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The Molecular Biology of How Dietary Supplements Support Optimal Human Health H. Reginald McDaniel, M.D. This manuscript has been assembled to present findings that are believed to build a case that further and more formal evaluations are justified in regard to the role played by micronutrients in preventing disease, maintaining and restoring health. This investigator has been a member of an investigative team composed of veterinarians, Ph.Ds., physicians and other basic scientists or special-niche trained professionals that have been progressively evaluating micronutrients since the mid-1980s. Despite initial skepticism on the part of each participant, it is now believed that pilot studies demonstrate that special dietary supplements that replace micronutrients low or missing in the modern, urbanized food chain are worthy of more formal research. This position comes from a growing body of evidence-based observations that need to be more critically examined and quantified. Research was initially on micronutrients that are
glyconutrients comprised of dietary sugars low or absent from
green-harvested and highly processed food.
There are also phytonutrients synthesized in plant cells when the
fruit and vegetables are allowed to plant ripen, that include a vast
array of free radical scavengers, anti-oxidants,
and micronutrients of various molecular species.
In addition, the micronutrients include phytogenins that are
plant-synthesized sterols in certain legumes and tubers, and rare trace
elements required to support cellular assembly of glycoproteins and
glycolipids and are incorporated into the structure of enzymes active in
cellular synthesis. The first challenge to established medical
therapeutic thought and practice is that too many favorable things
happen when the same combination of micronutrients are added to the diet
of individuals with compromised health.
One must first comprehend that the micronutrients constitute a
milieu of hundreds and possibly thousands of molecular species that are
used by cells in the complex biochemistry that conducts life.
The cells are provided a nutrient pool by dietary supplementation
upon which nutrient molecules are available, as required, to cope with
and balance environmental stresses encountered by the trillions of cells
in a human body. Such
adaptations are sensed and responded to by activation of genes that
transcribe the messenger ribonucleic acid (mRNA) that provides the
instructions for proper synthesis of molecules required to maintain,
regulate, or restore systems within cells and tissues to a “normal
state or zone.” The
healthy state cannot be maintained or restored if the molecular units,
or micronutrients, are not available for proper synthesis of
communication molecules that carry instructions between cells for
activity that must be conducted to restore balance within cells and
return the body to a “normal state of structure and function.”
The membranes within and surrounding cells are dynamic,
incredibly complex units of structure and function.
Cellular membranes are also synthesized within the bio-assembly
line in cells that require molecular resources to be able to be
correctly made and function properly.
The major supply of components for conducting the biochemistry of
living cells is supplied in the diet. To the casual observer, when health is restored by
providing nutrients the cells require for synthesis of cell activating
molecules (cytokines Gr.
cyto-cell, kine-activation), it appears that an active, interventional
treatment of disease was initiated.
That is not the reality for the activity that has been
successfully conducted. Roger
Williams, Ph.D., pioneer nutritional researcher, best described this
non-pharmaceutical natural phenomenon.
In his most important book, Nutrition
Against Disease, 1 1971, Dr. Williams states that the
theme of his life’s work and all his many books on nutrition is
captured in the statement, “The human body heals itself and nutrition
provides the resources to accomplish the task.”
The language of the Dietary Supplement Health and Education Act
of 1994 (DSHEA) codifies in legislation and the pilot scientific
observations in this monograph validate and support Dr. William’s
insight, understanding, and decades of pioneering research on nutrition.
Unfortunately, medical education gives very little
time or attention to nutrition. Therefore,
the viewpoint that explains the benefits revealed in this series of
papers requires a re-education for health care professionals.
A number of fundamental principles are required for comprehension
to grasp the full importance of the power of nutrition to support
health, prevent disease and restore health.
The most basic is an illustration Dr. Williams used in the cited
book. He describes a
chain on a table-top in a coiled-pattern.
At just over three-quarters of a turn the chain rises from the
table-top in the center to make a form like a snake ready to strike.
Each chain-link is described as representing a nutrient or
element required for cellular synthesis.
