When searching for some of the most effective anti cancer natural extracts accessible, low cost and non toxic, Curcumin will be one of the first we will come across. Curcumin is an extract from Tumernic a yellow-pigmented curry spice that is often used in Indian foods.
Curcumin relevance in cancer was so intensively researched so that today, a search on PubMed using “curcumin cancer” as search criteria will find 3329 published papers (Ref.), This research covers most types of cancers and uncovers the potential of curcumin to influence a wide range of human genes, major pathways in cancer, cell membrane, etc. leading to important anti cancer properties (Ref.). With this, Curcumin alone may kill cancer cells while also being chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs (Ref.).
Beyond cancer, Curcumin has multiple therapeutic actions including anti-inflammatory, anti-microbial, hepatoprotective, cardioprotective, thrombosuppressive, anti-arthritic, anti psoriasis. In addition, traditional Indian medicine has considered curcumin a drug effective for various respiratory conditions (asthma, bronchial hyperactivity, and allergy) as well as for other disorders including anorexia, coryza, cough, and sinusitis. (Ref.)
Due to the huge range of anti cancer mechanism connected to Curcumin, I am not going to start discussing them as it will probably take forever. Instead, I will focus on its application and to highlight its action I will just use pictures such as the one below from the enclosed reference (Ref.). This clearly indicates a wide range of activity of Curcumin.
Nevertheless, even this picture it only covers a little from what has been so far experimentally demonstrated that Curcumin can do. When reading the literature, it feels like Curcumin can address ANY problem, from bone disorders (Ref.) to brain challenges (Ref.). Due to this fact, I would consider Curcumin as a part of any anti cancer treatment protocol.
Curcumin downregulates cellular protein synthesis, and induces autophagy, lysosomal activation and increased ROS production, thus leading to cell death – mTOR inhibitor (ref.)
Curcumin inhibits glyoxalase 1: a possible link to its anti-inflammatory and anti-tumor activity. http://www.ncbi.nlm.nih.gov/pubmed/18946510 This may be one of the very relevant mechanism of Curcumin and due to thsi property it may make sense to combine Curcumine with most pro-oxidant treatment approaches including Chemo, 3BP or Methylglyoxal.
Next to the oral version, we have had Curcumin IV from time to time, for nearly two years, and we have a very positive feeling about it. During and after the IV we typically experience pain at the tumor site. Tremour has also been reported to take place for about 30min after the IV. This is probably present in about 50% of patients using Curcumin IV from what I understand. It is not yet clear what is the origin of the tremor but it is believed to be connected to the rise of uric acid as a result of the tumor lysis effect.
Many German doctors are “in love” with Curcumin IV.
“The first phase I clinical trial to test the toxicity, pharmacokinetics, and biological effective dose of curcumin was carried out by Cheng et al., in 2001 . Twenty-five patients who had either one of the following pre-malignant high cancer risk conditions were included: urinary bladder cancer, arsenic Bowen’s disease of skin, uterine cervical intraepithelial neoplasm (CIN), oral leukoplakia, and intestinal metaplasia of the stomach. An escalating oral dose of 500, 1000, 2000, 4000, 8000, and 12,000 mg was tried and treatment-related toxicity was not observed up to 8000 mg/day. Higher doses were found to be unacceptable to the patients, primarily due to bulky volume of the drug. Peak serum curcumin concentration was reached 1–2 h after intake, while it was undetectable in urine.” Ref.
Bio availability & Pharmacokinetics:
It has been found that 10 mg/kg of curcumin given intravenous in rats gave a maximum serum curcumin level of 0.36 µg/mL, whereas a 50-fold higher curcumin dose administered orally gave only 0.06±0.01 µg/mL maximum serum level in rat. (Ref.)
Indeed, it is well known that the bio-availability of orally administrated Curcumin is very low. However, the clinical trials discussed below indicate that 2g to 12g of Curcumin administrated orally to humans can lead to anti cancer effects.
Scientists are currently investigating various ways to increase Curcumin bio availability. One of the most simple and effective ways to increase the bio availability in humans is by co administration with another plant extract, i.e. piperine: “In humans, curcumin bioavailability was increased by 2,000% at 45 minutes after co-administering curcumin orally with piperine” (Ref.)
