SCIENCE AND REASEARCH OF GANODERMA

The table from HOBBS (1995), which I placed on the home page, lists a multitude of in vitro and
in Vivo effects, executed by Ganoderma lucidum.
Here on the info page I will try to discuss scientific evidence as much as possible for each
indication, listed on the HOBBS's table. The discussion will be in a commonly understandable
language, in order to make non-scientists comprehend the important findings of Gano research
activities.
For more and better access to the upcoming information I recommend the following medical
online dictionaries (sometimes it is hard to avoid specific terms) for additional explanation of
medical and Scientific keywords:

Analgesic effects
So far I only know 1 study which deals with the question of pain relieving properties of
Ganoderma. Koyama et.al. published their findings in the Planta Med. 1997, in which they noted
that ganoderic acids A, B, G and H have analgesic properties. It still has to be seen, how efficient
these effects are under clinical conditions.

Anti-allergic activity and bronchitis-preventative effects

Tasaka et.al. published in 1988 that oleic acids and cyclooctasulfur can be found in Ganoderma
and have to be considered as histamine blocking agents through membrane stabilizing effects of
mast cells.

Anti-bacterial effects
Ganoderma has shown so far a somewhat complex pattern in anti-bacterial effects. It doesnt
seem to have an effect on a couple of micro-organisms whilst moderate to very good effects on
others. I was not able to find a valuable classification of an anti-bacterial pattern, since research in
this area seems to be too scarce. Ganoderma in combination with modern antibiotics like
ampicillin, cefazolin, oxytetracycline and chloramphenicol seemed to result in synergistic or
additive effects in most cases, a few only showed antagonistic effects. These findings are also to
be seen in relation to the micro-organism used for the tests. Also here a classification is still
missing, but in general terms we can say, that there is a high probability that Ganoderma and
antibiotics together execute an additive effect on the repulsion of a bacterial infection. Later we
will see that Ganoderma executes another bactericidal effect indirectly through enhancing the
immune system.

Anti-oxidant, removing free radicals

Oxidative stress has been linked with the pathogenesis of many human diseases including cancer,
aging, and atherosclerosis. In this context it would be of interest if Ganoderma has a protective
potential. Wong et.al. published in 2004 the observation that Ganoderma protects the heart from
superoxide induced damage, through superoxide scavenging activities in mice. In the same year
Sun et.al. reported that a Ganoderma lucidum peptide (GLP) is the major antioxidant component
of Ganoderma lucidum and could play so an important role in the inhibition of lipid peroxidation
in biological systems through its antioxidant, metal chelating, and free radical scavenging
activities. Wachtel-Galor et.al. conducted in 2004 a double-blind, placebo-controlled, cross-over
intervention study which investigated the effects of 4 weeks Lingzhi supplementation on a range
of biomarkers for antioxidant status, Coronary Heart Disease risk, DNA damage, immune status,
and inflammation, as well as markers of liver and renal toxicity with 18 healthy adults. No side
effects have been reported, while the antioxidant capacity in urine and plasma increased
significantly. There are also reports that the anti-oxidant properties contribute to a better treatment
of nephrosis by Futrakul et.al. in 2003. Ganoderma seems to protect the cell membrane against
lipid oxidation and ultimately against cell death. Shieh et.al. observed 2001 a liver and kidney
protective mechanism due to its (Ganodermas) prominent superoxide scavenging effect. Lee
et.al. assumed in 2001 a chemopreventive potential of Ganoderma, through a specific
aminopolysaccharide fraction with a strong anti-oxidative performance found in this mushroom.
But terpenes like ganoderic acids A, B, C and D, lucidenic acid B and ganodermanontriol also
showed a significant amount of oxidative protection. At this point of time there do exist quite
some studies, pre-clinical and a few clinical, which give a strong indication about Ganodermas
potency to protect organs and tissue through the protection of DNA and cell membrane from
harmful oxidants.

