Nutrition and Cancer – Wellness and the Immune System
About the Lecture
Within the past few years a new understanding of the value of the microbiome underscores the value of dietary fiber. Prebiotics are found in fiber rich plant foods containing high molecular weight polysaccharides. Prebiotics provide nutrients for the microbes which then provide us with an active immune system that serves us both. This is a new world of Symbiotology or how life forms live synergistically with us. When this ecosystem is out of balance either because we don’t provide the right food (dietary fiber rich beans, vegetables and fruit) or because of damage to the cells such as a result of cancer treatment or broad spectrum antibiotic use then we need to address this.
Research into the microbiota or population of microbes that reside in the gastrointestinal tract using a specific strain of mice that lack the gene ATM has uncovered an important role in protection against genetic instability and DNA damage. These mice (Atm -/-) were protected from developing lymphoma and lived longer when housed in an environment that supported a healthier microbiome. This research opens the door for a deeper understanding of the link between diet, intestinal health and immune associated cancers.
Carolyn Katzin, MS, CNS, Oncology Specialist at the Simms/Mann – UCLA Center for Integrative Oncology, and Robert Schiestl, Ph.D., Professor of Pathology and Environmental Health and Radiation Oncology discuss nutrition and cancer with particular emphasis on how the “microbiome of the gut” may be a key factor in protection against cancer or in the development of cancer. Recent understandings of the microbiome (the healthy bacteria) of the gut appear to play a significant role in immune function and recent research in mice suggests the microbiome plays a role in immune regulated cancer such as lymphoma. While this research is in its early stages it has the potential to provide greater evidence for the value of food as medicine and prevention of cancer. In addition to some of this new science, specific information is presented on nutrition in cancer and ways to enhance health—including food and supplements strategies that protect against damage to cells and enhance well-being before, during and after cancer treatment.
Dr. Schiestl received his Ph.D. in Biology and Genetics from the University of Vienna, Austria, in 1983. He is currently a Professor of Pathology, Environmental Health and Radiation Oncology. Previously, he served as Assistant and Associate Professor in the Department of Cancer Cell Biology at the Harvard School of Public Health. He is Director of the UCLA Center for Environmental Genomics and a current member of the UCLA Cancer Center, UCLA Center of Occupational and Environmental Health, UCLA Interdepartmental Program in Molecular Toxicology (Faculty Advisory Committee), and UCLA ACCESS Graduate Program steering committee. He is also a member of the Planning Committee for the Environmental Mutagen Society meeting as well as Chair. He spoke at the Symposium on “Genetic Instability” which was held on March 11-15, 2003 in Miami Beach, Florida.
Carolyn F. Katzin, MS, CNS, MNT has 25 years of experience working in the field of oncology and nutrition. She received a Master of Science in Public Health in Nutritional Science from UCLA. She has extensive knowledge and experience counseling patients around wellness, nutrition, and physical activity as well as a wonderful understanding of the complex needs of patients with cancer. She has a long history of providing consultative educational sessions with patients on nutrition, supplements and how to improve one’s wellness while getting cancer treatment and beyond. She has also worked with individuals in developing healthy diet and lifestyle for cancer prevention. She is caring and compassionate in her care of patients and their families.
Carolyn Katzin has written two books, The Cancer Nutrition Handbook and The Everything Cancer-Fighting Cookbook. She has been a member of the American Cancer Society National Nutrition, Physical Activity and Cancer Control Committee and co-Chair of the California Division Board of Directors Nominating and Development Committee.
This is a summary of a lecture presented on April 8, 2014
At the Simms Mann Center, we help patients and their families optimize their wellness and address the challenges throughout the continuum of cancer care. As an integrative oncology specialist, I focus on nutrition and wellness as this is something positive and practical to address.
What is cancer and what does nutrition have to do with it? Cancer is a disease associated with over 100 different conditions according to the National Cancer Institute. These are malignant changes in DNA or cellular instructions either in the nucleus or mitochondria resulting in altered cell functioning. In 2000, Weinberg and Hanahan described several hallmark characteristics of cancer. They are: (1) cancer cells stimulate their own growth; (2) unlike normal cells, they resist inhibitory signals that might otherwise stop their growth; (3) they resist their own programmed cell death, called apoptosis; (4) they stimulate the growth of blood vessels to supply nutrients to tumors, called angiogenesis; (5) they can multiply forever; and (6) they can metastasize or invade local tissue and spread to distant sites.
