Reishi as a medical mushroom for cancer treatment

GL is also known as Reishi, Ling-Zhi, mannentake, and mushroom of immortality. As I already know the health benefits of it I can freely say that it has features to improve quality of life, heal the sick body, improve immune functions, and thus extend lifespan. When you see such a strong mushroom or any other plant then it is not surprising to you that It is used for hundreds of years. In Chinese medicine, GL is known for around 2000 years. Those properties are yield by specific compounds that mushroom contains rather than nutritional value.

If you want to enhance your energy level, vitality, stimulate the immune system to treat inflammatory-based disease or fight infection, and finally, if you want to prolong your life that’s a great choice. However, what I want you to know is that it might mean nothing if you don’t care for basic health-related issues. I’m taking here about sleep patterns, emotional disturbance, daily stress, poor eating habits. That probably won’t give you a piece of anything for such poor life habits.

I’m saying that because I just saw one clinical trial on which patients with metabolic syndrome (a triad of insulin resistance, hypertension, and poor glucose metabolism) didn’t achieve positive results when taking additional reishi supplement as a complementary treatment. You may feel powerful when taking another teaspoon of reishi powder after reading about miraculous things that this mushroom can make. But you can’t use one healthy thing against a bunch of shit. It doesn’t work the way we’d love to.

That’s especially an important note for cancer patients. In such a deadly disease with complex factors that affect disease appearance, development, progression, and treatment a wide treatment approach should be taken into account. Here, obviously, I’ll be talking only about reishi and studies results on cancer patients, in vitro, and so on.

Please remember, that if you suffer from cancer disease, reishi might be helpful, no doubt I’d probably be taking it. I’d be doing that, however with many other approaches to the disease. Among those would be dietary intervention, psychological, I’d check what relationships I have to work with, what are my stressors, how can I improve my sleeping habits and quality of sleep, what are my disruptive thoughts and what I can do with them, and so on. GL, Cordyceps Sinensis, curcumin, or Inonotus obliquus would be only a supplement to the diet. Exactly what they meant to be – supplements.

Most of the reishi is cultivated in China as it is rarely found in nature and human demands are well beyond that. You can buy different forms, like powder, supplements, tea, syrup, cream, and hair tonic. I like to use powders which I add to cocktails or coffee.

Highlights

  • Ganoderma lucidum (GL) modifies humoral and cellular immune functions,
  • Stimulates in vitro and in vivo activity of macrophages, dendritic cells, and natural killers,
  • Increases cytotoxic activity of naturals killers,
  • It has indirect and direct anticancer properties,
  • It stops cancer cells from proliferation and activates apoptosis,
  • Decreases glucose blood level, the main substrate for energy production for neoplastic cells,
  • Fights inflammation, stops angiogenesis, and metastasis.

Ganoderma lucidum bioactive substances

There are pharmaceutical properties rather than nutritional content that make reishi a strong mushroom. I like it to say that some plants and mushrooms shouldn’t be eaten to nourish the body but rather to adjust its functions. GL contains about 400 bioactive substance:

  1. Polyssacharides,
  2. Triterpenoids,
  3. Alkaloids,
  4. Benzopyran derivatives,
  5. Benzoic acid derivatives,
  6. Nucleotides,
  7. Sterols,
  8. Steroids,
  9. Fatty acids,
  10. Proteins, and
  11. Trace elements like magnesium, selenium, iron, zinc.

Among those substances, Ganoderma Lucidum polysaccharide (GLPS) has been identified as this major compound responsible for the observable physiological effects of GL consumption. They are also are major compounds by weight in which over 200 polysaccharides have been isolated. Among them, a pure glucose polymer called β-glucan (β-1-3 and β-1-6-D-glucans) is believed to be the one active ingredient in GLPS. Anticancer properties of reishi are attributed to polysaccharides and triterpenes. It doesn’t mean that the rest of the bioactive components are worthless or inactive, above mentioned are just two prominent ones.

You can find β-glucan in cereals, especially in oats

I want you to know, that β-glucan is a plant fiber that you can find in enormous amounts in cereals, especially in oats. In the whole oat seed, there is 4-7% of it, whereas in oat bran there is 6-9% of it. Most of the β-glucan in oat (80%) is water-soluble, thus can be helpful if one suffers constipation and needs to increase soluble dietary fiber intake.

