|Glioblastoma Treatments: Dichloroacetate (DCA)||
Dichloroacetate (DCA) is a very common, simple substance which selectively attacks the unique metabolism of cancer cells, called glycolysis. Aerobic glycolysis (glycolysis in the presence of oxygen) is one of the fundamental things which sets cancer cells apart from healthy cells.
Healthy cells generate energy (respiration) via several different metabolisms, but preferentially use normal glucose oxidation when sufficient oxygen is available. Under certain circumstances, normal cells may also perform respiration through glycolysis or ketone metabolism. Cancer cells, which paradoxically utilize aerobic glycolysis almost exclusively, appear to be less able to adapt to alternate routes of respiration, and many studies suggest that when glycolysis is inhibited, cancer cells die.
When you exercise (or if you are afflicted with one of several rare genetic disorders), healthy cells over-produce lactate and the concentration increases, contributing to the burning sensation you feel in your muscles when they are overworked. Long ago, DCA was found to reduce lactate by inhibiting a particular part of the citric acid cycle (or Kreb's energy cycle) called pyruvate dehydrogenase kinase (PDK). DCA facilitates the oxidation of lactate
That DCA is an inhibitor of glycolysis via PDK is a well-established fact, and DCA has been an FDA-approved drug for over 20 years in the treatment of certain mitochondrial disorders which cause the over-production of lactic acid. What is less clear is what happens to cancer cells in humans when glycolysis is inhibited by DCA.
In 2006, researchers at the Univ. of Alberta in Canada found that DCA had striking benefits against a wide variety of virulent cancer types, including glioma, in both cell lines and animal tests. Dr. Evangelos D. Michelakis was the lead researcher. In the abstract, they noted:
"DCA induces apoptosis, decreases proliferation, and inhibits tumor growth, without apparent toxicity."(4)
Furthermore, DCA didn't simply increase extracellular pH by reducing acid. In Michelakis' experiments, the effect of inhibiting PDK actually changed the metabolism of cancer cells. He wrote:
"DCA changes the metabolism of cancer cells from the cytoplasm-based glycolysis to the mitochondria-based glucose oxidation."
In other words, DCA normalized a fundamental differentiator of cancer cells, by converting their respiration from glycolysis to glucose oxidation. When this occurred, resistance to apoptosis decreased and the body's normal defense mechanisms destroyed the cells.
Every 6 months or so, Dr. Michelakis posts updates on how things are going at the Univ. of Alberta official DCA updates page:
These updates, along with anecdotal conversations with Dr. Michelakis indicate that the human trials are going well and DCA is continuing to show promise, however officially he needs to keep quiet until the trial is completed.
You can read a good lay article about the original Michelakis paper in New Scientist magazine:
Human clinical trials using DCA in glioblastoma (GBM) patients began in late 2007 and have not reported results yet. For this reason, DCA is not approved for use in any type of cancer yet, and because of this most doctors approach DCA with a high degree of skepticism. Currently, DCA is also being tested with temozolomide (TMZ) in newly diagnosed GBM(2).
DCA has several other physiological effects which may be beneficial to brain tumor patients, such as reducing hyperglycemia and increasing blood flow through the heart. It may also be therapeutic under conditions of cerebral ischemia, such as during stroke or hemorrhage, by improving blood flow.
Through inhibition of PDK, it is believed that DCA may increase tumor oxygen consumption, thereby decreasing local oxygenation within tumors and increasing hypoxia. Because hypoxic conditions are known to inhibit many chemo strategies, it is important to consider this mechanism when combining DCA therapy with other forms of treatment, such as radiation and certain types of chemo. This can also be used to the patient's advantage, because hypoxia is usually present only inside the tumor, not in normal tissue.
Researchers at Stanford have suggested an interesting, selective therapeutic strategy which exploits the ability of DCA to generate tumor hypoxia, by combining DCA with a hypoxia-specific cytotoxin. The researchers completed in vivo tests and reported that DCA "dramatically increases the effectiveness of a hypoxia-specific cytotoxin."(3)
Because of the potential in cancer treatment for DCA, and because DCA is already available from hundreds of manufacturers as a basic chemistry ingredient, biologist Jim Tassano and Dr. Joseph M. Ryan, a chemist, decided to create a website devoted to providing information about DCA.
