First Do No Harm

Cancer, Curcumin and Ayurveda
(Mewa Singh)

Instead of concentrating on treating the symptoms of an illness, ayurvedic medicine concentrates on treating the disease using treatments to eliminate its root cause. According to Ayurveda, cancer is a disease that is caused by lack of purpose, and is an emotionally caused disease.

Ayurvedic science says that diet, lifestyles and medicine play an important role in both the treatment and prevention of cancer. Either too much, too little or wrong diets tend to affect the vata, pitta and kapha of the body metabolism, and this in turn leads to cancer. It is a group of chronic disorders that affect the different dhatus and doshas which cause cancer.

Different people suffer from different forms of cancer, and its diagnosis and treatment change according to the prakriti of the patient. Treatment in Ayurveda for cancer consists in shodhan, which is the detoxification and purification of dosha and dhatu, shaman the pacification and rebalancing of the disturbed dosha and spoilt dhatu and rasayana which is rejuvenation. Snehana which is internal and external oiling of the body and swedan where sweating is induced is suggested for shodhan of the body.

There is basically no specific treatment for cancer in Ayurveda. Medication is used for restoring the normal functioning of organs of the body and to help the body fight the disease. Though there are some medicines that kill cancer cells, it is more of a supplemental therapy that aims at an overall management of the disease. Positive results have been reported with the use of heerak bhasma, which is prepared with diamonds, for treating cancer.

With the help of Ayurved, it is possible to reduce reactions to chemotherapy and radio therapy to an extent. A preparation of sea coral called Praval pishti is cooling and helps in reducing the intensity of the reactions in these procedures. However before starting this, it is better to consult an ayurvedic doctor as treatment changes from patient to patient.

It is possible to treat complaints like nausea and vomiting with ayurvedic combinations of equal amounts of shredded ginger, honey and lemon juice. This mixture should be taken before food to reduce nausea and vomiting.

Ayurvedic therapy for treating cancer includes taking fresh fruits and vegetables for natural vitamins and minerals, a light diet that is easy to digest, fresh air, support from family and most importantly, a positive attitude to life. Even ayurvedic tonics like shatavari kalpa with asparagus, badam pak with almond and Chyawanprash with amla help in coping with cancer.

Ayurvedic practitioners call turmeric the "golden spice of life." Its botanical name is "Curcuma longa," and it belongs to the Ginger family. Ayurveda, a 5,000 year old medical system, has used it for healing, eating and more. Turmeric was used in its earliest days as both a paste and a juice. When raw pieces of turmeric are crushed, the result is a translucent, reddish-yellow tasteless liquid which can be mixed with honey to give it some flavor. Turmeric liquid is used in Ayurveda as a blood purifier, and in cases of chronic illnesses and stomach problems. The paste is used to treat skin conditions, like eczema. Anticancerous Drug-Curcuma Longa Haldi(Circuma Longa), A Member Of Ginger Family, Is Well Known Drug In Ayurveda. In Charak Samhita It Is Catagorize Under Lekhniya,Vishaghna And Kushthaghna Mahakashaya. In Sushrut Samhita It Is Catagorize Under Haridradi Group.Bhavprakash Nighantu Described Haldi In Haritkyadi Group.

According Ayurveda,it Is Laghu , Ruksha In Guna,tikta In Rasa, Katu In Vipaka And Ushna In Veerya.It Has Potent Raktashodhak(Purifies The Blood- Means, It Removes All The Foreign Particles , Present In The Blood) Property And Aam Pachak(Improves Metabolic Activity) Activity. Astang Sangraha , An Ayurvedic Text Book,described That Haldi Is Effective In Karkatarbud(Anti Cancerous Effect) .

Nearly All Ayurvedic Text Books Described Its Vat-shamak Effect Due To Ushna Veerya And Useful In Skin Disorders. Chemical Composition;- The Most Effective And Active Ingredient Of Haldi Is Curcumin. It Is A Yellow Pigment.

Pharmacological Action: -
According Modern Researches, Curcumin, The Most Active Ingredient Of Turmeric, Is A Powerful Antioxident Substance. It Has Also Anti- Inflammatory Effect.It Inhibits Production Of The Inflammation –related Enjyme- Cyclo-oxygenase2(Cox-2), Levels Of Which Are Abnormally High In Certain Inflammatory Diseases. Curcumin Seems To Protect Skin During Radiation Therapy.

