Agaricus blazei

Metadata

Regulatory Status

Japan

• Status: Himematsutake is one of the most popular health foods in Japan, widely marketed as a dietary supplement and functional food.
• History: Adopted into Japanese health practice after being imported from Brazil in the 1960s-1970s by researcher Takatoshi Furumoto, who sent samples to Japanese mycologists.
• Market significance: Japan has historically been the largest single market for A. blazei products, with peak annual sales estimated at several hundred million USD.
• Pharmaceutical approval: None. Sold as a health food supplement.

Brazil

• Status: First identified in the Piedade region of Sao Paulo state. Widely cultivated and consumed as a medicinal food.
• Traditional use: Local populations in Piedade historically consumed the mushroom. Epidemiological observations suggested lower-than-expected cancer rates, sparking scientific interest.
• ANVISA: Regulated as a food supplement. Not approved for specific disease claims.

United States

• Dietary supplement: Marketed under DSHEA (1994). No FDA GRAS determination.

European Union

• Novel Food: Not authorized under Regulation (EU) 2015/2283 in most member states.
• No EMA/HMPC monograph.

China

• Not listed in the Chinese Pharmacopoeia. Used in some TCM formulations as Ji Song Rong, without official pharmacopoeia status.

Conditions & Indications

Primary Indications (Moderate Evidence)

• Immune modulation and cancer adjunctive therapy — Multiple RCTs demonstrate immune parameter enhancement in cancer patients. Ahn et al. (2004) showed significantly increased NK cell activity in gynecological cancer patients receiving A. blazei during chemotherapy versus placebo. Hetland et al. (2008, 2011) demonstrated that AndoSan reduced pro-inflammatory cytokines and increased anti-inflammatory markers in IBD patients. Tangen et al. (2015) showed immunomodulatory effects in multiple myeloma patients.
• Anti-inflammatory and anti-allergic effects — Ellertsen and Hetland (2009) demonstrated that A. blazei extract reduced Th2 cytokine responses and shifted the Th1/Th2 balance in allergic patients. Anti-inflammatory effects are mediated through NF-kB modulation.

Secondary Indications (Preliminary Evidence)

• Hepatoprotective and liver function support — Hsu et al. (2008) conducted an RCT showing improved liver function parameters (AST, ALT normalization) in chronic hepatitis B patients over 12 months. However, paradoxical hepatotoxicity case reports complicate this indication.
• Metabolic effects — Hsu et al. (2007) reported insulin resistance improvement in type 2 diabetes patients. Mechanisms include alpha-glucosidase inhibition and enhanced insulin sensitivity.
• Quality of life in cancer patients — Improvements in fatigue, appetite, and well-being reported across multiple adjunctive therapy trials.

Emerging/Preclinical Indications

• Anti-tumor activity (direct cytotoxicity) — Blazein induces apoptosis in cancer cell lines. Anti-proliferative effects demonstrated in vitro against various cancer cell lines.
• Anti-angiogenic effects — Ergosterol and sodium pyroglutamate demonstrate anti-angiogenic activity in animal tumor models.
• Gut microbiome modulation — Polysaccharide fractions modulate gut microbiota, increasing beneficial Bifidobacteria and Lactobacillus populations in preclinical models.

Mechanism of Action

Primary Mechanisms

1. Beta-glucan activation of innate immunity Agaricus blazei contains high concentrations of beta-1,3/1,6-D-glucans and, notably, alpha-1,4/1,6-glucans (uncommon among medicinal mushrooms). These polysaccharides activate innate immune cells through Dectin-1, complement receptor 3, and TLR-2. The presence of both alpha- and beta-glucans distinguishes A. blazei from most other medicinal mushrooms and may contribute to its particularly potent immune-stimulatory activity.

2. Proteoglycan-mediated immune modulation Unique proteoglycan complexes (ATOM, ABM-FI) consist of protein-bound polysaccharide structures that activate complement pathways and stimulate macrophage-mediated anti-tumor activity. These proteoglycans demonstrate anti-tumor activity exceeding that of the polysaccharide fraction alone.

