Shiitake Mushroom (Lentinula edodes)
1. Identity: Botanical and Chemical Names, Natural Source, and Common Forms
Taxonomy and Nomenclature
Shiitake mushroom (Lentinula edodes) is a Basidiomycete with extensive ethnomedicinal use, exhibiting significant nutraceutical and pharmaceutical potential. The species has carried several scientific designations over the course of mycological history. The most widely encountered synonyms in older literature and some modern research papers are Lentinus edodes (Berk.) Singer — the name under which a large body of Japanese clinical research was published — and Lentinula edodes (Berk.) Pegler, which is currently accepted as the correct binomial under modern fungal taxonomy. Both names refer to the same organism and appear interchangeably in the peer-reviewed literature.
The name "shiitake" is derived from Japanese, where shii refers to a type of hardwood tree (Castanopsis or similar) and take means mushroom — together meaning "mushroom that grows on trees," reflecting its natural growth habitat. In China, the mushroom is known as xiang gu (香菇), translating to "fragrant mushroom."
Natural Habitat and Cultivation
Shiitake mushrooms are native to East Asia, especially the forests of China, Japan, and Korea. They naturally grow on hardwood logs, such as oak, which provide a rich food source for their development. Shiitake has a scaly, light to dark brown cap approximately 5–12 cm in diameter on an approximately 3–5 cm high stem. Its flesh has a firm consistency and a strong aroma.
Today, China is the largest producer of shiitake mushrooms, accounting for approximately 90% of global production, followed by Japan, South Korea, and Taiwan.
Common Forms and Preparations
Shiitake is available in a wide variety of forms for both culinary and supplemental use. The principal commercially available preparations include:
- Whole fresh mushroom — consumed directly as a food.
- Dried whole mushroom — used in cooking or ground into powder. Research studies including the Dai et al. (2015) randomized trial used whole, dried shiitake.
- Hot water extract (fruiting body or mycelium) — a common form in standardized supplements; hot water extraction preferentially solubilizes polysaccharide fractions such as beta-glucans.
- LEM (Lentinula edodes Mycelia Extract) — a shiitake mycelia crude, hot water-extracted powder with potential immunomodulatory and antitumor properties.
- AHCC (Active Hexose Correlated Compound) — a proprietary alpha-glucan extract from sources including shiitake mycelia, popular as a supplement for cancer patients in Japan since 1987, and also taken for the treatment of HIV, HPV, and impaired liver function.
- Isolated lentinan (pharmaceutical grade) — a purified beta-glucan that has been used as an anticancer drug in combination with 5-fluorouracil for gastric cancer in Japan.
2. Traditional and Historical Use
China
The earliest records of shiitake mushrooms date back to Song Dynasty China (960–1279 AD), where they were recognized for both their culinary and medicinal properties. The cultivation of shiitake mushrooms traces back to China, where around 1,000 to 1,200 years ago, people began cultivating them, referring to the species as dongo or shanku. From about 600–1000 AD, the Chinese developed cultivation techniques for many medicinal and culinary mushrooms to meet ever-growing demand; the famous shiitake mushroom (Lentinus edodes) has been widely cultivated from about 1000 AD. A further cultivation text was written in 1313 by Wang Cheng, specifying techniques in greater detail.
During the Ming Dynasty, shiitake was esteemed as "the elixir of life" in Chinese culture. Shiitake has played a dual role in Traditional Chinese Medicine (TCM), serving not only as a dietary staple but also as a supplement believed to contribute to longevity and support healthy circulation. The most important treatise of TCM is undoubtedly Li Shizhen's monumental work published in 1578, Bencao Gangmu — a culmination of his 26 years of field study and reading of over 800 medical reference books. This compendium documented shiitake alongside hundreds of other medicinal substances.
In traditional East Asian medicine, shiitake is regarded as energetically sweet and neutral, making it a gentle, nourishing tonic for the body that lends itself to regular consumption; it has been used for thousands of years to strengthen weakness, in particular of the Spleen and Stomach — the digestive center. In doing so, it was believed to address digestive deficiencies manifesting in symptoms such as poor appetite and bloating, and to promote the flourishing of qi (energy), blood, and wei qi (immunity).