Anticancerous Effect:-
According The Researches,carried Out By Ohio State University Of Columbus,turmeric Has Demonstrated As Anticancerous Drug In All States Of Tumour Development In Rodents And Showed Potential Effect To Kill Cancer Cells And Prevent Normal Cells From Being Cancerous. Researches Says That Whole Turmeric Ingested Through Diet Is Better For Cancer Prevention Than Isolated Curcumin. Studies On Mice And Humans Have Shown Potential Biological Activity As Turmeric To Prevent Cancer. Through All Researches, It Seems That Turmeric Shows A Lot Of Promise In Delaying The Onset Of Cancer.

Mode Of Action:-
Turmeric Shows Anticancerous Effect Through Probably 2 Ways. Frist, As It Is Believe To Inhibit The Production Of Inflammatory Related Enjyme Cyclo-oxygenase2(cox-2) Levels Of Which Are Abnormally High In Certain Inflammatory Diseases And Cancers, Especially Bowel And Colon Cancer. Secondly, It Inhibits Irreversibly Aminopeptidase N(APN), An Enjyme That Is Responsible For Tumour Invasiveness And Angiogenesis.(blood Vessel Growth). Scientists Have Known That Curcumin Slows The Growth Of New Cancerous Cells. It Was Found To Arrest Angiogenesis. APN Is A Membrane-bound, Zink Dependent Metaloprotenase That Breaks Down Proteins At The Cell Surface And Helps Cancer Cells Invade The Space Of Neighbouring Cells. Curcumin Inhibits The APN Directly And Irreversibly.

Old and new interpretation of inflammation and cancer

Turmeric has always been considered an auspicious material in the Indian sub-continent, both amongst the Aryan cultures and the Dravidian cultures and its value extends far in history to the beliefs of ancient Indian population. Yellow and yellow-orange are colors with sacred and auspicious connotations in India, yellow being associated with God, and as the color of the space between chastity and sensuality. Orange signifies sacrifice, renunciation and courage. In Buddhism yellow is the color of the Bodhisattva . In South India, turmeric is considered very auspicious and therefore, is the first item on the grocery list. The medicinal history of turmeric is at least 2500 years old. Ayurveda, Unani, Siddha and Chinese medicine recommend turmeric for a large number of disorders and diseases. Susruta's Ayurvedic Compendium, dating to 250 BC, recommends an ointment containing turmeric to relieve the effects of poisoned food.

Traditional Indian medicine use the powder against billary disorders, anorexia, coryza, cough, diabetic wounds, hepatic disorders, rheumatic disorders, sprains and swellings caused by injury, and sinusitis. Externally, the dried rhizome has been applied to fresh wounds and to insect stings and to help the healing process in chickenpox and smallpox. Traditional Chinese medicine uses curcuma in diseases associated with abdominal pain, amenorrhea, dysmenorrheal, distending or pricking pain in the chest and abdomen; impairment of consciousness in febrile diseases, epilepsy, and mania; jaundice with dark urine.

Since the Ayurvedic times (1900 BC), numerous therapeutic activities have been assigned to turmeric for a wide variety of diseases and conditions, including those of the skin, pulmonary, and gastrointestinal systems, aches, pains, wounds, sprains, and liver disorders. Turmeric is also recommended under the Unani, Sidha and Chinese systems of medicine. Modern research has confirmed and provided a scientific basis for these various health claims, unlike many other traditional medicines. Since the isolation of curcumin as the main active constituent of turmeric about two centuries ago, much of the scientific interest has shifted to this molecule rather than on turmeric.

Observational studies point to the substantially reduced prevalence of Alzheimer’s disease, rheumatoid arthritis and disease of the gastrointestinal tract such as colon cancer and inflammatory bowel diseases in Asian countries compared to the western world as a consequence of the daily consumption of turmeric as a curry spice. For this reason, curcumin has been termed “the spice of life”.

