May 16, 2012
STORY AT-A-GLANCE
- The antioxidant resveratrol and curcumin (the active substance of the spice turmeric) both show promise as natural chemosensitizers — substances that can help overcome resistance to chemotherapy drugs
- Both nutrients have a wide spectrum of anti-cancer actions and functions
- By modulating inflammatory pathways and inflammatory molecules, resveratrol may also help alleviate many of the debilitating side effects of conventional cancer treatment, such as wasting, fatigue, depression, neuropathic pain, cognitive impairment and sleep disorders
- Among all nutrients, curcumin has the most evidence-based literature supporting its use against cancer. Researchers have found that curcumin can affect more than 100 different pathways, once it gets into a cell
- Epigenetic regulation constitutes an important mechanism by which dietary components can selectively activate or inactivate gene expression. Both curcumin and resveratrol induce epigenetic changes
By Dr. Mercola
The conventional cancer therapies currently available are surgery, radiotherapy and chemotherapy; aka the "cut, poison, burn" model. Chemotherapy is typically the main regimen for most cancers. However, many tumors develop resistance to these harsh drugs, known as chemoresistance,1 which can complicate matters, to say the least. Chemoresistance also leads to other complications.
Hence researchers are looking for effective chemosensitizers that can help overcome such resistance. This strategy basically uses one drug to enhance the activity of another, by modulating the mechanisms that cause the resistance.
A number of natural products and compounds have been shown to act as effective chemosensitizers. Two of the most promising are resveratrol and curcumin, which I'll address here. Many interesting studies were published on these two products over the years, pertaining to their value in the treatment of cancer.
Resveratrol: A Natural Chemosensitizer
Natural agents such as resveratrol, a potent antioxidant chemical found in red wine and other foods, have multitargeting properties,2 which make them ideally suited for anticancer drugs. In fact, more than 60 percent of the cancer drugs currently available are based on natural ingredients for this very reason. Natural compounds are also inexpensive, low in toxicity and are readily available.
In a 2011 review of dietary agents that sensitize tumors, making them more susceptible to the treatment with chemotherapy drugs, resveratrol was featured as a clear candidate.3 Specific types of tumors shown to respond favorably include:
Lung carcinoma
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Acute myeloid- and promyelocytic leukemia
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Multiple myeloma
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Prostate cancer
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Oral epidermoid carcinoma
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Pancreatic cancer
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The first evidence of resveratrol's anti-cancer effects was published in 1997. The findings received great interest from cancer researchers, and many studies have been devoted to this potent antioxidant since then. Resveratrol, which can be found in red wine, red grape skins, fruits, vegetables, legumes and weeds, has been found to have the following actions and functions:4
- Broad-spectrum antimicrobial
- Anti-infective
- Antioxidant
- Cardioprotective
- Anticancer
According to the review, published in the Annals of the New York Academy of Sciences:5
"The anticancer activities of resveratrol are mediated through modulation of several cell-signaling molecules that regulate cell cycle progression, inflammation, proliferation, apoptosis, invasion, metastasis, and angiogenesis of tumor cells.
It has been shown that resveratrol can sensitize resistant cells to chemotherapeutic agents by overcoming one or more mechanisms of chemoresistance. In some tumor cells, however, resveratrol has been shown to act as chemoprotector."
The fact that it can in some cases act as a chemoprotector, meaning, it can reduce the efficacy of chemotherapeutic agents, "present a major caveat for use of resveratrol as a chemosensitizer," the authors warn. In an earlier study, the researchers concluded that using resveratrol with the cancer drug Paclitaxel, for example, was detrimental in certain types of cancers, such as breast cancer.6
Resveratrol May Help Alleviate Cancer Treatment Side Effects
In another study published in the journal Experimental Biology and Medicine, resveratrol was found to help alleviate many of the debilitating side effects of conventional cancer treatments,7 such as:
Cachexia (wasting syndrome)
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Anorexia
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Fatigue
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Depression
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7Neuropathic pain
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Anxiety
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Cognitive impairment
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Sleep disorders
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Delirium (acute confusion)
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The authors point out there's mounting evidence indicating that these symptoms are primarily caused by dysregulation of inflammatory pathways in your body. Hence anti-inflammatory compounds that can modulate the inflammatory pathways and influence inflammatory molecules may help improve these symptoms in cancer patients. They name several nutritional agents known to do just that, including:
- Resveratrol
- Curcumin
- Genistein
- Epigallocatechin gallate (EGCG)
- Lycopene
According to the authors:8
"These nutraceuticals are chemically diverse and affect production of various inflammatory cytokines. Extensive research in recent years has indicated that chronic inflammation leads to various chronic disorders associated with cancer.
A central role in the induction of chronic inflammation is played by a set of genes encoding proinflammatory cytokines such as IL-1, IL-2, IL-6, TNFa and monocyte chemotactic protein 1. What is common to all these molecules is that they are regulated by the transcription factor NFkB. This makes NFkB an appealing target for therapeutic intervention.
