The Medicinal Mushrooms in Supportive Cancer Treatment

The culinary world has embraced mushrooms for their umami flavor, texture, and versatility. Medicinally, they have been used in Asian cultures for two thousand years for health and longevity. Modern science is discovering their therapeutic importance in cancer, for modulating immune function, inhibiting cancer growth, and providing a range of nutritional benefits for overall health and well-being.

There are hundreds of mushroom species throughout the world, but most of the research in cancer focuses on specific types. The available research is in the laboratory, commonly with mice, using human cancer cells, with limited clinical studies in patients. Because their benefits offer safe, non-toxic support in cancer care, hopefully, more clinical applications in patient treatment will move their potential from the bench to the bedside.

While medicinal supplemental forms of mushrooms are more concentrated, their availability as highly delicious and nutritious foods should prompt their culinary use as something that can easily be integrated into the diet, offering preventive and supportive benefits for overall health

Introduction

Mushrooms are a species of fungi which also includes yeast and mold. Yeast is commonly named candida and there is misinformation that eating mushrooms can stimulate the growth of candida, which does not occur as candida can’t utilize the B glucans in mushrooms to grow.

Some mold species are associated with human disease that is associated with water damage exposure. Pathogenic mold produces toxins, mycotoxins, that cause complex chronic diseases and can be differentiated from mushrooms from its lack of a fruiting body.

Different fungi have also changed medical therapies with discoveries of their pharmaceutical potential to control disease. Antibiotics; penicillin and streptomycin, used in TB, lovastatin form aspergillus fungus was the first drug inhibitor of cholesterol synthesis, and cyclosporin a molecule of mold used to prevent organ rejection.

While each geographic area of the world has its own unique number and species of mushrooms their health benefits are recognized and utilized worldwide, in all cultures.

The compounds in mushrooms offer multiple supportive elements which demonstrate their high status for healing over the centuries.

Fungal mycelium are the vegetative structures called hyphae that are the branch or thread like components that form a network that allow absorption of nutrients. The compounds used in medicine include penicillin, and the first cholesterol lowering statin, lovastatin, derived from aspergillus fungus.

These structures are also used ecologically as bio-packaging materials.

The fruiting body is the mushroom which provides proteins, vitamins and minerals. Studies have shown Lions Mane, Reishi( Ganoderma or Ling Zhi) and Cordyceps alos contain adaptogens that can help modulate stress responses and support adrenal function.

The cell walls contain long sugar molecules, Beta Glucans called polysaccharides that are shown to enhance the immune response by activating macrophages and NK, natural killer cells, that the immune system utilizes to for recognition and destruction of cancer cells, and other lymphocytes that are cytotoxic to cancer cells and block the growth of new blood vessels, angiogenesis.

Ergothione is an amino acid and acts as an antioxidant to help prevent cell damage.

Triterpenes are found in the fruiting body, the cap, stem and gills. Ganoderma or reishi mushrooms have large amounts which in laboratory studies have been shown to inhibit cancer growth and induce cell death.

Selenium is an important mineral that supports antioxidant and immune functions.

Polyphenols are organic molecules in geometric shapes allowing bonds to other molecules. These substances protect against oxidative free radicals and reduce the risk of cancer, chronic disease and heart disease.

Mushrooms used medicinally are available organically as powders and capsules and, ideally, should be taken between meals in 2 divided doses. Side effects are considered minimal and those commonly seen include rash, upset stomach or nausea, and changes in bowel movements at high doses. The digestive symptoms sometimes make tolerance difficult.

Chinese practitioners, when treating digestive diseases, are concerned about foods that cause dampness or excess fluids in the digestive system resulting in loose stools, or water retention in the extremities. But mushroom species like Zhu Ling (Polyporus) and Fu Ling (Poria) are mushrooms that are included in many digestive formulas used as diuretics to remove excessive fluids.

Mushrooms and Their Effects on Cancer

Cordyceps Mushrooms

In the wild, the cordyceps fruiting body parasitizes many insects, to extract nutrients.for growth. They are very rare and costly to gather so today they are cultivated on solid and broth media. They have been used as a treatment for infectious diseases, in Asia, for over two thousand years and today are still efficacious.

