King Agaricus KA21 (Outdoor-Cultivated Brazilian Agaricus; Agaricus blazei, Agaricus brasiliensis, Agaricus subrufescens) Demonstrates Potential to Promote Healthy Longevity and Help Prevent Ovarian Aging

Toei Shinyaku Co., Ltd. (Headquarters: Mitaka, Tokyo; President & CEO: Akitomo Motoi) announced the results of a collaborative study with the Institute of Natural Medicine, University of Toyama, the Institute for Health Sciences at Shigakkan University, and other research institutions, demonstrating the anti-aging potential of King Agaricus KA21, Toei Shinyaku's proprietary outdoor-cultivated Brazilian Agaricus ingredient (Agaricus blazei, Agaricus brasiliensis, also known as Agaricus subrufescens). The findings were presented on June 14, 2026, at the 76th Annual Meeting of the Japan Society for Oriental Medicine.

Research Highlights

- Collaborative research with the University of Toyama

- Presented at the 76th Annual Meeting of the Japan Society for Oriental Medicine

- Demonstrated potential to promote healthy longevity

- Improved resistance to oxidative stressDemonstrated potential to prevent age-related ovarian decline

- Patent application filed for an ovarian function-improving composition

- Direct comparison between outdoor-cultivated KA21 and conventional greenhouse-cultivated Agaricus

The study demonstrated that dietary supplementation with outdoor-cultivated Agaricus blazei / brasiliensis KA21 may contribute to healthy longevity, improve oxidative stress resistance, suppress age-related decline in ovarian function, and help maintain reproductive function.

Based on these findings, the research group has also filed a patent application for an "Ovarian Function-Improving Composition."

https://www.atpress.ne.jp/news/409266

King Agaricus KA21 (Outdoor-Cultivated Brazilian Agaricus)

Presentation

Title: Evaluation of the Anti-Aging Effects of Outdoor-Cultivated Agaricus brasiliensis KA21

76th Annual Meeting of the Japan Society for Oriental Medicine

Abstract No. P-072

Participating Research Institutions

- Institute of Natural Medicine, University of Toyama

- Institute for Health Sciences, Shigakkan University

- Other collaborating research institutions

Background

Although Japan has one of the world's longest life expectancies, extending healthy life expectancy—the period during which people can live independently in good health—has become an increasingly important social challenge.

A decline in healthy life expectancy is thought to be associated with age-related increases in oxidative stress, reduced physical performance, and deterioration of reproductive function. Consequently, growing attention has been focused on functional food ingredients capable of mitigating these age-related changes.

Study Findings

(1) Maintenance of Physical Activity—An Indicator of Healthy Longevity

In this study, researchers evaluated lifespan, locomotor activity, and resistance to oxidative stress in fruit flies (Drosophila melanogaster) fed outdoor-cultivated Agaricus KA21 for 35 days.

Drosophila is one of the world's most widely used experimental models for aging research because many biological mechanisms associated with aging are highly conserved.

The study found that supplementation with outdoor-cultivated Agaricus KA21:

- Significantly extended average lifespan

- Suppressed age-related decline in locomotor activity

- Increased resistance to oxidative stress

While locomotor activity normally declines with age in fruit flies, flies receiving outdoor-cultivated Agaricus KA21 maintained activity levels comparable to those observed in younger individuals, suggesting a potential role in promoting healthy longevity.

(2) Protective Effects on Ovarian Function

The researchers also investigated the effects of Agaricus KA21 on reproductive function and observed that supplementation:

- Suppressed the age-related reduction in ovarian size

- Reduced the age-related decline in egg production

Further histological analyses demonstrated that ovaries from aged flies receiving outdoor-cultivated Agaricus brasiliensis KA21 retained structural characteristics more similar to those of young flies.

These findings suggest that outdoor-cultivated Agaricus brasiliensis KA21 may contribute not only to healthy longevity but also to the maintenance of reproductive function during aging.

Differences Between Outdoor-Cultivated Agaricus brasiliensis KA21 and Conventional Greenhouse-Cultivated Agaricus

Mushrooms commonly referred to as Agaricus brasiliensis / blazei /  subrufescens vary considerably in their composition and biological properties depending on the strain, cultivation method, and place of origin.

Importantly, this study evaluated outdoor-cultivated Agaricus brailiensis KA21, rather than commercially available Agaricus mushrooms in general. Therefore, these findings should not be generalized to all Agaricus products, but are specific to the KA21 strain evaluated in this research.

Compared with conventional greenhouse-cultivated Agaricus, outdoor-cultivated Agaricus KA21 has previously been reported to:

- Grow to a larger size

- Contain higher levels of β-glucans

- Contain higher levels of vitamin D

- Exhibit more than five times greater antioxidant activity

Furthermore, this study directly compared outdoor-cultivated KA21 (KAOD) with greenhouse-cultivated KA21 (KAID). The healthy longevity-promoting effect was observed only in the outdoor-cultivated KA21 group.

These findings suggest that cultivation environment, in addition to mushroom strain, may play a critical role in determining biological functionality, providing important new evidence regarding the health-promoting properties of outdoor cultivation.

Left: Greenhouse-cultivated Agaricus brasiliensis

Right: Outdoor-cultivated Agaricus brasiliensis KA21

Comparison of Antioxidant Activity

Patent Application Filed Based on the Research Findings

Based on these findings, the collaborative research group has filed a patent application entitled "Ovarian Function-Improving Composition and Pharmaceutical, Food, Beverage, and Feed Products Containing the Same" (Japanese Patent Application No. 2024-147585).

Related press release:

https://www.atpress.ne.jp/news/409266

The research team plans to further investigate the potential applications of outdoor-cultivated Agaricus brailienis KA21 in supporting the health of women during menopause and in fertility support.

Future Perspectives

Although the present study was a basic research study using Drosophila melanogaster, the findings provide new evidence suggesting that outdoor-cultivated Agaricus KA21 may contribute to healthy longevity and the maintenance of reproductive function during aging.

Going forward, the research team plans to conduct human clinical studies while continuing collaborative research with universities and medical institutions to further strengthen the scientific evidence supporting the use of outdoor-cultivated Agaricus KA21 for healthy aging, healthy longevity, and women's health, including support during menopause.

About Toei Shinyaku Co., Ltd.

For more than 30 years, Toei Shinyaku Co., Ltd. has been the developer and manufacturer of King Agaricus KA21, its proprietary outdoor-cultivated Brazilian Agaricus ingredient.

King Agaricus KA21 is Toei Shinyaku's registered commercial name for its proprietary KA21 strain cultivated outdoors in Brazil. In scientific publications and commercial literature, this mushroom has been described using the names Agaricus blazei, Agaricus brasiliensis, and Agaricus subrufescens.

As of June 2026, research on King Agaricus KA21 has resulted in 34 peer-reviewed international publications, placing the company among the world's leading Agaricus research organizations. In addition, the company has obtained six Japanese patents and two U.S. patents.

Research collaborators include:

- Azabu University

- Keio Research Institute at SFC

- National Center for Geriatrics and Gerontology

- Juntendo University Faculty of Medicine

- Food Safety Research Center, The University of Tokyo

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

Through these collaborations, King Agaricus KA21 has been investigated across a broad range of health fields, including:

- Immune modulation

- Autonomic nervous system regulation

- Sleep and stress 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 expand collaborative research with universities and medical institutions worldwide and remains committed to generating new scientific evidence supporting the health benefits of King Agaricus KA21.