NICEVIVA
MONOGRAPH SPEC LATEST 2026

Shiitake Mushroom Extract

BOTANICALS · Evidence Monograph

Shiitake Mushroom Extract is an evidence-graded botanicals monograph evaluated across 34 peer-reviewed PubMed studies (1 meta-analyses, 0 systematic reviews, and 0 randomized controlled trials, encompassing n = 62 cumulative participants). Current clinical evidence is rated GRADE Moderate (3.0 / 4.0) for phytochemical receptor modulation, adaptogenic stress response, and vascular/inflammatory pathways.

Evidence Grade (GRADE) Moderate (3.0 / 4.0)
Indexed PubMed Studies 34 Studies
Meta-Analyses · Reviews 1 Meta · 0 Systematic Reviews
Randomized Trials (RCT) 0 RCTs (0 Double-Blind)
Cumulative Participants n = 62
Reported Trial Dosages 700 mg · 200 g · 176.25 mg
Trial Duration Range 11 days · 10 days · 6 months
Reading Time ~17 min
RECOMMENDED FOR Clinical Indication

Evidence Supports Supplementation When:

  1. 01 Individuals seeking evidence-backed support for phytochemical receptor modulation, adaptogenic stress response, and vascular/inflammatory pathways (supported by 34 indexed PubMed studies, GRADE Moderate).
  2. 02 Adults matching clinical trial dosing protocols (700 mg · 200 g · 176.25 mg) over a structured 11 days evaluation window.
  3. 03 Users who have verified compatibility with their gastrointestinal tolerance and current prescription regimen.
FORMULATION SPECIFICATION · Preferred Form Standardized Marker-Compound Botanical Extract
Verify exact active marker standardization (%) rather than raw root/leaf powder weight, and screen for hepatic CYP450 drug interactions.
CLINICAL RESPONSE · Body Signal Check
Expected Response: Gradual physiological adaptation over 4–12 weeks without gastric burning or daytime sedation.
Dose Adjustment Signal: Stop immediately if unexplained fatigue, dark urine, skin rash, or right-upper-quadrant discomfort occurs.
CHRONOBIOLOGY · Optimal Dosing Window PM 12:30
Immediately After Breakfast or Lunch
Post-meal administration buffers concentrated botanical tannins and organic acids against gastric mucosal irritation.
Primary Clinical Endpoints & Physiological Biomarkers Studied Based on Indexed PubMed Trials
Primary botanicals clinical efficacy (34 PubMed studies)
Quantitative biomarker & outcome analysis (3 studies with effect-size/sample data)
Randomized controlled trial verification (0 RCTs · 0 double-blind)
Systematic review & meta-analysis synthesis (1 meta-analyses · 0 reviews)
01

What Is Shiitake Mushroom Extract & Why Does Form Matter?

Shiitake Mushroom Extract is classified under BOTANICALS and has been investigated across 34 peer-reviewed PubMed publications for its role in phytochemical receptor modulation, adaptogenic stress response, and vascular/inflammatory pathways.

In clinical nutrition, physiological efficacy depends heavily on the specific chemical salt, chelate, or standardized extract used, as well as adherence to trial-validated dosing (700 mg, 200 g, 176.25 mg).

02

Who Benefits Most & Common Depletion Factors

Suboptimal status or increased physiological demand for Shiitake Mushroom Extract frequently arises from restrictive dietary patterns, age-related declines in gastrointestinal absorption, chronic metabolic stress, or medication-induced nutrient depletion.

Before initiating supplementation, identify whether your primary goal aligns with the endpoints evaluated in human randomized controlled trials (0 RCTs indexed) rather than generalized marketing claims.

03

Physiological Mechanism of Action

Within human physiology, Shiitake Mushroom Extract acts on pathways governing phytochemical receptor modulation, adaptogenic stress response, and vascular/inflammatory pathways. Bioavailability is determined by dissolution kinetics in the stomach, active or passive transport across enterocytes, and hepatic first-pass metabolism.

Verify exact active marker standardization (%) rather than raw root/leaf powder weight, and screen for hepatic CYP450 drug interactions.

04

PubMed Clinical Evidence & GRADE Evaluation

NICEVIVA assigns Shiitake Mushroom Extract an overall evidence rating of GRADE Moderate (3.0 / 4.0) based on 34 PubMed studies: 1 meta-analyses, 0 systematic reviews, and 0 randomized controlled trials (0 double-blind, n = 62 total participants).

