Medicinal Mushrooms & The Immune System

Medicinal mushrooms have been claimed to support the immune system for thousands of years, but it is only recently that scientists have made a concentrated effort to discern which specific compounds have bioactive properties. The mushrooms that have a strong line of evidence to promote a healthy immune response are Chaga (Inonotus obliquus), Reishi (Ganoderma lingzhi), Maitake (Grifola frondosa), Lion’s Mane (Hericium erinaceus), Cordyceps ( Cordyceps sp.), and Turkey Tail (Trametes versicolor). This article seeks to consolidate the most recent research on these fungi and how they can help improve our immune system. 

Chaga (Inonotus obliquus)

Chaga (Inonotus obliquus) is a mushroom that belongs to the Hymenochaetaceae family, and it has been used for centuries to promote a robust immune system response. Chaga grows at latitudes of 45º-50ºN and has been used traditionally in Russian and Eastern European folk medicine to treat cardiovascular or heart disease, diabetes, and gastrointestinal cancer^[1]

Recently Chaga has been studied in great detail by Western scientists and medicine for its potential anticancer, antiviral, and hypoglycemic properties. Eleven bioactive molecules have been extracted from Inonotus obliquus in the last 15 years. Each molecule that has been isolated from Chaga works in a unique way, but the majority of molecules isolated from Chaga show promise in slowing down the spread of tumor cells, having anti-diabetic effects, and providing the body with antioxidants. Antiviral properties of Chaga have also been suggested in the scientific literature. 

Traditional cancer therapy, such as chemotherapy and surgery, has many undesirable consequences and this has sparked the need to look for alternative approaches – the use of the Chaga mushroom is one of them. The use of Chaga in human trials is still in its infancy, but Chaga has been used to treat mice afflicted with cancer. One study conducted by Kim et. al (2006) showed a 4.07-fold increase in the survival rate of mice treated with melanoma^[2]. The mushroom did not kill the cancer cells directly but instead created an immunostimulating effect that increased the longevity of the animal. The specific cancer-fighting biological metabolites that are contained within Inonotus obliquus include Inotodiol^[3], Ergosterol peroxide^[4], 3β-Hydroxylanosta-8^[5], 24-diene-21-a^[5], Hispidin^[6], Lanosta-24-ene-3β, 21-diol^[7], Lanosta-7, 9(11), 23E-triene-3β, 22R, 25-triol^[7], and Betulinic acid^[8]. 

Chaga also has anti-diabetic effects. In the literature, Chaga has been reported to increase insulin sensitivity, decrease blood glucose levels, and improve the levels of HDL cholesterol. Antiviral properties of the birch fungus reduced the ability of Hepatitis C to infect cells within 10 minutes^[9]; Chaga was also able to prevent the replication of HIV in lymphoblast cells^[10]. 

It is interesting to note that traditional Russian and Eastern European folk medicine have been using Chaga for centuries and it is only recently that Western medicine is validating the same findings. This is a common theme when researching the ethnobotanical values of plants and fungi, and it makes one wonder how many people could have been helped if traditional medicine was a more accepted practice in Western countries. Long-term, standardized, clinical trials are needed to unlock the full potential of what Inonotus obliquus can do for the human population. 

Reishi (Ganoderma lingzhi, Ganoderma lucidum,)

Reishi (Ganoderma lingzhi) is known as the “mushroom of immortality” and has been used in Chinese medicine for over 2,000 years. The term Reishi does not apply to one specific species of fungus but is more a catch-all term for different fungal species within the Ganoderma genus. 

Ganoderma species contain diverse phytochemicals (compounds that are produced by plants) such as Ganoderic Acid, Danoderiol, Danderenic Acid, and Lucidenic Acid. These phytochemicals have a proven track record of increasing cytokine production. Cytokines are small proteins that control the growth and activity of immune system cells. When cytokines are released it kickstarts the immune system into doing its job.

Reishi can affect cancer through immunomodulation resulting in tumor destruction or it can have an effect on the tumor directly, such as slowing down cell growth. Ganoderma polysaccharides have been shown to decrease cell proliferation in mice afflicted with sarcoma^[2]. Ganoderic acid also has been shown to decrease tumor size and growth in mice that have lung cancer^[3]. Research indicates that Reishi also has the potential to increase immune cell activation in order to fight breast cancer, prostate cancer, leukemia, sarcoma, and colon cancer^[4]. 

Although most of the studies with Reishi have been done on those who are ill, there is evidence that shows that reishi can benefit healthy people as well. One notable study tracked football players who were taking Reishi capsules for six weeks during training. After the trial, the football players who had taken Reishi had improved lymphocyte function, which helps to fight infections^[5]. 

The immune response of Ganoderma is also dependent on the species of mushroom being used. One study compared red reishi (Ganoderma lingzhi) to purple reishi (Ganoderma sinense) and found that red lingzhi affected the genes involved in macromolecule metabolism, while the purple variety focused more on the pathways that correspond with inflammation and immune response^[6]. These genes regulate white blood cells which are a critical part of our immune systems. However, this was just one study, and regardless of color both the red reishi and purple reishi have been documented to elicit notable immune responses. 

