Kidney Ailments
Give everything to your dog's veterinarian for review. I don't know if
Dr.
Tanner's research will help straight kidney disease. PKD is a genetic defect
seen most often in Persian cats. My cat had PKD and Lymphoma at the same
time. Tanner's stuff DID help her as did the MaxEPA Omega-3. In fact 3 days
after I started the two things, I saw a BIG difference in her behavior BUT
PKD is where the animal is born with cysts on the kidneys. As the animal
grows, so do the cysts and as they grow they destroy the kidneys. Tanner's
research showed that he could "regain" a lot of kidney function but whether
that can be transferred directly to a regular renal failure animal, I just
don't know. I also have information on a drug another owner's vet is using
on her animal who has renal failure. It looks as though it's tailor made for
anemia due to kidney failure. If your vet isn't already using it, ask him to
look into it. It's called "Epogen". My understanding is that they can build
up a tolerance to this product to a point where it will fail to work, so you
don't want to give it as the first line of defense. I'd suggest Bio Beta
Glucan for a quick and long-term building of the immune system. MaxEPA
Omega-3 is a type of cold-water fish oil. (DO NOT SUBSTITUTE ANY OTHER TYPE
OF OIL FOR THIS - IT MUST BE MaxEPA Omega-3.) It can stop cachexia (loss of
muscle mass, loss of appetite, loss of weight) and is a heavy duty
anti-inflammatory. Two different vets at two different vet hospitals told me
they read canine kidney studies that showed MaxEPA Omega-3 could reduce the
rate of destruction of the nephrons of the kidney. I can only tell you that
I used that on my kidney cat and my friend used it on her kidney failure
dog. Both animals picked up for a time - - until the kidney failure overcame
what they were on. It is able to buy quality of life, which I feel is very
important. I don't have that study but there is a reference made to Omega 3
and 6 (which is what MaxEPA Omega-3 consists of in the paragraph following
the Epogen information. I am including a canine heart study and a human
cancer study that show how and why MaxEPA Omega-3 works. Perhaps your vet
can locate the canine kidney study my two vet hospitals read.
Two versions of Dr. Tanner's study: POTASSIUM CITRATE/CITRIC ACID INTAKE
IMPROVES KIDNEY FUNCTION DRAMATICALLY IN ANIMALS WITH POLYCYSTIC KIDNEY
DISEASE Washington, D.C. (July 1, 1998) -- In a study of animals with
polycystic kidney disease (PKD), potassium citrate/citric acid (KCitr)
intake was shown to completely prevent the decline in renal function
associated with the disease, a condition that afflicts 600,000 Americans.
Researchers at Indiana University School of Medicine reported that young
rats with PKD that were given a solution of KCitr to drink showed normal
kidney function and much smaller kidney cysts after three months of
treatment. These findings were reported in the July 1998 issue of The
Journal of the American Society of Nephrology, which is published by the
American Society of Nephrology (ASN).
"If such striking effects on renal function were to be seen in other
species, then intake of KCitr might prove to be a valuable treatment for
patients with PKD," commented lead author George A. Tanner, Ph.D., professor
of physiology and biophysics at Indiana University, who recommends further
research on other animals.
PKD is the most common life-threatening genetic disease in humans. It
afflicts more than 600,000 Americans, many of whom aren't even aware that
they have the disease. In people with PKD, cysts (which can grow to be the
size of grapefruits) form in the kidneys, hamper function and usually lead
to end-stage renal disease (ESRD), or total kidney failure. While present
from birth, PKD typically does not begin to impair kidney function until the
ages of 40 or 50. A rare form of the disease, however, afflicts infants who
often die before they can withstand a kidney transplant at the age of two.
PKD accounts for nearly 1,000 deaths a year in the United States, and
another 2,000 patients a year develop ESRD and require dialysis or a kidney
transplant to stay alive.
In the Indiana University study, 13 rats with PKD and 16 normal rats were
give either tap water or a solution of KCitr to drink starting at the age of
one month. After three months, the PKD rats that drank only tap water had
impaired kidney function and the usual pattern of interstitial abnormalities
and kidney cysts associated with the disease. PKD rats that were given KCitr
to drink, however, had near normal kidney function and, while their kidneys
were as enlarged as the water-drinking rats, they had fewer interstitial
abnormalities and smaller kidney cysts. KCitr intake did not affect body
weight or urine flow.
The genes that cause PKD were identified in 1994 and 1995. Practical
treatments to halt or slow the progression of the disease, however, have
been extremely limited.
ASN is a not-for-profit organization of 6,500 clinicians and researchers
dedicated to enhancing and assisting the study and practice of nephrology
(the science of the kidneys), providing a forum for the promulgation of
research on kidney diseases, and meeting the educational needs of its
members. More than 9,000 researchers and clinicians from around the world
attend ASN's annual meeting and scientific exposition. POTASSIUM
CITRATE/CITRIC ACID INTAKE IMPROVES KIDNEY STRUCTURE AND FUNCTION IN RATS
WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE G.A. Tanner, Department of
Physiology and Biophysics, Indiana University School of Medicine Hypokalemia
and acidosis appear to promote renal cystic disease in animals and patients.
Citrate is an alkalinizing agent, diminishes formation of urinary stones,
and reduces renal ammonia synthesis. In this study, I tested whether
drinking a solution of 55 mM K3citrate/67 mM citric acid (KCitr) might
ameliorate polycystic kidney disease (PKD). Male heterozygous Han:SPRD rats
with autosomal dominant PKD and littermate normal rats were provided with
tap water or KCitr to drink from the age of 1 to 3 months. Glomerular
filtration rate (GFR) was determined in the 3-month-old anesthetized rats
from the clearance of polyfructosan. In the animals which drank tap water,
GFR (in \'b5l/min-100 g body wt) averaged 503 \'b1 78 (S.D.) in 9 normal
rates and 242 \'b1 56 in 6 rats with PKD.