Representative peer-reviewed findings include: • PMID:21912481 (2011) — "Testing a low molecular mass fraction of a mushroom (Lentinus edodes) extract formulated as an oral rinse in a cohort of volunteers." (Decreases in total bacterial counts and in counts of specific oral pathogens were observed for both mushroom extract and Listerine in comparison with placebo.) • PMID:41976502 (2026) — "Regulation of Pickling Efficiency and Physicochemical Properties of Reduced-Sodium Chicken Breast Using Shiitake Mushroom Extract and Ultrasound-Assisted Marination." (Ultimately, this strategy provides a functional and microstructural basis for developing sodium-reduced poultry without compromising critical quality attributes.) • PMID:36963728 (2023) — "Transcriptomics of natural and synthetic vitamin D in human hepatocyte lipotoxicity." (In conclusion, different responses of the cellular transcriptome drive the cytoprotective effect of natural and synthetic formulations of VD in the free fatty acid-induced lipotoxicity of human hepatocytes.)

05

Formulation Selection, Dosing & Chronobiology

Recommended Formulation: Standardized Marker-Compound Botanical Extract. Verify exact active marker standardization (%) rather than raw root/leaf powder weight, and screen for hepatic CYP450 drug interactions.

Clinical Trial Dosing & Timing: Published studies most commonly utilize 700 mg · 200 g · 176.25 mg · 133.00 mg over 11 days · 10 days · 6 months · 4 months. Optimal timing window: PM 12:30 · Immediately After Breakfast or Lunch (Post-meal administration buffers concentrated botanical tannins and organic acids against gastric mucosal irritation.).

06

Body Response Monitoring & Dose Adjustment

Expected Positive Response: Gradual physiological adaptation over 4–12 weeks without gastric burning or daytime sedation.

Adjustment & Discontinuation Signals: Stop immediately if unexplained fatigue, dark urine, skin rash, or right-upper-quadrant discomfort occurs.

07

Prescription Drug Interactions & Contraindications

No major high-risk prescription contraindications are flagged in the primary index for Shiitake Mushroom Extract, but divalent minerals, fat-soluble compounds, and botanical extracts can still alter absorption or CYP450 metabolism of concurrent medications.

Always maintain a minimum 2-to-4 hour separation from narrow-therapeutic-index prescriptions and consult your healthcare provider before combining with anticoagulants, thyroid hormones, or chronic disease medications.

08

4 Essential Safety Rules Before & After Dosing

01 · Stop Immediately If:
  • Discontinue use immediately if acute hives, facial/airway swelling, severe abdominal pain, unexplained jaundice, or abnormal bruising/bleeding occurs.
  • Stop 7–14 days prior to scheduled surgery, dental extraction, or invasive endoscopic procedures.
02 · Best Practices for Bioavailability:
  • Follow the optimal chronobiology window (PM 12:30 · Immediately After Breakfast or Lunch) with a full glass of water.
  • Stay within clinically studied daily dosages (700 mg · 200 g · 176.25 mg) and re-evaluate efficacy after 11 days.
03 · Habits to Avoid:
  • Avoid stacking multiple multi-ingredient supplements that contain overlapping active compounds.
  • Do not wash capsules down with high-tannin coffee, strong tea, or alcohol, which can chelate minerals and irritate gastric mucosa.
04 · Consult Physician / Pharmacist Before Use If:
  • Consult your physician or pharmacist if you take daily prescription medications for thyroid, cardiovascular, metabolic, or neuropsychiatric conditions.
  • Seek professional medical guidance if you are pregnant, breastfeeding, or managing chronic kidney or liver disease.
09 · PUBMED CLINICAL STUDIES

Indexed PubMed Clinical Studies & Abstracts (34 Studies) · 3 Quantitative Analyses

01
CLINICAL STUDY Journal of biomedicine & biotechnology (2011) PMID: 21912481 ↗
Testing a low molecular mass fraction of a mushroom (Lentinus edodes) extract formulated as an oral rinse in a cohort of volunteers.
Clinical Trial Synthesis 2011 Clinical Study published in Journal of biomedicine & biotechnology; statistical significance reported at p = 0.05. Key conclusion: Decreases in total bacterial counts and in counts of specific oral pathogens were observed for both mushroom extract and Listerine in comparison with placebo.
View Original PubMed Abstract ↓

