Agaricus blazei Research
60 adults
The only human RCT on Agaricus blazei and allergy enrolled 60 birch-allergic blood donors. After seven weeks of pre-seasonal supplementation with an ABM-based extract, specific IgE against the main birch allergen fell 36-37% relative to placebo and basophils did not become more sensitive over the season. The detailed symptom score, however, showed no difference.
Mahmood et al., Nutrients, 2019
Gut-first
ABM acts through intestinal epithelial cell activation, not systemic absorption of beta-glucans
Th1 shift
ABM drives T helper cells toward infection-fighting mode, reducing the allergy-promoting Th2 dominance
19 days
in mice, ABM reduced anti-OVA IgE even when started 19 days after allergen immunization
Mahmood et al., Nutrients, 2019
View as image ↗How can a mushroom shift an immune response that took years to develop? That question sits at the center of the most interesting research on Agaricus blazei, the Brazilian royal sun mushroom commonly abbreviated ABM. Allergies aren't random misfires. They are the result of an immune system locked in a particular mode, producing too much of one response type and too little of another. The research on ABM shows it acts on the system that controls this mode, working through the gut to push the immune balance in a different direction.
This article is part of the complete guide to Agaricus blazei. For the Th1/Th2 balance research specifically, and for a deeper look at the cytokine data, see Agaricus blazei for Allergies: Th1/Th2 Balance Research.
Key Takeaways
- Agaricus blazei shifts the immune system from Th2 dominance (the allergy mode) toward Th1 dominance (the infection-fighting mode) by activating intestinal epithelial cells, which then trigger macrophage and T cell responses. This gut-first pathway was mapped by Bouike et al. (2011)
- The mechanism explains why oral supplementation works: ABM's beta-glucans are too large to enter the bloodstream intact, but they activate immune cells at the gut wall that send systemic signals
- Which receptor does the recognizing is genuinely unsettled, and depends on the extract. A cold water extract acted through TLR2 (Yamanaka 2012); a hemicellulase-derived mycelial fraction acted through CD14 and TLR4 (Kasai 2004). Dectin-1, the textbook beta-glucan receptor, was tested in the cold water extract and did not bind it
- In a mouse asthma model, oral ABM extract reduced OVA-specific IgE and IgG1 and airway eosinophils, while leaving the Th1-associated IgG2a antibody untouched — the precise signature a Th1/Th2 rebalancing predicts (Takimoto et al., 2008)
- Ellertsen and Hetland (2009) found that ABM reduced anti-OVA IgE in mice whether given a day before immunization or 19 days after it, suggesting the mechanism may modulate an already-committed allergic profile
- The only human RCT (Mahmood et al., Nutrients, 2019) is genuinely mixed. Specific IgE against the birch allergen Bet v 1 fell significantly and basophils stayed less reactive across the season, but the 12-item specific symptom score showed no difference from placebo
- ABM also acts directly on mast cells through a separate pathway: Choi et al. (2006) found an ABM water extract inhibited histamine release, reduced calcium uptake, and raised intracellular cAMP, independent of the Th1/Th2 mechanism
The Allergy Problem: Why Th2 Dominance Triggers Reactions to Harmless Things
The immune system has two main operational modes, coordinated by two families of T helper cells.
One mode (Th1) specializes in cellular immunity: hunting down and destroying infected cells, intracellular bacteria, and emerging cancer cells. Th1 cells produce a signaling molecule called interferon-gamma (IFN-γ), which functions as a directive to immune cells to kill rather than produce antibodies.
The other mode (Th2) specializes in antibody-based defense, originally evolved to fight parasitic worms. Th2 cells produce different signaling molecules (cytokines): IL-4, IL-5, and IL-13. These drive the immune system to produce IgE antibodies, a class of antibodies that are useful against parasites but, when overproduced in response to harmless substances like tree pollen or dust mite proteins, cause allergic reactions.
