Lymphoma, Chemotherapy, & Antioxidants

INTRODUCTION
Oxidative stress is defined as a type of physiological stress on the body caused by the damage done by free radicals inadequately neutralized by antioxidants. It has long been known that oxidative stress is an essential mechanism by which chemotherapy works to treat cancer. However, the question of whether this is always the case is seldom debated openly. Taking a deeper look into the research literature yields many examples where oxidative stress on cancer cells has been shown to be counterproductive. For example, a study using human Burkitt lymphoma cells found that oxidative stress actually interferes with the ability of the chemotherapy drugs doxorubicin, cisplatin, etoposide, and cytarabine to cause cancer cell death.
When oxidative stress levels are reduced in cancer cells, their growth is more easily controlled through a process called apoptosis. During apoptosis, cells are removed by the immune system before they lose their cell wall, thus avoiding an inflammatory response to the dying cells.
However, when oxidative stress levels go up, cancer cell death happens through a slower, messier, and less effective pathway called pyknosis or necrosis. Additionally, the ability of the body to “clean up” the resulting cellular debris from cancer cell death is also inhibited by oxidative stress. The body’s house-cleaning cells (called monocyte-derived macrophages) cannot function optimally under conditions of oxidative stress (i.e. low oxygen levels).
The authors of the above-mentioned study on Burkitt lymphoma cells and chemotherapy suggest that including antioxidants in the treatment protocol may enhance chemotherapy-induced apoptosis and phagocytosis. (Shacter, Williams et al. 2000) A second study, involving the chemotherapy drugs etoposide and calcimycin, confirms this finding: Human Burkitt’s lymphoma cells were unable to die quickly by apoptosis in the presence of oxidative stress and instead died using the slower and messier method of necrosis. In this study, it was found that oxidative stress inhibited apoptosis by depleting cells of their energy source, which is called adenosine triphosphate (ATP). (Lee and Shacter 1999)
Related to these observations about the relationship between cellular oxidative stress levels is the widely held view in medicine that the use of antioxidant dietary supplements diminishes chemotherapy’s effectiveness. However, when one looks more closely at the existing published science on how antioxidants and chemotherapy combine, the true answer is not so definitive. Many research studies, encompassing cell culture tests in the laboratory and also animal and some human studies, are coming to a conclusion often very different from the conventional perspective that chemotherapy and antioxidants should never be combined.
One example is a human study in which researchers discovered that higher levels of the antioxidant selenium in the blood of patients with aggressive B-cell non-Hodgkin’s lymphoma correlated with increased achievable doses of anthracycline based chemotherapy, better treatment response, achievement of long term remission, and longer overall survival. It is important to note that in this study, however, the level of selenium present in the blood of patients was from their diet; the study was not a test of supplemented selenium. (Last, Cornelius et al. 2003) As seen in this study, higher levels of natural antioxidants can help treatment outcomes.
On the other hand, the decreased levels of antioxidants (or oxidative stress) that are caused by many chemotherapy treatments correlates with increased side effects. In patients with Hodgkin’s lymphoma, chemotherapy with Adriamycin, bleomycin, vincristine, and dexamethasone significantly decreases antioxidant levels. (Kaya, Keskin et al. 2005) In children with acute lymphoblastic leukemia who received high-dose methotrexate, oxidative damage to proteins as well as other factors was related to toxic side effects. (Carmine, Evans et al. 1995)
Using antioxidants during chemotherapy is an important and controversial question among health care providers, patients, and their support teams. In previous issues of Avenues, we have researched this subject thoroughly for prostate, breast, lung, colon, and ovarian cancers. In this article, we turn our focus to lymphoma, conducting a systematic search for published research that would support or discourage the use of antioxidants in combination with chemotherapy. The overwhelming majority of studies find a favorable interaction between antioxidants and chemotherapy, providing evidence that antioxidants can decrease chemotherapy side effects, increase treatment effectiveness, and decrease resistance to chemotherapy.
For this paper, we searched for clinical or laboratory data published in peer-reviewed medical journals, conducted by cancer researchers in universities and medical research facilities around the world. Some of these studies are still in early stages and include only laboratory or animal data while others have advanced to include human volunteers. We organized these data into the major categories of specific chemotherapy drugs. Within each section for a specific drug are found the research on combinations of that drug with various antioxidants, grouped by the name of the antioxidant in alphabetical order. We also point out specifically which studies were conducted in a laboratory (i.e. used cancer cell cultures), used animals, or involved human volunteers. As each antioxidant appears in the paper for the first time, we provide some introduction to the antioxidant including what food sources naturally contain it, other common applications in clinical use, and typical dosages. The dosages given are not necessarily appropriate for all patients and should be individualized with practitioner guidance.