Research on curcumin is exploding with more than 3000 reports presently available. This is because of an extremely wide array of biological activities exhibited by the molecule. Curcumin acts at multiple targets and at multiple levels. The number of transcription factors and signaling pathways modulated by curcumin is, indeed, bewildering1,2. For this reason, curcumin is fast emerging as a cure-all, for valid reasons. Curcumin has demonstrated benefit for most, if not all, chronic diseases afflicting mankind. It is an antioxidant several times more potent than _-tocopherol and can effectively scavenge oxygen- and nitrogen free radicals. It is a complete anti-inflammatory modulating all the agents involved in the complex process of inflammation, including cytokines, chemokines, adhesion molecules, growth factors and transcription factors such ah NF-KB and AP-1, and a large number of kinases, notably the MAP kinases p38 and JNK. It is an inhibitor of histone acetyltransferases3,4 thereby preventing the transcription of inflammatory genes. In heart disease, curcumin can affect all the steps believed to be involved in the pathologic process of atherosclerosis. In diabetes, it can potentially reverse insulin resistance, the first clinically relevant stage of the disease. Further, it can sensitize insulin by inducing the transcription factor PPAR_, similar to the thiazolidinediones currently used for the purpose. Curcumin can be shown to be the only agent that can effectively address all the multiple factors involved in Alzheimer’s disease and rheumatoid arthritis. As an anticancer agent, it is a chemo preventive, affect cell cycle progression and transformation, cause apoptosis of malignant cells by more than one mechanism, prevents angiogenesis and metastasis, and is effective even against drug-resistant cancers. Whereas the present day cancer drugs are specific for one type of cancer, curcumin has been shown in preclinical studies to be effective against virtually all forms of human cancers. While common chemotherapeutic agents cause serious side effects, curcumin produces none. While the common anticancer drugs are Immuno-suppressors, curcumin is an immuno-restorer5,6. Furthermore, whereas the common anticancer drugs cannot cross the bloodbrain barrier, curcumin can. Curcumin exhibits activities similar to recently discovered drugs such as TNF inhibitors (e.g., Humira, Remicade, and Enbrel), a vascular endothelial cell growth factor (VEGF) blocker (e.g., Avastin), human epidermal growth factor receptor (EGFR) inhibitors (e.g., Erbitux, Erlotinib, and Geftinib), and the HER2 blocker (e.g., Herceptin), minus their toxic side effects.

Turmeric may contain well over a hundred chemical species, most of these originating from the essential oil part of turmeric. A complete analysis of all these constituents has not so far been undertaken. However, the major and characteristic components of turmeric are the three curcuminoids and volatile compounds of turmeric. Curcuminoids: Curcumin, Desmethoxy curcumin, Bisdesmethoxy curcumin Curcuminoids exist as a mixture of the keto- and enol tautomeric forms, their relative composition dependent on the pH of the medium.

The curcuminoids are diferuloylmethanes with curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl) -1,6- heptadiene-3,5-dione, see structure) as the main and the most active constituent. Compounds lacking either one or two methoxy groups in the aromatic rings (desmethoxycurcumin, and bisdesmethoxycurcumin, respectively) form the other two constituents of the curcuminoids fraction. Other functional groups, namely the phenolic OH- group and -unsaturated diketo Michael acceptor functions, are identical. The Michael acceptor property may be considered crucial for most of curcumin’s biological activity, the methoxy groups have apparently supportive roles in these activities because compounds lacking these groups are less active, with desmethoxycurcumin (lacking one methoxy group) being less active than curcumin, and bisdesmethoxycurcumin, lacking both methoxy groups, the least active. However, a recent report suggests that bis-desmethoxycurcumin was the most potent in correcting immune defects in AD patients1. The Michael acceptor functionality allows the curcuminoids to react or form complexes with a number of molecules, notably proteins, both covalently and non-covalently. For example, curcumin forms stable complexes with serum albumin which may be important in its transport within the human body. A recent study2 compared the relative ant-inflammatory, anti-proliferative, and antioxidant properties of the three curcuminoids, along with tetrahydrocurcumin and the turmerones. the relative potency for suppression of tumor necrosis factor (TNF)-induced nuclear factor-kappaB (NF-KB) activation was curcumin > desmethoxycurcumin > bisdesmethoxycurcumin; thus suggesting a critical role of methoxy groups on the phenyl rings. Tetrahydrocurcumin, which lacks the conjugated bonds in the central seven-carbon chain, was completely inactive for suppression of the transcription factor. Turmerones also failed to inhibit TNF-induced NF-KB activation. The suppression of NF-KB activity also correlated with down-regulation of cyclooxygenase-2 (COX-2), cyclin D1 and vascular endothelial growth factor (VEGF), all regulated by NF-KB. In contrast to NF-KB activity, the suppression of proliferation of various tumor cell lines by the three curcuminoids was found to be comparable; indicating the methoxy groups play minimum role in the growth-modulatory effects of curcumin. Tetrahydrocurcumin and turmerones were also found to be active in suppression of cell growth but to a much lesser extent than curcumin, DMC and BDMC. The antioxidant potential of all the curcuminoids were comparable, not influenced by the structural features.