I’m happy to say that the first time I heard about β-glucan was when I was studying and prof. Gibiński is one who wrote an excellent paper about it. He was one of the most likable lecturers during my studies because of his passion and the way he was speaking about the history of food products or nutrition. Polish readers can read the paper I’m mentioning here [Gibiński.2008]. You can read over there that besides anti-cancer properties, oats dietary fibers are an awesome option for diabetic or cardiologic patients. Now, who is gonna tell that healthy food is expensive?

You can provide at least 4g of healthy plant fiber by eating 100g of oats with milk, the fruits you like and other ingredients in one meal. That costs nothing in comparison to other food products. Besides oats in cereals, you can find in barley and wheat. Reishi that I describe here is a great source of it too, but you can find it also in Shiitake, Maitake, Hiratake, and oyster mushroom – a known mushroom that can be bought in shop, grown in the garden or gathered in the forest. Saccharomyces cereviviae contains them too. In comparison to 4-7% of β-glucan in oat, overmentioned mushrooms contains only 0.2-0,5% of it in dried mass.

What makes oats a better option than the overmentioned, is that Reishi, Shiitake, Maitake, and Hiratake (mushrooms) have mainly water-insoluble β-glucan (53-83%), yeasts fiber is completely insoluble. Oats seem to be the best option. However, reishi is still a great option for oncologic patients as it has overmentioned triterpenes (ganoderic acids, lucidenic acids, ganoderiol, ganodermantriol, lucialdehyde, and lanostanoid) with proved anti-cancer properties related particularly to ganoderic acids. If you have an opportunity, consider appropriate dietary supplementation with a personalized diet for your condition. You can read a lot about the health properties of β-glucan in polish publications (especially those written by Gibiński).

What are B lymphocytes, T lymphocytes and Natural Killers lymphocytes

Lymphocytes belong to white blood cells. They are very important for the immune system in recognizing antigens and fight infections. We can easily say that they are like leaders that point at the target for destruction. They recognize an invader or destroyed cell and decides to clean things up. Thus, they are everywhere in our bodies except our central nervous system (brain and spinal cord). They are like police, that track and patrol the body moving along the lymphatic and circulating system. In tissues, like the brain, thymus, lung, liver, and other, immune cells are deposited.

They are very important for the immune system, including cancer-fighting properties. There are different types of lymphocytes. Many studies have shown that GLPS has a strong impact on human body immune cells:

  1. B cells, B lymphocytes,
  2. T cells, T lymphocytes,
  3. Natural Killers, (NK)
  4. Macrophages,
  5. Dendritic Cells (DCs).

Let’s go through them briefly.

B lymphocytes, B cells (Bc)

They are ones that are produced mainly in the bone marrow. In percentage count, they are 15% of all lymphocytes. In contrast to other lymphocytes, they have B cell receptor that allows them to bind antigens and produce antibodies against those antigens. Antigens are specific parts of the bacterial, viral cell, or human body cell, or just a substance (eg. Pollen) that triggers an immune response. Depending on the antigen that binds to the receptor, a different response is seen. If B cell became activate with T helper cell (Th) assistance it starts to proliferate (increases the number of B cells). The antigen then is remembered (what is called immune memory).

Activated B cells are called plasmatic cells and they are able to produce antibodies. The latter, known as an immunoglobulin is a large, Y-shaped protein that binds specifically to antigen against which was produced based on immune memory. When an antibody binds to an antigen, an immune complex, also called antigen-antibody complex is formed and a further immune response is activated.

Macrophages that patrol the body recognizes quickly that the immune complex is formed, attaches to it, and destroy it by eating/digesting it (in a process called phagocytosis). That is how the thyroid gland is destroyed in the immune response in Hashimoto’s patients. It is similar to other autoimmune diseases or when neoplastic cells appear (it’s not a case for natural killer lymphocytes). If the immune system won’t recognize it, cancer may develop.

GLPS activates B cells, they increase their proliferation, differentiation, and immunoglobulins secretion. Spleen-derived lymphocytes that were stimulated by GLPS, increased the size of B cells as well as the percentage number of B cells by 2.5 – 4 times [Zhang.2002]. Similar results were reported in vivo. On the other hand, other immune cells increase their number in a similar amount after GLPS stimulation [Sohretoglu.2018].