Epogen:
Erythropoietin. Recombinant human erythropoietin (100 U/kg SC 3 X each week
until response [4-12 weeks] then 50 to 75 U/kg as needed to maintain HCT at
30% [D] to 25% [C])is available as a formulated product (EPOGEN; AMGEN Inc,
Thousand Oaks, CA; Procrit, Florida Infusion). The drug is indicated only in
cases of EPO deficiency such as may occur with chronic renal disease and
selected neoplasms. Antibodies may occur in greater than 25% of patients,
destroying endogenous as well as exogenous EPO, thus leading to a more
profound anemia. Once antibodies develop, the drug must be discontinued and
can not be started again. White blood cells and platelets do not seem to be
affected. Most patients also improved clinically (ie, appetite increase,
improved hydration). Iron supplementation is indicated. Hypertension should
be resolved prior to initiation of therapy and potentially hypertensive
animals should be cloasely monitored.
Granulopoietin (5 µg/kg sc sid to bid for 2 to 3 days or as needed to
maintain WBC) has been studied in both dogs and cats. rh-CSF increases
neutrophils within 12 hours and the increase persists for 2 to 3 weeks .
rc-CSF in dogs and cats increases wbc day 1 through 19 of cyclic
neutropenia, or cancer chemotherapy. However, antibodies are often present
by day 23. The canine recombinant product is much less likely than the human
recombinant product to cause the formation of antibodies in cats.
Indications for bone marrow stimulation have ranged from iatrogenic bone
marrow suppression associated with anticancer chemotherapy agents to
resolution of leukopenia (neutropenia) in parvo puppies. The human drug is
not generally available, but apparanently can be purchased. It is, however,
expensive (see AMGEN above).
Note the reference in this information to Omega 3 & 6 - - that is exactly
what MaxEPA Omega-3 consists of:
Other medications that may be used are androgens or erythropoiten (hormones
to help reduce the anemia associated with kidney disease), and calcitrol, a
substance which helps regulate the levels of calcium and phosphorus.
Additional vitamins or nutritional supplements for slowing the progression
of CIN may be beneficial. These products are fish oils containing the Omega
3 and 6 fatty acids, which may help, reduce kidney inflammation. Veterinarians
sometimes resort to more intensive treatments. For example, veterinary
specialists can perform dialysis (artificial blood filtering) and kidney
transplants. However, dialysis and transplants are labor- and
technology-intensive - and therefore very expensive. Dialysis requires
several hours of treatment several times a week - on an ongoing basis. And
canine kidney transplants have produced few long-term survivors, probably
because the genetic diversity among dogs increases the risk of organ
rejection. Future advances in anti-rejection drugs may make kidney
transplants a more viable option for dogs, although cost considerations may
still limit this practice.
MaxEPA Omega-3
(Additional information) (Buy from a health food store.)The only thing you
should not give with MaxEPA Omega-3 is a Warfarin product (a particular type
of blood thinner) as it may promote bleeding in the dog. If you ever do
surgery on this dog, either cut the amount of MaxEPA given in half or stop
it one week before and do not resume at full strength until after stitch
removal.
The amount of MaxEPA Omega-3 fish oil you give is 600 mg/kg. To figure the
amount for a 16 lb dog, for example, you multiply 16 X 0.45 to get the
weight converted to kg. So, 16 X 0.45 = 7.20 kg. Next, you multiply the kg
by the dosage of 600 mg. So, 7.20 kg X 600 = 4,320 mg. That means the dog
would get 5,000 mg MaxEPA Omega-3 fish oil per day (some will go on your
fingers and some will stay inside the gelcap). Do not heat the gel caps to
make the oil come out easier!!
I would give half in the a.m. (in this case, the contents of 3 gel caps) and
half in the p.m. (the contents of 2 gel caps). You do not need to give food
with this. I DO NOT give the dog the entire gelcap. I puncture the end
andsqueeze the fish oil into the dog's mouth or onto room temp. food. The
reason is that some dogs get sick from the gel cap material and vomit it up.
Also, this way you are sure that the dog is getting the oil. You don't have
to wonder how much he actually got if and when the gel cap dissolved. Most
MaxEPA Omega-3 comes in 1,000 mg gelcaps. You can use any brand that
contains the amounts listed below:
Each gel cap contains
EPA (eicosapentaenoic acid) - - 180 mg
DHA (docosahexaenoic acid) - - 120 mg
Vitamin E (d-alpha tocopherol) - 0 or 1 I.U.
I'm including two studies that show how MaxEPA Omega-3 works in heart dogs
and in cancer people.
WELLPET KEEPER
Fish Oil and Heart Disease art the loss of muscle mass in dogs suffering
"Fish oil supplements help heart disease, according to a study at Tufts
Univ. School of Veterinary Medicine. "We are very excited about these
results," said Dr. Lisa M. Freeman, a veterinary nutritionist at Tufts. "My
hunch is that a higher dose of fish oil might have even more of an effect,
but we need to do more studies in this area."Dogs with heart disease, like
people, experience a phenomenon called cachexia, or loss of muscle mass,
that decreases strength and immune function. When ill, the body produces
elevated levels of hormone-like substances called cytokines, the major one
being tumor necrosis factor, tohelp fight the offending pathoge. But at high
levels and for prolonged periods, cytokines can suppress appetite and cause
a loss of muscle mass. "People with heart disease have increased levels of
cytokines, probably as a compensatory response to the disease, but this
eventually can have detrimental effects for the patient," Freeman said. "We
wanted to study this mechanism to determine if it could be managed
nutritionally, and it turns out that fish oil does indeed reduce cytokine
levels." Although veterinarians have observed cachexia clinically in their
patients for years, the precise mechanism of the condition had not been
studied in dogs before. Freeman, who also is a researcher at the Jean Mayer
USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts, conducted
the fish oil study in collaboation with colleagues from the veterinary
school and the HNRCA. In the eight-week study, 28 dogs with congestive heart
failure caused by dilated cardiomyopathy, a naturally occurring disease that
weakens the heart muscle in some middle-age dogs and is generally fatal
within four to six months, were divided into two groups. One group was given
fish oil, and the other received a placebo. Both groups were also given
appropriate medical treatments for their condition. Fish oil is not a magic
bullet for treating canine heart disease, Freeman cautions, but the Tufts
researchers found a reduction in cytokine levels and an improvement in
muscle mass in these animals. "But even more exciting was the finding that
reductions in cytokine levels were associated with a longer survival time,"
Freeman said. "We'll need to study this further, certainly, but it looks
promising." The study was funded by the National Institutes of Health, Hills
Pet Products, the Mark Morris Institute and the American Society for
Parenteral and Enteral Nutrition.