If all the links or nutrient units are present, the coil can rise
supported by the other links to represent the state of well being and
good health. However, if
any element or nutrient, those identified and even those yet to be
discovered, is missing, cellular synthesis is compromised and symptoms
and then diseases occur. The link at the point the chain rises from the surface is
described as being the missing nutrient or element, and when absent the
chain falls to the table top to symbolize this nutrient deficiency
state. Furthermore, Dr.
Williams stated that the state of well being cannot be restored until
the missing nutrient is supplied. Those
familiar with iron deficiency anemia have observed the practical
validity of this illustration. My professional deviation from standard medical
orientation that health is restored only by surgery, drugs, radiation,
major life style changes and avoiding risk laden activity began with
joining a research team in 1985 that was seeking to determine why human
beings have used aloe vera leaf gel for over 5,000 years.
A labile white powder in the leaf gel was stabilized and
extracted from the plant tissues. This
material was eventually determined to be chains of mannose sugars hooked
together in variable lengths, or numerous molecular weights.
A great amount of time and money was expended trying to make a
medication of this substance. The
aloe polymannose was shown to promote innate activity of cells that was
antiviral 2, antibacterial 3, anti-neoplastic 4,
healing 5 , and to function for supporting
intracellular stability, balance, and adaptation in stressed cells 6,
animal models 7, and human subjects. 8 Entering the new drug approval process, the first
difficulty in Food and Drug Administration (FDA)-required evaluations of
a new pharmaceutical agent was that no toxicity could be elicited by
massive amounts of the substance in multiple animal models and humans. 9,
10, 11 This is not
expected nor do the regulations for a proposed new drug take into
consideration such a finding. The
Father of Pharmacology, Paracelsus, stated, “All drugs are poisons,
the benefit depends on the dose.”
This reality has not changed in 500 years, and the laws of
various nations conform to this known characteristic of pharmaceutical
agents. The drug laws
before 1994 made no concession for a non-toxic substance, even nutrients
that have a health-promoting property.
The second problem encountered with agency premises and practices
was that too many desirable responses were fostered by the addition of
the complex sugar of aloe leaf gel source to the chemistry of an animal
or human. There is a
serious dictum in medicine, “There are no panaceas.”
This position is taken to heart along with the mantra, “If it
appears too good to be true, it is not true.”
The wide spectrum of desirable health-promoting activities
fostered by use of this non-toxic complex sugar exceeded any substance
on record and the FDA is not organized for, nor receptive to evaluate
multiple benefit-producing substances.
Furthermore, those oriented in standard medical care cannot
readily assimilate nor accept such a heretical challenge to unquestioned
dogma long established in the attitudes of a professional priesthood
that follows a catechism of evidence-based medicine.
To attain such evidence, the medicine is to be as pure and
defined as possible. Multiple
heterogeneous molecular species within a formulation, with multiple
active moieties that interact and provide synergy in unknown ways, as
found in nature, is an anathema to medicinal developers, regulators and
physicians. To move forward into wide human usage, it took a
legislative action with that law’s preamble creating a new paradigm
and regulatory niche into which the health-promoting polymannose
isolated from the aloe plant gel would fit.
The DSHEA made it possible that this trace micronutrient could
fit in a regulatory category under which it could be classified and
regulated by government monitors of health products.
Another important event was contained in a review published in
1985 by a pair of biochemists Steven and Rosland Kornfeld. 12
In this paper a step-by-step bio-assembly line within all young
cells is described. Most
importantly, it is described that in the endoplasmic reticulum, during
the second major step in biosynthesis in all cells, nine molecules of
mannose are required to initiate assembly of glycoproteins and
glycolipids. This
stimulated recognition that the active principle, the sugar mannose,
isolated from the aloe gel where the plant had synthesized the
monosaccharide and polymerized it into long chains, was utilized for
cellular synthesis in this organelle within human cells. Thus, the biochemistry and electron microscopy of
why human beings have used aloe vera since the advent of recorded
history was scientifically described.
That is why the white powder had relatively no toxicity or side
effects. Its mode of action
was not like a drug because it is a cell required micronutrient, a
glyconutrient to be exact, utilized in the molecular assembly within
cells to start the synthesis of structure/function molecules.
