Many conventional vascular risk factors have overlapping mechanisms, synergism or complementary actions in the formation of arterial thrombosis, and there tends to be a greater incidence in the frequency of vascular events with increasing number and severity of risk factors.

This knowledge has fuelled a desire to find and utilize treatments that confer multifactorial vascular protection via favorable pleiotropic properties. Currently available therapies such as HMG-CoA reductase inhibitors (statins), renin–angiotensin system modulators and thiazolinediones are all believed to reduce vascular risk through additional mechanisms beyond their primary mode of action. Apart from efficacy through presumably varied actions, the recognition that single treatments with multiple pharmacologic actions could simplify treatment regimens, and thereby boost treatment adherence in the real world, has raised interest in the concept of a ‘polypill’that incorporates various vascular risk reduction drugs in the form of a single pill.

A promising single novel treatment that may simultaneously provide several vascular protective benefits for persons at risk for stroke is curcumin, which derives from the root of the plant Curcuma longa, and is regarded as the most biologically active constituent of the spice turmeric. Curcumin harbors several properties that could make it suitable for stroke prevention.

Neuroprotective:

Curcumin acts as a free-radical scavenger inhibiting lipid peroxidation and nitric oxide synthase expression. Curcumin exerts indirect antioxidant effects by enhancing the synthesis of glutathione, an important intracellular antioxidant . In fact, administration of curcumin after focal cerebral ischemia in rats significantly diminished infarct volume, improved neurological deficit, decreased mortality and reduced the water content of the brain in a dose-dependent manner.

Anti-inflammatory:

Curcumin suppresses the production of inflammatory cytokines such as IL-1β, TNF-α, IL-8 and the reactive astrocyte marker glial fibrillary acidic protein, as well as interfering with transcription factors NF-κB and activator protein-1.

Antilipemic:

Curcumin attenuates diet-induced hypercholesterolemia in rats, and a small clinical trial demonstrated that low doses of curcumin lowered total cholesterol and boosted high-density lipoprotein cholesterol levels.

Antiaggregant:

Curcumin preferentially inhibits platelet aggregation induced by platelet-activating factor and arachidonic acid. Since oxidative damage, inflammation and dyslipidemia all contribute to poor clinical outcomes in persons with or at risk for stroke, and several proven treatments for reducing stroke risk target these mechanisms, there is a rationale for testing the potential of curcumin to ameliorate stroke risk.

Since these known curcumin targets all play important physiological roles in stroke occurrence, a relatively low dose influencing all of these pathways might be expected to have as great a clinical benefit as higher doses without dose-related toxicity. Indeed, a preclinical study found an antiatherogenic effect of low dose of curcumin in a mouse model of atherosclerosis.

However, most of the preliminary toxicology has been examined in humans largely while investigating curcumin as an anticarcinogen or cancer chemopreventive agent.

Curcumin appears to be well tolerated in humans when administered daily (even up to doses as high as 8 g/day; the bulky volume of the drug is unpalatable beyond 8 g) over several months (up to 3 years in small trials) and dose-limiting toxicity has not been observed so far .

However, occasional reports of gastrointestinal adverse events, including nausea and diarrhea, during the first 1 month of use have been observed, and infrequent abnormal rises in serum alkaline phosphatase and lactate dehydrogenase levels noted .

Curcumin may also need to be used cautiously in patients with bleeding disorders and when being administered along with antithrombotic medications.

Relevant to a cerebrovascular disease population, which would consist largely of elderly persons, a study among persons with Alzheimer’s disease (mean age of 74 years; 62% female) tested the tolerability and safety of 4 g/day of curcumin in a 24-week, randomized, double-blind study.

Oral curcumin for the treatment of mild-to-moderate Alzheimer’s disease: tolerability and clinical and biomarker efficacy results of a placebo-controlled 24-week study.

Curcumin was well tolerated without any reported gastrointestinal side effects or elevated liver enzymes . In contrast to the extensive preclinical data on curcumin, the pharmacokinetic properties of curcumin in humans are still not completely understood .

Curcumin inhibits cytochrome P-450 isoenzyme 1A1 and undergoes avid metabolism by conjugation and reduction, and its disposition after oral dosing is characterized by poor systemic bioavailability 65% after oral administration).

However, the daily doses given in several of these human studies that actually assessed curcumin bioavailability generally did not exceed 500 mg of curcumin, so it is conceivable that higher doses of curcumin that furnish measurable plasma curcumin concentrations will be required to elicit clinically relevant antilipid, anti-inflammatory and antioxidant effects. Supporting this notion, analyses of serum and urine samples in a study where subjects consumed 3.6 g daily of curcumin showed the definitive presence of curcumin and its conjugates in both sample types, thereby providing a reliable and easy method for potentially testing the compliance of subjects consuming curcumin in clinical trials .