IgE antibodies attach to mast cells and basophils, the sentinel cells sitting in skin, mucous membranes, airways, and blood. When one of these cells, coated in IgE, encounters the allergen, it releases histamine and a cascade of inflammatory chemicals. That release is what causes hives, sneezing, airway narrowing, and anaphylaxis.
In people with allergies, the Th2 mode dominates the Th1 mode. The immune system produces too much IgE, sensitizes too many mast cells, and reacts to exposures that a healthy Th1/Th2 balance would ignore. The question the ABM research asks is whether supplementation can restore that balance.
Step by Step: How ABM Activates the Th1 Shift Through the Gut
The mechanism researchers have identified is not what most people would expect. ABM's active compounds, primarily beta-glucan polysaccharides (branched-chain carbohydrates in the mushroom's cell walls), are too large to be absorbed intact into the bloodstream. If they don't enter systemic circulation, how can they affect a systemic immune response?
A 2011 study by Bouike and colleagues answered this question by identifying the gut lining as the activation site.[1]
The cascade, as Bouike's team mapped it, goes like this:
- Oral ABM extract reaches the small intestine. Its beta-glucan compounds make contact with intestinal epithelial cells, the cells lining the gut wall.
- Intestinal epithelial cells detect the beta-glucans through pattern-recognition receptors — surface proteins evolved to identify structural signatures common to fungi and bacteria. This recognition activates the epithelial cells. (Which receptor does this for ABM is not settled; see the next section.)
- Activated epithelial cells send chemical signals that activate macrophages, the large immune cells patrolling gut tissue. Macrophages are among the immune system's most powerful coordinators.
- The activated macrophage compartment drives an IFN-γ-rich local environment. Bouike's team demonstrated this with a coculture of Caco-2 intestinal cells together with either splenocytes from OT-II mice or RAW 264.7 macrophages, in which ABM treatment significantly increased IFN-γ production.
- Naive T cells in the vicinity, encountering an IFN-γ-rich environment, differentiate into Th1 cells rather than Th2 cells.
- With more Th1 cells in circulation, the immune system produces more IFN-γ, which suppresses the Th2 cytokines (IL-4, IL-5) that drive IgE production.
The result: IgE production falls. Mast cells receive fewer sensitizing antibodies. Allergic reactivity decreases.
Bouike's team confirmed the systemic half of this in an OVA-sensitized mouse model (OVA, ovalbumin, is the standard allergen used in allergy research). Serum IgE fell significantly in the ABM group. IL-4 and IL-5 from OVA-restimulated splenocytes decreased significantly, and under anti-CD3ε/CD28 stimulation the ABM group also showed reduced IL-10, IL-4 and IL-5 alongside increased IFN-γ.[1]
Which Receptor Does the Recognizing? It Depends on the Extract
It is common to see ABM articles name a single receptor as the entry point for the whole mechanism — usually TLR4, sometimes dectin-1. The primary literature does not support a single answer, and Bouike's paper, which established the gut pathway above, did not test receptors at all.
Three studies did, and they used three different preparations.
Yamanaka and colleagues prepared a cold water extract of the ABM fruit body and set out to find what it bound.[2] Their first finding was a negative one: the 1,3-beta-glucan segment in this fraction was too small to interact with dectin-1, the canonical beta-glucan receptor. Screening in TLR-transfected HEK293 cells showed activation via TLR2, TLR4 and TLR5, but when they blocked receptors on actual splenocytes, only the anti-TLR2 antibody suppressed IL-6 production. The extract also bound TLR2 protein directly.
Kasai and colleagues, working seven years earlier with a hemicellulase-derived mycelial extract, landed somewhere else.[3] Their fraction induced IL-12 in human peripheral blood mononuclear cells, and that induction was blocked by anti-CD14 and anti-TLR4 antibodies but explicitly not by anti-TLR2. They also ruled out the obvious confounder: polymyxin B, which neutralises bacterial endotoxin, blocked their LPS control but did not blunt the mushroom fraction, so the effect was not contaminating endotoxin.
