Study Yields New Clues on Long-Term Cognitive Problems After Chemotherapy

By Kelli Miller Stacy
Reviewed by Louise Chang, MD
WebMD Medical News

Scientists have discovered that a popular chemotherapy drug affects healthy brain cells long after treatment ends. It’s a finding that provides further validation to the millions of Americans who develop long-term cognitive problems after receiving the cancer-killing medication.

Many cancer survivors report short-term memory loss and difficulty concentrating during and shortly after treatment, but for some the problems linger.

Until recently, doctors told cancer patients who developed memory loss, seizures, vision problems, and dementia that their ailments — collectively dubbed “chemo brain” — resulted from treatment-related fatigue, depression, and anxiety.

While more and more scientists agree that chemotherapy drugs may negatively affect brain function in certain cancer patients, how this occurs is largely unknown. Now, researchers at the University of Rochester and Harvard Medical School have provided what could be the first evidence of a biological cause of the lingering effects of chemo brain.

Reporting in a recent issue of Journal of Biology, researcher Mark Noble, PhD, director of the University of Rochester Stem Cell and Regenerative Medicine Institute, links the drug 5-fluorouracil (5-FU) to extensive damage among specific groups of cells in the central nervous system; 5-FU is a widely used chemotherapy drug that has been a part of America’s cancer-killing arsenal for more than 40 years. It is prescribed for those with a variety of cancers, including breast, stomach, colon, and pancreatic cancer.

For the study, Noble and colleagues performed tests on mice and in test tubes with varying doses of the cancer drug. The doses were comparable to those given to cancer patients.

After months of exposure, the drug caused considerable damage to central nervous system cells called oligodendrocytes and the dividing stem cells from which they developed.

The findings suggest that the drug directly targets oligodendrocytes. Oligodendrocytes produce myelin, the fatty substance that helps insulate and protect nerve-conducting fibers. Without adequate myelin, normal nerve signaling is disrupted.

“Our studies demonstrate that systemic treatment with 5-FU is associated with both acute and delayed toxicity reactions, outcomes that are of particular concern because of the use of this agent in the treatment of many cancers,” Noble writes.

The team’s findings parallel observations of earlier studies involving cancer survivors with cognitive difficulties in which brain scans revealed a loss of myelination.

“It is clear that, in some patients, chemotherapy appears to trigger a degenerative condition in the central nervous system,” Noble says in a news release.  “Because these treatments will clearly remain the standard of care for many years to come, it is critical that we understand their precise impact on the central nervous system, and then use this knowledge as the basis for discovering means of preventing such side effects.”

Originally Posted on Wednesday, May 21, 2008    

Longtime Massachusetts Democrat is likely diagnosed with glioblastoma multiforme, a cancer in which there has been no significant improvement in survival in 30 years

Senator Edward M. Kennedy, 76, the longtime Massachusetts Democrat has been diagnosed with a malignant brain tumor.  Preliminary results from the biopsy revealed a malignant glioma.  The most common type of malignant glioma is called glioblastoma multiforme or “GBM.”

As reported in the New York Times published on May 21, 2008, Kennedy’s doctors have stated that “the usual course of treatment includes combinations of various forms of radiation and chemotherapy” and that “decisions regarding the best course of treatment for Senator Kennedy will be determined after further testing and analysis.”

According to published medical information, survival for patients with GBM is typically about 12 months.  Our prayers go out to Mr. Kennedy and his family.  Perhaps this unfortunate diagnosis may initiate a more global discussion on the continued lack of progress in treating malignant brain cancers.

No Progress in 30 Years

Despite the occasional pronouncements of “breakthroughs” the improvement in survival for GBM is practically zero over the last 30 years.  According to The Central Brain Tumor Registry of the United States, the two year Relative Survival Rate for GBM from 1973-1994 was 8.8%.  It was 8.7% for the period 1973-2002.  The five year Relative Survival Rate for GBM from 1973-1994 was 3.4%.  It was 3.3% for the period 1973-2002.  And the ten year rate for GBM from 1973-1994 and 1973-2002 was 2.3%.  After nearly 30 years there has been essentially no improvement in survival despite the millions of dollars spent on research and treatment.