It also appears that concomitant administration of piperine boosts curcumin’s bioavailability in humans by 2000%. On the basis of extrapolating doses from rodents to humans (normalizing for the higher metabolic rate in rodents), the full range of doses to consider for likely efficacy in humans is presumed to range from 500 to 6000 mg/day. Curcumin is very hydrophobic and rapidly removed by tissues suggesting that CNS levels of 0.1 µM might be achievable at 4000 mg or lower doses. Small clinical trials have observed single-dose effects on lipid, inflammatory and oxidative risk factors of stroke.

For instance, 500 mg/day curcumin reduced markers for oxidative damage and total cholesterol while increasing HDL , while 1100–1200 mg/day has been used to control systemic inflammation .

Overall, curcumin appears to carry promise as stroke preventive agent. It may be worthwhile to conduct future clinical trials of oral curcumin supplementation in persons with, or at risk for stroke, to investigate its appropriate dosing, safety, and therapeutic activity.

Financial competing interests disclosure:

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Source: http://www.expert-reviews.com/doi/full/10.1586/14737175.8.8.1175?cookieSet=1

The history and chemistry of tumeric and curcumin and its many health benefits:

• A strong antioxidant.
• Relieves pain and inflammation.
• Helps prevent and may improve Alzheimer’s Disease.
• Prevents and suppresses cancer.
• Has many other amazing health benefits.
• Curcumin is safe.

History and chemistry.

Most everyone is familiar with the bright yellow color of Indian curry. Tumeric is the spice that gives curry much of its color. The spice is made from the powdered root of Curcuma longa, a member of the ginger family, Zingaberaceae.

Tumeric has been used for over a thousand years as a remedy in Ayurvedic (India) and Chinese medicine. In Ayurveda it used to inhibit inflammation. It was also prized by the ancient Romans and Greeks who valued its medicinal properties. The name “tumeric” derived from Latin, translates to “earth-merit”.

A group of chemical compounds in tumeric called curcuminoids are responsible for the color. The curcuminoids are extracted from the spice to concentrate them for medicinal use. This is "curcumin" and was initially extracted from tumeric over 100 years ago.

Three primary curcuminoids have been identified. They are curcumin (diferuloyl methane), demethoxycurcumin and bisdemethoxycurcumin. Curcuminoids are polyphenolic compounds that comprise 2-9% of tumeric.(1)

Curcumin extracts of tumeric are available as nutritional supplements. Some extracts indicate that they are standardized to contain 95% curcuminoids. This represents a 10-50X concentration of the curcuminoids found in their natural state in tumeric.

Curcumin concentration in the blood’s serum peaks 1-2 hours after taking it by mouth.(2)

A strong antioxidant.

Oxidation is a natural attribute of oxygen. Oxygen likes to combine with other molecules. As it does so they become oxidized. In nature the process of oxidation is seen when metal rusts and when fat goes rancid. The rusted metal is chemically different than non-rusted. Rancid fat has also been chemically altered by oxygen. In the human body oxidation can also damage molecules and tissues. The body protects itself with antioxidants. In every day terms antioxidants are like putting oil on metal to protect it from rust. Or putting butter in the refrigerator to prevent it from going rancid.

Many different nutrients serve as antioxidants. Vitamins C and E and selenium are examples of some. Plants produce their own antioxidants to protect themselves from the effects of oxygen. In the plant kingdom antioxidants often give the plant, fruit or vegetable its color.

In India tumeric has been used for centuries as a food additive for flavoring and to keep food from spoiling. In our body it does the same. It prevents damage from oxygen (oxidation), and in so doing protects our health.

One of the primary theories of aging says we grow old as the result of oxidation of our tissues. Our antioxidant systems can’t keep up with the damaging effects of oxygen. Eventually so much tissue damage occurs that our body systems begin to malfunction. Eventually the malfunctioning of our organs leads to death.

The damage of oxidation often occurs through an intermediary molecule called a free radical. Free radicals are very reactive transient molecules that swipe electrons from their neighbor molecules. If the nearest neighbor happens to be the cell’s DNA or genetic material, a free radical can damage DNA. Damaged DNA can cause the cell to go out of control, multiplying again and again. This is cancer. Carcinogens (chemicals that are known to cause cancer) mainly cause cancer by producing free radicals which damage the cellular DNA.

Researchers have shown that curcuminoids can prevent free radicals from forming. Once formed, curcuminoids are able to neutralize free radicals before they cause damage. Curcuminoids inhibit potent free radical molecules such as superoxide and hydroxyl radicals.(3) Still other researchers compared curcumin to vitamins C and E in its strong antioxidant activity.(4) One of the body’s core antioxidants is glutathione. When curcumin is added to cells in a tissue culture it increases intracellular glutathione levels.(5)

Relieves pain and inflammation.

Curcumin has strong anti-inflammatory activity. One researcher summarizes the findings this way:

”Turmeric, an approved food additive, or its component curcumin, has shown surprisingly beneficial effects in experimental studies of acute and chronic diseases characterized by an exaggerated inflammatory reaction. There is ample evidence to support its clinical use, both as a prevention and a treatment.”(6)

Researchers find the action of curcumin to two non-steroidal anti-inflammatory drugs, indomethacin (Indocin) and phenylbutazone, but without the side effects. The side effects of phenylbutazone are serious. They include suppression of production of white cells (immune system) and of red cells in the bone marrow resulting in anemia. Other side effects of prolonged use include those characteristic of other NSAID’s gastrointestinal ulcers and bleeding, and kidney damage.