In other words, these are cells that manage to evade detection by the body’s usual immune surveillance systems, grow in an uncontrollable manner, and derive their own energy supply as they grow. Solid tumors include carcinomas and sarcomas; cancers of blood and bone marrow origin include leukemias, lymphomas and myelomas and tumors can also originate in the central nervous system. From longitudinal large-scale observational studies, such as the Harvard Health Professionals Study, we have learned that more than two-thirds of all cancers are associated with diet and lifestyle and that at least one-third are linked to obesity and poor diet.
How do health and wellness affect prevention and detection of such malignancies? At its inception in 1946, the World Health Organization (WHO) defined health as a “state of complete physical, mental and social well-being and not merely the absence of disease or infirmity”. More recently, UC Davis has provided a concept of wellness as “an active process of becoming aware of and making choices towards a healthy and fulfilling life”. There are seven dimensions of wellness: social, occupational, physical, intellectual, emotional, spiritual and environmental wellness. It is the latter that is most relevant to our discussion of immunity and cancer as a state of wellbeing is when immune functioning is optimal.
Immune functioning is how each individual interfaces with the environment using a broadly diffused network of interrelating cells. Immune cells include white cells or leukocytes comprising lymphocytes (B cells, T cells and Natural Kill cells) and phagocytes that are organized into clumps or nodes of lymphoid tissue and organs. Organs of the immune system include thymus, spleen and bone marrow. Nodes of lymphatic tissue in the gastrointestinal tract are called Peyer’s patches or GALT. These immune cells comprise about 60% of all immune cells in the body emphasizing how important this interface with ingested foods, beverages, and medications. An immune response often includes inflammation, which is a recognized risk factor for carcinogenesis.
In 2007, the National Institute of Health launched the Human Microbiome Project. The microbiome can be imagined as an organ with its own ecosystem. Genomic data from human and microbial sources may also be described as a Metagenome. The first phase of the project used newly discovered sequencing methods, bioinformatics and culturing techniques to identify and characterize human microbial communities or “who’s there.” In addition to this project, there was a parallel MetaHIT, or Metagenomics of the Human Intestinal Tract, a project financed by the European Commission. These studies have shown that there are over 10,000 microbial species that occupy our human body, comprising 1-3% of our total mass. We have ten times as many microbial cells as our own cells, with 100 times as much DNA. In other words, we are outnumbered!
During the next phase of the Microbiome Project, researchers will gather an integrated dataset of the properties of the microbiome and associated diseases, essentially to find out “what are they doing?” Research gained from this study has led to a new concept, called Human Microbiome Therapeutics, on how to target dysbiosis, or microbial changes that are pathogenic or harmful, and to rebalance towards wellness. One example of a therapy that has arisen from this research is Fecal Microbial Transplant (FMT), a therapy that uses healthy donor fecal samples to reverse infection with Clostridium difficile. The NAP1 strain of C.difficile is a health epidemic affecting more people than MRSA; it accounted for 300,000 hospitalizations and 20,000 deaths in 2004. FMT is approved in the United Kingdom and Canada as a second-line option for treating infected patients with dramatic and rapid success. Currently, the FDA considers fecal transplant therapy as experimental. Despite its success in the UK and Canada, it can only be used for patients with drug-resistant C.difficile as long as donors are properly screened, and patients are fully informed that this is an experimental therapy. All other applications are required to follow investigational new drug procedures (IND).
Antibiotics are agents that destroy pathogenic bacteria, either directly by killing them or by slowing their growth. The modern antibiotic era dates from the mid-20th century with the discovery of sulfa drugs in 1935 and penicillin in 1941. Today, there are over 160 varieties of antibiotics; however, removing pathogenic bacteria may not be sufficient for health. Researchers are just beginning to understand the delicate balance between beneficial bacteria, other microbes, and more harmful ones. Every one of us has a unique microbiome that has been determined and shaped by (1) our birth (a vaginal birth exposes an infant to a broader spectrum of microbes compared to a C-section birth) and (2) by early exposure to antigens, which varies from breast-fed to formula-fed infants. In addition, we have seen that both fraternal and identical twins have closer microbiomes than other siblings, indicating their shared environmental exposures result in having similar microbiomes. Genes also play a role, and research has shown that mothers and daughters have closer microbiomes than mothers and sons. We also know that extreme diet changes may affect the balance of gut microbiota; however, we are not sure how long such changes persist. For example, a recent study at Harvard showed that switching from a high animal protein diet to a vegan one resulted in a change in the number of bile tolerant Bacteroides and caused a rise in Firmicutes, a kind of bacteria that metabolizes plant polysaccharides. Dietary fiber provides a favorable environment for Firmicutes to grow and flourish.
