Glycative Stress Research
Online edition : ISSN 2188-3610
Print edition : ISSN 2188-3602
Received : May 11, 2016
Accepted : July 7, 2016
Published online : September 30, 2016

Original paper

Effect on sleep quality of bedding with a high user rating in a post-marketingsurvey: A non-controlled open-label study
Wakako Takabe 1), Mari Ogura 1, 2), Masayuki Yagi 1), Yoshikazu Yonei 1)
1) Anti-Aging Medical Research Center and Glycative Stress Research Center, Graduate School of Life and Medical Sciences,
Doshisha University, Kyoto, Japan
2) Department of Food Science and Nutrition, Kyoto Bunkyo Junior College, Kyoto, Japan

Abstract

Objectives: An increasing number of studies have suggested the association of poor quality sleep and various medical
conditions. The objective of this study was to determine whether the use of a particular type of mattress, that received a highuser rating in a post-marketing questionnaire survey (i.e. the test mattress), can improve sleep quality, and also affect various
physical parameters.
Methods: In this non-controlled open-label study, a total of 11 men and women with sleep-related complaints (5 men and6 women; mean age 51.0 ± 6.3 years) were asked to use the test mattress for 4 weeks and then were examined for changes
in various physical parameters. The test mattress was provided by Nishikawa Sangyo Co., Ltd. (Tokyo, Japan). The subjects
underwent examination for subjective and objective symptoms, anthropometry, blood biochemistry, and urine and saliva
analysis before and at 4 weeks after the start of study. They were asked to record in a diary any adverse events occurring
during the study, and their severity, as well as the details of their lifestyle and dietary/exercise habits. This study was
conducted with the approval of an ethics committee.
Results: In the assessment using the Pittsburgh Sleep Quality Index (PSQI-J), significant improvements were observedin the sleep quality, time to fall asleep, difficulty sleeping and difficulty staying awake during the daytime at week 4. The
global PSQI score (PSQIG) was significantly improved from 9.5 ± 0.4, indicating severe disorder, to 7.1 ± 0.7, indicating mild
disorder. As for oxidative stress, a significant decrease was observed in the creatinine-adjusted concentration of 8-OHdG inurine. Among glycolipid metabolism parameters, while no significant change was observed in the fasting blood glucose levelor HbA1c, the HDL cholesterol level showed a 7.5% significant increase from the baseline value (73.7 ± 5.1 mg/dL) at week 4(p <0.01). Insulin-like growth factor-I (IGF-I), a second messenger for growth hormone, showed a 10.2% significant increase
from the baseline value (173.8 ± 17.4 ng/dL) at week 4 (p < 0.01).
Conclusion: These results suggest that the 4-week use of the test mattress improved sleep quality, as demonstrated by
improvement in subjective symptoms, and it promoted growth hormone/IGF-I secretion, reduced oxidative stress andimproved lipid metabolism, as demonstrated by biochemical analysis.

KEY WORDS: sleep quality, oxidative stress, glycative stress, lipid metabolism, insulin-like growth factor (IGF-I)
Introduction

Poor-quality sleep is an age-related change. ManyJapanese people, both adults and children, seem to sufferfrom a chronic lack of sleep. Various complaints due topoor sleep are reported by not only middle-aged to elderly
people, but also children in their childhood and adolescence
periods, indicating an association of poor sleep with various
lifestyle-related diseases and metal well-being 1-7). Growing
attention has also been paid to the association between poor
quality sleep, as manifested as sleep apnea syndrome orCorresponding author: Prof. Yoshikazu Yonei
Anti-Aging Medical Research Center and Glycative Stress Research Center,
Graduate School of Life and Medical Sciences, Doshisha University
1-3 Tatara Miyakodani, Kyotanabe City, Kyoto 610-0394, Japan
TEL & FAX: 0774-65-6394 Email: yyonei@mail.doshisha.ac. jp
Contact for Co-authors: Takabe W, wtakabe@mail.doshisha.ac. jp;
Ogura M, m-ogura@po.kbu.ac. jp; Yagi M, yagi@yonei-labo.com

other symptoms, and type-2 diabetes, a typical lifestylerelated disease associated with high glycative stress 8-12). It istherefore important to maintain high-quality sleep from theperspective of preventive medicine.
In order to maintain high-quality sleep, each individual
should use the appropriate mattress suited for their condition.
In this study, we asked a total of 11 men and women withsleep-related complaints to change their mattress from one
they were regularly using to the one that received a high user
rating in a post-marketing questionnaire survey (i.e. the test

_ 110 _

Glycative Stress Research 2016; 3 (3): 110- 123(c) Society for Glycative Stress ResearchGlycative Stress Researchmattress). After they used the test mattress for 4 weeks, weevaluated its effect on physical parameters, including sleep
quality, in a non-controlled open-label study. The primary
outcome measures included sleep-related parameters, as wellas parameters related to oxidative and glycative stress, which
are major risk factors for aging.

