Based on these findings, pharmaceutical manufacturer Toei Shinyaku has filed patents for improving ovarian function and for managing male menopause symptoms.
Toei Shinyaku specialises in developing health supplements containing KA21 as the active ingredient.
KA21 is cultivated in Brazil, with the outdoor-grown version said to contain a higher amount of beta-glucan, vitamin D, calcium, and copper. It is believed to have multiple health benefits, including for reproductive health, wound healing, and skin health.
Researchers recently confirmed the efficacy of KA21 in improving male menopause symptoms and ovarian function after assessing results from two studies.
The joint study on male menopause was conducted by Toei Shinyaku and Shigakkan University’s Faculty of Health Sciences.
For the study on ovarian function, Teoi Shinyaku worked with the Institute of Natural Medicine at Toyama University and the Department of Health Science at Shigakkan University.
The manufacturing firm has filed patents for both health claims based on the research findings.
“Going forward, we are targeting clinics that deal with male menopause and erectile dysfunction. Additionally, we plan to re-promote NKUP Volume Plus to hair growth clinics as a supplement for supporting hair loss patients who have developed erectile dysfunction due to taking finasteride or dutasteride – drugs for treating enlarged prostate.
“We will also promote this to women's clinics based on data related to ovarian function improvement,” said Akimoto Motoi, president of Toei Shinyaku.
NKUP Volume Plus was designed for both men and women as a hair growth supplement. It is available via medical institutions.
The firm is considering plans to re-position it as an anti-ageing supplement that alleviates male and female menopause symptoms, among other health claims centred around reproductive health.
To meet these new health claims, reformulation is needed.
NKUP Volume Plus contains 62.5% KA21, designed to deliver 800mg per day along with isoflavones and capsaicin. This was patented in Japan for hair growth until April 2024.
The firm will increase the daily KA21 dosage to 900mg using a previously patented formulation. This is to align with findings from the human clinical trial on male menopause, which was based on a daily KA21 dosage of 900mg.
The research
For the two-month trial, 24 male professional golfers were recruited. They were between 50–70 years old.
Each participant took three KA21 tablets a day. Every tablet contains 300mg KA21.
They also completed questionnaires at three time points – before the start of the trial, after the one-month mark, and after the two-month mark. This was to assess the effects of KA21 on AMS (ageing male symptoms), EHS (erection hardness score), and SHIM (sexual heath inventory for men).
AMS includes decrease in ability to perform sexually, a dip in libido, and decrease in beard growth and muscular strength. An AMS score of less than 26 indicates no significant symptoms consistent with a low testosterone level; a score of 27–36 indicates mild symptoms consistent with a low testosterone level.
The average AMS score among participants dropped from 35 at the start of the trial to 27 by the end of two months.
As for EHS, participants rated themselves based on a five-point system, where 0 indicated that the penis does not enlarge; 1 indicated that the penis is larger, but not hard; 2 indicated that the penis is hard, but not hard enough for penetration; 3 indicated that the penis is hard enough for penetration, but not completely hard; and 4 indicated that the penis is completely hard and fully rigid.
On average, participants rated themselves 2.6 points at the start of the trial. The score improved to 3 points by the end of two months.
Lastly, SHIM measured markers such as confidence and ability in maintaining erections, and satisfaction level during sexual intercourse. A higher score indicated better sexual health.
On average, participants scored 19 points at the start of the trial. Subsequently, the average score was 21 and 20 after one month and after two months respectively.
“Significant improvements were observed in AMS (ageing male symptoms) score – indicators for assessing male menopausal symptoms including mental, psychological, and physical aspects; EHS (erection hardness score) – for evaluating erectile dysfunction; and SHIM (Sexual Health Inventory for Men) – score for male sexual health assessment. [There was also improvement in] hair loss conditions,” wrote the researchers in an unpublished report.
These findings further support the efficacy of NKUP Volume Plus, which the firm is planning to re-formulate.
“While it’s primarily marketed for hair growth for both men and women, its scope is expanding to include anti-ageing benefits, such as alleviating female menopausal symptoms,” said Motoi.
KA21 for female reproductive health
Although the study on ovarian function is based on an animal model, researchers believe the benefits are translatable to humans.
For this study, female Drosophila flies were fed food containing 5% dried fruiting bodies of KA21 for 35 days.
During this time, changes in ovarian size were observed through microscope imaging.
The number of eggs laid by each fly within 24 hours was measured.
The results confirmed that ovarian size increased, indicating that the decline in ovarian size due to ageing was suppressed. Also, the number of eggs laid increased significantly, suggesting that reproductive decline due to ageing was suppressed.
These findings confirmed that administering the processed fruiting bodies of King Agaricus KA21 improves ovarian function in flies, said researchers.
Supplements for anti-ageing and reproductive health
Since research has indicated the potential of KA21 in managing ovarian function decline due to ageing, Motoi believes it can be used to treat human infertility.
“With the declining birthrate and ageing population, particularly in developed countries, there is a growing demand for products that mitigate the effects of reproductive ageing. Furthermore, the intake of KA21 is expected to relieve menopausal symptoms in women and men,” said Motoi.
If reformulated from NKUP Volume Up, the supplements will be in tablet form, which can be swallowed with water. However, when chewed, it will have the distinctive taste of mushrooms and the spiciness from capsaicin.
Currently, NKUP Volume Up is also branded as Beroot for sale in the retail space. It is available in China, Taiwan, Singapore, the Philippines, and Nepal.
The firm plans to expand its footprint in Asia within the next year. It is especially keen on South Korea and APAC regions with strong economic growth, where there is great emphasis on anti-ageing and maintaining beauty.