Japan and Korea
Shiitake was a known medicinal mushroom in Japan; in the year 199 AD, the 14th Japanese Emperor Chuai received shiitake mushroom as a gift from a native tribe. During the 12th–13th centuries, shiitake mushrooms were introduced more formally to Japan by Chinese monks traveling to spread Buddhism. The mushroom became popular among the nobility and monks due to its rich umami flavor and nutritional value. Traditional Chinese medicine, introduced mostly during the 7th–9th century AD, greatly influenced Japanese traditional medicine (Kampo). Kampo is similar to TCM with a stronger emphasis on using medicinal "herbs" — including mushrooms, especially shiitake.
Shiitake mushrooms have a long history of use in the medicinal traditions of China, Japan, Korea, and Eastern Russia. Throughout history, shiitake mushrooms have been valued not only as food but also as traditional medicine in both Chinese and Japanese healing systems. Ancient texts cite their ability to restore energy, boost the immune system, and aid in recovery.
3. Key Constituents and Active Compounds
Polysaccharides
Nutritional components include bioactive polysaccharides such as β-D-glucan, heteroglucan, xylomannan, and lentinan; free sugars including arabinose, arabitol, mannose, mannitol, trehalose, and glycerol; vitamins (B2, B12, D2); and dietary fibre.
Lentinan is the most extensively studied polysaccharide. The major active substance in L. edodes is a (1-6,1-3)-beta-glucan (lentinan). Lentinan is a type of sugar molecule called 1,3 beta glucan. In laboratory tests, lentinan does not kill cancer cells directly; instead, it enhances the immune system, which may aid in slowing the growth of tumors. Lentinan triggers signaling pathways such as MAPK, NF-κB, and Syk-PKC, via binding to pattern recognition receptors (TLRs, Dectin-1) and the complement receptor type 3 (CR3, also known as CD11b/CD18) on the membrane of various immune cells, particularly natural killers, macrophages, and T cells.
Eritadenine
The edible fungus, shiitake mushroom (Lentinus edodes), contains the hypocholesterolemic agent eritadenine, 2(R),3(R)-dihydroxy-4-(9-adenyl)-butyric acid. Eritadenine works by preventing cholesterol from being liberated from tissues, or it has been thought to speed up elimination of cholesterol from blood by boosting tissue absorption, but it has no effect on cholesterol production in the liver. Shiitake strains may exhibit up to ten times higher levels of eritadenine than previously reported for other strains, depending on variety.
Lenthionine and Sulfur Compounds
Lenthionine is a sulfur-containing antimicrobial compound found in shiitake mushrooms. It is responsible for a significant portion of the mushroom's characteristic aroma and has been studied for its antibacterial properties.
Sterols and Vitamin D Precursors
Ergosterol, a sterol found in the cell membranes of fungi, is a precursor to vitamin D2 (ergocalciferol) and is abundant in shiitake. GC–MS analyses identified α-tocopherol (vitamin E), oleic acid, linoleic acid, ergosterol, and butyric acid as bio-functional components present in L. edodes. UV exposure of shiitake converts ergosterol to vitamin D2, and sun-dried shiitake is recognized as an unusually rich natural source of this vitamin.
Ergothioneine
Shiitake mushrooms contain ergothioneine, a unique antioxidant that helps reduce oxidative stress and inflammation in blood vessels. Ergothioneine is a naturally occurring amino acid derivative present in only a small number of natural sources, and shiitake is among the richer fungal sources of this compound.
