By Dr. Mercola
According to the American Cancer Society, the odds you’ll develop cancer in your lifetime are one in two, if you’re a man, and one in three, if you’re a woman.1 But an experimental cancer drug shown to shrink tumors by correcting metabolic oddities in cancer cells shows promise in the fight against this deadly disease. The synthetic drug DCA (dichloroacetate) DOES indeed kill cancer cells, both in the lab and in human beings. However, whether it can reverse tumor growth without harming you in other ways remains to be seen.
The first clinical trial, although small, involving patients with brain cancer (glioblastoma) was encouraging, and the results were published in Science of Translational Medicine in 20102 . However, there is still a great deal more work to be done before DCA can be pronounced a safe and effective cancer treatment.
An interesting aspect of DCA is that it’s an inexpensive, non-patentable molecule, which makes it of minimal value to pharmaceutical companies that profit by patenting expensive new drugs. Therefore, clinical trials are slow to get going due to lack of funding by Big Pharma. Researchers must await sufficient money to trickle in from government sources and public donations before moving forward.
In the paragraphs below, my aim is to give you information from both sides of the story—the potential benefits as well as the possible risks.
Rats Fed DCA Showed Dramatic Tumor Regression
The impetus behind most of the DCA research has been cardiologist Evangelos Michelakis of the University of Alberta in Edmonton, Canada. In 2007, Michelakis and his colleagues sparked a firestorm of interest when they announced rats fed DCA showed rapid tumor regression without any apparent side effects. Michelakis has been the first to say these results are preliminary and cautions cancer patients to refrain from running out and buying the drug, prior to clinical trials.
Yet, many desperate cancer patients with few remaining options are doing just that, and side effects ARE being reported.
There are currently three clinical trials involving use of DCA to treat cancer that are currently recruiting participants3. Some of these studies plan to combine DCA with other chemotherapy drugs and radiation, all known to have damaging effects in your body. However, if you have cancer and are tempted to participate, there are some things you should know in order to make an informed decision about the risk versus the benefits of this experimental treatment.
Cancer Cells and Healthy Cells Have Different Metabolic Processes
In order to understand how DCA kills cancer cells, it is necessary to understand a bit about how the cellular metabolism of cancer cells differs from that of your normal, healthy cells. Cancer cells have very different metabolic processes than normal cells, in terms of how they derive their energy.4 It’s a rather complicated distinction, so please bear with me as I try to explain it in the simplest terms possible.
There are two major pathways your cells use to covert sugar into energy: glucose oxidation and glycolysis:
- Glucose oxidationis the primary energy metabolism in normal cells and takes place in your mitochondria, which are the little “power plants” inside your cell; it requires the presence of oxygen, as its name suggests. This is why you breathe and your heart beats to circulate oxygen throughout your body. Glucose oxidation is sometimes referred to as cellular respiration.
- Glycolysis takes place in your cell’s cytoplasm. It can occur without the presence of oxygen. Glycolysis is less efficient for normal cells, but it is acancer cell’spreferredmeans of energy metabolism, and it depends on the availability of sugar.
So, when your cells are oxygen-starved they have a backup plan. They can extract energy from sugar without the presence of oxygen, by glycolysis.
Pyruvate is required for glucose oxidation. There is an enzyme (pyruvate dehydrogenase kinase, or PDK) that acts as gatekeeper to regulate the flow of pyruvate into the mitochondria. If PDK is active, it suppresses the transport of pyruvate into the mitochondria, and your cell is forced to rely on glycolysis, even if oxygen is available. If PDK is inactive, pyruvate is shuttled into the mitochondria, even if oxygen is low.
Unlike normal cells, cancer cells are masterful at deriving energy from glycolysis—they have very active PDK. The way to make a cancer cell unhappy is by suppressing PDK, forcing the cell to use glucose oxidation, instead of glycolysis. This is called the Warburg theory of cancer, or the Warburg hypothesis5. This is where DCA comes in.
DCA Instigates Mass Suicide among Cancer Cells
DCA suppresses PDK (the mitochondrial gatekeeper), and this fires up the cell’s mitochondria. Not only does this force the cancer cell to abandon its preferred metabolic process, but it flips the cell’s “suicide switch” as well. This happens because mitochondria are the primary regulators of apoptosis, or cellular suicide—they are loaded with sensors that react to abnormalities by pushing the cell’s self-destruct button.
When a cancer cell’s mitochondria realize it’s a cancer cell, it spontaneously kills itself. This is the reason chemotherapy and radiation result in such terrible side effects—your healthy cells actually die much more easily because of this self-destruct button.