The complex polysaccharide meets the non-pharmaceutical
regulatory requirements demanded to warrant an exemption status in DSHEA
regulations for a dietary supplement.
This mechanism of action further solidifies the premise that
supplying a dietary supplement of this nature is not the treatment of
disease. Nutritional
support of instructions coded in genes that are programs for normal
physiology is operational. Such
instructional programs in genes require nutrient molecules to make it
possible to completely and correctly assemble structure/function
bioactive compounds made by the cells and thus optimize health. The bio-assembly line described in detail in the
Kornfeld review that is contained in each human cell is graphically
displayed in Graph I. This
is metaphorically referred to as the Rosetta Stone for Cell Biology.
This is due to its lucid description of the biochemistry and
ultra-structure that provide a conceptual matrix for why nutrition is so
vital in maintaining health, preventing disease, and restoring health.
This is the scientific foundation for the validity of the DSHEA
legislation and Dr. Roger William’s research theme. An important fact is that in the bioassembly line (demonstrated in the center of Graph I ) multiple sugars are not only metabolized to provide energy, but there is glycosylation (addition of sugars to peptides and lipid chains) in the endoplasmic reticulum and the Golgi. The significance of the coding capacity of sugars in glycoproteins and glycolipids is provided in a series of review articles in a glycoscience dedicated issue of Acta Anatomica. 13
The
perimeter structures start with the model of an idealized cell. The
central nucleus contains the chromosomes composed of chains of DNA that
provide the code for cellular synthesis to conduct life processes. In
the graph center is the progressive biochemistry that is conducted along
the bio-assembly line to synthesize the final structure and function
molecules shown at the bottom. A complementary working copy of the
inherited DNA code for life is made called RNA.
The RNA is audited for correct assembly (micronutrients are
required for operating this step), and methylated if there are no errors
and allowed to pass through the nuclear membrane into the cytoplasm.
In the cytoplasm the three major steps of bio-assembly take place
in the organelles called the (1) ribosomes, followed by the (2)
endoplasmic reticulum (ER) (3) and Golgi.
The peripheral cartoons are enlarged to show the idealized cell
at app. 500 magnification and organelle details at app. 100,000 magnification.
Amino acids are polymerized in the ribosome as the mRNA is drawn
through the organelle and read much like a player piano roll to start
the symphony of life by forming peptides and protein chains.
The peptide chain is taken to the ER and glycosylation (addition
of sugars) starts by adding 9 molecules of mannose-6-PO4
organized in three chains.
This three chain domain is the basis for coding bio-information
that is conveyed to cell membrane receptors.
The mannose-rich glycoform is then taken to the Golgi
for final assembly and code modification that includes substituting over
7 additional sugars for positions where mannoses had
been initially connected. 14
Glycosylation in the Golgi includes coding for a timer and
address to determine how long the complex molecule lasts and where in
the body the moiety is to be sent.
The complex sugar code on the three chains convey charge and
stereometric confirmation and constitute a means to communicate with
other cells by fitting into receptor sites on cellular membranes.
The component parts of the cellular membranes, including the
receptor sites where cytokines interact, are also made on this assembly
line. With this expanded viewpoint, the importance of supplying all the amino acids for the first step in bio-assembly in the ribosome and completion of glycoprotein and glycolipid synthesis in the Golgi was now recognized. It was realized that other dietary sugars are required in the Golgi to complete the proper complex assembly of structure/function molecules. The importance of fatty acids and related nutrients that are required to be able to properly synthesize lipoproteins cannot be ignored. To emphasized how intricate functional and nutritional requirements in cell synthesis are, in the Golgi not only is the core structure completed but each glycoform receives a coded address for its destination and a timer for how long the complex glycoprotein/glycolipid molecule is to exist. When the timer expires the ubiquitin system is activated via the lysosomal enzymes to initiate programmed cell death (apoptosis). Under ideal conditions this is accompanied by re-synthesis and replacement of the degraded structure/function glycoform that is initiated in the chromosomes by gene activation for replacement synthesis along the bio-assembly line described by the Kornfeld review. A wide array of micronutrients is required to accomplish all these normal tasks of life because each step is carried out by a cascade of bio-active molecules synthesized in each cell. There is a principle of biochemistry that must be understood to be able to grasp the all too often inadequacy of the widely accepted dictum, “All one requires nutritionally for good health is a good general diet with variety.” One will also be able to see the value of supplying concentrated micronutrients and why such a step is a means to marshal a principle of molecular biology to generate biochemical power for restoring optimal health. The Michaelis-Menten equation and the curve it describes follows: 14 Graph II
Caption Graph II: The
graphic display is a description of the fact that within cells, if cell
substrates are supplied, as in nutrient A that is combined with nutrient B to synthesize compound C, the more A
and B that is progressively supplied, the more rapidly and greater is
the amount of C that can be synthesized.