Targeted Therapies – “Disappointing”

In the last several years there has been research in the area of targeted therapies like vascular endothelial growth factor (VEGF).  VEGF is an important signaling protein involved in the growth of blood vessels.  A theory called “anti-angiogenesis” is based on the concept that it may be possible to starve a tumor by stopping the growth of new blood vessels that feed the cancer.  While the theory is promising, in clinical practice with malignant gliomas the results to date have been disappointing.  According to a report published in March of this year in the journal Expert Opinion on Emerging Drugs, “Experience with targeted therapeutics for malignant glioma has been to date disappointing. These agents are generally well tolerated, but activity is limited.”

Unconventional Thinking – Poly MVA and Antineoplastons

Has there been any progress whatsoever in treating GBM and other malignant gliomas?  There has been some intriguing results, but they have not come from leading medical centers or drug companies.

Poly MVA

Poly MVA was invented by Dr. Merrill Garnett, a biochemist.  It is a dietary supplement based on the nontoxic chemotherapeutic lipoic acid-palladium complex (LAPd).  LAPd is a liquid crystal that works in cancer cells by transferring excess electrons from membrane fatty acids to DNA via the mitochondria.  It has been used as a dietary supplement by thousands of cancer patients.  According to anecdotal reports published on websites some patients who have survived glioblastoma and other malignant brain tumors believe their use of this dietary supplement may have been partly responsible.  Are mainstream oncologists intrigued by these results?  No.  Nearly all conventional oncologists reject this dietary supplement as a potential therapeutic modality.

Dr. Burzynski’s Antineplastons

According to a National Cancer Institute Factsheet:

“Antineoplastons are a group of synthetic compounds that were originally isolated from human blood and urine by Stanislaw Burzynski, M.D., Ph.D., in Houston, Texas. Dr. Burzynski has used antineoplastons to treat patients with a variety of cancers. In 1991, the National Cancer Institute (NCI) conducted a review to evaluate the clinical responses in a group of patients treated with antineoplastons at the Burzynski Research Institute in Houston.  The medical records of seven brain tumor patients who were thought to have benefited from treatment with antineoplastons were reviewed by NCI. This did not constitute a clinical trial but, rather, was a retrospective review of medical records, called a “best case series.” The reviewers of this series found evidence of antitumor activity, and NCI proposed that formal clinical trials be conducted to further evaluate the response rate and toxicity of antineoplastons in adults with advanced brain tumors.” 

These clinical trials never occurred.  Nonetheless, the Burzynski Research Institute is conducting FDA approved clinical trials using antineoplastons for a variety of cancers.  Results in brain tumor continue to be encouraging. In a March 2006 study published in the journal Integrative Cancer Therapies, four patients with glioblastoma were treated with antineoplastons.  One of the four patients had survived (at the time of publication) more than 5 years.  The results of only four patients may not be statistically valid, but if they are validated with further results it would suggest a 5-year survival of 25% compared to 3.3% with conventional therapies. 

Are mainstream oncologists intrigued by the potential therapeutic value of antineoplastons?  No.  Nearly all oncologists reject this modality.

Conventional Oncologists Reject Unorthodox Approaches

Why do oncologists reject any potential therapy, like lipoic acid-palladium complex and Burzynski’s antineoplastons, that was not created by a major medical center or a pharmaceutical company?  There are many reasons possibly including:

1) These approaches represent fundamental shifts in thinking about how to treat brain cancer.  To understand how Poly MVA or antineoplastons may work in the human body requires a different understanding of the biochemistry of cancer and the role of our immune systems.
 
2) The experience and skills of mainstream oncologists are dictated to a large degree by what they leaned in medical school and the studies they have been involved in subsequent to their graduation.  These studies are often financed or partly financed by drug companies who focus on therapies that are easily patentable.  Chemotherapy fits this model. 

3) There may be an emotional investment.  In the case of malignant gliomas many oncologists have seen hundreds of their patients pass away.  To admit that they, the doctor, have been on the wrong path all along, maybe too tough to bear.