Once administrated, Curcumin is absorbed differently in Blood, Liver, Brain, Kidney, and Other Organs http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918523/figure/F3/
Clinical trials on humans:
Summary of clinical trials with curcumin in various cancers: http://www.mdpi.com/1420-3049/20/2/2728/htm
Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer: Radiologically stable disease was demonstrated in five patients for 2-4 months of treatment at doses between 440 and 2200 mg/day.
Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis: The combination of curcumin and quercetin appears to reduce the number and size of ileal and rectal adenomas in patients with FAP without appreciable toxicity. Randomized controlled trials are needed to validate these findings.
Phase II trial of curcumin in patients with advanced pancreatic cancer.: Two patients showed clinical biological activity. One had ongoing stable disease for >18 months; interestingly, one additional patient had a brief, but marked, tumor regression (73%) accompanied by significant increases (4- to 35-fold) in serum cytokine levels (IL-6, IL-8, IL-10, and IL-1 receptor antagonists). No toxicities were observed.
Administration and Dose:
A very helpful blog to read with a good amount of info on the use of oral and topical curcumin is here http://margaret.healthblogs.org
Oral administration: 30 to 60 min before food with a glass of water, 2 to 3x/day, 1-4g each time (leading to a total of 3 to 12g/day). Adding some oil (e.g. olive oil capsules and/or Nigella Dativa and/or fish oil) will help the absorption. If it doesn’t have already Piperine inside than add a small amount of black paper powder or Piperine capsule (like this one).
Oral administration has been shown to provide some benefit, but absorption and distribution kinetics do not always allow maximal benefit.
Option 1: The origin of this formulation is coming from a recent article sating the following: “We have developed a curcumin-based vaginal cream, which effectively eradicates HPV(+)cancer cells and does not affect non-cancerous tissue. Our preclinical data support a novel approach for thetreatment of cervical HPV infection” Ref The formulation used was: “Intravaginal formulation containing 2%, 5%, 10% and 20% (w/w) curcumin were prepared by mixing curcumin powder with a com-mercially available topical oil-in-water cream base called Vanicream (Pharmaceutical Specialties, Inc., Rochester, MN). Our tests showed that 5 g of Vacurin occupied a volumeof 5 ml. Therefore, in the rest of this report, we have expressed the concentrations of curcumin in Vacurin as 20% (w/v). The two compo-nents were thoroughly mixed using a spatula…”
Option 2: Here is another formulation from a different article: “Curcumin C3 Complex (>98% pure) was obtained from Sabinsa Corp. In vivo studies were conducted with curcumin (15 mg) suspended in a vanishing cream paste (15 mg/100 μL cream) for topical administration provided by our study compounding pharmacist (DB).” Ref.
IV administration: 150-400mg/m2 in 250 to 1000ml NaCl 0,9% during one to two hours, 2-4x/week, administrated via either a central or peripheral line.
- there are various forms of Curcumin for IV. If it contains Kolliphor than the IV has to be administrated in PVC free IV set or using a 0.2 um inline filter system to avoid the typical allergic reaction. In case Kolliphor is present, some clinics are administrating prior to the first IV the following mixture to avoid allergy: in 100 ml NaCl 0,9% add Fenistil 8 mg + Ranitidin 50mg + Dexamethason 8mg + Ondansetron 8mg
- some clinics in Germany are mixing Curcumin with DMSO (2 to 10ml) in the same NaCl bottle for increased effectivness. When that is done, the Curcumin dose is usually reduced to half of that administarted withouth DMSO.
- No other additives should be mixed in the IV bag with the curcumin and carrier solution
- Some are suggesting that oxidative treatments including IV Ascorbate over 20 grams should be separate by 24 hours
According to the following patent Curcumin IV can also be relatively easily prepared :
- http://www.google.com/patents/DE102012219219A1?cl=en in the following way:
- Curcumin 150 mg are dissolved in 4 ml of absolute ethanol with stirring and heating to about 70 ° C. After 15 minutes, a clear dark yellow solution was formed.
- In this solution, 34 mg of citric acid are dissolved in anhydrous form.
- 25.88 g Kolliphor ELP are mixed with 12.37 g of absolute ethanol. With the mixture thus prepared, the Curcuminlösung prepared above is filled up to 10 ml.
- The resulting solution is sterile filtered and autoclaved at 121 ° C.