Anti-aging properties
There are some hints, that Ganoderma might possess anti-aging capabilities as well, since some of
the reasons for aging, especially premature aging, are free radicals activities (see also the
chapter on this page Anti-oxidant, removing free radicals) and a reduced capability for DNA
and cell repair. In 1993 Lei and Lin administered Ganoderma polysaccharides to splenocytes of
aged (24 months old) mice. They showed a significant lower DNA polymerase activity (about
36%) as compared to 3 month old mice. Since this polymerase is responsible for the replication or
repair of DNA and ultimately for cell repair and reproduction, the entire repair mechanism is
slowed down by the decrease of this enzyme. Furthermore it was observed that the interferon
production and the ability for immunologic countermeasures against foreign antigens were
significantly reduced. The application of Ganoderma polysaccharides restored those parameters to
the levels of that of young mice in vitro. Since biochemical processes in humans and mice are not
identical, but similar, there might be a certain possibility that Ganoderma works in the same way
in humans.

Anti-tumour activity
Mushrooms may work wonders in cancer treatment prevention was the title of a press release of
Cancer Research UK http://info.cancerresearchuk.org/news/pressreleases/2002/august/40288 in
2002 shortly after an international symposium on "Medicinal mushrooms: their therapeutic
properties and current medical usage with special emphasis on cancer treatments." in Kiew.
Scientific efforts seem to focus on this special indication, since in first place polysaccharides, but
also triterpenes, have been isolated and which have shown considerable cytotoxic effects. In
addition immuno-modulating effects of Ganoderma form an additional pathway of fighting
the development and progression of cancer through the strengthening of the bodys immune
system. In most publications the researchers find polysaccharides responsible for a direct cancer
cell damaging effect and probably for the inhibition of metastasis, the outspread of cancer into
different organs as well. But also immune enhancing effects seem to be very important, since
cancer can suppress immunologic activity which results in better growth and development for the
cancer. Therefore the immuno-modulated anti-tumor effect of Ganoderma lucidum is considered
to be mediated by cytokines released from activated macrophages and T lymphocytes. But still
more clinical evidence is needed to confirm Ganoderma as a standard in the treatment of acute
cancer. There are some recommendations to use Ganoderma in tandem with the conventional
radiation and/or chemotherapy, since it has hardly any side effects and also seems to lower the
side effects of the conventional, normally aggressive anti-cancer therapy. The results are that
survival and recovery rates are significantly higher and quality of life of the patients improves.
Medicinal mushrooms in general seem to have a favourable effect when it comes to the prevention
of cancer. A survey conducted over 14 years among Japanese mushroom workers in the Nagano
Prefecture implied that a regular diet of edible medicinal mushrooms was associated with a lower
death rate from cancer than of other people in the Prefecture. The average cancer death rate in the
Prefecture was one in 600. But the rate dropped to one in 1000 among farmers who produced
edible mushrooms.

Anti-viral activitiy
Since viruses use the DNA replication mechanism of human cells to reproduce themselves, the
challenge of a treatment is, to block virus DNA replication without damaging the affected host
cells by cutting off their own replication or protein biosynthesis mechanisms. Anti-herpes and
influenza agents isolated were protein bound polysaccharides, which showed a promising antiviral
effect, which could be improved by the combination with interferon. Other authors isolated
several triterpenoids and triterpenes with anti-HIV characteristics. Iwatsuki et.al.
reported in 2003 findings of a triterpene acid which significantly inhibited Epstein-Barr viruses.
Hijikata et.al. showed the effect of Ganoderma on 5 patients with herpes zoster. All patients
experienced relief of pain within a few days and was complete after 10 days. They responded
quickly to the treatment and none of them developed post-herpetic neuralgia during the 1 year
follow-up period. Liu et.al. 2005 observed that protein based polysaccharides gained from
Ganoderma blocked herpes virus activities far more efficient, when they had been applied before
or during the virus infection. An application after the infection showed some effects, but less
efficient: The antiviral effects in pre-treated and treated during virus infection with GLPG were
more remarkable than the treatment of post-infection. Although the precise mechanism has yet to
be defined, our work suggested that GLPG inhibits viral replication by interfering with the early
events of viral adsorption and entry into target cells. Thus, this proteoglycan appears to be a
candidate anti-HSV agent. This leaves the impression that Ganoderma might have specific potent
protective capabilities against a herpes infection compared to its curative capabilities.
Yet it has to be shown in clinical trials, if and in how far Ganoderma can contribute efficiently to a
remedy of HIV and other virus related diseases.

