Society for Glycobiology
Transcription
Society for Glycobiology
TABLE OF CONTENTS Copies of Covers and Excerpts from: Introduction 1. Harper’s Biochemistry 25th edition, a Lange medical textbook 2. Glycobiology, Official Journal of the Society for Glycobiology Oxford University Press 3. Acta Anatomica, International Journal of Anatomy, Embryology and Cell Biology, 1998 Special Issue devoted to Glycosciences 4. Scientific American, A Cellular Zip Code, Nobel Prizes for 1999, January 2000 issue 5. Health Professionals Medical Education Materials, presented at the Comprehensive Cancer Conference 2000 6. Science, the weekly publication of the American Association for the Advancement of Science, special issue devoted entirely to Carbohydrates and Glycobiology, March 23, 2001 7. Physician’s Desk Reference (PDR) for Nonprescription Drugs and dietary Supplements, 2001, entries on Glyconutritional products from Mannatech 8. Sugars That Heal: The New Healing Science of Glyconutrients by Emil Mondoa, M.D., 2001 9. Scientific American, Changing Cancer Cells' Surface Sugars Can Inhibit Tumor Growth January 22, 2002 and Sweet Medicine, Building Better Drugs from Sugars, July 2002 issue 10. Proceedings, Of The Fisher Institute for Medical Research glucose galactose mannose fucose xylose N-acetylglucosamine N-acetylgalactosamine N-acetylneuraminic acid These 8 "essential sugars" Are…mannose, glucose, galactose, xylose, fucose (not fructose), Nacetylglucosamine, Nacetylgalactosamine, and N-acetylneuraminic acid. Most people only recognize two of these glucose and galactose. Introduction: Cutting-edge research in the rapidly evolving science of glyconutrients has broken the sugar code of biological information. As with any new scientific information, the progression of information begins in basic scientific research and finds its way to journal, textbooks and other books and articles. Eventually information that started out as arcane and esoteric research known only to a few finds its way to the ordinary public. That progression of information has happened in the field of glycobiology. In test after test, conducted at leading institutes around the world, scientific information reveals that the essential sugars yield long-term, fundamental benefits. They have been shown to: • Lower cholesterol • Increase lean muscle mass • Decrease body fat • Accelerate wound healing • Ease allergy symptoms • Allay autoimmune diseases such as arthritis, psoriasis, and diabetes • Help the body fight off infections of all kinds including bacterial infections as well as many viral infections from the common cold to the flu, from herpes to HIV • Assist the body to overcome the debilitating symptoms of chronic fatigue syndrome, fibromyalgia and Gulf War syndrome • Mitigate the toxic effects of radiation and chemotherapy in cancer patients while at the same time augmenting their cancer killing effects in prolonged survival and improved quality of life But beyond just information, even compelling information that saccharides can positively effect such a list of challenges and more, in the end that information must be realized and actualized. We ask ourselves, well, what does this mean for me? Sounds wonderful, but where are these eight essential saccharides, and how can I get them? Mannatech, Inc. has created the product that includes all eight of the essential sugars. Cutting-edge laboratory research has been realized in Ambrotose. The 1996 and subsequent editions of Harper’s Biochemistry, a widely used medical text book, devoted an entire chapter (Chapter 56) to Glycoproteins and on page 677 included a table of the eight principal sugars found in human glycoproteins. GLYCOBIOLOGY Official Journal of the Society for Glycobiology Oxford University Press Glycobiology About the Journal Established as the leading journal in the field, Glycobiology provides a unique forum dedicated to research into the structure and function of glycoconjugates (including glycoproteins, glycolipids, proteoglycans or free complex saccharides) or on any aspect of proteins that specifically interact with glycoconjugates (e.g. lectins, glycotransferases, glycosidases). Glycobiology is essential reading for researchers in biomedicine, basic science, and the biotechnology industries. By providing a single forum, the journal aims to improve communication between glycobiologists working in different disciplines and to increase the overall visibility of the field. Society for Glycobiology "The objectives of the SOCIETY FOR GLYCOBIOLOGY shall be to promote knowledge, encourage research, and to stimulate personal communications, in an inter-disciplinary sense, using as a common meeting ground an interest in the complex carbohydrates of glycoproteins, glycolipids, glycosaminoglycans, and the biological systems in which they are found" The society is a non-profit professional organization promoting the science of GLYCOBIOLOGY. The official journal of the society is "Glycobiology" published by Oxford University Press. The society organizes an annual conference. ACTA ANATOMICA FEATURES GLYCOSCIENCES REVIEWS IN FIRST ISSUE OF 1998. Acta Anatomica, International Journal of Anatomy, Embrology and Cell Biology devoted its first issue of 1998 to reviews of current research in the areas of the glycosciences (Acta 161;1-4.1998). This prestigious scientific journal was founded in 1945 and is published in Basel, Freiburg, Paris, London, New York, New Delhi, Bangkok, Singapore, Tokyo and Sydney. Access to full text and tables of contents can be obtained online at http://www.karger.com/journals/aan/aan_bk.htm. We became aware of this issue of Acta after we began working on the GlycoScience Nutrition Science Site and are delighted to feature it as our first NEWS item. It is a perfect example of the exponential growth in the very new and exciting area of glycoscience research. One of the goals of our site is to bring together, from all the scientific disciplines, the most current studies related to saccharides and nutrition. The Acta publication had a similar goal in that it was designed to provide an up-to-date reference source on research being done in the glycosciences and also to be a “valuable primer for scientists and graduate-level students from the fields of anatomy, histology, cell biology, pathology, cancer research, pharmacology and pharmaceutical chemistry.” Our