Martins and colleagues took an acid-treated polysaccharide-rich fraction and looked at human monocytes handling Candida albicans.[4] The fraction increased phagocytosis and upregulated both TLR2 and TLR4, with TLR4 expression tracking TNF-α output and TLR2 tracking IL-1. The beta-glucan receptor and the mannose receptor were unchanged.
Mechanism Audit · One Mushroom, Four Preparations
The Receptor Depends on Which Extract You Test
Articles about Agaricus blazei often name a single receptor as “the” mechanism. The primary papers do not support that. Each used a different fraction, and each landed on a different answer. The paper that established the gut pathway did not test a receptor at all.
Bouike 2011
Ref 1eCAM 2011Fraction tested
Agaricus blazei Murill extract (ABME), oral
System & readout
OVA-sensitised mice; Caco-2 + splenocyte / RAW 264.7 coculture
Receptor implicated
None testedYamanaka 2012
Ref 2Immunopharmacol Immunotoxicol 34(4)Fraction tested
Cold water extract of fruit body (ACWS)
System & readout
Murine splenocytes, IL-6 output; HEK293 TLR reporter screen
Receptor implicated
TLR2Explicitly ruled out in this paper
Kasai 2004
Ref 3eCAM 1(3)Fraction tested
Hemicellulase-derived mycelial extract (fraction H, ABH)
System & readout
Human PBMC, IL-12 output
Receptor implicated
CD14 + TLR4Explicitly ruled out in this paper
Martins 2017
Ref 4J Venom Anim Toxins Trop Dis 23Fraction tested
Acid-treated polysaccharide-rich fraction (ATF)
System & readout
Human monocytes, Candida albicans capture + cytokines
Receptor implicated
TLR2 and TLR4 both upregulatedExplicitly ruled out in this paper
Net position
There is no single established “Agaricus blazei receptor.” TLR2 and TLR4 are both supported, in different preparations, in different species, for different cytokine readouts. The most striking result is the negative one: dectin-1 and the beta-glucan receptor — the textbook route for fungal beta-glucans — are the two receptors that were specifically looked for and specifically not found.
The honest summary is that ABM preparations engage toll-like receptors, that TLR2 and TLR4 are both credibly implicated depending on the fraction and the readout, and that the receptor most people assume is responsible — dectin-1 — is the one that was checked and came back negative. This matters practically: "Agaricus blazei extract" is not one substance, and hot water, cold water, mycelial and acid-treated fractions are not interchangeable.
The Innate Immune Cascade: More Than Just T Cells
The gut epithelium activation is the entry point, but the immune shift involves a broader cascade of innate immune cells.
A 2011 review by Hetland and colleagues mapped ABM's effects across the innate immune system.[5] Beyond macrophages, ABM's beta-glucans stimulate monocytes (circulating cells that become macrophages in tissues), natural killer (NK) cells (cells that directly kill infected and cancerous cells), and dendritic cells (specialized cells that present foreign material to T cells to initiate adaptive immune responses).
Together, these innate immune cell types create a cytokine environment rich in IFN-γ and other Th1-promoting signals. This environment is what naive T cells read when deciding whether to become Th1 or Th2 cells. Tilt the environment toward IFN-γ, and T cell differentiation tilts toward Th1.
Hetland's review connected this anti-allergy mechanism to ABM's anti-tumor and anti-infection activities under a single framework: ABM's core immunological action is innate immune activation, and innate immune activation promotes Th1 dominance. Whether that Th1 shift helps depends on context — in allergy it counteracts Th2 dominance, in tumors it supports anti-tumor cellular immunity, in infection it aids pathogen clearance.[5] It is worth naming what this is: a review by the same Norwegian group that produced most of the clinical work, proposing a unifying framework for its own findings. That is a legitimate scientific activity and it is not independent confirmation.
For more on how the Th1 shift connects to ABM's anti-tumor research, see How Agaricus blazei Activates Anti-Tumor Immunity.
The Specific Numbers: What Animal Studies Show
Takimoto and colleagues tested oral ABM extract in a mouse allergic asthma model in 2008.[6] Allergic asthma is driven by the same Th2/IgE mechanism that drives hay fever and skin allergies: airways become sensitized through IgE and react to allergen exposure with inflammation and constriction.