Anti-hypertensive properties
Yihuai Gao et.al. reported in 2004 in a clinical study, double-blind, randomized, placebo
controlled, with 170 patients suffering from Coronary Heart Disease, that beside other positive
effects, the anti-hypertensive properties induced a drop of blood pressure for those who received
Ganoderma, from 142.5/96.4 mmHg to 135.1/92.8 mmHg after 12 weeks of treatment. Since the
anti-hypertensive effect of even modern drugs in not fully understood, we can assume a
multifactorial effect of Ganoderma on the circulatory system. Lee et.al. found in 1990 in an
experiment with rats and rabbits, where they measured BP in the animals femoral artery and
activities of the renal nerve, that the application of Ganoderma extract induced a drop of BP and
an inhibition of sympathetic nerve activity. The expression of these effects was dose dependant.
So they concluded that the mechanism of hypotensive action of Ganoderma lucidum was due to
its central inhibition of sympathetic nerve activity. Mizuno et.al. stated in earlier studies from the
80s that Ganoderma has been assumed to have both hypotensive and hypertensive components
(the so-called homeostasis).A peptidoglycan (molecular weight, 100,000) having a mild
hypotensive effect on rats (congenitally hypertensive) has been isolated from a hot water extract
of Ganoderma. According to a report, the blood pressure of about half the patients with essential
hypertension was reduced when a Ganoderma extract was administered to them. It was found
recently that a hypertension-related angiotensin-I-converting enzyme was inhibited by Ganoderic
acids (B, D, F, H, R, S and Y); Ganoderal A and Ganoderol A and B, which is a similar effect of
modern ACE blockers.

Enhancement of bone marrow nucleated cell proliferation/Immunmodulation

In 1999 Zhong et.al. reported an interesting observation about Ganoderma boosting the immune
system by increasing the bone marrow granulocyte-macrophage output by induction of the growth
of its forming colony unit. At the same time Ganoderma suppressed the growth of leukemic cell
colonies. With increasing dose leukemic cells could be transformed into more mature erythrocytic
cells. Their conclusion was, that Ganoderma could serve as a good medicine for leukemia
therapy.Specific notes, which substance or substance class in Ganoderma was responsible for
these beneficial effects, were not stated. Kuo et.al. 2005 examined the immune boosting effect of
Ganoderma by searching for an increase of interferon and nuclear activator factor (NF-kappaB) in
the presence of Ganoderma, which was observed after 8 hours of treatment and over the following
period of 3 days. They concluded:"These results provide supporting evidences for the
immunomodulatory effect of Ganoderma lucidum."

Platelet aggregation
In 1990 Tao et.al. found that in vitro the reaction speed of platelet aggregation was significantly
slowed down after application of Ganoderma extract in relation to its dosage. They continued their
studies with 15 healthy volunteers and 33 patients with atherosclerotic diseases administering
each person 3 grams a day for 2 weeks. This showed that Ganoderma reduced weight and length
of the thrombi and reduced the aggregation events statistically significantly. They concluded, that
The results of our experiments suggested that the Chinese herbal medicine GL may be an
effective inhibitory agent of platelet aggregation. In the same year Gau et.al. investigated on
possible problems arising from the aggregation blocking properties in HIV-positive hemophiliacs.
They found that Ganoderma, despite a high content of adenosine, which plays an important key
role in antiplatelet effects, did not execute any increased risk. Platelet aggregation tests before and
after administering of the extract showed no significant
changes. In 2000 Su et.al. were able to show, that beside high adenosine levels Ganodermic acid S
also contributes to the antiplatelet effects, by influencing the biochemical pathways of platelet
reaction. A normalization of platelet aggregation and thrombotic activities towards a physiological
level contributes to a lower blood viscosity, which relieves the cardiovascular system of additional
work load and improves therefore indirectly efficiency and O2 balance also of the coronary
system.

