Glycative Stress Research
Online edition : ISSN 2188-3610
Print edition : ISSN 2188-3602
Received : May 13, 2015
Accepted : May 29, 2015
Published online : June 30, 2015

Original article

A placebo-controlled, randomized, single-blind, parallel-group comparative study
to evaluate the anti-glycation effect of a functional soymilk beverage supplemented
with rice bran/rice bran oil
Yoshikazu Yonei1 1), Masayuki Yagi 1), Umenoi Hamada 1), Ikuo Imamura 2),
Sumie Okamura 3), Kazushi Yamamoto 3), Motonobu Matsumoto 4)
1) Anti-Aging Medical Research Center/Anti-Glycation Research Center, Graduate School of Life and Medical Sciences,
Doshisha University, Kyotanabe, Kyoto
2) Senrigaoka Kyouritu Clinic, Settsu, Osaka3) New Material Utilization Business Development Project, Sunstar Inc., Takatsuki, Osaka4) Research & Development Division, Health & Beauty Business Department, Sunstar Inc., Takatsuki, Osaka

Abstract

Objective: We evaluated the effect on glycation stress of a consecutive 12-week ingestion of a soymilk beverage supplemented
with rice bran and rice bran oil (test diet) in a placebo-controlled, randomized, single-blind, parallel-group comparison design.
Specifically, changes in soluble receptor for advanced glycation end product (sRAGE) and endogenous secretary RAGE
(esRAGE), among others, were evaluated.
Methods: : Women with high glycation stress, defined as an autofluorescence (AF) intensity of ≥ 2.0 on an AGE Reader, witha mean age of 47.24 ± 7.24, were randomized to receive either a control soymilk beverage (placebo; 11 subjects) or the test diet
(12 subjects, daily intake of rice bran and rice bran oil of 8.2 g and 2.7 g, respectively). After the 12-week ingestion of placeboor the test diet, subjects were assessed for skin elasticity, as measured with Cutometer, skin AF intensity, glycation stress-relatedparameters in blood, including carboxymethyl-lysine (CML), sRAGE and esRAGE, and skin color as measured with a colordifference meter.
Results: The following parameters were significantly improved in the test group compared to the control group: decreased
CML and improved skin elasticity index R6 in an overall analysis; and a slower increase in plasma glucose level and a slower
decrease in skin elasticity index R7 in a subclass analysis in the subjects with a BMI of ≥ 25. Although no significant intergroupdifference was observed, the following parameters were significantly improved only in the test group: decreased HbA1c,
increased sRAGE, increased esRAGE, and improved melanin index for skin color difference in the upper arm. No adverse
event occurred during or after the study period.
Conclusion: The ingestion of the test diet resulted in significant improvement in glucose metabolism, CML content in bloodand skin elasticity, as well as a significant increase in esRAGE, a decoy receptor for AGEs. These results suggest that the test
diet reduces glycation stress.

KEY WORDS: Rice bran, rice bran oil, advanced glycation end products, glycation stress
Introduction

A variety of byproducts can be obtained from rice,
Japan’s staple food, such as rice bran and rice bran oil. Ricebran consists of rice pericarp, seed coat, perisperm, aleurone
layer, and other byproducts of the pearling (polishing) ofbrown rice into white rice, and is known to be rich in oil,protein, minerals and B vitamins (especially B1) 1-7). Ricebran oil is a vegetable oil extracted from rice bran; it ischaracterized by a high ratio of oleic acid to total fatty acids,a high concentration of vitamin E and high resistance tooxidation on heating 8).
A previous in vitro study evaluated the effect of HighBref T M (Sunbran Co., Ltd., Yamagata, Japan), a functional
material made of powdered rice bran, on the inhibition of

Corresponding author:
1-3 Tatara Miyakodani, Kyotanabe City, Kyoto 610-0321, Japan
Anti-Aging Medical Research Center/Anti-Glycation Research Center,
Graduate School of Life and Medical Sciences, Doshisha University
Prof. Yoshikazu Yonei
TEL &FAX: 0774-65-6394 Email:yyonei@mail.doshisha.ac.jp
Contact for Co-authors: Masayuki Yagi: yagi@ yonei-labo.co.jp;
Umenoi Hamada: hamada@yonei-labo.co.jp; Ikuo Imamura: uraboshi@polka.ocn.ne.jp ;Sumie Okamura: sumie.okamura@jp.sunstar.com; Kazushi Yamamoto: kazushi.yamamoto@jp.sunstar.com;
Motonobu Matsumoto: motonobu.matsumoto@jp.sunstar.com_ 80 _

Glycative Stress Research 2015; 2 (2): 80-100(c) Society for Glycation Stress ResearchGlycative Stress Researchadvanced glycation end products (AGEs) produced by aglucose-human serum albumin (HSA) reaction. Both the
hot water and ethanol extracts of High-Bref T M inhibited the
production of fluorescent AGEs in a dose-dependent manner,suggesting that this material has an anti-glycation activity 8).
The objective of the present study in humans was to evaluate
the effect of a soymilk beverage supplemented with rice bran
and rice bran oil as the test diet, in terms of glycation stress
reduction.

Methods
Subjects

Healthy Japanese women between 35 and 60 years of age
who 1) have been found to have high blood glucose or HbA1clevels, 2) have diabetic parents or close relatives, and/or 3)
have a waist circumference of 90 cm or more were preferably
recruited. Eligible subjects were selected according to thecriteria below. A total of 67 subjects who provided written
informed consent to participating in the study underwent
screening assessments, including skin AGE deposition
and blood HbA1c level, and 25 subjects with a skin AGEs
deposition of ≥ 2.0, which is the average for 50-year-old
women (= 50 years of glycation age) and the highest HbA1clevels were eventually included in the study. Those with aglycation age younger than the chronological age, i.e. with askin AGE deposition lower than the average for the age of thesubject, were excluded. The principal investigator determinedthe eligibility of each candidate subject using the following
inclusion/exclusion criteria. Specifically, subjects were
excluded if they: 1) were smokers, 2) had an average sleep
time of less than 5 hours/night, 3) were regularly consuming
an anti-glycation diet and/or using an anti-glycation cosmetic,
4) were regularly consuming an anti-hyperglycemic diet, 5)
were regularly consuming a soymilk beverage, rice bran orrice bran oil, or health food containing any of these as the main
ingredient, 6) had food allergy or were allergic to specific foodmaterials (especially soybean allergy), or 7) were consideredineligible for other reasons as assessed by the principal
investigator.

Japan). Subjects were given a sufficient explanation of the
purpose and details of the study and participants’ rights andprovided written informed consent. They were also told thatearly withdrawal from the study would not disadvantage themat all.

Test diet

A beverage containing rice bran and rice bran oil wasused as the test diet. The test and control (placebo) diets were
provided by Sunstar Inc. (Takatsuki, Osaka). The daily intakesof each ingredient are shown in Table 1. The differential
compositions of the test and control diets are shown in Table 2.
The daily intake of each ingredient was as follows: 8.2 g ofrice bran and 2.7 g of rice bran oil in the test group, and 2.0 g
of rice flour and 5.5 g of corn oil in the control group.
The safety of the test diet was confirmed as follows. All
ingredients of the test diet have long been consumed andrecognized as safe food ingredients. Also the ingredients
being tested are contained at concentrations lower than thesafe concentrations demonstrated by safety testing. Rice flourand corn oil, which constituted the control diet in place of theingredients being tested, are also widely distributed in foodand have never been reported to cause any serious adverse
events. The test diet is produced by a food manufacturing
process which is strictly controlled to ensure product quality
from the receiving of raw materials through packaging. The
following batch release criteria are being applied to assure
the safety of the test diet as a food product. For productidentification, the test diet had to be a nearly homogeneous,milky-brown liquid while the control diet had to be a nearlyhomogeneous, milky colored liquid. Both products had to be
negative for coliform bacteria, with viable bacteria and fungal/
yeast counts of 0 cell/ml. A pilot study was conducted to test
Table 1. The estimated daily intake of ingredients/nutrientsof the test and control diets
Control diet (placebo) (195 g)

109
3.4
4.8
9.5
6.4
3.5

110
2.1
6.5
9.6
1.1
3.5

Calorie ( kcal)
Protein (g)Fat (g)Carbohydrates (g)Dietary fiber (g)Solid soybean

Study design

This placebo-controlled, randomized, single-blind,parallel-group comparative study was designed to include 25
eligible subjects who started taking the test diet as the fullanalysis set (FAS), which was further divided into the control(12 subjects) and test (13 subject) groups. Subjects allocatedto the control and test groups consumed a control diet (placebo)and the test diet for 12 weeks, respectively. During thisperiod, clinical evaluations were performed at four time points(weeks 0, 4, 8 and 12) and blood/urine tests and skin function
test performed at weeks 0, 8 and 12.
Each subject consumed a bottle (195 g) of the test or
control diet once daily before the evening meal. Subjects were
instructed to consume the investigational diet even when nothaving a meal. In the event of a missed dose, the subject drankthe investigational diet as soon as possible within the day. The
mean compliance rate was 99.8% in the control group, 98.5%
in the test group, and 99.1% in the entire study population.
This study was conducted between September 2013 andDecember 2013 at Senrigaoka Kyouritu Clinic (Settsu, Osaka,

Test diet (195 g)

Table 2. Compositions of the test and control diets
Test dietControl diet

Soymilk
Rice bran

Soymilk
Rice flour
Corn oil

Rice bran oil
Indigestible dextrin
Honey
Isomaltooligosaccharide
Maltitol
Sucralose
Emulsifier
Stabilizer(polysaccharide thickener)―
Honey
Isomaltooligosaccharide
Maltitol
Sucralose
Emulsifier
Stabilizer(polysaccharide thickener)

The control diet is formulated with rice flour and corn oil, rather than rice bran,rice bran oil and indigestible dextrin, as contained in the test diet.