The reason cancer is so fast growing is that the mitochondria have been deactivated, so the cells evade apoptosis, as well as being able to grow in the absence of oxygen (glycolysis)6. DCA reverses this.In effect, DCA directly causes cancer cell apoptosis and works synergistically other cancer therapies, such as radiation, gene therapy, and viral therapy. A number of scientific studies have been performed to date, and most are encouraging.
DCA–Cancer Research Review
Most of the studies thus far have been done on cell cultures in the lab (in vitro), as opposed to on cancer patients themselves (in vivo). Yet the results are impressively consistent across the board, suggesting DCA is effective against a wide variety of cancer types. The DCA Site7 has a good list of all clinical studies through 2011.
The study that sparked the DCA excitement appeared in Cancer Cell in January 20078 According to an article in the Edmonton Journal9 in the 2007 rat study, DCA killed lung, breast, and brain cancer cells but left healthy cells alone. The rats’ tumors decreased by up to 70 percent in three weeks of DCA treatment, without negative side effects.
This announcement led to a cyclone of excitement from cancer patients everywhere who scrambled to get their hands on the new “cancer cure,” in spite of warnings from Michelakis himself (and others) against prematurely self-medicating with the compound. Several more studies soon followed, including the first clinical trial2 involving brain cancer patients. In that trial, the research team selected five glioblastoma patients with a particularly aggressive form of brain cancer. They treated them with oral DCA for 15 months.
Tumor tissue was compared before and after DCA treatment in three of the five patients. In all three, there were signs that the tumor growth had slowed, and more cancer cells were undergoing programmed cell death after the treatment with DCA. Unfortunately, one of the five patients died. Another had “debulking” surgery before completing the full course of DCA treatment.Below are some of the other DCA cancer studies, all within the past five years. (Note that none of these involved human subjects.)
- Endometrial Cancer: DCA causes apoptosis in endometrial cancer cells.10
- Prostate Cancer: DCA produces significant cytotoxic effects in prostate cancer cells11
- Breast Cancer: DCA has anti-proliferative properties against breast cancer cells and caused apoptosis of those cells12
- Colorectal Cancer: DCA reduced colon cancer tumors by 20 to 40 percent13
- Cervical Cancer: Researchers concluded DCA is a quick and effective cure for advanced cervical carcinoma14
For comprehensive information about DCA’s method of action, history, and related scientific research, refers to The DCA Site7, and to this 2011 article in the International Journal of Cancer15. It should be noted that caffeine may radically increases the effects of DCA16. In fact, this effect is so pronounced that some researchers are working on developing a “DCA-caffeine” cancer treatment protocol.
Now that you’re aware of DCA’s cancer-fighting effects, let’s take a look at the adverse effects identified thus far.
DCA’s Side Effects Can Be Daunting
DCA is not a natural agent—it’s a chemical produced in the water chlorination process. It’s a small molecule, which accounts for one of its major advantages: DCA is easily absorbed by your body and can reach areas other drugs can’t, such as your brain, which is why it’s of particular interest for treating brain cancers. This, however, can be a two-edged sword, because any compound that easily permeates your brain can exert all sorts of unexpected and worrisome neurological effects.
DCA is a byproduct of another chemical called trichloroethylene (TCE), a volatile organic compound believed to cause cancer. TCE is used mainly as a solvent to remove grease from metal parts, but is also used in adhesives, paint removers, and typewriter correction fluids. The Agency for Toxic Substances and Disease Registry reports TCE is “reasonably anticipated to be a human carcinogen” and may cause birth defects. They state TCE may also cause the following17:
- Skin rashes
- Nerve, kidney, and liver damage
- Impaired heart and immune function
When DCA is added to the drinking water of laboratory mice, it causes liver cancer. While DCA may offer hope and a novel approach to treating cancer, it is far from a “miracle cure.” Of course, chemotherapy drugs are quite toxic as well!
DCA has been used successfully in children with metabolic disorders, with no signs of toxic poisoning. But adults appear to suffer more adverse effects—especially peripheral neuropathy and encephalopathy, such as the case described in a letter to the editor of the Journal of Neurology18. According to a survey performed by The DCA Site19, there are a fair number of serious side effects reported by those taking DCA, many of them neurological. Research suggests the side effects are at least somewhat dose-dependent, but safe dosing guidelines have not yet been established.
In the online survey, the side effects reported by DCA users include:
Tingling and numbness in the fingers, toes and lips; peripheral neuropathy Leg weakness Hand tremors Ankle swelling Increased urination Mild nausea Anxiety and depression Dizziness Sleepiness Breathing “heavier” than usual
In some studies, under some circumstances, DCA seems to actually make cancer cells stronger. For example, an in-vitro animal study20 published in May 2010 revealed that some types of colon cancer cells are actually protected by DCA when grown under anoxic conditions or as xenografts in mice (xenografts are tissues transplanted into one species from a dissimilar species). And when DCA is combined with frontline drugs, it sometimes interferes with their effectiveness. The neurological side effects are compounded when DCA is used with other anti-cancer drugs, which are also neurotoxic.