Reprinted with permission of Canine Times,, a publication of CFNA, Inc.
509-332-3956. Anita Campus
From The April 1998 issue of Nutrition Science News Fish Oil Slows Cancer
Cachexia
By Richard N. Podell, M.D.
For cancer patients with a poor prognosis, good news, no matter how slim, is
still good news. The American Cancer Society (ACS), nationally headquartered
in Atlanta, estimates that 29,000 Americans will be diagnosed with
pancreatic cancer in 1998. Of those patients, the ACS predicts 18 percent
will survive at least one year after the diagnosis and only 4 percent will
survive more than five years. The slim bit of good news comes from research
that shows fish oil helps slow or reverse cachexia, a condition of physical
wasting and malnutrition often developed by cancer patients. Cachexia is
especially common to pancreatic cancer, where rapid weight loss is often the
dominant symptom. Weight and muscle mass drop off rapidly and out of
proportion to the accompanying loss of appetite. Neither more food nor
intravenous nutrition reverses the problem. Cachexia directly accounts for
an estimated 10 to 22 percent of all cancer deaths. Many experts believe
cachexia reflects an increased metabolic rate caused by inflammatory
biochemicals that cancer triggers. The best way to reverse cachexia is to
treat the cancer. However, pancreatic cancer does not have a safe, effective
treatment. Pharmacological treatments such as hydrazine sulfate and
ibuprofen may be helpful, but both have limitations, especially ibuprofen,
which can cause gastrointestinal bleeding.
The Fish Oil Alternative In test-tube experiments, fish oils and their
omega-3 fatty acids inhibit the growth of several types of human
cancer, including pancreatic. Fish oil also inhibits certain cancers in mice
and, through a separate effect, can reverse their cachexia.
This month's featured study is from the University of Edinburgh, Department
of Surgery, Royal Infirmary in Scotland.4 Eighteen patients with inoperable
pancreatic cancer received a daily dose of 12 1 g capsules of a fish-oil
dietary supplement that contained 18 percent eicosapentaenoic acid (EPA) and
12 percent docosahexaenoic acid (DHA). All of the patients had been losing 3
pounds per month on average before taking fish oil. In the first three
months of supplementation their average weight increased by about two-thirds
of a pound per month. Eleven of the 18 patients gained weight, three
remained stable and four continued to lose weight, but more slowly. Tests
showed that the weight gain was not caused by fluid retention. Both patients
and doctors in the study were aware of the treatment. However, there are
several reasons to believe the weight gain was not a placebo effect. First,
the weight loss in previous months had been large and progressive with no
reversal. Second, the fish-oil patients did much better than another group
who were treated with intravenous gamma linolenic acid (GLA), a different
type of oil. The intravenous treatments with GLA, given by the same
doctors, were ineffective in reversing weight loss. Therefore, there was no
significant placebo effect. The authors concluded: "Oral fish-oil
supplementation significantly altered the progression of cachexia in a group
of pancreatic cancer patients. Before supplementation, all of the study
group experienced progressive weight loss; however, following administration
of fish oil, three-quarters of the group were either weight-stable or
actually gained a small amount of weight. is unlikely that the observed
changes in weight were caused by a placebo effect since administration of
GLA to a matched group of weight-losing pancreatic cancer patients had no
significant influence on the overall pattern of weight loss."
Limited Success
The most important limitation of this study was its short duration. Three
month's benefit is important, especially in an aggressive cancer like
pancreatic. However, this brief reprieve should not give false hope. There
is some reason to suspect that had the study continued, progressive weight
loss would likely have resumed. Why did researchers expect fish oil to help?
Mainly because pancreatic cancer produces an inflammatory state in the body.
This can be measured by a blood test called C-reactive protein. Typically,
as the cancer progresses so does the C-reactive protein level. After one
month on fish oil the C-reactive protein levels of test patients decreased
by about one-third. This fits, because fish oil is known for its
anti-inflammatory effect. However, after three months of treatment the
C-reactive protein levels had risen back to their high baseline levels.
Therefore, we should not be surprised if weight loss resumed after four or
five months. The fish-oil treatment appeared to slow weight loss, however,
we do not know from this study if it also affected the cancer.
Unfortunately, no imaging studies were done to see if tumor volume
decreased. I know of only one other study that used fish oil to treat cancer
in humans, and it measured tumor growth rather than weight loss. Among 12
patients with advanced breast cancer, tumor progression continued in 11.
Only one showed a partial response to the fish oil. Animal studies using
fish oil are encouraging. One study showed reduced cachexia in mice with
cancer. Other studies showed fish oil decreased the subject's tendency to
break down fat and increased the ability to preserve muscle mass. This
month's clinical study builds on an increasing number of animal studies that
find various foods and natural products valuable in cancer treatment. These
include: soy protein, melatonin, vegetable mixes, modified citrus pectin,
curcumin, Co-Q10, cow's milk whey and shark liver oil.
