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Beta Glucan High Dose, Highly Purified
Proven Immune System Support
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BETA GLUCAN SUPPLEMENTS BACKED BY
SCIENTIFIC RESEARCH
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Integrative Treatment
of Multiple Myeloma
Integrating allopathic and alternative medical therapies in the
treatment of a patient with Multiple Myeloma and Vancomycin
resistant Staphylococcus aureus pneumonia
Authors: Arcie G.
Mizelle, N.D., Ph.D. , Eric A. Scheinbart, M.D.
.................................................................................................
Background
Multiple myeloma is a neoplastic disease characterized by
infiltration of bone and bone marrow by myeloma cells forming
multiple tumor masses that lead to pathological fractures. The
condition is usually progressive and fatal. Symptoms include
anemia, renal damage, and high globular levels in blood and
increased susceptibility to bacterial infections. The impaired
abnormal immunoglobulin production observed in multiple myeloma
may be due to the presence of a monocyte or macrophage that
suppresses the maturation of normal B-lymphocytes into Antibody
secreting plasma cells. Life expectancies are related to the
extent of the disease at diagnosis and response to treatment.
Median life expectancy of responding patients is two to three
years. High levels of M protein in serum or urine, bone lesions,
hypercalcemia, pancytopenia, and renal failure are unfavorable
signs.
Review
The patient is a 56-year-old white male, a retired supervisor at a
nuclear energy plant, in previous good health. He initially
presented to the office on September 30, 1998, complaining of
tiredness, weakness, general malaise, abdominal discomfort,
productive cough, and was concerned about attending his daughter's
wedding.
Physical examination revealed a 56-year-old white male with
chronic low back pain, sinusitis, bronchitis, mild anemia, and in
no acute distress. A non fasting comprehensive metabolic profile
(chem12), amylase, lipase, lipid profile, thyroid screen and
complete blood count (CBC) were ordered and the patient was
instructed to visit the hospital laboratory. Initial evaluation of
the chemistry results showed an elevated total protein of 13.1
g/dl with normal albumin level of 3.5 g/dl. The BUN and creatinine
results were elevated at 54 mg/dl and 3.2 mg/dl respectively.
Other abnormal chemistry results were potassium 5.3 mmol/L,
chloride 109 mmol/L, calcium 12.8 mg/dl and phosphorus 5.4 mg/dl.
The protein result was repeated and the original result was
confirmed. Initial CBC was unremarkable aside from mild anemia
(hemoglobin 10.3 g/dl and hematocrit 31.2%) with a normal WBC of
7.17x103/cmm and platelet count of 269x103/cmm. Reflex testing of
immunoglobulins was performed and the laboratory report indicated
that the IgA value was elevated at 6020 mg/dl with a depression of
the IgG of 266 mg/dl and IgM of 37 mg/dl. Protein electrophoresis
was ordered and a sample was sent to the reference laboratory for
analysis. The protein electrophoresis confirmed the presence of a
M-spike in the gamma region. Immunofixation revealed an IgA kappa
monoclonal immunoglobulin detected along with free monoclonal
kappa light chains. Suppression of IgG and IgM was confirmed by
the reference laboratory. Radiologist review of the abdominal
series performed during the initial evaluation revealed
degenerative changes of the lumbar spine with disc degeneration at
the mid and lower lumbar levels, no acute abdominal abnormality,
and symmetrical hyperinflation consistent with obstructive airway
disease. No acute cardiopulmonary disease was evident.
The patient was referred to an oncologist in Augusta Georgia and
during a subsequent visit to the county hospital on December 23,
1998 for laboratory testing it was determined that his hemoglobin
and hematocrit had fallen to 8.4 g/dl and 26.7% respectively with
a normal WBC of 7.13x103/cmm and platelet count of 274x103/cmm.
His oncologist initiated a standing order for a two-unit
crossmatch whenever the hemoglobin dropped below 9.0 g/dl and two
units were administered during this visit. He continued to visit
his oncologist in Augusta Georgia and was also referred to a
clinic in Arkansas for further evaluation and treatment.