Phenolics, Coumarins, Terpenoids, and Other Compounds
The bioactive constituents of L. edodes include lentinan, eritadenine, lenthionine, guaiacol, syringol, diterpenes, triterpenoids, flavonoids, organic esters, tocopherols, and polyunsaturated fatty acids. Chemical investigations of the fruiting bodies and mycelium of shiitake mushrooms have afforded five new compounds named lentinmacrocycles A–C and lentincoumarins A–B, along with fifteen known compounds. Anti-inflammatory activity tests showed that lentincoumarins A and specific hydroxymellein compounds exhibited strong NO inhibitory effects (IC50 < 35 μM), and that additional hydroxymellein compounds exhibited potent TNF-α inhibitory effects (IC50 < 80 μM).
Lentinic acid, shiitakeols A/B, and lanostanoids show anti-inflammatory activity; lentinan and latcripin derivatives possess anticancer effects; sterols, β-glucans, and eritadenine are hepatoprotective. Lentinan promotes immunomodulation, while eritadenine, ergosterol, and β-glucans contribute to cardiovascular health.
4. Scientific Evidence by Area of Use
4.1 Immune Function
Clinical Evidence
The most methodologically rigorous human study on shiitake and immunity is the Dai et al. (2015) randomized dietary intervention. Mushrooms are widely cited for their medicinal qualities, yet very few human intervention studies had been done using contemporary guidelines at the time. The aim of this study was to determine whether consumption of whole, dried Lentinula edodes (shiitake) mushrooms could improve human immune function. This parallel RCT in 52 healthy adults (21–41 years) found that consuming 5 or 10 g/day of shiitake for four weeks resulted in a 60% increase in γδ-T cell proliferation (p<0.0001). The randomized dietary intervention found that shiitake improved several immune function markers and reduced CRP in healthy adults.
A separate crossover, placebo-controlled study investigated the oral administration of a soluble beta-glucan (Lentinex) from L. edodes mycelium. The effect and safety of a beta-glucan from L. edodes mycelium, Lentinex, was evaluated in healthy elderly subjects in a double-blind, crossover, placebo-controlled trial. Forty-two subjects were randomly allocated to two groups given orally either 2.5 mg/day Lentinex or placebo for 6 weeks; then after a washout period of 4 weeks, the alternate supplementation was given for 6 weeks. The changes in the number of B-cells were significantly different between the groups. The number of NK cells increased significantly in both groups, but there was no significant difference between the groups. Other factors of the immune response (immunoglobulins, complement proteins, cytokines) were not altered. The safety blood variables were not influenced by Lentinex, and the number, nature, and severity of adverse events were similar to placebo. Lentinex given orally to elderly subjects was safe and induced an increase in the number of circulating B-cells.
Mechanistic Evidence
In mouse macrophage models, lentinan selectively inhibited AIM2 inflammasome activation and up-regulated pro-inflammatory cytokines, inducing expression of inflammasome-related genes through toll-like receptor 4 signaling. These are preclinical findings and do not directly establish human therapeutic outcomes.
Evidence Strength
Moderate, based on a small number of human RCTs. The Dai et al. (2015) study was well-designed but enrolled only 52 participants. The Lentinex crossover study enrolled 42 elderly subjects. Additional well-powered RCTs across diverse populations are needed before definitive conclusions can be drawn.
4.2 Oncology — Lentinan as Adjuvant to Chemotherapy
Regulatory and Clinical Context
Lentinan has been approved as an adjuvant therapeutic drug both in China and Japan for treating cancers since the 1980s. Its use in clinical oncology is primarily as an intravenously administered adjunct to standard chemotherapy, not as a stand-alone cancer treatment.
Clinical Trial Evidence
A randomized study of mitomycin C + 5-FU versus the same combination plus lentinan was conducted in 166 patients comprising 115 cases of gastric cancer and 51 cases of colorectal cancer. Significant increases were observed in the survival rates for the lentinan group (p < 0.05) for both patients with gastric and colorectal cancer.
A study at a Japanese hospital enrolled 78 patients with metastatic or recurrent gastric cancer receiving S-1-based chemotherapy. Median overall survival was significantly longer in the lentinan group than in the chemotherapy-alone group (689 days vs. 565 days, P = 0.0406).