Having said this I want to make one thing crystal clear: Self-treatment for
cancer makes no sense. People with cancer should work with an oncologist, or
a physician specializing in cancer treatment. While many, probably most,
oncologists remain wary of "alternative medicine," a substantial number are
recognizing that something important is brewing in the nutrition/cancer
literature. I know several oncologists who are talking to nutritionists
about how to help patients. My sense is that oncologists are among the most
caring and open-minded physicians. So if a patient chooses to add natural
therapies to cancer treatments, my advice is to ask both the oncologist and
alternative advisors to discuss with each other how best to contribute to
patient care. NSN
Richard N. Podell, M.D., is clinical professor of family medicine at the
UMDNJ-Robert Wood Johnson Medical School in New Brunswick, N.J., and
director of the Podell Center for Medical Treatment, Prevention and Natural
Healing in New Providence, N.J.
REFERENCES
1. Tisdale, M. J Nat Cancer Inst, 89: 1763-73, Dec. 3, 1997.
2. Chlebowski, R.T., Heber, D., et al. Cancer Res, 44: 857-61, 1984.
3. Wigmore, S.J., Falconer, J.S., et al. Br J Cancer, 72: 185-88, 1995.
4. Wigmore, S., Ross, J., et al. Nutrition (Suppl.), 12(1): S27-S30, 1996.
5. Beck, S.A., Smith, K.L., et al. Cancer Res, 51: 6089-93, 1991.
6. Tinsdale, M.J. & Beck, S.A. Biochem Pharmacol, 41: 103-7, 1991.
7. Smith, K.L. & Tisdale, M.J. Br J Cancer, 68: 314-18, 1993.
8. Yan, L., Yee, J., et al. Cancer and
Nutrition, 29: 1-6, 1997.
9. Lissoni, P. European Urology, 31: 178-81,
1997.
10. Rijnkels, J., et al. Nutrition and Cancer 29: 90-95, 1997.
11. Plenta, K.J. J Nat Cancer Inst, 87: 348-53, 1997.
12. Nagabthushan, M. J Am Col Nut, 11(2): 192-98, 1992.
13. Lockwood, K., et al. Molecular
Aspects of Medicine, 15: s231-40, 1994.
14. Kennedy, R., et al. Anticancer
Research, 15: 2643-50, 1995.
15. Storm, H., et al. Lipids, 28: 555-59, 1993.
DIET info from by Susan G. Wynn, D.V.M.
Nutrition and health care for the longevity of dogs and cats
Kidney Disease: For years, diets for aging pets were formulated
with less protein. This formulation decision was based on rat studies that implicated
excess protein in the development of kidney damage. But research in dogs actually suggests
the opposite. Not only does dietary protein not accelerate age-related kidney
degeneration, but older animals may actually need adequate protein to maintain immune
function and tissue repair mechanisms.13,14 On the other hand, animals with
existing kidney disease as well as elevated creatinine or blood urea nitrogen, which
indicates reduced renal function, do benefit from diets that have restricted phosphorus
content.15 Phosphorus is added by manufacturers to produce a balanced diet.
Once a veterinarian diagnoses renal disease, prescription diets or specially formulated
home-prepared diets may be appropriate.
Recent studies at the University of Georgia in Athens suggest that the addition of
menhaden (fish) oil to dog diets preserves renal function compared to supplementation with
safflower oil or beef tallow.16 I recommend fish oil capsules for a variety of
degenerative diseases, including renal disease.
13. Devaux C, et al. What role does dietary protein restriction play in management of chronic renal failure in dogs? Vet Clin North Am 1996;26(6):1247.
14. Finco DR, et al. Effects of phosphorus/calcium restricted and phosphorus/calcium replete 32% protein diets in dogs with chronic renal failure. Am J Vet Res 1992;53:157.
15. Brown SA, Finco DR. Fatty acid supplementation and chronic renal disease. In: Carey DP, editor. Recent advances in canine and feline nutritional research. Proceedings of the 1996 Iams International Nutrition Symposium; Wilmington, OH: Orange Frazer Press; 1996. p 159-67.
16. Winter JC. The effects of an extract of Ginkgo biloba, EGb 761, on cognitive behavior and longevity in the rat. Physiol Behav 1998 Feb 1;63(3):425-33.
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Below is Belfield's
program, however, if I were trying to strengthen my
dog's immune system quickly and most effectively, I wouldn't be
using Belfield's program. Since you probably need something effective and
quick, I'm giving you information on Bio Beta Glucan Maitake liquid by
Natures Answer (formerly known as D-Fraction Maitake). Bio Beta Glucan Maitake liquid
enhances the immune system quickly and should give results in 3-5 days. As with
everything else given here, run this by your
vet before using it on your dog.) My advice is to ONLY
use Natures Answer brand because there is no alcohol in it and you need less
drops per milligram of weight than any of the other products I've seen on
the market. If your local health food store doesn't have it, go on line and
get the Natures Answer site. They have a map that will show you who in your
area carries their products, OR, you can telephone them. They are in
Hauppauge, NY at 1-800-439-2324.
The amount you would give is: 1 mg/kg.
On the Bio Beta Glucan Maitake liquid but it is the same product), I know
someone at Linus
Pauling Institute who very kindly checked out studies and sent his best
guess on the amount to give to a cancer animal (I am involved mostly with
cancer dogs).
The rat dose in the study he quoted was 1 mg/kg, BUT researchers gave 5 and
10
times that amount to animals and got no
toxic effects. If you stick with 1 mg/kg and use Nature's Answer brand of
liquid Bio Beta Glucan, every 2 drops equal 1 mg. So, for a 16 lb dog, for
example,
you multiply 16 X 0.45 (to convert the pounds to kg) which equals 7.20 kg.
So, add 7.20 twice because 2 drops = 1 mg and you would have to give 14
drops per day divided into either 2 or 3 doses to equal 14 drops per day
total.
Below is information on what this can do. Again, I am involved mostly with
cancer
animals, not kidney dogs, so I have no kidney studies. See what your vet
thinks.
D-Fraction Maitake:
What makes Maitake D-fraction so important and how does it compares to other
mushrooms ?