This mushroom contains all the essential amino acids, vitamins E and K and the water soluble vitamins B1,2 and 3 and B12, and multiple trace elements.
It is unique in that it increases oxygen utilization which enhances the production of ATP, our cellular energy source, which has been demonstrated to reduce fatigue.
It relaxes bronchial smooth muscle, improving asthma
Increases sperm motility.

Cordyceps And Cancer Treatments

A study using extracts of cordyceps showed it stimulates IL-1B which stimulates immune support in cancer as well as TNF-alpha which targets blood vessels cancer cells are utilizing for nutrition. It also showed its antioxidant, anti infective and antitumor effects.The anti tumor effects were tested and successful on specific human cancer cells, in the laboratory, on breast, non small cell lung cancer, colon and cervical cancers. Cordyceps also decreased the side effects of chemotherapy.

A 2024 article reviewed multiple databases of the use of cordyceps as an additional therapy in patients with Lung cancer. There were 12 randomized controlled studies, which included over 900 patients. The addition of cordyceps;

Improved:

Tumor response
Immune function of CD8, NK cells, and antibodies Ig A/M/G
Quality of life
Decreased adverse drug reactions, including bone marrow suppression

In another study, the researchers were trying to develop ways to enhance breast cancer treatment using PD-1 checkpoint inhibitor drugs which are only effective in 30% of patients. PD-1 therapies unblock the immune system allowing an enhanced attack of the cancer cells.Cordyceps extracts were tested to assess changes in up regulation of the immune response to damage associated molecular patterns( DAMP’s) and apoptosis of cancer cells using mouse and human breast cancer cells.

The surveillance cells recognizing DAMP’s, or cell damage, showed an increase in tumor specific immune T cell production which was cytotoxic to the cancer. Cordyceps also induced apoptotic, or programmed cancer cell death. The conclusion encouraged more clinical trials to evaluate cordyceps potential to enhance cancer cell death in breast cancer and when combined with immune checkpoint inhibitors which could potentially enhance treatment in PD-1 breast cancer patients.

Using a human cancer cell line, cordyceps was studied in the lab to assess its effect.

Cordyceps was shown to inhibit cancer cell proliferation by inducing programmed cell death and blocking the PI3K-AKT- mTor pathway which prevented the cancer cells from recycling damaged cellular components for use.

Maitake D fraction (Grifola frondosa)

The Maitake mushroom has been a dietary stable for hundreds of years in Japan and has an established safety record. Studies have expanded an understanding and documentation of its beneficial effects, originally based in folklore to scientific confirmation of its anticancer effects.

The Maitake D fraction of the Grifola mushroom is a water soluble protein bound combination of glucan fractions which are isolated from the fruiting body via hot water extraction.

This D fraction fraction has been used in cancer studies in animal models, showing enhanced anticancer activities by activating immune system macrophages, natural killer cells(NK) cells and T cells. In a patient study, in 2003, while in a very small sample group, NK cell levels increased, tumor markers decreased and there was an inhibition of metastasis.

Similar animal models using Maitake -D fraction revealed that it increased IL12 (interleukin 12). Interleukins are sugar protein molecules produced by the white blood cells that regulate the immune system and IL 12 activates Nk cells. Maitake-d has also been shown to block new blood vessel formation by cancer cells.

Ganoderma or Reishi, also called Ling Zhi

Has been used in Traditional Chinese Medicine (TCM) for multiple centuries and is used in treatment to enhance digestive function, calm the mind and diminish cough and asthma.

The ingredients include proteins, enzymes, vitamins, amino acids, flavonoids, triterpenoids and polysaccharides.

The molecules of triterpenoids and polysaccharides are the active cancer compounds and their effect on multiple cancer types was summarized in a 2023 review paper. The authors referenced twenty years of data on lab research using human cancer cells.

Ganoderma’s bioactivity has been shown to:

Inhibit cancer cell proliferation and metastasis
Induce apoptosis
Regulate autophagy, or the recycling of cellular components from damaged cells.

The largest number of studies involved GI diseases but blood, breast, lung, cervical and brain, showed similar effects.

