Schizophyllum commune

Schizophyllum commune (Split-Gill Mushroom): A Comprehensive Reference

1. Identity, Taxonomy, and Natural Source

Scientific name: Schizophyllum commune Fr. (described by Elias Magnus Fries in 1815). Synonyms used in the pharmaceutical literature include references to its principal bioactive extract under the names schizophyllan, sizofiran, sonifilan, and SPG.

Taxonomic placement: Schizophyllum commune (SC) is a species of fungus in the family Schizophyllaceae and is probably the most widespread fungus in existence. It is a basidiomycete — a member of the class Agaricomycetes — and is commonly called the split-gill mushroom, a name derived from its distinctive morphology: the gills on the underside of its fan-shaped fruiting body are split lengthwise, an adaptation that allows them to curl inward and protect the spore-bearing surface during dry conditions, reopening upon rehydration.

Global distribution and ecology: Schizophyllum commune is an edible and medicinal mushroom widely distributed in the world. It grows on the dead or dying wood of a very wide range of hardwood and occasionally softwood trees, functioning as a white-rot wood-decomposing saprotrophic fungus. Its global distribution spans all continents except Antarctica.

Common preparations and dosage forms: S. commune is encountered in several distinct forms depending on the context of use:

• Whole fruiting body: Consumed fresh or dried as food; sold in fresh condition in traditional markets across Southeast Asia and Africa.
• Dried powder / extract: The dried fruiting body is ground and used in teas, soups, and broths. Ethanol, methanol, and aqueous (hot-water) extracts of the fruiting body are the most common forms used in laboratory research.
• Fermentation-derived schizophyllan (SPG): Schizophyllan is an exopolysaccharide elaborated by the basidiomycete Schizophyllum commune and appreciated as a multipurpose compound applicable in many fields, including food industry and pharmacy. Produced commercially by submerged (liquid) fermentation of the organism, it is isolated from the culture filtrate and purified. Sizofiran (Schizophyllan, SPG, Sonifilan, Sizofilan) is a soluble beta-D-glucan produced by the Basidiomycetes fungus, Schizophyllum commune Fries, with potential immunomodulating and antitumor activities.
• Pharmaceutical intramuscular injection: Purified SPG (sizofiran) is administered intramuscularly in clinical oncology settings in Japan and South Korea.
• Cosmetic/skin formulations: SPG from Schizophyllum commune fungus is a commercially important β-glucan with applications in the health food industry, pharmacy, and cosmetics.

2. Traditional and Historical Use

SC has been widely consumed by people for a long time, with the effect of maintaining body health and treating neurasthenia. SC is used as a traditional food throughout Southeast Asia and India. This mushroom is known for its various biological and medicinal activities and has been widely used in Japan, China, and Taiwan.

Ethnomycological documentation of S. commune spans multiple continents and indigenous traditions:

• Indonesia (Sulawesi): Schizophyllum commune Fr. is a wild macro fungus species, which is often used as a food source by the indigenous Kaili tribe along the Palu-Koro fault, Central Sulawesi, Indonesia. In this region, the fruiting bodies are sold in local markets in fresh condition and are processed into a traditional preparation called Uta Dada.
• Africa: In sub-Saharan Africa, including the Democratic Republic of Congo, the mushroom is commercialized as a food source, and its nutritional and antioxidant properties have been the subject of recent characterization studies.
• Northeast India: The split gill mushroom, Schizophyllum commune Fr., naturally occurs on decaying wood during the rainy season and is consumed as a food source in many parts of North-East India due to its medicinal properties.
• East Asia (China, Japan, Taiwan): In East and Southeast Asian folk cuisine, this mushroom is used as a healthy food, typically simmered in soups and stews for seasonal resilience and overall recovery from health challenges.