It is essential to look at conditions (1) at the left where small
amounts of C are synthesized.
This is the status of foods as found in nature.
For example, aloe leaf gel is 98.5% water.
Fresh fruits and vegetables are over 90% water.
A human cannot consume the volume of food to raise the cellular
synthesis rate to the maximal production level shown at the top of the
curve. However, by
freeze-drying, as indicated by (2), through the removal of water one can
place as a dry powder in a spoon, capsule or tablet, held easily in the
hand several times a day, and
consume the amount it would takes weeks to consume as A and B occur in
nature. In this manner,
defense and healing mechanisms that serve to bring influenza or a common
cold to an end naturally, can be stimulated to a new level of activity
that can suppress HIV-1, hepatitis C viruses and other infectious
agents. Thus,
the power of innate mechanisms of defense and repair coded in the genes
can be boosted to be effective against infectious agents and compromises
in health that no medication
has ever been effective. This
is accomplished with virtually no toxicity and at a cost that is a
fraction of pharmaceuticals. To demonstrate the application of the
Michaelis-Menten dynamics in dietary supplementation, the principle
should and has been tested in cell systems designed to display the
impact of increasing the nutrient supply of glyconutrients to cells
involved in synthesis of defensive and reparative cytokines (see Graph
III). One should note how
closely several cytokines of the inflammatory cascade conform to the
dynamics predicted by the Michaelis-Menton curve. Only synthesis of interferon alpha is not
increased by increasing the supply of aloe polymannose in the
mixed-leukocyte cultures. Graph III
Caption Graph III: The series of bar graphs display the average for three or more leukocyte cultures to which standard medium has been used as the control and then three progressive increase in concentrations of aloe polymannose has been added to the cultures 15. The control ELISA assays are at the far left of each cytokine assayed. Note that there is a general increase in cytokine production as each increment of the glyconutrient is increased, except for interferon alpha. Clinical results in human subjects with health compromises follow the same general response trend. The
informed critic might now state, “This in vitro study 15
indicates that there is an increase in the production of cell to cell
communication molecules that would be active in up-regulating the
general defense of the body. How
do you know that these cytokines are functional and carry out
instructions to destroy an infectious agent or abnormal cells?”
In 1993 the first of a series of experiments to demonstrate
whether effector leukocytes receive and respond to the increase release
of cytokines and are recruited into a defensive activity. 16
Graph IV demonstrates the summation of this work.
A tissue culture cell line is seeded with a herpes virus that the
cells will take into their cytoplasm.
Chromium-51 is added to the medium and it is taken into the
virus-seeded cells. All
excess virus and radioactive isotope is washed out of the culture.
The virions and radioactive isotope are now only present within
the living cells contained within intact cellular membranes.
Leukocytes are incubated in the same manner as in Graph III, then
harvested after a 24- hour growth period in an increasing concentration
of aloe polymannose-enriched
medium. These mixed
leukocytes contain presumably activated natural killer lymphocytes (NK).
The mixed leukocytes are added to the target cultures of
previously prepared virus and isotope-loaded target cells.