Effects on serum cholesterol levels

In 1989 Li Khva Ren et.al. found in in vitro studies that It has been shown that Ganoderma
lucidum and Lentinus edodes possess pronounced antiatherosclerotic properties.
In the same year Komoda et.al. reported in a rat based animal study potent cholesterol
biosynthesis blocking properties of Ganoderma. In 2003 Berger et.al. from the Nestle Research
Center, Lausanne , Switzerland, found that Ganoderma has the ability to lower not only total
serum cholesterol, but also LDL, which is beside VLDL the critical factor of cholesterol content.
They conclude: Innovative new cholesterollowering foods and medicines containing Ganoderma
lucidum are envisioned. A more recent publication from Hajjaj et.al. also from the Nestle
Research Center in Switzerland, showed that triterpenoids are responsible for inhibiting lanosterol
to be transformed into cholesterol. These findings are important in so far, since 60 70% of body
cholesterol is synthesized and only 30 40% is added through intake of food. Controlled
cholesterol intake and cholesterol synthesis inhibition seem to be the most promising and
complementary measures for a regulated and normal serum level.

Anti-diabetic effects
In 1990 Kino et.al. showed in insulin dependant diabetic mice, that in comparison to an untreated
control group, Ganoderma treated mice had no incidents of insulitis, an inflammation of the
insulin producing units, and practical normal amounts of insulin producing cells. No cumulative
incidence of diabetes mellitus was observed in the Ganoderma treated group, while cumulative
incidences of 70% and 60% were observed in the untreated group followed up to 42 weeks of age.
Ling Zhi-8 (LZ- 8), an immunomodulatory protein having in vivo immuno-suppressive activity,
was recognized to be the active substance for these effects.
Alloxan is a chemical which induces diabetes by destroying insulin producing cells via
superperoxide built-up. Zhang et.al. in 2003 treated mice and found a subsequent decrease of
insulin producing cells, while Ganoderma treated mice showed no decrease. Since free radicals
are considered to play the damaging role, the Ganoderma effect is that of scavenging these free
radicals and eliminating them before they are able to destroy the insulin producing units
(Langerhans islets). In 2004 the same group found that Ganoderma polysaccharides increased the
Ca2+ influx into the pancreatic beta cells and induced hence a higher insulin release of these beta
cells, which explains the blood sugar lowering effects of Ganoderma.

Neuroprotection/Neurasthenia
Zhu et.al. reported in 2005, that administering Ganoderma oil extract from spores showed
neuroprotective characteristics in mice, which had been injected with MPTP, a substance which
artificially induces Parkinsons Disease (PD): The mice in the Ganoderma spores oil + MPTP
group presented significantly less involuntary movement of the limbs in the pole test than the
mice in MPTP group. Also the number of surviving neurons was greater in the Ganoderma group
than in the control group. Ganoderma could thereby also have a positive effect on PD in
prevention or therapy, which yet has to be confirmed in controlled studies. Tang et.al. 2005
reported about a controlled study with 132 neurasthenia patients over a period of 8 weeks. The
group with Ganoderma showed a significantly improved Global Clinical Impression, compared
with the placebo group. The application of Ganoderma seemed to be responsible for decreasing
signs of insomnia, headaches, irritability etc.

Prostate enlargement / cancer

Fujita et.al. 2005 found a strong intervention of Ganoderma extracts on the metabolism of
testosterone into dihydrotestosterone through 5alpha-reductase inhibition. The biological activity
of dihydrotestosterone is 2 times higher than that of testosterone and its receptor-binding
capability is 5 times the capacity of testosterone. The authors concluded that Ganoderma lucidum
might be a useful ingredient for the treatment of benign prostatic hyperplasia (BPH). Sliva D.
et.al. 2003 described in a series of publications the possible use of Ganoderma in lung and
prostate cancer, where it has clearly shown to inhibit the outspread and migration of tumor cells,
which limits or even prevents metastasis of malignant cancer cells.
Jiang et.al. 2004 found out, that Ganoderma prevents the growth of prostate cancer cells and
induces cell death of malignant cells through a complex system of biochemical and molecular
interactions. They concluded that Ganoderma seems to have potential therapeutic use for the
prevention and treatment of cancer. Liu et.al. 2006 isolated two triterpenoids, ganoderic acids,
which showed remarkable 5alphareductase inhibitory activities.