A meta-analysis published in 2017 pooled data from seventeen prospective controlled trials involving 1,423 patients. Twelve trials included gastrointestinal cancer (GIC), three trials included lung cancer (LC), and two trials included both cancer types. There was an increase in one-year survival rate (RR 1.46, P = 0.001) and overall response rate including both complete and partial response (RR 1.28, P = 0.005). There was also a reduction in progressive disease (RR 0.57, P = 0.0005), non-severe adverse events (RR 0.88, P = 0.004), and severe adverse events (RR 0.73, P = 0.007). Limited trials reported data on median overall survival and time to treatment failure, and the data were insufficient for quantitative analysis; no significant difference was found in two-year survival rate. Adjuvant lentinan used with chemotherapy achieved improvements in one-year survival rate, response rate, and adverse events in advanced cancer, with similar effects across cancer types.
A review of 12 years of clinical studies in China surveyed over 9,474 lentinan-associated cancer treatment cases. The cases include lung cancer (3,469 cases), gastric cancer (3,039 cases), colorectal cancer (1,646 cases), ovarian cancer (183 cases), cervical cancer (130 cases), and non-Hodgkin lymphoma (70 cases), evaluated from 135 independent studies conducted in China during 2004–2016.
Mechanism
Lentinan (1,3 beta-D-glucan) is thought to be responsible for its beneficial effects. Although it has been shown to have anticancer effects, lentinan is considered a biological response modifier, rather than having a direct cytotoxic effect on tumor cells. Lentinan also kills viruses and microbes directly in laboratory studies.
Evidence Strength
Moderate-to-good for lentinan as a chemotherapy adjunct in gastric and colorectal cancer. The meta-analysis is limited by the heterogeneity of included trials (mostly Japanese and Chinese, variable regimens) and the lack of statistically significant two-year survival data. Several clinical trials show that lentinan combined with chemotherapy extends survival in patients with stomach, prostate, colorectal, and liver cancers, but additional studies are needed.
4.3 HIV Infection
Clinical Evidence
Lentinan is a beta 1→3 glucan isolated from Lentinus edodes with immune-modulating properties. Two Phase I/II placebo-controlled trials were conducted on a total of 98 patients. In one study at the San Francisco General Hospital (SFGH), ten patients each were administered 2, 5, or 10 mg of lentinan or placebo intravenously once a week for eight weeks. In the second study at the Community Research Initiative in New York (CRI), two groups of 20 patients each were administered 1 or 5 mg of lentinan intravenously twice a week for 12 weeks, and ten patients received placebo. Entry criteria were an HIV-positive test, CD4 levels of 200–500 cells, and age 18–60 years, without current opportunistic infections.
Patients in the study showed a trend toward increases in CD4 cells and, in some patients, neutrophil activity. Because of the small numbers, these values did not have statistical significance. The study confirms, in Caucasian subjects also, the good tolerability of lentinan observed in Japanese cancer patients.
Evidence Strength
Preliminary and inconclusive. The Phase I/II trials established safety and tolerability but were underpowered to demonstrate efficacy. No large, well-powered RCTs in HIV have been published to date.
4.4 HPV Clearance — AHCC
Clinical Evidence
Daily use of AHCC was linked to markers of improved immune function and to the clearing of HPV after six months of supplementation, according to a study published in Frontiers in Oncology. AHCC is a unique natural cultured extract derived from the cell wall of the mycelia of Lentinula edodes (shiitake) mushrooms. It is rich in alpha glucans and other immune-modulating polysaccharides, and has been the subject of more than 20 human clinical studies and over 50 papers published in Medline-indexed journals.
Two pilot studies were conducted. Study 1 showed that 4 out of 8 women (50%) cleared HPV within 3–6 months with 3 g daily. Study 2 showed that 4 out of 9 women (44%) cleared HPV within 7 months with 1 g daily. These promising results led to a Phase II trial. Conducted by Dr. Judith Smith, this trial involved 50 women with persistent HPV infections: Group 1 took AHCC daily for 6 months, followed by a placebo for 6 months; Group 2 took a placebo only. Of those who received six months of daily AHCC treatment followed by six months of placebo, 63.6% (14 of 22) cleared the infection with no adverse side effects.