T lymphocytes, T cells (Tc)

There are different subtypes of Tc with distinct functions: Same as Bc, Tc is produced mainly in bone marrow but they are activated in the thymus. That is why it is said that B cells are bone marrow-dependent and Tc are thymus-dependent. They are very important in recognizing and tracking invaders, they activate Bc so they can become plasmatic cells (and thus, produce antibodies).

T lymphocytes can be divided further on subsubtypes and thus, there are:

  1. T helpers (Th),
  2. Memory T cells,
  3. Regulatory T cells (Treg), Suppressor T cells formerly,
  4. Cytotoxic T lymphocyte (CTL, also known as T-killer cell, CD8+ T-cell),
  5. Natural killers (NK), and
  6. Mucosal associated invariant T cells.

They are specific to their function and for example, cytotoxic lymphocytes mean to kill invaders, cancer cells, or virus while T helpers, as you know are necessary for B or killer T cell activation. However, before such activation, antigen needs to be presented to B or T cells by macrophage or dendritic cell. Dendritic cells, macrophages are other types of immune cells, and with B lymphocytes (and with Langerhans cells) belong to antigen-presenting cells (APCs). They all are capable of binding antigen, and further processing and presenting them in the closest lymph node to T helper cells. That process is called antigen-processing and presentation. When Th recognize antigen, it starts to produce different compounds (chemokines) that recruit immune cells. Then activates them. What is the target? Everything that has processed antigen What is the purpose? To destroy it as efficiently as it is possible.

T regulatory cells are ones that modulate the immune system. They are very important in autoimmune diseases In which dietary intervention or lifestyle intervention points to increase their concentration or improve their function. They maintain tolerance towards antigens of their tissues and thus, prevent autoimmune disease development.

Natural killers lymphocytes

Cytotoxic cells and natural killers are similar in their roles. They directly kill infected or damaged cells. However, they are distinct. They are the first line of innate immunity defense and they come from bone marrow lymphocyte progenitor cells. In opposite to other immune cells, they can recognize stressed or neoplastic cells without antibodies and major histocompatibility complex (MHC, a complex by which antigens are presented) and that’s why they are called natural killers.

They consist on average 10 to 15% of all circulating lymphocytes.

The NK works cytotoxically through few mechanisms:

  • By releasing granzyme and perforine,
  • Through direct interaction with death receptors,
  • Through indirect interaction with death receptors by released cytokines: IFN, TNF, IL-3, granulocyte-colony stimulating factor GCSF, monocyte-colony stimulating factor MCSF.

What are dendritic cells?

They are the main and most efficient cells presenting antigens to other effector cells. They are a type of macrophage and connect innate with adaptive immunity. It is up to them what your immunological tolerance is.

GLPS increases expression of the cluster of differentiation (CD) molecules on the cell membrane of DCs as well as human leukocyte antigen-DR (HLA-DR) and interleukins. It happens by the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and p38 mitogen-activated protein kinase (MAPK) pathways.

What are macrophages

They are grown monocytes. They are the most important “digesting” immune cells that “eat” cellular debris, bacteria, virus, or cancer cells in a process called phagocytosis. If you are a medical or student of human nutrition you probably heard about atherosclerosis and so-called foam cells. Those cells are macrophages, that engulfed oxidized cholesterol in the cardiovascular wall in an enormous amount and deposited there, which builds up atherosclerotic plague.

GLPS increases phagocytosis of macrophages against cancer cells. Besides that, they increase the production of cytokines and chemokines.

Lymphocytosis and Lymphocytopenia

All lymphocytes are working in cooperation, as you see. Ones bind antigens (APCs) and present them to Th, that further recruits other immune cells to present such antigen and activate the immune response. Lymphocytes patrol the body and communicate with each other. If necessary, they produce compounds that inform other cells that they are in need, in a particular area of the body.

That is why it is important to make regular blood tests. Thus you know that something might not be working properly if your lymphocytes drop or increase above the normal range. For example, if you got you white blood cells with lymphocytes increased (lymphocytosis) you can suspect acute infection. If the issue is lymphocytopenia (decreased level of lymphocytes below normal range) that may mean that you are undernourished (deficiency of vitamin C, zinc, selenium, omega-3, and others), have malabsorption, gastrointestinal issues, or disrupted processes of white blood cells production (eg. Because of night-shift work, poor sleeping habits, stress, toxins exposure).