In the asthma-induced mice, Agaricus extract treatment significantly downregulated OVA-specific IgG1 and IgE — but not IgG2a. That exception is the most informative part of the result. IgG2a is the antibody isotype associated with Th1 activity, so a genuine Th1/Th2 rebalancing predicts exactly this pattern: the Th2-driven antibodies fall while the Th1-driven antibody holds. A nonspecific suppression of antibody production would have knocked all three down.
The same mice showed significantly decreased total cell numbers, IL-5 levels, and eosinophil numbers in bronchoalveolar lavage fluid. Eosinophils are white blood cells that accumulate in allergic airways and contribute to asthmatic inflammation; IL-5 is the Th2 cytokine that recruits them. IFN-γ production by anti-CD3-stimulated spleen cells increased.
Critically, Takimoto tested the same extract in tumor-bearing mice in the same paper and found it raised IFN-γ production there too, in a context where Th1 activity is typically suppressed.[6] This cross-context result is the empirical basis for Hetland's unified mechanism argument: ABM appears to push toward Th1 regardless of what pushed the balance away from it.
What Ellertsen's 2009 Study Found About Established Allergy
Most allergy prevention research tests interventions given before or during allergen exposure. Ellertsen and Hetland's 2009 study asked a different question: what if the allergic immune response is already established?
Their team gave AndoSan — a mushroom extract that is 82% ABM, with 15% Hericium erinaceus and 3% Grifola frondosa — to mice at two different points relative to OVA immunization.[7] One group received it a day before immunization. The other received it 19 days after. All mice were sacrificed on day 26.
Both groups showed reduced anti-OVA IgE compared with controls. Anti-OVA IgG2a, the Th1-associated isotype, was not reduced in either — the same selective pattern Takimoto saw. The cytokine data were weaker: the authors report only a tendency toward reduced Th2 relative to Th1 cytokine levels in the AndoSan groups, which is their language for a difference that did not reach statistical significance.[7]
So the headline finding — that ABM lowered IgE even when started well after immunization — is real, and it is an antibody finding rather than a cytokine finding. The authors' own conclusion was that the extract "may both prevent allergy development and be used as a therapeutical substance against established allergy."
Two caveats matter. First, this is an induction model on a 26-day timeline; 19 days after immunization in a mouse is not equivalent to decades of established allergic programming in a human. Second, the paper does not report that IgE was measured at day 19 to confirm the allergic response was fully established before treatment began.
The Parallel Mechanism: What ABM Does at the Mast Cell Level
The Th1/Th2 rebalancing mechanism is upstream: it reduces IgE production and therefore reduces the sensitization of mast cells to the allergen. Research by Choi and colleagues in 2006 identified a second pathway that acts downstream, directly at the mast cell.[8]
Mast cell degranulation (the release of histamine and other inflammatory molecules) requires a calcium ion influx into the cell. When IgE on the mast cell surface binds its allergen, calcium channels open. The calcium influx is the trigger that causes the cell to release its contents.
Choi's team found that an ABM water extract dose-dependently inhibited histamine release from rat peritoneal mast cells, whether those cells were triggered through IgE (anti-DNP IgE) or through a non-IgE route (compound 48/80). Pretreatment with the extract reduced compound 48/80-induced calcium uptake into those cells. Intracellular cAMP rose significantly, and the extract also prevented the cAMP drop that compound 48/80 normally causes. Higher cAMP suppresses the signaling cascade that leads to degranulation.