site has an additional goal of bringing together older studies that have been “lost in the literature” but that bear on topics of saccharides and nutrition. In the Editor’s Note for the Acta publication, Dr. H.W. Denker wrote “Research on the biological roles of glycoconjugates has made impressive progress in recent years. This has left footprints in virtually all fields of biology and medicine, not only immunology (e.g. lymphocyte homing), but also in general cell biology, developmental and reproductive biology, and neurobiology. It has become increasingly difficult for anyone but a few insiders to keep pace with this rapid growth of knowledge. So, as the Guest Editors of this series of special issues of Acta Anatomica mention in their Preface, many of the ‘secrets of glycosciences are only accessible to a closed circle of aficionados’, who appear to be the only ones to understand the ‘meaningful words of a sweet language of life.” The back cover of the journal contains a quote, “Glycosylation is the most common form of protein and lipid modification, but its biological significance has long been underestimated. The last decade has witnessed the rapid emergence of the concept of the sugar code of biological information. Indeed, monosaccharides represent an alphabet of biological information similar to amino acids and nucleic acids, but with unsurpassed coding capacity.” www.usa.glycoscience.com Copyright © 2000 Mannatech ™ Incorporated All Rights Reserved. This site is provided by Mannatech™ Incorporated as an educational site for use in the United States. Specific handling of printed documents from this site is covered in detail under Legal Notices and Terms of Use. Acta Anatomica, the International Journal of Anatomy, Embryology and Cell Biology, is an international forum for communication among scientist interested in morphology (study of structure and form) at all levels of organization with emphasis on humans and higher vertebrates. Volumes 161 through 163 published in 1998 were special issues devoted entirely to Glycosciences because, in the words of H.W. Denker, the editor of Acta Anatomica, “It has become increasingly difficult for anyone but a few insiders to keep pace with this rapid growth of [glycoscientific] knowledge.” Quoting the guest editors in their Preface to these series of special issues of Acta Anatomic, Dr. Denker says, “Many of ‘the secrets of Glycosciences are only accessible to a closed circle of aficionados’, who appear to be the only ones to understand the ‘meaningful words of a sweet language of life’.” These special volumes were dedicated to disseminate the knowledge of the rapidly expanding field of glycobiology. January 2000 issue The Nobel Prizes for 1999 A CELLULAR ZIP CODE GÜNTER BLOBEL Howard Hughes Medical Institute and the Rockefeller University Oil and water don't mix. So how do proteins--watery, water-loving molecules that they are--traverse intracellular membranes, which are essentially oily barriers that divide a cell into various compartments? That question launched biochemist Günter Blobel on the research path that culminated in his receiving the 1999 Nobel Prize in Physiology or Medicine. The first key to understanding how proteins move across membranes came in 1971, when Blobel was working in the laboratory of George Palade at the Rockefeller University. Blobel and his colleague David Sabatini proposed that each newly made secreted protein has a short stretch--which they called a signal peptide--at one end that allows it to snake through a membrane's fatty environment. Over the next three decades, Blobel expanded the signal hypothesis by figuring out how the process of protein translocation works and by discovering that signal peptides also serve as "zip codes" for directing new proteins to their correct places within a cell, as depicted in the illustration below. The process is a universal one: it operates similarly in plant, yeast and animal cells, including those of humans. Many serious diseases--such as cystic fibrosis and familial hypercholesterolemia, a genetic disorder that leads to very high blood cholesterol levels--arise when the proteinaddressing system of a cell goes awry. Blobel's findings are paving the way to a better understanding of the causes of and the potential treatments for these disorders. Image: KEITH KASNOT PROTEINS CROSS MEMBRANES at many places within a cell. Those destined for secretion--such as some hormones--spool off ribosomes as they are synthesized (1) and enter the endoplasmic reticulum. Short sequences called signal peptides help to direct ribosomes to the endoplasmic reticulum by binding to signal-recognition particles (SRPs), which in turn bind to SRP receptors. The signal peptides are cleaved off once the proteins are translocated across the endoplasmic reticulum. The proteins are packaged into membrane vesicles that subsequently pass through the Golgi apparatus and fuse with the cell's plasma membrane to spew their contents. Proteins that will remain stuck in the cell membrane, such as receptors for receiving biochemical messages from other cells, go through a similar pathway (2). Besides a signal peptide, however, transmembrane proteins also have a "stop-transfer" peptide that keeps them anchored in the membrane. When vesicles bearing the proteins drift to and fuse with the plasma membrane, the proteins become integral parts of the membrane. A different type of signal peptide allows proteins that act in the nucleus (3), where the genes reside, to home in on specialized structures called nuclear pore complexes. Other signal peptides ensure that proteins with jobs in various cellular organelles-such as the energy-producing mitochondria (4)--get to their appropriate positions within the cell. At conferences dedicated to medical education, health professionals are beginning to learn about the vast body of cutting-edge research in the science of glycobiology. The 2000 Comprehensive Cancer Conference in Washington, D.C. was sponsored by the University of Texas-Houston Medical School, the National Cancer Institute and The National Center for Complementary and Alternative Medicine. This educational forum included a presentation of case studies featuring an impressive list of positive effects from supplementing the diet with glyconutrients in combination with standard cancer therapy. A Technical