Abstract

This report has been authored by Rui Shuhama, as part of her research activities in the Dai-ichi Life Mental Healthcare Collaboration Research Course at Faculty of Medicine Shimane University, and was written under the supervision of psychiatrists.



• The report introduces a collaborative study conducted by Dai-ichi Life and Faculty of Medicine at Shimane University, which was accepted as part of Kanagawa Prefecture’s ME-BYO policy through the Kanagawa ME-BYO Living Lab program (Study title: Comparison of the Brief Job Stress Questionnaire and Oxidative Stress Markers). The study examined the relationship between employees’ self-recognition of psychological stress and urinary biopyrrin levels, exploring the potential for health support during the pre-disease (ME-BYO) phase. The results were published in the international peer-reviewed journal Medicine (September 2025) under the title “Relationship between psychological and physical work-related stress and urinary biopyrrin levels: A cross-sectional study.” The findings showed that psychological factors such as job suitability and sense of work fulfillment, as well as health awareness factors such as the desire for regular urine-based stress testing, were associated with urinary stress markers, with particularly notable differences in the group requesting regular testing.
• The visualization of both alignment and mismatch between subjective stress and physiological indicators provides not only a path for disease prevention but also a foundation for developing metrics that support diversity in ways of working and living. This study highlights the importance of awareness and support in the ME-BYO phase, and also suggests potential applications in evaluating well-being and subjective happiness as future indices.

1. Introduction

Japanese society is facing the rapid progression of declining birthrates and population aging. In this context, maintaining the health of the working generation and securing labor productivity are critical issues directly tied to social sustainability. Among these, mental health has emerged as a particularly serious social concern. In 2011, Japan’s Ministry of Health, Labour and Welfare (MHLW) positioned mental disorders alongside cancer, stroke, acute myocardial infarction, and diabetes as the nation’s “five major diseases.” Furthermore, with the revision of the Industrial Safety and Health Act, since December 2015 all workplaces with 50 or more employees, regardless of industry, have been required to administer an annual stress check to employees. The law also stipulates penalties for failing to submit results to the Labor Standards Inspection Office or for submitting falsified reports. However, the number of workers taking leave or filing compensation claims due to mental disorders has not decreased. For example, while 1,515 cases of work-related compensation for mental disorders were reported in the year immediately following the mandate, the number had risen to 2,683 cases by FY2022, showing a continuing upward trend (MHLW, 2021). These figures demonstrate that, despite the institutionalization of stress checks, mental health problems in the workplace remain a major challenge.

Against this backdrop, the key question is how to identify and respond to conditions at the pre-disease phase—what in Japan is called “ME-BYO”. The Kanagawa ME-BYO Living Lab is an innovative program operated by Kanagawa Prefecture to empirically evaluate ME-BYO interventions through collaboration among industry, academia, government, and local communities.

Between 2022 and 2023, Dai-ichi Life Holdings, Inc. utilized this framework and, in collaboration with Faculty of Medicine at Shimane University, conducted a clinical study to examine the relationship between psychological stress and physiological stress responses in the workplace. The study combined psychological assessment using the Brief Job Stress Questionnaire (BJSQ) with measurement of urinary biopyrrin levels, an oxidative stress biomarker (Study title: Comparison of the Brief Job Stress Questionnaire and Oxidative Stress Markers). Biopyrrins are explained in more detail in a later section of this article.

The results of this research were recognized for their scientific validity and published in September 2025 in the international peer-reviewed journal Medicine under the title “Relationship between psychological and physical work-related stress and urinary biopyrrin levels: A cross-sectional study.” Building on those academic findings, this article explores the significance of visualizing ME-BYO in the workplace, both from the perspective of Kanagawa Prefecture’s ME-BYO policy and in terms of potential applications for corporate health management in a super-aged society.

2. The ME-BYO Concept

“ME-BYO” is a concept that originated in ancient China and, in modern usage, refers to “all physical and mental conditions that lie between health and disease” (Otsuki et al., 2025; Nakamura et al., 2023). It represents an approach that emphasizes identifying early signs before symptoms become apparent and promoting behavioral and environmental changes to prevent the onset or progression of disease—ultimately extending healthy life expectancy. This preventive and holistic perspective is also directly connected to addressing broader social challenges such as controlling healthcare expenditures and securing a sustainable labor force.

In Kanagawa Prefecture, health is not viewed in the binary framework of “healthy” or “sick,” but rather as a continuum of gradual change (Material 1). The entire process of change between health and illness is defined as ME-BYO. Since the March 2017 declaration “Kanagawa ME-BYO Improvement Statement,” Governor Yuji Kuroiwa has led efforts to promote the ME-BYO concept domestically and internationally, contributing greatly to its public recognition and adoption.