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Fasting May Improve Chemo.

Standard Dietary recommendations during cancer treatment are based on the prevention or reversal of nutrient deficiencies to preserve lean body mass and minimize nutrition-related side effects, such as decreased appetite, nausea, taste changes, or bowel changes [16]. Consequently, for cancer patients who have been weakened by prior chemotherapy cycles or are emaciated, many oncologists could consider a fasting-based strategy to be potentially harmful. Nevertheless studies in cell culture and animal models indicate that fasting may actually reduce chemotherapy side effects by selectively protecting normal cells [9]. Following the publication of this pre-clinical work,several patients, diagnosed with a wide variety of cancers, elected to undertake fasting prior to chemotherapy and shared their experiences with us. In this heterogeneous group of men and women fasting was safely repeated in multiple cycles for up to 180 hours prior and/or following chemotherapy. Minor complaints that arose during fasting included dizziness, hunger, and headaches at a level that did not interfere with daily activities. Weight lost during fasting was rapidly recovered in most of the patients and did not lead to any detectable harm.

Ralph Moss, a wonderful writer, asks what is the actual science of fasting and its relationship to cancer treatment? Recently Dr. Valter D. Longo, Fernando M. Safdie and colleagues at the University of Southern California (USC) Andrus Gerontology Center and Department of Biological Sciences, have shown that a 48-hour fast protects normal cells and mice, but not cancer cells, against high-dose chemotherapy.
They also described 10 patients who voluntarily fasted prior to and/or following chemotherapy. None of these reported side effects caused by fasting other than lightheadedness and, of course, hunger. However, most patients reported less fatigue, weakness or gastrointestinal side effects from chemotherapy if they also fasted before and/or after receiving the drugs.
Nor did fasting decrease the effectiveness of the chemotherapy. These USC scientists therefore suggest that fasting, in combination with chemo, is “feasible, safe, and has the potential to ameliorate side effects.” They also recommend consulting one’s physician before undertaking a fast, and I totally agree. There are certainly individuals with cancer who should not fast. But fasting should be feasible for other patients, is cost-free and, at least in this preliminary report, effective at reducing the side effects of chemotherapy.
The full text of the study in the National Library of Medicine can be found here

Fasting May Improve Chemo « Cancer Advisor: Ralph Moss on Cancer News
Alex Comments: It appears a good case is being made for fasting before and after chemotherapy. It is definitely worth taking a close look into. As for my own chemotherapy treatments, I did not know this information and I approached chemo. with an"eat my way through it" mentality (which is how I approach lots of things that are anxiety producing). My chemo. If I had to do it all over again I would probably fast around my chemotherapy. Tell me your experience.

Advances Elusive in the Drive to Cure Cancer

Alex Writes:  This NY Times article reviews the history of survival rates of various cancers in wonderful interactive graphs and more... The best part are the letters from readers in response to this article.  

In 1971, flush with the nation’s success in putting a man on the Moon, President Richard M. Nixon announced a new goal. Cancer would be cured by 1976, the bicentennial.

Forty Years’ War

An Expensive Priority

Articles in this series will examine the struggle to defeat cancer.

Multimedia

Interactive Graphic

A Stubborn Disease

Graphic

Still Deadly

Related

As Other Death Rates Fall, Cancer’s Scarcely Moves (April 24, 2009)

Readers' Comments

Readers shared their thoughts on this article.

• Read All Comments (311) »

When 1976 came and went, the date for a cure, or at least substantial progress, kept being put off. It was going to happen by 2000, then by 2015.

Now, President Barack Obama, discussing his plans for health care, has vowed to find “a cure” for cancer in our time and said that, as part of the economic stimulus package, he would increase federal money for cancer research by a third for the next two years.

Cancer has always been an expensive priority. Since the war on cancer began, the National Cancer Institute, the federal government’s main cancer research entity, with 4,000 employees, has alone spent $105 billion. And other government agencies, universities, drug companies and philanthropies have chipped in uncounted billions more.

Yet the death rate for cancer, adjusted for the size and age of the population, dropped only 5 percent from 1950 to 2005. In contrast, the death rate for heart disease dropped 64 percent in that time, and for flu and pneumonia, it fell 58 percent.