Evidence Strength
Preliminary but increasingly substantive. The Phase II trial results are promising, but the trials are small (n = 8–50), and AHCC is a proprietary alpha-glucan extract distinct in composition from standard shiitake supplements. Larger, independently funded RCTs are required before clinical recommendations can be made.
4.5 Cardiovascular Health and Lipid Metabolism
Clinical Evidence
Sixty-eight individuals were randomly allocated to a placebo group (n = 32) or an intervention group (n = 36). Blood samples were collected at 0, 33, and 66 days, and biochemical markers (triglycerides, total cholesterol, LDL, HDL, and glucose) and oxidative stress biomarkers (reduced glutathione, catalase, and thiobarbituric acid reactive substances) were assessed. Participants in the intervention group showed a 10% reduction in triglycerides after 66 days of consuming the shiitake bars (P = 0.0352). In oxidative stress biomarkers, L. edodes increased the main endogenous antioxidant reduced glutathione and reduced lipid peroxidation. Exposure to L. edodes triggered dermatitis in 10% of individuals sensitive to the mushroom.
Small randomized studies found shiitake to be a useful adjuvant for preventing dyslipidemia in adults with borderline high cholesterol, and to modulate intestinal microbiota in hypercholesterolemic adults.
Mechanistic Evidence (Eritadenine and Beta-Glucans)
Eritadenine is frequently discussed as a lipid-related compound in shiitake, with animal studies showing changes in lipid metabolism pathways. This supports plausibility, but it is not the same as clinical proof of cholesterol-lowering in humans until more human clinical data become available.
In a laboratory anti-atherosclerotic study, the hexane fraction of shiitake most potently inhibited lipid peroxidation, low-density lipoprotein oxidation, and the activity of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGR) — the same enzyme targeted by statin drugs. These are in vitro findings only.
Evidence Strength
Preliminary in humans. The double-blind RCT by Spim et al. (2021) showed modest reductions in triglycerides and improvement in oxidative stress markers, but did not demonstrate significant LDL-C reduction. The bulk of mechanistic evidence for cholesterol-lowering remains from animal and in vitro studies.
4.6 Antimicrobial and Antiviral Effects
Laboratory Evidence
Shiitake mushrooms have demonstrated antibacterial potential against both Gram-positive and Gram-negative bacteria, suggesting their application for food preservation, pharmaceuticals, and alternative medicine. The ethyl acetate extract exhibited the strongest antibacterial activity in vitro, with the largest inhibition zone observed for E. coli ATCC25922 (30.00 ± 0.00 mm). MIC and MBC assays confirmed the superior antibacterial potential of the ethyl acetate extract, particularly against S. aureus DMST20654 (MIC = 1.95 mg/mL, MBC = 31.25 mg/mL).
Shiitake has promising antibacterial, antifungal, antiviral, hepatoprotective, antihyperglycemic, and immunomodulatory effects. The most studied compound is lentinan, a polysaccharide with an effect against bacteria, viruses, and tumors.
Preclinical studies conducted with shiitake extracts revealed immunostimulatory, antiviral, hepatoprotective, antihypercholesterolemic, antiproliferative, cytotoxic, antimutagenic, and anticaries properties.
Evidence Strength
The antimicrobial evidence is predominantly in vitro (cell culture and bacterial inhibition assays). Human clinical trials for infectious disease indications other than HPV and HIV are absent. These findings suggest biological plausibility but cannot be extrapolated to clinical efficacy.
4.7 Hepatoprotective Effects
Preclinical and Limited Clinical Evidence
Reviews of shiitake research report that these mushrooms reduce oxidative stress, protect liver function, regulate lipids, lower blood pressure, and improve glycemic control — though most of this evidence derives from preclinical models. Sterols, β-glucans, and eritadenine are identified as hepatoprotective compounds in L. edodes. In patients with advanced gastrointestinal cancer, an orally administered shiitake mycelial extract decreased the incidence of chemotherapy-associated adverse effects.