_ 81 _

Anti-Glycation Effect of a Functional Soymilk Beverage Supplemented with Rice Bran/Rice Bran Oil
administration of the test diet at a dosage of 16 g/day for 12
weeks to 13 volunteers and confirmed no adverse event related
to the test diet (Sunstar in-house data). In another pilot study,
a total of 8 volunteers were given the test diet at a dosage of
20 g/day for 8 weeks and no abnormal changes were observedin liver function or routine laboratory parameters (Sunstar inhouse data).

Test procedure

Anti-Aging QOL Common Questionnaire (AAQol)
Subjective symptoms were divided into physical andmental symptoms and evaluated on a 5-point scale using
the Anti-Aging QOL Common Questionnaire (AAQol), as
described previously 8, 9).
Physical examination
The following physical parameters were recorded: height(cm), body weight (kg), body composition (body fat percentage,
fat mass, fat-free mass, muscle mass, and basal metabolic rate),systolic and diastolic blood pressure (mmHg) and pulse rate
(beats/min). Body composition was analyzed using Well Scan
500 (Canon Lifecare Solutions Inc., Chuo-ku, Osaka).
Blood biochemistry
The following routine laboratory parameters were
evaluated: hematological parameters, including white blood
cell (WBC) count, red blood cell (RBC) count, hemoglobin(Hb), hematocrit (Ht), mean corpuscular volume (MCV),
mean corpuscular hemoglobin (MCH), mean corpuscularhemoglobin concentration (MCHC), differential WBC
count, and platelets; biochemical parameters, including total
protein, albumin, total bilirubin, AST (GOT), ALT (GPT),
alkaline phosphatase (ALP), lactate dehydrogenase (LDH),
γ-GTP, blood urea nitrogen (BUN), creatine phosphokinase(CPK), creatinine (CRE), uric acid (UA), sodium (Na),chloride (Cl), potassium (K), calcium (Ca), iron (Fe), totalcholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol(HDL-C), triglyceride (TG), fasting plasma glucose (FPG),
HbA1c [JDS] [NGSP], insulin (immunoreactive insulin: IRI)
and glycated albumin; and AGEs and their intermediates,
including carboxymethyl-lysine (CML), pentosidine, and3-deoxyglucosone (3DG). The serum concentration of soluble
receptor for AGE (sRAGE) was measured with Human
RAGE Quantikine ELISA Kit DRG00 (R&D Systems Inc.,
Minneapolis, MN, USA) and that of endogenous secreted
RAGE (esRAGE) was measured with esRAGE Human
ELISA Kit K1009-1 (B-BridgeInternational Inc., Cupertino,
CA, USA). Except for 3DG, which was measured at SRL,
Inc. (Tokyo, Japan), all laboratory parameters were measured
at LSI Medience Corporation (Tokyo, Japan).
Skin AGE fluorometry
Skin AGE deposition was analyzed as a measure ofglycation using AGE Reader™ (DiagnOptics, Groningen,
Netherlands) 10, 11). This non-invasive test detects uniqueautofluorescence (AF) emitted from AGEs accumulated
in skin tissue as excited by ultraviolet irradiation. Skin AF
emission has been shown to be well correlated with the skinaccumulation of typical AGEs, such as fluorescent pentosidine
and non-fluorescent CML, in studies using skin biopsies fromdiabetic and dialysis patients. As described previously 12), a
subject was instructed to rest his/her cheeks in his/her hands,
and AF intensity was measured at a site about 10 cm fromthe elbow on the medial aspect of the right upper arm. The

average of three measurements at the same site was reported.
CML content in stratum corneum
Stratum corneum was sampled using the tape stripping
technique and used for protein extraction and the subsequent
measurement of CML and protein contents 13). CML wasquantified using N ε - (carboxymethyl) lysine ELISA Kit
CY8066 (CircuLex Inc, Nagano, Japan). A sample of stratum
corneum was collected from the medial aspect of the rightupper arm (about 10 cm from the olecranon toward theshoulder).
Skin elasticity test
Skin elasticity, as previously described 14-16), was measured
using Cutometer ( Dual MPA580, Courage + Khazaka,
Cologne, Germany) 17-19). Using a single suction technique, fivemeasurements were obtained at and around the measurementsite. The average of three measurements, excluding the
maximum and minimum values using the value of elasticity
index R2 as the reference value, was reported. This test was
performed in the left cheek (at the center between the bottomof the earlobe and the lip end) and the medial aspect of theright upper arm (at about 10 cm from the olecranon toward theshoulder) on a subject placed in a supine position.
Skin color difference analysis
Skin color difference was analyzed using a spectrophotometer(CM-600d, Konica Minolta Inc., Tokyo, Japan), as described
previously 20) . Five measurements were obtained at the centerof the measurement site. The average of three measurements,
excluding the maximum and minimum values using L* value
as the reference value, was reported. This test was performed in
the left cheek (at the center between the bottom of the earlobe
and the lip end) and at the medial aspect of the right upper arm(at about 10 cm from the olecranon toward the shoulder).
All of these skin parameters were measured after washing
the measurement site or face and a 20-minute acclimation ina room with temperature and humidity controlled at 21°C and50%, respectively.
Statistical analysis
Results were reported as the mean ± standard deviation.
For AAQol assessment, Dunnett’s test was used to compare
data obtained before diet intake with those obtained 4, 8 and
12 weeks after diet intake, and the unpaired t-test was used tocompare absolute and percent changes from baseline (before
diet intake) between groups. For measured data, Dunnett’s test
was used to compare data obtained before diet intake with thoseobtained 8 and 12 weeks after diet intake, and the unpaired
t-test was used to compare absolute and percent changes frombaseline (before diet intake) between groups. All statisticalanalyses were performed using SPSS Statistics 20.0 software(IBM Japan, Tokyo, Japan). Differences were consideredsignificant for a two-tailed significance level of 0.05.
Ethical considerations
This study was conducted at Senrigaoka Kyouritu Clinic,
Settsu, Osaka, in compliance with the ethical principles
based on the Declaration of Helsinki, the Private Information
Protection Law and the Ministerial Ordinance on Good
Clinical Practice (GCP) for Drugs (Ministry of Health andWelfare Ordinance No. 28 of March 27, 1997). The protocolof this study was reviewed for the ethical aspects andappropriateness of the study and approved by the institutional
review board at Tokyo Synergy Clinic (Chuo-ku, Tokyo,_ 82 _Glycative Stress Research

Japan). The study was conducted according to the approved
protocol. This study is registered with UMIN (#000017141).

Results

Analysis sets

The FAS consisted of 25 subjects (mean age 47.2 ± 7.2
years) who were enrolled in the study and consumed theinvestigational diet. One subject in the control group wasprematurely withdrawn from the study and the remaining 24
subjects completed the study. Another subject in the control
group who was taking more than one supplement was excluded
from the analysis, and the remaining 23 subjects were includedin the per-protocol set (PPS) and used for efficacy analysis.

AAQol

The results of AAQol assessment are summarized inTables 3 and 4.
The parameters that were significantly improved after
diet intake only in the test group were physical symptom“easily breaking into a sweat” at week 12 ( p = 0.038) and skin
symptom “make-up does not apply smoothly” at week 8 ( p= 0.037). No significant intergroup difference in scores wasfound for these parameters.
The only parameter that was significantly improved in
the test group compared to the control group was lifestyle
behavior “exercise”, in particular the absolute change in scorefrom baseline to week 4 ( p = 0.029), absolute and percent
changes from baseline to week 8 ( p = 0.007 and 0.014,
respectively), and absolute and percent changes from baseline
to week 12 ( p = 0.036 and 0.032, respectively).

Insulin resistance

The results of analysis of insulin resistance-relatedparameters and subclass analysis are shown in Tables 5 and 6,
respectively.
An overall analysis with the PPS (n = 23) showed thatsignificant improvements were observed in HbA1c [JDS]at week 8 ( p = 0.015) and HbA1c [ NGSP] at week 8 ( p =0.009) after diet intake in the test group, with no significant
difference between groups.
In a subclass analysis of the subjects with a body massindex (BMI) of ≥ 25 ( i.e. the cut-off for mild obesity) (n =19), significant improvements were observed in HbA1c [JDS]at week 8 ( p = 0.025) and HbA1c [ NGSP] at week 8 ( p =0.015) after diet intake in the test group. Increased FPG level
was noted at week 8 in both the test and control groups, witha significantly greater increase in the control group comparedto the test group ( p = 0.023 and 0.023 for the absolute andpercent changes at week 8, respectively).