Syllabus Provided For Use By Health Care Professionals By: THE FISHER INSTITUTE FOR MEDICAL RESEARCH Ph: (972) 660-1733 Fax: (972) 660-1245 e-mail: Helen@fisheri.org Health Professionals Health Professionals Medical Education Materials Presented at: Comprehensive Cancer Conference 2000 The Center for Mind-Body Medicine Washington, DC June 9-11, 2000 Hyatt Regency Crystal City, Arlington, Virginia Sponsors: The University of Texas-Houston Medical School The National Cancer Institute The National Center for Complementary and Alternative Medicine OneBody.Com Is There a Role for Dietary Supplementation in Combination with Standard Cancer Therapy H.R. McDanial, M.D. Medical director – Mannatech Inc. Comprehensive Cancer Care 2000 Conference Sponsors: National Center for Alternative and Complementary Medicine of the NIH, National Cancer Institute, University of Texas HSC, Houston, Texas Center for Mind-Body Medicine. Hyatt Regency Crystal City, Arlington, Virginia, June 6, 2000 Abstract: A Role for Dietary Supplementation in Standard Cancer Treatment? H. Reg McDaniel, M.D., Fisher Institute for Medical Research, Grand Prairie, Texas, This scientific conference is regarded as an appropriate forum to review alternative ideas in cancer management to determine if there is a basis for further development. A challenge confronts participants of this forum. Each individual is presented with new vistas in intellectual pursuits that may one day be transformed into science through the experimental process. This activity constitutes a gauntlet to overcome due to the human proclivity to reject the new and unknown. Medical tradition expands this trait to limit revisionist thought and actions, maintain a revered status for fixed-orthodoxy, to have contempt for new diagnostic or therapeutic modalities, and to reject peers who venture into uncharted territory. This presentation is not represented to be formal science or designed to establish public policy or serve as a guide for professional recommendations or practice. Two series of anecdotal cases are presented. Set A contains extended survival of cases unresponsive to standard therapy or judged terminal in the mid-80s. Current cases in set B are pancreatic cancer patients with inoperable complications that are over two years post-diagnosis. Experiments that provide a scientific rationale for the clinical benefits observed include: the supply of glyconutrients to mixed-Ieukocyte cultures increases the synthesis of cytokines: (IL-1, IL-2, IL-6, TNF, GMCF, & y-interferon), on a dose-response basis (Marshall 1993). Similar cell cultures demonstrated an increase in NK Iyphocyte 4-hour cytolysis of target cells on a glyconutrient concentration basis (Marshall 1993). Murine Norman sarcoma 100% fatality was reduced to 33% bya bi-weekly IP injection of glyconutrients (Campbell 1997). Feline leukemia had a 75% increase in expected survival and became negative for salivary and serum antigen following the receipt of glyconutrients (Sheets 1991). A medical researcher with lingual squamous carcinoma and an initial NK cell cytolysis ranging from 250 to 500 units rose to in excess of 80,500 units (N->40,000) by the addition of a glyconutrient dietary supplement to his diet. No return of the cancer has occurred in 2 years. Anecdotal reports have been received and a series of 100 patients (Hyland 1999) were presented by an oncologist reporting a clinical impression that patients' malignant cells have an increased susceptibility to radiation or cytotoxic chemotherapy, while normal cells are protected from free- radical and reactive oxygen specie damage. Protection was most noted in bone marrow elements. To explore this phenomenon, liver cells were scanned by a Meridian Cell Analyzer after the addition of 50 ug/dL of glyconutrient that resulted in a 50% increase in intracellular reduced- glutathione in 300 sec. This increase in intracellular oxidative stress protection combined with the biochemical activity of normal cells in the GI and malignant cells in the SI cell-cycle phase provides a plausible molecular mechanism for the clinically beneficial differential effects observed (Stockdale 1987). It is concluded that further investigation of the role dietary supplementation may provide in combination with standard medical treatment is warranted. Provided by the Fisher Institute for Medical Research, P .0. Box 530689, Grand Prairie, Texas 75053 Email: helen@fisheri.org (972) 660- 3219 FAX-(972) 660-1245 Comprehensive Cancer Care II: Oral Presentation: Integrating Complementary & Alternative Therapies, Sponsored by Center for Mind-Body Medicine & National Cancer Institute, Hyatt Regency Crystal City, Arlington, VA, June 1999 A PILOT SURVEY: STANDARD CANCER THERAPY COMBINED \VITH NUTRACEUTICAL DIETARY SUPPLEMENTATION IMPROVES TREATMENT RESPONDS AND PATIENT QUALITY OF LIFE G. Hyland, M.D., D. Miller, M. T., Medcenter One, Dept. Radiation Oncology, Bismark, North Dakota In thousands of cancer cases evaluated by H. Foster, 87% percent of those with "spontaneous remissions" had made major dietary changes prior to tumor regression. The Dietary Supplement Health Education Act of 1994 resulted in millions of US citizens adding a plethora of supplements to their diets. A favorable response by 5 patients that failed all cancer therapy was noted after it was stopped. We found that they had consumed glyconutrient, phytonutrient and phytogenin containing dietary supplements. A search revealed that Busbee et. al 1994 found that a glyconutrient in these diet supplements increased IL-l, IL-6, INF and TNF production in monocyte cultures. See et. all 1999 reported enhanced NK lymphocyte cytolytic function in response to multiple glyconutrients. Barhomi et. al 1997 found that glyconutrients increased intracellular reduced-glutathione protection 50% in liver cells. Such activity provides a potential differential effect for tumor cell destruction and normal cell protection. To increase our observations, patients malignancies were solicited from a 3 state area and 127 volunteered to add nutraceuticals to their diet. 100 patients returned a quality of life survey focusing on weight loss, fatigue, nausea, vomiting, pain control, ability to complete treatments on schedule, physical activity and sense of well being. 40% of the group had failed standard therapy and were in a state of progressive disease. 