Curcumin has also been shown to have activity similar to aspirin, but without the side effects.(7)

Researchers are beginning to understand how curcumin’s anti-inflammatory activity works. Remember the “Cox-2 inhibitors” like Celebrex and Vioxx? These drugs were designed to inhibit the action of an enzyme that is involved in the inflammatory process. By inhibiting the enzyme, inflammation could be decreased. Unfortunately when the enzyme was blocked by these drugs it through other important and vital chemical reactions out of balance. This is what creates the harmful side effects of these drugs and the other NSAID’s.

Curcumin, being composed of a number of active molecules, has a broader action than single drugs. We know that this action is also more balanced and in tune with the body’s need. This is obvious because of the lack of harmful side effects with curcumin. It acts on several major inflammatory pathways in the body. The biochemistry of inflammation is complex. The key idea here is that curcumin exerts a more gentle action on several different inflammatory pathways, producing an overall result comparable to what is achieved with drugs.

Here is how researchers summarize the biochemical actions of curcumin with regard to inflammation.

“The anti-inflammatory effect of curcumin is most likely mediated through its ability to inhibit cyclooxygenase-2 (COX-2), lipoxygenase (LOX), and inducible nitric oxide synthase (iNOS).(8)

An oil extract of tumeric was shown to decrease arthritis in rats.(9)

A preparation of tumeric containing eye drops effectively treated bacterial conjunctivitis, a condition in which the eye becomes inflamed because of a bacterial infection. Eye redness and burning improved after 3 days of treatment. After six days 23 out of the 25 participants in the study reported relief of all their symptoms.(10)

Researchers gave 18 patients with rheumatoid arthritis 1200 mg of curcumin daily. After two weeks they reported improvement in morning stiffness, walking time and joint swelling.

Curcuminoids have been shown to help post-surgical pain. 40 men who had undergone surgery for hernia’s were given curcumin at a dose of 1200 mg per day. After five days the reported relief in swelling, tenderness and pain was the same as that reported for NSAID phenylbutazone.

Three more researcher’s in a study titled “Role of curcumin in health and disease” summarize the research findings on curcumin and inflammation this way:

“Curcumin has the potential to treat a wide variety of inflammatory diseases including cancer, diabetes, cardiovascular diseases, arthritis, Alzheimer's disease, psoriasis, etc, through modulation of numerous molecular targets.”(11)

Another research group praised curcumin’s properties this way:

“[Curcumin] has been proven to exhibit remarkable anticarcinogenic, anti-inflammatory, and antioxidant properties.”(12)

When I (Dr. Mittag) suffered a herniated disc, during the first week I was in such severe pain I needed a steroid injection and narcotics. As it became less severe I shifted to large doses of curcumin, a few other herbs and a couple alternative treatments. Just one and one-half weeks after my initial hospitalization I was off all drugs and pain free.

Can help prevent and may improve Alzheimer’s Disease.

The rate Alzheimer’s disease in India is perhaps the lowest in the world. Scientists find that cultures that consume the greatest amount of tumeric have the lowest incidence of Alzheimer’s disease in the world. India’s rate of Alzheimer’s is one-quarter that of the United States. Only 1% of Indians over the age of 65 suffer from the degenerative brain condition.

In Alzheimer’s protein deposits form amyloid plaques in the brain. In a sense these plaques gum up the works, disrupting brain function. When plaques form in synapses—the communication junctions between nerve cells—nerve cells fail to communicate with each other effectively. Memory loss is one result. Researchers have shown that oxidative damage and inflammation contribute to the formation of these plaques. It has been shown that in a test tube curcumin inhibits the formation of the protein that makes up these plaques.(11) It has been confirmed that curcuminoids in the blood stream do cross the blood brain barrier and enter the brain.(13) In animals with an Alzheimer’s like disease, curcumin even decreased the amount of amyloid plaques.(13-15)

The promise of curcumin for Alzheimer’s has resulted in a number of clinical trials now in progress.(16) These studies are looking at curcumin both as a way to prevent and to treat Alzheimer’s disease. In the mean time I’m taking my curcumin supplements and enjoying more curry in my diet.

Can prevent and suppress cancer.

Cancer arises when cells multiply out of control. Cell multiplication is normally under the control of genetic material within the nucleus of the cell. This genetic material is chemically called DNA. Damage to the DNA can initiate the process of out of control multiplication. Damage is known to occur through exposure to carcinogens such as the chemicals in cigarette smoke, radiation, other toxic chemicals and even infections. Hormone imbalances can also over stimulate cells resulting in cancer formation.