Despite its extensive use, no comprehensive review had yet integrated its ethnomycology, pharmacology, and mycochemistry until recently. A scoping review was conducted using Scopus, PubMed, Web of Science, and Google Scholar, identifying 5 papers on ethnomycology, 78 papers on pharmacology, and 33 papers on mycochemistry. The small number of ethnomycological papers relative to pharmacological ones reflects that formal documentation of its traditional uses remains limited compared to the research literature on its bioactive constituents.

3. Nutritional Composition

Proximate composition values vary according to substrate, geographic origin, and whether samples are fresh or dried. Several representative analyses have been reported:

• The S. commune cultivated on a substrate composed of 94% grape residue showed the following chemical composition: 8.40 ± 0.53% moisture, 6.36 ± 0.22% ash, 16.59 ± 0.12% protein, 2.95 ± 1.37% fat, 59.61 ± 0.36% dietary fiber, and 6.09 ± 0.01% carbohydrates.
• A study of samples from the Democratic Republic of Congo showed protein (28.28–35.2 g/100 g DM), carbohydrate (29.98–30.56 g), and fiber (20.5–23.9 g) contents.
• It is valued both as a food source and in traditional medicine due to its rich nutritional composition, featuring high protein (24.5%) and fiber content (19.9%) along with a low-fat profile.

The fungus is valued for its content of fiber, carbohydrates, proteins, lipids, and functional compounds like schizophyllan, flavonoids, saponins, and ergosterol.

Ergosterol is a major sterol component: Ergosterol serves as the predominant sterol metabolite, present at levels of 37–69 mg per 100 g dry weight, acting as a precursor to vitamin D upon UV exposure. The cell walls of the fungus also contain chitin, which is the structural polysaccharide of the fungal cell wall and is largely indigestible in humans.

Quantification of the major bioactive compounds present in the extract showed the following order: phenol > flavonoid > ascorbic acid > β-carotene > lycopene.

4. Key Bioactive Constituents and Active Compounds

About 19 mycochemicals have been identified, including polysaccharides, proteins, aldehydes, alkaloids, sesquiterpenes, and phenolic acids. The most extensively studied compound is schizophyllan, but recently, various functional ingredients have been found in S. commune, such as PSH (polysaccharide-protein complexes), alkaloids, phenolic compounds, terpenoids, ergosterol, iminolactones, vitamins, etc.

4.1 Schizophyllan (SPG / Sizofiran)

Schizophyllan is the signature and most clinically relevant molecule derived from S. commune. Schizophyllan (SPG) is a polysaccharide of Schizophyllum commune with a β-(1→3)-glucan backbone structure, which has been discussed in recent years for its extensive biomedical applications.

Molecular structure: Schizophyllan is a non-ionic, water-soluble homoglucan which possesses a β-(1→3)-linked backbone with single β-(1→6)-linked glucose side chains at approximately every third residue. SPG is a high molecular weight (450 kDa) (1→3)-β-D-glucan that has a 1,6-β-monoglucosyl branch in every three 1,3-β-glucosyl residues on the main chain.

Triple helix conformation: This exopolysaccharide consists of a β-(1,3)-glucan backbone with single β-(1,6)-glucose monomers linked to every third residue, with a molecular weight up to 1.3 × 10⁷ g/mol. It dissolves in water as a trimer of three single chains that form a semi-flexible rod with a triple helical structure, resulting in a highly viscous solution. Schizophyllan has a high stability, illustrated by the fact that the triple helical structure melts at temperatures above 135 °C or at a pH above 12.

Modifiable side chains: Its unique triple helix structure offers various advantages as a carrier for genes or other biomolecules. The side chains of SPG can be effectively modified to change its neutral state and produce aldehyde or carboxylate groups.

4.2 Other Phenolic and Secondary Metabolites

Mushrooms like S. commune are rich in polysaccharides, flavonoids, saponins, and ergosterol, contributing to their antioxidant, antibacterial, antiviral, anti-inflammatory, and immunomodulatory properties.