Blocks androgen receptors on prostate cells limiting hormone stimulation of the cancer

Reduces fatigue, anxiety and depression in breast cancer patients

Inhibits EBV virus which has associations with naso pharygeal, hodgkins and and some types of stomach cancer

Using an animal model, a 2024 animal study showed how Ganoderma’s prebiotic effects in the gut are able to modulate the immune system and that these features inhibited tumor growth and enhanced antitumor activity in colorectal cancer, while also improving gut dysbiosis.

A study using triterpenes extracted from Ganoderma, the laboratory, demonstrated its ability to suppress a human colorectal cell type which had been transplanted into an animal model. Its actions were associated with interference of cell replication and inducing programmed cell death.

A study using both Ganoderma and Agaricus mushrooms taken in the diet with each representing 50%, in mice, for 14 weeks inhibited sarcoma cancer cell growth, enhanced the cellular immune system by increasing CD4, immune helper cells and CD 8 cytotoxic cells and decreasing the humoral immune system the CD 19 or B lymphocyte cells. This modulation improved the immune balance of T cells to B cells to create a greater anti cancer effect suggesting that the B glucan polysaccharides might help direct the immune system toward attacking cancer.

Button Mushroom (Agaricus Mushrooms)

These are familiar mushrooms commonly seen in markets. If it has a white fruiting body or cap it is called a button mushroom and if the cap is brown, it is named a cremini mushroom. Their components include amino acids, unsaturated fatty acids,, vitamin B and C, phenols, indoles, vitamin D and B-Glucans and an organic molecule called triterpene.

The Agarius fruiting body offers :

Antioxidant,
Antibacterial
Anti Inflammatory
Anti tumor

And immune modulating properties

Using the Agaricus mushroom, in a laboratory setting, a polysaccharide or molecule with many bonded sugars was shown to inhibit the spread and invasion of colon cancer cells in a specific human cancer cell line.
A study evaluated the effect of Agaricus mushroom powder in patients with prostate cancer and a continuously rising PSA, indicating possible recurrent cancer. There were 36 patients and 36%, 13 patients had their PSA decrease below baseline levels and 2 patients had undetectable PSA which remained so for almost 3 years. The authors concluded that Agaricus had decreased immunosuppressive factors.

TurkeyTail (Coriolus)

Turkey tail mushroom is referenced over two thousand years ao in Chinese medicine as beneficial for health and longevity. It is known for its ability to enhance immune function, being useful for those with weakened immunity. It also acts as a prebiotic which supports the growth of friendly commensal bacteria, and as an antioxidant, reducing reactive oxidative molecules.

A component of Coriolus, PSK, (polysaccharide K), as it is called in Japan or PSP in China, is extracted from this mushroom. It is rich in amino acids that are essential for building proteins, immune cells and enhancing energy. There are also B vitamins, trace minerals.

Most of its clinical applications come from studies done in Japan in the early1990’s with over a dozen trials related to treatment with PSK for stomach (gastric) cancer. The uniform results were based on patients receiving two chemotherapies following surgical removal of the stomach cancer, with the addition of PSK. The data showed that adding PSK to the treatment protocol extended survival and the disease free period.

In 1994, the Lancet, the premier British medical journal published a paper from Japan in which took 262 patients that were randomized to standard chemotherapy or standard care plus PSK. Survival at 5 years was 73% with PSK and 60% with chemotherapy, while those that remained disease free were 70% on PSK and 59% on standard treatment.

In triple negative breast cancer cells, in a laboratory study, an extract of Coriolus was shown to modify the tumor microenvironment changing immune macrophages from tumor promoting cells to antitumor agents.

Herceptin (Trastuzumab) is a monoclonal antibody utilized to treat breast and gastric cancer in patients with a positive HER 2 protein, to block thisreceptor on the cancer cells which otherwise can lead to more rapid growth and spread of the cancer. Herceptin’s effectiveness appears to rely partly on the activity of NK, natural killer cells, from the immune system.

Using breast cancer cell lines, a study using PSK from Coriolus mushrooms was designed to assess its ability to activate NK cells. The study did demonstrate NK enhancement, suggesting that PSK could potentiate the effect of Herceptin in HER-2 positive cancers.