The development of cancer is a complex multi-step process. If cells multiply out of control but do not spread, the result is a benign tumor. Cells that are multiplying out of control can also invade neighboring tissues. In the process the don’t act or look like the cells they once were. These cells spread throughout the body or metastasize. This is called metastasis (or spread) and makes the cancer malignant (literally meaning “bad”). As they invade tissues elsewhere in the body they begin to disrupt body functions and as we all know, can eventually cause death.

Clinicians have classified the stages of a malignant cancer’s growth.These stages are called initiation, promotion and progression. Initiation involves permanent damage to the cellular DNA or genetic material. Viruses, radiation and environmental chemical toxins are all thought to cause of “initiation”. With promotion the cell begins to multiply or grow out of control. The carcinogenic chemicals in tobacco smoke, environmental pollutants, drugs and hormones are all promoters. With progression the cell begins to invade neighboring tissues. It has lost its identity in terms of its normal structure and function. It is now a rogue destructive opportunist.

Curcumin to the rescue. Hear what researchers have to say with regard to curcumin’s anticancer properties and the three stages of cancer formation.

“Carcinogenesis encompasses three closely associated stages: initiation, progression, and promotion. [Curcumin] has been shown to possess anti-inflammatory, antioxidant, and antitumor properties. [It] has also been shown to be beneficial in all three stages of carcinogenesis.”(17)

Normally diseased cells will self destruct. This is sort of a safety mechanism programmed into human cells. The process is called apoptosis. Cancer cells skirt this safety net as they metastasize throughout the body.

Curcumin was demonstrated to increase apoptosis or self destruction of prostate cancer cells in men.(18) The rate of prostate cancer in India versus the United States is revealing. Remember that East Indians tend to consume lots of curcumin. In India the rate of prostate cancer ranges from 5.0 to 9.1 per 100,000/year. In the United States is 110.4 per 100,000/year or more than 10X’s. For African Americans the rate of prostate cancer is even higher.(19)

In fact, curcumin has been shown to protect the body from cancer in many ways, and in many stages of the cancer formation process. Researchers recognize the value of this when they state…

“Curcumin… has emerged as one of the most powerful chemopreventive and anticancer agents. Its biological effects range from antioxidant [and] anti-inflammatory to inhibition of angiogenesis, and [it] is also shown to possess specific antitumoral activity.”(20)

Cancer refers to the process that can happen to many different cells in the body. Researchers are finding that curcumin works against many types of cancer, not just a single type:

“Pre-clinical studies in a variety of cancer cell lines including breast, cervical, colon, gastric, hepatic, leukemia, oral epithelial, ovarian, pancreatic, and prostate have consistently shown that curcumin possesses anticancer activity in vitro and in pre-clinical animal models.”(21)

The study of the cancer preventative and suppressive effects of curcumin continue. Researchers are also moving to develop anticancer drugs based on the chemicals found in curcumin.

Many other amazing health benefits.

Many other health benefits of curcumin have been verified.

• Nervous system protection. We’ve seen that curcumin protects against and may help to reverse Alzheimer’s Disease. Researchers find that curcumin “has at least 10 known neuroprotective actions…” which make it “a strong candidate for use in the prevention or treatment of major disabling age-related neurodegenerative diseases like Alzheimer’s, Parkinson’s and stroke.”(22)
• Protects against cataracts. Oxidative stress is thought to be the basis of cataract formation. Curcumin is known to be a strong antioxidant. Two studies have found that curcumin protected the eye lenses of rats from cataract formation. The opacification (clouding) that is characteristic of cataract formation was significantly reduced when rats were fed curcumin.(23)
• Stimulates wound healing. Rats given curcumin had skin wounds heal faster than those who didn’t.(24) This was found to also be true in diabetic rats and mice. Normally wounds in diabetic animals are known to heal more slowly.(25)
• Curcumin has also shown promise in the treatment of multiple sclerosis(26), psoriasis(27), cystic fibrosis(28), dementia(29) and more.

Curcumin is safe.

Curcumin has been demonstrated to be absolutely safe for humans. Curcumin containing tumeric has been used in Indian and Asian cooking for over one thousand years.

Researchers also say that curcumin is safe. In one study 25 subjects took 8000 mg of curcumin daily for three months without any toxic effect. A total of six studies have looked at the safety of curcumin for human consumption. After reviewing all of these studies the scientists concluded that “Curcumin has been demonstrated to be safe in six human trials and has demonstrated anti-inflammatory activity.”(30) Consumption of 20-40 mg of curcumin has been reported to increase gall bladder contraction in healthy people.(31-32) Gall bladder contraction is a normal physiological activity, occurring after ingestion of fats.

References:

(1) Lechtenberg M, Quandt B, Nahrstedt A. Quantitative determination of curcuminoids in Curcuma rhizomes and rapid differentiation of Curcuma domestica Val. and Curcuma xanthorrhiza Roxb. by capillary electrophoresis. Phytochem Anal. 2004;15(3):152-158.

(2) Cheng AL, Hsu CH, Lin JK, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001;21(4B):2895-2900.

