A little ‘history
Turmeric is a perennial herbaceous plant belonging to the ginger family (Zingiberaceae). It is known and used by Ayurvedic medicine as an anti cancer and other remarkable properties, for almost 4000 years, but the biological characteristics begin to be studied only in 1949. In that year, in an article published in “Nature” , it was found that it has antibacterial properties towards Staphylococcus aureus strains , paratiphi Salmonella and Mycobacterium tuberculosis. It was not until 1970 that Turmeric become the subject of scientific investigation and some features are discovered such as the reduction of cholesterol, anti-diabetic , anti-inflammatory and anti-oxidants meanings. In 1980 Kuttan demonstrates the anti cancer activity of curcumin both in vitro and in vivo. In 1995, the group leaded by Aggarwal evidenced that curcumin is able to inhibit the nuclear factor transcription pioneering the scientific understanding of the molecular mechanisms of spice. To date, there are nearly 7,000 articles listed in the National Institutes of bank PubMed.
Turmeric in tumor therapy
Turmeric alone or in combination with other agents such as quercetin, piperine, soy isoflavones, and others, has been shown to have an interesting action of various types of cancers especially colorectal, pancreatic, breast, and prostate cancers skin.
Modern research has shown that curcumin is able to fight cancer at multiple levels, in other words is an agent that acts in the multi-target neoplastic cell on several metabolic pathways altered simultaneously.
In particular, it was observed that:
It inhibits the activation of genes that trigger tumor.
It Inhibits the proliferation of cancer cells
It Inhibits the transformation of a normal cell in neoplastic.
It Kills many cells that have undergone transformation.
It Prevents metastasis or the spread of cancer
It Amplifies the effects of chemotherapy and radiotherapy.
In trials it was found that curcumin performs these actions against 20 types of cancer, and at present, there is no other natural substance that has demonstrated this level of effectiveness against cancer.
Faced with an enormous amount of experimental animal studies, where curcumin incontestably proves to have strong anti cancer properties, the same, on a human clinical level, counts a few studies because the spice can not be patented and does not stimulate investment by pharmaceutical companies.
Big Pharma in 1993 , presented six patent applications for curcumin, given the clear evidence about its therapeutic properties, but the “United States Patent and Trademark Office” (US Patent Office) in 1998, has rejected all.
In a complex study published in “Clinical Cancer Reaserch” 2001 was measured the concentration of glutathione-S-transferase in response to the assumption of turmeric capsules as a dietary supplement with doses ranging between 440 mg and 2,200 mg /per day in 15 patients suffering from advanced colon cancer and refractory to standard chemotherapy.
The increase of this substance is closely correlated with an increased risk of developing colorectal cancer, ovarian cancer and clear cell renal carcinoma Furthermore, the glutathione-S-transferase is a modulator of the proteins that regulate programmed cell death (apoptosis). In other words the increase of that substance is associated with the onset of tumors and leads to resistance against chemotherapeutic drugs.
These are the premises for the understanding of the study in which the administration of 440 mg of turmeric daily during 29 days (the equivalent of 36 mg of pure curcumin) was accompanied by a decrease of 59% of the glutathione-S-transferase inside white blood cells.
A radiological stabilization of disease was demonstrated in 5 patients , for two to four months of treatment.
An important objective of the trial is to have demonstrated the possibility in ill people, to reduce the concentration of a molecule favoring the cancer with the use of a natural and non-toxic substance. Curcumin alone can not “heal” a tumor, it may stabilize it for a certain period of time, but in combination with other substances, such as chemotherapy, it can increase the expectations for improvement. This is what goes on through the association with Quercetin in the “Familial adenomatous polyposis” (FAP).
This is a genetic disease characterized by the formation of hundreds of colorectal polyps that eventually invariably transform into carcinomas.
In this study published in “Clinical Gastroenterology and Hepatology” 2006 , five FAP patients with previous colectomy received 480 mg of curcumin and 20 mg of quercetin to three times per day in oral administration. The number and size of polyps were assessed at baseline and after therapy.
All five patients had a decrease in both the number and size of polyps after 6 months of therapy. As a percentage , the decrease of the parameters was 60% without any side effect. One patient , between the 3rd and 6th month of therapy , has developed an increasing in the number of adenomas because of a wrong adherence to the regimen. Just restored with regularity and constancy intake of substances, between the 6th and 9th month of therapy, the number of polyps was again declined. This association of spices has been useful in the containment and reduction of rectal polyposis colon.