Methods
Subjects

We recruited 31 healthy men and women aged 40 to 65
years who were not obese or too thin who had sleep-related
complaints, such as difficulty falling asleep, waking after
sleep onset, waking in the early morning, and difficulty
achieving deep sleep. These candidates were interviewed and
12 of them were selected as the subjects for this study
according to the inclusion and exclusion criteria. Although
the target male/female ratio was 1:1, 1 subject was withdrawn
due to a personal reason and the remaining 11 subjects (meanage 51.0 ± 6.3 years), including 5 men (47.2 ± 3.7 years) and6 women (54.2 ± 6.4 years), were included in the analysis.
Subjects had to to meet the following inclusion criteria:
1) healthy male or female aged ≥ 40 and <65 years at the timeof informed consent for participation in the study;2) good health status and currently not receiving any treatment
for a medical condition;3) BMI from 18.5 kg/m2 to < 25.0 kg/m2;4) have sleep-related complaints, such as difficulty falling
asleep, waking after sleep onset, waking in the early morning,and difficulty achieving deep sleep;5) have a duration from going to bed (turning the light off)
to waking up of ≥ 4 hours;6) have a habit of going to bed (turning the light off) andgetting up at consistent times every day, with a bedtime(light-off time) of before 24:00;
7) have a habit of sleeping on a Japanese futon mattress on adaily basis;8) able to sleep on the test mattress during the study period;9) able to sleep alone during the sleep assessment period;10) able to comprehend the full explanation of the purposesand details of the study, have the ability to give consent, andvoluntarily decide to participate in the study based on a fullunderstanding by providing a written informed consent; and11) deemed by the investigator to be appropriate for inclusionin the study.
Subjects were excluded from the study for the following
reasons:
1) receiving medication therapy for a chronic disorder;2) suspected of having sleep apnea syndrome (SAS) or has acurrent or previous history of treatment for SAS;3) suspected of having nocturia, prostatic hyperplasia oroveractive bladder at present or in the past;4) a current or previous history of severe liver disorder, kidney/
heart disease, lung disease, gastrointestinal disorder (including
gastrectomy), organ failure, diabetes, thyroid disease, or otherserious diseases;5) skin conditions, such as atopic dermatitis and cutaneous
hypersensitivity;
6) current or previous history of hepatitis or similar disease;7) severe anemia;8) a resting systolic blood pressure of ≥ 160 mmHg or a resting
diastolic blood pressure of ≥100 mmHg;9) were taking, or took within the past 3 months, or werescheduled to take during the study period on a regular basis
any of the following products that may affect test results:
medicinal drugs, quasi drugs, foods with health claims (foods
for specified health use), health food, and supplements;
10) a mean daily alcohol consumption of > 60 g/day;11) donated > 200 mL of blood within the past 1 month or> 400 mL within the past 3 months;12) were likely to have any change in sleep environment orlifestyle during the study period (e.g. night shift work, longterm trip, transfer to a new workplace);13) were currently participating in another human clinicalstudy or had participated in such a study within 3 months
before screening;14) were pregnant, nursing, suspected of being pregnant, or
planning a pregnancy; or15) were considered by the investigator to be inappropriate
for inclusion in this study for other reasons.

Study design

This study was conducted as a non-controlled open-label
study
The Seiatu® Shiki-Futon mattress (REGULAR HF2521R;
Nishikawa Sangyo Co., Ltd., Tokyo, Japan) was used as thetest mattress. The test mattress was of single size (9×97×200cm) and was provided with a fitted sheet by Nishikawa
Sangyo. At the beginning of the study, subjects wereasked to replace the mattress they were using with the test
mattress.
The core of the test mattress was designed with newcomputer-controlled technology to achieve an ideal, unique
3D structure that supports the whole human body at about
1,900 points to mitigate the feeling of being compressed
while allowing ventilation. In terms of safety, the productwas placed on the market in September 2001, and a total of369,911 mattresses were sold as of September 2015, with noserious adverse event having been reported to date regarding
the use of the product.
Subjects underwent an examination for subjective andobjective symptoms, anthropometry, blood biochemistry andtests for measuring oxidative, glycative and psychosomaticstresses before and 4 weeks after the start of study. All study
participants were asked to record in a diary any adverse
events occurring during the study, as well as their severity,and the details of their lifestyle and dietary/exercise habits.
This study was conducted between November 2015 andMarch 2016.

Outcome measures(1) Subjective symptoms
Sleep quality was assessed using the Pittsburgh Sleep Quality
Index (PSQI-J) 13). According to the PSQI scoring table,
scores were calculated for each of the following variables:
sleep quality, time to fall asleep, sleep length, sleep efficiency,
difficulty sleeping, use of sleep medicine, and difficulty
staying awake during the daytime. The scores for each variable
were summed to obtain the PSQI global (PSQIG) score.
The obstructive sleep apnea (OSA) sleep inventory MA
version 14, 15) was used to score time to go to bed, time to get up
and sleep length in a 4-point scale. Results were summarized
for each of the following 5 factors: factor 1 “sleepiness on
rising”; factor 2 “initiation and maintenance of sleep”; factor 3“frequent dreaming”; factor 4 “feeling refreshed; and factor 5_ 111 _

Sleep Study of a Mattress Highly Rated in a Post-Marketing Survey“sleep length”.
Subjective symptoms were assessed using the Anti-AgingQOL Common Questionnaire (AAQOL) 16). Subjective
symptoms were divided into physical and mental symptoms
and scored in a 5-point scale of 1 to 5.
(2) Anthropometry
Anthropometric parameters included body height
and weight, body fat percentage, body mass index (BMI),
systolic and diastolic blood pressures and pulse rate. Body
composition measurement was performed using a bodycomposition analyzer (DC-320, Tanita Co., Ltd., Tokyo,
Japan).
(3) Blood biochemistry
The following blood biochemical parameters were
evaluated: total protein, albumin, A/G ratio, total bilirubin,liver/kidney function tests [AST (GOT), ALT (GPT), γ -GTP,
CPK, uric acid, urea nitrogen (BUN) and creatinine], glucose
metabolism-related [fasting blood (plasma) glucose level,
HbA1c [NGSP] (whole blood), pentosidine (plasma)], lipid
metabolism-related [total cholesterol (TC), HDL cholesterol(HDL-C), LDL cholesterol (LDL-C) and triglyceride (TG)]and serum electrolytes (sodium, potassium, chloride, calcium
and iron). The following circulating hormones were measured:insulin-like growth factor-I (IGF-I), dihydroepiandrosteronesulfate (DHEA-s), cortisol, 3 fractions of catecholamine(adrenaline, noradrenaline and serotonin in plasma) andserotonin in whole blood. Except for pentosidine, which wasmeasured at the Japan Institute for the Control of Aging,
NIKKEN SEIL Co., Ltd. (Shizuoka, Japan), all otherparameters were measured at Health Sciences ResearchInstitute Inc. (Yokohama, Japan). Unless specifically indicatedas “plasma” or “whole blood”, all parameters were measured
in serum samples.
(4) Urinalysis
The first urine collected after rising was used as the
sample. Subjects were asked to collect the first urine aftergetting up on their own and record urine volume, time ofvoiding in the morning and last time of voiding during
the night. Oxidative stress-related parameters, including
8-hydroxy-2’-deoxyguanosine (8-OHdG) 17) and 15-isoprostaneF2t) 18), were measured and the rate of production of thesesubstances was calculated. The following steroid hormone
metabolites were measured: free cortisol and 17-ketosteroid(17-KS) fractions (androsterone, etiocholanolone, DHEA,
11-keto-androsterone, 11-keto-etiocholanolone, 11-OHandrosterone and 11-OH-etiocholanolone). All urinalysis
parameters were measured at the Japan Institute for theControl of Aging, NIKKEN SEIL Co., Ltd.
(5) Saliva analysis
A saliva sample was collected immediately after rising
using a saliva sampling swab for the measurement of salivary
melatonin level (at Health Sciences Research Institute Inc.).
(6) Sleep assessment by Sleepscan
A Sleepscan sleep meter (SL-503; Tanita) was used toassess the quality of sleep. The sleep meter was placed under
the test mattress before a subject went to bed and turned on
to start measurement. Subjects were instructed to sleep alone
on the mattress. Sleeping with a pet was also prohibited.
The parameters measured included the dates of starting/finishing measurement, sleep length, sleep score and sleep

stage (4 stages from waking/shallow sleep to deep sleep). The
sleep quality score was calculated from the results of thesemeasurements. This measurement was performed during a
1-week period before the start of use of the test mattress andanother 1-week period starting 3 weeks after the start of useof the test mattress.