In February 1999 his hemoglobin dropped below 8.8 g/dl and he was
given two units of packed red blood cells. At this time his
platelet count was still normal at 478x103/cmm. During the second
half of February he underwent the first of three unsuccessful bone
marrow transplants. The initial post transplant WBC was 0.5x103/cmm
with a hemoglobin of 8.9 g/dl, hematocrit of 27.3% and platelet
count of 65x103/cmm. Despite repeated transfusions of packed red
blood cells and platelet pheresis packs as well as Procrit and
Neupogen treatments his red blood cell and platelet counts
continued to decline. Renal function continued to deteriorate over
the next several months as measured by BUN and creatinine which
were higher at 70 mg/dl and 4.8 mg/dl respectively. He developed
mild acidosis and his potassium continued to rise to a high of 6.9
mmol/L. Total protein was normal at 6.8 g/dl. The CBC demonstrated
a WBC of 2.95x103/cmm, hemoglobin 10.0 g/dl, hematocrit 29.3% and
platelet count of 44x103/cmm.
On September 8, 1999, the patient visited this office with a
productive cough with rhonchi. A pa and lateral chest film was
ordered and the results were compared to films made one year
earlier on September 30, 1998. The chest films were reviewed by
the radiologist. His report indicated, right medial basilar
bronchietatic change with atelectasis and bronchial wall
thickening which has developed since the last examination.
Bronchial wall thickening may reflect active bronchial
inflammation. No focal air space infiltrate was demonstrated.
Laboratory evaluation revealed continued mild anemia, hemoglobin
9.3 g/dl and hematocrit 27.5% with a WBC of 4.21x103/cmm and
continued decreased platelet count of 42x103/cmm. There were no
additional visits until after the patient returned from an
extended trip to Arkansas for the final bone marrow transplant.
The patient visited the hospital laboratory for evaluation, on
November 5, 1999, after the last bone marrow transplant. Protein
electrophoresis performed during this visit revealed a decrease
Total protein and albumin, 5.5 g/dl and 3.0 g/dl respectively and
the electrophoretic interpretation was essentially normal. Urine
protein electrophoresis revealed no abnormal urine protein.
Creatinine clearance was 24.8 ml/min with a micro protein of 33
mg/dl. BUN and creatinine values had remained elevated and were
now 99 mg/dl and 4.7 mg/dl respectively. Hematology results were
as follows; hemoglobin 8.8 g/dl, hematocrit 25.8%, WBC 4.54x103/cmm
and platelet count 23x103/cmm. Throughout the remainder of
November and December in spite of multiple PRBC and platelet
transfusions the platelet count remained at or below 25x103/cmm
with hemoglobin at or below 9.5 mg/dl.
The patient continued to lose weight and reached a low of 140 lbs.
from an original weight at diagnosis of 175 lbs. In late December,
he presented at the emergency department and was transferred to
Doctor's Hospital in Augusta, Georgia with a low grade fever,
pneumonia and possible sepsis. Additional symptoms were shortness
of breath, cough, diarrhea, nausea, vomiting and anorexia. Sputum
and blood cultures performed on admission to the referral facility
were positive for Vancomycin resistant Staphylococcus aureus. He
remained in the hospital for seven days, after which, he was
instructed to return home to "get his affairs in order,"
with a diagnosis of multiple myeloma unresponsive to three bone
marrow transfusions and Vancomycin resistant Staphylococcus aureus
pneumonia.
Of major significance at the time was the patient's morale. He
requested that the family leave him alone to die and was now
bedridden and housebound. On presentation of the patient's wife
and daughter and because of previous discussions of the
application of alternative medicine in this case and the desire of
the patient and family to try anything a program of alternative
therapy was prescribed. The patient began a daily regimen of what
we have termed an "alternative MOP therapy":
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Beta-1,3-D glucan
500mg T.I.D.
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MAK-4 1 tsp.
T.I.D.