Even today , it is the fourth most common cause of cancer death worldwide. The mortality rate is about the same as the number of tumors in the pancreas actually diagnosed. As soon as its diagnosis, pancreatic cancer is surgically resectable only in 10-20% of patients, and in over 50% of cases distant metastases are already detectable.
The prognosis is accured even at the initial stages of the tumor and survival does not exceed 12 months for less developed forms and 6 months for the more advanced.
We will try to better understand the lethality of this tumor and the experimental data of treatment attempts of the tumor with curcumin.
There are very few clinical studies on this subject, one important published in “Nutrition and Cancer” in 2010, concerns the administration of turmeric in combination with gemcitabine; classic chemotherapy used routinely in this disease with very little results.
The reason for this association is that turmeric has the remarkable property to act in a chemo-sensitizing, that makes cancer cells more sensitive to the action of chemotherapy.
Of the 17 patients enrolled , 11 patients continued experimentation and were evaluated. The treatment consisted in the administration of 8 grams of turmeric daily, together with 1000 mg gemcitabine three times a week for three weeks.
Of the 11 evaluable patients, 1 (9%) had a partial response, 4 (36%) had stable disease, and 6 (55%) had tumor progression. Tumor progression was 1 to 12 months and overall survival was 1 to 24 months.
The authors concluded that the efficacy of the combination was modest.
In another study published in “Clinical Cancer Reaserch” 2008, 21 patients with advanced pancreatic cancer, were given 8 grams of turmeric a day alone with checks every two months. 2 patients showed a clinical response and have had stable disease for more than 18 months; 1 patient had a brief but clear regression of the tumor. The conclusion is that the spice had biological activity in some patients.
Breast cancer is the second most common cause of cancer death in women. The Docetaxel is a common chemotherapy used in metastatic disease alone or in combination with other agents in the early stages of the tumor.
In a preliminary study, there were given 6 grams per day of turmeric in combination with docetaxel and this attempt was tested on 14 patients with advanced or metastatic breast cancer. Some improvements have been observed in clinical and biological responses in a sufficient number of patients who have encouraged the continuation of the trial with the initiation of studies in Phase 2. In this type of cancer there is very little literature and the results very uncertain . We are expecting the conclusion of new studies underway.
A tumor marker of proven utility in the diagnosis in prostate cancer is the PSA (prostate specific antigen). Values modestly increased (4-10 mg / ml) are compatible with benign conditions, values greater than 10 mg / ml orient to the presence of the tumor.
In a study published in “Prostate” in 2010, an association of curcumin and soy isoflavones has been tested in the treatment of cell lines prostate cancer and also was made a clinical study on men who had a high PSA value. 85 patients were enrolled and divided into two groups one of which has been treated for 6 months with 100 mg of curcumin associated with 40 mg of isoflavones ; the other one with placebo. The group of curcumin on the sixth month had a net decline in PSA compared to placebo, but the very interesting thing is that , in vitro studies on cancer cells showed that curcumin lowered the PSA through the suppression of the androgen receptor, well known to be implicated in genesis of cancer.
Multiple myeloma and gammopathy
Multiple myeloma is a malignancy characterized by the accumulation in the bone marrow of special immune cells called plasma cells which produce antibodies in healthy people and on the other hand, in people with such a disease, they secrete a “paraprotein” particularly detectable in serum and in urine so important for the diagnosis .
The “monoclonal gammopathy of undetermined significance” (MGUS) is a plasma cell proliferative disorder with an ongoing risk to progress to multiple myeloma. The paraprotein never have to exceed 30 g / liter . in case of exceed, we must overt myeloma diagnosis. It is a common disorder as it affects 3% of the population over the age of 50 and 5% over 70. No treatment is recommended but only a “watchful waiting.”
Early intervention with the goal of reducing the concentration of paraprotein represents a therapeutic and innovative tool and in preliminary studies we have seen a drop of this protein in plasma from 5% to 30% in patients taking turmeric.
In a study published in “Clinical Cancer Research” 2009 Golombick wanted to determine the effect of curcumin on the plasma cells in patients with monoclonal gammopathy of undetermined significance. The results deserve attention.