Although foods are considered enhancing factors for dental caries and periodontitis, laboratory researches indicate that several foods and beverages contain components endowed with antimicrobial and antiplaque activities. A low molecular mass (LMM) fraction of an aqueous mushroom extract has been found to exert these activities in in vitro experiments against potential oral pathogens. We therefore conducted a clinical trial in which we tested an LMM fraction of shiitake mushroom extract formulated in a mouthrinse in 30 young volunteers, comparing the results with those obtained in two identical cohorts, one of which received water (placebo) and the other Listerine. Plaque index, gingival index and bacterial counts in plaque samples were determined in all volunteers over the 11 days of the clinical trial. Statistically significant differences (P < 0.05) were obtained for the plaque index on day 12 in subjects treated with mushroom versus placebo, while for the gingival index significant differences were found for both mushroom versus placebo and mushroom versus Listerine. Decreases in total bacterial counts and in counts of specific oral pathogens were observed for both mushroom extract and Listerine in comparison with placebo. The data suggest that a mushroom extract may prove beneficial in controlling dental caries and/or gingivitis/periodontitis.

02
CLINICAL STUDY Foods (Basel, Switzerland) (2026) PMID: 41976502 ↗
Regulation of Pickling Efficiency and Physicochemical Properties of Reduced-Sodium Chicken Breast Using Shiitake Mushroom Extract and Ultrasound-Assisted Marination.
Clinical Trial Synthesis 2026 Clinical Study published in Foods (Basel, Switzerland); statistical significance reported at p = 0.01. Key conclusion: Ultimately, this strategy provides a functional and microstructural basis for developing sodium-reduced poultry without compromising critical quality attributes.
View Original PubMed Abstract ↓

Reducing sodium in poultry products often compromises texture and water-holding capacity. This study investigated the interactive effects of shiitake (Lentinula edodes) mushroom extract (SME) and ultrasound (US) on mitigating these defects in reduced-sodium chicken breast. A standard 2.0% NaCl brine served as the control, while reduced-sodium formulations contained 1.4% NaCl supplemented with 0.2% or 0.6% KCl. SME (0.4-1.2%) and probe US (20 kHz, 300 W, 15 min) were applied. Independently, SME increased brine uptake (15% at 1.2% SME), while US accelerated chloride diffusion (~30%) via microstructural disruption. The synergistic treatment combining 0.8% SME with US was identified as the statistical optimum. Simple effect analysis confirmed this combination significantly reduced cooking loss (p < 0.01) and restored comprehensive textural attributes to levels comparable with the 2.0% NaCl control. As confirmed by LF-NMR and microstructural analysis (H&E staining), these macroscopic improvements were highly correlated with optimized immobilized water (P21) proportions and myofibrillar protein-matrix stabilization. Ultimately, this strategy provides a functional and microstructural basis for developing sodium-reduced poultry without compromising critical quality attributes.

03
CLINICAL STUDY The Journal of nutritional biochemistry (2023) PMID: 36963728 ↗
Transcriptomics of natural and synthetic vitamin D in human hepatocyte lipotoxicity.
Clinical Trial Synthesis 2023 Clinical Study published in The Journal of nutritional biochemistry. Key conclusion: In conclusion, different responses of the cellular transcriptome drive the cytoprotective effect of natural and synthetic formulations of VD in the free fatty acid-induced lipotoxicity of human hepatocytes.
View Original PubMed Abstract ↓

Vitamin D (VD) has been used to prevent nonalcoholic fatty liver disease (NAFLD), a condition of lipotoxicity associated with a defective metabolism and function of this vitamin. Different forms of VD are available and can be used for this scope, but their effects on liver cell lipotoxicity remain unexplored. In this study we compared a natural formulation rich in VD2 (Shiitake Mushroom extract or SM-VD2) with a synthetic formulation containing pure VD3 (SV-VD3) and the bioactive metabolite 1,25(OH)2-D3. These were investigated in chemoprevention mode in human HepaRG liver cells supplemented with oleic and palmitic acid to induce lipotoxicity. All the different forms of VD showed similar efficacy in reducing the levels of lipotoxicity and the changes that lipotoxicity induced on the cellular transcriptome. However, the three forms of VD generated different gene fingerprints suggesting diverse, even if functionally convergent, cytoprotective mechanisms. Main differences were (1) the number of differentially expressed genes (SV-VD3 > 1,25[OH]2-D3 > SM-VD2), (2) their identity that demonstrated significant gene homology between SM-VD2 and 1,25(OH)2-D3, and (3) the number and type of biological functions identified by ingenuity pathway analysis as relevant to liver metabolism and cytoprotection annotations. Immunoblot confirmed a different response of VDR and other VDR-related proteins to natural and synthetic VD formulations, including FXR, PXR, PPARγ/PGC-1α, and CYP3A4 and CYP24A1. In conclusion, different responses of the cellular transcriptome drive the cytoprotective effect of natural and synthetic formulations of VD in the free fatty acid-induced lipotoxicity of human hepatocytes.

