Toei Shinyaku Reports Human Clinical Trial Results on Outdoor-Cultivated Agaricus brasiliensis KA21 for Symptoms of Late-Onset Hypogonadism (LOH)

Toei Shinyaku Co., Ltd., a leading Japanese manufacturer and researcher of outdoor-cultivated Brazilian Agaricus, announced the results of a human clinical trial evaluating the effects of continuous intake of outdoor-cultivated Agaricus brasiliensis KA21, the proprietary KA21 strain commercially marketed as King Agaricus KA21. The mushroom has been described in scientific literature under the names Agaricus blazei, Agaricus brasiliensis, and Agaricus subrufescens. The study investigated its effects on symptoms of late-onset hypogonadism (LOH), sexual function, and quality of life (QOL) in middle-aged and older men. The findings were presented at the 26th Annual Meeting of the Japanese Society of Anti-Aging Medicine.

King Agaricus KA21, Outdoor-Cultivated Agaricus brasiliensis KA21

Highlights

- Randomized, double-blind, placebo-controlled crossover clinical trial in men aged 40 years and older

- Significant improvements in sexual-function-related outcomes and early morning erections were observed in participants with moderate or greater LOH symptoms

- Reduced serum cortisol levels, suggesting potential benefits for maintaining and improving quality of life (QOL) in middle-aged and older men

In this randomized, double-blind, placebo-controlled crossover study involving men aged 40 years and older, participants with moderate or greater Aging Males' Symptoms (AMS) demonstrated improvements in sexual-function-related outcomes and early morning erections after continuous intake of outdoor-cultivated Agaricus brasiliensis KA21. A reduction in the stress hormone cortisol was also observed, suggesting that the ingredient may contribute to maintaining and improving quality of life in middle-aged and older men.

Presentation Overview

Conference

26th Annual Meeting of the Japanese Society of Anti-Aging Medicine

Presentation Title

Effects of Continuous Intake of Outdoor-Cultivated Agaricus brasiliensis KA21 on Quality-of-Life Parameters Specific to Middle-Aged and Older Men

Collaborating Institutions

- Shigakkan University

- National Center for Geriatrics and Gerontology

- Gloo LynQ Inc.Lyka Inc.

- D Clinic Shinjuku

- Institute of Natural Medicine, University of Toyama

- eHealth Clinic Shinjuku

- and other collaborating institutions

Background

Late-onset hypogonadism (LOH syndrome) is characterized by an age-related decline in androgen levels and is associated with a variety of physical and psychological symptoms, including fatigue, poor sleep quality, depressed mood, reduced motivation, decreased libido, and erectile dysfunction.

Outdoor-cultivated Agaricus brasiliensis KA21 has been extensively studied as a functional food ingredient rich in β-glucans and vitamin D. Previous studies have demonstrated its potential roles in immune modulation, fatigue reduction, and improvements in sleep quality and overall quality of life.

In addition, an earlier human clinical study involving senior professional male golfers demonstrated improvements in LOH-related symptoms, erectile function, and reduced libido. Based on these findings, a Japanese patent covering the use of the ingredient for LOH-related applications was granted.

Related press release:

https://www.atpress.ne.jp/news/575710

Study Results

This randomized, double-blind, placebo-controlled crossover study enrolled 15 men aged 40 years and older, who consumed either 800 mg/day of outdoor-cultivated Agaricus brasiliensis KA21 or a placebo for eight weeks.

The study demonstrated:

- Significant improvements in sexual-function-related outcomes among participants with severe LOH symptoms

- Improvements in early morning erections among participants with moderate or greater LOH symptoms

- Suppression of worsening depressive mood

- Reduced serum cortisol levels

These findings suggest that outdoor-cultivated Agaricus brasiliensis KA21 may contribute to maintaining and improving quality of life in middle-aged and older men.

The study also highlights the potential of outdoor-cultivated Agaricus brasiliens KA21 as a scientifically supported functional food ingredient for healthy aging in men. The findings are expected to support further clinical research, broader adoption in medical settings, and the development of new dietary supplement products.

About Toei Shinyaku Co., Ltd.

Toei Shinyaku is internationally recognized as a pioneer in scientific research on the KA21 strain of Brazilian Agaricus and has built one of the world's most extensive bodies of scientific evidence for this proprietary ingredient.

The company's proprietary ingredient is marketed under the registered trade name King Agaricus® KA21. The KA21 strain has been described in scientific publications under the names Agaricus blazei, Agaricus brasiliensis, and Agaricus subrufescens.

For more than 30 years, Toei Shinyaku has conducted collaborative research with leading universities and medical institutions. As of June 2026, research on the KA21 strain has resulted in 34 peer-reviewed international publications—one of the largest scientific portfolios among Agaricus manufacturers—as well as six Japanese patents and two U.S. patents.

Research collaborators include:

- Azabu University

- Keio Research Institute at SFC

- National Center for Geriatrics and Gerontology

- Faculty of Health Sciences, Shigakkan University

- Juntendo University Faculty of Medicine

- Food Safety Research Center, The University of Tokyo

- Department of Immunology, Tokyo University of Pharmacy and Life Sciences

Research on the KA21 strain has been published across a broad range of health fields, including:

- Immune modulation

- Autonomic nervous system regulation

- SleepStress management

- Healthy longevity

- Men's health and late-onset hypogonadism (LOH)

- Gut microbiota (including Akkermansia muciniphila)

- Weight managementHair health

- Cognitive functionLiver health

- Cardiovascular health

Toei Shinyaku continues to collaborate with universities and medical institutions in Japan and internationally to expand the scientific evidence supporting the health benefits of the KA21 strain and to develop new evidence-based applications for human health.