Maitake (Grifola frondosa)

Maitake (Grifola frondosa) has a high amount of bioactive polysaccharides, especially D-fraction, MD-fraction, and SX-fraction. The majority of research with Maitake has focused on D-fraction which has well-documented immunomodulatory and antitumor activities associated with it. To assess the effectiveness of D-fraction studies have been conducted in vitro (cell cultures) and in vivo (animals and humans)^[1]. 

The immune system is our first line of defense when it comes to microbial infections. D-fraction has been shown to increase macrophages by 2.7x and the bacterial activity of T-cells by 2.6x^[2]. Macrophages are a type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. T-cells on the other hand are key players in our immune response to viruses. T-cells are responsible for directly killing infected host cells, activating other immune cells, and producing cytokines.

D-fraction also appears to be a potent immunomodulator in terms of cancer cell growth^[3]. Studies have shown that D-fraction is capable of slowing down the cancer cell growth in mice at very high levels. One leading scientist, Hiroaki Nanba, has studied medicinal mushrooms for 15 years and claims that Maitake “has the strongest activity in tumor growth inhibition both when administered orally and intraperitoneally^[3].”  Hiroaki Nanba studied mice bearing MM46 (breast cancer) and fed them a diet of 20% Maitake for 31 days. At the end of the trial, four out of the ten mice had tumors that had gone into remission, and the remaining six had a 90% suppression rate of the tumors when compared to the control mice^[4].  

Within the same study, D-fraction also increased the number of natural killer cells (NK cells) and T-cells by 1.5-2.2 times^[4]. NK cells provide a rapid response to cells infected with viruses and other pathogens. NK cells also respond to tumor formation and are able to destroy faulty cells with the presence of antibodies. T-cells on the other hand are primed to recognize a specific threat in our body by detecting antigens on a foreign cell surface. Both NK and T-cells are crucial to the healthy functioning of our immune system. 

In addition to Maitake’s robust immunological response, Maitake has also been shown to have anti-HIV activity. These findings were confirmed by both the Japan National Institute of Health and the U.S. National Cancer Institute in early 1992.

There is also a considerable amount of research that suggests taking Maitake in conjunction with Vitamin C can improve the outcomes of cancer patients^[5]. The synergistic effects of taking Maitake and Vitamin C seem to alleviate various side effects of chemotherapy while also increasing the effectiveness of the chemotherapy. The D-fraction contained in Maitake holds promise at being effective against cancers of the breast, lung, liver, prostate, and the brain. Some limited human trials have provided evidence of tumor remission at these specific sites^[4]. 

Maitake has been consumed by the Japanese people for hundreds of years so it is unlikely to exhibit any toxicity to people who like to supplement their immune system with this mushroom. 

Note: In the literature, D-fraction is also known as PDF. 

Sources Cited

Chaga (Inonotus obliquus)

1. Cui, Y., Kim, D. S., & Park, K. C. (2005). Antioxidant effect of Inonotus obliquus. Journal of Ethnopharmacology, 96, 79–85. https://doi.org/ 10.1016/j.jep.2004.08.037
2. Kim, Y. O., Park, H. W., Kim, J. H., Lee, J. Y., Moon, S. H., & Shin, C. S. (2006). Anti-cancer effect and structural characterization of endopolysaccharide from cultivated mycelia of Inonotus obliquus. Life Sciences, 79, 72–80. https://doi.org/10.1016/j.lfs.2005.12.047
3. Li, X., Wu, Q., Bu, M., Hu, L., Du, W. W., Jiao, C., … Yang, B. B. (2016). Ergosterol peroxide activates Foxo3-mediated cell death signaling by inhibiting AKT and c-Myc in human hepatocellular carcinoma cells. Oncotarget, 7, 33948–33959. https://doi.org/10.18632/oncotarget. 8608
4. Li, Y., Zhang, W. T., Chen, C., Zhang, C. P., Duan, J. Y., Yao, H. K., … Shi, J. (2018). Inotodiol protects PC12 cells against injury induced by oxygen and glucose deprivation/restoration through inhibiting oxidative stress and apoptosis. Journal of Applied Biomedicine, 16, 126–132. https://doi. org/10.1016/j.jab.2017.11.004
5. Ham, S. S., Kim, S. H., Moon, S. Y., Chung, M. J., Cui, C. B., Han, E. K., … Choe, M. (2009). Antimutagenic effects of subfractions of Chaga mushroom (Inonotus obliquus) extract. Mutation Research, 672, 55–59. https://doi.org/10.1016/j.mrgentox.2008.10.002
6. Chen, W., He, F. Y., & Li, Y. Q. (2006). The apoptosis effect of hispolon from Phellinus linteus (Berkeley & Curtis) Teng on human epidermoid KB cells. Journal of Ethnopharmacology, 105, 280–285. https://doi. org/10.1016/j.jep.2006.01.026
7. Taji, S., Yamada, T., Wada, S., Tokuda, H., Sakuma, K., & Tanaka, R. (2008). Lanostane-type triterpenoids from the sclerotia of Inonotus obliquus possessing anti-tumor promoting activity. European Journal of Medicinal Chemistry, 43, 2373–2379. https://doi.org/10.1016/j.ejmech.2008. 01.037
8. Géry, A., Dubreule, C., André, V., Rioult, J. P., Bouchart, V., Heutte, N., … Garon, D. (2018). Chaga (Inonotus obliquus), a future potential medicinal fungus in oncology? A chemical study and a comparison of the cytotoxicity against human lung adenocarcinoma cells (A549) and human bronchial epithelial cells (BEAS-2B). Integrative Cancer Therapies, 17, 832–843. https://doi.org/10.1177/1534735418757912
9. Shibnev, V. A., Mishin, D. V., Garaev, T. M., Finogenova, N. P., Botikov, A. G., & Deryabin, P. G. (2011). Antiviral activity of Inonotus obliquus fungus extract towards infection caused by hepatitis C virus in cell cultures. Bulletin of Experimental Biology and Medicine, 151, 612–614. https://doi.org/10.1007/s10517-011-1395-8
10. Shibnev, V. A., Garaev, T. M., Finogenova, M. P., Kalnina, L. B., & Nosik, D. N. (2015). Antiviral activity of aqueous extracts of the birch fungus Inonotus obliquus on the human immunodeficiency virus. Voprosy Virusologii, 60, 35–38.