60% were starting radiation or chemotherapy. 85% reported improvements in the above clinical parameters. The phytogenin supplement contains plant sterols for nutrient based endocrine support. Ovarian, breast, uterine, and prostate malignancy patients were discouraged from taking this nutrient. But, some elected to add the phytogenin to their diet and they reported the best preservation of appetite, muscle mass, and had the least side-effects during treatment. Patient with a diagnosis of ovarian carcinoma, astrocytoma grade IV, lymphoma with mild marrow suppression, a massive pelvic myxosarcoma, and colon adenocarcinoma with brain metastasis had unprecedented responses. Conclusions: Nutraceutical dietary supplements: 1) Do not inhibit tumor cell destruction by radiation and chemotherapy 2) Enhance tumor cell destruction 3) Protect normal cells from radiation and cytotoxic damage 4) Induce reductions in tumor mass in malignancies resistant to all treatments. 5) Improve quality of life for patients by reducing toxicity and side effects from radiation and chemotherapy. Provided by Fisher Institute for Medical Research, P .0. Box 53069, Grand Prairie, Texas 75053 E.Mail helen@Fisher.org 1-972-660-3219 FAX 1-972-660-1245 Science, The weekly publication of the American Association for the Advancement of Science devoted an entire issue to Carbohydrates and Glycobiology in its March 23, 2001 edition (Vol. 291, No. 5512, pages 22632502). Introductory remarks note that “the important roles that carbohydrates play in biology and medicine have stimulated a rapid expansion of the field of glycobiology, the focus of the special section of this issue.” CARBOHYDRATES AND GLYCOBIOLOGY 2337 Cinderella’s Coach Is Ready NEWS 2338 Searching for Medicine’s Sweet Spot Saving Lives With Sugar After the Fall Sugar Separates Humans From Apes The Best of Both Worlds? Bent Out of Shape REVIEWS 2344 Toward Automated Synthesis of Oligosaccgarides and Glycoproteins P. Sears and C.-H. Wong 2351 Glycoprotein Structure Determination by Mass Spectrometry A. Dell and H.R. Morris 2357 Chemical Glycobiology C. R. Bertozzi and L. L. Kiessling Intracellular Functions of N-Linked Glycans A. Helenius and M. Aebi 2364 2370 Glycosylation and the Immune System P.M. Rudd, T. Elliott, P., Cresswell, I.A. Wilson R.A. Dwek VIEWPOINT 2376 Glycosylation of Nucleoctoplasmic Proteins: Signal Transduction and O-GlcNAc L. Wells, K. Vosseller, G. W. Hart COVER 2357 The cell surface landscape is richly decorated with oligosaccharides ancored to proteins or lipids within the plasma membrane. Cell surface oligosaccharides mediate the interactions of cells with each other and with extracellular matrix components. The important roles that carbohydrates play in biology and medicine have stimulated a rapid expansion of the field of glycobiology, the focus of the special section in this issue. [Illustration: Cameron Slayden] The 2001 Physician’s Desk Reference (PDR) for Nonprescription Drugs and Dietary Supplements includes an entry on Mannatech, Inc. (pages 819) and listings for Mannatech’s Ambrotose, PhytAloe and Plus (pages 819-820) along with a color picture product identification guide (page 508). Sugars That Heal Editorial Review: It isn't often that you find the words sugar and heal together when discussing health matters, but Dr. Emil Mondoa is working hard to change that. As founder of the Glyconutrients Research Foundation and author (along with Mindy Kitei) of Sugars That Heal, he has found that the addition of essential sugars to your diet can affect everything from the immune system to cholesterol levels. But this doesn't mean you should start heaping table sugar on every meal! Rather, Mondoa proposes that through the use of a few simple supplements, you may be able to fight off colds, lower your blood pressure, or simply have more energy. Mondoa is cautious when mixing research with anecdote and praise. While some people benefit tremendously from supplements, he points out that "many supplements aren't well absorbed or assimilated and are of doubtful efficacy." He later goes on to recommend consultations with your health care provider before beginning any of his specific regimens. The sources for these sugar-based supplements vary from shellfish to mushrooms, onions, and bovine tracheal cartilage, and he cautions against using the supplements without checking the ingredients, as those with allergies can experience serious reactions. Mondoa does include a few simple recipes for mushroom tea and vegetable sauce, but most of the glyconutrients are added to your diet through pills, powders, or tinctures; contact information for supplement sources is found at the end of the book. Specific chapters on the immune system, diabetes, chronic fatigue syndrome, and cancers detail the exact combinations of sugars most likely to heal. Are we looking at a source of new "miracle" cures here? Perhaps. But Mondoa, in his role as intelligent advocate, would be the first to preach caution and patience along with hope. -- Jill Lightner Book Description: "Sugars That Heal" sounds like a contradiction in terms, but it's the key to one of the most important breakthroughs in recent medical science. We've all been bombarded with warnings about the evils of consuming too much sugar. But, in fact, for our bodies to function properly, we need small amounts of eight essential sugars, only two of which--glucose and galactose--are commonly found in our limited, overprocessed diets. When all eight sugars are available, the health benefits can be breathtaking: Individuals regain their ability to fight disease, reactivate their immune systems, and are able to ward off infection. Based on cutting-edge research in the rapidly evolving science of glyconutrients, Sugars That Heal is an exciting new approach to health and disease prevention. As medical doctor and scientific researcher Emil Mondoa explains, these eight essential sugars, known as saccharides, are the basis of multicellular intelligence--the ability of cells to communicate, cohere, and work together to keep us healthy and balanced. Even tiny amounts of these sugars--or lack of them--have profound effects. In test after test conducted at leading institutes around the world, saccharides have been shown to lower cholesterol, increase lean muscle mass, decrease body fat, accelerate wound healing, ease