3. Ergosterol peroxide anti-angiogenic activity Ergosterol peroxide inhibits tumor angiogenesis by suppressing VEGF-mediated endothelial cell tube formation and migration. This anti-angiogenic mechanism complements the immune-stimulatory effects.

4. Th1/Th2 balance modulation A. blazei extracts shift the immune response from Th2-dominant (allergic) toward Th1 dominance through increased IL-12 and IFN-gamma production, suppressing Th2 cytokines responsible for IgE production and allergic inflammation.

Key Active Compounds

Pharmacological Note

Unlike reishi, which has a dual polysaccharide-triterpenoid pharmacology, Agaricus blazei’s primary activity is driven by its polysaccharide and proteoglycan fractions, extracted by hot water. The mushroom contains unusually high concentrations of both beta- and alpha-glucans. Hot water extraction captures the principal bioactive fractions. The presence of agaritine (also found in common button mushrooms) introduces a toxicological consideration absent from most other medicinal mushrooms; agaritine is largely degraded by cooking and drying (>90% reduction).

Clinical Evidence Summary

Systematic Reviews

Key Individual Trials

Evidence Limitations

• Extract preparations vary significantly across studies (AndoSan, ABMK, various hot water extracts).
• Most trials have small sample sizes (n=21-100) and relatively short durations.
• Most evidence focuses on immune biomarkers rather than hard clinical endpoints.
• The agaritine safety question has not been adequately addressed in long-term studies.
• Publication bias may favor positive results.

Safety Profile

General Assessment

Consumed as a food in Brazil for generations and as a supplement in Japan for decades. Generally well-tolerated in clinical trials (up to 12 months). However, hepatotoxicity case reports and the presence of agaritine distinguish it from most other medicinal mushrooms.

Contraindications

• Autoimmune disease: Potent immune-stimulatory properties may exacerbate autoimmune conditions.
• Active liver disease: Given hepatotoxicity case reports, patients with pre-existing hepatic disease should avoid or use only under medical supervision with liver function monitoring.
• Pre-surgical: Discontinue 2 weeks before surgery.
• Pregnancy and lactation: Insufficient data; avoid.

Drug Interactions

• Immunosuppressants: May counteract immunosuppressive therapy. Severity: High.
• Chemotherapy agents: Used adjunctively in clinical trials; use only under oncologist supervision. Severity: Moderate.
• Antidiabetic agents: May lower blood glucose. Severity: Low-to-moderate.
• Hepatotoxic drugs: May increase liver injury risk. Severity: Moderate.
• Anticoagulants: Limited evidence for antiplatelet effects. Severity: Low-to-moderate.

Side Effects

• Common: GI upset (nausea, diarrhea, bloating), mild and transient.
• Uncommon: Allergic reactions.
• Rare but serious: Hepatotoxicity. Mukai et al. (2006) reported severe liver damage in three cancer patients. Hsu et al. (2008) did not observe hepatotoxicity in their 12-month RCT, suggesting product quality or individual susceptibility as factors.
• Agaritine concern: Metabolized to mutagenic diazonium ions, but substantially degraded (>90%) by cooking/drying. Risk at dietary doses assessed as very low by food safety authorities.

Pregnancy and Lactation

• Category: Avoid. The presence of agaritine provides additional theoretical reason for avoidance.