AGE-related parameters

The results of analysis of AGE-related parameters andsubclass analysis are shown in Tables 7 and 8, respectively.
In the PPS (n = 23) analysis, 1 subject in the control group
was excluded due to a negative value of parameter [sRAGE- esRAGE]. Compared to the baseline values, significant
improvements were observed in skin AGE deposition, glycationage (calculated from skin AGE deposition) and the difference

between glycation age and chronological age at week 8 ( p =0.004 for all parameters) in the test group and at week 8 ( p =0.014 for all parameters), week 12 ( p = 0.001 for all parameters)in the control group. The parameters that were significantly
improved after diet intake only in the test group were sRAGE
at week 12 (p = 0.001), esRAGE at week 12 (p = 0.003), and[sRAGE - esRAGE] at week 8 (p = 0.040) and week 12 (p =0.002). The parameters with significant differences between
the test and control groups were the difference between
glycation age and chronological age at week 8 (p = 0.042 forintergroup comparison of measured values) (Fig. 1) and CML
at week 12 ( p = 0.047 for intergroup comparison of measured
values) (Fig. 2a).
In a subclass analysis of the subjects with a BMI of ≥25 (i.e. the cut-off for mild obesity) (n = 19), where 1 subject
in the control group was excluded due to a negative value ofparameter [sRAGE - esRAGE], significant improvements
were observed compared to the baseline values in skin
AGE deposition, glycation age (calculated from skin
AGE deposition) and the difference between glycation
age and chronological age at week 8 ( p = 0.002 and 0.037,
respectively) and week 12 (p = 0.049 and 0.003, respectively)
in both groups. The parameters that were significantly
improved after diet intake only in the test group were sRAGE
at week 12 (p = 0.001), esRAGE at week 12 (p = 0.003), and[sRAGE - esRAGE] at week 8 ( p = 0.030) and week 12 (p =0.001). A significant difference between the test and control
groups was observed in CML at week 12 ( p = 0.019 forintergroup comparison of measured values) (Fig. 2b).

Skin assessment

The results of analysis of skin-related parameters andsubclass analysis for the subjects with a BMI of ≥ 25 (i.e. thecut-off for mild obesity) (n = 19) are shown in Tables 9 and
10, respectively.
The only parameter that was significantly improved
after diet intake only in the test group was melanin index, as
determined by the measurement of skin color difference inthe upper arm, at week 8 ( p = 0.016). The parameters thatwere significantly worsened after diet intake only in thecontrol group were skin elasticity indexes R2 ( p = 0.003 atweek 8 and p = 0.003 at week 12) and R7 ( p = 0.004 at week8) measured in the cheek. The only parameter that showeda significant improvement in the test group compared tothe control group was skin elasticity index R6 measured in
the cheek. Although a significant intergroup difference wasseen in cheek R6 at week 0, an intergroup comparison of
the absolute change in this parameter showed a significant
improvement at week 8 in the test group ( p = 0.028, Fig.
3a). In a subclass analysis of the subjects with a BMI of ≥ 25
(i.e. the cut-off for mild obesity) (n = 19), the only parameterthat was significantly improved after diet intake only in thetest group was melanin index for skin color difference in theupper arm at week 8 ( p = 0.020). The parameters that weresignificantly worsened after diet intake only in the control
group were skin elasticity indexes R2 ( p = 0.027 at week
8 and p = 0.018 at week 12) and R7 ( p = 0.041 at week 8)
measured in the cheek. In both groups, a decrease in elasticity
index R7 in the upper arm was observed at week 12. In thecontrol group, the decrease in R7 was significant at weeks 8( p = 0.021) and 12 ( p < 0.001), with a significantly greater
decrease compared to the test group ( p = 0.013 and 0.016 forthe absolute and percent changes at week 12, respectively)(Figs. 3b and 3c).

_ 83 _

-

-

Mean

45.64 ± 7.05

SD

49.25 ± 7.57

-

0.951

2.64 ± 1.21

2.73 ± 1.10

11
0.772

1.73 ± 0.90

1.91 ± 0.83

11
0.346

1.64 ± 0.92

1.27 ± 0.65

Test group 12

11
0.076
0.053

3.58 ± 0.90
2.73 ± 1.49

3.17 ± 0.83

3.27 ± 1.68

11

0.834

1.55 ± 0.82

1.45 ± 0.69

_ 84 _
0.130
1.000

2.17 ± 0.72
1.64 ± 0.81

1.75 ± 0.75

1.64 ± 0.67

Test group 12

11

Early satiety

Anorexia

2.00 ± 1.00
1.58 ± 0.51

0.637
0.009

1.82 ± 1.08
2.08 ± 0.67

11

2.00 ± 1.00
1.33 ± 0.49
1.18 ± 0.40
1.92 ± 1.00
1.09 ± 0.30

0.159
0.086
0.818
0.311
0.194

1.82 ± 0.98
1.67 ± 0.78
1.18 ± 0.40
1.83 ± 0.72
1.55 ± 0.69

1.25 ± 0.45

1.27 ± 0.47

1.50 ± 0.67

1.18 ± 0.40

Test group 12

11

Test group 12

11

Control

Control

Control

2.27 ± 1.01

Control

1.50 ± 0.52

1.75 ± 0.87

1.64 ± 0.67

1.83 ± 0.58

1.73 ± 0.79

2.00 ± 0.60

1.18 ± 0.40

1.08 ± 0.29

3.91 ± 1.14

4.08 ± 0.79

1.36 ± 0.67

1.50 ± 0.67

1.45 ± 0.69

1.50 ± 0.80

2.18 ± 1.47

2.75 ± 1.06

3.09 ± 1.70

3.58 ± 1.00

1.45 ± 1.21

1.67 ± 0.65

1.91 ± 0.94

2.50 ± 0.67

2.82 ± 1.08

2.09 ± 0.83

11

-

-

-

0.943

0.160

0.818

0.945

0.532

0.942

0.976

0.862

1.000

0.958

0.285

0.780

0.698

1.000

1.000

0.973

1.000

0.963

1.000

0.903

0.414

0.275

0.753

0.076

0.809

0.188

1.000

0.252

0.951

0.395

-

SD p values

3.00 ± 0.85

-

-

Mean

8w

Test group 12

Test group 12

ThirstSkin problems

0.862

1.75 ± 0.87

1.92 ± 1.00

Controlgood healthNo feeling of

0.960

2.00 ± 1.18

2.09 ± 0.94

11

Control

0.068

0.698

2.33 ± 1.07

1.18 ± 0.40

1.83 ± 0.83

1.09 ± 0.30

Test group 12

11

ControlLethargy

0.432

1.25 ± 0.45

1.08 ± 0.29

thin

Test group 12

11

Control

0.499

4.18 ± 1.08

3.91 ± 1.22

Weight loss;

0.973

3.92 ± 1.00

4.00 ± 1.04

Test group 12

gain weight

Tendency to

0.798

1.45 ± 0.82

1.36 ± 0.67

11

Control

1.000

1.58 ± 0.67

1.58 ± 0.79

breathTest group 12

Control

11

Shortness of

0.559

0.414

1.58 ± 0.67

2.18 ± 1.40

1.42 ± 0.67

2.55 ± 1.57

Test group 12

11

Control

Palpitations

0.082

2.92 ± 1.00

2.33 ± 0.89

Test group 12

Control

Test group 12

Control

0.028

1.83 ± 0.83

1.33 ± 0.49

Control

0.252

2.50 ± 0.90

2.08 ± 0.79

Test group 12

Control

0.836

2.83 ± 1.11

2.67 ± 0.49-

Test group 12--

SD p values

4w

stiffness

Muscular pain/

Stiff shoulders

Eye pain

Blurry eyes

Tired eyes

Control

Mean

11

Age

Year Test group 12

0w

Age

n

Unit

Parameter

Physical symptoms

Group

Table 3. Results of AAQol assessment (physical and mental symptoms)

-

-

-

1.27 ± 0.47

2.17 ± 1.03

1.18 ± 0.40

1.50 ± 0.67

2.27 ± 1.27

2.08 ± 0.51

1.91 ± 1.22

2.00 ± 0.74

1.82 ± 0.98

2.00 ± 0.74

2.09 ± 1.04

2.08 ± 0.90

1.18 ± 0.40

1.08 ± 0.29

3.73 ± 1.10

4.17 ± 1.03

1.64 ± 0.67

1.83 ± 0.94

1.55 ± 0.69

1.75 ± 0.87

2.27 ± 1.19

2.75 ± 1.14

2.91 ± 1.76

3.67 ± 1.07

1.91 ± 1.04

1.58 ± 0.67

2.36 ± 1.29

2.58 ± 0.90

2.91 ± 1.45

0.943

0.013

0.818

0.416

1.000

0.009

0.848

0.978

0.719

0.492

1.000

0.521

0.698

1.000

0.766

0.831

0.083

0.524

0.834

0.087

0.630

0.275

0.260

0.027

0.043

0.397

0.143

0.138

0.731

0.836

-

SD p values

2.83 ± 1.11

-

-

Mean

12w
8w

12w

0.903 0.090 0.051

0.031 0.437 0.045

0.001 0.157 0.066

0.796 0.840 0.546

0.097 0.731 0.861

0.074 0.029 0.503

0.610 0.565 0.565

0.381 0.815 0.394

0.657 0.754 0.932

0.701 0.684 0.263

0.021 0.030 0.130

0.003 0.036 0.011

0.592 0.570 0.211

0.078 0.217 0.901

0.519 0.393 0.970

4w

8w

12w

0w

4w

8w

12w

Inter-group analysis
by measured values

0.764 0.149 0.134 0.183 0.338 0.017 0.015

0.048 0.475 0.058 0.907 0.075 0.432 0.190

0.001 0.290 0.015 0.029 0.454 0.217 0.639

0.346 0.723 0.336 0.655 0.868 0.528 0.829

0.055 0.648 0.618 0.708 0.111 0.459 0.619

0.033 0.031 0.680 0.495 0.486 0.359 0.985

0.610 0.715 0.715 0.952 0.708 0.506 0.506

0.451 0.729 0.586 0.849 0.546 0.677 0.335

0.714 0.599 0.925 0.484 0.683 0.633 0.572

0.318 0.801 0.342 0.895 0.904 0.886 0.540

0.040 0.021 0.253 0.699 0.159 0.296 0.337

0.003 0.023 0.008 0.853 0.118 0.415 0.222

0.630 0.123 0.201 0.802 0.597 0.602 0.379

0.063 0.178 0.406 0.612 0.053 0.097 0.638

0.809 0.718 0.623 0.865 0.688 0.657 0.889

4w

Inter-group analysis Inter-group analysis
by change values
by % change

Anti-Glycation Effect of a Functional Soymilk Beverage Supplemented with Rice Bran/Rice Bran OilPhysical symptoms