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MAK-5 1 tablet
T.I.D.
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Pro-Boost Thymic
formula 1 packet sublingual T.I.D.
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Gerovital GH3 1
tablet T.I.D.
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Maitake mushroom
extract 2 droppers full T.I.D.
In order to insure
that he met minimum nutrient targets his diet included daily
portions of fresh fruits, vegetables, and supplementation with a
liquid protein supplement as tolerated. Along with these oral
medications counseling to reinforce the need for a positive mental
attitude and guided imagery to see himself well was also included
in the protocol. To his credit he was extremely compliant and
followed the alternative clinical protocol as directed
religiously.
Within a period of one week ulceration of the mouth had resolved
and the patient was somewhat better in appearance and was
ambulatory. Laboratory results indicated that the BUN and
creatinine were slightly lower and his electrolyte status was
improved although he continued to be acidotic. All laboratory
results during this period were copied and sent to his physicians
in Augusta and Arkansas. He also maintained a positive mental
attitude. During January and early February, 2000 the patient
continued exclusive treatment with the alternative therapies and
traveled to the clinic in Arkansas for follow-up. It was during
this visit that it was determined that the patient was
"miraculously in remission and without pneumonia." Upon
his return home the patient insisted on continuation of the
alternative therapy. The platelet count began to rise in the
second half of February and during the last week of February the
oncologist began therapy with Thalidomide. Subsequent platelet
counts began to drop and the Thalidomide therapy was discontinued.
Platelet counts again began to rise and during the last week of
March 2000 the platelet count rose above 50x103/cmm for the first
time in more than six months. BUN and creatinine results had
dropped to 50 mg/dl and 3.2 mg/dl respectively and protein/albumin
results were now normal.
He began to improve significantly and resumed many of his former
activities. During this period of well being he decided without
notifying either his physicians or family, to decrease his
medications and within a period of two weeks his laboratory
results began to reflect a slide in his condition. He was
counseled as to the necessity to maintain the clinical protocol as
instructed and again after a short period of optimum compliance
his health and laboratory results began to improve.
The electrolyte status is currently normal as well as CBC and
differential and globulin levels. He has resumed many of the
activities he was accustomed to prior to diagnosis to include
favorite pastimes of driving, fishing, playing golf, visiting
friends, and eating out.
Discussion
A greater number of Americans are turning to alternative therapies
for the treatment of a wide variety of health conditions either as
a way to enhance their traditional medical care as a substitute
for conventional methods of treatment. Patients seek alternative
therapies to promote wellness, to enhance the quality of their
lives, or to practice disease prevention. In order for an
alternative therapy to truly qualify as integrative or
complementary we feel it must meet three basic criteria:
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It should not
interfere with any traditional therapy the patient may already
be receiving
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It should provide
protection from the toxic effects of the traditional therapy
the patient is receiving
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It should be
capable of supporting the patient as a stand alone therapy.
In this patient's
treatment we thought that since the macrophage plays an essential
role in initiation and maintenance of the immune response we would
target our alternative therapy at stimulating macrophage activity.
The macrophage is the oldest and most consistently preserved
immunologically a competent cell known. The macrophage must be
activated, a process involving a number of morphological changes,
in order to function defensively. In addition, a cascade of
metabolic changes occur resulting in the production of a number of
cytokines which in turn act as internal regulators of the immune
system. Macrophage stimulation or activation can be initiated by a
variety of different stimuli such as endotoxin, bacteria, viruses
or chemicals. However, these activators can be too toxic or
pathogenic to be medicinally useful. Beta-1,3-D glucan on the
other hand is orally effective, completely safe and non-toxic and
is a very powerful stimulator of the immune response.(1) Not all
types of beta glucan are physiologically active. Beta-1,3-D glucan
derived from the cell wall of yeast is probably the most
physiologically active form, and in addition to beta-1,3-D glucan,
a broad spectrum glucan source, the Maitake extract(2) was added.
