Agaricus Blazei Murrill and Cancer Prevention and Treatment

By Dónal P. O'Mathúna, PhD. Dr. O'Mathúna is Senior Lecturer in Ethics, Decision-Making & Evidence, School of Nursing, Dublin City University, Ireland; he reports no financial relationships relevant to this field of study.

Mushrooms have a long history as medicinal agents. Reishi mushrooms have been recommended for thousands of years as a general health food in traditional Chinese medicine. Shiitake mushrooms have been used in Japan to stimulate the immune system. "Magic mushrooms" are known for their psychedelic effects, while "Death Cap" (Amanita phalloides) is a clear reminder that some mushrooms are extremely toxic. All of these attest to the potent pharmacological agents present in some mushrooms.

One particular mushroom has been attracting much attention for the prevention and treatment of cancer. About half a million people in Japan are believed to use an extract of Agaricus blazei Murrill mushrooms to prevent cancer or as an adjunct to chemotherapy.¹ The mushroom is sometimes abbreviated as ABM, but will be referred to here as Agaricus.

Herbal remedies are especially popular among cancer patients, both those undergoing chemotherapy and those on palliative care.² Overall, about one-third of cancer patients use complementary and alternative medicine (CAM), although definitions and patterns of use vary widely.³ While many cancer patients use CAM along with conventional medications, awareness of the potential for herb-drug interactions is often limited. Clinicians should be aware of all the supplements being used by patients, especially newer remedies that are growing in popularity, like Agaricus.

Background

The Agaricus mushroom came to popular attention in Brazil, where its common name means "mushroom of God" or "mushroom of life."⁴ Japanese researchers brought it to Japan in the 1960s where it is called Himematsutake. It was identified as a new species and given the scientific name, Agaricus blazei Murrill. However, controversy exists as to whether it is a distinct species or is the once-popular Agaricus subrufescens.⁵ This species was widely cultivated and sold in the Eastern United States until early in the twentieth century when it was replaced by the edible button mushroom.

Regardless of debate over its scientific name, Agaricus has developed a reputation for treating cancer and other diseases that has made it one of the most widely used medicinal mushrooms in Asia and South America. Surveys of Japanese patients with urological cancer have found that the most commonly used form of CAM is "health food," which includes Agaricus.⁶ A similar survey of Japanese breast cancer patients found that Agaricus was the most popular nutritional supplement.⁷ A recent survey of cancer patients in Norway found that Agaricus was one of the most popular supplements used to "fight cancer generally."² Word of this interest is making its way to the US and Europe where web and mass media advertising are marketing Agaricus dietary supplements with claims that often exceed any clinically demonstrated benefit for patients.⁴

Mechanism of Action

Extracts of Agaricus contain a variety of polysaccharides which are believed to be the source of anticancer activity. Foremost among these compounds are glucans, in particular a range of alpha-glucans and beta-glucans.⁴ These polysaccharides contain long chains of branching sugars that interact in different ways with various receptors on cell surfaces, triggering other biochemical responses.

In vitro and animal studies have shown that various components of Agaricus extracts have direct anticancer activity, antimutagenic effects, and immunostimulating effects.⁸ Antiangiogenic substances have also been isolated from Agaricus.¹ The different compounds may have additive or synergistic effects in the prevention or treatment of cancer. However, few details are known regarding the specific mechanism of action for the compounds isolated. Also, the yield and structure of glucans in any one Agaricus extract can vary considerably depending on the stage of maturity of the mushrooms when they were harvested. Such details are rarely reported in articles on the extracts, making it difficult to determine which extracts and ingredients are most active.⁴

Clinical Studies

While several surveys have reported on the widespread popularity of Agaricus among cancer patients, only one clinical trial with cancer patients was located. One hundred patients receiving chemotherapy for various gynecological cancers were recruited in South Korea.⁸ All patients received either carboplatin plus etoposide or carboplatin plus taxol every three weeks for three cycles. The participants were randomly assigned to receive either a Japanese commercial Agaricus extract or placebo, each taken orally three times daily. The study was conducted in a double-blind fashion. Blood was withdrawn and analyzed for immunological status and the patients completed a quality of life questionnaire. A significant increase in natural killer cell activity occurred among those receiving Agaricus compared to placebo (P < 0.05). No significant differences were found in the levels of lymphokine-activated killer cells, monocytes, white blood cells, lymphocytes, or monocytes. The quality of life questionnaires demonstrated significant improvements for those taking Agaricus in the area of appetite, nausea and vomiting, insomnia, body strength, and mental stability.

Adverse Effects

Agaricus extracts are generally considered safe. In a clinical trial of diabetic patients, three of the 29 who received Agaricus for 12 weeks experienced hypoglycemic-like symptoms and two developed skin itching.⁹ In a pilot study involving four hepatitis patients, one year of treatment with Agaricus produced neither major nor minor adverse effects.¹⁰ However, three case reports have been published in which patients with previously treated ovarian or breast cancer developed severe liver dysfunction.³ All three were taking Agaricus extracts and no other conventional or complementary drugs. These reports do not establish a direct causal connection, although one patient's liver function improved when she stopped taking Agaricus and deteriorated when she started taking the extract again.

Formulation

A variety of Agaricus extracts are commercially available with variable amounts of active ingredients. No information is available on the effectiveness of different formulations or doses. The clinical trial described above used a Japanese product available in packs which are dissolved in water.⁸ Subjects took one pack three times daily. Surveys have found that most people take one pack daily.¹¹

Conclusion

Agaricus extracts have an interesting profile of biologically active compounds. Many of these have been shown to have some potential in helping patients with cancer. The finding that the mushrooms contain compounds which could act against cancer by a variety of different mechanisms is particularly interesting. However, only one clinical study using Agaricus in cancer patients could be found, making it impossible to provide evidence-based conclusions to inform practice.

Recommendation

The widespread popular use of Agaricus extract, in Japan in particular, should not be taken to demonstrate its effectiveness. Given the almost complete lack of clinical research, cancer patients should be cautioned against its use. The three cases of liver dysfunction in previously treated cancer patients are particularly concerning. While Agaricus blazei holds out much potential as a source of chemotherapeutic agents, much more basic and clinical research is needed before the extracts can be recommended to cancer patients.

References

1. Takaku T, et al. J Nutr. 2001;131:1409-1413.

2. Engdal S, et al. Support Care Cancer. 2008;16:763-769.

3. Mukai H, et al. Jpn J Clin Oncol. 2006;36:808-810.

4. Firenzuoli F, et al. Evid Based Complement Altern Med. 2008;5:3-15.

5. Kerrigan, Richard W. Mycologia. 2005;97:12-24.

6. Yoshimura K, et al. Support Care Cancer. 2005;13:685-690.

7. Kamizato M, et al. Nutritional supplements users with breast cancer in Japan. Support Care Cancer. 2007;15:770.

8. Ahn W-S, et al. 2004;14:589-594.

9. Hsu CH, et al. J Altern Complement Med. 2007;13:97-102.

10. Hsu CH, et al. J Altern Complement Med. 2008;14:299-301.

11. Talcott JA, et al. BMC Complement Altern Med. 2007;7:32.