- Statistical analysis

For statistical analysis, statistical analysis software SAS
9.4 (SAS Institute Japan, Tokyo, Japan) or SPSS (Statistics19;
Japan IBM, Tokyo, Japan) was used to perform paired t-test.
Differences were considered significant and marginallysignificant at significance levels of 5% and 10%, respectively.
No criteria were defined for determining outliers. For missing
data due to testing problems or major weakness in thereliability of data, no substitution was performed.

- Ethics review

This study was conducted in compliance with the
Declaration of Helsinki (revised at the WMA General
Assembly, Fortaleza, Brazil, 2013) and the Ethical Guidelines
for Medical Research in Humans (notification from the
Ministry of Education, Culture, Sports, Science andTechnology and the Ministry of Health, Labour and Welfare).
The ethical aspects and appropriateness of the present study
were reviewed by the human research ethics committee atGeneral Incorporated Association Oriental Occupational
Health Association Tokyo Branch (Tokyo, Japan). The study
was started after approval by the committee and conductedaccording to the approved protocol. The study was registeredin advance with UMIN #000020017.

Results

Subjective symptoms

The 4-week use of the test mattress resulted in
improvement in subjective symptoms, as detailed below.
In the PSQI-J assessment, significant improvement wasobserved in the scores for sleep quality (p = 0.008), time tofall asleep (p = 0.034) and difficulty sleeping (p = 0.046)( Table 1 ). The PSQIG score was significantly improved
from 9.5 ± 0.4, indicating severe disorder, to 7.1 ± 0.7,
indicating mild disorder (p = 0.005). The score for difficulty
staying awake during the daytime was also significantly
improved from 1.7 ± 0.1 at baseline to 0.7 ± 0.2 at week 4 (p= 0.002).
In the assessment using the OSA sleep inventory,
significant improvements in scores were observed for factor
1 “sleepiness on rising” (p = 0.036), factor 2 “initiation andmaintenance of sleep” (p = 0.014) and factor 4 “feelingrefreshed” (p = 0.048) ( Table 1 ).
In the AAQOL assessment, significant improvements
in scores were observed for 3 of 33 physical symptoms,
including “eye pain” (p = 0.039), “muscular pain/stiffness”(p = 0.046) and “lethargy” (p = 0.008), and 5 of 21 mental
symptoms, including “shallow sleep” (p = 0.014), “difficultyin falling asleep” (p = 0.038), “inability to solve problems” (p= 0.034), “inability to sleep due to worries” (p = 0.026) and“feeling tense” (p = 0.025) ( Table 2 ). No significant change
was observed in other symptoms.
The assessment using Sleepscan showed no significant
difference between the sleep quality during the first 1 week
after the start of use of the test mattress and that during the_ 112 _Glycative Stress Research

Table 1. Sleep quality evaluation

PSQI-J

OSA sleep
Questionnaire

BeforeAfter 4 weeks

p valueSleep quality

2.1 ± 0.1

1.5 ± 0.2

0.008

Time to fall asleep

2.3 ± 0.3

1.7 ± 0.3

0.034

Sleeping time

1.6 ± 0.2

1.5 ± 0.3

0.157

Sleep efficiency

0.4 ± 0.2

0.6 ± 0.2

0.257

Difficulty sleeping

1.4 ± 0.2

1.0 ± 0.0

0.046

Use of sleep inducers

0.1 ± 0.1

0.1 ± 0.1

1.000

Daytime difficulty waking

1.7 ± 0.1

0.7 ± 0.2

0.002

PSQIG

9.5 ± 0.4

7.1 ± 0.7

0.005First factor

9.9 ± 0.5

11.8 ± 0.6

0.036

Second factor

11.2 ± 0.6

14.3 ± 0.6

0.014

Third factor

6.7 ± 0.3

7.0 ± 0.2

0.405

Forth factor

6.7 ± 0.3

8.2 ± 0.5

0.048

Fifth factor

5.2 ± 0.3

5.8 ± 0.3

0.223

49.6 ± 4.2

46.4 ± 4.5

0.110

Sleep quality score

Results are expressed as mean ± standard error mean, paired t test, n=11. PSQI-J, Pittsburgh Sleep Quality Index (Japan version) questionnaire;
PSQIG, PSQI global score; OSA, obstructive sleep apnea syndrome; Sleep quality score is measured by Sleepscan.

Table 2. AntiAging QOL Common questionnaire

BeforeAfter 4 weeks

p valueEye pain2.30 ± 0.30

1.50 ± 0.20

0.039

Muscular pain/stiffness

3.60 ± 0.40

2.90 ± 0.40

0.046

Lethargy

3.20 ± 0.30

2.50 ± 0.20

0.008

Shallow sleep

3.60 ± 0.30

2.80 ± 0.40

0.014

Difficulty in falling asleep

3.50 ± 0.30

2.90 ± 0.40

0.038

Inability to solve problems

2.30 ± 0.20

1.70 ± 0.20

0.034

Inability to sleep because of worries

2.80 ± 0.30

1.80 ± 0.20

0.026

A sense of tension

2.60 ± 0.30

2.20 ± 0.30

0.025

Physical symptoms

Mental symptoms

Data are expressed as mean ± standard error mean, paired t test, n=11.

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Sleep Study of a Mattress Highly Rated in a Post-Marketing Survey

last 1 week of use of the test mattress ( Table 1 ).

showed a slight but marginally significant increase from 0.04
± 0.01 μg/mL at baseline to 0.06 ± 0.01 μg/mL at week 4 (p= 0.057).

Anthropometric parameters

No significant change was observed in body weight, BMI,
body fat percentage or blood pressure during the observation
period (Table 3).