Immunomodulatory and anti-tumour activities of Ganoderma lucidum polysaccharide

It was found, that GLPS enhances T-cell and B-cell proliferation which means that their number increases. As you read above they are part of the immune system and yet if decreased, immune functions are compromised.

Another thing is that GLPS binds to a specific receptor called toll-like receptor (TLR), TLR2, and TLR4 on B-cells and with accompany of lymphocyte membrane immunoglobulin (mIG) it increases the production of Ig protein and Blimp-1 protein that regulates immune response.

GLPS acts also on T-cells increasing their cytotoxicity. This is through the increased production of IFN-γ, granzyme B protein, and TNF-α. It was noted, that NK cytotoxicity increases as well. When dendritic cells, which are the main antigen-presenting cells in our body were treated with GLPS they increased the expression of specific proteins and led to activation and maturation of immature DCs (through NF‐κB and p38 MAPK pathways).

In points, GLPS:

  • Increases the production of immunoglobulin protein,
  • Stimulates proliferation and differentiation of Tc and Bc,
  • Increases the cytotoxicity of Tc and NK,
  • Increases cell numbers of NK,
  • Activates DCs and stimulates the maturity of immature ones.

GLPS strengthens the immune system and its capacity to fight cancer. GLPS is safe to be taken with chemo- and radiotherapy. It strengthens therapy and improves the health of the patient. In studies done on different cancer cell lines, GLPS inhibited cell growthangiogenesistumor metastasis, and induced apoptosis. So GLPS doesn’t affect cancer only indirectly by modulating the immune system but had a direct effect on neoplastic cells.

GLPS cancer-related effect. Arrows represent activation, bars contrary represents inhibition [Sohretoglu.2018].

In the paper published by Sohretogu and Huang Ganoderma lucidum Polysaccharides as anti-cancer agent authors describe mechanisms through which GLPS modulates immune functions, inhibits tumor growth by anti-proliferative and cell-death promoting properties, and finally, inhibits cell motility and invasion. The latter is important as metastatic cancers are one of the main reasons for death in oncologic patients. One of the ways by which glucan interacts with effector cells is that it binds to membrane complement receptor type 3 (CR3, αMβ2 integrin, or CD11b/CD18) thus, activates the complementary system. An interesting paper was published in 2018 by Zhao et al. in which on a murine hepatocellular carcinoma (Hepa1-6-bearing C57 BL/6 mouse model) the use of GL resulted in an inhibition of tumor growth and proliferation [Zhao.2018]. The analysis revealed, that those effects were associated with inhibition of Jak-STAT, T cell receptor, and PI3K-Akt pathways.

For those who like to go deeper at mechanisms, I adapted from Sohretoglu.2018 graphic descriptions of biological mechanisms of GLPS. For further information interested may find in the referred paper.

Mechanisms of Ganoderma lucidum immunomodulatory function. Arrows represent activation, bars contrary represents inhibition [Sohretoglu.2018].


Antiproliferative and proapoptotic properties of Ganoderma lucidium polysaccharides on tumor cells. Arrows represent activation, bars contrary represents inhibition [Sohretoglu.2018].

Antimetastatic properties of Ganoderma lucidium polysaccharides on tumor cells. Arrows represent activation, bars contrary represents inhibition [Sohretoglu.2018].

Other biological activities of Ganoderma lucidum polysaccharide

The properties mentioned here are the ones that are necessary not only in the sick body but also in healthy ones. If you want to stay healthy, you have to take care of your oxidative stress level or glucose metabolism and inflammatory processes.

GLPS have antioxidative properties

Every plant that I’m reading about has those properties and that’s normal and usual as all plants have some biologically active substances that can scavenge reactive free radicals or have other antioxidative properties. Besides fighting free radicals, GLPS increases the expression of glutathione peroxidase, superoxide dismutase, and catalase. All three enzymes that fight oxidative stress in the body and are very important in health and disease. Oppositely, GLPS decreases the expression of prooxidative proteins like NOS (nitric oxide synthase) and NOX (NADPH oxidase). The latter one, NOX is the main produce of reactive oxygen species in the body, especially in type 2 diabetes because of increased glucose level and polyol pathway activity.