Taking probiotics as supplements may help rebalance your individual microbiome after taking antibiotics or when traveling. It is also important to make sure you are eating a high amount of dietary fiber to maintain your improved probiotic numbers and activity. There are several things to look for when you purchase a probiotic supplement. First, look for accurate labeling. Then you want to know the number of colony forming units (CFUs), the number of viable microbial cells. Some companies, however, count both dead and alive microbes in their total. You will want to know the number of viable live cells when you buy it. Unfortunately, many companies don’t clarify when CFUs are assessed or when the product was manufactured, which means a number of the CFUs listed may include dead or nonviable cells. It doesn’t help to take 5 billion dead cells!
There are several products that contain patented strains of probiotics. Culturelle ® has a strain of Lactobacillus called LactobacillusGG that has been selected for its anti-inflammatory properties. Align ®, licensed by Proctor & Gamble, has a strain of Bifidus infantii 35624 called Bifantis ®, known to assist in reducing infant diarrhea. Dupont has licensed a combination of strains called HOWARU ® for use in several beverages, foods and supplements around the world. Probiotic supplements provide more cells than typical fermented foods; however, there is still no consensus on whether it is number or type of cells that is more important to promote overall wellness. During chemotherapy, one of these patented strains may be effective in reducing the gastrointestinal distress often associated with such treatment. Researchers are also finding new applications for probiotic use, such as include mood management; a recent French study showed a reduction in measured anxiety when healthy humans took an oral probiotic in the form of a patented strain of Bifidus longum for 30 days.
Lactic acid bacteria (LAB) and Bifidobacteria are the two main groups of probiotics. LAB are mostly anaerobic and are used in fermentation processes as they are acid tolerant. Bifidobacteria are Gram-positive anaerobes capable of fermenting oligosaccharides to form lactic and acetic acids using a unique fructose-6-phosphate ketolase pathway. Bifidobacteria are thought to communicate with the cells lining the intestinal tract and may ameliorate inflammation in this way.
In the new era of human microbiota science, several new terms are gaining recognition:
- Prebiotics are non-digestible substances that provide a beneficial physiological effect for the host by selectively stimulating the favorable growth or activity of a limited number of indigenous bacteria. Prebiotics are fermentable ingredients added to cookies, breakfast cereals, protein bars, chocolate, spreads and dairy products to encourage probiotic activity.
- Probiotics are living microorganisms that, when administered in adequate amounts, confer a health benefit on the host. Probiotics are the antithesis of antibiotics.
- Synbiotics are examples of foods that contain both prebiotics and probiotics and are found in fermented foods. One-third of all food in the world involves a fermentation stage, and these foods provide valuable and necessary pre-and probiotics. Examples include bread, cheese, beer, wine, yogurt, tempeh, tofu, Natto, miso, sauerkraut and kimchi. Marmite is a fermented yeast extract favored in England and a similar product in Australia is Vegemite. Both stimulate umami taste buds.
Oligofructose, inulin, galacto-oligosaccharides and lactulose are ingredients that support probiotic activity and may be described as prebiotics or synbiotics if involving more than one probiotic.
Fermentation is valuable in the food and beverage industry, where it is a carefully structured chemical process. However, when fermentation occurs inside our own digestive system, it can produce unwanted gas and discomfort. Irritable Bowel Syndrome (IBS) is a condition that can be exacerbated by foods that contain fermentable prebiotics. FODMAP’s (Fermentable, Oligo, Di-Mono-saccharides, And Polyols) may cause bloating and discomfort. Many people find eliminating or reducing these foods help with their IBS symptoms.
We are learning so much about the contribution of each microbiome, and we have identified nutrients that support health and immunity. Examples include:
- Omega-3 fatty acids, such as ALA, that is found in grass. Grass fed beef is more likely to have fatty tissue that has omega-3 fats. Corn disturbs the normal bacterial balance in the rumens; this means corn-fed beef is less healthy for you than grass-fed beef.