SC has many bioactive components including schizophyllan, cerebrosides, adenosine, and lectins. GC-MS analysis of an endophytic S. commune extract revealed the presence of 3-n-propyl-2,4-pentanedione, n-heptadecanol-1, trans-geranylgeraniol, 3-ethyl-2-pentadecanone, 1-heneicosanol, and squalene as some of the compounds. Alkaloids and sesquiterpenes are also present among the identified mycochemicals.

5. Mechanisms of Action

5.1 Immunomodulation via Dectin-1 Receptor

The best-characterized mechanism of schizophyllan's biological activity is its interaction with innate immune pattern-recognition receptors. β-glucans are potent immunomodulators, with effects on innate and adaptive immune responses via dectin-1 as the main receptor. SPG binds to Dectin-1 and triggers a signaling cascade leading to NF-κB activation. Detection of β-glucans by the Dectin-1 receptor leads to the CARD9-dependent activation of NF-κB and MAP kinases.

A more detailed molecular study found that SPG and dectin-1 interaction up-regulates LPS-induced IL-10 expression. The regulative effect of SPG on IL-10 expression is dependent on prolongation of nuclear translocation activity of the NF-κBα pathway induced by LPS. LPS-induced phosphorylation of mitogen- and stress-activated protein kinase 1 (MSK1) and cAMP-responsive-element-binding protein (CREB), followed by up-regulation of IL-10, was stimulated by SPG priming via activation of the spleen tyrosine kinase (Syk).

5.2 Activation of Innate Immune Effector Cells

Although sizofiran's exact mechanism of action has yet to be fully elucidated, this agent appears to stimulate the immune system by increasing cytokine production, activating macrophages and Langerhans cells, and enhancing the activity of polymorphonuclear leukocytes (PML) and natural killer (NK) cells.

Preclinical studies have further characterized macrophage activation: researchers tested anti-tumor activities of macrophages treated with a neutral polysaccharide, schizophyllan (SPG), against syngeneic and allogeneic tumor cell lines, finding that SPG was a macrophage stimulant which was not mitogenic to lymphocytes. In vitro studies with ultrasonic-treated SPG showed that more enhancement of NO production in macrophages RAW264.7, lymphocyte proliferation rates, IL-2 and TNF-α levels from spleen lymphocytes, and T-47D cell inhibition rates were observed in USPG fractions groups.

5.3 Antioxidant Mechanisms

S. commune shows strong antioxidant activity, protecting cells from oxidative stress and DNA damage. In animal studies, the S. commune extract-treated fish exhibited an increase in the level of antioxidant enzymes, namely catalase, superoxide dismutase, and glutathione reductase, as well as histoprotective effects on various organs.

5.4 Antidiabetic Mechanisms

Preliminary screening for in-vitro activity was carried out using an α-glucosidase inhibition assay. An endophytic isolate Sch1, identified to be Schizophyllum commune Fr. on a molecular basis, exhibited more than 90% α-glucosidase inhibitory activity and was selected for further studies. This enzyme inhibition mechanism parallels that of some oral antidiabetic drugs (such as acarbose), slowing post-prandial carbohydrate digestion and glucose absorption.

6. Scientific Evidence by Area of Use

6.1 Cancer Immunotherapy / Oncology

This is the area with the strongest and most direct clinical evidence for S. commune products. Schizophyllan (SPG), one of the most studied β-glucans isolated from S. commune, has been utilized in clinical trials to treat patients receiving anticancer therapy as an immunopotentiator. Sonifilan is used as a biological response modifier (BRM) with radiation therapy for cancer treatment in Japan.

6.1.1 Cervical Cancer

Schizophyllan (Sizofiran), a polysaccharide extract from Schizophyllum commune, is licensed in Japan for the treatment of cervical cancer and, in a 5-year multi-centre study, has been shown to significantly extend time to recurrence and improve survival rates in patients with stage II cervical cancer but not in those with stage III cancer. It was launched for cervical cancer in South Korea in 1998.