A number of compounds have been identified that can suppress NFkB activation, including antioxidants, protease inhibitors, proteasome inhibitors, salicylates, immunosuppressants and anti-inflammatory agents."
This brings us to the next interesting fact about natural products like resveratrol and curcumin, namely their impact on your genetic expression. As just mentioned, your genetic expression plays a central role in chronic inflammation, and certain nutrients can have a potent protective influence by either turning genes on or off.
Understanding Epigenetics
The role of epigenetics in health and disease is becoming ever clearer, and I firmly believe this field of study will eventually supplant the current medical paradigm. The conventional belief has been that genes controlled their own expression and were therefore the direct cause of certain diseases. This laid the groundwork for the idea that your genes predetermined your health.
But genes are in fact not self-regulating. Having "bad genes," does not at all mean you're doomed to suffer some inevitable fate like cancer!
Genes are merely blueprints, and these blueprints are activated and controlled by something else entirely, namely their environment. This environmental information — which includes diet, toxic exposures, as well as thoughts and emotions, and more — can create more than 30,000 different variations from each blueprint, allowing for an astounding amount of leeway in modifying the expression or "read-out" of each gene.
As a result of these findings, we're now finally seeing science alter its course to investigate the power of optimal nutrition to improve health and prevent chronic disease from occurring in the first place. A 2011 study investigating curcumin's ability to affect epigenetic regulation was published in the journal Genes & Nutrition.9 The authors write:
"Epigenetic regulation, which includes changes in DNA methylation, histone modifications, and alteration in microRNA (miRNA) expression without any change in the DNA sequence, constitutes an important mechanism by which dietary components can selectively activate or inactivate gene expression.
Curcumin, a component of the golden spice Curcuma longa, commonly known as turmeric, has recently been determined to induce epigenetic changes ... [E]pigallocatechin gallate (EGCG), and resveratrol, have [also] been shown to alter epigenetic mechanisms, which may lead to increased sensitivity of cancer cells to conventional agents and thus inhibition of tumor growth."
Curcumin: A Potent Anticancer Herb
Curcumin currently has the most evidence-based literature supporting its use against cancer among all nutrients.10 Interestingly this also includes the metabolite of curcumin and its derivatives, which are also anticancerous. Best of all, curcumin appears to be safe in the treatment of all cancers, and has been shown to be nontoxic.11 Researchers have found that curcumin can affect more than 100 different pathways, once it gets into the cell. More specifically, curcumin has been found to:
Inhibit the proliferation of tumor cells12
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Decrease inflammation13
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Inhibit the transformation of cells from normal to tumor14
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Inhibit the synthesis of a protein thought to be instrumental in tumor formation15
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Help your body destroy mutated cancer cells so they cannot spread throughout your body16
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Help prevent the development of additional blood supply necessary for cancer cell growth (angiogenesis)17
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Have chemosensitization activity18
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Have radiosensitization activity19
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Another study published in the 2011 Natural Product Reports describes curcumin as being therapeutic for a wide range of diseases aside from cancer,20 such as:
Lung and liver diseases
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Neurological diseases
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Metabolic diseases
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Autoimmune disorders
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Cardiovascular diseases
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Inflammatory diseases
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A persistent question has been: How can a single agent possess such diverse effects? Part of the answer lies in the herb's ability to affect signaling molecules. For example, curcumin has been shown to directly interact with:
Inflammatory molecules
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Cell survival proteins
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Histone
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Human immunodeficiency virus type
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1 (HIV1) integrase and protease
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DNA and RNA
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Various carrier proteins and metal ions
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According to the authors of the NPR paper:21
"The molecular basis of a disease is related to dysregulation of an array of signaling molecules. With the advent of advanced molecular tools, we now know that over 500 different genes of the signaling pathways control any given disease.
However, most currently available treatments are based on the modulation of a specific single target. Curcumin is a functionally labile molecule with the potential to modulate the biological activity of a number of signaling molecules either indirectly or directly..."
How to Use Curcumin
To get the full benefits curcumin has to offer, you need to understand that it is very poorly absorbed. You simply can't blindly choose a supplement and expect to achieve the results described in this paper. There is extensive research going on by a number of organizations to provide a commercial product.
You can look for a turmeric extract that contains 100 percent certified organic ingredients, with at least 95 percent curcuminoids. The formula should be free of fillers, additives and excipients (a substance added to the supplement as a processing or stability aid), and the manufacturer should use safe production practices at all stages: planting, cultivation, selective harvesting and then producing and packaging the final product.
Unfortunately, at the present time there really are no concentrated commercial formulations available for the use against cancer. Keep in mind that concentrated curcumin is really only needed by people who seek to use it as a drug, in which case you need it in very high doses in order to achieve therapeutic effect. The most classic case would be those using it to treat, not prevent, cancer. If you do not have cancer, then using a turmeric supplement is sufficient.
According to Dr. William LaValley, one of the leading medicine cancer physicians I personally know, typical anticancer doses are up to 3 grams of good bioavailable curcumin extract, three to four times daily. One work-around is to use the curcumin powder and make a microemulsion of it by combining a tablespoon of the powder and mixing it into 1 to 2 egg yolks and a teaspoon or two of melted coconut oil. Then use a high speed hand blender to emulsify the 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 put it in room temperature water and heat the water and curcumin.