GLPS improves lipid and glucose metabolism

In studies done on mice GLPS  significantly reduced total cholesterol, triglyceride, LDL-C, fasting blood glucose level, and increased HDL-C and insulin level (in diabetic models). In one study done on the diabetic mice model, GLPS had a stronger impact on measured parameters than cyclosporine A and N-acetyl-cysteine (NAC). Such properties are very important for cancer patients as glucose, especially increased glucose level stimulates protein kinase B activity and mTOR activity what strongly stimulates neoplastic growth.

GLPS or Ganoderma lucidum in oncologic clinical trials and case studies

There have been few clinical trials done on cancer patients. Laboratory studies and preclinical ones bring positive results regarding the use of this mushroom against cancer. However, clinical trials are still lacking. On those clinical trials done already, some have methodological issues or were done on small groups of patients.

In 2016 the Cochrane analysis of clinical trials authors conclude, that reishi can improve quality of life, conventional treatment effects (chemo and radiotherapy), and immune functions [Jin.2016]. Their analysis consists of 5 randomized clinical trials. It is important to note, that GL alone didn’t demonstrate the regression rate as was reported in combined therapy. Chemo or radiotherapy was less effective than combined therapy. GL taken along with chemo/radiotherapy increased the chances of patients to respond positively for conventional treatment by 50% (RR 1.50).

Analysis of immune functions suggested, that:

  • GL increases the percentage of CD3 by 3.91% (95% CI 1.92% to 5.90%, P < 0.01),
  • CD4 by 3.05% (95% CI 1.00% to 5.11%, P < 0.01),
  • And CD8 by 2.02% (95% CI 0.21% to 3.84%, P = 0.03).
  • Leukocyte, NK-cell activity and CD4/CD8 ratio were marginally elevated.

The conclusion is that if a patient is taking conventional therapy, GL might augment its effects and we know, that it can simultaneously protect healthy cells from the toxic effect of therapy. In another meta-analysis of RCTs that were published in 2019 [Zhong.2019] authors found that either GL or Coriolus Versicolor – another mushroom with anticancer properties [Habtemariam.2020], improves overall survival and quality of life in cancer patients [Zhong.2019]. Besides this meta-analysis showed that:

  • C. Versicolor and GL related natural products had a favorable effect on elevated levels of CD3 (MD: 9.03%; 95% CI: 2.10, 16.50),
  • CD4 (MD: 9.2%; 95% CI: 1.01, 17.39),
  • But didn’t have an impact on the levels of CD8 (MD: −5.52%; 95% CI: −23.17, 12.13),
  • CD4/CD8 (MD: 0.73; 95% CI:-0.45, 1.91),
  • or NK(MD: 5.87%; 95% CI: −1.06, 12.8).

Here I want to describe studies done on humans with GL use. If you go to clinicaltrials.gov, you won’t find much about reishi-cancer studies. We are lacking a lot. Reishi is an Asian-origin mushroom, thus more might be found in the China database. Cochrane scientists that did such research didn’t find more. We have a big gap here. Noteworthy, what current studies bring puts GL in a good light.

Ganoderma lucidum improves immune functions in advanced-stage cancer-patients

In the study of Gao et al. scientists were studying the effect of GLPS extract on immune functions in advanced-stage cancer patients from various tissues [Gao.2003]. One of their inclusion criteria was a life expectancy of more than 12 weeks. In the final analysis, there were 34 patients, mainly with lung, breast, liver, colon, prostate, bladder, and brain. Most of them had metastasis or nodes. During the study, 2 patients were compliant, 1 was lost to follow up, and 1 diet because of liver cancer consequences. Nothing points out that GL was a cause of death. Patient stopped taking it at week 4 and diet at week 7.

The GLPS used in the study was Ganopoly® GL extract. Patients were treated with it at a dose of 1800mg daily TID (three times daily, 600mg per dose) before meals for 12 weeks. The extract contained 25% weight per weight (w/w) GLPS. This is equal to 450mg of GLPS daily being taken by patients. If the fruiting body of the mushroom GL consists of 5% of GLPS the daily dose of GL extract was equal to 270g of it.

Scientists put a measure on immune cytokines in the plasma of patients before and after treatment. The level of IL-2, IL-6, and IFN-γ increased, while IL-1 and TNF-α decreased. When specific CD markers were measured, the treatment had little or no effect on total peripheral blood cell counts (PBC) or the ratio CD4:CD8 T lymphocytes. However, the number of CD56 cells increased significantly.