Whatever the reasons, the result has been no dramatic improvement in survival with GBM over decades.  Because patients who are the ultimate consumer of these therapies generally put their lives in their doctor’s hands, there is no “market demand” for thinking outside the box.  Because drug companies finance the lion’s share of research in this area, corporations continue to decide what is developed and what is not based on their own financial incentives.  Because doctors get paid regardless of whether their patients live or die there is no burning incentive for physicians to break from the status quo.  What all this means, unfortunately, is that the lack of progress will most likely continue.

But, there is hope for Mr. Kennedy and other patients diagnosed with malignant gliomas.  If you are willing to be your own best advocate and expand your universe of possible treatment modalities outside of chemo, radiation, and surgery, you may be able to blaze your own path to health as others have done.
 
Original story can be viewed at http://www.cancermonthly.com/iNP/view.asp?ID=216

Increased use of dietary supplements in the

• Supplementing with calcium-vitamin D could help seniors avoid hospitalization for hip fractures, as well as prolonged stays in nursing facilities. Five-year savings: $16.1 billion.

• If 25 percent of the 44 million American women of childbearing age not currently taking folic acid began taking 400 mcg daily, neural tube defects could be prevented in 3,000 babies. Five-year savings: $1.4 billion.

• Elderly people taking 1800 mg of omega-3 fatty acids per day could help them avoid approximately 374,301 hospitalizations for coronary heart disease. Five-year savings: $3.2 billion.

• About 191,000 people with age-related macular degeneration could prevent loss of vision and the dependent care related to it by taking 6-10 mg of lutein-zeaxanthin every day. Five-year savings: $3.6 billion.

Despite the fact that the Journal of the American Medical Association published a review advocating that every adult take a multi-vitamin to reduce the risk of disease, still a significant percentage of doctors seem to oppose nutritional supplements, both directly and through nondisclosure.

This leads many people to wonder…….are dietary supplements safe?

Frankly, we at AMARC understand in theory some of the reasons doctors are concerned, and while we may not agree in practice, we think you too should understand before you start taking a supplement. So here are some of the common reasons doctors hesitate to encourage nutritional supplements:

- Doctors worry that patients will use nutritional supplements as a substitute for regular medical care, a good diet, or other important health habits. These are real concerns. Everyone should see a practitioner regularly. And no pill can replace a good diet and exercise; we encourage you to do your own homework on the benefits of both. Nutritional supplements are a good health habit, too — just don’t use them as a crutch for bad health habits.

- Doctors have heard scare stories about extreme dosages, drug interactions and poor quality. These are real concerns too. Some patients are cavalier about extreme dosages. Several herbs have interactions with drugs that aren’t yet well understood. Toxins and even drugs have been found in supplements from second-rate manufacturers. But these problems are easily dealt with. Make sure you are taking a pharmaceutical–grade and researched supplement, and tell your healthcare providers about any supplements you are taking. And again, research particular supplements, their benefits, potential interactions, etc. Make informed decisions about your health instead of merely relying on your practitioner or others to tell you what is right for you.

- Doctors are skeptical about claims made for nutritional supplements. There are sometimes ridiculous claims made for bogus products such as some weight loss pills. It’s just too bad that many doctors associate legitimate products with these bad practices. (Noteworthy: In comparison, and ironically, the pharmaceutical industry has had many instances of bad products and falsified data just to make a profit.)

- Most medical schools fail in nutritional instruction. Doctors tend to underestimate the importance of nutrition in general. No wonder: most doctors receive a mere few hours’ nutritional training in med school, and lack adequate time to keep up on the latest research. Their practice is based on disease screening, not prevention, with an emphasis on drug therapies, not nutrition. Such doctors naturally think that nutritional supplements have little therapeutic value. This is changing, especially among recent medical school graduates. Even oncologists at leading cancer institutes are advocating vitamin supplements for their patients. But it will take years before nutrition is a part of most doctors’ methods.

Choosing the right vitamin and supplements is vital but it can be confusing. There are conflicting claims about nutrients and dosages. Because of weak regulations, the labels on products are incomplete and misleading. Science in this area is rapidly evolving. And the number of choices at the vitamin store can be overwhelming. How do you decide what to do? Here’s our guide to finding the best nutritional supplements.