Clinical Dosage

Hot Water Extract

• Standard dose: 1-3 g/day of hot water extract powder, standardized to beta-glucan content
• Clinical trial dose (Ahn et al.): Equivalent of 3 g/day of dried fruiting body extract

AndoSan Liquid Extract

• Standard dose: 60 mL/day in divided doses (30 mL twice daily)
• Note: AndoSan contains 82.4% A. blazei, 14.7% H. erinaceus, 2.9% G. frondosa

Dried Fruiting Body

• Standard dose: 3-9 g/day
• Preparation: Decoction (simmered 30-60 min) or dried powder in capsules
• Note: Drying and cooking substantially reduce agaritine content

Tablet/Capsule Formulations

• Standard dose: 500-1500 mg/day of concentrated extract in divided doses
• Clinical trial dose (Hsu et al.): 1,500 mg/day (500 mg three times daily)

Sources

• 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
• Hetland G, Johnson E, Lyberg T, Bernardshaw S, Tryggestad AM, Grinde B. Effects of the medicinal mushroom Agaricus blazei Murill on immunity, infection and cancer. Scand J Immunol. 2008;68(4):363-370
• Hetland G, Johnson E, Lyberg T, Kvalheim G. The mushroom Agaricus blazei Murill elicits medicinal effects on tumor, infection, allergy, and inflammation through its modulation of innate immunity and amelioration of Th1/Th2 imbalance and inflammation. Adv Pharmacol Sci. 2011;2011:157015
• Tangen JM, Tierens A, Caers J, et al. Immunomodulatory effects of the Agaricus blazei Murill-based mushroom extract AndoSan in patients with multiple myeloma undergoing high dose chemotherapy and autologous stem cell transplantation. Biomed Res Int. 2015;2015:718539
• Hsu CH, Liao YL, Lin SC, Hwang KC, Chou P. The mushroom Agaricus blazei Murill in combination with metformin and gliclazide improves insulin resistance in type 2 diabetes. J Altern Complement Med. 2007;13(1):97-102
• Hsu CH, Hwang KC, Chiang YH, Chou P. The mushroom Agaricus blazei Murill extract normalizes liver function in patients with chronic hepatitis B. J Altern Complement Med. 2008;14(3):299-301
• 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
• Fortes RC, Novaes MR, Recova VL, Melo AL. Immunological, hematological, and glycemia effects of dietary supplementation with Agaricus sylvaticus on patients’ colorectal cancer. Exp Biol Med (Maywood). 2009;234(1):53-62
• Mukai H, Watanabe T, Ando M, Katsumata N. An alternative medicine, Agaricus blazei, may have induced severe hepatic dysfunction in cancer patients. Jpn J Clin Oncol. 2006;36(12):808-810
• Ellertsen LK, Hetland G. An extract of the medicinal mushroom Agaricus blazei Murill can protect against allergy. Clin Mol Allergy. 2009;7:6
• Firenzuoli F, Gori L, Lombardo G. The medicinal mushroom Agaricus blazei Murill: review of literature and pharmaco-toxicological problems. Evid Based Complement Alternat Med. 2008;5(1):3-15
• Wisitrassameewong K, Karunarathna SC, Thongklang N, et al. Agaricus subrufescens: A review. Saudi J Biol Sci. 2012;19(2):131-146
• Kerrigan RW. Agaricus subrufescens, a cultivated edible and medicinal mushroom, and its synonyms. Mycologia. 2005;97(1):12-24

Connections

• Compare with other medicinal mushroom immunomodulators: Turkey Tail (PSK/PSP, pharmaceutical-grade evidence), Reishi (dual polysaccharide-triterpenoid pharmacology, Cochrane review), Maitake (D-fraction beta-glucans)
• A. blazei is notable for containing both alpha- and beta-glucans, and its unique proteoglycan complexes (ATOM) may contribute additional immune-stimulatory mechanisms not found in other species
• Shares cancer adjunctive therapy evidence profile with Turkey Tail and Shiitake, though PSK/lentinan have stronger evidence (approved pharmaceuticals)
• The hepatotoxicity concern distinguishes A. blazei from most other medicinal mushrooms; compare with the rare hepatotoxicity case report for Reishi (Wanmuang et al. 2007)
• The anti-allergic Th1/Th2 rebalancing effect is shared to some extent with Reishi (ganoderic acid-mediated anti-histamine activity), but through different molecular mechanisms
• AndoSan, the most clinically studied preparation, contains Lion’s Mane and Maitake as minor components, complicating attribution of effects to A. blazei alone