Proprietary Approach to Discovering Ingredients that Improve Sleep Quality

Why do humans sleep? Science has yet to completely answer this fundamental question. Dr. Monoi, with a decade of experience in sleep research under his belt, remarks, “In the last ten years, the relationship between sleep and general health has become clearer. There are two kinds of sleep that comprise the sleep cycle: REM and non-REM sleep. The quality of the sleep cycle is believed to affect the risk of developing lifestyle diseases such as high blood pressure and diabetes.”

Lion recognized the importance of good sleep early on, and started developing sleep medicines in 1966. Then, in 2010, Lion started developing supplements to support sleep. Researcher Mr. Nagamori explains, “We took a completely different approach to ingredient exploration to develop this supplement, which is unlike conventional sleeping pills.”

There are three big problems when it comes to getting a good sleep: trouble falling asleep, waking up in the middle of the night and shallow sleep. Trouble falling asleep after retiring to bed interferes with daily life. Waking up in the middle of the night refers to when one wakes up several times during the night and has difficulty falling back asleep. Shallow sleep refers to not feeling adequately rested, even after sleeping an objectively sufficient number of hours.

Most conventional sleep medicines and supplements aim to improve sleep onset. Lion’s research team chose instead to focus on shallow sleep and worked to find ingredients that would lead to deeper sleep.

We initially picked 80 different candidate substances. From there, we narrowed down the list through several tests, including clinical trials. As a result, we arrived at sake yeast GSP6 (hereinafter, “sake yeast”).

Researcher Ms. Sawada reflects on the effect of serendipity on the development process, in which a casual conversation over dinner led to the discovery. “We came across it when the team was sharing a meal. Somebody asked why we all get sleepy after drinking alcohol, and I had a eureka moment. I remembered that sake yeast was one of the candidates we were looking at. However, we had found that sake itself doesn’t actually contain sake yeast, rather it is a substance used during the brewing process. Nevertheless, the next day, I tried using sake yeast in my research, and it was a winner!”

Challenges in visualizing sleep quality

Once we decided to develop products using sake yeast, the next research topic was more sophisticated—sleep improvement. Sleep efficiency can be enhanced through better living habits as well as supplements. Creating an individualized proposal to maximize each person’s sleep efficiency plays a key role. Here, the visualization of sleep quality is essential.

Researcher Dr. Monoi explains his idea, “To put it simply, we first decided to conduct sleep health checkups. Everyone’s REM and non-REM sleep cycle is different, so the sleep problems will be different for each person. However, it’s not possible to see your own sleep issues while you’re actually asleep, and there’s no way to visualize it. Therefore, I thought that if we could analyze sleep quality in the same way that annual health checkups quantify physical condition and suggest improvements, we would be able to propose individually tailored sleep improvement ideas.

First, we needed to find a way to objectively visualize sleep data, which could only be judged subjectively at the time. Specifically, we needed to develop a tool to sense sleep status as well as a system to determine sleep quality, and then provide specifically optimized methods to improve an individual’s sleep. This challenging project started in 2016.

Our first task was to accurately measure sleep. Although headgear-type electroencephalographs (EEG) were an option for measurement, they can’t be used in everyday life and the equipment itself hinders sleep. What kind of tool can a sleeper wear comfortably that easily measures sleep?

Mr. Nagamori looks back on the development process and explains, “We tried various ideas, and we found that wristband devices were the easiest to use and didn’t affect sleep.”

To visualize sleep quality using a wristband device, we needed to collect actual sleep condition data. The new wristband device estimates brain waves during sleep based on such data as body movement and heart rate. Therefore, our next question was how accurate the data the wristband device collected based on body movement and heart rate measurement actually was.

Ms. Sawada explains, “To have a thorough base of evidence, both quantity and quality of data are crucial. When we started the study, we were collecting one data point per minute, but we eventually increased to 120 data points per minute.” She then goes on to add, “We ended up recruiting hundreds of collaborators from both inside and outside Lion to collect our data. As a result, we were able to compile a huge database—consisting of 120 data points per minute times hours of sleep times hundreds of collaborators—which we used for our experiments.”

After a sufficient quantity of data is achieved, the next step is quality. To confirm the accuracy of the data collected by the wristband device, collaborators were asked to wear a simplified EEG in addition to the wristband device when sleeping to ensure correct EEG data. Because EEG data is viewed as the standard in terms of accuracy, it was compared with the brain wave estimation data collected by the wristband device, based on which modifications were made to the data collection process, including to the devices’ sensitivity.

“To reduce the burden on the collaborators, we had them use a simplified EEG with four electrodes on the forehead. It may have been simplified, but they still had to learn how to put it on correctly. Since we had hundreds of subjects, it took quite a bit of effort to ensure this,” says Mr. Nagamori. However, just as we finished collecting the data, there was an unexpected response from the collaborators.