Understanding the essential nutrients your body needs

There is sometimes a danger to you in the way nutritional supplements are marketed. Some of those marketers would have you believe there’s a different product for every problem — the antioxidant vitamin, the vitamin B-complex, mood boosters, energy vitamins, herbal nutritional supplements — the list of vitamins and herbs goes on and on. Maybe each one of those supplements does have its own role. But there is often much confusion, and married with a sometimes lack of education, that concerns us.

The interaction of certain supplements is unknown. And this approach sometimes ignores the basic wisdom of your body: your body will naturally seek to balance itself if you give it the right foundation of nutritional support. That’s why we encourage each and every person to research diet and supplements in order to increase their knowledge of the roles and interactions of each, separately and in conjunction with each other.

This approach is based on how our bodies really work. Every day our bodies need certain raw materials to support the vast biological mechanisms that fuel our physical and mental activity, support our immune defenses, and regenerate skin, muscle, blood, tissue, and bone. This fuel comes in the form of macronutrients — protein, carbohydrates, and fat — and micronutrients: vitamins and minerals (which fall into four more categories: water-soluble vitamins, fat-soluble vitamins, major minerals, and trace minerals).

Some of these nutrients are familiar from the labels on food and vitamin packages. Fat-soluble vitamins like A and D have the capacity to be stored in our bodies. Others, like vitamin C and some of the Bs, are water-soluble, which means they are eliminated in our urine and sweat and must be replenished regularly. We also require essential fatty acids, which are often overlooked.

Our bodies need a ready supply of all these nutrients on hand to function properly. They serve as anti-oxidants, chelating heavy metals and attracting free radicals to detoxify our systems. Some help fight infection, clot blood, heal wounds, and strengthen bones. Others contribute to hormone production, convert food into energy and support healthy cell regeneration. Adequate levels of EFA’s help prevent inflammation and contribute to stable cholesterol levels which affect hormonal balance.

In this way, every essential nutrient has a vital task in our bodies. Moreover, each one usually works in concert with one or several others. For example, vitamin E works more efficiently in the presence of vitamin C. Calcium has a much higher absorption rate when taken with magnesium. And zinc may assist a variety of other nutrients to bolster the immune system. It’s almost impossible to isolate the effect of each vitamin — just as it’s almost impossible to isolate a single vitamin deficiency as the cause of any given symptom. For example, vitamin B deficiency can result in symptoms resembling vitamin D deficiency, and so on. That’s why the best vitamin supplements are well-rounded — to ensure that we benefit from the synergistic effect of all the nutrients working together. There are certain situations that are very specific but they are few and far between when we speak of general health and well being.

Bioavailability: the acid test of a multivitamin

Not everything we swallow is absorbed by our bodies. Every nutrient has to survive the chemicals and turmoil of the digestive system, be absorbed through the intestinal wall, and get past the liver to reach the bloodstream. Not everything we swallow is absorbed by our bodies. Every nutrient has to survive the chemicals and turmoil of the digestive system, be absorbed through the intestinal wall, and get past the liver to reach the bloodstream.

Scientists use the term bioavailability to measure what’s absorbed by the body versus what’s wasted. Unfortunately, in many ordinary multivitamins a great deal of the nutrients do not benefit the body at all — because they’re not bioavailable. The scandal is that you would never know that by reading their labels. The label only shows what’s in the multivitamin; it gives you no idea how much is bioavailable.

A basic problem is getting past the digestive system. In a pharmaceutical–grade vitamin supplement, many of the nutrients are chelated, or tied to another molecule which acts as an escort until it reaches the bloodstream. Both universities and private companies have developed and patented such chelated compounds. Because they are relatively expensive to license they are rarely seen in ordinary multivitamins.

A second problem is processing methods. Many ordinary multivitamins use inexpensive processes and rely on additives. These processes can destroy the nutritional value of the supplements or render them unrecognizable to the body.

This is why the half of Americans who take multivitamins is not noticeably healthier than the half that doesn’t. Many of them are taking ordinary vitamins that lack the range of nutrients their bodies need or low-price or discount vitamins that are less effective due to their processing methods and the limited bioavailability of their nutrients.