So, if you’re already using a cancer medication, DCA’s effects are going to be unpredictable and potentially dangerous. This underscores the importance of fully understanding the mechanisms of action of an agent before it enters clinical trials.
A Safer Alternative: FOODS that Cause Cancer Cells to Self-Destruct
What if there were natural agents that induced cancer cell suicide, without the side effects of DCA? As it turns out, these agents DO exist—and you may already have some in your kitchen pantry or supplement cabinet. Here are a few21:
- Curcumin (the active agent in the spice turmeric)
- Capsaicin (the compound that makes hot peppers hot)
- Se-methylselenocysteine aka methylselenocysteine (found in garlic and broccoli)
- Ellagic acid (from pomegranates and other fruits)
There are many all-natural cancer-prevention strategies, and research shows they may cut your risk in half. Consequently, by implementing multiple strategies, you can radically lower your risk of cancer as well as other chronic diseases.
Lifestyle Factors that Influence Your Cancer Risk
A healthful lifestyle encourages proper gene expression, as the science of epigenetics has shown. We now know you are in control of your genes, instead of being controlled by them. You actually have tremendous power to shape and direct your health! Your thoughts, your environmental exposures, and your food choices all directly affect your gene expression.
The best “cancer cure” is to prevent it from taking hold in the first place. Cancer cells are circulating in everyone, all the time. The stronger your immune system is, the less likely your cellular function will run amok. Your diet is extremely important in keeping your immune system strong. One of the primary cancer-promoters is sugar. Cancer cells love sugar and use it to fuel their rapid proliferation (by glycolysis, as discussed earlier). This includes ALL forms of sugar, including fructose and grains. The higher your blood glucose level, the more prolific the cancer cells will be.
According to breast cancer expert, author, and board certified surgeon Dr. Christine Horner:
“To me, sugar has no redeeming value at all, because they found that the more we consume it, the more we’re fuelling every single chronic disease,” Dr. Horner says. “In fact, there was a study done about a year ago… and the conclusion was that sugar is a universal mechanism for chronic disease. It kicks up inflammation. It kicks up oxygen free radicals. Those are the two main processes we see that underlie any single chronic disorder, including cancers. It fuels the growth of breast cancers, because glucose is cancer’s favorite food. The more you consume, the faster it grows.”
Your diet is the one of the best ways to either feed or prevent cancer. Processed foods, soft drinks, red meat from CAFO-raised animals, trans fats, and any food containing or contaminated with xenoestrogens promote cancer growth. Plant foods, particularly cruciferous vegetables and flax seeds, as well as many herbs and spices are cancer-preventive. Beneficial fats of particular importance for cancer prevention are omega-3 and omega-9, which effectively slow down tumor growth in estrogen-sensitive cancers, such as those of the breast, prostate and colon.
Generally speaking, your diet should focus on fresh, whole, unprocessed foods (vegetables, meats, raw dairy, nuts, and so forth) that come from healthy, sustainable, local sources, such as small organic farms. For the highest nutrient content, you will want to make raw food a significant portion of your diet.
Personally, I aim to eat about 80 to 85 percent of my food raw, including raw eggs and humanely raised organic animal products that have not been raised on a CAFO (confined animal feeding operation).
For more information about which foods to eat and which to avoid, please consult my comprehensive nutrition plan.
Vitamin D May Cut Your Cancer Risk in Half
If you currently have cancer, evidence shows that higher blood levels of vitamin D—probably around 80-90 ng/ml—are beneficial. If natural sun exposure is not practical, then a safe tanning bed or oral supplement are the next best things. Just keep in mind that it’s BEST to get your vitamin D from natural sun exposure. It appears vitamin D may play an important role in sulfur metabolism, and taking it orally may not provide the same benefit as deriving it from the sun. To learn the details about how to optimize your vitamin D, including dosage and blood testing, please review our comprehensive vitamin D article.
Vitamin D has been found to offer protection from cancer by several mechanisms, including:
- Regulating genetic expression
- Increasing apoptosis of defective, mutant cells thereby reducing cancer cell replication
- Causing cells to become differentiated (cancer cells often lack differentiation)
- Choking off the growth of new blood vessels from pre-existing ones, which is a step in the transition of dormant tumors turning cancerous
Exercise Can Also Slash Your Cancer Risk
If you are like most people, when you think of reducing your risk of cancer, exercise doesn’t immediately come to mind. However, there is some fairly compelling evidence that exercise can slash your cancer risk. One of the primary ways exercise lowers your risk for cancer is by reducing elevated insulin levels, which creates a low sugar environment—and remember, cancer cells LOVE sugar! Additionally, exercise improves the circulation of immune cells in your blood. Consider integrating exercise with intermittent fasting to greatly catalyze your healing and rejuvenation.