Studies done by Dr. Nanhr, a foremost authority on medicinal mushroom, have
demonstrated its greater effectiveness compared to other mushrooms when
taken orally, a very key point considering that oral use is the most
commonly available form. D-fraction was shown to be over twice as effective
in inhibiting tumors than Lenthinan or LEM. It has been studied and proven
effective in stimulating the body's own defenses. Research has demonstrated
that it simulates a variety of different immune cells including macrophages,
NK-cells, Th, Tc and Tdh.
_______________________________________________________________________
From The February 1999 issue of Nutrition Science News
Immune Enhancers
BY MARCIA ZIMMERMAN, C.N.
The immune system is the body's ultimate defense against infectious agents
such as bacteria and viruses. It also protects against genetic mistakes made
in cellular replication that result in tumor or cancer growth.
The immune system is complex, containing many interacting blood cells,
proteins and chemicals. A healthy immune system contains elements that are
in balance with one another. In a compromised immune system, the components
are unbalanced and unable to protect the body against harmful agents or
processes.
Western medical doctors seek to bolster immune system activity by providing
either chemotherapeutic agents such as methotrexate, an antimetabolite, that
arrest aberrant cellular growth, or bioengineered molecules similar to
elements of our own immune complex, such as the alpha-interferon used for
genital warts, that will fight for us. The modern medicine bag also contains
vaccines,which may contain either dead or weakened bacteria or viruses or
other materials such as inactive toxins. Upon injection, the vaccine, which
is typically not strong enough to cause an infection, stimulates the body's
immune system to produce antibodies against the perceived pathogen. Despite
their overall saftey, vaccines and other methods can sometimes produce side
effects and upset the immune system's balance.
In contrast, traditional medical practitioners use botanicals and other
natural substances to stimulate or potentiate the body's own defense
mechanisms rather than substitute for them. This way the body's natural
balance is preserved, and side effects are either not present or
substantially reduced. Although both vaccines and botanicals elicit an
immune response, vaccines boost the body's response to a specific pathogen
whereas botanicals tend to enhance overall immunity. Immune-potentiating
botanicals are also used to increase the effectiveness of drugs and reduce
side effects. The Chinese call this Fu Zheng therapy,which means to support
the body's natural balance.
Many of the following botanicals--shiitake, maitake, licorice, echinacea,
ligustrum and astragalus--owe their effects to a group of polysaccharides.
These complex sugars have the ability to activate macrophages, which are
white blood cells that process antigens and present them to T cells
(lymphoid cells that migrate from the bone to the thymus).
These polysaccharides also stimulate T cell formation and differentiation,
as well as activate a group of more than 25 blood proteins that play a vital
role in the body's immune defenses.
Medicinal Mushrooms--An Umbrella of Protection An estimated 100,000
varieties of mushrooms exist; some 700 are used for food,
and about 50 appear to have medicinal value. For centuries, mushrooms have
been used in Asia both as food and as medicine. Two of the more popular
varieties of edible, medicinal mushrooms are shiitake and maitake.
* Shiitake mushrooms (Lentinus edodes) are highly prized, both for their
culinary use and as immune-potentiating agents. Their most studied active
principle, lentinan, is a polysaccharide composed of beta-1,3-glucans with
beta-1,6-glucan side chains.1,2 Lentinan stimulates the antioxidant activity
of both superoxide dismutase (SOD) and macrophages in vitro, especially when
levels of these detoxification agents are low.1,3 Other active principles
also occur in shiitake, namely KS-2, a glycoprotein that is isolated in what
is called a D-fraction from shiitake mycelia and in RNA isolated from
spores. The former stimulates interferon production in animal models when
administered orally. Interferon, produced by white blood cells, prevents
viral protein synthesis. The RNA fraction appears to increase protection
against influenza in mice, at least when administered intravenously.4,5
It is wrong to focus exclusively on individual agents, however, since
multiple active principles appear to be involved in the effectiveness of
shiitake. This efficacy has been borne out by its long history of use in
traditional medicine. Although scientific investigation must focus on a
single isolated compound to pinpoint specific activity, using the whole herb
takes advantage of shiitake's multiple benefits.
* Maitake mushrooms (Grifola frondosa), may have medicinal benefits more
potent than those of shiitake. This is because maitake's polysaccharides are
beta-1,6-glucan with beta-1,3-glucan side chains, which result in a more
complex branching structure. Since maitake is a newcomer in the medical
field, U.S. studies are just being completed on what components are
effective and how they work.6,7
The effects of maitake D-fraction on cancer were studied by Hiroaki Nanba,
Ph.D., and colleagues from the department of microbial chemistry at Kobe
Pharmaceutical University in Japan. An uncontrolled study on mice found
maitake to be most effective in inhibiting cancer growth of the breast,
lung, liver and prostate. Effectiveness ranged from 73.3 to 45.5 percent
reductions in cancer growth. It was also somewhat effective in cases of
leukemia (25 percent), stomach cancer (33.3 percent) and bone cancer (0 to
16 percent). Maitake was also effective when combined with chemotherapy (an
added 4 to 13 percent
benefit).8 In fact, maitake reduced the side effects of chemotherapy so it
was better tolerated and more effective. This latter effect has been
attributed to the fractions named X and ES found in the mycelia of the
mushroom. Therefore, in cancer treatment, it was suggested a D-fraction
concentrate be combined with mushroom mycelia.
The D-fraction has been found to activate natural killer (NK) cells,
macrophages and memory T cells. A second study by the same researchers
showed T cells are responsible for maitake's ability to help the body resist
cancer metastases. This is because memory T cells help the immune system
remember the cells that promoted the original tumor and tag them for
destruction before they can promote tumor growth in other parts of the
body.9 Therefore, maitake is effective not only in reducing cancer tumors
but also in preventing their recurrence. Maitake also activates several
cytokines, which are proteins produced by white blood cells. The cytokines,
namely interleukins 1 and 2 (IL-1 and IL-2), attach to T cell lymphocytes,
helping them essentially clone themselves into an army of cells that attack
tumor-promoting cells.