allergy symptoms, and allay autoimmune diseases such as arthritis, psoriasis, and diabetes. Bacterial infections, including the recurrent ear infections that plague toddlers, often respond remarkably to saccharides, as do many viruses--from the common cold to the flu, from herpes to HIV. The debilitating symptoms of chronic fatigue syndrome, fibromyalgia, and Gulf War syndrome frequently abate after adding saccharides. And, for cancer patients, saccharides mitigate the toxic effects of radiation and chemotherapy--while augmenting their cancer-killing effects, resulting in prolonged survival and improved quality of life. Sugars That Heal offers a revolutionary new health plan based on the science of glyconutrients--foods that contain saccharides. It gives authoritative guidance for getting all eight saccharides conveniently into your diet through supplements and readily available foods, as well as detailed information on correct dosages. Here, too, are chapters dealing with the special nutritional needs of people suffering from cancer, heart disease, asthma, and neurological disorders, and methods for using glyconutrients to treat depression, obesity, and ADHD. The more doctors learn about glyconutrients, the more excited they become about their long-term fundamental health benefits. Now, with this new book, the breakthroughs in the study of glyconutrients are available to everyone. Whether your goal is to prevent disease, live longer and better, or treat a serious illness that has eluded conventional medicine, Sugars That Heal is your essential guide to complete health. In addition to personal stories about how they work, today there is a HUGE body of scientific evidence that supports the potential benefits of glyconutrients for various health conditions. This new book published by Random House and available at most book stores, summarizes some of the benefits. Here are some of the headings from the table of contents: • • • • • • • • • • Introduction to the Immune System Key Cells in the Body's Immune Response & how Glyconutrients Improve their Functioning Preventing the Common Cold and Other Viruses Treating Bacterial, Fungal, and Parasitic Infections Alleviating Allergies, Asthma, and Other Pulmonary Diseases Healing Skin Disorders, Burns, and Wounds Addressing Chronic Fatigue Syndrome, Fibromyalgia, and Gulf War Syndrome Managing Arthritis, Diabetes, and Other Chronic Illnesses Inhibiting Cancer Fighting Hepatitis, HIV, and Opportunistic Infections TURN BACK THE CLOCK • • • • • • • • • • • • • Glyconutrients as Preventive Self-Care Glyconutrients Slow Down Aging; Build Endurance, Sexual Function, and Fertility Glyconutrients help you Lose Weight and Gain Muscle Glyconutrients and Prevention of Sun Damage, Osteoporosis, and Cataracts Working with Memory, Insomnia, Anxiety, Depression, and ADHD Glyconutrients Improve Memory and Learning Glyconutrients and ADHD Glyconutrients Lower Anxiety and Improve Sleep Reversing Heart Disease Raising "Good" Cholesterol and Lowering "Bad" Cholesterol with Glyconutrients Glyconutrients, Blood Pressure, and Heart Failure Prescription for the Future Glyconutrients and the Science of Medicine THIS NEW SCIENCE IS CLEAR... NOT HAVING THESE ESSENTIAL GLYCONUTRIENTS IN YOUR DIET INCREASES YOUR PROPENSITY TOWARD DISEASE AND ACCELERATED AGING. About the Authors: Emil I. Mondoa, M.D., is a practicing, board-certified pediatrician affiliated with Our Lady of Lourdes Medical Center in Camden, New Jersey; South Jersey Medical Center in Vineland, New Jersey; and the Alfred I. duPont Hospital for Children in Wilmington, Delaware. He also holds an MBA from the Wharton School, with a focus on health-care management. He is founder of the Glyconutrients Research Foundation. Mindy Kitei is an editor, writer, and instructor who works in Philadelphia. A graduate of the University of Pennsylvania and the Medill School of Journalism at Northwestern University, a former editor at TV Guide and Philadelphia Magazine. She has taught journalism at Temple University and Rosemont College. July 2002 Sweet Medicines A new generation of drugs will be based on sugars--a neglected set of molecules Sugars play critical roles in many cellular functions and in disease. Study of those activities lags behind research into genes and proteins but is beginning to heat up. The discoveries promise to yield a new generation of drug therapies…By Thomas Maeder Now that the human genome has been deciphered, much of the fanfare surrounding it has transferred to the proteome, the full complement of proteins made from the genetic “blue-prints” stored in our cells. Proteins, after all, carry out most of the work in the body, and an understanding of how they behave, the press releases say, should translate into a font of ideas of curing all manner of ills. Yet living cells are more than genes and proteins. Two other major classes of molecules-carbohydrates (simple and complex sugars) and lipids (fats)-play profound roles in the body as well. These Substances, too, need to be considered if scientists are to truly understand how the human machine operates and how to correct it maladies. Sugars in particular perform an astonishing range of jobs. Once regarded mainly as energyyielding molecules (glucose and glycogen) and as structural elements, they are now known to combine with proteins and fats on cell surfaces and, so situated, to influence cell-to-cell communication, the functioning of immune system, the ability of various infectious agents to make us sick, and the progression of cancer. They also help to distinguish one cell from another and to direct the trafficking of mobile cells throughout the body, among other tasks. So ubiquitous are these molecules that cells appear to other cells and to the immune system as sugarcoated. Recognizing the importance of sugars in health and disease, increasing numbers of researchers in academia and the biotechnology industry have recently stepped up efforts to learn the details of their structures and activities and to translate those findings into new therapeutic agents. These pioneers have also gained support from the federal government. In October 2001 the National Institutes of Health awarded a five-year, $34-million “glue” grant to the Consortium for Functional Glycomics, a group of 54 investigators around the world who aim to coordinate and facilitate