Evidence Strength
Largely preclinical (animal models). Results in non-human subjects such as animals have shown positive outcomes, but further research is required because of varying results. The evidence of beneficial effects of shiitake in humans is scarce, and clinical studies are required.
4.8 Anti-Inflammatory and Antioxidant Effects
Bioactive compounds such as polysaccharides, purines, proteins, fatty acids, polyphenols, and sterols in shiitake mushrooms have been shown to have high nutritional value and enhance human health by promoting anti-inflammatory, antioxidant, antitumor, antiviral, antibacterial, and immunostimulatory effects. Most of the isocoumarin compounds in mycelium metabolites have anti-inflammatory and antioxidant activities. The clinical evidence for these effects is primarily from the Dai et al. (2015) and Spim et al. (2021) RCTs, which observed reductions in serum CRP and oxidative stress markers, respectively. These are surrogate endpoints, and larger trials focusing specifically on inflammatory disease outcomes are lacking.
4.9 Antidiabetic Effects
Reported therapeutic actions of shiitake include improving glycemic control, though this evidence is predominantly from preclinical models. Because of the presence of many bioactive compounds, shiitake can simultaneously act as an antidiabetic and antihyperlipidemic agent, but results in non-human subjects have shown positive outcomes yet further research is required because of varying results; the evidence of beneficial effects in humans is scarce, and clinical studies are required.
5. Body Systems Associated with Shiitake Mushroom
- Immune system: Documented clinical effects on innate immune cell proliferation (γδ-T cells, NK cells, B cells), CRP reduction, and mucosal immunity.
- Cardiovascular system: Mechanistic evidence (eritadenine, beta-glucans, HMG-CoA reductase inhibition) and preliminary human data on triglyceride reduction and lipid peroxidation.
- Oncology: Established adjuvant use with chemotherapy (lentinan) approved in Japan and China; evidence for gastric, colorectal, and lung cancer.
- Hepatic system: Preclinical hepatoprotective evidence; limited human data from chemotherapy supportive care studies.
- Reproductive/Gynecological system: Emerging evidence for AHCC in clearance of high-risk persistent HPV.
- Metabolic/Endocrine system: Animal and early human evidence for glycemic and lipid regulation.
- Infectious disease: Laboratory evidence for antibacterial and antiviral activity; limited clinical evidence in HIV (Phase I/II tolerability data).
- Musculoskeletal/Bone: Ergosterol → vitamin D2 conversion supports potential relevance to bone health, though specific clinical evidence for this endpoint is not established.
- Dermatological: Emerging evidence supports a role in dermatological health.
6. Dosage Forms and Study-Reported Dosages
The following dosages are drawn directly from cited research publications; they represent dosages used in specific studies and are not generalizable treatment recommendations.
- Whole dried shiitake (oral, food form): Participants consumed either 5 g or 10 g of dry shiitake (Lentinula edodes) daily for 4 weeks in the Dai et al. (2015) immune function RCT.
- Lentinan (intravenous, pharmaceutical grade): In the SFGH HIV study, 2, 5, or 10 mg of lentinan was administered intravenously once a week for eight weeks. In the CRI study, 1 or 5 mg was administered intravenously twice a week for 12 weeks.
- Lentinex (oral beta-glucan, mycelium extract): 2.5 mg/day Lentinex was administered orally for 6 weeks in the elderly crossover trial.
- AHCC (oral, HPV pilot studies): Study 1 used 3 g daily for 3–6 months; Study 2 used 1 g daily for up to 7 months.
- AHCC (oral, breast cancer supportive care): A retrospective study of 41 women receiving chemotherapy for breast cancer found that 3 g of AHCC daily resulted in significantly less neutrophil-related side effects from chemotherapy.