Mean
1.27 ± 0.47
1.92 ± 0.79
1.45 ± 0.69

1.27 ± 0.65

1.58 ± 0.67

1.18 ± 0.40

Test group 12

11

1.73 ± 0.90

1.73 ± 0.79

_ 85 _

2.18 ± 1.40

2.00 ± 1.26

11
2.55 ± 1.44

2.00 ± 1.10

Test group 12

11
3.18 ± 1.25

3.09 ± 1.30

11
1.91 ± 0.83

2.18 ± 1.08

11
1.45 ± 0.82

1.36 ± 0.67

11
1.17 ± 0.39
1.64 ± 0.92

1.25 ± 0.45

1.55 ± 0.93

11

0.467
0.778
0.268

2.25 ± 0.97
2.09 ± 1.22
2.08 ± 1.08

2.00 ± 0.85

2.27 ± 1.49

2.50 ± 1.00

11

Test group 12

11

Test group 12

11

0.948

1.64 ± 0.81

1.73 ± 0.65

11Control

0.763

1.92 ± 0.79

1.75 ± 0.75

Test group 12

urination

0.836

2.73 ± 1.49

2.91 ± 1.45

ControlFrequent

Control

Control

into a sweat

Easily breaking

Edematous

0.561

1.73 ± 1.19

1.55 ± 0.82

Test group 12
0.501

1.92 ± 0.79

0.613

2.18 ± 1.40

Control

1.58 ± 0.79

1.000

1.000

0.265

0.747

0.619

0.867

0.515

0.708

0.046

0.965

0.270

0.276

0.970

0.689

0.363

1.000

0.248

0.631

0.143

0.738

0.438

1.000

1.91 ± 1.30

11

Arthralgia

2.25 ± 1.14

1.18 ± 0.40

2.25 ± 0.97

Test group 12

11

Control

1.18 ± 0.40

Lumbago2.00 ± 0.74

1.67 ± 0.65

Test group 12

Control

Test group 12

Control

1.67 ± 0.89

1.50 ± 0.67

Test group 12

Control

2.17 ± 0.94

1.75 ± 0.62

Test group 12

Control

3.08 ± 1.38

2.75 ± 0.97

Test group 12

Control

2.33 ± 0.89

2.25 ± 0.97

Controldifficulty

HearingTinnitus

Dizziness

HeadacheGray hair

Hair loss

2.08 ± 1.16

1.75 ± 0.97

Test group 12

Control

11

Constipation

1.83 ± 0.58

1.42 ± 0.51

Test group 12

1.82 ± 1.08

1.55 ± 0.82

11Diarrhea

1.92 ± 0.90

1.33 ± 0.65

Test group 12

ControlsputumControl

Control

1.000

SD p values

11

SD

4w
1.58 ± 0.79

Mean

0w

1.58 ± 0.67

n

Test group 12

Group

Coughing and

Unit

colds

Liable to catch

Epigastralgia

Parameter
1.000

1.36 ± 0.67

2.00 ± 0.74

2.55 ± 1.51

2.08 ± 0.90

2.09 ± 1.22

2.00 ± 0.95

1.55 ± 1.04

2.00 ± 0.74

1.82 ± 1.33

2.25 ± 1.14

1.09 ± 0.30

1.50 ± 0.67

1.45 ± 0.82

1.17 ± 0.39

1.55 ± 0.69

1.58 ± 0.79

1.91 ± 0.83

2.17 ± 0.72

3.45 ± 1.29

3.00 ± 1.13

2.64 ± 0.92

2.42 ± 0.79

2.27 ± 1.49

1.50 ± 0.67

2.00 ± 1.00

1.67 ± 0.89

1.73 ± 0.90

2.25 ± 0.97

1.64 ± 0.81

1.83 ± 1.03

1.36 ± 0.67

0.215

0.495

0.398

0.268

0.778

1.000

1.000

0.327

0.973

1.000

0.721

0.758

0.747

0.619

0.466

0.887

0.708

0.046

0.318

0.492

0.173

0.818

0.393

0.585

0.401

0.633

0.845

0.011

0.376

0.651

0.924

SD p values

1.58 ± 1.00

Mean

8w

0.124
0.747
1.000
0.721
0.541
0.229
0.198
0.903
0.954
0.778
0.038
0.836
0.959
0.948

1.64 ± 1.12
1.67 ± 0.98
1.27 ± 0.65
2.50 ± 1.38
2.36 ± 1.29
2.08 ± 1.16
1.64 ± 1.03
2.08 ± 1.00
2.45 ± 1.29
1.83 ± 0.83
2.73 ± 1.49
1.83 ± 0.94
1.64 ± 0.81

0.466

1.55 ± 0.82
1.08 ± 0.29

1.000

0.510

1.82 ± 0.98
1.50 ± 0.80

0.004

0.541

2.33 ± 0.89

0.762

3.36 ± 1.43

0.103

2.73 ± 1.68
2.92 ± 1.31

0.970

0.941

2.09 ± 1.58
2.33 ± 0.78

0.970

0.942

1.64 ± 1.03
1.83 ± 1.03

0.976

0.247

1.50 ± 0.67

0.006

2.00 ± 1.41

0.083

1.91 ± 1.14
2.33 ± 0.89

0.149

0.924

1.36 ± 0.92
2.08 ± 1.08

0.717

SD p values

1.75 ± 0.87

Mean

12w
8w

12w

0.434 0.074 0.612

0.576 0.891 0.168

0.106 0.478 0.780

0.640 0.242 0.315

0.359 0.741 0.592

0.105 0.610 0.741

0.172 0.952 0.093

0.701 0.506 0.307

0.049 0.130 0.021

0.443 0.708 0.757

0.288 0.214 0.226

0.610 0.090 0.979

0.173 0.944 0.502

0.390 0.075 0.260

0.855 0.568 0.624

1.000 0.708 0.801

4w

8w

12w

0w

4w

8w

12w

0.335 0.069 0.516 0.939 0.411 0.043 0.597

0.984 0.554 0.432 0.435 0.246 0.377 0.087

0.297 0.842 0.538 0.602 0.731 0.843 0.447

0.226 0.100 0.146 0.911 0.655 0.236 0.342

0.407 0.899 0.393 0.481 0.899 0.411 0.809

0.066 0.610 0.981 0.044 0.004 0.076 0.274

0.187 0.830 0.098 0.357 0.142 0.307 0.113

0.510 0.298 0.242 0.633 0.559 0.904 0.894

0.057 0.165 0.018 0.248 0.495 0.434 0.200

0.616 0.923 0.576 0.481 0.860 0.378 0.443

0.348 0.262 0.256 0.567 0.672 0.546 0.472

0.384 0.197 0.590 0.598 0.856 0.119 0.645

0.050 0.880 0.263 0.271 0.744 0.407 0.708

0.199 0.082 0.272 0.498 0.814 0.196 0.502

0.962 0.363 0.337 0.095 0.152 0.618 0.710

4w

Inter-group analysis
by measured values

0.726 0.527 0.583 0.271 0.263 0.546 0.312

Inter-group analysis Inter-group analysis
by change values
by % change

Glycative Stress ResearchPhysical symptoms

Mental symptoms

1.36 ± 0.67
2.50 ± 1.09
2.09 ± 1.30
2.50 ± 1.00
2.00 ± 1.26
2.25 ± 0.75
2.36 ± 1.21
2.08 ± 0.67
2.36 ± 1.12