The dark side of the curcumin story is its poor systemic availability due to poor absorption from the intestines and rapid metabolism of the compound in the body. This has largely curtailed its progress from the lab to the clinic, and no clinical trials have progressed beyond the phase I stage. All these have led to the general impression that curcumin’s benefits are largely unrealizable in the human body. Early experiments indicated that curcumin undergoes transformation during absorption from the intestine. www.curcumincare.com has resolved many of these issues and that is why the formulation from www.curcumincare.com showed its results in volunteers just in 10 days. Other formulation when administered orally to rats in a dose of 1 g/kg, curcumin was excreted in the feces to about 75%, while negligible amounts of curcumin appeared in the urine1. Measurements of blood plasma levels and biliary excretion showed that curcumin was poorly absorbed from the gut. No apparent toxic effects were seen after doses of up to 5 g/kg. When intravenously injected or when added to the perfusate of the isolated liver, curcumin was actively transported into bile, against concentration gradients of several hundred times. The major part of the absorbed drug was, however, metabolized. In suspensions of isolated hepatocytes or liver microsomes 90% of the added curcumin was metabolized within 30 min. The authors concluded that in view of the poor absorption, rapid metabolism and excretion of curcumin, it is unlikely that substantial concentrations of curcumin occur in the body after ingestion. This study, which appeared as early as 1978, appears to summarize our current understanding of the metabolic fate of curcumin in vivo. Later studies have more or less confirmed these findings. Oral and intraperitoneal doses of [3H] curcumin led to the fecal excretion of most of the radioactivity2. Intravenous and intraperitoneal doses of [3H] curcumin were well excreted in the bile of cannulated rats. The major biliary metabolites were glucuronides of tetrahydrocurcumin and hexahydrocurcumin. The major route of elimination of the label was the feces; the urinary excretion of the label was very low regardless of the dose; however, its metabolites, namely, glucuronide and sulfate, were present3. After i.p. administration of curcumin (0.1 g/kg) to mice, about 2.25 μg/ml of curcumin appeared in the plasma in the first 15 min4. One hour after administration, the levels of curcumin in the intestines, spleen, liver, and kidneys were 177.04, 26.06, 26.90, and 7.51 μg/g, respectively. Only traces (0.41 μg/g) were observed in the brain at 1 h. Thus, in mice, absorption of curcumin appears to be significantly higher compared to rats. The intestinal tract plays an important role in the metabolic disposition of curcumin. Accordingly, a study explored curcumin metabolism in the subcellular fractions (cytosolic and microsomal) of human and rat intestinal tissue, and compared it with metabolism in the corresponding hepatic fractions5. Quantitatively, major differences were observed between human and rat tissues. In humans, microsomal glucuronidation occurred to a much higher level in the intestine than liver, while the reverse was true in the case of rat. In the rat, dietary curcumin yielded low drug levels in the plasma, between 0 and 12 nM, whereas tissue concentrations of curcumin in liver and colon mucosa were 0.1 to 0.9 nmol/g and 0.2 to 1.8 μmol/g, respectively6. In comparison with dietary administration, suspended curcumin given i.g. resulted in more curcumin in the plasma but much less in the colon mucosa. The authors conclude that curcumin mixed with the diet achieves drug levels in the colon and liver sufficient to explain the pharmacological activities observed and suggest that this mode of administration may be preferable for the chemoprevention of colon cancer. A prospective phase-I study7 evaluated pharmacokinetics, toxicology and biologically effective dose of curcumin in cancer patients. Curcumin was given orally for 3 months. Biopsy of the lesion sites was done immediately before and 3 months after starting curcumin treatment. The starting dose was 500 mg/day. If no toxicity _ grade II was noted in at least 3 successive patients, the dose was then escalated to another level in the order of 1,000, 2,000, 4,000, 8,000, and 12,000 mg/day. The concentration of curcumin in serum and urine was determined. A total of 25 patients were enrolled in this study. There was no treatment-related toxicity up to 8,000 mg/day. Beyond 8,000 mg/day, the bulky volume of the drug was unacceptable