Material 1. The ME-BYO Concept

Source: Kanagawa Prefectural Government “Healthcare New Frontier”

Moreover, ME-BYO has been incorporated into Japan’s national health strategy, not merely as a Kanagawa-specific initiative. In the government’s Second Basic Health and Medical Strategy (2020), ME-BYO was explicitly defined as “a concept that captures health and disease as a continuous spectrum rather than a dichotomy,” and emphasized the need for measurable indicators. The Third Strategy (2025) continues to refer to “ME-BYO” and underscores the importance of developing and utilizing quantitative indices to guide implementation (Prime Minister’s Office of Japan, 2020, 2025).

At the core of Kanagawa’s policy framework stands the Healthcare New Frontier (HCNF) initiative. Confronting the challenges of a super-aged society, the prefecture established the “Kanagawa ME-BYO Living Lab” to provide an environment in which Kanagawa Prefecture residents can actively engage in improving their ME-BYO status. The Kanagawa ME-BYO Living Lab aims to solve local health issues, foster new social systems, and nurture the ME-BYO-related industry by connecting municipalities, corporations practicing “Health and Productivity Management (KENKO KEIEI),” academia, and residents. Through field-based Proof of Concepts, it evaluates the functions and effects of products and services, and translates the findings into practical applications. This initiative serves as a model of Public–Private Partnership (PPP), demonstrating how to balance policy sustainability with industrial innovation.

3. Dai-ichi Life and ME-BYO

Since 2014, Dai-ichi Life has been a member of the ME-BYO Industry organized by Kanagawa Prefecture Government, building initiatives in line with the ME-BYO policy (Material 2).

In September 2019, Dai-ichi Life’s insurance discount service “Kenshin Wari (Health Checkup Discount),” was certified under the ME-BYO BRAND. “Kenshin Wari” was the industry’s first health check-linked premium discount program as of the launch in 2018, through Dai-ichi Life’s insurance product known as “JUST”.

In the Group’s Medium-Term Management Plan FY2021–2023, announced in March 2021, Dai-ichi Life declared its intention to take on the challenge of prevention and ME-BYO in the health and medical domain, leveraging synergies with the core life insurance business.

In November 2022, Dai-ichi Life applied to the Kanagawa ME-BYO Living Lab and was selected for the program. At the ME-BYO Summit Kanagawa 2022 held in Hakone, Kanagawa that same month, Dai-ichi Life hosted a luncheon seminar titled “Our Challenge for ME-BYO care in the life insurance business: Visualizing Stress”, moderated by the author (Material 3). The luncheon introduced the company’s collaboration with Kanagawa Prefecture and announced the launch of a joint research project with the Department of Psychiatry at Faculty of Medicine, Shimane University. The presentation emphasized the goal of preventing mental health–related leave or resignation through evidence-based interventions, enabling early detection of diseases, ME-BYO care, and a society where people can live without fear of sudden mental health decline.

Material 2. History of Dai-ichi Life’s Engagement with ME-BYO Initiatives

Source: Created by the author based on the Dai-ichi Life Luncheon Seminar at the ME-BYO Summit Kanagawa 2022

Material 3. The ME-BYO Summit Kanagawa 2022 Dai-ichi Life Luncheon Seminar “Our Challenge for ME-BYO care in the life insurance business: Visualizing Stress”

Source: Kanagawa Prefectural Government HP “ME-BYO Summit Kanagawa 2022”

In 2023, Dai-ichi Life and Shimane University established the Dai-ichi Life Mental Healthcare Collaboration Research Course within Faculty of Medicine. This course aims the development of a comprehensive mental healthcare system by integrating knowledge of psychiatry, government, and business. Through these research activities and public engagement, Dai-ichi Life has raised awareness of the significance of ME-BYO within the insurance industry, while also serving as a bridge between ME-BYO policy, academia, and industry.

The joint research conducted under the framework of the Kanagawa ME-BYO Living Lab, combining the Brief Job Stress Questionnaire (BJSQ) with urinary biopyrrin levels, represents a concrete example of visualizing ME-BYO in the workplace. Its results, published in the international journal, Medicine in September 2025, reinforced the scientific validity of the ME-BYO concept and provided insights valuable to policy, industry, and academia.

4. Study Background, Objectives, and Methods

This study—formally titled “Comparison of the Brief Job Stress Questionnaire and Oxidative Stress Markers”—was approved by the Medical Research Ethics Committee at Faculty of Medicine, Shimane University (Approval No. KS20220726-1). Its purpose was to clarify the relationship between psychological stress and physiological stress responses in the workplace, and to explore possibilities for early detection and intervention during the ME-BYO phase. Including the preparation period, the study was conducted from October 2022 through March 2023 and was accepted for the Kanagawa ME-BYO Living Lab program in November 2022. Participants were employees of companies based in Kanagawa Prefecture, recruited under the supervision of the Kanagawa ME-BYO Living Lab Committee.