- Fat-soluble vitamins A, D, E and K are important for supporting healthy microbiota and immune functioning.
- Trace elements zinc and selenium are found in many plant foods that provide prebiotics such as nuts and seeds. Zinc plays an important role in cancer prevention as regulatory regions of the human genome called zinc fingers are associated with this trace element. Good food sources of zinc include lean meat, fish, nuts, and seeds. Oysters are an especially rich sources of zinc.
The microbiome is sometimes called “the forgotten organ,” but it plays a very crucial role in wellness and immune health. The Metagenome is a composite term used to describe our genome and microbiome, and it varies from person to person. The main phyla of microbes that predominate are Bacteroidetes, Firmicutes, and Actinobacteria. When the phyla of microbes becomes disordered—either as a result of infection, inflammation or from a loss of intestinal barrier integrity—we call that dysbiosis. Synbiosis is the term we use to describe how these different microbial populations live in health together; they benefit from the prebiotics we eat from plant-based foods, and they support our wellness in a dynamic manner.
In 2005, two Australian researchers, Barry Marshall and Robin Warren, were awarded the Nobel Prize in Physiology or Medicine for their discovery of the role of the bacteria Helicobacter pylori, which causes inflammation and infection which results in stomach ulcers. Whether Pylori results in ulcer formation or is benign is determined by individual factors such as whether or not you are genetically susceptible, whether or not you already have antigens present in your gastrointestinal tract lumen, environmental triggers, and your immune response.
Dr. Robert Schiestl has developed a strain of mice that have errors, or deletions, in their DNA; having errors or damages to DNA is a known factor in how cancer develops. These special mice are missing a piece of a gene that codes for color and is detected not only on their fur, but also in their retinal pigment epithelium, which provides researchers with a way to quantifiably assess the effect of a carcinogen in the mice. Research using these specially developed mice has shown them to be sensitive to their environment; they have been reared germ-free, in sterile environments and laboratories at Harvard and UCLA. Mice that have been reared in a sterile or germ-free environment have distinctive microbiota, for example, Helicobacteraceae Spp., opportunistic pathogens that include Pylori.
Dr. Schietl’s research has recently evaluated the rate of onset of lymphoma in mice raised in a sterile environment compared with those raised in a conventional laboratory environment. Even though his special strain of mice have DNA deletions that raises their risk of lymphoma, he found that he could reduce their risk of DNA damage by adding a single strain of bacteria Lactobacillus johnsonii 456 to their diet. Like all species of the Lactobacillus genus, Lactobacillus johnsonii 456 is an anaerobic, Gram-positive bacterium that lives in the human intestine. Adding this simple probiotic bacteria to the diet of mice modified their circulating blood white cells, reduced the number of natural killer cells in their peripheral blood, reduced their percentage of T cells and NK cells in the spleen, and significantly modified the infiltration of T cells in the liver. These changes reduced the number of inflammatory cytokines IL-1beta, IL-12 and IFN-gamma in both their blood and liver and increased the cytokines that modify inflammation, including IL-4, IL-10, and TGF-beta, in their liver. Since cancer is one of a variety of conditions that is associated with chronic inflammation, Dr. Shiestl’s research supports the hypothesis that some specific strains of common bacteria that inhabit the intestinal tract of mammals may have profound positive effects on the inflammatory aspect of an immune response. In the most basic terms, feeding this basic probiotic to mice that were predisposed to develop lymphoma, decreased their risk of developing this cancer! Dr. Schiestl’s research showed it was possible to modify and reduce genetic instability. Adding this probiotic to their diet reduced the risk of these mice developing lymphoma.
This research is certainly exciting and shows the potential for potential for modifying our internal microbiome environment with diet and perhaps specific beneficial strains of probiotics. It provides scientific proof that your diet and probiotic use has an exciting potential for preventing and managing inflammation, which affects us all and is now believed to be the cause of many diseases.
Studying the microbiome is very new, but the research is very exciting and very applicable to our lives. We can make simple diet modifications to enhance our health based on this new research—add some dietary fiber to each meal (e.g., add some ground chia or hemp seeds to a breakfast smoothie or oatmeal, include beans or brown rice at main meals) and include servings of fermented foods in your diet (e.g., kimchi, sauerkraut, yogurt or other fermented foods).