(3) Reddy, A.C.P., and Lokesh, B.R. (1992). “Studies on Spice Principles as Antioxidants in the Inhibition of Lipid Peroxidation of Rat Liver Microsomes,” Mol. Cell. Biochem. 111:117.

(4) Toda S, Miyase T, Arich H, et al. Natural antioxidants. Antioxidative compounds isolated from rhizome of Curcuma longa L. Chem Parmacol Bull 1985;33:1725-1728.

(5) Dickinson DA, Iles KE, Zhang H, Blank V, Forman HJ. Curcumin alters EpRE and AP-1 binding complexes and elevates glutamate-cysteine ligase gene expression. Faseb J. 2003;17(3):473-475.(6) Bengmark, S. Curcumin, an atoxic antioxidant and natural NFkappaB, cyclooxygenase-2, lipooxygenase, and inducible nitric oxide synthase inhibitor: a shield against acute and chronic diseases. JPEN J Parenter Enteral Nutr. 2006 Jan-Feb;30(1):45-51.(7) Srivastava, V, et al. Effect of Curcumin on Platelet Aggrefation and Vascular Prostacyclin Synthesis, 1986. Arzneim. Forsch./ Drug Res. 36:715.

(8) Menon, VP, Sudheer, AR. Antioxidant and Anti-inflammatory properties of curcumin. Adv Exp Med Biol. 2007;595:105-25. Review.

(9) Chandra, D, Gupta, S.S. Sodium Curcumanate as an Effective Anti-Inflammatory Agent”, 1972. Ind. J. Exp. Biol. 10:235.

(10) Srinvas, C, Prabhakaran, K.V.S, Science of Life, 1989. 8:279.

(11) Pari L, Tewas D, Eckel J. The role of curcumin in health and disease. Arch Physiol Biochem. 2008 Apr;114(2):127-49.

(12) Phan TT, See P, Lee ST, Chan SY. Protective effects of curcumin against oxidative damage on skin cells in vitro: its implication for wound healing. J Trauma. 2001 Nov;51(5):927-31.

(13) Deodhar SD, Sethi R, Srimal RC. Preliminary study on antirheumatic activity of curcumin (diferuloyl methane). Indian J Med Res. 1980;71:632-634.

(14) Yang F, Lim GP, Begum AN, et al. Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem. 2005;280(7):5892-5901.

(15) Frautschy SA, Hu W, Kim P, et al. Phenolic anti-inflammatory antioxidant reversal of Abeta-induced cognitive deficits and neuropathology. Neurobiol Aging. 2001;22(6):993-1005.

(16) Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci. 2001;21(21):8370-8377.

(17) National Institutes of Health. Clinical Trials.gov. 2005.

(18) Thangapazham RL, Sharma A, Maheshwari RK. Multiple molecular targets in cancer chemoprevention by curcumin. AAPS J. 2006;8(3):E443-9.

(19) Asok Mukhopadhyay, Carlos Bueso-Ramos, Devasis Chatterjee, Panayotis Pantazis and Bharat B Aggarwal. Curcumin downregulates cell survival mechanisms in human prostate cancer cell lines. Oncogene (2001)20,7597-7609.

(20) Hebert JR, Ghumare SS, Gupta PC. Stage at diagnosis and relative differences in breast and prostate cancer incidence in India: comparison with the United States. Asian Pac J Cancer Prev. 2006 Oct;7(4):547-55.

(21) Li M, Zhang Z, Hill DL, Wang H, Zhang R. Curcumin, a dietary component, has anticancer, chemosensitization, andradiosensitization effects by down-regulating the MDM2 oncogene through the PI3K/mTOR/ETS2 pathway. Cancer Res. 2007 Mar1;67(5):1988-96.

(22) Johnson JJ, Mukhtar H. Curcumin for chemoprevention of colon cancer. Cancer Lett. 2007 Apr 18.

(23) Cole GM, Teter B, Frautschy SA. Neuroprotective effects of curcumin. Adv Exp Med Biol. 2007;595:197-212.

(24) Am J Clin Nutr 1996 Nov;64(5):761-6.

(25) Wound Repair Regen 1998 Mar-Apr;6(2):167-77.

(26) Wound Repair Regen 1999 Sep-Oct;7(5):362-74.

(27) Bright JJ. Curcumin and autoimmune disease. Adv Exp Med Biol. 2007;595:425-51.

(28) Thangapazham RL, Sharma A, Maheshwari RK. Beneficial role of curcumin in skin diseases. Adv Exp Med Biol. 2007;595:343-57.

(29) Gautam SC, Gao X, Dulchavsky S. Immunomodulation by curcumin. Adv Exp Med Biol. 2007;595:321-41.

(30) Ng TP, Chiam PC, Lee T, et al. Curry consumption and cognitive function in the elderly. Am J Epidemiol. 2006 Nov 1;164(9):898-906.

(31) Chainani, Wu N. Safety and anti-inflammatory activity of curcumin: a component of tumeric (Curcuma longa). J Altern Complement Med. 2003 Feb;9(1):161-8.