(1) Participation Procedure:

• Individuals who wished to participate gave informed consent online and answered questionnaires covering demographics, stress factors, coping behaviors, and other attributes.
• Each participant received a manual, a urine-collection kit, and a return envelope by mail.
• Participants completed the Brief Job Stress Questionnaire (BJSQ) and collected a urine sample at home using the kit.
• Urine samples were mailed back to Faculty of Medicine, Shimane University.
• Measurements were performed by the lab technicians at Faculty of Medicine, Shimane University.
• Participants received their individual stress-check results combining BJSQ and biopyrrin analysis. (Those with concerns about their results could consult the Department of Psychiatry, Faculty of Medicine, Shimane University.)

(2) Brief Job Stress Questionnaire (BJSQ):

The BJSQ was developed by a research group under Japan’s Ministry of Health, Labour and Welfare. Its reliability and validity have been verified in numerous studies, and it is widely used as the standard survey tool in Japan’s national stress-check program. However, as a self-administered questionnaire, it reflects only subjective evaluations and may not capture latent stress factors that employees themselves are unaware of. In recent years, biomarkers have attracted attention as a means to identify such hidden stress responses objectively.

(3) Urinary Biopyrrins as a Stress Biomarker:

In the human body, reactive oxygen species (ROS) are produced naturally through respiration and metabolism. In small amounts, ROS are harmless, but factors such as ultraviolet radiation, smoking, psychological stress, excessive exercise, and irregular lifestyles can increase ROS production. When excessive, ROS damage cells, a burden known as oxidative stress. High oxidative stress has been linked to aging, lifestyle-related diseases, and mental-health disturbances (Otsuki et al., 2025). Bilirubin, a yellow pigment produced when red-blood-cell hemoglobin is broken down, acts as a natural antioxidant that neutralizes ROS. When bilirubin reacts with ROS, it itself becomes oxidized (metabolized) into biopyrrins, which are then rapidly excreted in the urine without being reduced back to bilirubin. Thus, the urinary concentration of biopyrrins reflects how much bilirubin has been consumed to counter oxidative stress, serving as a real-time indicator of the body’s oxidative-stress status (Material 4).

Material 4. Mechanism of Biopyrrins Generation in the Human Body

Source: Created by the author based on research data belonging to the Dai-ichi Life Mental Healthcare Collaboration Research Course

Recognizing the potential of urinary biopyrrins as a stress-related biomarker, Dai-ichi Life began collaborating with the Department of Psychiatry at Faculty of Medicine, Shimane University, which had been conducting research on the relationship between biopyrrins and various mental illnesses. Recent medical studies, including those from Shimane University, have reported that urinary biopyrrin levels rise with excessive psychological stress and during the onset of psychiatric disorders (Otsuki et al., 2025; Wake et al., 2022). Even before a clinical diagnosis is made, biopyrrin levels may increase during the ME-BYO phase, when psychological stress begins to manifest as subtle physical or mental changes. Measuring urinary biopyrrin levels therefore offers a way to objectively evaluate stress-related oxidative responses, enabling early detection and preventive interventions to reduce the risk of mental illness.

Following the above procedure, urine samples collected from participants were stored at −80 °C at Faculty of Medicine, Shimane University, thawed immediately before analysis, and assayed for urinary biopyrrin concentration.

The 57 items of the BJSQ comprise four evaluation categories (subscales — aggregated question groups): (1) job stressors (17 items), (2) psychological and physical stress responses (29 items), (3) social support (9 items), and (4) job and life satisfaction (2 items). In this study, the primary endpoint was the relationship between the psychological stress-response score and urinary biopyrrin concentration, while secondary analyses examined correlations between urinary biopyrrin levels and individual subscale scores, as well as differences in biopyrrin concentrations for each question item.

5. Results

A total of 105 employees from 8 companies in Kanagawa Prefecture participated in this study. After excluding incomplete or invalid responses, data from 96 participants (valid-response rate 95.2%) were included in the final analysis. The participants’ mean age was 43.3 years, mean body-mass index (BMI) was 22.3, and mean urinary biopyrrin concentration was 1.09 ± 0.53 µmol/g creatinine (Material 5).

Material 5. Basic Information of Study Participants (Simplified Version)

Source: Created by the author based on research data belonging to the Dai-ichi Life Mental Healthcare Collaboration Research Course

No significant correlations were found between overall BJSQ stress-response scores and urinary biopyrrin levels. However, among the BJSQ subscales, suitable jobs and meaningfulness of work showed positive correlations with urinary biopyrrin levels—the higher the score, the higher the urinary biopyrrin levels.