_______________________________________________________________________
As for the specific effects of the X and ES fractions found in mushrooms, an
initial laboratory study on the adaptogenic properties of maitake, and
specifically its effects on glucose/insulin metabolism, has just been
completed at Georgetown University Medical Center in Washington, D.C. Head
researcher Harry Preuss, M.D., announced the promising results of maitake's
antihypertensive and antidiabetic effects in animal models at the annual
meeting of the American College of Nutrition, held October 1998 in
Albuquerque, N.M.7 Preuss expects to begin Phase II trials immediately.
As the medicinal effects of shiitake and maitake are more clearly defined,
we can better appreciate how highly esteemed these edible mushrooms have
been, both in the Asian diet and in traditional medical practice.
Flora for Immune Fortification
*Licorice root (Glycyrrhiza glabra, G. uralensis) is one of the oldest
recorded remedies. It has been used in Chinese medicine to assist the
therapeutic effects of other herbs and to reduce their potential side
effects.
Glycyrrhizin, the primary identified active principle in licorice,
glycyrrhizin is a triterpene saponin. Triterpene refers to the 30 carbon
molecules attached to a compound's chemical structure. Saponins are widely
distributed in nature--most saponins are triterpenes--and form a frothy,
soaplike solution when shaken in water. Glycyrrhizin has a chemical
structure similar to that of steroid molecules. Its similarity to steroids
may account for its anti-inflammatory action, one of licorice's important
effects on immune response.10
Hirohiko Akamatsu, M.D., and colleagues from the department of dermatology
at Kansai Medical University in Japan, identified the ways in which licorice
appears to exert its beneficial effects. Rather than demonstrating
steroidal, cortisonelike effects on inflammation--reduction of tissue
swelling from histamine, increased blood flow and leukocyte infiltration of
damaged or infected tissues--licorice root has been shown in in vitro
studies to effectively reduce inflammation by mopping up excess free
radicals liberated in a free radical burst at the site of inflammation.11
Superoxide, hydrogen peroxide and hydroxyl radicals are released during
inflammation to disable targeted bacteria and viruses, a beneficial effect
that is often overdone. Similar results were obtained in a 1983 study in
which licorice root reduced the number of free radicals liberated by
macrophages.12
The activity of licorice on the immune system has been described as
"nonspecific" by most investigators.13 This means licorice stimulates,
activates or promotes an immune response in multiple ways. Earlier studies
identified several of these effects. For example, researchers found that
licorice appears to promote proliferation of B (from the bone) and T cells
and stimulate production of interleukin-19, which stimulates T cells.7
Licorice also appears to stimulate the production of gamma-interferon by
lymphocytes14,15 and the differentiation of T3, T4 and T8 cells, specific
kinds of activated lymphocytes.14-16
* Echinacea (Echinacea purpurea, E. angustifolia) contains a polysaccharide
fraction that, like licorice's, has anti-inflammatory activity. However,
echinacea appears to use a different method that inhibits leukocyte
migration to the area of inflammation rather than interrupting the enzymatic
activities or free radical burst of the white blood cells.17,18 Barbara
Müller-Jakic, M.D., and her colleagues at the University of Munich in
Germany found that echinacea also inhibits inflammatory prostaglandin
formation in both human and animal cell cultures. In this case, the alkamide
fraction, a chemically active component of echinacea, was identified as the
inhibiting factor.19
Because macrophages are often first to sound the intruder alarm, macrophage
activation is one of the most important events in immune resistance.
Echinacea polysaccharides are powerful macrophage activators as demonstrated
by two studies in the late 1980s.20,21 A study completed in 1997 by Darryl
See, M.D., and colleagues from the University of California at Irvine
Medical Center confirmed these earlier findings in vitro. The study also
showed extracts of E. purpurea and Panax ginseng enhanced cellular immune
function of peripheral blood mononuclear cells (PBMC), from both normal
individuals and patients with depressed cellular immunity. The extracts also
increased antibody-dependent cellular cytotoxicity of PMBC from all subject
groups. Natural killer cell activity was enhanced in cells taken from these
individuals.22
A 1997 study found several fractions containing specific components of
echinacea activated macrophages. Roger Burger, Ph.D., from Utah State
University in Logan, reported that "the multiplicity of compounds found in
the unfractionated extract may provide a greater immune stimulatory
capability." Researcher cited upregulation of the interleukins IL-6 and
IL-10 and tumor necrosis factor in macrophages obtained from acute-phase
infection respondents. These cytokines, in turn, activate T and B
lymphocytes to produce antibodies, fight bacteria and viruses, and produce
deadly chemicals that destroy a variety of organisms.23 Such studies help
explain the traditional Native American practice of using the whole
echinacea plant.
This brings us to two studies that examined the effects of echinacea against
Listeria monocytogenes and Candida albicans. Both organisms occur naturally
in the body but cause trouble when the immune system is weakened. One study
reported that macrophages were more active and effective after echinacea
administration, even when the mice were given cyclosporin, an antibiotic
that inhibits macrophage activity.24 This study confirmed earlier research
reporting the same results in mice.25
Finally, echinacea is reported to be a potent inhibitor of human tumor cells
cultivated in the laboratory.26 Other research demonstrates that it
activates production of lymphokines by lymphocytes, a kind of large
phagocytic white blood cell.27
* Ligustrum (Ligustrum lucidum) fruit has been used for several centuries in
Chinese medicine. Substantial empirical evidence indicates ligustrum
possesses immune-modulating effects, including cancer inhibition.28 Today,
ligustrum is an important herb for immune-system restoration after
chemotherapy (as part of Fu Zheng therapy), as are astragalus and shiitake.