to the patients. The serum concentration of curcumin usually peaked at 1 to 2 hours after oral intake of curcumin and gradually declined within 12 hours. The average peak serum concentrations after taking 4,000 mg, 6,000 mg and 8,000 mg of curcumin were clinically relevant at 0.51 ± 0.11 μM, 0.63 ± 0.06 μM and 1.77 ± 1.87 μM, respectively. Urinary excretion of curcumin was undetectable. This study demonstrated that curcumin is not toxic to humans up to 8,000 mg/day when taken by mouth for 3 months. In another phase I study8, 15 patients with advanced colorectal cancer refractory to standard chemotherapies consumed curcumin (0.45 to 3.6 g per day) for up to 4 months. Blood, urine and feces were collected on days 1, 2, 8, and 29. Blood was collected before dosing and after 0.5, 1, 2, 3, 6, and 8 h after dose. Curcumin was detected in plasma samples taken 0.5 and 1 h postdose from 3 patients consuming 3.6 g of curcumin daily, with a mean concentration of 11.1 ± 0.6 nmol/L on day 1, 2, 8, and 29 of intervention. Glucuronides and sulfates of curcumin were detected at levels of 15.8 ±0.9 and 8.9 ± 0.7 nmol/L, respectively. Presence of metabolites arising out of metabolic reduction, e.g. hexahydrocurcumin, was not reported. They were apparently absent. Curcumin and itsmetabolites, unexpectedly, were present in high amounts in the urine of the 6 patients consuming 3.6 g curcumin daily, but not in the urine of patients consuming lower doses. The urinary levels varied between 0.1 and 1.3 μmol/L (curcumin), 19 and 45 nmol/L (curcumin sulfate), and 210 and 510 nmol/L (curcumin glucuronide). This is the only study which found unchanged curcumin in the urine. Considering that curcumin is insoluble in water, this result needs reconfirmation. The quantities excreted through feces amounted to 25 to 116 nmol/g dried feces. In another trial, 12 patients with confirmed colorectal cancer received curcumin at dose levels of 450, 1800, or 3600 mg per day (4 patients per dose level) for 7 days prior to colectomy9. Samples of peripheral blood were taken 1 h post dose and surgery was done 6-7 h after the last dose of curcumin. Curcumin levels in the plasma of patients were below the limit of quantization (3 nmol/L). Levels in the normal and malignant tissues ranged from 7 to 20 nmol/g tissue. Normal mucosa from the caecum and ascending colon contained more curcumin than normal mucosa from the transverse, splenic flexure, and the descending colon. In patients who had received 1800 or 3600 mg curcumin, the concentration of curcumin was 21.7±8.2 and 6.8±3.7 nmol/g in the right and left colon, respectively. This difference was not reflected by curcumin levels in tumor tissue originating from different sites of the bowel. Curcumin metabolites were not detected in the plasma. Extracts of colorectal mucosa of 7 of the 8 patients who received 1800 or 3600 mg curcumin showed the presence of curcumin sulfate, and two patients from the highest dose indicated the presence of curcumin glucuronide. However, the concentrations of these conjugates were very low at about 1 pmol/g tissue. The results of this study thus suggest that a daily dose of 3.6 g curcumin achieves pharmacologically efficacious levels in the colorectum. Curcumin’s metabolic fate is decided by the phase I, II and III detoxifying enzymes. Curcumin is, simultaneously, a substrate for these enzymes, an inducer of these enzymes, as well as an inhibitor of these enzymes, depending on context. Curcumin was shown to inhibit sulfotransferases28-30. Inhibition29,31-33, as well as induction34,35, of UDP-glucuronosyl-transferase have been described. A similar situation exits with glutathione S-transferase (GST) another phase II enzyme, where again curcumin has been shown to be an inhibitor as well as an inducer. The chemo preventive action of curcumin significantly depends on the induction of these enzymes. Inhibition of these enzymes is relevant in the context of overcoming drug resistance in cancer chemotherapy. Thus, the metabolism of curcumin may depend on many external factors, and probably may explain the confusing results reported. Although some questions remain unanswered regarding the pharmacokinetics of curcumin in humans, there is no denying the fact that considerable proportion of ingested curcumin is excreted through feces, and at least about one-half of absorbed curcumin is metabolized. The quantity of curcumin that reaches tissues outside the gut are probably pharmacologically insignificant. These results have, apparently, dampened the spirits of researchers and halted curcumin’s progress from Phase 1 trials.