Shiitake (Lentinus Edodes)

Shiitake mushroom B-Glucan is known to have anticancer properties. Using a mouse model of breast cancer, the Shitake B-glucans, multiple bonded sugar molecules, were shown to inhibit tumor growth and inflammation and induced programmed tumor cell death, apoptosis.

Lentinan is the active molecule in Shitake mushroom. In rodent related studies it inhibited tumor angiogenesis or new blood vessel formation in lung and colon cancer

Chaga Mushroom

Its composition contains protein, trace minerals and proteins along with complex sugars, b glucans, and terpenoids

It possess multiple beneficial medicinal characteristics including:

Anti cancer
Antioxidant
Antiviral immune modulating
Gene protection

Its anti-cancer effects are its ability to inhibit NF-Kb which can increase inflammation in the tumor microenvironment and stimulate tumor growth, enhance new blood vessel formation for tumor spread and prevent cell death.

It has been shown in animal models using human cancer cells to affect breast, colon and B cell lymphoma.

Enokitake, Enoki or Golden needle mushroom (Flammulina velutipes)

This mushroom has been cultivated for its nutritional value in China and Japan for centuries. It contains amino acids, trace minerals, protein and lipids along with the active molecules of glycoproteins, sugar and proteins, phenols( flavonoids) which are antioxidant and sesquiterpenes.

The studies are using human cancer cells in the laboratory has shown:

One study using the enoki extract in breast cancer cells having estrogen positive and negative receptors showed in both types that cancer growth was inhibited and cell death increased.

A study from 2024 an enoki extract was used to treat adenocarcinoma lung cancer cells and was shown to inhibit the cancer cell growth and spread and also increased cell death through the mitochondrial pathway.

Pleurotus Ostreatus (Oyster Mushroom)

Clinically

A study in patients on pleurotus ostreatus and control patients measured the anti-tumor activity of their cellular immune system, in hormone dependent breast cancer, stage 1-3. In the pleurotus group, there were significant increases in CD 4, t helper cells, CD8, cytotoxic T cells, CD3 cells that act on T cell receptors to activate them, and CD 19 cells that activate B cells that which are antibody producing against foreign cancer cells.

Lion’s Mane ( Hericium Erinaceus)

This mushroom has been used for centuries in Chinese medicine for GI diseases, especially gastric problems such as chronic gastritis and gastric ulcer, and assists in repair of damaged gastric mucosa. It also has been shown to be active against H Pylori.

In animal studies with mice, lion's mane increased cancer cell death, apoptosis, and inhibited cancer growth.
In animal studies, in colon cancer, it demonstrated an increase in natural killer (NK) cells and a decrease in angiogenesis or new blood vessel formation that allows cancer to spread. It does this by regulating cell replicating pathways.
Interestingly, lion’s mane shifts the microbiota toward increased bacteria that produce short chain fatty acids (SCFA) which protect against colon cancer.

AHCC (Active Hexose Correlated Compound)

This is a hybridization of several mushrooms

In women with persistent high risk HPV, human papillomavirus, associated with cervical cancer, AHCC eliminated HPV in 63% at 6 months of treatment.
In ovarian cancer lines, in the lab, AHCC inhibited cancer cell growth

Breast Cancer Studies

Studies related to breast cancer show the effects of the varieties of mushroom extracts, listed in this article, in lab testing, animal models and clinical applications which have inhibitory effects on breast cancer.

Agarius (Agaricus Mushrooms)

Clinical patient studies, double blind randomized control showed reduced GI side effects caused by chemotherapy

And

Increases red blood cell counts, monocytes and T lymphocytes

Modulates improved immune function, Inhibits breast cancer growth,

Improves sensitivity when paired with doxorubicin

Coriolus (TurkeyTail)

Clinical patient studies

When combined with the Chinese herb DanShen, which activates and nourishes the blood and is used to treat early breast abscess in Chinese medicine, together they increase T helper cells (CD4) and cytotoxic T cells (CD8).

And

When combined with chemotherapy improves overall survival

Suppressed cancer cell growth, enhances T cell activity against breast cancer, and cytotoxic

Ganoderma