After boiling it for 10 minutes you will have created a 12 percent solution that you can drink once it has cooled down. It will have a woody taste. The curcumin will gradually fall out of solution however. In about six hours it will be a 6 percent solution, so it's best to drink the water within four hours. Dr. LaValley is also helping us beta test new curcumin preparations that will radically simplify this process.
( Note: For a selection of the latest bioavailable curcumin supplements, see Consumer Lab review link: https://www.consumerlab.com/reviews/turmeric-curcumin-supplements-spice-review/turmeric/ )
Cancer Prevention 101
It is certainly encouraging to see cancer research on herbs such as turmeric, and antioxidants like resveratrol. However, it's virtually impossible to discuss cancer prevention and treatment without touching on one of the absolute best cancer prevention nutrients ever discovered, namely vitamin D.
As a powerful neuro-regulatory steroid, vitamin D is likely more potent than curcumin, as its epigenetic influence covers more than 2,000 genes in your body — or about 10 percent of all genes! There are also more than 830 peer reviewed scientific studies showing vitamin D's effectiveness in the prevention and treatment of cancer. In terms of protecting against cancer, vitamin D has been found to offer protection in a number of ways, including:
- Regulating genetic expression22
- Increasing the self-destruction of mutated cells (which, if allowed to replicate, could lead to cancer)23
- Reducing the spread and reproduction of cancer cells24
- Causing cells to become differentiated (cancer cells often lack differentiation)25
- Reducing the growth of new blood vessels from pre-existing ones, which is a step in the transition of dormant tumors turning cancerous26
Personally, I believe it is virtually malpractice to not optimize vitamin D levels when treating someone with cancer. In this case, your vitamin D levels should be around 60 to 80 ng/ml. For more information about optimizing your vitamin D levels, please see my article “For Optimal Health, Make Sure You Have a Vitamin D Level of 60 ng/mL.”
Other Natural (and Epigenetic) Cancer Prevention Strategies
When it comes to cancer and other chronic diseases, effective prevention trumps progressive treatments in my eyes. I believe you can virtually eliminate your risk of ever developing cancer (and radically improve your chances of recovering from cancer if you currently have it) by following some relatively simple risk reduction strategies — all of which help promote a healthful biological environment in which your cells can thrive and combat disease naturally.
You don't read or hear much about these strategies because they have not been formally "proven" yet by conservative researchers. Beyond what's already been covered above, the remainder of my cancer prevention strategies include:
1.Reduce or eliminate your processed food, fructose and grain carbohydrate intake.
2.Control your fasting insulin and leptin levels — Normalizing your insulin levels is one of the most powerful physical actions you can take to lower your risk of cancer, and improved insulin and leptin control is the natural outcome of reducing or eliminating fructose, grains, and processed foods from your diet.
3.Normalize your ratio of omega-3 to omega-6 fats by taking a high-quality krill oil or fish oil and reducing your intake of most processed vegetable oils.
4.Get regular exercise — One of the primary ways exercise lowers your risk for cancer is by reducing elevated insulin levels, which creates a low sugar environment that discourages the growth and spread of cancer cells.
Controlling your insulin levels is one of the most powerful ways to reduce your cancer risks.27 Additionally, exercise improves the circulation of immune cells in your blood.28 Your immune system is your first line of defense against everything from minor illnesses like a cold right up to devastating, life-threatening diseases like cancer.
The trick about exercise, though, is understanding how to use it as a precise tool. This ensures you are getting enough to achieve the benefit, not too much to cause injury, and the right variety to balance your entire physical structure and maintain strength and flexibility, and aerobic and anaerobic fitness levels.
If you have limited time, I invite you to try the Nitric Oxide Dump, a high intensity interval workout that offers potential effects on your mitochondria. This workout only takes three or four minutes, and should be repeated three times a day, with a minimum of two hours in between sessions.
5.Get regular, good quality sleep.
6.Reduce your exposure to environmental toxins like pesticides, household chemical cleaners, synthetic air fresheners and air pollution.
7.Limit your exposure and provide protection for yourself from EMF produced by cell phone towers, base stations, cell phones and WiFi stations — On May 31, 2011, the International Agency for Research on Cancer (IARC), an arm of the World Health Organization (WHO), declared that cell phones are "possibly carcinogenic to humans."29 Two government-funded studies have also shed light on this link.30
8.Avoid frying or charbroiling your food — Boil, poach or steam your foods instead.
9.Have a tool to permanently reprogram the neurological short-circuiting that can activate cancer genes — Even the CDC states that 85 percent of disease is caused by emotions.31 It is likely that this factor may be more important than all the other physical ones listed here, so make sure this is addressed. Energy psychology seems to be one of the best approaches and my particular favorite tool, as you may know, is the Emotional Freedom Techniques.
10.Eat at least one-third of your diet in the form of raw food.
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