DO HERBS, VITAMINS, AND ANTIOXIDANTS ADVERSELY AFFECT CANCER THERAPIES?

preliminary report by Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine, Portland, Oregon

For more than 30 years now, Chinese herbs and materials derived from the herbs, such as long chain polysaccharides, have been used as adjunct therapies for cancer patients. This modern application was first developed clinically in China and Japan during the 1970s and was relayed to the rest of the world in 1983 through an international conference in Beijing which was followed up by press reports in English and other languages (see: Physiological responses to immunologically active polysaccharides). The Institute for Traditional Medicine (ITM) made an effort to alert practitioners of Chinese medicine in the U.S. to this promising role for Chinese herbs immediately after that conference, with updated information provided as available over the years. The utilization of Chinese roots, leaves, and fruits (e.g., astragalus, gynostemma, ligustrum, and lycium), and several mushrooms (e.g., coriolus, ganoderma, cordyceps, and lentinus) for cancer patients is now a routine procedure when these patients visit acupuncturists, naturopathic physicians, and others offering adjunctive cancer health care.

Within the past couple of years, however, an increasing number of patients have been told by their oncologists to avoid herbs, and to more generally avoid supplements (such as vitamins), or, even more broadly, simply avoid anything with antioxidant potential while they are undergoing cancer therapies. The admonition itself is difficult to interpret, since all foods contain antioxidants and vitamins, and they also contain most of the other substances offered in dietary supplements. Most fruits, vegetables, beans, and nuts differ only slightly from herbs. A more specific recommendation is needed. But first, the question arises: why are doctors giving these instructions? What kind of information is being released to the public?

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Antioxidants with Chemotherapy

My patients that are receiving chemo. and/or radiotherapy tell me that their Dr's. tell them not to take antioxidant nutritional supplements. Upon investigation it appears that a prescribed known anti-oxidant drug Amifostine is used to protect against the side effects of chemo. and radiation and that antioxidant rich foods are not prohibited by Oncologists during treatment. So the picture of the use of antioxidants may be more nuanced than what Oncologists are saying. Below are literature reviews published in respected journals that shed more light on this issue. Alex

Antioxidants and Other Nutrients Do Not Interfere With Chemotherapy or Radiation Therapy and Can Increase Kill and Increase Survival, Part 2 (pdf)
Charles B. Simone II, MD; Nicole L. Simone, MD; Victoria Simone, RN; Charles B. Simone, MD
Alternative Therapies in Health and Medicine Mar/Apr 2007 • Vol 13, No. 2

Should Patients Undergoing Chemotherapy and Radiotherapy Be Prescribed Antioxidants?

Ralph W. Moss, PhD Cancer Communications, Lemont, Pennsylvania,
Integrative Cancer Therapies, Vol. 5, No. 1, 63-82 (2006)

I welcome your comments.

QUOTES FROM DR JULIAN WHITAKER, M.D. ABOUT CONVENTIONAL CANCER THERAPY

DR JULIAN WHITAKER, M.D.
http://www.drwhitaker.com/

We know that conventional therapy doesn’t work—if it did you would not fear cancer any more than you fear pneumonia. It is the utter lack of certainty as to the outcome of conventional treatment that virtually screams for more freedom of choice in the area of cancer therapy. Yet most so-called alternative therapies regardless of potential or proven benefit, are outlawed, which forces patients to submit to the failures we know don’t work, because there is no other choice.

The FDA, NCI and ACS, and the large treatment centres work to eliminate choice of cancer therapies, particulary better ones. They openly attack breakthroughs made by "mavericks", which they define as anyone outside their ranks. Folks, any serious study of how these entities work together to destroy hopeful approaches to cancer reveals a trail of corruption, conspiracy, dishonesty, and inhumanity that warrants desigantion of evil……..We continue to use them not because they work, but because those who perform them have so vigorously eliminated any other choice.

What I wouldn’t do if I had cancer

First, I would not even check in with a conventional oncologist, particulary not one from a prominent cancer institution. Their expertise is in implementing the erroneous paradigm that cancer must be purged from the body with toxic methods. This is, in my opinion, no more valuable than maps from the Flat Earth Society. When there is a paradigm shift---and we definitely are in the middle of one with cancer treatment---those sitting on the lofty perches of authority are the last to make the change, because they are guarding the paradigm about to be replaced. I don’t buy maps of a flat earth, and I wouldn’t go to the NCI or Memorial Sloan-Kettering Centre for cancer treatment.

What I Would Do.

I’d turn my back on 50 years of institutionalised expertise, because it follows the wrong paradigm. Everything that is done in medicine today or in any other discipline fits some paradigm. The paradigm I use for cancer is that it is a systemic problem in which the normal control mechanisms of your body are altered. Your immune system likely bears the largest burden for this control; thus, all techniques that enhance it are promising. Those that damage it are not.