When PBC was tested regarding their response to the phytohaemagglutinin (PHA, a plant lectin, that acts as a mitogen and stimulates immune cells to proliferation or cytokine production) it was shown a significant improvement in 80% of patients. In 2 patients (6.7%) it remained unchanged and decreased in 4 patients (13.3%). In a short answer, the immune response to the PHA in most studied patients improved despite the disease or chemo and radiotherapy).

The activity of NK cells (cytotoxicity) were measured before and after treatment against NK-sensitive K562 tumor cells. The mean NK activity increased from mean 26.6 ± 8.3% to 34.5 ± 11.8% at a 40:1 effector to target ratio. The authors also found a strong positive correlation between IL-2 and NK activity.

In the summary cancer-advanced patients, taking 1800mg of Ganopoly® GL extract (containing 450mg GLPS) TID:

  • Prevented the loss of the cytotoxic properties of immune cells and immune cells count. Moreover, GL extract increased the cytotoxicity of NK. As authors of the study discuss, the NK activity in cancer-advanced patients is significantly decreased, and their cytokine production is impaired what worsens disease prognosis,
  • GL extract negated the negative effects of chemotherapy and radiotherapy in cancer patients,
  • GL extract decreased TNF-α which is thought to attribute to cancer cachexia, thus GLPS may be a useful approach in countering it.

Ganoderma lucidum non-significantly improves immune functions in advanced-stage colorectal patients

Another study with cancer-advanced patients although here are only colorectal ones [Chen.2003]. This was a non-randomized CT open study of which 74 patients were given  5.4g TID (1800mg/capsule) of Ganopoly® daily for 12 weeks.

It is surprising to note, that in contrast to results from other studies, authors here note changes in cytotoxicity to PHA, NK cytotoxicity, cytokine levels, or particular CD immune cells. However, those changes were all non-significant what Sohretoglu and Huang didn’t mention in their review paper [Sohretoglu.2018]. The data were collected from 41 assessable patients and the small sample size is discussed by authors as a limitation of the study.

Ganoderma lucidum improves immune functions in advanced lung cancer patients

Chen et al. didn’t show treatment response to GLPS in the study published in 2003 on advanced colorectal cancer patients. This time Gao et al. (2003) in a randomized double-blind, placebo-controlled, multicenter clinical trial they enrolled 68 patients with advanced lung cancer. They were given 1800mg of Ganopoly® daily in three doses (600 mg per dose) for 12 weeks.

One of the inclusion criteria was “no recent or concomitant anticancer therapy”. Significantly more patients from the intervention group (13/37, 35.1%) achieved stable disease compared to the placebo group (7/31, 22.6%). They also reduced cancer-related symptoms (such as fever, cough, weakness, sweating, and insomnia) what was also observed in some patients from the placebo group. Karnofsky’s performance scale that measures performance status increased in more patients from the intervention group than from placebo, however, some didn’t.

Immune modulation was observed only in patients receiving GLPS®:

  • There was an increase in mitogenic activity of lymphocyte after concanavalin A stimulation,
  • CD3 increased by percentage,
  • NK activity increased.
  • A slight increase was observed for CD4 and a decrease of CD8 with a marginal change of CD4/CD8 ratio.

Undesirable effects were observed in 3 patients taking Ganopoly® which were nausea (2) and vomiting (1). Only one patient from the placebo group was vomiting.

Recently there was another study published done on non-small cell lung cancer patients [Liu.2020]. In this study, the Reishi & Privet Formula (RPF) was used along with chemotherapy (paclitaxel plus cisplatin or paclitaxel plus carboplatin) for 6 weeks. This formula consists of a combination of sporederm-broken spores of GL and water and ethanol extract of dried mature fruit of Ligustrum lucidum and is aimed to have a synergistic effect. Patients were taking, in total 3.4g of formula per day in 3 doses in which GL consists of 53% w/w and Ligustrum lucidum 39%.

As a result, a combination of GL and Ligustrum lucidum had a positive effect on maintaining the quality of life and emotional well-being among patients with non-small cell lung cancer undergoing chemotherapy. It’d be nice to know what differences would be if compared to the same group patients receiving only GL or Ligustrum l. It can be speculated, as authors suggest that both compounds strengthen their properties [Liu.2020]. At least it was shown on a macrophage cell line that GL taken along with Shiitake (Lentinula edodes) and Maitake (Grifola frondosa) have a synergistic effect on the expression of cytokines [Mallard. 2019].

