The answer came later in the 60's, when Dr. Nicholas
DiLuzio at Tulane University experimented with beta-1,3-glucan2 . In the late
1980's Dr. Joyce Czop, at Harvard University, described the mode of action of this
material in stimulating the immune system: there is a specific receptor for
beta-1,3-glucan on the surface of certain cells, called macrophages3 that when
activated, stimulate a cascade of events turning the body into "an arsenal of
defense".
Macrophages play an essential and pivotal role in
the initiation and maintenance of the immune response. From an evolutionary point of view,
the macrophage is the oldest and most consistently preserved immunologically competent
cell known. Not only humans and higher animals, but primitive invertebrates such as Hydra,
which have no other immunological effector cells, have macrophages. In order to function
immunologically, the macrophages must pass through a state of activation which involves
certain morphological changes but also, most importantly, a whole sequence of metabolic
changes which result in the production of series of so-called cytokines which act as
internal regulators of the immune system. Activation can be initiated by a variety of
different stimuli, such as endotoxin, bacteria, viruses or chemicals which can be too
toxic or pathogenic to be useful. Beta-1,3-glucan is not only orally effective, completely
non-toxic and safe, but is one of the most potent stimulators of the immune response.
Considerable attention has been recently given to Aloe Vera extract,
which was found to carry one of the macrophage activating polysaccharides, mannan or
polymannose. While mannan has some macrophage activating potential, it is very slight
compared to that of glucan4. There are several different glucans with different
levels of activity, the most active of which is beta-1,3-glucan from the cell wall of
yeast. A three dimensional model of this molecule shows it to be a helix, and the research
at Harvard has shown that there exist, on the macrophage cell membrane, receptors for a
small number of residues, approximately seven5 . The fact that such a small
number of glucose units can activate this receptor is very remarkable. What is more
remarkable still, is that there should be a specific receptor for this sort of
polysaccharide chain on the surface of the most ancient sugar cell in the immune cascade. There
is now evidence to show that glucan is, from an evolutionary point of view, the most
widely and most commonly observed macrophage activator in nature6. The
same enhancing mechanisms have been found in all branches of the animal, bird, fish and
plant kingdoms7,8.
The activated macrophages is a veritable powerhouse in terms of
activity. Not only can a macrophage recognize and kill tumor cells non-specifically, as
well as removing foreign debris, but it can produce a number of essential cytokines that
are able to stimulate the immune system in general and boost bone marrow production.
Individuals, who by reason of age and other factors, such as chronic infection or poor
nutrition, have a compromised immune defense system, are liable to all of the following
problems: arthritis, reduced wound healing capacity, reduced bone marrow proliferation
with resulting lowered white cell counts and anemia, increased incidence of cancers,
increased incidence of all kinds of viral, fungal, and bacterial infection. It is well
understood that one of the main elements of the aging process is a lowering of
effectiveness of the immune function9,56,57 : all the problems mentioned above
occur in old age. In addition, during ordinary living, the chances that the immune system
is impaired may be surprisingly high. Not only environmental influences like UV
radiation, electro-magnetic fields, food preservatives and antibiotics can cause temporary
immunosuppression but also stress and heavy physical exercises have these negative
effects. It is well-documented that after heavy exercise, generally healthy athletes
frequently suffer from influenza or pneumonia because of the depressive effect on their
immune system10. The same immunosuppression is observed in people
under physical or emotional stress and in patients with stress-related diseases, such as
coronary disease. Under these influences the number of macrophages available are reduced
and unable to participate in the immune cascade which causes even deeper
immunosuppression. Beta-1,3-glucan has been proven to both stimulate and activate
macrophage cells11 which will counter these negative effects.
In the 1970's after extensive studies in animals, human experiments with
glucan began. Dr. Peter Mansell reported that after injection of glucan into subcutaneous
nodules of malignant melanoma they resolved within a few days. When the biopsy of the
injection sites were done no evidence of melanoma was found, just a collection of
obviously activated macrophages12.
A follow up of that study was to treat a number of women with recurrent
malignant ulcers of the chest wall following mastectomy and radiation for breast cancer.
After an application of glucan in a vehicle these normally very indolent ulcers healed
completely. Subsequently, the same material had been used in the therapy of large pressure
ulcers at the New Orleans Charity Hospital with complete resolution of the ulcers, some of
which went down to the sacrum. An unexpected benefit was the complete lack of infection
and the rapidity of the reappearance of normal skin13.
The first human study on this specific glucan's systemic effect was done
in the mid1980's on advanced HIV infection. Even in these deeply immunologically deficient
individuals, an increase in serum cytokines IL-1, IL-2 and Interferon was measured14.
Results of another clinical trial showed significant mortality decrease from infectious
complications in severe trauma patients15.
At that time a crude preparation containing beta-glucan was already
registered in Eastern Europe for injection in patients for treatment of the effects of
bone marrow suppression from radiation or chemotherapy. In contrast to the crude mixture
called Zymosan, beta-1,3-glucan, a substance that is highly purified and active when taken
by mouth, is effective in very small dosages11.
One of the most remarkable oral studies with beta-1,3-glucan was done at
the US Armed Forces Radiobiology Institute. In a well controlled study, 70% of
rats given a lethal dose of radiation were completely protected from radiation effects
when given a dose of yeast beta glucan by mouth AFTER the radiation16.
Dr. Myra Patchen discovered that beta-glucan is also a free radical scavenger. It is able
to protect blood macrophages from free radical attack during and after the radiation
allowing these cells to continue to carry their important functions in the irradiated body
and release factors important to the restoration of normal bone marrow production17.