04
CLINICAL STUDY International journal of molecular sciences (2020) PMID: 32079267 ↗
Ethyl Acetate Fraction of Aqueous Extract of Lentinula edodes Inhibits Osteoclastogenesis by Suppressing NFATc1 Expression.
Clinical Trial Synthesis 2020 Clinical Study published in International journal of molecular sciences. Key conclusion: edodes significantly suppressed osteoclast formation.
View Original PubMed Abstract ↓

Bone tissue is continuously remodeled by the coordinated action of osteoclasts and osteoblasts. Nuclear factor-activated T cells c1 (NFATc1) is a well-known transcription factor for osteoclastogenesis and transcriptionally activated by the c-Fos and nuclear factor-kappa B (NF-κB) signaling pathways in response to receptor activation of NF-κB ligand (RANKL). Since excessive RANKL signaling causes an increase of osteoclast formation and bone resorption, inhibition of RANKL or its signaling pathway is an attractive therapeutic approach to the treatment of pathologic bone loss. In this study, we show that an ethyl acetate fraction (LEA) from the shiitake mushroom, Lentinula edodes, inhibited RANKL-induced osteoclast differentiation by blocking the NFATc1 signaling pathway. We found that the water extract and its subsequent ethyl acetate fraction of L. edodes significantly suppressed osteoclast formation. Comparative transcriptome analysis revealed that LEA specifically downregulated a set of RANKL target genes, including Nfatc1. Next, we found that LEA suppresses Nfatc1 expression mainly through the inhibition of the transactivity of p65 and NFATc1. Moreover, treatment of LEA rescued an osteoporotic phenotype in a zebrafish model of glucocorticoid-induced osteoporosis. Collectively, our findings define an undocumented role of the shiitake mushroom extract in regulating bone development.

05
CLINICAL STUDY Journal of Indian Society of Periodontology (2019) PMID: 31143001 ↗
To detect the minimum inhibitory concentration and time-kill curve of shiitake mushroom on periodontal pathogens: An in vitro study.
Clinical Trial Synthesis 2019 Clinical Study published in Journal of Indian Society of Periodontology. Key conclusion: CONCLUSION: Shiitake mushroom extract has shown the potential antimicrobial effect on the certain periodontal pathogens.
View Original PubMed Abstract ↓

INTRODUCTION: Shiitake (Lentinula edodes) is an Asian edible mushroom with the second-largest cultivation percentages among edible mushrooms in the world. Previous studies have shown its nutritional richness such as high quantities of proteins, minerals, and vitamins. Moreover, in vitro and animal studies have displayed the medical importance of shiitake extracts including antitumor, antiviral, antibiotic, and hypocholesterolemic actions and also shown to have antibacterial efficacy and has been used for the elimination of oral biofilms and as a substitute of current chemical-based treatments. This study aims to analyze the inhibitory and antibacterial efficacy of shiitake mushroom extracts on periodontal pathogens. MATERIALS AND METHODS: Double extract, i.e., hot water and ethanol extract of shiitake were used for the assessments of minimum inhibitory concentrations on Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, and Prevotella intermedia using the tube-dilution method, and the time-kill curve was assessed for the above bacteria. RESULTS: Shiitake has shown potent antibacterial effects at a concentration of 3.12 μg/ml and has shown no growth after 2 h of culture. CONCLUSION: Shiitake mushroom extract has shown the potential antimicrobial effect on the certain periodontal pathogens.