Blood tests, urinalysis and saliva analysis (Table 4)

In the serum electrolyte analysis, significant increases,
although mild and within the reference range, were observedin sodium (+1.1%, p = 0.001), potassium (+4.7%, p = 0.039)
and chloride (+1.4%, p = 0.006) levels. For liver function
parameters, a significant change within the reference rangeof AST (+28.9%, p = 0.001) was observed. No significant
change was observed in any of the kidney function
parameters or serum proteins. The results of oxidative/
glycative stress, lipid metabolism and endocrine parameters
are described separately in the following sections.

Oxidative stress parameters

For oxidative stress-related parameters, 8-OHdG andisoprostane levels in the first urine collected in the earlymorning were measured. The creatinine-adjusted concentrationof 8-OHdG was significantly improved from 9.87 ± 0.84
ng/mg crea at baseline to 7.13 ± 0.45 ng/mg crea at week 4(-27.8%, p = 0.006). No significant change was observed in
the rate of 8-OHdG production. No significant finding wasobserved for isoprostane.

Glycative stress parameters

Among the glycative stress-related parameters tested,no significant change was observed in the fasting blood
glucose or HbA1c levels while the plasma pentosidine level

Lipid metabolism parameters

Among the lipid metabolism parameters tested, the TC
level was significantly increased from 209.50 ± 7.90 mg/dL
at baseline to 222.40 ± 7.60 mg/dL at week 4 (+ 6.2%, p =0.011) while no significant change was observed in LDL-C
level or atherogenic index. The HDL-C level was alsosignificantly increased from 73.70 ± 5.10 mg/dL at baseline
to 79.20 ± 5.20 mg/dL at week 4 (+ 7.5%, p = 0.006).

Endocrine parameters

The endocrine parameters tested included IGF-I and
DHEA-s, which are known to be related to hormonal age
in the anti-aging medicine field, sleep-related hormone
melatonin in saliva, and psychosomatic stress-related factors,
including cortisol, adrenaline, noradrenaline, dopamine,
serotonin and urinary steroid hormone metabolites.
The serum IGF-I level was significantly increased from173.84 ± 17.40 ng/mL at baseline to 191.54 ± 15.88 ng/mL
at week 4 (+10.2%, p = 0.008). No significant change wasobserved in serum DHEA-s level or salivary melatonin level.
The plasma noradrenaline level was significantly
increased from 508.30 ± 46.90 pg/mL at baseline to 634.70± 54.60 pg/mL at week 4 (p = 0.011). The blood serotoninlevel was significantly decreased from 211.15 ± 32.29 ng/mL
at baseline to 197.05 ± 32.95 ng/mL at week 4 (p = 0.024).
Significant increases were observed in the urine levelsof the following DHEA metabolites: androsterone from 0.73
± 0.18 mg/day at baseline to 1.02 ± 0.24 mg/day at week 4(p = 0.037); and etiocholanolone from 0.80 ± 0.18 mg/day
at baseline to 1.03 ± 0.21 mg/day at week 4 (p = 0.023). No
significant change was observed in the other metabolites.

Table 3. Anthropometry

BeforeHeightcm

164.06 ± 8.23

Weightkg

Body fat
BMI

After 4 weeks--

57.52 ± 8.08

57.69 ± 7.52

0.584

%

25.21 ± 5.43

25.44 ± 5.22

0.327

-

21.27 ± 1.64

21.35 ± 1.57

0.515

Blood pressure (systolic)mmHg

117.3 ± 3.4

116.2 ± 4.0

0.738(diastolic)mmHg

73.4 ± 2.5

72.5 ± 3.0

0.530

/min

69.1 ± 2.8

70.2 ± 3.3

0.616

Pulse

Data are expressed as mean ± standard error mean, paired t test, n=11. BMI, body mass index.

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p valueGlycative Stress Research

Table 4. Blood, urine, salivary examination
Blood chemistry

BeforeAfter 4 weeks

p value

Total bilirubin

mg/dL

0.62 ± 0.07

0.62 ± 0.07

1.000

AST

U/L

17.3 ± 1.5

22.3 ± 1.6

0.001

ALT

U/L

16.5 ± 1.6

17.6 ± 1.7

0.361

γ - GTP

U/L

31.8 ± 9.0

28.6 ± 6.2

0.299

CPK

U/L

122.1 ± 28.0

175.6 ± 43.3

0.075

Uric acidmg/dL

4.59 ± 0.44

4.76 ± 0.37

0.266

BUN

mg/dL

12.7 ± 0.9

12.9 ± 0.6

0.784

Creatinin

mg/dL

0.73 ± 0.05

0.70 ± 0.04

0.084

Na

mEq/L

140.9 ± 0.4

142.4 ± 0.4

0.001

K

mEq/L

4.26 ± 0.10

4.46 ± 0.08

0.039

Cl

mEq/L

103.2 ± 0.7

104.6 ± 0.5

0.006

Ca

mg/dL

9.47 ± 0.06

9.57 ± 0.04

0.161

Fe

μg/dL

89.4 ± 9.9

96.2 ± 8.1

0.484

Total protein

g/dL

7.19 ± 0.08

7.31 ± 0.06

0.058

Albumin

g/dL

4.42 ± 0.06

4.43 ± 0.03

0.839

1.61 ± 0.06

1.55 ± 0.04

0.064

A/G ratio
Oxydative stress markers in urine
8-OHdG

ng/mL

10.2 ± 2.5

6.9 ± 1.1

0.124

Creatinine

mg/dL

98.0 ± 18.0

98.6 ± 15.6

0.953

8-OHdG [creatinine-adjusted]

ng/mg crea

9.9 ± 0.8

7.1 ± 0.5

0.006

8-OHdG production rate

ng/kg/hr

7.1 ± 1.3

5.3 ± 0.6

0.181

Isoprostane

ng/mL

3.0 ± 0.6

3.4 ± 0.8

0.655

Isoprostane [creatinine-adjusted]

ng/mg crea

3.0 ± 0.3

3.4 ± 0.4

0.405

Isoprostane production rate

ng/kg/hr

2.1 ± 0.3

2.6 ± 0.6

0.471

mg/dL

95.1 ± 2.6

97.8 ± 3.1

0.294

%

5.5 ± 0.1

5.5 ± 0.1

0.779

Pentosidine

μg/mL

0.04 ± 0.01

0.06 ± 0.01

0.057

Total cholesterol

mg/dL

209.5 ± 7.9

222.4 ± 7.6

0.011

LDL-C

mg/dL

120.5 ± 7.6

127.5 ± 7.2

0.063

HDL-C

mg/dL

73.7 ± 5.1

79.2 ± 5.2

0.006

TG

mg/dL

83.4 ± 12.0

84.6 ± 8.3

0.833

1.95 ± 0.22

1.90

0.17

0.567

Glycative stress related markers
FPG
HbA1c [NGSP]Arteriosclerosis index_ 115 _

Sleep Study of a Mattress Highly Rated in a Post-Marketing Survey

Hormonal examination

BeforeAfter 4 weeks

p value

Melatonin (saliva)

