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: [email protected]
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: [email protected] (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 [email protected]
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.