 Reishi (Ganoderma lingzhi, Ganoderma lucidum, etc.  )

1. Gao, Yihuai, et al. “Antimicrobial activity of the medicinal mushroom Ganoderma.” Food Reviews International 21.2 (2005): 211-229.
2. Wang PY, Zhu XL, Lin ZB. Antitumor and immunomodulatory effects of polysaccharides from broken-spore of Ganoderma lucidum. Front Pharmacol. 2012 Jul;3:135.
3. Wang G, Zhao J, Liu J, Huang Y, Zhong JJ, Tang W. Enhancement of IL-2 and IFN-gamma expression and NK cells activity involved in the anti-tumor effect of ganoderic acid Me in vivo. Int Immunopharmacol. 2007;7(6):864–870.
4. Guggenheim, A. G., Wright, K. M., & Zwickey, H. L. (2014). Immune Modulation From Five Major Mushrooms: Application to Integrative Oncology. Integrative medicine (Encinitas, Calif.), 13(1), 32–44.
5. Zhang, Y et al. “Effect of Ganoderma lucidum capsules on T lymphocyte subsets in football players on “living high-training low”.” British journal of sports medicine vol. 42,10 (2008): 819-22. doi:10.1136/bjsm.2007.038620
6. Cheng, Chun-Huai et al. “The effects of two different ganoderma species (Lingzhi) on gene expression in human monocytic THP-1 cells.” Nutrition and cancer vol. 62,5 (2010): 648-58. doi:10.1080/01635581003605516

Maitake (Grifola frondosa)

1. Konno, Sensuke. “Synergistic potentiation of D-fraction with vitamin C as possible alternative approach for cancer therapy.” International journal of general medicine vol. 2 91-108. 30 Jul. 2009, doi:10.2147/ijgm.s5498
2. Kodama N, Yamada M, Nanba H. Addition of maitake D-fraction reduces the effective dosage of vancomycin for the treatment of Listeria-infected mice. Jpn J Pharmacol. 2001;87:327–332.
3. Nanba H. Maitake D-fraction: healing and preventive potential for cancer. J Orthomol Med. 1997;12:43–49.
4.  Nanba H. Effect of Maitake D-fraction on cancer prevention. Ann N Y Acad Sci. 1997;833:204–207.
5. Morishige F. The role of vitamin C in tumor therapy (human) In: Meyskens FI Jr, Parasad KN, editors. Vitamins and Cancer: Human Cancer Prevention by Vitamins and Micronutrients. Clifton, NJ: Humana Press; 1986. pp. 399–427.

Medicinal Mushroom Powders in North America

If you are to consume medicinal mushroom supplements in the form of powders and capsules, please check out our guides below. This will help you identify high quality medicinal mushroom powders and capsules in the United States and Canada.

• Best Chaga supplements
• Best Cordyceps supplements
• Best Lion’s Mane supplements
• Best Reishi supplements
• Best Turkey Tail supplements

Medicinal Mushroom Supplements in Australia

If you are looking for top quality medicinal mushroom supplement powders in Australia, check out the following guides:

• Chaga mushrooms in Australia
• Cordyceps mushrooms in Australia
• Lion’s Mane mushrooms in Australia
• Maitake mushrooms in Australia
• Reishi mushrooms in Australia
• Turkey Tail mushrooms in Australia
• Tremella mushrooms in Australia