The pivotal randomized controlled study underpinning licensure is well-documented in the literature. To evaluate the clinical effect of a biological response modifier (BRM), sizofiran (SPG), combined with irradiation, a randomized controlled study was performed in patients with stage II or III cervical cancer involving the collaboration of 52 institutes throughout Japan. Patients were randomly allocated to the control group (radiotherapy only) and the SPG group (radiotherapy + SPG). SPG was given intramuscularly, 40 mg once and 20 mg twice a week concomitantly with radiotherapy. A total of 315 patients were enrolled for the study, but 23 were excluded from analysis. Of the remaining 292 patients, 121 were of stage II (43 controls and 78 SPG) and 171 of stage III (49 controls and 122 SPG).

Key efficacy results from this trial: The complete response (CR) rate among stage II patients was higher in the SPG group (91.0%) than in the control group (79.1%); also the CR rate among stage III patients was significantly higher in the SPG group (77.9%) than in the control group (61.2%). The SPG group showed significantly rapid recovery from decreased lymphocyte counts due to radiotherapy. Side effects, probably associated with SPG administration, were observed in 11 cases (5.2%).

A subsequent 5-year randomized controlled follow-up study, conducted across 19 institutions in Japan, confirmed the earlier findings: the effectiveness of sizofiran (Schizophyllan: SPG) to prolong the survival and time to recurrence of the patients with stage II or III cervical cancer was evaluated in a 5-year randomized controlled study. Of the overall patients with stage II or III cancer, time to recurrence and survival rate in the SPG group were significantly longer than in the control group. In the stage II patients, there was significant difference in time to recurrence, and survival of the SPG group tended to be longer than that of the control group. However, in the stage III patients, there was no significant difference in either time to recurrence or survival rate.

Evidence strength: Moderate-to-good for stage II cervical cancer. Multiple randomized controlled trials conducted in Japan, including multi-institutional studies with hundreds of patients, support a statistically significant benefit for stage II disease in combination with radiotherapy. Stage III disease showed inconsistent results across trials. The clinical regulatory context (Japan license) reflects this evidence base.

6.1.2 Gastric Cancer

Adjuvant immunochemotherapy using schizophyllan (SPG), an extract from the culture broth of Schizophyllum commune Fries, was prescribed at random for 326 Japanese patients with resectable gastric cancer. The overall survival rates for 3 years did not differ between the SPG and control groups. In 62 patients with stage I gastric cancer and 67 with stage II, there was little difference in the 3-year survival rates. The survival rates for 100 patients with stage III were enhanced at p = 0.0811 in the SPG group, as compared to the controls. The survival rates in 97 patients with stage IV cancer were much the same.

A further controlled study in advanced gastric cancer reported that in the case of unresectable cases, the SPG group survived longer (p = 0.009 in the MF method and p = 0.003 in the F method) than did the control group (chemotherapy only). In the resectable setting, although the overall survival rates for 5 years did not differ between both groups, the 5-year survival rate for stage III in the SPG group was superior to the findings for stage III in the control (p = 0.0105).

Evidence strength: Weak-to-moderate and inconsistent. Sizofiran was found rather ineffective against gastric cancer, but extended survival time in patients with head and neck cancer. The body of gastric cancer trials, while representing randomized designs, generally showed overall survival benefits confined to stage III subgroups, with no clear benefit across all cancer stages, and results were borderline statistically significant.

6.1.3 Head and Neck Squamous Cell Carcinoma

A phase II randomized controlled trial was carried out to evaluate the clinical efficacy and tolerability of Schizophyllan (SPG) used in combination with standard chemotherapy in the neoadjuvant setting in patients with locally advanced head and neck squamous cell carcinoma. Several immunological parameters were considered to assess the immunoregulatory activity of SPG in the same patients. The clinical and immunological evaluations were performed both before and at the end of the study (4 months later).

The dosing regimen used was: SPG was administered weekly at a single dose of 40 mg intramuscularly for 4 months in addition to standard chemotherapy. Twenty-six patients were enrolled, 22 of whom were evaluable. Thirteen patients were assigned to Arm A (treatment with SPG associated with chemotherapy) and 9 patients to Arm B (treatment with chemotherapy alone). The overall response rate was not significantly different between the two Arms (92.3% in Arm A vs. 100% in Arm B), although a higher number of complete responses (3 = 23.1%) was registered in Arm A.