Beside known IL-6 and TNF-α authors decided to measure the level of IL1-α instead of IL1-β as the former cytokine was found to be correlated with tumor regression [Mallard.2019 followed by Voronov.2013]. Results showed, that the mixed-use of mushrooms yield to a synergistic effect on the expression of the pro-inflammatory IL1-α, IL-6, and TNF-α, and an antagonistic effect on the expression of anti-inflammatory IL-10 [Mallard.2019].

Ganoderma lucidum improves immune function in immunocompromised children with cancer (Acute lymphoblastic leukaemia, Acute myeloid leukaemia)

In this randomized, double-blind, placebo-controlled, parallel-group CT cancer patients in the age of 2-18 years old were recruited [Shing.2008]. They were during maintenance for leukemia or within weeks following chemotherapy for solid tumors.

Patients received placebo or Lingzhi, 4 to 6 capsules per day of 300 mg GL according to age for 6 months. In total, children received 1200-1800 mg of mushroom.

The lymphoproliferative responses of peripheral blood mononuclear cells (PBMC) to mitogens were compared between the placebo and intervention groups. The authors used PHA, concanavalin A, and pokeweed mitogen (PWM) as a mitogen in the study. GL-group had significantly higher stimulation indices for PHA (364) and PWM (83) compared to the placebo-group (-134 and -1). Concanavalin A stimulated PBMC slightly at a significant level. The stimulation indices of PBMC to PHA and PWM in the GL-group were significantly improved compared to placebo.

There was no hematologic or biochemical derangement in patients after 6 months of 1200-1800mg of GL daily taken in capsules. In conclusion: GL augments the immune response to mitogens in immune-compromised children with cancer.

Ganoderma lucidum increased CA72-4 marker in gastrointestinal cancer patients

As we read in the paper published by Yan et al. in the Integrative Cancer Therapies, GL spore treatment caused an increase of CA72-4 serum marker in 5 patients after 1-2 months of supplementation [Yan.2014]. This one is the most valuable one for monitoring therapeutic effects in patients receiving treatment for gastrointestinal cancer.

The level came back to normal after GL spores were withheld or discontinued. It might be thought that intervention brought negative effects because of the increase of CA72-4 is related to disease progression. But the increase of the marker (on the level on average 250% from baseline) was reported also when cytotoxic drugs were used eg. Oxaliplatin for metastatic colorectal cancer or others like doxorubicin, tamoxifen in metastatic breast cancer patients. Those observations were explained by stronger chemotherapy used and caused by neoplastic cell lysis.

It can’t be said what was the reason for the increase of CA72-4 marker in the described patients. But as we know there are a few ways through GLPS that have antitumor properties and may cause cancer cell death. The authors conclude, that “GLS should be used with caution, and patients should be carefully monitored and followed-up”.

Ganoderma lucidum improves cancer-related fatigue in breast cancer patients

In this pilot study, 48 breast cancer patients with fatigue caused by the disease were assigned to the control or intervention group. Appropriate questionnaires data were collected to study the effect of the GL. The intervention group received spore powder of GL 1000mg three times a day for 4 weeks.

At the end of the study, patients who received spore powder of reishi:

  • Improved the domains of physical well-being,
  • Augment cancer-related fatigue (CRF),
  • Improved quality of life and reported less anxiety and depression.

The concentration of TNF-α of both groups at the beginning and the end of the study. The TNF-α level in the intervention group dropped from 129 to 72 pg/mL (by 44%) after 4 weeks [Zhao.2012].


The concentration of IL-6 of both groups the beginning and at the end of the study. The IL-6 level in the intervention group dropped from 62 to 38 pg/mL (by 40%) at the 4 week of the study [Zhao.2012].

The are no known firm mechanisms responsible for CRF, however, TNF-α and IL-6 are suspected to be implicated in this. From other studies, the authors knew, that GL can interact with immune functions and cytokine release. Thus besides collected questionnaires, they measured the level of the over-mentioned compound at the beginning and after treatment.

Both TNF-α and IL-6 were found to be correlated with CRF. The mean serum level of cytokines was higher before the study than 4 weeks later and they dropped only in the experimental group.