research in the area, such as by developing a library of synthetic sugar chains and structural database available to all. The grant, say James C. Paulson of the Scripps Research Institute in La Jolla, Calif., the consortium’s principal investigator, is “a vote of confidence” in the field. Overview/Sugars Sugars modify many proteins and fats on cell surfaces and participate in such biological processes as immunity and cell-to-cell communication. They also play a part in a range of diseases, from viral infections to cancer. Scientists are finally overcoming the obstacles impeding efforts to decipher the structures of complex sugars and to synthesize sugars for use in research and as drugs. The advances are leading to new medicines for a variety of ills. January 22, 2002 Changing Cancer Cells' Surface Sugars Can Inhibit Tumor Growth The key to halting cancer cells may lie in their sugary coats, scientists say. Carbohydrate molecules surround all cells and help them to identify and interact with one another. Now new research, published today in the Proceedings of the National Academy of Sciences, indicates that altering some of the surface sugars associated with cancer cells can control tumor growth. The findings suggest that the sugars could one day serve as targets for new anti-cancer therapies. Previous research had suggested that certain features of the polysaccharide sugars surrounding tumor cells might indicate either the stage or aggressiveness of the cancer. Whether changes to the coating were a cause or a consequence of the disease, however, remained unclear. To investigate the control a cancer cell's sugar jacket exerts over its growth, Ram Sasisekharan and colleagues at the Massachusetts Institute of Technology employed two enzymes capable of cutting the sugar heparan sulfate in different places. They injected cancerous mice with both the enzymes and the two sugar fragments they produce. Injection of heparinase 1 (hep 1) or its corresponding sugar fragment promoted growth of melanoma tumors in the mice. Injection of heparinase III (hep III) or its product, in contrast, inhibited tumor growth and prevented spread of the disease to other organs. The researchers also investigated the mechanism by which the two sugar fragments act on cancer cells and determined that the sugars bind to, and hence disrupt, the activity of certain signaling molecules involved in tumor activity. The opposing effects that the two molecules have on tumor growth suggest that cancer could involve a biological balancing act. "Tumors might be kept in check by the body's production of specific enzymes that in turn release sugar fragments that keep tumor cells dormant," Sasisekharan explains. "Or, perhaps in response to pathophysiological changes, a tumor cell releases different enzymes that enable the tumor to grow more rapidly." -Sarah Graham The New Era of Glyconutrients The most important discovery of this century for the immune system may be something called glyconutrients. They are not vitamins, minerals, herbals, homeopathics or enzymes. They are a class all to themselves. They are supplements derived from nature that have been formulated based on a new understanding in biochemistry of how our bodies maintain health at the cellular level. Our Immune Systems at Risk Cancer, cardiovascular disease, autoimmune diseases (e.g. lupus, rheumatoid arthritis, multiple sclerosis), osteoporosis, genetic diseases, foreign viruses, AIDS, and infant mortality seem to be more prevalent today than ever. Why are we experiencing these mounting health challenges? The reasons are quite simple. According to the 1992 Earth Summit, the USA has the worst soil in the world - 85% depleted. This means the potency of our food supply is not able to sustain optimum health. The amount of toxins in our environment has reached a level where the FDA now has designated "permissible" levels of dioxin and other harmful chemicals in the environment. Today we have over 300 chemical toxins including dioxin in the tissues that were not found in any human before 1940.1 These toxins have been shown to bind to receptors, blocking important enzymatic reactions in the body. One of the harmful effects of toxins such as DDT and dioxins is that they mimic hormones in the body causing disruption and confusion in the endocrine system.2 Processed food and fast foods are depriving us of even more essential nutrients. Many scientists believe that commercial farming, which burns out nutrients and adds poisons to the soil, as well as shipping foods "green" to ripen upon trucks, are major contributors to ill health. Many corporations continue activities harmful to our health to increase profits at the cost of our ecosystem and food chain. They do not inform the public about the true extent of the problem created by toxic substances and harmful additives in our foods nor about the environmental pollution generated from their manufacturing plants. The recent movie, A Civil Action, depicts this lack of accountability in the corporate arena. Finally, according to research scientist named Andreas Hartman "A class of broad spectrum antibiotics in drinking water is causing toxicity to human DNA!"3 Given these harsh challenges, one might seriously ask how can we best protect ourselves and optimize our health? Our Body's Capability to Defend and Protect Itself Every human is equipped with natural killer cells that identify and kill tumor cells and cells infected with viruses or some types of fungi or bacteria. Thus, the body has the genetic capacity to defend itself against viruses and bacterias, to cleanse itself of destructive toxins, to absorb and utilize nutrients for fuel, and to heal itself from practically any kind of damage or disease. So why doesn’t it always perform these functions? Research studies that have followed our immune system function over time have shown that on average, Americans have lost over 25% of natural killer cell function (our first line of defense) over the past 15 years due to toxins, viruses, and daily stresssors.4 It seems we have the ability, but are lacking the energy required to adequately protect, detoxify, and heal. New Discoveries in Glycobiology Healthy bodies, comprised of many components working together in sophisticated harmony, must have accurate biochemical communication to function correctly. In its most basic