Overall, the SPG treatment does not seem to have induced significant changes of the immunological parameters of the patients; this may be due to both the advanced cancer stage and the effect of chemotherapy, which are both well-known causes of immunodepression.

Evidence strength: Preliminary and inconclusive. This phase II trial was small (22 evaluable patients), lacked statistical power to detect a meaningful clinical difference, and showed no significant improvement in overall response rate. Its results cannot be considered definitive.

6.2 Antidiabetic Activity

Detailed in-vivo investigations for antidiabetic potential of an ethyl acetate extract of S. commune, at two different doses, were carried out in streptozotocin-induced diabetic Wistar rats. Treatment of diabetic rats with S. commune extract caused significant decrease in blood glucose level and increase in body weight after a 14-day experimental period. It significantly restored renal parameters including creatinine, blood urea nitrogen, fractional excretion of sodium, and potassium level in diabetic rats. Improvement in lipid profile and levels of antioxidant parameters, namely reduced glutathione, thiobarbituric acid reactive species, and superoxide anion generation, was also observed after treatment.

Evidence strength: Preliminary — animal and in-vitro data only. No published human clinical trials on S. commune for diabetes management have been identified. All antidiabetic evidence is from cell-based or rodent models and cannot be extrapolated to clinical recommendations.

6.3 Antioxidant and Genoprotective Activity

S. commune shows strong antioxidant activity, protecting cells from oxidative stress and DNA damage. It also demonstrates genoprotective and organoprotective effects, particularly against environmental toxins like Bisphenol A.

In an in-vivo study using freshwater fish (Channa punctatus) exposed to bisphenol A, a significant decrease in the considered parameters for DNA damage (% micronuclei and comet assay) was recorded in fish treated with S. commune extract compared to the untreated bisphenol-A-exposed group.

Evidence strength: Preliminary — in-vitro and animal data only. The antioxidant capacity of S. commune extracts has been consistently demonstrated across multiple analytical platforms (DPPH radical scavenging, ABTS, FRAP), but human clinical data validating these effects are absent.

6.4 Antimicrobial Activity

Its antibacterial and biofilm-disrupting activities target multidrug-resistant pathogens. Recent studies have revealed acetaldehyde production from schizophyllan, which has strong anti-microbial activity. The oxidized form of schizophyllan is applicable against a broad range of bacteria (both gram-positive and gram-negative).

These compounds are associated with antioxidant, antimicrobial, cytotoxic, antidiabetic, immunomodulatory, anti-inflammatory, antitumour, and wound-healing effects, as demonstrated in both in vitro and in vivo studies.

Evidence strength: Preliminary — in-vitro data only. Antimicrobial effects of S. commune extracts and schizophyllan-derived compounds have been demonstrated in laboratory settings, but there are no human clinical studies of S. commune as an antimicrobial agent.

6.5 Antiviral Activity and SARS-CoV-2 Receptor Reduction

Clinical relevance has been noted in infectious-disease contexts: clinical studies in chronic hepatitis B patients have demonstrated augmentation of HBV nucleocapsid-antigen–specific T- and B-cell responses.

A more recent in-vitro and cell-culture study investigated S. commune's potential against SARS-CoV-2: recent studies have shown that SC extracts have potential therapeutic effects including antioxidant, antitumor activity, antivirus, and immunomodulating properties, as well as ACE inhibitory activity.

Evidence strength: Very preliminary. Antiviral effects are supported only by cell-culture experiments and limited immunological studies. No clinical trial data exist on S. commune for any viral infection in the context of dietary supplementation.