The collaborators who wore the wristband devices and EEG monitors to collect data were able to see a visualization of their own sleep quality in the numerical data. For most of them, it was the first time they had ever seen an accurate view of their sleep conditions. Everyone was very interested in the results and, while some people found the objective measurement of sleep state matched their perceived sleep condition, others were surprised by the difference between how they felt and the reality of their sleep state. These people believed they had slept well, but the objective data showed that their sleep was not ideal. This difference led to our next development.

Visualizing the Sleep Process and Developing Solutions

Based on the correct measurement data from the EEG, detailed corrections were made to the algorithm that analyzes the data collected via the wristband device, resulting in the algorithm becoming sufficiently accurate. This means that the tool to easily visualize sleep quality was complete.

“The next thing we needed to do was consider methods to improve sleep quality,” notes Mr. Goto, a business development leader. Now that each individual’s sleep quality could be viewed objectively, we needed to devise solutions. Based on Lion’s accumulated sleep research knowledge and data, this study was repeated with sleep research experts outside Lion. During a discussion amongst the team members, everyone agreed not to make any baseless or incorrect proposals. In addition to the sleep supplements we had developed thus far, we proposed an app-based system to improve sleep, including living habit tips such as stretching before bed and avoiding napping after work. We then conducted an experiment with the system to test its effectiveness.

“The experiment was a single-blind, randomized, parallel group study,” recalls Ms. Sawada, going on to explain the experiment in detail. The subjects of the study were 81 men and 28 women who worked during the daytime and were experiencing sleep problems. The study was divided into two groups to test the effectiveness of the sleep improvement suggestions: a control group that only took measurements, and a “check and care” group that took measurements and tried sleep improvement suggestions. Ms. Sawada adds, “The group with higher sleep satisfaction also experienced significant improvement in their daytime productivity.”

The finished sleep check and care service was named “Condition Navi” after the experiments confirmed the effectiveness of the sleep improvement suggestions. This is a new service for Lion, and is offered on a one-on-one basis.

The next question was figuring out how and to whom to market the new service. Mr. Sugawara, who is involved in business development with Mr. Goto, explains, “Better sleep leads to better health, so we thought that companies involved with health and productivity management would be interested.” However, even with evidence of sleep-improving effects, it is difficult to claim immediately effective, direct and visible benefits. Therefore, we made a change in direction.

Mr. Goto continued, “We wondered if we could connect improved sleep quality to safety. We thought that the management side would be interested if workplace accidents would decrease with improved sleep quality and physical condition. Car accidents are the most common workplace accident that occurs as a result of lack of sleep, so we narrowed our focus to the commercial and passenger transportation industries.”

Providing One-on-One Services to the Commercial Transport Industry

At that moment, the COVID-19 pandemic started around the world. The world would undergo major changes that would affect business development, but Mr. Goto saw an opportunity, saying, “COVID-19 made things difficult in the passenger transport industry, but the growing demand for online shopping services due to stay-at-home lifestyles increased logistics demands and placed a greater burden on delivery drivers.”

A driver’s physical condition is highly influenced by sleep quality. Lack of sleep is known to lead to poor concentration and diminished alertness, which, in turn, leads to traffic accidents.*

* “Sleep Guidelines for Health Promotion 2014,” Ministry of Health, Labour and Welfare.

https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/kenkou_iryou/kenkou/ suimin/

Mr. Sugawara describes the details of the service, emphasizing its biggest benefit: supporting safe driving. He explains, “Condition Navi is a mobile app that helps drivers visually monitor their sleep quality based simply on data from a wristband device that measures their sleep patterns, depth of sleep, occurrences of waking up in the night and total sleep time. The app is able, based on the individual driver’s specific characteristics, to offer specifically optimized advice around living habits and also suggests balancing these with supplements. In addition, an operations manager can view their drivers’ physical condition (sleep or fatigued) using a centralized, computerized management tool.”

The use of Condition Navi to visualize sleep conditions will benefit companies in the transportation industry by helping reduce accidents. At these companies, it is a rule for every driver to participate in morning and evening roll-calls. In the past, managers would have to depend on driver’s self-reports, so, even if a driver looked unwell, there was nothing to be done if they insisted they were fine. However, after introducing Condition Navi, operations managers can monitor their drivers’ sleep data in real time and manage their condition.

Mr. Sugawara explains the merits, saying, “If a manager mentions a driver’s sleep data during roll-call, the driver will feel reassured that their physical condition is understood, and communication quality will naturally improve.” For the transportation industry, reducing accidents is very valuable. Managers can also monitor the drivers’ real-time fatigue levels throughout the work day. A manager can decide that a driver needs a break based on fatigue level, and they can promptly tell the driver to do so.”

Sleep is the foundation for good health. Not only does good sleep help prevent accidents due to falling asleep at the wheel, but it also helps prevent illness. Visualization of sleep quality is essential to improving sleep quality on an individual, optimized level. Lion is aiming to become an advanced healthcare company for general health, and will first establish its service for high-quality sleep in the B-to-B field and then expand it for the B-to-C range as well.

Affiliations are as of the time of the interview. (Interviewed October 2022)