(32) Rasyid A, Lelo A. The effect of curcumin and placebo on human gall-bladder function: an ultrasound study. Aliment Pharmacol Ther. 1999;13(2):245-249.

(33) Rasyid A, Rahman AR, Jaalam K, Lelo A. Effect of different curcumin dosages on human gall bladder. Asia Pac J Clin Nutr. 2002;11(4):314-318.

(34) http://www.mittag-holistic-chiropractic.com/curcumin.html

Oxidant begins when the body defense system reacts against strange substances, such as microorganism. The said oxidants are: super-oxide, hydrogen peroxide, free radicals and lipid peroxide. The existence of bacteria also influence the body defense system by producing natural oxidant which has the capability of killing the bacteria. Such oxidant, however, also kills normal/healthy cells (1.2).

Another oxidant produced by a human body is cytochrome enzyme which can be much found in lungs and liver. Human organs also protect the body against external oxidant entering through air, water and food (1).

Curcumin has the ability to tie those free radicals/oxidants. The fact has been proven by researchers who did the tests on animals and man. In the research carbon tetrachloride was added to increase lipid peroxide rate, it significantly decreased by giving Curcumin (3).

REFERENCE:

1. L. Goldwyn, 1997, The Real Spice of Life. Life Extension Magazine, December.
2. Hill BT., Alternative to Liver Disease.
3. Jentzsch K., P. Spiegl and R. Kamitz, 1970. Curcumin Dyes in Different Zingiberaceae Drugs. Sci Pharm; March 31:50-8.

Curcumin maintains the liver function health by influencing the output and production of gall by liver cells. This has been proven with the research done over 19 patients suffering from jaundice/yellow decease. When they were Curcumin, there was an increase k olagogum effect (increase of gall production) (1).

The hepatoprotector effect from Curcumin was tested by adding carbon tetrachloride to the tested animal. The carbon tetrachloride can damage/poison the liver. The animal was then given temulawak extract (Curcumin). There was an increase of liver parencym cells formation which could be signed by the decrease of SGOT and SGPT enzymes as the indicators.

REFERENCE:

1. Hadi S., Manfaat Temulawak Ditinjau Dari Segi Kedokteran. Proceeding of National Symposium on Temulawak. Pajajaran University Research Institute.

Curcumin is also good to lower the rate of total and LDL cholesterols and increase HDL cholesterol by increasing the gall acid flow/gall's liquid from liver.

This gall acid is produced at the liver and functions in assisting the absorption process in the digesting pipe (stomach). The gall's liquid contains water, gall's salts, gall's color element, cholesterol, and fat. In line with the increasing production and output of gall's liquid, it will also increase the output from cholesterol and fat. Therefore, it will lower the exceeding rate of cholesterol in the body (1).

The herbal plant of temulawak seems to be able to prevent various kinds of deceases, for instance cholesterol, coronary heart, stroke, and rheumatic, as temulawak contains an active compound of curcumin which acts as antioxidant and imunostimulator/imunomodulator, said the Head of Drugs and Food Control Agency of the Republic of Indonesia, H. Sampurno, MBA, in the socialization of Drink Temulawak National Campaign (GNMT) at the Head Office of Drugs and Food Control Medan (BBPOM). (Waspada, 21/11/05).

REFERENCE :

1. Hadi S. Manfaat temulawak ditinjau dari segi kedokteran. Proceeding of National Symposium on Temulawak. Pejajran University Research Institute, Bandung . Pp. 139-44

If liver is unhealthy, detoxification will not be fast and more toxin is spread out to all of the body via blood. It will lead to various chronic deceases.

Can we say that we are lucky not knowing that our lives are surrounded by toxin? If we know it, we will be scared of doing the activities, going out, having socialization, and eating. But we are more lucky if we know that toxin is everywhere. The more we know, the wiser we will be in maintaining the our body and life.

The explanation is like this. Nowadays people live in an instant and polluted era. Due to served instantly, food is also preserved. Pollution is everywhere. Whether people like it or not, they live side by side with toxin. Poisonous substances are in the food we consume, the water we drink, and the air we breathe.

Directly or indirectly, we bring fertilizers into our body via food, chemical elements and addictive in the food, for example artificial color and preservatives. In addition, air pollution from cigarettes smoke, vehicles' emition, pesticydes, and industries' pollutants enter our body.

Those toxin must be thrown out from the body, not including the toxin produced by the body itself. Naturally the body produces toxin through liver by detoxification, or detox for short.

A healthy liver does detox in two mechanism, known as phase 1 and phase 2. At phase 1, the enzymes in the body moves the poisonous elements for more easily processed at phase 2. At phase 2, there are other enzymes that change the toxin into a more easily dissolved in the water. The body then brings them out of the body through urine or feces.

Unhealthy liver cannot do the detoxification as fast as the healthy one. It is easy to guess that if detoxification process is slow, the liver which has not finished the detox process will be attacked by other poisons it has to detox. As a result, there will be more poisons circulate to the whole body through blood.