6.6 Anti-inflammatory Activity

Schizophyllan has numerous biological activities that are widely used in medicine, including antitumor, antibacterial, antiparasitic, hepatoprotective, and anti-inflammatory properties. The Dectin-1/NF-κB signaling pathway described above is central to how SPG modulates inflammatory cytokine cascades. However, evidence for anti-inflammatory efficacy in human disease is indirect and extrapolated from immunomodulatory effects observed in oncology trials.

Evidence strength: Preliminary — primarily mechanistic and in-vitro/animal. The molecular basis for anti-inflammatory effects has been partially elucidated in cell culture, but no human trials exist addressing S. commune supplementation for inflammatory conditions as a primary endpoint.

7. Body Systems and Health Areas Associated with S. commune

• Immune System: The most evidence-supported application area. Schizophyllan modulates both innate and adaptive immunity via Dectin-1 receptor signaling, macrophage activation, NK cell enhancement, and cytokine regulation. Human clinical data exist specifically in oncology settings.
• Oncology (adjuvant): Licensed clinical use as an immunoadjuvant in cervical cancer (Japan, South Korea); clinical trial evidence in gastric cancer and head and neck cancer.
• Metabolic/Endocrine System: Preclinical evidence for α-glucosidase inhibition and blood glucose reduction in diabetic animal models; no human data.
• Cardiovascular System: These compounds suggest potential in preventing and managing chronic diseases such as cancer, cardiovascular issues, diabetes, and neurodegenerative conditions. This claim remains extrapolated from constituent-level data (e.g., β-glucan fiber, ergosterol) rather than clinical outcome evidence.
• Respiratory System: Respiratory tract is one of the most vulnerable organs to S. commune infections, resulting in sinusitis, allergic bronchopulmonary mycosis (ABPM), and pneumonia. This association is pathological (infection risk), not therapeutic.
• Dermatology/Wound Healing: Preliminary data from in-vitro and animal studies suggest wound-healing properties related to the immunomodulatory and anti-inflammatory actions of its polysaccharides.
• Hepatoprotective: Listed as a property of schizophyllan in multiple reviews; supported by animal data but not clinical trials.

8. Dosage Forms and Dosages Reported in Studies

The following dosages are reported in published peer-reviewed studies; no dosage recommendations are implied:

• Cervical cancer (intramuscular, clinical RCT): SPG was given intramuscularly, 40 mg once and 20 mg twice a week concomitantly with radiotherapy.
• Head and neck cancer (intramuscular, phase II RCT): SPG was administered weekly at a single dose of 40 mg intramuscularly for 4 months in addition to standard chemotherapy.
• Gastric cancer adjuvant (intramuscular, RCT): In the SPG group, SPG was administered intramuscularly 40 mg/week concurrently with the start of oral tegafur.
• Antidiabetic in-vivo rat study: Detailed in-vivo investigations for antidiabetic potential of ethyl acetate extract of S. commune (Sch1), at two different doses, were carried out in streptozotocin-induced diabetic Wistar rats. (Specific mg/kg dose values were not retrievable from the available abstract; the study was published in AMB Express, 2021.)
• Immunoregulatory in-vitro/in-vivo (murine): Murine peritoneal adherent cells harvested 4 days after a single IP injection of SPG at a dose of 100 mg/kg body weight of mouse showed the most pronounced anti-tumor macrophage activity.

All clinical dosages reported above pertain to the purified injectible pharmaceutical preparation (sizofiran/SPG), not to dietary supplementation with whole mushroom powder or extracts. No standardized oral dosing regimen for S. commune as a dietary supplement has been established in the peer-reviewed literature.

9. Safety Considerations

9.1 General Safety Profile

Toxicity studies confirm safety of S. commune, though monitoring is needed in immunocompromised individuals. Schizophyllan, classified as a beta-glucan and extracted from the fungus Schizophyllum commune, showed no quantifiable adverse reactions through independent scientific procedures. With its classification as a beta-glucan, schizophyllan is generally recognized as safe (GRAS) by the United States FDA. Schizophyllan and other β-glucans have been orally administered safely in a variety of vertebrate species showing immunomodulation: mice, canines, horses, and humans. In 2012, mushroom-derived beta-glucans were deemed GRAS by direct FDA review.