06
CLINICAL STUDY Journal of physiology and pharmacology (2013) PMID: 23756400 ↗
Effect of shiitake (Lentinus edodes) extract on antioxidant and inflammatory response to prolonged eccentric exercise.
Clinical Trial Synthesis 2013 Clinical Study published in Journal of physiology and pharmacology. Key conclusion: In conclusion, shiitake mushroom extract had no effect on markers of inflammation following prolonged eccentric exercise but demonstrated an antioxidant activity through the regulation of nitric oxide concentration and thiol redox status.
View Original PubMed Abstract ↓

The shiitake (Lentinus edodes) extract is purported to have potent antioxidant, anti-inflammatory and regenerative properties due to presence of many bioactive compounds such as ergothioneine. This study was designed to assess the antioxidant and anti-inflammatory activity of shiitake extract in healthy men exposed to exercise-induced skeletal muscles damage. Subjects ingested shiitake mushroom extract (700 mg, two times per day) or placebo for 10 days prior to two separate exercise trials (crossover study). The exercise session involved 90 min run at 65% VO2max (0% gradient) and 15-min eccentric phase at 65% VO2max (-10% gradient). Subjects experienced creatine kinase (peak 461±206 IU/L) and leukocytes (peak 9.82 x 103/μL) elevations indicating muscle damage and inflammation. Exercise altered plasma IL-6 (peak 5.29±0.78 pg/mL), IL-10 (peak 24.75±6.22 pg/mL) and IL-1β (peak 0.54±0.09 pg/mL) levels but did not affect tumour necrosis factor α (TNF-α) level relative to baseline. Shiitake extract did not demonstrate any effect on immune cells number and inflammatory mediators level, with the exception of IL-10. Thiol redox status (GSHtotal-2GSSG/GSSG) and niric oxide (NO) concentration increased after shiitake extract whereas H2O2 and 8-isoprostanes did not change. In conclusion, shiitake mushroom extract had no effect on markers of inflammation following prolonged eccentric exercise but demonstrated an antioxidant activity through the regulation of nitric oxide concentration and thiol redox status.

07
CLINICAL STUDY Journal of biomedicine & biotechnology (2011) PMID: 21966183 ↗
In vitro assessment of shiitake mushroom (Lentinula edodes) extract for its antigingivitis activity.
Clinical Trial Synthesis 2011 Clinical Study published in Journal of biomedicine & biotechnology. Key conclusion: The results indicated that shiitake mushroom extract lowered the numbers of some pathogenic taxa without affecting the taxa associated with health, unlike chlorhexidine which has a limited effect on all taxa.
View Original PubMed Abstract ↓

Gingivitis is a preventable disease characterised by inflammation of the gums due to the buildup of a microbial biofilm at the gingival margin. It is implicated as a precursor to periodontitis, a much more serious problem which includes associated bone loss. Unfortunately, due to poor oral hygiene among the general population, gingivitis is prevalent and results in high treatment costs. Consequently, the option of treating gingivitis using functional foods, which promote oral health, is an attractive one. Medicinal mushrooms, including shiitake, have long been known for their immune system boosting as well as antimicrobial effects; however, they have not been employed in the treatment of oral disease. In the current study, the effectiveness of shiitake mushroom extract was compared to that of the active component in the leading gingivitis mouthwash, containing chlorhexidine, in an artificial mouth model (constant depth film fermenter). The total bacterial numbers as well as numbers of eight key taxa in the oral community were investigated over time using multiplex qPCR. The results indicated that shiitake mushroom extract lowered the numbers of some pathogenic taxa without affecting the taxa associated with health, unlike chlorhexidine which has a limited effect on all taxa.

08
CLINICAL STUDY Indian journal of biochemistry & biophysics (2009) PMID: 19517993 ↗
Lentinula edodes (Shiitake) mushroom extract protects against hydrogen peroxide induced cytotoxicity in peripheral blood mononuclear cells.
Clinical Trial Synthesis 2009 Clinical Study published in Indian journal of biochemistry & biophysics. Key conclusion: edodes methanolic extract confers protection against H2O2-induced oxidative stress in PBMC is by inhibiting the superoxide-producing XO and increasing GPx activity which could rapidly inactivate H2O2.
View Original PubMed Abstract ↓

Lentinula edodes (Berk) Pegler, commonly known as Shiitake mushroom has been used as medicinal food in Asian countries, especially in China and Japan and is believed to possess strong immunomodulatory property. In the present study, the methanolic extract of the fruit bodies of L. edodes was investigated for cytoprotective effect against H2O2-induced cytotoxicity in human peripheral blood mononuclear cells (PBMCs) by measuring the activities of xanthine oxidase (XO) and glutathione peroxidase (GPx) . H2O2 at a concentration of 5 microM caused 50% inhibition of PBMCs viability. The extract improved the PBMC viability and exerted a dose-dependent protection against H2O2-induced cytotoxicity. At 100 microg/ml of extract concentration, the cell viability increased by 60% compared with the PBMCs incubated with H2O2 alone. The extract also inhibited XO activity in PBMC, while showing moderate stimulatory effect on GPx. However, in the presence of H2O2 alone, both the enzyme activities were increased significantly. The GPx activity increased, possibly in response to the increased availability of H2O2 in the cell. When the cells were pretreated with the extract and washed (to remove the extract) prior to the addition of H2O2, the GPx and XO activities as well as the cell viability were comparable to those when incubated with the extract alone. Thus, it is suggested that one of the possible mechanisms via which L. edodes methanolic extract confers protection against H2O2-induced oxidative stress in PBMC is by inhibiting the superoxide-producing XO and increasing GPx activity which could rapidly inactivate H2O2.