- This gives a storable pharmaceutical formulation containing curcumin in dissolved form.
Note: my idea was to use DMSO and not ethanol as suggested in the patent. This is because in order to get Curcumin soluble in ethanol there is a need to increase temperature to 75C (as suggested by the patent) while if we chose for the DMSO mixture, that can be performed at room temperature. Note: I never prepared – is just an idea.
Another relevant patent on how to formulate Curcumin for intravenous administration is here https://patents.google.com/patent/EP3275430A1 This was actually a product used by German clinics until 2016 when CFB manufacturer (lead by dr. Fernando) was shut down due to unknown reasons.
Other formulation ideas from Dr. Mercola:
- Make a microemulsion using raw curcumin powder. Combine one tablespoon of the powder with 1-2 egg yolks and a teaspoon or two of melted coconut oil. Use a high speed hand blender to emulsify it. Keep in mind that curcumin is a very potent yellow pigment that can permanently discolor surfaces, so take precautions to avoid “yellow kitchen syndrome.”
- Boil the curcumin powder. Another strategy that can help increase absorption is to put one tablespoon of the curcumin powder into a quart of boiling water. It must be boiling when you add the powder as it will not work as well if you first put it in room temperature water and then heat the water and curcumin. After boiling it for 10 minutes you will have created a 12 percent solution that you can drink once cooled. It will have a woody taste. The curcumin will gradually fall out of solution however. In about six hours it will be down to a six percent solution, so it’s best to drink the water within four hours.
Oral: There are various sources each with the claim that it is the most bio-available. Meriva seems to be one of the best source. We are using this one: http://www.iherb.com/Doctor-s-Best-Best-Curcumin-C3-Complex-with-BioPerine-1000-mg-120-Tablets/12137 Also, I like Curcucell: https://www.essential-foods.de/catalog/product_info.php?products_id=626
We should make sure we use Curcumin (i.e. the extract from Turmeric) and not the Turmeric powder since Turmeric powder contains about 3.14% Curcumin only, according to the following reference http://www.ncbi.nlm.nih.gov/pubmed/17044766
IV: there are several German pharmacies providing the IV form:
- http://apotheke-koenigstein.de/ – containing Kolliphor
- http://cfb-eigenherstellung.de/ – not containing Kolliphor – update 30.07.2019: this source is not available anymore but here is their patent explaining how they formulated their product https://patents.google.com/patent/EP3275430A1
- http://www.curafaktur.de/ – whole plant extract, not containing Kolliphor (this is the one we are using and it is easier to administrate since it is not containing Kolliphor but this lab has a different model – the doctor is going to the lab and prepares the IV himself) – update 08.08.2019: the name and the website of Curafaktur has been changed to https://uniqsana.de
Curcumin Sensitizes Silymarin to Exert Synergistic Anticancer Activity in Colon Cancer Cells http://www.jcancer.org/v07p1250.htm
We studied combinatorial interactions of two phytochemicals, curcumin and silymarin, in their action against cancer cell proliferation. Curcumin is the major component of the spice turmeric. Silymarin is a bioactive component of milk thistle used as a protective supplement against liver disease. We studied antiproliferative effects of curcumin alone, silymarin alone and combinations of curcumin and silymarin using colon cancer cell lines (DLD-1, HCT116, LoVo). Curcumin inhibited colon cancer cell proliferation in a concentration-dependent manner, whereas silymarin showed significant inhibition only at the highest concentrations assessed. We found synergistic effects when colon cancer cells were treated with curcumin and silymarin together. The combination treatment led to inhibition of colon cancer cell proliferation and increased apoptosis compared to single compound treated cells. Combination treated cells exhibited marked cell rounding and membrane blebbing of apoptotic cells. Curcumin treated cells showed 3-fold more caspase3/7 activity whereas combination treated cells showed 5-fold more activity compared to control and silymarin treated cells. When DLD-1 cells were pre-exposed to curcumin, followed by treatment with silymarin, the cells underwent a high amount of cell death. The pre-exposure studies indicated curcumin sensitization of silymarin effect. Our results indicate that combinatorial treatments using phytochemicals are effective against colorectal cancer.
Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3535097/
Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn’s disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin’s pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF–κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E2, prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the effect of curcumin has been investigated.
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