Twenty-six patients with MGUS were treated with 4 grams per day of curcumin and randomly divided into two groups: 17 patients in the first group was given curcumin, in the second group 9 patients who received placebo.
The results demonstrate that curcumin in oral administration is able to reduce the concentration of paraprotein in the blood in 10 patients in which these values were greater than 20 g / liter; 5 of these patients had a reduction from 12% to 30% of paraprotein during treatment with curcumin. Furthermore, 27% of patients treated had a decrease of 25% of the paraprotein in urine.
The study suggested the therapeutic potential of the spice in this disease that deserves further study experimental and clinical.
Vhadan-Raj in a study published in “Blood” in 2007, evaluated the clinical efficacy of curcumin in 29 patients diagnosed with multiple myeloma and also studied the impact of spice on the concentration of some biological factors important for tumor progression such as nuclear factor (NF-kB) and the cyclo-oxygenase-2 (COX-2).
The incongruous activation of NF-kB is frequently observed in many cancers and its increase has been linked to multiple myeloma. Its suppression sharply restricts cell proliferation, so drugs that inhibit this factor are studied actively for therapeutic applications anti cancer.
Curcumin without any toxic effect is able to decrease this factor and limit the progression of the tumor. In 1995, Aggarwal was the first to demonstrate this very important properties of the substance.
Another matter is for cyclooxygenase which also increased in many tumors and can stimulate tumor progression. In this case curcumin performs a suppressive action on the synthesis of the substance in the majority of patients.
These observations suggest the use of curcumin in multiple myeloma and requires further clinical studies with more patients to confirm these results.
It is well known that smokers excrete significant amounts of mutagens in the urine and are at high risk of developing lung cancer.
A study published in “Mutage” 1992, has evaluated anti-mutagenic effects in curcumin in 16 chronic smokers and 6 non-smokers who served as control. Turmeric was administered at a dose of 1.5 g / day for 30 days and it has seen that it has significantly reduced the excretion of mutagenic substances in smokers without affecting nonsmokers. This effect is due to the strong antioxidant properties of spice.
On “Phytomedicine” in 2007,it was reported a study on 100 patients with oral lichen planus (chronic autoimmune dermatitis), to evaluate the efficacy of curcuminoids administered at 2 g / day for 7 weeks.
The first results on 33 participants showed no significant difference compared to placebo and therefore the study was completed before the deadline.
In another study published in “Anticancer Research” in 2001, it is experienced the use of curcumin in prevention in patients with evolutionary or pre – malignant high risks lesions.
For this study are enrolled patients with various cancers such as resected bladder cancer , Bowen’s disease (skin lesion pre-malignant), uterine cervical intraepithelial neoplasia (CIN), oral leukoplakia (whitish lesion of the mouth with evolution to malignancy in 5- 25 % of cases) and intestinal metaplasia of the stomach.
The results: one of the 4 patients with CIN and one of 7 with oral leukoplakia have developed malignancies evolutionary despite treatment with curcumin.
In the contrary, regarding histological diagnosis, ie the diagnosis made with the microscope on the diseased tissue (pre-cancerous lesion), there was improvement in 1 of 2 patients with resected bladder cancer , in 2 of 7 patients with oral leukoplakia, in 1 of the 6 patients with intestinal metaplasia of the stomach, and in 1 of 4 patients with CIN and in 2 of 6 patients with Bowen disease.
This study demonstrates the possible therapeutic applications of the spice in prevention rather than in actual treatment of the disease even if at a numerical level, the results are modest.
Beyond the enthusiastic and often exaggerated statements, expressed especially in the network, the anti cancer properties of turmeric, at the level of experts tones , are much more subdued because the spice , while demonstrating its interesting therapeutic activities in experiments on patients , has given very modest results.
Certainly in the prevention of many forms of cancer, turmeric plays an important action, but in the treatment of established disease , by itself it takes the step and in fact we are studying more and more doses in combination with other compounds.
A search field in turmoil is the study of innovative processes of extraction which deal to the isolation of new active properties of the spice which in part are already available for research but not for common use in the form of dietary supplements. Chinese researchers are an example , as mentioned on “Courrent Cancer Drug Targets” in 2014, on how they’re giving news of isolation and testing of a derivative of turmeric called B63 which in colon cancer has two times more activity than normal curcumin basis.
Doctor Claudio Sandri
The bibliography can be found on the following page.
Translated by Ms Jeanne Marie Arcaini