"Conventional Medicine is locked into a dogma that believes that its way is the only way. Conventional doctors deny you have any alternatives to their drugs and surgeries. But you do have choices. And these enlightened treatments are far superior to the risky methods of modern medicine. . .which can be extremely dangerous to your well-being. . . . This enlightened new approach to health will lead contemporary medicine out of the Dark Ages of drugs and surgery, because it does work better. I know, because I use these alternative therapies every day in my medical practice. . . .Many of the patients I see are 'medical refugees' who have been abused and abandoned by conventional medicine. . . .The results we see are truly impressive, more so than with any drugs and conventional treatments they gave us in medical school. . . .The 'drugs or surgery only' approach that modern medicine uses to treat today's diseases is archaic."—Julian Whitaker, M.D.

I AGREE. ALEX

Herbs and Nutrients with Anti-cancer Activity Abound

Here I go again: More natural substances that have research as being effective in cancer in a number of ways:

• Promoting apoptosis (cell death)
• Inhibiting the known pathways that cancers use to develop ie... VEG-F or NF kappa B, MMPs (and that many new cancer drugs work on)
  
• Decreasing the side effects of toxic cancer drugs.

So here are a few I came across in the last day:

Inhibitory effect of a mixture containing ascorbic acid, lysine, proline and green tea extract on critical parameters in angiogenesis.

This research is based on off the shelf nutrients available in probably any health food store.

The apoptotic effect of cordycepin on human OEC-M1 oral cancer cell line.

cordycepin is an extracted component of the chinese herb Cordyceps. I use it in my practice frequently to improve lung function.

Antiproliferative and apoptotic effects of silibinin in rat prostate cancer cells.

silibinin is an extracted component of Milk Thistle.

Baicalein induces apoptosis through ROS-mediated mitochondrial dysfunction pathway in HL-60 cells.

Baicalein is the exracted component of the chinese herb scutellaria huang qin. I use this herb frequently for many conditions.

If you click through to the links in the pubmed you will see numerous studies for each of the herbs and nutrients I have listed. The point is that there are many natural ways to prevent and treat cancer. This kind of stuff abounds. The use of these substances in the preventitive approach is relatively simple because everything listed here is non-toxic. How they may interact with on-going conventional therapy is another matter entirely that needs examination on a case by case basis.

Mushroom extract improves performance of Doxirubicin

The anticancer drug doxorubicin (Dox) has been shown to induce apoptosis (programmed cell death) in cancer cells. However, higher doses can damage healthy cells. In a study published in the British Journal of Cancer, the effect of the PL mushroom on Dox-induced apoptosis was investigated in prostate cancer cells.³ Researchers showed that PL or Dox, at relatively low doses, could not kill these cells. However, combination treatment at low doses of PL and Dox results in a synergistic effect and brought about death in prostate cells.

These findings indicate that PL has a synergistic effect with Dox to activate a beneficial decline in prostate cancer cells.³ Not only did these researchers find that the combination was just as effective in killing cancerous cells as larger doses of the drug alone, it did so without harming healthy cells.³

There is a lifetime maximum number of doses of this drug due to its cardiotoxicity. There is also research on antioxidants used in combination with this drug to prevent cardiotoxicity (future post). So this study may be poignant if it can be followed up by larger studies and eventually a human trial. But this is a big if...

This issue of improving the efficacy of chemotherapy or reducing the side-effects appears to be mostly disregarded as unsubstantiated or at least outside of the standard of care by oncologists. Given the way that profit is organized in the medical business an insight like this study implies will have a lot of trouble making it into animal studies or a human trial because it is about using less Doxirubicin. Read - less profitable. The makers of this drug are probably not going to be in favor of pursuing alternatives that may lead to them selling less drug. This is an example where the "invisible hand of capitalism" does not do what is best for the consumer.

What would happen if something really simple, common and relatively cheap was found to be as effective or more effective than Doxirubicin at a fraction of the cost? I don't have one yet, but there are all kinds of treatments out their for cancer that need to be critically evaluated. The main person I know that does this is Ralph Moss. I have posted his writings on this blog many times. It appears that it is the patients will to pursue their health that can drive the alternatives and complimentary strategies for cancer.

The life and death issues around cancer make standard of care issues potential legal issues as well. (This can be overcome by proper informed consent.) Oncologists, it appears to me, tend not to be the most alternative of health care practitioners and granted patients are scared and looking to experts with experience to guide them.

I am looking for some who are interested in integrating with acupuncture with cancer treatment and at least consider the use of natural medicine in conjunction with the normal standard of care. If anyone knows an onco. or group in the Los Angeles area that takes this approach please contact me.