It is a normal act of defensive physiology for NK cells to detect
virus-laden cells and to destroy them, so as to prevent further
synthesis of virus particles. This is done by the NK cells releasing perforin, an
enzyme that cuts holes in the virus infected cell’s cellular membrane
to destroy it. If the
NK cells are activated to attack and destroy virus infected cells by
cytokine transmitted instructions, and if the amount of cytokines
synthesized influences the rate at which holes are cut in the virus
laden cells, then the release into the medium of the radioisotope will
be proportional to the amount of aloe polymannose supplied in the
initial leukocyte cultures. Note
that Graph IV demonstrates that the release of Cr-51 into the target
culture cell medium, evidence for destruction of virus infected cell,
and the level of isotope follows the amount of mannose supplied to the
leukocytes in Graph III that demonstrates enhanced step-wise synthesis
of defensive cytokines. Graph
IV
Destruction of
virus loaded Cells
The
confirmed cynic or cautious observer will undoubtedly respond that this
series of experiments are all in cell cultures and the results cannot be
transferred to inferences about what might be expected to happen in an
animal or man. These in
vitro experiments in no way include or contain the complex
interactions of multiple defense mechanisms that are active in the human
body or in vivo in an intact animal.
That is correct. If an antiviral study was conducted in human beings, an
expensive and ethically challenging project, there would be multiple
confounding variables ranging from genetic make-up to dietary
variations. However, 20 cats divided into 10 controls and 10
intervention subjects, on the same diet were challenged with a feline
rhinotracheitits virus nasal wash. 17
The test animals had a dietary loading with aloe polymannose 15
mg/KG administered 6 hours before the viral challenge while the controls
were given sterile saline nasally. There was a 100% infection rate in the controls with
all animals having symptoms for over 30 days.
One control died of pneumonia.
In the intervention group that received a single aloe polymannose
prior to the exposure, 8 animals had no symptoms what so ever. Two had red eyes and nasal discharge for two days and were
free of symptoms. At
this point it is a reasonable question to ask why, as follows in the
following pilot studies, the status of such different health problems in
human subjects can be improved by the addition of micronutrients to the
diet? And why don’t all
health providers know and use this simple, effective, and economical
nutritional technology? More
specifically, how can the same micronutrients being represented as
active in preventing or arresting infections, improving body
composition, percent fat, percent muscle, and increase bone density, be
related in any manner to behavior and learning problems of children with
attention deficit disorder (ADD)? To
do the research in order to supply the detailed answers modern science
demands will require millions of dollars.
The publication of pilot studies is to provide information that
may assist in initiating an interest and the granting of funds to
support inquiry into this approach for managing or eliminating health
compromises. The status of
micronutrients is not one for being recommended as a national policy or
professional recommendations. Further study is judged to be warranted.
Unfortunately, a block to this has been found to be attitudinal
in nature. It is not a
unique trait of scientists to reject and seriously question new ideas or
methods to address old unanswered problems.
It is a human characteristic to hold something newly discovered
or recognized as suspicious, if not a candidate to be shunned or
rejected. The intent of
this research team is to trudge forward on the demanding road of
evidence based-medicine. The
end of this journey is recognized to be beyond the horizon or far in the
distance. The
reaction to a different idea or new method can be complicated.
If, for example, micronutrients were to be added to the diet for
millions of school children and grades and deportment significantly
improved, it just might be responded to as an indictment of those who
have spent billions in public funds unsuccessfully trying to correct
such a serious national problem. The
school system of California is in the process of spending 5 billion
dollars on this educational problem.
Thus far, no statistically significant progress can be detected. 18
There are those in positions regarded as experts and
authorities in positions of power, respect, and responsibility with
reputations built on other approaches to solving the problem in the
schools. Teaching and
training programs at universities offer special programs providing
qualifications and specialties that would destroy professional empires
if micronutrition solved this problem in public education.
Thus, what appears to be a simple correction of a public problem
attacks an industry based on the problem not being solved and certainly
not by something as simple as giving micronutrients.
This scenario also applies to leaders and those of prominence in
science and medicine regarding other unsolved compromises in health.
The following pilot studies provide suggestions for further study
that only scratch the surface for multiple
observations for improved health benefits associated with better
nutrition. Those in
scientific and medical research and teaching who for decades in the
past, and anticipate in the future, receiving public and private sources
for funding decades of research could be less than thrilled to find that
micronutrients seriously alter or eliminate their future career plans.