I consider thedcasite.com website the best place to find information about DCA, although its discussion forums are as anecdotal and incomplete as any good cancer discussion forum. Many patients who are taking DCA post frequently on the site and information related to DCA gets added quickly. Some of the comments relating to DCA use by brain tumor patients is a little alarmist for my taste, but the moral is, like any drug, that you should follow recommended guidelines for its use.
Thedcasite.com has gotten in trouble with the FDA for helping patients find DCA without a doctor's prescription, but I am grateful for their help. DCA is very inexpensive (about $15 for a month's supply in raw form) and has very few side-effects when administered appropriately. It is extremely difficult to get a doctor's prescription for DCA in the U.S. However, it is relatively easy to buy DCA yourself without a prescription, or you can get it from Canada where several clinics have gotten government permission to provide DCA treatments to cancer patients based on the fact that DCA is already a well-documented, 20 yr old drug. The best Canadian cancer clinic to get DCA treatments from is Medicor Cancer Centre, which will provide treatment remotely so that patients don't have to travel:
DCA inhibits itself after several days of metabolism, so you must use a on/off schedule. Michelakis reports that the benefits of DCA are dose-dependent, beginning at about 10 mg/kg/day. Neuropathy is usually the dose-limiting toxicity and occurs at different dosages in different patients. Thiamine (the water-soluble Vitamin B1) may help decrease peripheral neuropathy(5) as a dosage of at least 300 mg, divided equally into 3 mealtime dosages. Benfotiamine, a derivative of Vitamin B1, may be a suitable replacement. In fact, I believe DCA was once proposed to be called Vitamin B15(6). Dr. Khan also suggests taking the R+ form of alpha lipoic acid (ALA), 450 mg divided into 3 equal doses.
Incidentally, I have concerns about any chemo patient taking ALA because it is a powerful anti-oxidant and probably increases intracellular glutathione levels in cancer cells, thereby contributing to chemoresistance. In addition, Dr. Michelakis reports that DCA preferentially increases reactive oxygen species (ROS) in cancer, but not healthy cells, which helps induce apoptosis. I have concerns that ALA could also help reduce the effectiveness of DCA. This is all just theoretical at this point and has not been tested at all to my knowledge.
The DCA dosages used by Dr. Khan at Medicor Cancer Centre start at 20 mg/kg/day and range up to 27 mg/kg/day. If side-effects develop, patients take lower doses or take a break for a couple weeks. Caffeine, at doses of 50 mg/day or more, reportedly potentiates the effects of DCA. Dr. Khan uses a 2 weeks on/1 week off schedule. He reports seeing results in as little as 5 days in some patients. Dosages may have to be changed considerably from person to person, and DCA may be significantly affected by other treatments/supplements, especially anti-oxidants.
Cell lysis in the brain could potentially be a problem for brain tumor patients. In other words, DCA could potentially be so effective at killing cancer cells that the resulting cell material could cause toxicities. Jim Tassano at theDCASite.com is concerned that he has seen this in brain tumor patients, so he cautions such patients to be very careful about DCA dosages, watch for signs of toxicity, and immediately back off if you see adverse effects. The formal name for this risk is tumor lysis syndrome.
In general, as most studies report, DCA causes few adverse side-effects in the dosage ranges mentioned here. My personal experience with it was zero side effects in the 20 mg/kg/day. A dosage calculator on theDCASite.com can help you see what DCA measurements might be used for different patient weights using different dosage targets:
Moreover, DCA is something I believe all high grade brain tumor patients should seriously consider taking. It may not be a cure, but it may help make fundamental changes in body chemistry to help fight cancer systemically. I suggest that patients use DCA under the guidance of an experienced doctor such as Dr. Khan, however it is certainly possible to administer yourself. Compared to the risk of death from a high grade brain tumor, the risk of adverse effects or death from DCA appears to be extremely small. Since DCA is relatively safe, inexpensive, and potentially very effective, it comes up high on my list of potential treatments for high grade brain tumor.
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