Him-che Yeung, Ph.D.,of the Institute of Chinese Medicine in Los Angeles,
suggests that ligustrum increases white blood cell count and shows antitumor
and antibacterial effects.29
An in vitro study of human cellular response compared the T cell response of
19 cancer patients with 15 healthy subjects. Researchers found that cells
pretreated with ligustrum extract returned to normal more quickly after they
had been exposed to chemotherapeutic agents.30 They attributed this activity
to a nonspecific immune activation by ligustrum.
* Astragalus (Astragalus membranaceus) contains biologically active
components of two classes, polysaccharides and saponins.10 However, the
reviewed studies used the whole herb, rather than isolated fractions.
Astragalus and ligustrum are customarily used together in Fu Zheng therapy.
One study found increases in the number and activity of phagocytic cells
obtained from normal subjects after pretreatment with the two herbs. These
herbs also enhanced the differentiation of T cells into active helper T
cells. These, in turn, help other immune cells fight bacteria, viruses,
parasites, fungi, toxins and diseased cells.31
Astragalus also reduces autoimmune response (and thus allergy, Rheumatoid
arthritis and lupus erythematosus), and stimulates B cells and antibody
production.
Researchers confirmed that astragalus enhances T cell activity and
stimulates macrophages, which produce cytokine tumor necrosis factor--a
potent immune weapon--and interleukin-6 which mediates acute-phase
response.32 At the same time, astragalus suppressed tumor growth and
restored immune function compromised by tumor growth.33 These findings
confirmed earlier observations.34 Both studies were animal in vitro studies.
All the botanicals discussed in this article can be taken to prevent the
onset of illness, but they are equally effective during acute illness or in
combination with drug therapy. Cell and animal studies are now defining how
and why botanicals are effective, research that may someday validate, in
Western terms, the rich history of Chinese and European herbal medicine.
Marcia Zimmerman, C.N., is author of The ADD Nutrition Solution:
A Drug-Free 30-Day Plan (Henry Holt/Owl Books, 1999).
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Intl J Immunopharmacol 1986;8(8):919.
2. Kerékgyártó C, et al. Strain differences in the cytotoxic
activity and TNF production of murine macrophages stimulated by lentinan.
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3. Fehér J, et al. Effect of lentinan on superoxide dismutase enzyme
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4. Suzuki F, et al. Antiviral and interferon-inducing activities of a new
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Antibiot 1979 Dec;32(12):1336.
5. Suzuki M, et al. Antitumor and immunological activity of lentinan in
comparison with LPS. Intl J Immunopharmacol
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6. Press release. Maitake D-fraction obtained IND for clinical
study. 1998 Feb 1.
7. Press release. Georgetown University announced effects of maitake
mushroom extract on CVD. 1998 Oct 16.
8. Nanba Hiroaki, et al. Results of non-controlled clinical study for
various cancer patients using maitake D-fraction. Explore 1995;6(5):19-21.
9. Nanba, H. Activity of maitake D-fraction to inhibit
carcinogenesis and metastasis. Cancer Prev--Ann NY Acad Sci, 1995 Sep.
30;768:243-245.
10. Tang W, Eisenbrand G. Chinese drugs of plant origin. Berlin:
Springer-Verlag; 191-7, 567-91.
11. Akamatsu H, et al. Mechanism of
anti-inflammatory action of
glycyrrhizin: effect on neutrophil functions including reactive oxygen
species generation. Planta Medica 1991;57:119-21.
12. Igaku A, et al. The effect of glycyrrhizin and glycyrrhetic acid on
production of superoxide and hydrogen peroxide by macrophages. Chem
Abstracts 1983;98:155082a.
13. Chavali SR, et al. An in vitro
study of immunomodulatory effects of some
saponins. Intl J Immunopharmacol 1987;9:675.
14. Nara IZ. The role of interferon-gamma (IFN-gamma) producing
cells in clinical immunology. Chem Abstracts 1984;35:424.
15. Sugawa I. OK432, glycyrrhizin and CCA (lobenzarit disodium) are good in
vitro inducers of IFN-gamma production. Chem Abstracts 1991;114:135740j.
16. Shinada M, et al. Enhancement of
interferon-gamma production in
glycyrrhizin-treated human peripheral lymphocytes in response to
concanavalin A and to surface antigen of hepatitis B virus. Proc Soc Exp Bio
Med 1986;181:205.
17. Tubaro A, et al. Anti-inflammatory
activity of a polysaccharide fraction
of Echinacea angustifolia. J Pharm Pharmacol
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18. Tragni E, et al. Anti-inflammatory activity of Echinacea
angustifolia fractions separated on the basis of molecular weight. Pharmacol
Res Comm 1988;20(V Suppl);87.
19. Müller-Jakic B, et al. In vitro inhibition of cyclooxygenase and
5-lipoxygenase by alkamides from Echinacea and Achillea species. Planta
Medica 1994;60:37.
20. Stimpel M, et al. Macrophage activation and induction of
macrophage cytotoxicity by purified polysaccharide fractions from the plant
echinacea. Infect Immun 1984 Dec;46(3):845.
21. Luettig B, et al. Macrophage activation by the polysaccharide
arabinogalactan isolated from plant cell cultures of Echinacea purpurea. J
Natl Cancer Inst 1989 May;81(9):669.
22. See DM, et al. In vitro effects of echinacea and ginseng on
natural killer and antibody-dependent cell cytotoxicity in healthy subjects
and chronic fatigue syndrome or acquired immunodeficiency syndrome patients.
Immunopharmacology 1997;35:229.
23. Burger R, et al. Echinacea-induced cytokine production by human
macrophages. Intl J Immunopharmacol
1998;19(7):371.
24. Steinmüller C, et al. Polysaccharides isolated from plant cell cultures
of Echinacea purpurea enhance the resistance of immunosuppressed mice
against systemic infections with Candida albicans and Listeria
monocytogenes. Intl J Immunopharmacol
1993;15(5):605.