A number of curcumin analogues have been tested, but in most cases they were found to be less effective than curcumin itself. One exception has been dimethoxycurcumin1. This derivative was found to be more bioavailable. Nearly 100% of curcumin, but < 30% of dimethoxycurcumin was degraded in HT116 cells treated for 48 h, and incubation with liver microsomes confirmed the limited metabolism of dimethoxycurcumin. The absence of free phenolic groups in dimethoxycurcumin probably prevents its conversion to glucuronide and sulfate. Piperine, an inhibitor of glucuronosyltransferase, administered along with curcumin has been found to significantly enhance the plasma curcumin concentration in animals and in humans2. However, piperine is toxic at least to experimental animals. Curcumin formulated with lecithin was found to increase its bioavailability in rats about 5-fold3. In contrast, curcumin concentrations in the gastrointestinal mucosa after ingestion of the formulation were somewhat lower than those observed after administration of unformulated curcumin. Fluorometric data on the association of curcumin with phosphatidylcholine indicate that one molecule of curcumin could bind six molecules of phosphatidycholine4. Thus, the formulated products would have low curcumin content, and large amounts of lecithin would have to be consumed in relation to the required curcumin dose.

www.curcumincare.com has been working with Turmeric and curcimin since 2003. The scientists of this company have achieved a major success to improve its activity where no other formulation has been reported. The IC50 of this formulation is less than 1micromole. The formulation has been used by more than 200 volunteer and all been benefitted for their inflammation and pain problems. A proposed clinical trial is on its way for cancer prevention after chemotherapy . Another trial is also proposed for arthritis and psoriasis.

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Antony B, A composition to enhance the bioavailability of curcumin, WO2006129323 (2006) to Arjuna Natural Extracts Ltd.

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ung S, Orberg N, Thiede G, et al. Innovative liposomes as a transfollicular drug delivery system: penetration into porcine hair follicles, J Invest Dermatol, 2006, 126:1728-32.

i L, Bratiteh FS, Kurzrock R, Liposome-encapsulated curcumin: In vitro and in vivo effects on proliferation, apoptosis, signaling, and angiogenesis, Cancer, 2005, 104:1322-31.

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arkatou E, Gionis V, Chryssikos GD, et al. Molecular interactions between dimethoxycurcumin and Pamam dendrimer carriers, Int J Pharm, 2007, Mar 12; Epub ahead of print; PMID 17428628. isht S, Feldmann G, Soni S, et al. Polymeric nanoparticle-encapsulated curcumin (nanocurcumin): a novel strategy for human cancer therapy, J Nanobiotechnol, 2007, 5:3.

www.cancer.org/Treatment/TreatmentsandSideEffects/.../turmeric

csn.cancer.org › CSN Home Cancer specific Uterine Cancer

www.youtube.com/watch?v=Ugx2Qm-ysls

www.slideshare.net/alternativecareers/curcumin-and-caner-cure

www.mayoclinic.com/health/curcumin/AN01741

naturalsociety.com/curcumin-turmeric-spice-reduces-tumors-by-81-p

Some drugs are in pipeline from www.curcumincare.com and www.nanomeda.com


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