form, this communication occurs at the cellular level and is referred to by molecular biologists as cell-to-cell communication. When you look at any body function, it is clear they all require cellular communication. A major breakthrough has occurred recently with the discovery of how our cells communicate; that cells have a language, made up of "letters" and "words." The "words" are called glycoproteins made up of various sugar molecules known as saccharides attached in pearl-like strands to protein stems. Some of the connections for the saccharides are to lipids forming glycolipids. These "words" extend off the surface of every cell and can change thousands of times in a second. Cells actually touch each other to communicate reading each other’s cell surface messages. Disease and dysfunction occurs when the components necessary for cell-to-cell communication are absent.5 As John Hodgson wrote in an article called "Capitalizing on Carbohydrates", "Almost without exception, whenever two or more living cells interact in a specific way, cell surface carbohydrates will be involved. From the first meeting of sperm and egg, through embryo genesis, development and growth, carbohydrate molecules confer exquisite specificity upon cell-cell interactions."6 The Key to Healthy Cells and Healthy Bodies An increasing number of research scientists and doctors believe that eight specific carbohydrates (saccharides), represent the key to cellular communication as these sugars combine with proteins to create the glycoprotein chemical messengers. Only two of the eight are commonly found in our typical modern diets: glucose and galactose. The other sugars are Mannose, Fucose, Xylose, N-Acetylglucosamine, N-Acetylgalactosamine, and NAcetylneuraminic acid. The body has the potential to convert glucose and galactose to the other six through enzyme exchanges. However, the conversion process requires considerable energy, and is susceptible to interference from certain disease processes, various medications and free radicals. Oxidative damage from free radicals can also cause destruction of existing glycoprotein structures, making it necessary to convert some sugars into others to repair the damage. Living in our current environment, our bodies simply cannot keep up with this conversion/repair process. Further validation of the essential nature of these carbohydrates can be found in an article about the immune-enhancing benefits of breastfeeding.7 Five of the eight carbohydrates thought to be essential for cell-to-cell communication are ingredients in human breast milk and also in the glyconutrient formulas. Early Research Results with Glyconutrient Supplementation The potential for supporting our immune systems and enhancing cell-to-cell communication with glyconutrients is profound. One immunologist, Dr. Darryl See has found that natural killer cell activity increases by 50 percent after glyconutritional supplementation in the average healthy person. With glyconutritional supplementation among chronic fatigue patients who have impaired immune system function, natural killer cell activity has been shown to increase by over 400 percent.8 There is a growing body of scientific studies supporting the potential health benefits of glyconutritional supplementation for various health conditions including fibromyalgia, chronic fatigue, ADHD, diabetes, osteoarthritis, rheumatoid arthritis, and lupus9,10 A new study, published in February, 1999 reported a 95% killing activity of the Candida Albicans yeast in incubation with glyconutritional supplementation.11 More studies are now underway due to the breakthrough findings in this initial research period. In summary, glyconutritional supplements seem to allow the human body to manifest more of its potential by enhancing cellular communication. These nutrients may be a critical component in supporting the natural function of the immune system which is at risk in our toxic, denatured environment. By Debra Yemenijian Born with a severe lung infection, Matthew Wolf lived his first weeks shrouded by an oxygen hood in neonatal intensive care. At 10 months old, he contracted bronchial pneumonia, after which he developed severe chronic asthma. Those times were scary, remembered Matthew's mother, Kelli Wolf. "I used to sit at night and watch my sleeping child struggle to breath," she said. As he grew, Matthew's lung health worsened, dragging down the rest of his body with it. If a playmate passed him a cold, Matthew developed coughing fits that lasted for months. His joints ached severely, and it pained him too much to stand up, let along run, skip or jump. This article is featured in the July/August 2002 issue of Advance for Managers of Respiratory Care Wolf ushered her son to doctors weekly, but his respiratory difficulties failed to improve. "They (doctors) gave me shopping bags full of medicine," Wolf said. She recalls one office visit when a nurse poured her a bottle of prednisone like it was candy. In seven years, Matthew visited 30 pediatricians and six specialists in Nevada. At times, his lung capacity was less than 60 percent. Wolf found herself losing hope. "It was a nightmare and really sad to watch my little boy grow up that way," she said. As Matthew's health declined, she even considered looking for caskets. Than Matthew visited Michael Schlachter, MD, a pulmonologist at the Lung Institute of Nevada. After hearing about the child's medical odyssey and examining him thoroughly, Dr. Schlachter began supplementing Matthew's diet with glyconutrients, a set of eight essential sugars that include glucose, galactose, mannose, fucose, xylose, n-acetylneuraminic acid, n-acetylgalactosamine and nacetylglucosamine. Reports have suggested that when glyconutrients are present in proper amounts, they can decrease over stimulation in the immune system, thus suppressing inflammation associated with asthma. 1 Within two weeks of using glyconutrients, Matthew showed a profound change in his asthma symptoms, and he was later able to reduce his medications. Wolf noticed color returning to her son's face and he gained energy. 