Additional analysis using supplementary questionnaires revealed that employees who expressed a desire for regular stress checks using urine tests had significantly higher urinary biopyrrin levels than those who did not (1.19 ± 0.53 vs. 0.79 ± 0.43 µmol/g creatinine; p < 0.001) (Material 6). No significant differences in urinary biopyrrin levels were observed among the participating companies (A–H). Regression analysis also confirmed that “preference for regular urine-based stress testing” was a significant predictor of urinary biopyrrin levels.

Material 6. Comparison of Urinary Biopyrrin Levels by Preference for Regular Urine-based Stress Testing

Source: Created by the author based on research data belonging to the Dai-ichi Life Mental Healthcare Collaboration Research Course

6. Discussion

In this study, we combined the BJSQ with urinary biopyrrins measurements to examine the relationship between psychological stress and physiological stress responses in the workplace. The results showed no clear correlation between overall psychological stress response scores on the BJSQ and urinary biopyrrin levels. However, individuals who felt that their jobs suited them and who experienced a stronger sense of fulfillment in their jobs tended to show higher urinary biopyrrin levels. This suggests a gap between comprehensive self-reported stress assessments and actual physiological reactions, highlighting the possible presence of “latent stress” that employees themselves may not fully recognize.

In addition, a significant difference was found between employees who expressed a desire for regular urine-based stress testing and those who did not. This indicates that not only actual stress levels, but also psychological factors such as “interests in one’s health” or “anxiety about the future,” may be associated with biopyrrin scores. In this sense, biopyrrin testing may function not only as a biomarker but also as a tool to visualize not only physiological stress responses but also an individual’s psychological orientation toward health, including health awareness and literacy.

These findings are closely linked with the ME-BYO concept, which emphasizes detecting small changes before the onset of disease and prompting timely behavioral adjustments. The identified “mismatch between self-reports and physiological markers” and the “distinct characteristics of employees who request regular urine-based stress testing” both provide important insights into detecting ME-BYO states. They also reinforce the value of combining subjective questionnaires with objective biomarkers.

At the same time, several limitations should be acknowledged when interpreting these results. First, the sample size was approximately 100 participants, smaller than initially expected, which limited the statistical power of the analysis. Future studies should include a larger population. Second, the study was restricted to companies within Kanagawa Prefecture, meaning regional bias may be present; future research should extend to wider areas and industries. Third, because participants were drawn from different companies, organizational culture and work environment may have influenced the results. Fourth, as a self-administered questionnaire, the BJSQ responses may include under- or over-reporting. Fifth, urinary biopyrrin levels can also be influenced by other factors such as lifestyle and general health status, which could not be fully controlled in this study. Finally, the study did not include high-stress individuals or people not currently working, groups that should be examined separately in future research.

7. Conclusion

This study examined the relationship between psychological stress and physiological stress responses in the workplace, presenting a new approach to visualizing ME-BYO conditions among employees. By combining self-assessment through the BJSQ with the objective biomarker of urinary biopyrrin levels, we were able to identify patterns of latent stress and health-related concerns that are difficult to capture through conventional stress checks alone. In particular, the finding that employees who requested regular urine-based stress testing exhibited significantly higher urinary biopyrrin levels suggests two important insights: first, that even in the absence of conscious awareness, individuals may still be experiencing strong physiological stress responses; and second, that health awareness and preventive attitudes themselves may be linked with measurable biological reactions. These results support the philosophy of Kanagawa Prefecture’s ME-BYO policy, which emphasizes detecting small changes before the onset of disease and translating them into early interventions. They also offer practical value for corporate health management, providing evidence-based approaches to help prevent mental health–related leave or resignation among employees. Furthermore, conducting this research within the framework of the Kanagawa ME-BYO Living Lab exemplifies how academic findings can be bridged into policy and workplace practice, underscoring its broader social significance.

Looking ahead, combining biopyrrins with other physiological markers alongside multidimensional psychosocial data will be essential for constructing a more sophisticated “visualization model of ME-BYO.” Such efforts will help close the gap between self-perception and physiological response. This study represents an important first step in that direction, offering a pathway for translating scientific knowledge into real-world implementation.

Ultimately, visualizing ME-BYO is not only about disease prevention but also about illuminating the future of diverse ways of working and living. The gap revealed between self-reported stress and physiological stress responses points to new opportunities for developing well-being indicators that capture subjective happiness and life satisfaction. Dai-ichi Life will continue its collaboration with Faculty of Medicine, Shimane University to advance research at the intersection of science and practice, contributing to a society where people can live and work with health and security.

Original in Japanese:
https://www.dlri.co.jp/report/ld/525895.html