Some of the toxin are not changeable or can be changed just a little bit or are difficult to be sent away from the body because they slip off of the liver function. As a consequence, those toxin are hiding at the fatty tissue, brain, and at nervous system cells. Those hidden toxin will slowly go into the blood vessels and cause chronic deceases, for instance: liver decease which may lead to hepatitis, and become more dangerous into cirrhosis (liver cancer).

Some of the ways to acknowledge the initial symptoms that there is a disorder of liver function in detoxification due to a lot of toxin than cannot be processed and settle in the body are easily exhausted, weary, dull skin, and easily get sick. Do not neglect if you feel the following symptoms (as revealed by American Liver Foundation) as they may indicate that you might suffer from more serious liver decease. Please contact a physician since it is much better to detect it early rather or it is too late to handle.

• Change of skin color or eyes to yellow.

• Swollen stomach, or severe pain at stomach.

• Prolonged irritation on skin.

• Dark urine color or pale feces.

• Chronic weariness, queasy or losing appetite.

Healthy from Food

Since all food and drink entering our body will surely pass the liver, so we must pay a careful attention to keep our liver healthy.

Consume healthy and nutritious food proportionally. Reduce fatty and oily fried food. Doctors ensure us that the risk of gall's bag sickness (including gall's stone, decease related to liver) can be reduced by avoiding high fatty and cholesterol food.

If you are positive of suffering from a liver decease, please reduce the consumption of smoked, preserved, and salted food. Taste your food first before adding it with salt, As substitutes, you may add to your cooking with lemon juice, garlic, onion, pepper, clove, and other spices.

It is better to change the too sweet desserts, snack, and high calorie drink with fruits.

Please maintain your ideal weight. The medical researchers confirm direct correlation between obesity and the increasing gall decease. Those suffering from obesity or diabetes will have more risk and potentials of getting serious liver decease called non-alcoholic-steatohepatitis.

Don't forget to exercise regularly, two or three times a week, to help you keep your liver healthy.

Natural Benefits

Not so many people realize how important the liver function in detoxification is. When the sickness is getting more serious, only then he/she goes to see a doctor.

Some people realize the importance of liver health and look for healing method by detoxification

May be you have ever seen at malls or public practicing places people offer detoxification at a certain amount of money.

Instead of taking actions without knowing the side effects, it is better to consult a doctor. There is one way to help maximize the liver function safely using natural substances.

For decades the people have been using temulawak commonly to heal the liver. Previously the herb having the Latin term Curcuma Xantorrhizae were scrapped, and then squeezed to get the juice and drunk for healing purpose. Today with high technology, temulawak is produced in extract and packed modernly as a tablet.

Temulawak extract is useful as antihepatotoxin and in fixing the liver cells. This herb together with Letichin (Phosphotidylcholine) and vitamin E function to optimize the liver function as detoxification organ.

Liver

* The fatal organ in the body functioning as blood vessel cleanser and filter.

* The biggest organ in the body having a big amount of blood, flowing through it at every minute of man's live.

* Size:
Diameter (the biggest): 21-22.5 cm
Height (the biggest): 15-17.5 cm
Thickness (the biggest): 10-12.5 cm
Weight: 1,200 - 1,600 grams

* Functions:

1. Responsible in production of gall's water kept at gall's bag and released when needed in fat digestion.
2. Keep glucose in the form of glycogen which will be changed again into glucose when needed as energy.
3. Has an important role in protein and fat metabolism. Liver keeps vitamin A, D, K, B12, and folat and unite blood clotting factors.
4. As detoxifier (detox tool), breaking or changing the elements such as ammonia, metabolism, medicine, alcohol and chemical wastes, to be sent away from the body. When seen under a microscope, we can see a line of liver cells separated by rooms acting as filters.

The liver filter is designed to expel the poisonous substances, such as dead cells, micro- organism, chemical elements, medicine, and particle wastes, from the blood vessels. This liver filter is called sinusoidal system, containing particular cells known as Kupffer cells which break and destroy poisonous substances.

Source: liverdoctor.com

The Curcuma xanthorhiza rox content, curcumin, contains a million of benefits for health improvement.

Indonesian is known as a tropical country with the second mega biodiversity, rich with plants known empirically or through a lab research as useful herbal medicine. One of them is temulawak, which belongs to ginger family (zingiberaceae). Temulawak ( Curcuma xanthorhiza rox ) is Indonesian original herbal plant. However, the spread of the plant popularly known as curcuma javanica is limited on Java, Maluku, and Kalimantan islands only. Temulawak grows as herbaceous bushes. Starting from its base or foot grows long and straight leaves stick. The plant can grow 2-2.5 meters tall. Its leaves are long and oval like banana leaves. Its leaves are overlapping one and another forming a stem.

The plant, the core of which is easy to digest, can grow rapidly at lowland to an area reaching the height of 750 meters above sea level. Temulawak is ready for harvest after reaching the age of 8-12 months, when its leaves become yellowish and look like to die. Tubers will appear from its foot, their colors are dark yellow or light brown, their length can be 15 centimeters with a diameter of 6 centimeters. It smells good and tastes bitter and a little bit hot.