2 SCIENCE BEHIND GLYCONUTRIENTS Investigations into glycobiology and the science behind glyconutrients began as early as the 1960s, but researchers didn't make any major advances into the area until the mid-1990s. This research suggested that glyconutrients combine in different sequences to form transmitters and receivers that are necessary for cellular communication. When glyconutrients aren't present or are synthesized incorrectly, cellular communication can break down, thus causing a disruption in the immune system. 2 "The immune system is a fine-tuned, multi-faceted system, and some researchers believe asthma is a dysfunction of this system," Dr. Schlachter said. Adding glyconutrients to asthma patients' diets promotes cellular communication and avoids the dysfunction, he explained. At first, this concept may seem radical to physicians, Dr. Schlachter admitted. "The idea that a simple blend of sugars ingested by a person can have 'medicine-like' effects goes against everything that has been taught in the past 100 years about sugars and their use by the body," he said. But anecdotal evidence about glyconutrients' success is growing. C.E. Pippenger, PhD, the Peter C. and Pat Cook research professor in the department of biomedical/health sciences at Grand Valley State University in Allendale, Mich., has heard some anecdotal accounts from pediatric pulmonologists who have seen patients helped tremendously by glyconutrients. Their reports spurred him to conduct one of the countries few double-blind, phyto-controlled studies of nutritional supplements in children with asthma. In his study, Dr. Pippenger followed 100 patients with asthma and their use of glyconutrients, phytonutrients and a combination of both starting in January 2001. Ninety-two patients from the original group completed the study by June 2002. Most patients who didn't complete the study left it due to compliance problems. He expects results will be available sometime this fall. "We began the study because we believe the science surrounding glycobiology and receptors and interrelationships between sugars, cell function and the immune system are justified," Dr. Pippenger said. "If we can demonstrate that there's an effectiveness to nutritional supplements, then we can have a strong foundation for administering these to asthmatic children. They may decrease the amount of other medications the children are using." Sharon Riesen, MD, assistant professor of pediatrics at Loma Linda University, Loma Linda, Calif., also has been studying glyconutrients and their effects on children with asthma. Preliminary results of her open-label, controlled crossover study, 60 percent to 70 percent of the participants who used glyconutrients reported improvement of their asthma symptoms. Glyconutrients appeared safe, and no child involved in the study needed to stop due to side effects, "which is incredibly rare, even with the placebo," she said. "My passion is to get this information out to physicians that they could be using glyconutrients instead of medicines like prednisone," Dr. Riesen said. "The side effects of so many of the asthma medicines are intense. To have the kind of success that glyconutrients appear to have with asthma without side effects and have the majority of physicians not know anything about it is a shame." PROCEED WITH CAUTION While he has heard of glyconutrients, Gailen Marshall, MD, PhD, associate professor and director of the division of allergy and clinical immunology at the University of Texas, said it's still far from clear whether or not the supplements would be efficacious in all asthma patients. He wants to see the objective evidence from randomized, controlled clinical trials before he will recommend nutritional supplements as a part of asthma therapy. 3 "If individuals whose asthma symptoms are reasonably controlled by medications that have demonstrated effectiveness abandon them in favor of a more 'natural' solution that doesn't work for them, the risk for morbidity and mortality is not trivial in their case," Dr. Marshall said. Glyconutrients don't require a physician's prescription of approval and can be purchased as nutritional supplements, concentrates or extracts. A few companies sell the supplements, Dr. Schlachter said, but the Food and Drug Administration forbids marketing a specific nutrient as having direct or indirect association with a disease. Asthma patients should never discontinue use of any medication without the supervision of their physician, Dr. Schlachter stressed. Similarly, patients choosing to supplement their therapy with products like glyconutrients should inform their doctors so they can follow the patients' disease states closely and adjust pharmaceutical therapy as needed. For example, in Matthew's case, he now only needs his albuterol inhaler in case of an asthma flare-up or if he develops a deep cough. Today, at age 12, Matthew is a happy and healthy middle school student. He loves to cook and plays violin, which his mom says is exceptional because his motor skills suffered from the medications he took for so long. He's even completed the mile run in gym class and rarely needs to use his inhaler before or after participating. "Matthew shows a lot of heart, and running the mile was exciting for him," his mom said. "He's like a brand-new kid." REFERENCES 1. Purcell BS. Case report: observed improvements in respirator airflow in asthmatics following dietary supplementation. Journal of the American Nutraceutical Association. 1997 Aug 1;1:24-5. 2. McAnalley BH, Vennum E. Introduction to Glyconutritionals. Glycoscience and Nutrition. Jan 2000. Accessed via: www.usa.GlycoScience.com. RESOURCES 1. Rest, RF, Farrell CF, Naids FL. Mannose inhibits the human neutrophil oxidative burst. J Leukoc Biol. 1998 Feb.; 43:158-64. 2. Kamel M, Hanafi M, Bassiouni M. Inhibition of elastase enzyme release from human polymorphonuclear leukocytes by N-acetyl-glucosamine. Clin Exp Rheumatol. 1991 Jan; 9:17-21. 3. Kuby J. Immunology. New York: W.H. Freemen and Co.; 1997. 4. Lincoln JA, Lefkowitz DL, Grattendick KJ, et al. Enzymatically inactive eosinophil peroxidase inhibits proinflammatory cytokine transcription and secretion by macrophages. Cell Immunol. 1999 Aug.; 196:2333. 5. Hasegawa S, Baba T, Hori Y. Suppression of allergic contract dermatitis by alpha-L-fucose. J Invest Dermatol. 1980 Sept; 75:284-87. 6. Kai H, Murata Y, Ishii T, Nishimima S, Murahara K, Ogasawara S, Sugiyama N, et al. Anti-allergic effect of N-acetylnueraminic acid in guinea pigs. J Pharm Pharmacol. 1990 Nov; 42:773-77. Debra Yemenijian is editorial assistant of ADVANCE.