They confirmed the effect in living animals as well: compound 48/80-induced systemic anaphylaxis-like reaction, ear swelling response, and passive cutaneous anaphylaxis were all inhibited, as was IgE-mediated passive cutaneous anaphylaxis.[8]
A separate 2012 study by Song and colleagues found that a chloroform-soluble extract of ABM — a lipophilic fraction, not the water-soluble beta-glucan material discussed everywhere else in this article — inhibited degranulation and reduced IL-6, prostaglandin D2 and leukotriene C4 production in mouse bone marrow-derived mast cells, apparently by suppressing Akt phosphorylation.[9]
One claim worth retiring: ABM is sometimes described as a COX-2 blocker. The corpus points the other way. Smiderle and colleagues found that semi-purified polysaccharide extracts of Agaricus brasiliensis (the accepted synonym for A. blazei) increased transcription of COX-2, along with IL-1β and TNF-α, in differentiated THP-1 monocytes — while the same extract reduced those markers when they were driven by bacterial LPS.[10] The authors called this "programmable immunomodulation." It is a good description of a substance whose effect depends on what the immune system was already doing, and a poor fit for the word "blocker."
For a focused look at the full mast cell stabilization data, see Agaricus blazei and Mast Cell Stabilization: Why It May Help Allergic Asthma.
The Human Evidence: What the Only Clinical Trial Found
The animal and in-vitro mechanistic evidence points in one direction. The human evidence comes from a single published randomized controlled trial.
Mahmood et al. (2019) · Nutrients
- Population
- 60 blood donors with self-reported, IgE-verified birch pollen allergy and/or asthma; single-centre, Oslo University Hospital
- Intervention
- AndoSan (82% A. blazei, 15% H. erinaceus, 3% G. frondosa), 60 mL once daily for 7 weeks before the birch pollen season
- Comparator
- Matched placebo, double-blind, randomised, two-armed: 29 to AndoSan, 31 to placebo. Registered as NCT03198455
- Finding
- Specific IgE against Bet v 1 and against birch pollen extract (t3) fell 36-37% relative to placebo (p = 0.007 and p = 0.01). Total IgE did not differ (p = 0.14). Basophils in the placebo arm became roughly ten-fold more allergen-sensitive across the season while the treated arm's did not (between-group p = 0.028). The 12-item specific allergy symptom score showed no difference between groups (p = 0.51).
mixed The immunological endpoints are the strong ones and they are internally consistent with the proposed mechanism. The symptom evidence is weaker than the trial is usually reported to be: the significant general-symptom result (p = 0.02) is a comparison against the previous pollen season rather than a direct between-group contrast during it, and the asthma results come from the roughly 13 participants who had pollen-induced asthma at inclusion.
Mahmood et al., Nutrients, 2019; 11(10):2339. Ref 11
Participants received either AndoSan or placebo at 60 mL daily for seven weeks before the birch pollen season, then were followed through it.[11] This is a prophylactic design, not a treatment-during-symptoms design, and the distinction matters for anyone trying to map the trial onto their own use.
The results are better understood endpoint by endpoint than as a single verdict.
Trial Ledger · Mahmood 2019, n = 60, NCT03198455
Which Endpoints Actually Separated From Placebo
The trial is usually summarised in one sentence. Broken out by endpoint, it reads as a strong antibody result, a strong result in a small asthma subgroup, and a genuinely null result on the detailed symptom instrument.
Year-over-year comparison (2015 season vs. 2016 season), not a direct mid-season contrast.
The detailed symptom instrument showed no separation between groups.
Asthmatics only: 26% of the 29-person Andosan arm and 18.5% of the 31-person placebo arm — about 13 people in total.
The endpoint the Th1/Th2 mechanism actually predicts.
Specific IgE moved; the total antibody pool did not.
How to read this
The immunological endpoints — specific IgE and basophil sensitivity — are the cleanest results in the trial, and they are the ones the gut-to-Th1 mechanism predicts. The subjective symptom picture is weaker: the detailed 12-item score found nothing, and the headline symptom result comes from a comparison against the previous pollen season rather than a direct contrast during it.
The antibody result is the one the mechanism predicts. If ABM shifts the immune system toward Th1, allergen-specific IgE should fall — and it did, by 36-37% relative to placebo for both the purified Bet v 1 allergen and the whole birch pollen extract. Notably, total IgE moved only 16% and did not reach significance.
The basophil result is the other strong finding, and it is a functional measurement rather than a self-report.