At AMARC, we’re concerned that sometimes the labeling regulations can be misleading for consumers. But bioavailability is a relatively new area of nutritional science that is evolving rapidly, and we don’t expect to see standardized measurements of bioavailability of nutritional supplements for many years. In the meantime, you have to rely on the quality of the research and the manufacturing methods that are behind your vitamin supplements when choosing a multivitamin.

The controversy over RDA’s and vitamin dosages

A few of us may remember growing up when rickets and scurvy were commonplace. These diseases led to the development during WWII of the Required Daily Allowances (RDA’s) for vitamins and minerals, and the familiar Food Pyramid as an eating plan. Cereals and white flour were fortified with basic nutrients. Now “deficiency diseases” like rickets and scurvy are common only in third world countries.

Unfortunately the RDA’s are not a good guide for consumers who want to use nutritional supplements to support optimal health and prevent disease. That’s because RDA’s were meant to be bare minimums, not optimal dosages. And while nutritional science has made stunning progress in the last 60 years, there is no consensus yet about optimal dosages for multivitamins or multi-minerals, add to the each persons own unique chemistry and you can see why it might be difficult.

A good example is the new information surfacing about vitamin D. Not only is it important for calcium absorption, it also appears to help in weight loss, strengthen bone, and protect against cancer and depression. Our bodies seem designed for large amounts of vitamin D, as we create 20,000 IU of vitamin D in just 20 minutes of sun exposure. Yet the RDA for vitamin D is only one-tenth of that — for example, 200 IU for a woman age 31–50.

What we do know today is that significantly higher doses of vitamins and minerals are needed for optimal health than are recommended in the RDA’s. A study in the Journal of the American Medical Association, for example, established therapeutic dosages many times higher than the RDA’s. What’s needed is long-term study of the effects of different dosages, plus a better understanding of how nutritional supplements might be personalized to each individual’s needs. In the meantime, our approach is to recommend a conservative but therapeutic dose based on the latest nutritional science.

The Institute of Medicine, which advises the FDA, has undertaken a complete revision of RDA’s based on the latest findings. These new Daily Reference Intakes (DRI’s) will be based on RDA’s but reflect our changing need for nutrients as we age and provide for a broader range of dosages. We hope it will rectify some of the larger gaps left in our nutrition by the current guidelines. It will use updated RDA’s as minimums and over time establish upper limits on what is recommended. Of course, that process will take many years.

So what is the best multivitamin

We have strong views about the qualities of the best multivitamin/supplement. Here is how we would describe the perfect formulation:

-Complete. Based on the latest nutritional science, we need at least 30 vitamins and minerals, plus a rich essential fatty acid formula (i.e., omega–3 and omega–6 fatty acids).

-Bioavailable. The nutrient forms must be the most bioavailable. And of course it must meet USP standards for solubility.

-Natural. No artificial preservatives, dyes, allergens or other contaminants. The fatty acid formula (derived from marine lipids) must be certified to be free of mercury and lead.

Reliable. We’ve been waiting over 10 years for the FDA to issue manufacturing standards for nutritional supplements. In the meantime, there are several sets of standards that have earned international recognition. The manufacturer must meet at least one of these recognized standards.

-Laboratory tested. As is true for pharmaceutical drugs, every production batch of a nutritional supplement must be tested in a laboratory (i.e., “standardized”) to ensure that it contains exactly what is on its label.

-Makes a difference. You are the final test. If the nutritional supplement doesn’t improve your health and or help to make you feel better within the first 30-60 days, (depending on your concerns of course) try another formula. It may not resolve all your symptoms in that time, but you should feel improvement.

In short, we don’t care which or whose multivitamin/supplement you take, as long as it’s a good one and it works for you. You will be amazed at the difference it can make. Patient after patient — even the most skeptical — cannot say enough about how good Poly-MVA and our other supplements make them feel. And that is what abundant nutrition is all about — feeling fit, energized, and living well.

At AMARC, we don’t think it is enough just to live longer. We want you to live well and enjoy every minute in the best of health. We know this can be possible with the help of good dietary choices and beneficial supplements. So really, the only thing we all have to lose by not following this advice is our health — and who can afford that?