Restore Your Sleep
Getting proper sleep is critical, both in terms of getting enough sleep and sleeping during the right hours. According to Ayurvedic medicine, the ideal sleeping hours are between 10 pm and 6 am. Modern research has confirmed the value of this recommendation as certain hormonal fluctuations occur throughout the day and night, and if you engage in the appropriate activities during those times, you’ll “ride the wave,” so to speak. Working against your biology by staying awake when you should be sleeping, or vice versa, interferes with these natural hormone rhythms.
Manage Your Stress
Research tells us that if you experience a traumatic or highly stressful event, such as a death in the family or loss of a job, your risk of breast cancer is 12 times higher in the five years that follows. It is imperative to your health and longevity that you address your emotional well-being. Stress has a direct impact on inflammation, and inflammation drives many of the chronic diseases that kill people prematurely every day.
Meditation, prayer, yoga, and EFT (an energy psychology tool) are all viable options that can help you maintain emotional/psychological equilibrium. I’m sure you can think of others—the bottom line is, find what works best to de-stress yourself and practice it daily.
Avoid as Many Chemicals, Toxins, and Pollutants as Possible
Just as stress is toxic to your emotional health, chemical overload is toxic to your physical health, and both can weaken your immune system. Get rid of as much toxic junk as you can. This includes harsh chemical household cleaners, soaps, personal hygiene products, air fresheners, bug sprays, lawn pesticides, insecticides and the rest. Replace them all with green, non-toxic alternatives.
For more suggestions about how to prevent and heal from cancer, please refer to the cancer section of our website, which contains a wealth of free, research-based information.
Cancer & Metabolism20142(Suppl 1):P9
© Rooke et al; licensee BioMed Central Ltd. 2014
Published: 28 May 2014
Sarcomas are cancers that arise from tissues of mesenchymal origin and there has been limited improvement in treatments over the last 30 years. The Warburg effect is a widespread metabolic phenotype of cancer, where glycolysis is favoured despite the presence of oxygen. Dichloroacetate (DCA) is a pyruvate dehydrogenase kinase (PDK) inhibitor in clinical use that can reverse the Warburg effect, inhibiting growth and enhancing apoptosis in a range of cancers. We have investigated its effectiveness against sarcoma cells in vitro and in vivo.
Materials and methods
Three cell lines (mouse fibrosarcoma S180, mouse osteosarcoma K7M2 and human fibrosarcoma HT1080-luc2) were examined for cell viability after DCA treatment in vitro (neutral red uptake assay), alone and in combination with doxorubicin. In vivo, K7M2 cells were injected s.c. into Rag1-/- mice (2 sites per mouse, 7-9 mice per group) and established tumours were treated with DCA in the drinking water (0, 0.5, 1.0 and 1.5 g/L, delivering 0, 70, 125 and 165 mg/kg/day, respectively). Tumour growth was monitored with callipers. Plasma was collected on d1 and d15 for measurement of DCA levels (LC-MS).
DCA significantly reduced the total viable cell number after 48 h of treatment in the mouse sarcoma lines (~15% at 0.5 mM DCA, and 30-40% at 5 mM DCA), however HT1080-luc2 cells showed only a 10% reduction in cell number with 5 mM DCA. There was no morphological indication of apoptosis, suggesting DCA was decreasing proliferation. Chronic treatment of the mouse cells (5 mM DCA for 2 weeks) resulted in significantly slower growth rates as measured over 48 h (7 and 13% total cell number compared to untreated S180 and K7M2 cells, respectively). DCA did not synergise with doxorubicin but was additive at lower concentrations of doxorubicin. In vivo, 1.0 and 1.5 g/L DCA significantly reduced tumour growth (33.0 and 33.1% reduction in tumour size on d13, p=0.001 and 0.01 respectively). Plasma DCA was undetectable on d1 of treatment, but by d15, 1.0 and 1.5 g/L DCA delivered 2-44 uM. Tumour DCA concentrations were also measured and found to be in the range of 25-470 uM, much lower than those typically used in in vitro studies.
DCA was effective against an in vivo sarcoma model, with tumour DCA concentrations in the micromolar range. These concentrations are achievable clinically, thus DCA warrants further investigation for sarcoma treatment.
Supported by the Sarah-Grace Sarcoma Foundation and Cancer Australia.
(1)John Curtin School of Medical Research, Australian National University
(2)Mass Spectrometry Facility, Australian National University
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