2.17 ± 1.03

2.45 ± 1.44

2.17 ± 0.72

2.45 ± 1.13

2.42 ± 0.51

2.27 ± 1.01

2.00 ± 0.74

2.09 ± 0.94

Test group 12

11

Test group 12

11

Test group 12

11

Test group 12

11

Test group 12
0.356
0.584
0.959

2.00 ± 0.74
2.00 ± 1.10
2.00 ± 0.60

1.75 ± 0.62

1.73 ± 0.79

1.92 ± 0.79

Test group 12

11

Control

Test group 12

No feeling of

happiness

Nothing to look

_ 86 _
0.541
1.000

1.55 ± 0.82
1.75 ± 0.87

1.82 ± 0.98

1.75 ± 0.75

11

Test group 12

0.944
0.492

1.55 ± 1.21
1.67 ± 0.49

1.45 ± 0.69

1.42 ± 0.51

11

Test group 12

Depressed

0.976
0.969

2.08 ± 0.67
1.91 ± 1.38

1.64 ± 0.67

2.17 ± 0.83

2.00 ± 1.26

11

Test group 12

11

Pessimism

falling asleep

Control

Control

0.766

0.492

2.17 ± 1.19

1.92 ± 1.00

11

Test group 12
1.82 ± 1.08

1.000

1.82 ± 0.75

1.82 ± 0.75

Control

0.104

2.08 ± 1.08

1.83 ± 1.03

Test group 12

Shallow sleep

Difficulty in

0.066

1.36 ± 0.50

1.73 ± 0.65

11Controluselessness

Feeling of

0.925

1.83 ± 0.72

1.75 ± 0.75

Test group 12

Control

0.445

1.36 ± 0.67

1.55 ± 0.52

11

Control

talk with others

Reluctance to

0.417

2.08 ± 1.00

1.75 ± 0.62

Test group 12

Lose confidenceControl

0.971

1.73 ± 0.79

1.82 ± 0.98

11

Test group 12

Daily life is not

Control

0.091

2.00 ± 0.60

1.58 ± 0.67

enjoyable

0.610

1.45 ± 0.69

1.73 ± 1.01

11

Control

forward to in life

0.583

2.18 ± 1.17

0.500

2.33 ± 0.89

1.91 ± 0.70

Loss of2.08 ± 0.90

0.554

0.952

0.969

0.823

0.175

0.255

0.162

0.497

0.767

11

Control

Control

Control

Control

Control

0.935

SD p values

1.55 ± 1.04

Mean

11

SD

4w
1.42 ± 0.67

Mean

0w

1.50 ± 0.67

n

Test group 12

Group

ControlUnitmotivation

Easily angered

Irritability

Get tired easily

Cold skin

Hot flashParameter
1.000

2.18 ± 1.33

1.83 ± 0.58

1.64 ± 0.81

1.83 ± 1.03

2.00 ± 0.77

1.75 ± 0.97

1.55 ± 0.52

1.50 ± 0.67

1.55 ± 0.69

1.67 ± 0.65

1.55 ± 0.69

1.58 ± 0.67

1.55 ± 0.69

1.83 ± 0.72

1.55 ± 0.69

1.75 ± 0.62

1.36 ± 0.50

1.67 ± 0.89

1.64 ± 0.67

1.67 ± 0.89

1.82 ± 0.98

1.83 ± 0.83

1.82 ± 0.98

2.25 ± 0.75

1.91 ± 0.94

2.33 ± 0.78

2.09 ± 1.38

2.25 ± 0.62

2.36 ± 1.57

2.33 ± 1.07

1.36 ± 0.92

0.812

0.428

1.000

0.958

0.802

0.821

0.513

0.958

0.944

0.925

1.000

0.850

0.541

0.976

0.596

0.715

0.391

0.500

0.970

0.933

0.970

0.500

0.554

0.451

0.350

0.971

0.329

0.956

0.934

0.880

0.767

SD p values

1.50 ± 0.80

Mean

8w
1.000

1.91 ± 1.30

2.17 ± 0.94

1.36 ± 0.67

2.00 ± 1.13

1.91 ± 1.04

1.83 ± 1.03

1.45 ± 0.52

1.83 ± 0.83

1.64 ± 0.92

1.67 ± 0.78

1.64 ± 0.67

1.75 ± 0.97

1.36 ± 0.50

1.92 ± 1.00

1.55 ± 0.69

1.75 ± 0.75

1.64 ± 0.67

1.67 ± 0.65

1.64 ± 0.67

1.83 ± 0.72

1.55 ± 0.93

2.33 ± 0.98

1.64 ± 1.03

2.33 ± 1.07

2.27 ± 1.01

2.50 ± 1.00

2.45 ± 1.44

2.42 ± 0.90

2.64 ± 1.57

2.67 ± 0.89

1.55 ± 1.21

0.969

1.000

0.499

0.958

0.967

1.000

0.208

0.130

0.702

0.925

0.858

1.000

0.166

0.846

0.596

0.715

0.973

0.500

0.970

0.933

0.361

0.500

0.176

0.233

1.000

0.971

1.000

0.476

0.664

0.194

1.000

SD p values

1.50 ± 0.80

Mean

12w
8w

12w

0.984 0.200 0.843

0.853 0.762 0.326

0.285 0.206 0.807

0.017 0.331 0.034

0.977 0.548 0.331

0.565 0.508 0.784

0.196 0.381 0.182

0.201 0.291 0.239

0.404 0.776 0.708

0.944 0.981 0.548

0.944 0.607 0.115

0.498 0.090 0.018

0.394 0.470 0.835

0.039 0.087 0.475

0.127 0.345 0.363

4w

0.728 0.527 1.000

8w

12w

0w

4w

8w

12w

0.984 0.272 0.635 0.711 0.699 0.436 0.589

0.830 0.680 0.456 0.443 0.472 0.618 0.120

0.489 0.145 0.499 0.968 0.507 0.503 0.863

0.018 0.241 0.017 0.215 0.160 0.859 0.211

0.525 0.568 0.406 0.339 0.492 0.669 0.933

0.325 0.924 0.813 0.462 0.249 0.895 0.749

0.186 0.385 0.205 0.843 0.174 0.338 0.113

0.220 0.245 0.293 0.507 0.359 0.462 0.505

0.322 0.989 0.340 0.620 0.056 0.332 0.914

0.808 0.736 0.967 0.939 1.000 0.928 0.506

0.831 0.868 0.102 0.612 0.728 0.968 0.063

0.592 0.053 0.067 0.799 0.482 0.248 0.127

0.319 0.396 0.856 0.677 0.787 0.251 0.593

0.031 0.052 0.766 0.469 0.303 0.720 0.940

0.121 0.244 0.191 0.585 0.421 0.957 0.955

4w

Inter-group analysis
by measured values

0.572 0.844 0.686 0.901 0.852 0.708 0.916

Inter-group analysis Inter-group analysis
by change values
by % change

Anti-Glycation Effect of a Functional Soymilk Beverage Supplemented with Rice Bran/Rice Bran Oil

_ 87 _

2.09 ± 0.94

Test group 12

2.25 ± 0.75
1.64 ± 0.81
2.08 ± 0.79

2.25 ± 0.62

1.64 ± 0.67

1.83 ± 0.72

11

Test group 12

Inability to solve

2.83 ± 0.83
2.64 ± 1.21

2.58 ± 0.79

2.09 ± 1.04

Test group 12

11

Stressful

Control

1.36 ± 0.92

1.45 ± 0.82

Vague feeling of

11

1.50 ± 0.67

1.58 ± 0.67

Test group 12

Control

1.55 ± 0.69

1.45 ± 0.69

11

Controlfear

1.92 ± 0.79

1.58 ± 0.67

11

Test group 12

1.91 ± 1.14

1.91 ± 0.70

Control

1.83 ± 0.72

1.83 ± 0.58

Test group 12

A sense of

Feeling ofanxiety for no
special reason

1.55 ± 0.82

1.82 ± 0.98

tension1.83 ± 0.83

1.83 ± 0.83

11

Control

Test group 12

Inability to sleep

because of worries

1.45 ± 0.52

1.73 ± 0.65

11Control

1.92 ± 0.79

1.92 ± 0.79

Test group 12

Inability to makejudgments readily

1.45 ± 0.52

1.64 ± 0.81

11

Control

problems

Inability toControl

Control

0.188

0.140

0.425

0.958

0.903

0.944

0.211

1.000

1.000

0.610

1.000

0.409

1.000

0.719

0.425

1.000

1.000

0.454

SD p values

2.36 ± 0.81

Mean

11

SD

4w

Test group 12

Mean

0w
2.33 ± 0.78

n2.67 ± 0.78

Groupconcentrate

Lapse of memory

Unit
1.000

2.36 ± 1.12

2.58 ± 0.79

1.27 ± 0.47

1.42 ± 0.51

1.45 ± 0.52

1.67 ± 0.65

1.82 ± 0.75

1.92 ± 0.79

1.55 ± 0.69

1.58 ± 0.67

1.55 ± 0.69

1.92 ± 0.67

1.45 ± 0.52

1.83 ± 0.58

1.82 ± 0.87

2.33 ± 0.78

2.27 ± 0.90

0.637

1.000

0.763

0.559

1.000

0.947

0.981

0.928

0.610

0.397

0.702

1.000

0.719

1.000

0.807

0.958

0.952

SD p values

2.67 ± 0.65

Mean

8w
0.397

2.27 ± 1.27

2.75 ± 1.06

1.45 ± 0.93

1.42 ± 0.51

1.36 ± 0.67

1.92 ± 0.90

2.00 ± 0.77

2.33 ± 0.65

1.91 ± 1.30

1.83 ± 0.83

1.55 ± 0.69

1.75 ± 0.87

1.45 ± 0.69

1.83 ± 0.83

1.64 ± 0.67

2.50 ± 1.00

2.09 ± 1.04

0.848

0.715

1.000

0.559

0.944

0.211

0.981

0.016

0.973

1.000

0.702

0.696

0.719

1.000

1.000

0.491

0.454

SD p values

2.92 ± 0.79

Mean

12w
8w

12w

0.339 0.479 0.970

0.979 0.957 0.562

0.345 0.731 0.220

1.000 0.636 0.242

0.465 0.948 0.811

0.307 0.527 0.966

0.147 0.527 0.527

1.000 0.780 0.528

4w

0.842 0.741 0.119

8w

12w

0w

4w

8w

12w

0.253 0.230 0.550 0.214 0.651 0.590 0.337

0.928 0.865 0.588 0.683 0.688 0.492 0.904

0.599 0.818 0.279 0.654 0.246 0.401 0.113

0.709 0.876 0.517 0.779 0.852 0.763 0.275

0.524 0.651 0.935 0.968 0.414 0.895 0.868

0.209 0.359 0.877 0.539 0.117 0.204 0.540

0.510 0.590 0.844 0.543 0.037 0.115 0.251

0.582 0.473 0.933 0.034 0.074 0.150 0.025

4w

Inter-group analysis
by measured values

0.855 0.680 0.123 0.370 0.507 0.241 0.044

Inter-group analysis Inter-group analysis
by change values
by % change

Differences were considered significant for p < 0.05. Dunnett's test was used to compare data obtained before diet intake with those obtained 4, 8 and 12 weeks after diet intake. The independent samples t-test (the unpaired t-test on SPSS)
was used to compare absolute and percent changes in scores from baseline (before diet intake) between groups.