Basophil Activation Test · Mahmood 2019
A Pollen Season Made Placebo Basophils Ten Times Twitchier
How much birch allergen it takes to trigger a basophil, before and after the season. Lower means the cell fires on less allergen — that is worse, not better. Each arm is indexed to its own pre-season value; the axis is logarithmic.
Placebo
Basophils became more sensitive
within-group p = 0.004
AndoSan (AbM extract)
Sensitivity held, then some
within-group p = 0.312 (no change)
What it means
A pollen season normally leaves an allergic person more reactive than it found them, and that is exactly what the placebo arm shows. The supplemented arm did not follow it down. The between-group difference in that drift was significant at p = 0.028. This is a functional cell measurement rather than a questionnaire, which is what makes it one of the more persuasive results in the trial — and it still rests on a single study of 60 people.
The Hetland 2020 narrative review, the research group's most comprehensive synthesis of work on ABM, Hericium erinaceus and Grifola frondosa, places the Mahmood trial within a framework connecting the antitumor, anti-inflammatory and antiallergic effects of these mushrooms.[12] It is a narrative review rather than a systematic one — it does not report a search strategy, inclusion criteria, or a risk-of-bias assessment — so it should be read as expert synthesis rather than as an independent evidence appraisal.
- Mechanistic and receptor work in cellscompleted
Bouike 2011 (Caco-2 / splenocyte / RAW 264.7 coculture), Yamanaka 2012 (TLR2), Kasai 2004 (CD14/TLR4), Martins 2017 (TLR2 and TLR4 on human monocytes), Choi 2006 (rat peritoneal mast cells), Song 2012 (mouse BMMCs), Smiderle 2011 (THP-1 monocytes). Refs 1, 2, 3, 4, 8, 9, 10.
- Animal allergy and asthma modelscompleted
Takimoto 2008 reduced OVA-specific IgE and IgG1 and airway eosinophils while sparing IgG2a. Ellertsen 2009 reduced anti-OVA IgE whether dosed a day before or 19 days after immunization. Choi 2006 confirmed mast cell effects in vivo. Refs 6, 7, 8.
- A single small randomised controlled trialcurrent
Mahmood 2019: 60 birch-allergic blood donors, 7 weeks pre-seasonal AndoSan at 60 mL/day, NCT03198455. Significant reductions in specific IgE and in basophil sensitisation drift; no difference on the 12-item specific symptom score. Ref 11.
- Independent, adequately powered replicationmissing
No trial from a group unaffiliated with the product's manufacturer has tested ABM in allergic disease. No trial has isolated ABM from the Hericium and Grifola components of AndoSan, and no dose-ranging work in allergy has been published.
- Meta-analysis of allergy outcomesmissing
Not possible with one trial. The available syntheses, including Hetland 2020, are narrative reviews authored by the same research group. Ref 12.
The mechanistic and animal layers are unusually well populated for a medicinal mushroom, and they cohere: the same selective pattern (allergen-specific antibodies down, Th1-associated antibodies untouched) appears in mice and in humans. The clinical layer is one 60-person trial from the group whose senior author co-founded the company that makes the product. That is the rung the claim is standing on.
Refs 1-12
Reading the Claim
What 'clinically proven to rebalance your immune system' does and does not mean
The claim
“Agaricus blazei is clinically proven to shift your immune system out of allergy mode and relieve allergy symptoms.”
A real randomised trial with real positive immunological endpoints, summarised in one sentence that drops the endpoints which did not separate from placebo.
What research shows
OverstatedOne 60-person RCT tested a specific multi-mushroom product at 60 mL/day for seven weeks before pollen season. Specific IgE fell 36-37% (p = 0.007) and basophil sensitisation held steady (p = 0.028). Those are genuine results and they match the mechanism.
In the same trial, the 12-item specific allergy symptom score showed no difference between groups (p = 0.51), total IgE did not change significantly (p = 0.14), medication frequency was only a trend (p = 0.11), and the significant general-symptom finding came from comparing against the previous year's season rather than against placebo during the season. 'Rebalances your immune system' is a fair description of the antibody data. 'Relieves allergy symptoms' is stronger than the symptom data supports.