pg/mL

17.55 ± 4.26

17.76 ± 3.67

0.931

IGF-I

ng/mL

173.8 ± 17.4

191.5 ± 15.9

0.008

DHEA-sμg/dL

163.3 ± 36.3

166.3 ± 34.4

0.751

Cortisol

μg/dL

9.02 ± 0.95

9.91 ± 0.68

0.309

Adrenaline

pg/mL

46.7 ± 6.8

45.7 ± 6.7

0.806

Noradrenaline

pg/mL

508.3 ± 46.9

634.7 ± 54.6

0.011

Serotonin

ng/mL

211.15 ± 32.29

197.05 ± 32.95

0.024

Free cortisol

μg/day30.35 ± 5.73

26.59 ± 5.80

0.232

Androsterone

mg/day0.73 ± 0.18

1.02 ± 0.24

0.037

Etiocholanolone

mg/day0.80 ± 0.18

1.03 ± 0.21

0.023

DHEA

mg/day0.19 ± 0.09

0.15 ± 0.04

0.630

11-keto-androsterone

mg/day0.02 ± 0.00

0.02 ± 0.00

1.000

11-keto-etiocholanolone

mg/day0.19 ± 0.06

0.20 ± 0.06

0.516

11-OH-androsterone

mg/day0.58 ± 0.18

0.48 ± 0.13

0.098

11-OH- etiocholanolone

mg/day0.17 ± 0.07

0.18 ± 0.07

0.607

Steroid hormone metabolites in urine

Data are expressed as mean ± standard error mean, paired t test, n=11. BMI, body mass index; IGF-I, insulin-like growth factor-I;
DHEA, dehydroepiandrosterone; DHEA-s, DHEA-sulfate; Arteriosclerosis index = (TC−HDL-C)/HDL-C.

Discussion

Sleep is a major component of a person’s lifestyle. Poor
quality sleep leads to an impairment of quality of life (QOL).
A nationwide epidemiological survey of sleep conducted
in 1997 showed that the prevalence of insomnia was 17.3%(14.6-20.0%) in men and 21.5% (18.8-24.3%) in women,that of poor quality sleep was 17.8% (15.3-20.3%) in men
and 20.2% (17.6-22.7%) in women, and that of regularhypnotic use was 3.5% (2.3-3.7%) in men and 5.4% (4.16.8%) in women 19).
The quality of sleep decreases with age. Aging is
associated with decreased melatonin secretion from thepineal gland 20), changes in the sleep-wake rhythm and sleep
structure, greater difficulty in falling asleep, shallower sleep,
reduced length of sleep with a feeling of sound sleep, andan increased incidence of sleep-related problems, such as
awakening early and difficulty in achieving deep sleep 21, 22).
Maintaining a good quality sleep is important to achieve
healthy longevity 23). Sleep disturbance is also observed inyounger people; for example, various sleep disorders havebeen reported in college students 24-29). There is an increasingawareness of the importance of preventing depression
in the area of workplace mental health. Considering thatpoor quality sleep is often observed in an early stage ofthe onset of depression, it is of great significance to detect

poor quality sleep early so that the onset of depression canbe prevented at an early stage 30, 31). In order to establish a
comfortable sleep environment and improve sleep quality,each individual should use an appropriate mattress suited fortheir condition.

Assessment of sleep quality and mattress quality

Various attempts have also been made in Japan to assess
sleep quality and mattress quality. These include the use ofquestionnaire forms 32-38), polysomnography 39), ActiGraph(Actigraph Corp., Pensacola, FL, USA) 40) or other types of
3D acceleration sensors for body motion monitoring 41-43),
assessment of autonomic function by frequency analysis of
the acceleration pulse wave a-a interval 44), and measurementof psychosomatic stress markers in saliva [chromogranin A 45) ]and oxidative stress markers in blood [diacron reactive
oxygen metabolites (dROM 46)] or urine [8-OHdG 47)], in
addition to a questionnaire. In this study, although conductedin a non-controlled open-label design, we observed significant
improvement in subjective symptoms, as well as a decreasein the creatinine-adjusted concentration of 8-OHdG in urine(-27.8%), a measure of oxidative stress, and an increase in
IGF-I level (+10.2%), a measure of hormonal age.

_ 116 _Glycative Stress Research

Subjective symptoms and background factors

Known influencing factors for sleep quality include room
temperature 48), noise 49), alcohol consumption 50), work load 51)
and frequent urination 52). The present study also included
these factors in the analysis, but identified no significant
findings.
The use of the test mattress resulted in improvement insubjective symptoms, as detailed below.
In the AAQOL assessment, significant improvement inscores were observed for 3 physical symptoms, including“eye pain”, “muscular pain/stiffness” and “lethargy”, and5 mental symptoms, including “shallow sleep”, “difficultyin falling asleep”, “inability to solve problems”, “inability
to sleep due to worries” and “feeling tense”. In a previous
study where an α-Gel Mat was used as the test mattress 47),
significant improvement was observed in physical symptoms“tired eyes”, “lethargy” and “coughing and sputum”, andmental symptoms “no feeling of happiness”, “shallow sleep”
and “difficulty falling asleep”, of which the physical symptom“lethargy” and mental symptoms “shallow sleep” and“difficulty falling asleep” were also improved in the present
study. The discrepancy between the two studies in terms ofsymptoms with significant changes before and after use of
the test mattress may be explained by the differences in theage/gender distribution of subjects and subjective symptoms
evaluated. Improvement in the scores for physical symptoms“eye pain” and “tired eyes” can both be interpreted as an
improvement of eye strain, although “eye pain” is more severe
than “tired eye” in terms of the severity of eye symptoms.
Recent development in IT devices, such as smartphones, has
posed an increasing burden on eye function. The differential
impact on improvement of sleep quality between physicalsymptoms “eye pain” and “tired eyes” may reflect this social
situation.
In the PSQI-J 13) assessment, improved scores for sleep
quality, time to fall asleep and difficulty sleeping resulted ina significant improvement in the PSQIG score from “severe”
to “mild” disorder, which was likely associated with an
improvement in the daytime activity and a significant
improvement in the score for difficulty staying awake during
the daytime.
The OSA sleep inventory is a psychological scale used
for the self-evaluation of sleep immediately after rising in
middle-aged to elderly people, and is characterized by therequirement of a relatively short length of time to complete
and ease of use in clinical practice 14, 15). This inventory
consists of 16 questions of 5 factors, including factor 1“sleepiness on rising”, factor 2 “initiation and maintenanceof sleep”, factor 3 “frequent dreaming”, factor 4 “feelingrefreshed” and factor 5 “sleep length”. In the present study,
significant improvement was observed in factors 1, 2 and 4.