This closes the experiences with the attitudes and actions of
peer investigators who might be threatened by this nutritional
technology. One
should know that dozens, if not hundreds of anecdotal reports from a
wide geographic range, including multiple countries and ethnic groups,
are received about improvements seen in a diagnostic entity or study
focus, before a pilot study is organized.
The results for problems reported are quite narrow and small
compared to the total experience of the last 16 years of seeing and
hearing of patient responses directly or from their physician.
If
the following simple summary is not the mechanism of action for all the
observations reported in this monograph, then this correspondent is
clueless to the cause and effect for the wide range of benefits that are
being reported and even a wider spectrum of favorable responses that
have been observed in many persons.
Each
of the trillions of cells in the human body contain the bio-assembly
line described in more detail above.
This bio-assembly line requires thousands of nutrient molecules
and elements to be able to assemble the compounds that make up the
structure and function of the body.
Instructions for the synthesis conducted on the bio-assembly line
are inherited from our parents and stored as coded instructions in
chains of DNA in the center of each young cell.
(Skin cells and erythrocytes are examples of cells that lose the
nuclear DNA and bio-assembly line as they mature.)
The biochemical processes we observe as life require the
synthesis of complex molecules to form the structures of the human body
and operate the cells, tissues, and organs.
Nutrition to supply all molecules required for cellular synthesis
is absolutely vital for normal function and to restore proper operation
of the body. The
fundamental relationship and interdependency for nutrients to support
biochemical synthesis and function for all cells is paramount to each
and every cell. A complete
supply of nutrients is vital to restore physiological balance and
communication within the body for a distended adipose tissue cell loaded
with fatty substances that need to be mobilized and utilized for energy
through action of the pituitary, thyroid, adrenals and mitochondria.
A network of neurons in the brain of a youth require optimization
of nutrients to be able to learn facts, operate the mechanisms of
recall, process cognition, relate such knowledge to needs for performing
on tests or living, sometimes surviving each day.
It is an almost revolutionary premise to exclaim that in the
functions of the human body conducted ultimately at the cellular level,
and recovery from disease orchestrated at the cellular level, that the
supply of all nutrients optimizes the function of all cells under normal
conditions or efforts to restore normalcy.
This nutritional requirement includes not only the nutrition to
support the act of running from a life threatening danger or sprinting
to receive a reward, but the thinking, cognitive processes that
determine the direction that is appropriate for the individual to choose
and then follow to survive or be honored. It has taken the reader only a few minutes to
follow the narrative provided in an attempt to share experiences that
have taken almost two decades for the author to travel.
Few could have been more skeptical when first informed in 1985
that AIDS patients were reporting significant benefits from drinking a
specially stabilized aloe beverage.
The slow addition of other micronutrients to the diet that are
low or missing in the modern urban food chain has been found to far
exceed what has been provided in the manuscripts that follow in this
monograph. It is hoped that this information will drive the reader
to test the assertions and representation that have been made. A final testament to the simplicity of this
nutritional technology is the fact that these principles are not based
on new dynamics that have recently begun to occur within living cells. The health benefits that follow in the papers
provided relate to recently recognized phenomena of life that are as old
as living cells, that is, life itself.
The intricate design and engineering of the bio-assembly line
present in each and every young living cell is awesome to contemplate.
However, consider now that in natural food, whole foods, that the
micronutrients that have been identified in recent years are required
for proper biochemistry. These
nutrient molecules provided in the environment of earth have a profound
impact on optimizing the health of human beings and are naturally
present in plants. There
seems to be an intelligent provision integrated with the biochemical
engineering requirements of cells to conduct life on this planet that
simply is a supply of nutrients that cells require for good health, to
prevent disease, and restore health, as is stated in the preamble of the
DSHEA. Certain
necessary nutrients for proper cellular synthesis, the glyconutrients
and fatty acids, can be uniquely found in human mother’s breast milk 19
not in cow’s milk or other mammal’s milk.