The ability for schizophyllan to produce a physiological response is directly correlated with the extraction process and subsequent processing the compound endures.

9.2 Adverse Events in Clinical Trials

In the large Japanese cervical cancer randomized controlled study, side effects, probably associated with SPG administration, were observed in 11 cases (5.2%). No severe adverse events specifically attributable to SPG were highlighted in the major oncology trials reviewed, though the intramuscular route of administration in these trials differs substantially from oral supplementation.

9.3 Opportunistic Infection Risk in Immunocompromised Hosts

A clinically important safety consideration is the dual nature of S. commune: while its purified polysaccharides are used to stimulate immunity in oncology, the intact organism can itself act as a pathogen. Schizophyllum commune has garnered increasing attention in the medical field due to its capacity to cause a variety of infections in humans. This opportunistic pathogen predominantly affects immunocompromised individuals, particularly those with underlying hematological malignancies or organ transplantation.

The opportunistic pathogen predominantly affects immunocompromised individuals, particularly those with underlying hematological malignancies or organ transplantation. The clinical manifestations of SC infections can range from localized sinusitis to disseminated and potentially life-threatening conditions.

The most frequently infected regions are the sinus, sino-orbital, bronchopulmonary, and extra-pulmonary areas, ranging from allergic respiratory conditions to severe life-threatening brain lesions in both immunocompetent and immunocompromised hosts.

S. commune is a well-known mushroom-forming fungus which is an edible one due to its nutritive value. It exhibits a special wood-degrading mechanism to grow in decay matters by releasing a series of enzymes. These enzymes might make it an opportunistic pathogen which has been reported to infect various animals and human beings.

Treatment of S. commune infection: Clinicians should pay great attention to pulmonary infections caused by S. commune especially in immunocompromised patients. Azole antifungals are the preferred agents for S. commune infection. Good prognosis will be achieved under proper antifungal therapy and the course of the treatment should be individualized.

9.4 Chitin Content and Gastrointestinal Tolerance

Due to its high chitin content, which is indigestible for humans, overconsumption should be avoided to prevent gastrointestinal discomfort, and individuals with allergies or compromised immunity may experience adverse reactions such as respiratory issues.

9.5 Processing and Bioactivity Dependence

High doses of schizophyllan are not the primary determinant of an immunological response; rather, the extraction method and molecular conformation of SPG determine its biological activity. This means that crude whole mushroom preparations may deliver substantially different and less-characterized pharmacological effects compared to pharmaceutical-grade sizofiran.

10. Overall Characterization of the Evidence Base

The evidence for Schizophyllum commune and its principal bioactive extract schizophyllan spans a wide but uneven landscape. Further investigations are needed to validate traditional uses, elucidate mechanisms of action, and evaluate toxicity and safety profiles, thereby supporting its future development for medical and food applications.

The strongest and most reproducible human clinical evidence is confined to the pharmaceutical preparation sizofiran (SPG) administered by intramuscular injection as an adjuvant in cervical cancer (stage II) with radiotherapy in Japan, where it holds marketing authorization. For all other claimed benefits — including antidiabetic, antioxidant, anti-inflammatory, antiviral, and broader antimicrobial effects — the evidence base remains at the in-vitro and/or animal-model level and cannot be extrapolated to support clinical recommendations for dietary supplementation.

The identified compounds are associated with antioxidant, antimicrobial, cytotoxic, antidiabetic, immunomodulatory, anti-inflammatory, antitumour, and wound-healing effects, as demonstrated in both in vitro and in vivo studies. However, the gap between these laboratory findings and established clinical benefit in humans remains large for most of these areas.