Mental symptoms

Parameter

Glycative Stress Research

Lifestyle behavior

Skin symptoms(ℓ/day)Water

11_ 88 _

9.10 ± 14.40

Control
1.04 ± 1.48
2.09 ± 2.42

Control
6.89 ± 0.63

Control
1.41 ± 0.44

Control
5.27 ± 3.68

Concerned about
3.91 ± 1.14
2.42 ± 0.67
2.45 ± 1.04

Control

Test group 12

Control

Dry skin3.27 ± 1.35

Control
2.00 ± 1.10

Control
3.27 ± 1.10
2.83 ± 1.03
3.70 ± 1.06
2.17 ± 0.72
1.82 ± 0.75

Control

Test group 12

Control

Test group 12

Control

Make-up runs

easilyPoor complexion
11

11

11

3.58 ± 0.67

Test group 12111.75 ± 0.75

Test group 12112.75 ± 0.45

Test group 12

Concerned aboutspots or freckles

Itchy skin2.55 ± 1.13

Control
11

2.33 ± 0.78

Test group 12

11

11

3.25 ± 0.75

Test group 12

pores

11

Control

11

1.41 ± 0.48

Test group 12

11

6.50 ± 0.64

Test group 12

11

Test group 12

11

3.21 ± 6.10

5.54 ± 2.87

Oily face

1.000

0.518
1.77 ± 2.40

1.21 ± 1.72

0.00 ± 0.00

0.00 ± 0.00

0.955

0.999
1.68 ± 2.22

0.90 ± 1.61

0.00 ± 0.00
0.747

0.330

SD p values

12w
0.00 ± 0.00

Mean SD p values Mean

8w

0.488

1.82 ± 0.87

2.00 ± 0.85

2.73 ± 1.68

3.00 ± 0.95

2.73 ± 1.35

3.42 ± 1.08

2.00 ± 1.00

2.08 ± 0.90

2.55 ± 1.51

2.58 ± 0.67

2.27 ± 1.49

2.00 ± 0.43

2.45 ± 1.21

2.50 ± 0.52

3.55 ± 1.04

3.08 ± 1.00

6.09 ± 3.05

5.33 ± 1.78

1.35 ± 0.46

1.30 ± 0.53

6.86 ± 0.60

6.63 ± 0.61

1.64 ± 2.41

1.88 ± 2.13

1.000

0.693

0.002

0.710

0.087

0.860

1.000

0.183

0.003

0.756

0.634

0.219

1.000

0.963

0.203

0.821

0.670

0.972

0.825

0.488

0.992

0.755

0.289

0.025

8.48 ± 12.95 0.968

3.96 ± 6.04

2.00 ± 0.89

2.00 ± 0.60

3.00 ± 1.41

2.67 ± 0.78

3.00 ± 1.48

3.25 ± 0.97

1.82 ± 1.17

1.92 ± 0.67

2.73 ± 1.49

2.33 ± 0.78

2.45 ± 1.04

2.00 ± 0.74

2.64 ± 1.12

2.50 ± 0.80

3.45 ± 1.13

2.83 ± 0.83

5.82 ± 2.76

5.83 ± 2.62

1.28 ± 0.39

1.36 ± 0.50

6.95 ± 0.61

6.54 ± 0.66

1.32 ± 2.24

1.54 ± 1.64

8.48 ± 13.86

3.42 ± 5.88

0.735

0.693

0.025

0.710

0.557

0.448

0.741

0.688

0.028

0.125

0.975

0.219

0.825

0.963

0.086

0.205

0.866

0.930

0.317

0.899

0.842

0.986

0.032

0.247

0.968

0.974

0.865

2.00 ± 1.18

2.25 ± 0.87

2.73 ± 1.27

2.67 ± 0.78

2.73 ± 1.35

3.67 ± 0.78

2.09 ± 1.22

2.08 ± 0.67

2.82 ± 1.17

2.25 ± 0.97

2.09 ± 0.94

2.08 ± 0.67

2.64 ± 0.92

2.58 ± 0.67

3.55 ± 1.13

2.92 ± 1.08

6.00 ± 3.97

4.92 ± 2.23

1.27 ± 0.41

1.17 ± 0.49

7.02 ± 0.64

6.63 ± 0.88

1.23 ± 2.14

1.25 ± 1.23

0.735

0.942

0.002

0.710

0.087

0.978

0.953

0.183

0.077

0.053

0.249

0.434

0.825

0.784

0.203

0.367

0.740

0.601

0.267

0.029

0.409

0.755

0.015

0.830

8.98 ± 14.12 1.000

3.60 ± 6.98

11 323.18 ± 454.60 305.00 ± 418.60 0.972 323.18 ± 486.48 1.000 336.36 ± 482.10 0.989

Test group 12

Controlhours

Frequent pimples

1.86 ± 2.55

1.42 ± 1.96

0.00 ± 0.00

0.00 ± 0.00

Mean SD p values

4w

Test group 12 175.00 ± 235.97 247.92 ± 283.74 0.210 218.75 ± 248.89 0.594 220.83 ± 290.34 0.560

1.86 ± 2.55

Test group 12(hour/day)(hour/day)T (g/day)(ml/day)

Control

1.19 ± 1.93

0.00 ± 0.00

SD(times/week) Test group 12

ControlMean

0w

0.00 ± 0.00

Sleeping hours

VDT workingn

11

Exerciseconsumption

Group(Cigaretts/day）Test group 12

Unit(dat/week)

Converted intoethanol

Alcoholconsumption

alcohol drinking

Frequency of

SmokingParameter

Table 4. Results of AAQol assessment (lifestyle behavior and skin symptoms)

8w

12w

0.562 0.268 0.763

0.005 0.188 0.043

0.316 0.880 0.021

0.228 0.172 0.399

0.088 0.654 0.886

0.825 0.554 0.462

0.762 0.793 0.968

0.572 0.911 0.928

0.314 0.827 0.183

0.662 0.583 0.450

0.446 0.906 0.961

0.029 0.007 0.036

0.077 0.732 0.815

0.056 0.586 0.661

0.237 0.647 0.758

4w

8w

12w

0w
4w

8w

12w

Inter-group analysis
by measured values

0.478 0.238 0.555 0.268 0.619 1.000 0.567

0.003 0.124 0.029 0.067 0.643 0.486 0.891

0.206 0.950 0.015 0.419 0.189 0.634 0.051

0.360 0.201 0.520 0.528 0.835 0.804 0.985

0.122 0.769 0.397 0.244 0.940 0.445 0.216

0.623 0.387 0.382 0.602 0.569 0.236 0.982

0.646 0.578 0.496 0.917 0.910 0.738 0.875

0.707 0.962 0.754 0.123 0.288 0.146 0.187

0.614 0.522 0.183 0.846 0.470 0.989 0.424

0.461 0.663 0.273 0.997 0.812 0.689 0.583

0.442 0.965 0.987 0.159 0.353 0.134 0.233

0.072 0.014 0.032 0.219 0.804 0.786 0.975

0.347 0.839 0.937 0.230 0.309 0.282 0.253

0.172 0.912 0.713 0.349 0.703 0.519 0.490

0.403 0.723 0.303 0.479 0.641 0.522 0.339

4w

Inter-group analysis Inter-group analysis
by % change
by change values

Anti-Glycation Effect of a Functional Soymilk Beverage Supplemented with Rice Bran/Rice Bran Oil