A three dimensional model of beta-1,3-D glucan shows it to be a
helix, and research at Harvard University has shown that receptors
for approximately seven sugar residues exist on the macrophage
cell membrane.(3) The fact that such a small number of glucose
units can activate these receptors and that there are specific
receptors for this sort of polysaccharide chain on the surface of
the most ancient cell in the immune system is very remarkable.(4)
There is now evidence to show that beta glucan may be the most
ubiquitous macrophage activator in nature. Once activated the
macrophage, through its ability to initiate a cascade of cellular
responses, becomes the central conductor of the immune symphony. A
macrophage can recognize and kill tumor cells nonspecifically, as
well as remove foreign debris. When activated by the combination
of beta-1,3-D glucan and Maitake extract, the macrophage produces
either directly or through stimulation of additional cells a
number of essential cytokines (IL-1, IL-2, IL-6, TNF and INF) that
are able to stimulate the immune system and boost bone marrow
production.
Research has established that glucans provide a protective effect
against an extensive list of microorganisms to include:
Staphylococcus aureus, Eschericia coli, Candida albicans,
Pneumocystis carinii, Listeria monocytogenes, Leishmania donovani,
Herpes simplex, Ascaris sp. Numerous studies support the theory
that an antibiotic and a macrophage activator, such as glucan,
work synergistically. Experimental peritonitis in rats was used to
show a synergy between the widely used antibiotic ampicillin and
glucan. A 100% survival was the result of the combination
treatment, while glucan alone gave 30% survival, and ampicillin in
the given dose elicited 65% survival (20% survival in the control
group). All the results were statistically significant.(5),(6)
The protective effect of yeast glucan on bone marrow in radiation
therapy is well established and documented with the mechanism of
enhancing hemopoietic recovery and by regenerating the host's
ability to resist life-threatening opportunistic infections.(7)
However, it also has been demonstrated that host resistance to
opportunistic infection in glucan-treated irradiated animals is
enhanced even prior to the detection of significant hemopoietic
regeneration. This early enhanced resistance to a microbial
invasion could be correlated with enhanced and/or prolonged
macrophage, but not granulocyte, function.
Experimental data suggest that glucan can also function as an
effective free-radical scavenger (primarily toward hydroxyl
radical). Because the macrophage has been shown to selectively
phagocytize and sequester glucan, it is possible that these
specific cells may be protected by virtue of glucan's free-radical
scavenging ability.(8) Oral application of yeast beta-1,3-D-glucan
for 20 consecutive days after a single, near lethal, dose of
radiation resulted in 70-90% survival versus 30% in the control
group.
Another aspect of glucan therapy is it's ability to also protect a
patient from leukocytopenia associated with chemotherapy. Studies
have shown that oral administration of glucan can prevent the
decrease in the number of peripheral leukocytes induced by the
administration of 5-fluorouracil. Proliferative responses of bone
marrow cells to granulocyte/macrophage colony stimulating factor
(GM-CSF) or granulocyte colony stimulating factor (G-CSF) were
suppressed by the administration of 5- fluorouracil, and their
recoveries were enhanced by glucan and serum levels of cytokines
such as IL-1 and IL-6 were increased.(9)
In addition to the immunostimulatory function of beta-1,3-D
glucan, it was necessary to minimize the damage caused by free
radical oxidation(10). Maharishi Amrit Kalash-4 (MAK-4) and
Maharishi Amrit Kalash-5 (MAK-5) are complex herbal mixtures rich
in vitamin C, vitamin E, beta-carotene, polyphenols, bioflavonoids,
and riboflavin.(11) Research shows that MAK is one thousand times
more effective at scavenging free radicals than the well-known
antioxidant vitamins C and E. There are hundreds of different
types of free radicals. Being a complex of herbs high in
antioxidant activity, MAK is the only known antioxidant that
protects against the full spectrum of free radicals. Additionally,
MAK is a potent anti-tumor agent(12) which enhances the immune
response by stimulating macrophage activity and increasing serum
levels of Interleukin-2.(13) The herbs in MAK also provide support
for minimizing the adverse symptoms associated with chemotherapy.