The exquisite and detailed requirements for optimal biochemistry
conducted in the cells is not only provided for in mother’s milk
during dependent infancy, but is then present in nature for the adult as
described in Genesis 1-29.
Amid the oldest coherent human writing that is available in the
scrolls of the Torah we find stated, “And I give you the herbs and
seed bearing plants, for you it shall be meat,” (KJ, 1611
translation). Hebrew
scholars state that the translation to English is good poetic imagery
and accurate, but a more literal statement would be, “….for you it
shall be sustenance.” The growing evidence is that this simple phrase
echoing wisdom across the ages in not only poetic, but factual and of an
immense value to humankind.
HRMcD
4/24/2002 Bibliography 1. Williams, R.J., Nutrition Against Disease, 1971, Bantam Book, Pitman Pub. Corp. 2. J. B. Kahlon, et. al., Inhibition of AIDS Virus Replication by Acemannan in vitro, Mol. Biother., Vo. 3, Sep. 1991. 3. S. S. Lefkowitz, D.L. Lewkowitz, Killing of Escherichia coli and Staphyloccus aureus by Murine Macrophages Activated in vitro with Glyconutrients, Proc. Fish. Inst. Med. Res., Vol. 2, 2000. 4. E. A. Merriam, et. al., Enhancement of Immune Function in Rodents Using a Complex Plant Carbohydrate which Stimulates Macrophage Secretion of Immunointeractive Cytokines, Advances in Anti-Aging Medicine Vol. 1, R. M. Klatz. Ed. Mary Ann Liebert, Inc. pub. 1996. 5. I. R. Tizard, et. al., Comparison of the effects of Acemannan on Wound Healing in Young, Old Obese and Old Calorie-Deprived Rats, European Wound Healing Society, Abstract #102, Aug. 1993. 6. R. Barhoumi, et. al., Enhancement of Glutathione Levels and Protection from Chemically Initiated Glutathione Depletion in Rat Liver Cells by Glyconutritionals, Proc. Fish. Inst. Med. Res., Vol. 1, Nov. 1997. 7. C. J. Gauntt, et. al., Coxsackieviruses and Inflammatory Diseases of the Pancrease and Heart in Mouse Models: a review, Proc. Fish. Inst. Med. Res., Vol. 1, Nov. 1997. 8. H. R. McDaniel, CD4 and CD8 Lymphocyte Levels in Acemannan Treated HIV-1 Infected Long-Term Survivors, Abstract # PO-B29-2179, IXth International Conf. on AIDS, Berlin, 1993. 9. R. W. Fogleman, Subchronic Oral Administration of Acemannan in the Rat and Dog, Vet. Human Tox. Vol. 34, No. 2, April 1992. 10. R. W. Fogleman, Toxicologic Evaluation of Injectable Acemannan in the Mouse, Rat and Dog, Vet. Human Tox. Vol 34, No.3, June 1992. 11. FDA Corporate New Drug File, unpublished data. 12. R. Kornfeld, S. Kornfeld, Assembly of Asparagine-Linked Oligosaccharides, Ann. Rev. Biochem., 1985. 13. Acta Anatomica, Vol. 161, 1998. (Dedicated issue with 12 reviews on glycoscience.) 14. R.K. Murray, Ed. Harper’s Biochemistry, 25rd Ed., Chapter 15, 56. 15. G. D. Marshall, Human cytokines Induced by Acemannan, Am. Acad. Aller. Immuno. Abst., 1992. 16. G. D. Marshall, J.P. Druck, In Vitro Stimulation of NK Activity by Acemannan, Amer. Assoc. Immuno. Abst., 1993. 17. R.H. Carpenter, H. R. McDaniel, B.H. McAnalley, In Vivo Antiviral Effect of Acemannan on Feline Rhiontracheitis, Tex. Soc. Path., Abst . 1988. 18. R.G. Ehrenberg, et.al. Does Class Size Matter? Sci. Amer., November 2001. L. A. Hanson, Breastfeeding Stimulates the Infant Immune System, Sci. and Med., Vol. 4, No. 6, 1997. |