_ 89 _

3.36 ± 1.36

Control
2.83 ± 1.03
3.00 ± 1.48

Control
2.73 ± 0.90

Control

2.08 ± 0.51
2.82 ± 1.40

Test group 12

Control
2.83 ± 1.03
3.45 ± 1.44

Control

2.50 ± 0.80
2.73 ± 1.10

Test group 12

Control

Make-up does not
apply smoothly

Good skincondition

Skin moisture

Skin smoothness

Skin elasticity

Not anemic face

Skin brightness

2.45 ± 1.51

Control

Skin clearness
2.58 ± 0.79
2.73 ± 1.01

Control
3.18 ± 0.75

Control
2.55 ± 1.29

Control
2.36 ± 1.29

Control
2.50 ± 0.90
2.73 ± 1.10

Control
2.55 ± 1.04

Control
2.90 ± 1.29

Control
11

2.83 ± 1.03

Test group 12

11

2.58 ± 0.79

Test group 12

11

Test group 1211

2.33 ± 0.78

Test group 12

11

2.58 ± 0.90

Test group 12112.83 ± 0.72

Test group 12

11

Test group 1211

11

2.33 ± 1.07

Test group 12

11

Test group 12

11

Dull,
fragile nails

Dull skin

3.09 ± 1.45

Control

Bags under eyes

112.58 ± 1.00

Test group 12112.83 ± 0.72

Test group 12

11

Test group 12

11

3.00 ± 0.95

Test group 12

11

2.27 ± 0.79

SD

Control

Mean

0w
2.08 ± 0.67

n

Test group 12

Group

Concerned aboutrough skinFrequent
exposure to UVConcerned about
crows feet

Not elastic,
not glossy

Coarse skinUnit2.82 ± 1.47

2.67 ± 1.07

2.82 ± 1.25

2.67 ± 0.78

2.91 ± 1.04

2.58 ± 0.67

2.55 ± 1.29

2.42 ± 0.67

2.91 ± 1.14

2.67 ± 0.49

2.91 ± 0.83

2.83 ± 0.72

2.64 ± 0.81

2.75 ± 0.45

2.73 ± 1.10

2.58 ± 0.51

2.64 ± 1.63

2.67 ± 1.15

2.73 ± 1.42

2.75 ± 0.87

2.09 ± 1.22

2.58 ± 1.31

2.36 ± 1.43

2.33 ± 0.78

2.18 ± 0.87

2.67 ± 1.07

3.18 ± 1.66

2.92 ± 1.24

3.18 ± 1.40

2.83 ± 0.83

2.09 ± 0.94

2.08 ± 0.79

1.000

0.994

0.854

0.884

0.976

0.935

0.947

0.956

0.964

0.683

0.965

0.756

1.000

0.984

0.768

1.000

0.963

0.836

0.323

0.007

0.940

0.073

0.132

0.031

0.500

0.119

0.840

0.829

0.968

0.837

0.860

0.793

2.45 ± 1.51

2.17 ± 0.72

2.82 ± 1.17

2.83 ± 0.83

3.00 ± 1.10

2.83 ± 0.58

2.64 ± 1.12

2.58 ± 0.90

2.73 ± 0.90

2.83 ± 0.83

3.00 ± 1.10

2.75 ± 1.06

3.00 ± 0.89

2.75 ± 0.62

2.73 ± 0.65

2.67 ± 0.65

2.27 ± 1.35

2.25 ± 1.14

2.64 ± 1.12

2.58 ± 0.67

2.00 ± 1.18

2.17 ± 0.83

2.36 ± 1.50

2.33 ± 0.89

1.73 ± 0.65

2.08 ± 0.67

2.82 ± 1.66

2.58 ± 0.67

2.91 ± 1.45

2.50 ± 0.67

2.36 ± 1.29

1.92 ± 0.67

8w
0.536

0.560

0.037

0.884

0.635

0.821

0.210

0.872

0.534

0.939

0.541

0.907

0.962

0.732

0.768

1.000

0.784

0.836

0.966

0.002

0.387

0.039

0.975

0.031

0.500

0.002

0.013

0.829

0.566

0.233

0.156

0.965

1.000

2.09 ± 1.30

2.50 ± 0.90

2.45 ± 1.13

2.75 ± 0.75

2.45 ± 1.13

2.75 ± 0.75

2.18 ± 0.87

2.33 ± 0.89

2.36 ± 1.12

2.83 ± 0.58

2.55 ± 0.93

2.83 ± 0.58

2.45 ± 0.69

2.75 ± 0.75

2.64 ± 1.03

2.25 ± 0.75

2.45 ± 1.37

2.42 ± 1.24

2.82 ± 1.33

2.92 ± 1.08

1.91 ± 1.22

2.42 ± 1.08

2.55 ± 1.44

2.50 ± 1.17

1.73 ± 0.90

2.25 ± 0.62

2.55 ± 1.44

2.92 ± 1.08

3.09 ± 1.45

3.00 ± 0.95

2.00 ± 0.89

0.135

0.435

0.995

0.847

0.821

0.424

0.956

1.000

0.939

0.541

0.164

1.000

0.732

0.768

0.977

0.527

1.000

0.966

0.019

0.940

0.020

0.412

0.130

0.959

0.002

0.062

0.218

0.968

0.617

1.000

0.541

SD p values

12w
2.08 ± 0.51

Mean SD p values Mean SD p values Mean

4w
8w

12w

4w

8w

12w

0w

4w

8w

12w

Inter-group analysis
by measured values

0.918 0.598 0.353 0.621 0.827 0.265 0.894 0.779 0.574 0.388

0.760 0.964 0.669 0.367 0.651 0.825 0.922 0.728 0.972 0.465

0.852 0.855 0.239 0.454 0.724 0.362 0.593 0.379 0.649 0.465

0.873 0.965 0.672 0.346 0.544 0.551 0.946 0.771 0.901 0.685

0.620 0.861 0.362 0.510 0.807 0.388 0.935 0.507 0.773 0.214

0.490 0.852 0.120 0.488 0.815 0.101 0.268 0.817 0.583 0.380

0.540 0.786 0.354 0.637 0.909 0.538 0.706 0.687 0.442 0.339

0.802 0.649 0.678 0.792 0.694 0.408 0.575 0.699 0.825 0.312

0.640 0.763 0.835 0.766 0.686 0.993 0.825 0.959 0.965 0.945

0.015 0.109 0.018 0.037 0.343 0.229 0.244 0.963 0.891 0.847

0.008 0.044 0.006 0.012 0.028 0.002 0.126 0.363 0.698 0.303

0.172 0.172 0.117 0.111 0.169 0.179 0.335 0.950 0.953 0.934

0.211 0.475 0.217 0.249 0.387 0.095 0.757 0.251 0.209 0.119

0.780 0.792 0.045 0.684 0.579 0.038 0.756 0.667 0.669 0.490

0.968 0.901 0.490 0.861 0.698 0.467 0.463 0.472 0.406 0.859

0.527 0.495 0.253 0.497 0.658 0.215 0.539 0.984 0.319 0.785

4w

Inter-group analysis Inter-group analysis
by change values
by % change

Differences were considered significant for p < 0.05. Dunnett's test was used to compare data obtained before diet intake with those obtained 4, 8 and 12 weeks after diet intake. The independent samples t-test (the unpaired t-test on SPSS)
was used to compare absolute and percent changes in scores from baseline (before diet intake) between groups.

Skin symptoms

Parameter

Glycative Stress ResearchAnti-Glycation Effect of a Functional Soymilk Beverage Supplemented with Rice Bran/Rice Bran Oil
Table 5. Insulin resistance-related parameters
Parameter

Unit

Group

n

0w
Mean

8w
SD

Mean

Inter-group
analysisby change values

12w

Inter-group
analysisby % changeInter-group
analysisby measured values

SD p values Mean SD p values

8w

12w

8w

12w

0w

Fasting plasma mg/mL Test group 12 89.92 ± 6.54 92.50 ± 8.59 0.107 92.25 ± 9.32 0.153
glucoseControl
11 88.55 ± 11.03 94.82 ± 14.00 0.010 89.36 ± 12.09 0.888

0.147

0.549

0.140

0.608

0.718 0.634 0.526

Insulin

0.208

0.063

0.020

0.029

0.366 0.816 0.791

0.116

0.733

0.132

0.830

0.914 0.492 0.816

0.124

0.633

0.136

0.701

0.973 0.574 0.833

0.058

0.152

0.062

0.163

0.443 0.802 0.693

μU/mL Test group 12

5.40 ± 3.21

6.19 ± 2.31

0.262

6.00 ± 3.49

0.443

Control

11

6.67 ± 3.40

6.50 ± 3.86

0.951

5.62 ± 3.33

0.211

Test group 12

5.18 ± 0.31

5.06 ± 0.29

0.015

5.21 ± 0.25

0.621

Control

HbA1c [JDS]%

HbA1c [NGSP]%

Glycoalbumin%

11

5.19 ± 0.39

5.16 ± 0.42

0.713

5.25 ± 0.48

0.298

Test group 12

5.56 ± 0.33

5.43 ± 0.33

0.009

5.59 ± 0.28

0.615

Control

5.56 ± 0.42

5.53 ± 0.46

0.595

5.63 ± 0.50

0.240

Test group 12 14.00 ± 1.05

13.83 ± 0.99

0.075 13.95 ± 0.95

0.744

Control

13.74 ± 0.82

0.784 13.81 ± 0.71

0.243

11

11 13.69 ± 0.82

8w

12w

Differences were considered significant for p < 0.05. Dunnett's test was used to compare data obtained before diet intake with those obtained 8 and 12 weeks after dietintake. The independent samples t-test (the unpaired t-test on SPSS) was used to compare absolute and percent changes in values from baseline (before diet intake)between groups. SD, standard deviation; FPG, fasting plasama glucose.