In the study, GL spores improved the physical and psychological health of the patients and decreased pro-inflammatory cytokines level augmenting cancer-related fatigue. There were no serious “side” effects of the treatment, most of them were mild dizziness. I don’t like to write “side effects” as there are none, there are always effects. If they are negative, they are called “side”. There were also no changes in alanine aminotransferase, aspartate aminotransferase, and blood urea level at the end of the study.

Ganoderma lucidum for recurrent gynecologic cancer

In a randomized double-blind, placebo-control study Suprasert et al. used different extracts of GL in a salvage setting of gynecologic cancer treatment [Suprasert.2015]. The authors used water extract and GL spore type extract or placebo on 60 patients. The groups were ingesting 6000 mg/d of extract or placebo for 12 weeks. Unfortunately, half of the patients were withdrawn from the study because of the rapid progression of the disease, and only 11, 8, and 9 patients were left in the water-, spore-extract, and placebo group. That’s a strong limitation of the study. Stable disease was achieved by 38%, 50%, and 0% in consecutive groups. Also, the one-year survival rate was higher than in the placebo group and was as follows 64%, 60%, and 44%.

Both extracts showed a better impact on patients than placebo in 12 weeks. There were no differences between groups in regards to hematologic parameters, immunomodulatory level, and quality of life.

Is Ganoderma lucidum safe? Toxicity, negative “side” effects, and interactions

According to the results, no serious toxic effects were reported when high doses of GL were administered in water extract to mice. However, alcoholic extracts on humans should be taken with caution when taken with:

  • Anti-diabetic drugs,
  • Anti-hypertensive drugs,
  • Anti-coagulants.

GL may augment the effect of those drugs and their dose might be reduced or adjusted. This is because GL by itself fights diabetes and has anticoagulant properties. Because of the latter, the supplementation with GL should be consulted with the medical specialist if any operation is on the way or patient have gastrointestinal bleeding or gastric ulcers.

Reishi has anti-microbial, anti-parasitic, anti-viral, and anti-fungal properties and that might be an additional feature that puts it worthy to take by oncologic patients. In the study done by Yoon et al. (1994) GL taken along with four kinds of antibiotics (ampicillin, cefazolin, oxytetracycline, and chloramphenicol) have additive, synergistic or antagonistic properties. Thus it seems to be a great option for reducing the dosage of antibiotics without detriment of antimicrobial properties.

The pregnant and breast-feeding woman shouldn’t supplement GL as its safety hasn’t been tested yet (2020).

In the analysis of Cochrane, some negative effects of supplementation were recorded, which were nausea and insomniaHematological and hematological toxicity wasn’t reported at a significant level.

Is Ganoderma lucidum safe to being taken with chemotherapy?

From studies described above on humans, we know that GL is generally safe and enhances the therapeutic effects of chemo- and radiotherapy. Preclinical studies done on animal models and in vitro brings similar results. Based on the effect of GLPS on immune cells, such intervention may even make drug-resistant cells became vulnerable to the treatment [Huang.2010]. Most studies done on GL was with concomitant conventional therapy. It augments therapeutic effects and protects healthy cells from the toxic effect of radio or chemotherapy [Lam.2020].

For example, in the study on mice GL mitigated a negative impact of cyclophosphamide on immune functions [Nonaka.2008]. When different endometrial cancer lines were incubated with cisplatin and Cordyceps Sinensis or Ganoderma lucidum with Agaricus blazi Murill the combined solution had a stronger effect than cisplatin alone [Hahne.2014]. GL protects the body from the nephrotoxic and global toxic effect of cisplatin use and cardiac muscle from the toxic use of doxorubicin [Ahmad.2020].

Conclusion

There are some difficulties in forming firm conclusions based on the current data. Ganoderma lucidum seems to contain immune-modulating compounds, that regulate and stimulate immune functions that improve its anti-cancer properties. They uphold the immune system of cancer patients during chemo or radiotherapy and prevent the decrease of activity or number of immune cells. Moreover, GL interacts also directly with cancer cells inhibiting their growth or metastasis. At the same time, they protect healthy cells from the toxic effect of conventional therapy. Most patients usually react positively to the GL supplementation, however, not everyone was responding positively to the intervention. Some patients had an adverse effects (nausea, vomiting, dizziness) but they were very rare.

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