References

• Bioactive compounds, health benefits, and practical applications of edible mushroom Schizophyllum commune Fr.: A decade-long critical review — PubMed (2025)
• Schizophyllum commune as a source of mycochemicals with therapeutic relevance for human health — Discover Food, Springer Nature (2026)
• Bioactive compounds, health benefits, and practical applications of edible mushroom Schizophyllum commune Fr. — Food Chemistry, ScienceDirect (2025)
• Schizophyllum commune Reduces Expression of the SARS-CoV-2 Receptors ACE2 and TMPRSS2 — PMC (2022)
• Schizophyllum commune, an underrated edible and medicinal mushroom: farm to industry — MaxaPress (2025)
• Research progress on production and biomedical applications of Schizophyllan as a tailor-made polysaccharide: A review — PubMed (2024)
• Schizophyllan: A review on its structure, properties, bioactivities and recent developments — ScienceDirect (2013)
• Schizophyllan — ScienceDirect Topics Overview
• Functions of the cell wall polysaccharide schizophyllan during vegetative growth of Schizophyllum commune — PMC (2025)
• Clinical and immunological evaluation of schizophyllan (SPG) in combination with standard chemotherapy in patients with head and neck squamous cell carcinoma — PubMed (2011)
• Clinical evaluation of schizophyllan adjuvant immunochemotherapy for patients with resectable gastric cancer — A randomized controlled trial — Surgery Today, Springer (1984)
• [Clinical efficacies of schizophyllan (SPG) on advanced gastric cancer] — PubMed (1989)
• Clinical evaluation of sizofiran combined with irradiation in patients with cervical cancer. A randomized controlled study; a five-year survival rate — PubMed (1989)
• Clinical effect of sizofiran combined with irradiation in cervical cancer patients: a randomized controlled study — PubMed (1992)
• Clinical evaluation of schizophyllan combined with irradiation in patients with cervical cancer: A randomized controlled study — Cancer (Wiley, 1986)
• Schizophyllum commune β-glucan: Effect on interleukin-10 expression induced by lipopolysaccharide from periodontopathic bacteria — PubMed (2021)
• Immunoregulatory and antitumor activity of schizophyllan under ultrasonic treatment — PubMed (2015)
• Schizophyllan (SPG)-treated macrophages and anti-tumor activities against syngeneic and allogeneic tumor cells — Cancer Immunology, Immunotherapy, Springer (1984)
• NCATS Inxight Drugs — SIZOFIRAN (Schizophyllan) Entry
• An endophytic Schizophyllum commune Fr. exhibits in-vitro and in-vivo antidiabetic activity in streptozotocin induced diabetic rats — PMC (2021)
• An endophytic Schizophyllum commune possessing antioxidant activity exhibits genoprotective and organoprotective effects — PMC (2022)
• Diversity of substrate type, ethnomycology, mineral composition, proximate, and phytochemical compounds of Schizophyllum commune Fr. in Central Sulawesi, Indonesia — PMC (2023)
• Mushroom-derived polysaccharides as broad-spectrum antimicrobial agents — Frontiers in Microbiology (2026)
• Human infections due to Schizophyllum commune: Case report and review of the literature — ScienceDirect (2019)
• Pneumonia due to Schizophyllum commune in a Patient with Acute Myeloid Leukemia: Case Report and Literature Review — Infection & Chemotherapy (2020)
• Pneumonia caused by Schizophyllum commune — Medicine (LWW, 2023)
• Resolving the pathogenicity factors of a novel opportunistic fungus Schizophyllum commune at molecular level — PubMed (2019)
• Chemistry: Schizophyllan — HandWiki (sourced from peer-reviewed references)
• Schizophyllan Beta-glucan from Schizophyllum commune; a Dectin-1 ligand — InvivoGen Technical Data Sheet
• The versatility of Schizophyllum commune in nature and application — ScienceDirect (2025)
• Improving the Proteome-Mining of Schizophyllum commune to Enhance Medicinal Mushroom Applications — PMC (2025)
• Optimizing Growth and Bioactive Compound Production in Split Gill Mushroom (Schizophyllum commune) Using Methyl Jasmonate — MDPI Resources (2024)