In the light of what we know about free radicals today and their
potential to accelerate aging, cause cancer and other diseases, this particular effect of
beta-1,3-glucan is especially important. Free-radical scavenging assays were repeated in
different models and which confirmed the antioxidant effect18.
Recent experiments completed at Baylor College of Medicine in the
laboratory of Professor Phil Wyde also prove the oral effectiveness of beta-1,3-glucan to
stimulate nonspecific immunity11. Peritoneal macrophages doubled their
phagocytic activity in mice fed with beta-1,3-glucan. This systemic effect of oral
application of beta-1,3-glucan is comparable to that achieved using injections, which
makes this material a unique and very valuable oral immunostimulant.
When beta-1,3-glucan was added to antibiotic regime in animals
challenged with different bacterial (Staphylococcus aureus, Klebsiella
pneumoniae,
Escherichia coli and others) and viral (Herpes virus) pathogens, a reduced amount of
antibiotics or antivirals was needed to cope with the infection11. It also has
an antifungal effect, shown in experiments with Candida albicans11. Such a
broad anti-infective spectrum of beta-1,3-glucan can be explained only by the fact that
the immunostimulation produced by this unique material is non-specific.
Continuing research with oral application of beta-1,3-glucan revealed
that it increases the effectiveness of other oral cholesterol-reducing agents, such as
Niacin and Lopid19. Interestingly, recent research has also demonstrated the
anti-diabetic effect of IL-1 cytokine, which increases insulin production resulting in
lowering of blood glucose level20. Macrophages are the main source of IL-1 in
the body and it's production can be boosted by beta-1,3-glucan supplementation. Mindful of
the extremely high rate of atherosclerotic complications and the extraordinary requirement
for antioxidants in diabetic patients, beta-1,3-glucan is an obvious adjuvant for an
improved lifestyle in these conditions.
As is repeatedly shown in the multitude of studies concerning the
activity of beta glucan as an immune stimulator, or perhaps more descriptive, a
"biological defense modifier", there are enormous benefits to be obtained by the
use of beta-1,3-glucan as a nutritional supplement. The aging process has been defined as
"the sum total of life's physical embarrassment due to adverse conditions"; in
this regard, beta-1,3-glucan may well be the first and only true anti-aging supplement. It
is defensive to negative events such as infection, tumors and radiation damage and
adjunctive to the positive effects of antioxidants, lipid balance enhancers, antibiotics
and other therapeutics. The result is improved general health which means more
enjoyment of life, less infirmities, less time and money required for medical needs and
potentially dramatic savings in Medicare and other health related expenditures over time.
Beta-1,3-glucan is effective in all mammals as it is in fish and birds.
It successfully prevents vibriosis, yersiniosis and furunculosis in Crustacea when it is
added to the feed7,21,22. The new devastation of the shrimp farm, the Taura
Syndrome, which has been recently identified as viral disease, causes high mortality with
survival of less than 20% of the shrimp farm population. Feeding shrimp with
beta-1,3-glucan increases their survival rate up to 90%23.
Beta-1,3-glucan basically is a highly purified form of a food product.
Technically it is a polysaccharide molecule completely made with glucose. Glucose is a
simple saccharide that the body transforms to energy as ATP and stores in muscles, liver
and other tissues in a form of glycogen. Beta-1,3- glucan is different from energy-storing
glucose-containing polysaccharides because the connection between the glucose units is
different, more specifically, it is the beta-1,3-linkage, which makes this compound so
unique. It is Generally Recognized As Safe (category GRAS according to FDA) and has no
toxicity or side effects24.
To summarize, beta-1,3-glucan is a safe and very potent nutritional
supplement with a systemic effect that can be described as non-specific immune stimulation
combined with it's free-radical scavenging activity. Some of the biological events
illustrating this stimulation are:
-
Activation of macrophages, expressing increased nonspecific phagocytic
ability allowing macrophages to destroy pathogens more efficiently, frequently preventing
disease.
-
Release of important cytokines, such as IL-1, IL-2 among others,
initiating immune cascade and triggering other cell lines, such as T-cells. Release of
colony-stimulating factors, boosting bone marrow production.
-
Cholesterol-reduction through cell activation and anti-oxidant activity.
Groups of people that are considered to benefit from beta-1,3-glucan
supplementation:
-
People with impaired immunity from any cause including but not restricted
to HIV infection; people with high occurrence of infectious diseases, tumors and
undergoing chemotherapy and radiotherapy; age 40+ when the natural aging process starts to
slow down immune reactivity, geriatric patients, and others with a compromised immune
response.
-
People that are possibly can be affected by extra free-radical production
caused by external sources: ones frequently exposed to low-dose radiation, including sun
light, other types of exposures such electromagnetic fields; lack of raw fruits and
vegetables in diet and eating preserved food. Extra free-radicals can also be a result of
a chronic disease such diabetes or chronic inflammation.
-
People who exercise excessively, professional and amateur athletes as
well as people who workout intensively and also those under physical or emotional stress
who have a temporary immune deficiency which can result in infection. Beta-1,3-glucan will
provide them with nonspecific immunostimulation that can increase their resistance to
illness.
-
People with high risk of atherosclerosis should definitely add
beta-1,3-glucan to their diet whether they are taking cholesterol-reducing drugs or not.
Macrophage activation will not only help to draw extra cholesterol from the blood but it
also can prevent further plaque formation on the arterial walls and phagocytize existing
plaque which is recognized as a foreign body.
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