in India have documented increased antibodies and more immune action in mice given curcumin.

Curcumin stops angiogenesis

All of the above actions of curcumin stop cancer before it has a chance to become detectable. If cancer grows to the point that it is a detectable tumor, curcumin can still have an effect.

Certain enzymes enable tumors to create a blood supply for themselves. Known as "angiogenesis," this phenomenon allows tumors to invade surrounding tissue and spread. Working with blood vessels of the eye (where angiogenesis creates big problems for vision), researchers at Tufts University were able to inhibit blood vessel formation by using curcuminoids. Curcumin blocks AP-1, which enhances angiogenesis.

Curcumin may also inhibit angiogenesis by chelating metals used by enzymes that promote the growth of blood vessels. Some of the enzymes that promote angiogenesis are known as "metalloproteinases." Metalloproteinases require metals to work. Curcumin chelates iron and probably copper-both of which help metalloproteinases create new blood vessels for tumors. In a study on a highly invasive form of human liver cancer, curcumin inhibited metastasis 70% by suppressing metalloproteinase-9. Curcumin appears to be very protective against liver cancer. In a more recent study, the incidence of liver cancer was slashed 62%, with the number of tumors decreasing by 81% in mice given curcumin four days before a carcinogenic chemical.