Ref 11
Honest About the Evidence: What This Research Can and Can't Tell Us
The mechanistic picture is unusually well-developed for a mushroom: gut epithelial activation, toll-like receptor engagement, macrophage involvement, T cell polarization, IgE suppression, and mast cell stabilization through separate pathways. The 2019 human RCT shows specific IgE reduction and preserved basophil thresholds in 60 allergic adults.
But the evidence has identifiable limits that matter for anyone evaluating it honestly.
The clinical evidence has a financial interest attached. All published clinical research on ABM and allergy comes from one research group based at Oslo University Hospital, using one commercial product. AndoSan is supplied by Immunopharma AS of Oslo, which imports the extract as mushroom juice from ACE Co. in Gifu, Japan. In the Mahmood trial's own disclosure, senior author Geir Hetland "is a cofounder and shareholder of Immunopharma."[11] The company provided the product free of charge and the authors state it had no other role, and the trial was pre-registered — all of which is the right way to handle such a relationship. It remains a relationship that independent replication has not yet tested.
Independent replication has not been published. Single-group replication is the central gap in the clinical evidence base, and no amount of mechanistic depth substitutes for it.
The trial was small and its symptom evidence was mixed. Sixty participants — 29 randomised to AndoSan and 31 to placebo — is small for an RCT, and the asthma findings, among the most striking in the paper, come from the subset who had pollen-induced asthma at inclusion: 26% of one arm and 18.5% of the other, or roughly 13 people in total. Larger trials are needed to confirm effect sizes, identify who responds, and detect adverse effects a 60-person study cannot see.
AndoSan is not pure ABM extract. It is 82% ABM, 15% Hericium erinaceus and 3% Grifola frondosa. Whether the allergy effects are attributable to ABM specifically, to the combination, or to particular fractions within ABM has not been isolated.
"Agaricus blazei extract" is not one thing. As the receptor work shows, cold water, hot water, mycelial and chloroform-soluble fractions of the same mushroom behave differently and engage different receptors. Results from one preparation do not automatically transfer to a product made another way.
The Th1/Th2 binary is a simplification. Regulatory T cells play important roles in allergic tolerance, and while Ellertsen and Hetland did measure Treg cytokines, the ABM literature has not characterised Treg involvement in the depth the mechanism would warrant.
Practical Context
ModeratePromising immunological signal, not an allergy treatment
Concern
ABM is an immune stimulant, which is not a neutral property. The mechanism described in this article works by pushing the immune system toward a more active Th1 state, and the same research group's framework explicitly connects that activity to tumor and infection contexts. Substituting a supplement for effective allergy or asthma treatment carries real risk, and untreated or undertreated asthma can be dangerous.
What the research says
The human evidence supports a measurable effect on allergen-specific IgE and basophil sensitivity in one 60-person trial of one specific product at 60 mL/day taken before pollen season. It does not support ABM as a replacement for antihistamines, inhaled corticosteroids, or allergen immunotherapy, and the trial itself allowed participants to continue their regular medication.
Particularly relevant for: People who are pregnant or breastfeeding, immunocompromised, taking immunosuppressants, or living with an autoimmune condition should be especially cautious with immunostimulatory mushroom extracts and should speak to a clinician first. Anyone with a mould or mushroom allergy should avoid them. People with asthma should not reduce prescribed controller medication on the basis of this evidence.
What to do
This article is research analysis, not medical advice. Discuss any supplement with a qualified healthcare professional, particularly if you take prescription medication or have an existing health condition.
Refs 5, 11, 12
For more on the active compounds responsible for ABM's immune effects, see Agaricus blazei Bioactive Compounds: Beta-Glucans and Blazein.
For a comparison with reishi mushroom's different approach to allergic airway disease, see Ganoderma lucidum and Asthma: Can Reishi Help?.
