Supplemental Mushrooms

Supplemental mushrooms are gaining popularity in cancer care. Traditional Chinese Medicine (TCM) has included mushrooms in its regime for cancer treatment and other disease for millennia. Western Medicine is becoming more aware of the beneficial effects as science is demonstrating the mechanism of action, the laboratory effects in cancer cell lines and animal models and in clinical studies on patients affected by cancer.

Active Compounds

The active compounds contained within mushrooms vary with the type but among them are the Beta-glucans and other polysaccharides. These compounds are responsible for the Biological Response Modifier action of mushrooms and why they are referred to as immunoceuticals (Ayeka PA 2018).

Mechanism of Action

The main mechanism of action is immunomodulation. From a therapeutic point of view, this refers to any process in which an immune response is altered to a desired level. For mushrooms, this includes:

1. Stimulating lymphocytes, NK cells and macrophages: these are responsible for fighting and preventing cancer cells from forming as well as mopping up the debris from their breakdown

2. Enhancing cytokine production: cytokines are the proteins released by cells responsible for communication between them. Not only is cytokine production stimulated by mushrooms but they have also been shown to upregulate the genes responsible for the production of anti-inflammatory and anticancer cytokines

3. Inhibiting proliferation of cancer cells: this occurs through the production of free radicals such as reactive oxygen species (ROS) and inflammatory mediators that cause cell cycle arrest

4. Promoting apoptosis: this is programmed cell death, it occurs when there is impaired cell function or DNA mutation as is the case in cancer cells, it is the main mechanism of action utilised by the conventional therapies (chemotherapy and radiotherapy)

5. Prevention of angiogenesis and metastasis: angiogenesis is the name given to the blood supply that the cancer creates for itself to sustain its growth and proliferation, the active compounds in mushrooms have been shown to help block this process from occurring

6. Direct cytotoxic effect on cancer cells

An additional way that mushrooms can create their anti-tumour effect is indirectly through the alteration of enzyme activity. For example, the compounds contained in the Agaricus bisporus (white button) mushrooms alter aromatase enzyme activity which is responsible for turning androgens into oestrogens and therefore has an effect on preventing the oestrogen-related cancers such as endometrial carcinoma. This would be a similar action to Tamoxifen and the Aromatase Inhibitors used as adjuvant endocrine therapy in hormone- sensitive (ER/PR+) breast cancer.

Which to use?

Although there are a variety of mushrooms that exert their effect whether in edible or in extract form, the following four varieties are recommended in supplemental doses as an adjunct to conventional therapy or following completion of conventional therapy.

1. Trametes (Coriolus) versicolor (Yun Zhi): common name: Turkey Tail: 3 grams twice a day of mushroom extract

2. Agaricus blazei: dose up to 5.4g/day of mushroom extract shown to be safe and well tolerated (Ohno et al 2011), exercise caution in hormone-sensitive tumours (Dong et al 2012) and liver dysfunction

3. Ganoderma lucidum: common name: Reishi: 6-12 grams per day of mushroom extract, exercise caution when used with anticoagulants, immunosuppressants or in liver dysfunction

4. Grifola frondosa: common name: Maitake: 3mg/kg twice daily of mushroom extract, exercise caution when used with oral hypoglycaemic agents or anticoagulants

The form the mushroom is taken (raw or extract) as well as whether the fruit, the bulb or the mycelium is used all matter and will influence the recommended dose. Consultation with a Traditional Chinese Medicine Practitioner is therefore recommended.

Clinical Studies – A Selection

The strongest evidence is seen for Turkey Tail and Agaricus blazei. These should be prioritised when making a selection of which supplemental mushrooms to use.

1. Turkey Tail

A meta-analysis published in 2012 analysing the use of Turkey Tail in 13 randomised, double-blind, placebo-controlled clinical trials showed it to improve survival with a 9% absolute risk reduction in mortality and 1 extra patient alive for every 11 treated (Eliza et al 2012). This result was more marked in colorectal, breast and gastric cancer and less evident in nasopharyngeal and oesophageal carcinoma.

The same meta-analysis showed dose ranges of turkey tail between 1-3 grams/day to be effective, however almost all used a dose of 3g/day on average. A Phase 1 Clinical Trial published in 2012 assessed dose escalation of Trametes (Coriolus) versicolor (Turkey Tail) in breast cancer patients (n=9) who had completed primary treatment including adjuvant chemotherapy and radiotherapy (Torkelson et al 2012). It showed that 9g/day of oral preparation is safe to use however, it was not necessarily superior to 6g/day in increasing the numbers of immune cells, but 6g/day was superior to 3g/day.