The benefits of temulawak for health actually has been acknowledged empirically and through experiences for generations from our forefathers. For decades temulawak has been used as antibiotic, arouse someone's appetite, cure yellow decease, diarrhea, gastritis, filled with air stomach, and weariness. Temulawak can also lower blood fat, hamper blood clotting as antioxidant, and maintain health by increasing immunity. Some of those benefits are clinically proven. Looking at the various benefits of temulawak, with no doubt the Indonesian government announced “drink temulawak national campaign” since 2 years ago.

Help Liver Destroy Toxin

Temulawak rhizome contains several chemical compounds, such as atsiri oil, fellandrean and turmerol, camphor, glucocyde, foluymetic carbinol, and curcumin. Curcumin is known as a compound with various benefits, especially as anti-hepototoxic and antioxidant.

The mechanism of curcumin in surviving the “symbol of romanticism” is still unclear. However, a study an a tested animal reported that curcumin strongly hampers cytochrome 4501A1/1A2 enzyme in the liver. This enzyme is isoenzyme which is actively participated in bioactivation of some toxin, including benzo[a]pyrene . Curcumin is also found out in preventing the formation of covalent ties between cytochrome P450 and DNA. The researchers concluded that curcumin might hamper carcinogenesis by chemicals with the modulation of P450 function.

Besides, curcumin is also found to be able to protect liver against alcohol toxicity. This effect was proven in a study done over rats which were induced with ethanol 25%. The rats which were given curcumin 80 mg/kg BB experienced the reduction of liver enzyme rate and the reactive tiobarbiturat acid product. Another study also showed that curcumin decreases liver destruction through reduction of lipid peroxidation. It was observed over rats which were induced with ferrum. Still according to a pre clinical test, curcumin was reported to increase the activity of glutathione-S-transferase . This enzyme is very important in detoxification process.

Curcumin Clinical Test

A moderate clinal test was done in Indonesia to find out the benefits of curcumin in fixing the liver function. The study involved 38 patients with liver problems or having SGPT and SGOT above the normal rate in 7 cities (Bogor, Bandung, Semarang, Solo, Surabaya, Palembang, and Jakarta). The patients were given a mix of curcumin 25 mg, essential phospholipid 100 mg, and vitamin E 100 mg. The study used seeding trial method or without comparison. The observation was done by around 20 researchers in the period of July-December 1998.

The parameter used is SGPT and SGOT rates. SGPT is an enzyme produced by hepatocytes, the cells abundantly found at the liver. The rate of SGPT in the blood will increase in line with the damage of hepatocytes cells due to hepatitis virus infection, alcohol, medicines which induce the damage of hepatocytes, and due to other reasons such as shock or medicine poison.

The normal SGPT rate is 0 - 35 units per liter (u/l). The acceleration of SGPT rate by 50 times of the normal rate indicates the short of blood flow at the liver, hepatitis, or liver cells decay caused by chemical medicine/compound, such as CCl4. The increase of SGPT from low to medium rate may be caused due to hepatitis, cirrhosis, liver cancer, and alcohol. Sometimes at cirrhosis, the increase of SGPT rate is only 2-4 times higher than the normal rate.

Meanwhile, SGOT is much found at heart, liver, skeleton muscles, pancreas, lungs, red blood cells, and brain cells. When the cells are damaged, SGOT will be released into the blood. As a result when being measured, it can be seen the correlation the amount or level of cell damages. The normal rate of SGOT is around 3 - 45 units per liter (u/l). The escalation of SGOT rate may be caused with the existence of hepatitis C. At acute hepatitis, the escalation may reach up to 20 times of the normal rate.

The study shows, according to the statistic calculation, there is a significant decrease of SGOT and SGPT. After 14 days of therapy, the decrease of SGOT of the total patients reached 2.89 times, while for SGPT reached 3.28 times compared to before treatment. The similar result was also found at a person suffering from hepatitis and non hepatitis. The hepatitis patients experienced the decrease of SGOT at 3.48 times and SGPT at 3.82 times, compared to before treatment. On the other hand, at the non hepatitis patients, there is a decrease of SGOT around 1.91 times and SGPT at 2.15 times.

Digging up Other Benefits.

Until today, there are many studies done to find out other benefits from this valuable tuber. The study which was seriously done recently is to see the use of curcumin as anti tumor to heal cancer deceases. A number of reports show that curcumoid, including curcumin, has the activity of chemo preventive and curative against cancer. The study generally was done on animal with different giving routes and tested using in vitro system. Recently a few study has been started on man.

Another benefit of curcumin aimed is the replication obstruction of Human Immunodeficiency Virus (HIV). A study shows that curcumin hampers the fusion stage of the virus cells at HIV replication cycle. A various studies were continuously done to reach the breakthrough. In case all studies are clinically proven, the plants containing curcumin will be rich in benefits. And Indonesia will also be happy because curcumin is the Indonesian original herbal plant.

Source: ULAS OBAT November 2006 edition (Vol. 6 No. 4), by andra.