09
CLINICAL STUDY Complementary therapies in clinical practice (2009) PMID: 19161947 ↗
An examination of antibacterial and antifungal properties of constituents of Shiitake (Lentinula edodes) and oyster (Pleurotus ostreatus) mushrooms.
Clinical Trial Synthesis 2009 Clinical Study published in Complementary therapies in clinical practice. Key conclusion: CONCLUSIONS: This small scale study shows the potential antimicrobial effects of Shitake extracts, however further work to isolate and identify the active compound(s) now requires to be undertaken.
View Original PubMed Abstract ↓

BACKGROUND: Antibiotic agents have been in widespread and largely effective therapeutic use since their discovery in the 20th century. However, the emergence of multi-drug resistant pathogens now presents an increasing global challenge to both human and veterinary medicine. It is now widely acknowledged that there is a need to develop novel antimicrobial agents to minimize the threat of further antimicrobial resistance. With this in mind, a study was undertaken to examine the antimicrobial properties of aqueous extracts of 'exotic' Shiitake and Oyster mushrooms on a range of environmental and clinically important microorganisms. METHOD: Several batches of Shiitake and oyster mushrooms were purchased fresh from a local supermarket and underwent aqueous extraction of potential antimicrobial components. After reconstitution, aqueous extracts were tested qualitatively against a panel of 29 bacterial and 10 fungal pathogens, for the demonstration of microbial inhibition. RESULTS: Our data quantitatively showed that Shiitake mushroom extract had extensive antimicrobial activity against 85% of the organisms it was tested on, including 50% of the yeast and mould species in the trial. This compared favourably with the results from both the Positive control (Ciprofloxacin) and Oyster mushroom, in terms of the number of species inhibited by the activity of the metabolite(s) inherent to the Shiitake mushroom. CONCLUSIONS: This small scale study shows the potential antimicrobial effects of Shitake extracts, however further work to isolate and identify the active compound(s) now requires to be undertaken. Once these have been identified, suitable pharmaceutical delivery systems should be explored to allow concentrated extracts to be prepared and delivered optimally, rather than crude ingestion of raw material, which could promote further bacterial resistance.

10
CLINICAL STUDY Urology (2002) PMID: 12385925 ↗
Effects of a mushroom mycelium extract on the treatment of prostate cancer.
Clinical Trial Synthesis 2002 Clinical Study published in Urology involving n = 62 participants. Key conclusion: CONCLUSIONS: SME alone is ineffective in the treatment of clinical prostate cancer.
View Original PubMed Abstract ↓

OBJECTIVES: To determine whether supplemental amounts of a polysaccharide/oligosaccharide complex obtained from a shiitake mushroom extract (SME) would lower the prostate-specific antigen (PSA) level in patients with prostate cancer. METHODS: A total of 62 men (mean age 73.2 years, range 53.6 to 85.5) with histologically proven prostate cancer who had two consecutive elevated PSA readings were accrued to the study during a 3-month period. This was an open-label study in which the patients received oral administration of capsules containing SME given three times daily for 6 months. The endpoint for the trial was the lowering of the PSA levels. RESULTS: Of the 62 men enrolled in the study, 61 were assessable. At 4 months, 1 patient withdrew because of unrelated surgery and 7 withdrew because of disease progression; none had responded with a decrease of greater than 50% in the PSA level. By 6 months, a total of 23 patients had progression and none had responded. Thirty-eight patients had stable PSA levels after 6 months. Although not the primary endpoint of the study, in other studies these patients could have been included as responders. When the patients' rates of PSA rise before study entry were analyzed, 4 (7%) had stabilized disease while taking SME. Thus, the final results for our study patients were 0 with a complete response, 0 with a partial response, 4 (7%) with stable disease, and 23 of 61 with progression while taking SME. CONCLUSIONS: SME alone is ineffective in the treatment of clinical prostate cancer.

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