- Shiitake bars (oral, lipid RCT): The Spim et al. (2021) double-blind RCT used shiitake-containing bars administered for 66 days, with blood samples collected at 0, 33, and 66 days. The total shiitake dose per bar was reported in the original publication (International Journal of Medicinal Mushrooms, 2021, Vol. 23, Issue 7).
7. Safety Considerations and Interactions
Flagellate Dermatitis (Shiitake Dermatitis)
The most clinically distinctive adverse effect associated with shiitake consumption is flagellate dermatitis (also called shiitake dermatitis or toxicoderma). Shiitake mushroom-induced flagellate dermatitis, also known as flagellate erythema, is an intriguing rash associated with consuming raw or undercooked shiitake mushrooms. Flagellate dermatitis caused by the consumption of undercooked or raw shiitake mushrooms usually occurs 48–72 hours after ingestion. It presents as papular, petechial, or vesicular lesions in a crisscrossed, linear pattern, primarily on the trunk, upper limbs, neck, and face, accompanied by marked pruritus.
The pathologic mechanism may be related to toxicity to lentinan, a thermolabile polysaccharide that induces the production of IL-1 and causes vasodilation and rash. However, only 9 of 519 patients who were treated with intravenous lentinan showed cutaneous side effects, hinting at possible cofactor interaction, including exposure to sunlight and medications such as angiotensin-converting enzyme inhibitors or diuretics.
Shiitake flagellate dermatitis is a toxic reaction to lentinan, found in fresh, powdered, or lightly cooked shiitake mushrooms. This thermolability may alter lentinan's toxic or allergenic potential and explain why cooked shiitake mushrooms are generally not associated with adverse reactions. Shiitake flagellate dermatitis is a self-limiting condition. There is generally improvement within 2 days and complete resolution after 3 weeks. Future attacks can be prevented by ensuring that shiitake mushrooms are thoroughly cooked before eating.
The ingestion of shiitake mushrooms can cause a direct toxicity reaction. There are also reports of allergic reactions such as asthma, allergic contact dermatitis, and alveolitis in individuals who were in direct contact with the fungus or its spores, for example, during occupational exposure in shiitake mushroom cultivation fields.
Gastrointestinal Side Effects
Digestive issues that have been reported in some people after eating shiitake mushrooms include nausea, upset stomach, diarrhea, vomiting, bloating, and gas. Researchers note that abdominal distention and bowel obstruction (from eating whole shiitake mushrooms) have also occurred.
Infusion-Related Reactions (Intravenous Lentinan)
In the SFGH intravenous study where administration was over a ten-minute period, there were nine side effects severe enough to be reported to the FDA (including one case each of anaphylactoid reaction, back pain, leg pain, depression, rigor, fever, chills, granulocytopenia, and elevated liver enzymes). In the CRI study, where infusion was over a 30-minute period, there were no side effects reportable to the FDA. Most side effects resolved promptly after discontinuation of medication, and all were relieved within 24 hours.
Clinical Trial Dermatitis Rate
Exposure to L. edodes triggered dermatitis in 10% of individuals sensitive to the mushroom in the Spim et al. (2021) double-blind RCT, consistent with the known risk in susceptible individuals.
Drug Interactions
Shiitake mushrooms could interact with immunosuppressant medications, blood clotting medicines, liver-processed medications, or dietary supplements. These interactions are theoretically based on the immunomodulatory activity of lentinan and the hepatic metabolism of various compounds within shiitake, and are not yet definitively characterized by human pharmacokinetic studies.
Safety in Studies
In the Lentinex crossover trial, safety blood variables (differential cell count, liver function, kidney function, and other blood chemistry) were not influenced by Lentinex, and the number, nature, and severity of adverse events were similar to placebo. Advances in processing technologies have mitigated the toxicity risks associated with prolonged use, thereby enhancing the safety profiles for therapeutic applications.
Occupational Exposure
There are reports of allergic reactions including asthma and alveolitis in individuals in direct contact with the fungus or its spores during occupational exposure in shiitake cultivation fields. This form of exposure, involving inhalation of spores over extended periods, presents a different risk profile from oral dietary or supplemental consumption.
References
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