Oxidative stress

Poor quality sleep, such as the lack of sleep, sleep
deprivation and intermittent sleep, leads to the activation of
the oxidative stress production mechanism in various organs,including the brain. This high oxidative stress condition, if
transient and mild in severity, can be managed by activating
anti-oxidative enzymes, such as superoxide dismutase (SOD)
and glutathion peroxidase (GPX) to eliminate oxidative
stress. However, chronic impairment of sleep quality or
the presence of severe and persistent sleep disorders, suchas SAS, leads to damage to brain cells and a subsequent
increase in the risk of cognitive impairment, depression andanxiety 53). Melatonin, an anti-oxidant secreted during sleep,
protects the brain from oxidative damage during sleep 20).
Since melatonin secretion decreases with age, the defense
function against oxidative stress also declines with age.
In experimental animals, sleep disruption resultes indecreases in SOD activity and the level of reduced glutathione(a substrate for GPX) and an increase in the level of oxidized
glutathione in the brain. Continued arousal has also beenshown to increase the level of oxidative stress in the brain 53).
These observations suggest that sleep protects the brain by
reducing oxidative stress.
8-OHdG is an oxidative damage product of guanine,
a component of DNA. Several reports have been available
regarding the correlation between sleep quality and urinary
8-OHdG level. In a study involving 146 workers in sales
occupations, the creatinine-adjusted urinary concentrationof 8-OHdG showed a U-shape correlation with the previous
night’s sleep length in women, but not in men, with theminimum value recorded in women with a sleep length of
7 to 7.5 hours 54). In a clinical study conducted with αGel
Mat as the test mattress in 20 subjects with a Pittsburgh
Sleep Quality Index (PSQI) of ≥ 7, a significant decrease in
the creatinine-adjusted urinary concentration of 8-OHdG
was observed 47). In another study, night sleep deprivation in
healthy subjects resulted in no significant change in urinary
8-OHdG concentration 55). In this sleep deprivation study,
while subjective sleepiness was improved to the baseline
level after 1 night of normal sleep ( 7 hours), fatigue,
confused feeling and higher cognitive functions could only
be improved after at least 2 nights of normal sleep. Thus,
controversy remains regarding the relationship between
sleep quality and 8-OHdG.
SAS is a major condition associated with poor quality
sleep. In particular, obstructive sleep apnea (OSA) has
been associated with abnormalities of various cytokines,
including inflammatory cytokines such as tumor necrosis
factors (TNF-a) and interleukins (IL)-1 and -6, adipocytokines
such as leptin, adiponectin and plasminogen activator
inhibitor-1 (PAI-1), and vascular endothelial growth factor(VEGF) 56, 57). OSA patients have significantly higher levelsof thiobarbituric acid reactive substances and peroxides
and a significantly lower level of antioxidant enzyme
paraoxonase-1 58). OSA has also been associated with anincreased activity of the sympathetic nervous system,suggesting the involvement of sympathetic activity in cytokine
abnormalities in OSA 57). It has also been suggested thatintermittent hypoxia in OSA mimics ischemic reperfusion oftissues and resulting hypoxic stress and oxidative stress leadto the activation of transcription factors and the subsequent
induction of expression of various cytokines.
Through these mechanisms, poor quality sleep leads toincreased oxidative stress. In the present study, the use of
the test mattress resulted in a significant improvement in thecreatinine-adjusted urinary concentration of 8-OHdG from9.87 ± 0.84 ng/mg crea at baseline to 7.13 ± 0.45 ng/mg crea
at week 4, which is comparable to the corresponding changereported in a previous study (from 7.66 ± 1.87 ng/mg crea
at baseline to 6.38 ± 1.87 ng/mg crea at week 4), suggestingthat an improvement in sleep quality led to a reduction inoxidative stress. However, the precise mechanism for thisremains unknown. Although no significant change wasobserved in salivary melatonin level in this study, increased_ 117 _

Sleep Study of a Mattress Highly Rated in a Post-Marketing Survey
melatonin secretion resulting from improved sleep quality
is expected to lead to reduced oxidative stress via the antioxidative effect of melatonin 20). It is impossible to determine
the daily melatonin secretion only by measuring the salivary
melatonin level once in the morning. Future studies should
therefore include measurement of the urinary concentrationof melatonin metabolites, such as 6-hydroxy-melatonin
sulfate 59).