The Bottom Line
Agaricus blazei works on the allergic immune response through at least two parallel pathways: a gut-mediated Th1 shift that reduces allergen-specific IgE upstream, and direct mast cell stabilization that reduces histamine and inflammatory mediator release downstream. The gut pathway (intestinal epithelial cell activation → macrophage involvement → an IFN-γ-rich environment → Th1 T cell differentiation) explains why oral supplementation affects a systemic immune response even though ABM's beta-glucans are too large to enter the bloodstream. Which receptor initiates it is unsettled and fraction-dependent: TLR2 in a cold water extract, CD14/TLR4 in a mycelial fraction, and not dectin-1 in either study that looked. The human clinical evidence is one 60-person pre-seasonal RCT using AndoSan, which found a 36-37% relative reduction in specific IgE against the birch allergen and preserved basophil activation thresholds, but no difference from placebo on the detailed 12-item symptom score. That trial's senior author co-founded the company supplying the product, and independent replication is the main gap in the evidence base.
Frequently Asked Questions
Sources & References
- 1RTHM-00205·Bouike, Go et al. (2011). “Oral Treatment with Extract of Agaricus blazei Murill Enhanced Th1 Response through Intestinal Epithelial Cells and Suppressed OVA-Sensitized Allergy in Mice..” Evidence-based complementary and alternative medicine : eCAM.Study breakdown →PubMed →↩
- 2RTHM-00273·Yamanaka, Daisuke et al. (2012). “Effect of Agaricus brasiliensis-derived cold water extract on Toll-like receptor 2-dependent cytokine production in vitro..” Immunopharmacology and immunotoxicology.Study breakdown →PubMed →↩
- 3RTHM-00071·Kasai, H et al. (2004). “IL-12 Production Induced by Agaricus blazei Fraction H (ABH) Involves Toll-like Receptor (TLR)..” Evidence-based complementary and alternative medicine : eCAM.Study breakdown →PubMed →↩
- 4RTHM-00483·Martins, Priscila Raquel et al. (2017). “Agaricus brasiliensis polysaccharides stimulate human monocytes to capture Candida albicans, express toll-like receptors 2 and 4, and produce pro-inflammatory cytokines..” The journal of venomous animals and toxins including tropical diseases.Study breakdown →PubMed →↩
- 5RTHM-00215·Hetland, Geir et al. (2011). “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..” Advances in pharmacological sciences.Study breakdown →PubMed →↩
- 6RTHM-00146·Takimoto, Hiroaki et al. (2008). “Amelioration of skewed Th1/Th2 balance in tumor-bearing and asthma-induced mice by oral administration of Agaricus blazei extracts..” Immunopharmacology and immunotoxicology.Study breakdown →PubMed →↩
- 7RTHM-00153·Ellertsen, Linda K et al. (2009). “An extract of the medicinal mushroom Agaricus blazei Murill can protect against allergy..” Clinical and molecular allergy : CMA.Study breakdown →PubMed →↩
- 8RTHM-00095·Choi, Yun Ho et al. (2006). “Inhibitory effects of Agaricus blazei on mast cell-mediated anaphylaxis-like reactions..” Biological & pharmaceutical bulletin.Study breakdown →PubMed →↩
- 9RTHM-00263·Song, Hyuk-Hwan et al. (2012). “Anti-inflammatory and anti-allergic effect of Agaricus blazei extract in bone marrow-derived mast cells..” The American journal of Chinese medicine.Study breakdown →PubMed →↩
- 10RTHM-00234·Smiderle, Fhernanda R et al. (2011). “Polysaccharides from Agaricus bisporus and Agaricus brasiliensis show similarities in their structures and their immunomodulatory effects on human monocytic THP-1 cells..” BMC complementary and alternative medicine.Study breakdown →PubMed →↩
- 11RTHM-00579·Mahmood, Faiza et al. (2019). “Agaricus blazei-Based Mushroom Extract Supplementation to Birch Allergic Blood Donors: A Randomized Clinical Trial..” Nutrients.Study breakdown →PubMed →↩
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