25. Roesler J, et al. Application of purified polysaccharides from cell
cultures of the plant Echinacea purpurea to mice mediates protection against
systemic infections with Listeria monocytogenes and Candida albicans. Intl J
Immunopharmacol 1990;15(5):605.
26. Voaden DJ, et al. Tumor inhibitors. Identification and synthesis of an
oncolytic hydrocarbon from American coneflower roots. J Med Chem
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27. Coeugniet EG, et al. Immunomodulation
with Viscum album and
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28. Sun Y, et al. Preliminary observations on the effects of the
Chinese medicinal herbs Astragalus membranaceus and Ligustrum lucidum on
lymphocyte blastogenic response. J Biol Response Modifiers 1983;2(3):227.
29. Yeung H. Handbook of Chinese herbs and formulas. Volume 1. Los Angeles:
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Intl J Immunopharmacol 1997:19(7):359.
33. Liang H, et al. The effect of astragalus polysaccharides on cell
mediated immunity (CMI) in burned mice. Chin J Plast Surg Burns 1994
Mar;10(2):138.
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______________________________________________________________________
Int Conf AIDS. 1992 Jul 19-24;8(3):30 (abstract no. PuA 6116). Unique
Identifier : AIDSLINE ICA8/92404198 Nanba H; Yamasaki P; Shirota M; Suzuki
T; Kobe Women's College of Pharmacy, JPN.
Abstract: OBJECTIVES: 1. Maitake extract, MT-2, was believed to have in vivo
immune stimulating activity both by injection and oral administration which
is unique to MT-2. 2. Sulfated MT-2 was believed to show potent anti-HIV
activity in vitro. METHODS: 1. Enhancement of cellular immune system has
been examined using tumor-bearing mice with CH3 mice as control.
Difference of immune activities between MT-2 treated and non-treated cell
were observed. 2. Anti-HIV activities were examined on sulfated MT-2 by
micro plate method. RESULTS: 1. Activities of macrophage, killer cells and
cytotoxic T cell were significantly increased by 1.4, 1.86, and 1.6 times
respectively compared to those of non MT-2 treated tumor-bearing mice which
results in 86% tumor growth inhibition in tumor-bearing host. (Similar
results were obtained by oral administration of dried powder of Maitake
mushroom). 2. Micro plate test of sulfated MT-2 demonstrated potent anti-HIV
activity in vitro. CONCLUSIONS: Significant immune stimulating activity of
MT-2 was confirmed even with oral administration. Anti-tumor activity in
vivo as well as anti-HIV activity in vitro were confirmed. It is suggested
that significant activation of immune response system by MT-2 may contribute
strongly to the inhibition of various diseases caused by secondary
infarctions among HIV carriers.
#2
Japanese Mushroom Helps
Block AIDS Says Researcher
United Press International (03/11/93)
Tokyo--A Japanese mushroom can help inhibit HIV and can also restrain breast
cancer, according to a researcher in Kobe, Japan. Prof. Hiroaki Namba of
Kobe Women's College of Pharmacy discussed both trials conducted among AIDS
patients in the United States and tests on mice with the Kyodo News Service
Thursday. He said the tests demonstrated that a polysaccharide called glucan
extracted form the mushroom, called maitake, incites action in helper
T-cells. Namba said, "It remains unknown why glucan from the maitake
mushroom activates the body's immune functions. But given its effectiveness
against symptoms of AIDS, it could be used for the treatment of AIDS
patients together with anti-AIDS drugs." Namba worked with two American
physicians to perform trials involving 26 AIDS patients, aged 20-40, to
determine if glucan would activate helper T-cells. The AIDS patients were
administered powdered maitake and glucan tablets, weighing three grams each,
daily for two weeks in April 1992, Kyodo reported. The number of T-cells
increased in 13 patients, and they stopped decreasing in the other 13. In
some instances the number of T-cells doubled. A report on Namba's study is
expected to be presented at a meeting of the Japan Society of Pharmacy in
Osaka, reported the news service.
__________________________________________________________
Chem Pharm Bull (Tokyo) 1989 Feb;37(2):410-3 Antitumor and immunomodulating
activities of a beta-glucan obtained from liquid-cultured Grifola frondosa.
Suzuki I, Hashimoto K, Oikawa S, Sato K, Osawa M, Yadomae T
The effects of the beta-1,3-glucan, LELFD, obtained from liquid-cultured
mycelium of Grifola frondosa, on the growth of syngeneic tumors and immune
responses in mice were examined. In Meth A or IMC solid tumor systems, LELFD
administered intraperitoneally (i.p.) or intralesionally (i.l.) exhibited
significant antitumor effects.
However, the growth of L1210 and P388 leukemias was unaffected by the
injection of LELFD. The injection of LELFD i.p. enhanced the activities of
natural killer cells and macrophages in mice. LELFD also enhanced the
antibody response when it was injected i.p. with sheep red blood cells into
mice. Furthermore, it was found that LELFD could activate the alternative
complement pathway.
ANTI TUMOR STUDY (more mice): J Pharmacobiodyn 1986 Oct;9(10):861-4
Antitumor activity of a beta-1,3-glucan obtained from liquid cultured
mycelium of Grifola frondosa. Ohno N, Adachi Y, Suzuki I, Oikawa S, Sato K,
Ohsawa M, Yadomae T
The antitumor activity of a branched beta-1,3-glucan "grifolan LE" purified
from liquid cultures of Grifola frondosa (Ohno et al. Chem. Pharm. Bull.,
34, 1709-1715 (1986] was examined on an allogeneic murine tumor system. By
intraperitoneal (i.p.) administration (100-200 micrograms/mouse/d X 5) at
days 1 to 9 from the tumor transplantation, grifolan LE showed marked
inhibitory activity on the growth of solid form sarcoma 180 in ICR mice.
Significant activity was also observed in intravenous (i.v.) or intratumoral
(i.t.) administrations.