Hormonal age

The secretion of growth hormone (GH) and its second
messenger hormone IGF-I start to decline around 30 years ofage, and decreased levels of these hormones lead to a poorer
prognosis and impaired QOL 60). Decreased secretion of these
hormones is referred to as somatopause, which not only causes
reduced cell divisions and protein synthesis, but is also deeply
associated with declines in neuropsychiatric function,
reproductive function, digestive function and bone metabolism.
Somatopause has also been associated with lifestyle-relateddiseases, such as fatty liver 61). Lifestyle improvement toprevent the decline of GH/IGF-I secretion is effective forthe maintenance of youth and health. High-quality sleep,
adequate exercise, appropriate protein/amino acid intake,and eating on hunger and the resulting promoted ghrelinsecretion are known to promote GH secretion. In contrast,lack of sleep, lack of exercise, impaired sleep quality due
to psychosomatic stress and excessive carbohydrate intake
are associated with suppressed GH secretion. SAS is
associated with a poorer sleep quality, as well as decreased
GH secretion and a subsequent decrease in IGF-I levels
during sleep, and therefore it requires active intervention. A
significant increase in IGF-I level (+ 10.2 %) was observedin the present study. This is likely because improved sleep
quality achieved by the use of the test mattress resulted inincreased GH secretion and a subsequent increase in the
IGF-I level.
Dihydroepiandrosterone (DHEA) is an important hormone
for the determination of hormonal age. DHEA is the mostabundant steroid hormone in the human body as a precursorof more than 50 kinds of hormones, including reproductive
hormones and cortisol 62). It is secreted from the adrenal
cortex and its secretion declines with age. DHEA in circulation
exists either as the stable sulfate form (DHEA-s), which
accounts for 99% of all DHEA, or as free DHEA, which
accounts for 1%. Thus, the routine measurement of DHEA
targets DHEA-s. Decline in DHEA-s secretion is referred
to as adrenopause, which has been associated with impaired
immunological function and decreased resistance to stress,
as well as increased risk of metabolic syndrome (MetS), fatty
liver, diabetes, hyperlipidemia, hypertension, osteoporosis
and other lifestyle-related diseases 63).
Various steroidal hormone metabolites are present inurine; 17-ketosteroid (17-KS) is a group of neutral steroids
having a keto group at position C-17 among C-19 compounds,
which account for a large proportion of all androgens. 17KS is further divided into 11-deoxy-17-KS and 11-oxy17-KS; the former consists of 3 fractions (androsterone,
etiocholanolone and DHEA) which are produced in the adrenal
gland and testis, while the latter consists of 4 fractions(11-keto-etiocholanolone, 11-OH-androsterone, 11- OHetiocholanolone and 11-keto-androsterone) which are derived
from glucocorticoid (cortisol) 64). In healthy adult men, about

a quarter of all 17-KS compounds originate from the testis
and the remaining from the adrenal gland. In contrast, themajority of 17-KS compounds in children and womenoriginate from the adrenal gland and are derived from DHEA
and DHEA-s. In the present study, significant increases
in the levels of androsterone and etiocholanolone, but not
11-oxy-17-KS fraction steroids, were observed following
the use of the test mattress. The fact that only the levels of
11-deoxy-17-KS fraction steroids (i.e. DHEA metabolites
originating from the adrenal cortex) were increased suggeststhat the use of the test mattress leads to an increase in the
DHEA-s/cortisol ratio in circulation. Although no significant
change was observed in the circulating DHEA-s or cortisol
level in this study, the results of analysis of urinary steroid
hormone metabolites suggest that the use of the test
mattress resulted in improved sleep quality and a subsequent
improvement in the psychosomatic stress balance.

Psychosomatic stress

In an anti-aging medical checkup, psychosomatic stressis assessed based on the serum DHEA-s/cortisol ratio 62). The
intensity of psychosomatic stress, resistance to stress, andstress balance are generally evaluated based on the cortisol
level, DHEA-s level, and DHEA-s/cortisol ratio, respectively.
The DHEA-s/cortisol ratio is generally considered optimal
if it is 20-25 μg/dl, suboptimal at 15-20 μg/dl, borderline at
10-15 μg/dl and poor at <10 μg/dl 65). The detection of anabnormally high level of DHEA-s warrants close examinationof the adrenal gland.
In this study, we observed no significant change in theserum DHEA-s or cortisol level, rather we noted increases
in DHEA metabolites in the analysis of urinary 17-KS
fractions (steroid hormone metabolites), as mentioned above,
suggesting improved stress hormone balance as a result of
the use of the test mattress.
Psychosomatic stress is also closely related to the onset
of depression and affects serotonin/adrenaline metabolism.
In the human body, 90% of serotonin is distributed in theintestine, 8% in the blood and 2% in the brain. Intestinal
serotonin is involved in gastrointestinal peristalsis andpromotes digestion and absorption. In the stomach, serotonergic
nerves distributed in the antrum induce contraction of thepyloric sphincter. In blood, the majority of serotonin ispresent in platelets and it contributes to vasoconstriction
and subsequent hemostasis. Massive destruction of platelets
due to injury or other causes and the subsequent release ofserotonin into blood causes nausea/vomiting. Serotonin isalso suggested to be involved in migraine attacks, as evidenced
by a decreased serotonin level in platelets and an increased
serotonin level in plasma during a migraine attack 66). Brain
serotonin interacts with the sympathetic nervous system
to adjust the body’s internal clock and maintain arousal(a condition in which a person can vigorously perform
activities). Serotonin is also involved in the control of moodand emotion and the suppression of impulsive and dependent
behaviors by regulating dopamine and noradrenaline actions.
Other functions of serotonin include the suppression ofpain sensory nerve activity and the regulation of memory
and learning processes in the hippocampus. Although thesignificance of the plasma serotonin level has not been fully
elucidated, several reports have shown increased plasma
serotonin levels in association with increased psychosomaticstress induced by visual display terminal (VDT) work 67) and_ 118 _Glycative Stress Researchin severely depressed patients with strong suicidal ideation 68).
High plasma serotonin levels have also been reported indiabetic patients 69). Serotoin also contributes to the progressionof arteriosclerosis by promoting vascular smooth muscle
contraction and platelet aggregation 70). The platelet poor
plasma (PPP) serotonin to whole blood (WB) serotonin ratio(PPP/WB) significantly correlates with the Framingham
Risk Score (FRS) for the 10-year risk of having a coronary
heart disease, and thus can be a new biomarker for predicting
the risk of arteriosclerotic cardiovascular diseases 71). In thepresent study, there was a significant decrease in the plasma
serotonin level from 211.15 ± 32.29 ng/mL at baseline to197.05 ± 32.95 ng/mL at week 4, suggesting reduced
psychosomatic stress. It is also likely that a reduced plasma
serotonin level has a favorable effect on serotonin-relatedheadaches. In contrast, one study showed that foot massaging
results in a decreased plasma noradrenaline level and decreased
blood pressure and pulse rate, whereas the plasma serotoninlevel increases 72). Since different results may be obtained byassessing the short-term change in the plasma serotonin level
or by measuring the serotonin level before its change isobserved, further analyses are needed to establish the optimal
method for assessing plasma serotonin levels.
Change in the noradrenaline level is associated with adepressive state. Serotonin-noradrenaline reuptake inhibitors(SNRIs) exert an anti-depressive effect by increasing theavailability of serotonin and noradrenaline in postsynaptic
cells in the brain. Recent evidence suggests reuptake of
dopamine by noradrenaline autoreceptors, suggesting thepossibility of enhanced dopamine signaling by SNRIs.
Tricyclic antidepressants are known to increase not only
plasma serotonin but also noradrenaline levels 73). Exercise
therapy for depression treatment is suggested to improve
psychiatric symptoms by stimulating the noradrenergic
nervous system and suppressing depression by maintaining
activity 74). As a measure for improving the psychosomaticfunction of young women in the late luteal phase, comfortableself-paced exercise has been shown to significantly increase
the plasma noradrenaline level and increase the psychologicalscores for vitality and pleasure 75).
The plasma noradrenaline level is used for the diagnosisof orthostatic hypotension. The diagnosis of orthostatic
hypotension is based on a ≥ 20 mmHg decrease in the systolicblood pressure or a ≥10 mmHg decrease in the diastolicblood pressure in a standing test or a head-up tilt test, andis further supported by the absence of an increased plasma
noradrenaline level in patients with orthostatic hypotension 76).
The plasma noradrenaline level is also used as a measure ofshort-term change in stress levels, for such purposes as stress
reduction during indwelling needle puncture for securing avenous line 77). Essential hypertension patients are known tohave higher resting plasma noradrenaline levels compared toindividuals with optimal blood pressure 78).
Little is known about the significance of measuring a
resting plasma noradrenaline level. The present results showeda significant increase in this parameter from 508.30 ± 46.90
pg/mL at baseline to 634.70 ± 54.60 pg/mL at week 4. The
mean systolic and diastolic blood pressure measurements
were 117.30 ± 3.40 and 73.40 ± 2.50 mmHg, respectively,
which included the data from the hypotensive subjects withlow plasma noradrenaline levels. Autonomic nervous systemdisorder due to excessive psychosomatic stress is one of
the known causes of hypotension 79-81). Thus, improved
psychosomatic stress balance resulting from improved sleep
quality is expected to lead to improvement of hypotension.