2. Agaricus blazei

A randomised, double-blind study of 100 patients with gynaecological malignancies undergoing chemotherapy published in 2004 showed that the use of the Agaricus blazei species both increases the count of natural killer cells compared with the placebo group and improved quality of life (Ahn et al 2004). The treatment group showed improvements in the chemotherapy-related side effects including appetite, alopecia, emotional stability and general weakness compared with the non-treatment group. Other studies have also shown improvements in quality of life using this mushroom species (Ohno et al 2013).

3. Reishi

A Cochrane systematic review of Reishi (Jin et al 2016) conducted a meta-analysis of 5 randomised controlled trials pooling the results of 373 participants. These showed improved response to chemotherapy and radiotherapy when Reishi was used as an adjunct to these but not when used in isolation. The authors expressed concern about the methodology of the 5 studies and extrapolating results from a homogenous population. Regardless, the authors conclude that the use of Reishi enhanced the response to conventional treatment when used as an adjunct.

4. Maitake

A non-randomised trial of 36 patients who either declined chemotherapy or had to cease it due to side effects showed promising results (Kodama et al 2002). Maitake extract was administered and symptom improvement or cancer regression was seen for breast, liver and lung cancer but minimal for leukaemia, stomach and brain. However, most of the evidence for Maitake is in the laboratory (He et al 2019) and more extensive clinical studies are required to substantiate its use.

Safety

There are studies that investigate the use of mushrooms both subsequent to conventional care and during conventional care. They generally appear safe to use, however caution should be exercised depending on the other medications being taken (eg oral hypoglycaemic agents, anticoagulants), the type of cancer being treated (eg whether it is hormone-sensitive) and liver function. As always, consultation with the treating medical team is advised or a formal conversation with an Integrative Consultant or Traditional Chinese Medicine Practitioner to ensure there is no interaction with the formal conventional protocol, interactions with other medications, allergies, contraindications or for individualisation of the supplemental mushroom regime.

References

1. Ayeka PA. Potential of Mushroom Compounds as Immunomodulators in Cancer Immunotherapy: A Review. Evid Based Complement Alternat Med. 2018;2018:7271509. Published 2018 Apr 22. doi:10.1155/2018/7271509

2. Ohno S, Sumiyoshi Y, Hashine K, Shirato A, Kyo S, Inoue M. Phase I Clinical Study of the Dietary Supplement, Agaricus blazei Murill, in Cancer Patients in Remission. Evid Based Complement Alternat Med. 2011;2011:192381. doi:10.1155/2011/192381

3. Dong S, Furutani Y, Suto Y, et al. Estrogen-like activity and dual roles in cell signaling of an Agaricus blazei Murrill mycelia-dikaryon extract. Microbiol Res. 2012;167(4):231-237. doi:10.1016/j.micres.2011.09.003

4. Eliza WL, Fai CK, Chung LP. Efficacy of Yun Zhi (Coriolus versicolor) on survival in cancer patients: systematic review and meta-analysis. Recent Pat Inflamm Allergy Drug Discov. 2012;6(1):78-87. doi:10.2174/187221312798889310

5. Torkelson CJ, Sweet E, Martzen MR, et al. Phase 1 Clinical Trial of Trametes versicolor in Women with Breast Cancer. ISRN Oncol. 2012;2012:251632. doi:10.5402/2012/251632

6. Ahn WS, Kim DJ, Chae GT, et al. Natural killer cell activity and quality of life were improved by consumption of a mushroom extract, Agaricus blazei Murill Kyowa, in gynecological cancer patients undergoing chemotherapy. Int J Gynecol Cancer. 2004;14(4):589-594. doi:10.1111/j.1048-891X.2004.14403.x

7. Ohno S, Sumiyoshi Y, Hashine K, Shirato A, Kyo S, Inoue M. Quality of life improvements among cancer patients in remission following the consumption of Agaricus blazei Murill mushroom extract. Complement Ther Med. 2013;21(5):460-467. doi:10.1016/j.ctim.2013.07.001

8. Jin X, Ruiz Beguerie J, Sze DM, Chan GC. Ganoderma lucidum (Reishi mushroom) for cancer treatment. Cochrane Database Syst Rev. 2016;4(4):CD007731. Published 2016 Apr 5. doi:10.1002/14651858.CD007731.pub3

9. Kodama N, Komuta K, Nanba H. Can maitake MD-fraction aid cancer patients?. Altern Med Rev. 2002;7(3):236-239

10. He Y, Zhang L, Wang H. The biological activities of the antitumor drug Grifola frondosa polysaccharide. Prog Mol Biol Transl Sci. 2019;163:221-261. doi:10.1016/bs.pmbts.2019.02.010

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