The Actual Product Strain BP-412 of Beni-Koji Choleste Help Was Not Used in Co-Culture Testing — The Issue of an Industrial Mutant Strain Recognizable by Authorities —

Kobayashi Pharmaceutical Red Yeast Rice Incident

The Actual Product Strain BP-412 of Beni-Koji Choleste Help Was Not Used in Co-Culture Testing

— The Issue of an Industrial Mutant Strain Recognizable by Authorities —

Formal Objection to the Yoshinari Paper (Yoshinari et al. 2025) Published by the National Institute of Health Sciences (NIHS)

Regarding health incidents linked to red yeast rice supplements, verification of the mechanism behind the causative substance remains ongoing.

Kunsei Club Co., Ltd. (Hayashima-cho, Tagokori District, Okayama Prefecture; President and Pharmacist Masaaki Mori) has filed a formal objection to the Yoshinari paper (Yoshinari et al., Proc. Jpn. Acad., Ser. B 101, 2025) published by the National Institute of Health Sciences (NIHS), based on the facts outlined below. This document records the facts confirmed by our company in chronological order.

Fact ① The strain used in Beni-Koji Choleste Help is BP-412, an industrial mutant strain derived from NBRC 4520

The red yeast rice strain BP-412 used in the production of Beni-Koji Choleste Help is an industrial mutant strain created by Gunze Limited through UV irradiation mutagenesis of Monascus pilosus NBRC 4520, as explicitly stated in their public patent (JP2009095304A) (survival rate approximately 0.5%, mortality rate approximately 99.5%). This strain was transferred to Kobayashi Pharmaceutical in 2016. Kobayashi Pharmaceutical officially announced the use of strain BP-412 in a press release dated July 17, 2018.

[Source] Gunze Limited, Public Patent JP2009095304A / Kobayashi Pharmaceutical Co., Ltd., Official Press Release (July 17, 2018)

Fact ② On April 19, 2024, NIHS announced the implementation of co-culture testing

The NIHS document released by the Ministry of Health, Labour and Welfare on April 19, 2024 ("Measures Regarding the Case Involving Foods Containing Red Yeast Rice Produced by Kobayashi Pharmaceutical Co., Ltd.") includes the following statements:

· "Verification through co-culture experiments that the identified compound can be produced under coexistence of red yeast mold and blue mold"

· "Co-culture experiment of red yeast mold and blue mold (B) → Coexistence possible"

At this point, the name and origin of the red yeast mold strain used were not disclosed in any of the published materials.

[Source] Ministry of Health, Labour and Welfare Public Document (April 19, 2024), "Measures Regarding the Case Involving Foods Containing Red Yeast Rice Produced by Kobayashi Pharmaceutical Co., Ltd. (National Institute of Health Sciences)"

Fact ③ The Yoshinari paper explicitly states derivation from NBRC 4520 but makes no mention of BP-412

The Introduction of the Yoshinari paper, published in March 2025, contains the following statement:

· "The M. pilosus strain used to prepare RYR was derived from M. pilosus NBRC 4520."

While the paper explicitly states that the strain is derived from NBRC 4520, it makes no mention in the text of the strain being BP-412—an industrial mutant strain—or its relationship to Gunze's patent JP2009095304A.

[Source] Yoshinari T. et al., Proc. Jpn. Acad., Ser. B 101 (2025) 302–316

Fact ④ The red yeast rice strain used in the co-culture test was NBRC 4520, not the actual product strain BP-412

Section 2.7 of the Yoshinari paper states:

· "M. pilosus NBRC 4520 and P. adametzioides strain 11-1 were cultured on a solid rice medium and a PD agar plate, respectively."

The red yeast rice strain used in the co-culture test was NBRC 4520—the parent strain—rather than BP-412, the industrial mutant strain used in actual product manufacturing.

Additionally, the footnote to Table 2 states, "This strain was provided by the RYR manufacturer (= Kobayashi Pharmaceutical)," indicating that NIHS received the strain directly from Kobayashi Pharmaceutical. It is therefore reasonable to assume that NIHS was in a position to recognize that the provided strain was a mutant of NBRC 4520 upon receipt.

[Source] Yoshinari T. et al., Proc. Jpn. Acad., Ser. B 101 (2025) 302–316, Table 2 footnote

Fact ⑤ No mention of "industrial mutant strain," "BP-412," or "Gunze patent" in 2024 media reports or official announcements

Following the emergence of the issue in March 2024, our investigation found no mention of "industrial mutant strain," "BP-412," or "Gunze patent JP2009095304A" in official documents released by the Ministry of Health, Labour and Welfare, NIHS, Osaka City Health Department, Consumer Affairs Agency, or Ministry of Agriculture, Forestry and Fisheries, nor in major media reports at the time. The fact that the strain used was not a traditional red yeast rice strain with a thousand-year history of food use, but rather an industrial mutant strain modified via mutagenesis for high production of specific components, was not disclosed to the public from the initial response phase.

Core of the Objection Filed with NIHS

Based on the above facts, our company has raised the following objections to NIHS regarding the Yoshinari paper:

· Although the actual health-incident-related product was manufactured using BP-412 (an industrial mutant strain), the co-culture experiment conducted to verify the mechanism of substance generation used its parent strain NBRC 4520 instead of BP-412. Industrial mutant strains and parent strains are genetically distinct, and UV irradiation mutagenesis may alter the composition and production patterns of metabolites. In the absence of scientific assurance that the metabolites are identical, using the results of a co-culture test with the parent strain NBRC 4520 to explain the generation mechanism of the actual product strain BP-412 is insufficient for causal verification.

· While the Yoshinari paper explicitly states that the strain is derived from NBRC 4520, it makes no mention of the existence of the industrial mutant strain BP-412 or its relationship to the Gunze patent. We request clarification on the reasons for this omission and the scientific basis for this judgment.

Conclusion

This case potentially explains the mechanism of substance generation based on verification results using a strain (NBRC 4520) different from the one used in the actual product (BP-412), raising the need for re-evaluation of its scientific validity. Our company will continue to verify, based on published documents and scientific literature, the accountability of administrative bodies and the reproducibility of research. Progress on disclosure requests and formal objections related to this matter will be announced via press releases as appropriate.

[Company Overview]

Company Name: Kunsei Club Co., Ltd.

Address: 611-1 Maekata, Hayashima-cho, Tagokori District, Okayama Prefecture

Representative: President and Pharmacist Masaaki Mori

Business: Food manufacturing and sales

TEL: 086-483-0602　　E-mail: sales@kunsei.co.jp

Red Yeast Rice Information: https://kunsei.com/archives/category/benikoji