The increased noradrenaline levels in these hypotensive
subjects may be reflected in the present results.

Glycative stress

A logistic multiple regression analysis showed a correlation
between decreased sleep quality and an increased risk of
MetS 82). This analysis also showed an increased prevalenceof hypertriglyceridemia and a high insulin resistance index(HOMA-IR) in subjects with a sleep length of ≤ 5 hours or ≥ 9hours and also an increased prevalence of hypertriglyceridemia,
hypo-HDL-cholesterolemia and high fasting insulin and high
HOMA-IR in the poor sleep group 82). In a study to compare
the prevalence of arteriosclerotic risk factors between 207
OSA patients (OSA group) and control subjects who
underwent a comprehensive medical checkup (control group),a significantly higher prevalence of visceral fat obesity,
hypertriglyceridemia and hypo-HDL-cholesterolemia, as wellas higher fasting glucose levels (findings suggestive of
insulin resistance) were observed in the OSA group 83). In a
study to examine the association between the apnea hypopnea
index (AHI) and various physical parameters in 121 men who
underwent a comprehensive medical checkup, significant
correlations were observed between the AHI and BMI,
blood pressure, HDL-C, HOMA-IR and blood insulin
concentration 84). A study on the association between OSA
and insulin resistance/MetS showed a high prevalence of
insulin resistance in OSA (58.1%) and a significant correlation
between insulin resistance and BMI, liver enzyme, triglycerideand HDL-C levels 85). An association between SAS andHDL-C has also been suggested in other studies, althoughsome studies have demonstrated an association between
poor quality sleep and decreased HDL-C 86, 87), while yetothers showed no significant change in HDL-C 88, 89).
Abnormal changes in lipid metabolism parameters
observed in this study included increased TC (+ 6.2%),
increased LDL-C (+ 5.8%) and increased HDL-C (+ 7.5%)
levels. The mean baseline LDL-C level was 120.50 ± 7.60
mg/dL, which included the data from subjects with hypoLDL-cholesterolemia. The observed increase in LDL-C level
may reflect an improved physical condition and appetite in
the subjects with low baseline LDL-C levels and a subsequent
increase in LDL-C levels. The week-4 LDL-C level was
127.50 ± 7.20 mg/dL. LDL-C levels less than 130 mg/dL
should not raise any concern. In contrast, the HDL-C levelsignificantly increased from 73.70 ± 5.10 mg/dL at baseline
to 79.20 ± 5.20 mg/dL at week 4. Although the only factor
known to increase the HDL-C level was exercise/physicalactivity, the results of the present study suggest the potentialof improved sleep quality as an additional factor contributing
to an increased HDL-C. The mechanism by which improved
sleep quality leads to increased HDL-C remains to beelucidated. The observed increase in TC was likely to be theresult of increases in both LDL-C and HDL-C levels.
We measured the level of pentosidine, an advanced
glycation end product (AGE), as a measure of glycative
stress 90). The pentosidine level changed from 0.04 ± 0.01
μg/mL at baseline to 0.06 ± 0.01 μg/mL at week 4, witha significant increase observed only in its percent change.
This change in pentosidine level was considered negligible,
as the pre- and post-intervention change was within therange of physiological variation; the absolute values wererelatively small, and the statistical analysis of the measured
values and their change showed no significant difference.

_ 119 _

Sleep Study of a Mattress Highly Rated in a Post-Marketing Survey
Thus, these changes were considered negligible.

SafetyNo adverse event was observed in association with theuse of the test mattress. Although significant changes insome electrolytes (sodium, potassium and chloride) wereobserved in blood biochemistry, these changes were mild
and within the range of physiological variation and considered
likely due to thickening of blood caused by the bloodcollection procedure. Thus, these changes were considerednegligible.

increase in HDL-C level (a lipid metabolism parameter). In
the analysis of urinary 17-KS steroid hormone metabolites,no significant change was observed in cortisol metabolites
while significant increases were observed in DHEA
metabolites. Other findings included a significant increase in
the plasma noradrenaline level and a significant decrease in
the plasma serotonin level, changes that improve a depressive
state. These findings suggest that the use of the test mattress
improves sleep quality and has favorable effects on various
physical parameters, including parameters related to oxidative
stress, psychosomatic stress and lipid metabolism.

Acknowledgements

Conclusion

We conducted a non-controlled open-label study of the
4-week use of the test mattress in 11 men and women witha sleep disorder who had a PSQIG score of ≥7 according
to the PSQI-J. We observed a significant improvement insubjective symptoms, as well as a significant decrease in
the creatinine-adjusted concentration of 8-OHdG in urine(a measure of oxidative stress), a significant increase in
IGF-I level (a measure of hormonal age), and a significant

A part of this work was supported by JSPS KAKENHI
Grant Number 26350917.

Conflict of Interest Statement

The present study was partly supported by Nishikawa
Sangyo Co., Ltd.

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