In studies involving patients with breast cancer undergoing
chemotherapy MAK was shown to significantly control loss of
appetite, weight loss and vomiting,(14) better levels of
performance, as well as reductions in the side effects of the
chemotherapy, i.e., fever, pain, and stomatitis.
In addition, thymic protein plays a pivotal role in the
programming of immature T-4 cells and it is necessary to provide
supplementation of this gland. Thymic Protein, an
"intact" 500 amino acid chain which fits the receptor
site on the T-4 cell, successfully programming the T-4 cells, sets
off a cascade of cytokine and lymphokine formation and
release.(15) The released cytokines and lymphokines act as
messengers to further stimulate target cells to attack and destroy
certain invading pathogens. The activated T-4 helper cells also
stimulate bone marrow to produce white blood cells, red blood
cells and specific CD56 natural killer cells which play a key role
in the destruction of cancer cells.
In summary it has been two years since the initial diagnosis of
Multiple Myeloma. The combination of immunostimulants,
antioxidants, and thymic protein replacement therapy showed:
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Remission of
multiple myeloma
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Resolution of
Vancomycin resistant Staphylococcus aureus pneumonia
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Absence of toxic
side effects of alternative treatments
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Improvement in
longevity and in quality of life
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Comparatively
inexpensive treatment
References
1. The formulation of beta 1,3-D glucan used was the Beta Right
brand manufactured by A. J. Lanigan, (877) 407-3999
2. Maitake mushroom D-fraction manufactured by Maitake Products,
Inc. New Jersey, (201) 229-0101
3. Zymosan, the cell wall from Saccharomyces cerevisiae, was
reported to be a macrophage activator through its beta-glucan over
30 yr ago. Nevertheless, the identity of the beta-glucan receptor
has been controversial. This study showed that the alpha M beta
2-integrin, CR3 (Mac-1, CD11b/CD18) served as the beta-glucan
receptor through one or more lectin sites located outside of the
CD11b I-domain that contains the binding sites for iC3b, ICAM-1,
and fibrinogen.
4. Thornton BP; Vetvicka V; Pitman M; Goldman RC; Ross GD;
Department of Pathology, University of Louisville, KY 40292, USA.;
J Immunol, 156: 3, 1996 Feb 1, 1235-46
5. Research Summary; "Beta 1,3-D Glucan Activity in Mice:
Intraperitoneal and Oral Applications, " Baylor College of
Medicine 1989.
6. Glucan-based macrophage stimulators may prevent infections in
trauma and surgical patients Reported from Drug & Therapy
Perspectives 1996 Aug 19; 8(4): 6-7
7. Research report; "Radioprotective Effect of Oral
Administration of Beta 1,3-D glucan." Armed Forces
Radiobiology Research Institute, Bethesda, MD, 1987.
8. Patchen M.L., Alesandro M.M., Brook I., Blakely W.F. McVittie
T.J., Glucan: Mechanisms Involved in Its Radioprotective Effect J
Leuc Biol.; 42:95-105.
9. Miyazaki 1992
10. Gerovital GH3, distributed by Nutriceutics Corporation,
Florida, (800) 391-0114.
11. Amrit, Maharishi Amrit Kalash, by Maharishi Ayurvedic Products
International, Inc., Colorado, (800) 255-8332.
12. The Amrit Protection MAK-4 formula significantly induced
morphological differentiation (neurite formation) and biochemical
differentiation (a 15-fold increase in tyrosine hydroxylase
activity) in 75% of neuroblastoma cells in culture. This is
indicative of a reversal of the malignant process.
13. Journal of Applied Nutrition, Vol. 48, Nos. 1 and 2, pp.
10-21, 1996
14. Proceedings of the XVI International Cancer Congress, 1994,
pp. 3099-3102.
15. Pro-Boost Thymic Protein, by Longevity Science, Klabin
Marketing, (212) 877-3632.
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