Table 6. Insulin resistance-related parameters (subclass analysis)
Parameter

Unit

Group

n

0w
Mean

SD

Mean

8w

12w

SD p values MeanInter-group
analysisby change values

Inter-group
analysisby % changeInter-group
analysisby measured values

SD p values

8w

12w

8w

12w

0w

Fasting plasma mg/mL Test group 11 89.64 ± 6.79 91.55 ± 8.31 0.274 91.82 ± 9.65 0.196
glucoseControl
8 91.00 ± 11.28 99.38 ± 12.97 0.011 93.38 ± 10.51 0.566

0.023

0.947

0.023

0.820

0.767 0.126 0.742

Insulin

0.342

0.151

0.064

0.125

0.230 0.455 0.774

0.233

0.604

0.262

0.692

0.352 0.188 0.272

0.177

0.500

0.195

0.558

0.362 0.192 0.246

0.167

0.231

0.170

0.231

0.554 0.812 0.770

μU/mL Test group 11

5.60 ± 3.28

6.27 ± 2.41

0.403

5.99 ± 3.67

0.718

Control

87.58 ± 3.59

7.40 ± 4.03

0.972

6.48 ± 3.43

0.384

Test group 11

5.17 ± 0.33

5.05 ± 0.31

0.025

5.21 ± 0.27

0.622

Control

HbA1c [JDS]%

HbA1c [NGSP]%

Glycoalbumin%

8

5.33 ± 0.36

5.29 ± 0.44

0.669

5.40 ± 0.47

0.249

Test group 11

5.55 ± 0.35

5.43 ± 0.34

0.015

5.59 ± 0.29

0.615

Control

5.71 ± 0.38

5.68 ± 0.45

0.681

5.80 ± 0.47

0.177

Test group 11 13.95 ± 1.08

13.81 ± 1.04

0.165 13.94 ± 1.00

0.990

Control

13.70 ± 0.87

0.904 13.81 ± 0.73

0.263

8

8 13.66 ± 0.89

8w

12w

Differences were considered significant for p < 0.05. Dunnett's test was used to compare data obtained before diet intake with those obtained 8 and 12 weeks after dietintake. The independent samples t-test (the unpaired t-test on SPSS) was used to compare absolute and percent changes in values from baseline (before diet intake)between groups. SD, standard deviation; FPG, fasting plasama glucose.

_ 90 _Glycative Stress Research

Table 7. AGE-related parameters
Parameter

Unit

Group

n

0w
Mean

SD

p values

Mean

2.27 ± 0.22

2.05 ± 0.35

0.004

2.12 ± 0.31

0.055 0.422 0.406 0.261 0.505 0.258 0.121 0.630

112.40 ± 0.31

2.25 ± 0.24

0.014

2.18 ± 0.27

0.001

Test group 12

66.07 ± 12.77

53.45 ± 19.73

0.004

57.76 ± 17.75

0.055 0.422 0.406 0.164 0.596 0.258 0.121 0.630

1173.45 ± 17.49

65.01 ± 13.76

0.014

61.15 ± 15.22

0.001

Test group 12

16.82 ± 9.74

4.20 ± 17.97

0.004

8.51 ± 15.57

0.055 0.422 0.406 0.208 0.185 0.074 0.042 0.316

1127.82 ± 17.58

19.37 ± 15.37

0.014

15.51 ± 17.10

0.001

pmol/mL Test group 12

81.05 ± 34.88

93.36 ± 24.13

0.233 123.04 ± 32.85 ＜0.001 0.420 0.714 0.286 0.555 0.833 0.546 0.919

Control

year

Control

Glycation age– chronologicalage
Pentosidine(serum)SD

year

Control

MeanInter-group
Inter-group
Inter-group
analysisanalysisanalysisby change values by % change by measured values

12w

Test group 12

Skin AGE
fluorescence
Glycation age

8w

SD

p values

8w

12w

8w

12w

0w

8w

12w

11

78.22 ± 28.19

100.24 ± 29.49

0.018 124.43 ± 31.36 ＜0.001

ng/mL Test group 12
3deoxyglucosone
Control
11(serum)19.01 ± 13.87

26.98 ± 25.16

0.497

28.86 ± 11.74

0.358 0.378 0.769 0.281 1.000 0.948 0.326 0.758

19.34 ± 9.51

18.31 ± 15.19

0.984

26.83 ± 19.00

0.467

μg/mL Test group 12

1.17 ± 0.31

1.56 ± 0.39

0.001

1.55 ± 0.31

11

1.38 ± 0.44

1.85 ± 0.45 ＜0.001

1.86 ± 0.41

CML (serum)Control

Control

0.001 0.525 0.424 0.896 0.986 0.190 0.113 0.047＜0.0010.001 0.262 0.178 0.815 0.621 0.206 0.167 0.143

sRAGE(serum)pg/mL Test group 12 798.00 ± 384.57 878.25 ± 471.09 0.078 944.83 ± 528.76

esRAGE(serum)ng/mL Test group 12

0.37 ± 0.18

0.40 ± 0.22

0.231

0.44 ± 0.25

0.003 0.153 0.168 0.328 0.526 0.682 0.381 0.343

11

0.33 ± 0.19

0.33 ± 0.15

0.907

0.36 ± 0.14

0.452

sRAGE –
esRAGE

pg/mL Test group 12 432.17 ± 236.87 481.58 ± 278.83 0.040 507.33 ± 312.86

Skin corneum
CML

μg/mg Test group 12
proteinControl
10

Control
Control
Control

11 627.00 ± 209.99 660.36 ± 188.02 0.431 686.91 ± 197.86

10 329.70 ± 187.25 357.60 ± 145.02 0.465 360.10 ± 149.03

0.097

0.002 0.459 0.299 0.392 0.425 0.281 0.220 0.189
0.409

46.68 ± 30.91

27.92 ± 22.16

0.102

46.10 ± 28.70

37.71 ± 15.57

0.359

0.460

0.484 0.962

0.238

Differences were considered significant for p < 0.05. Dunnett's test was used to compare data obtained before diet intake with those obtained 8 and 12 weeks after dietintake. For skin corneum CML, the paired t-test was used to compare data obtained before diet intake with those obtained 12 weeks after diet intake. The independent
samples t-test (the unpaired t-test on SPSS) was used to compare absolute and percent changes in values from baseline (before diet intake) between groups. SD, standard
deviation; AGEs, advanced glycation end products; 3DG, 3-deoxyglucosone; CML, carboxymethyl lysine; RAGE, receptor for AGE; sRAGE, soluble RAGE; esRAGE,
endogenous secreted RAGE.

50.00

Glycation age−Choronological age [year]

Test diet (n = 12 )Control diet (n = 11)

40.00

30.00

20.00

*p = 0.042

10.00

0.00
0w

8w

-10.00-20.00

Fig 1. Difference between glycation age and chronological age.
Results are expressed as mean ± stndaed deviation. Student’s t test.

_ 91 _12 w

Anti-Glycation Effect of a Functional Soymilk Beverage Supplemented with Rice Bran/Rice Bran Oil
Table 8. AGE-related parameters (subclass analysis)
Parameter

Unit

Group

n

0w
Mean

Skin AGE
fluorescence
Glycation age

SD

p values

2.25 ± 0.23

2.00 ± 0.33

0.002

2.09 ± 0.31

0.049 0.402 0.395 0.255 0.506 0.229 0.097 0.616

82.40 ± 0.28

2.24 ± 0.21

0.037

2.16 ± 0.18

0.003

Test group 11

65.08 ± 12.89

51.00 ± 18.68

0.002

56.08 ± 17.58

0.049 0.402 0.395 0.167 0.612 0.229 0.097 0.616

873.39 ± 16.18

64.27 ± 11.91

0.037

59.64 ± 10.05

0.003

Test group 11

16.44 ± 10.12

2.37 ± 17.63

0.002

7.45 ± 15.86

0.049 0.402 0.395 0.270 0.207 0.134 0.068 0.490

12.14 ± 11.77

0.003

Control

Glycation age– chronological
age

year

SD

Mean

Inter-group
Inter-group
Inter-group
analysisanalysisanalysisby change values by % change by measured values

12w

Test group 11
Control

year

8w
Mean

SD

p values

8w

12w

8w

12w

0w

8w

12w

8

25.89 ± 16.11

16.77 ± 13.05

0.037

pmol/mL Test group 11

71.78 ± 14.31

90.94 ± 23.73

0.016 119.68 ± 32.22 ＜0.001 0.669 0.741 0.501 0.823 0.626 0.490 0.966

876.21 ± 24.53

99.53 ± 29.38

0.030 120.26 ± 24.43 ＜0.001

ng/mL Test group 11
3deoxyglucosone
Control
8(serum)19.51 ± 14.44

28.48 ± 25.82

0.476

29.29 ± 12.22

0.420 0.495 0.299 0.305 0.396 0.920 0.456 0.250

20.12 ± 10.39

20.47 ± 17.00

0.998

22.18 ± 13.70

0.942μg/mL Test group 11

1.15 ± 0.32

1.53 ± 0.39

0.003

1.52 ± 0.31

0.003 0.608 0.266 0.931 0.810 0.188 0.130 0.019

8

1.40 ± 0.49

1.85 ± 0.50

0.001

1.95 ± 0.41

Pentosidine(serum)CML (serum)Control
Control

Control＜0.0010.001 0.140 0.155 0.367 0.327 0.409 0.275 0.249

sRAGE(serum)pg/mL Test group 11 815.91 ± 398.06 905.36 ± 484.16 0.061 977.55 ± 541.68

esRAGE(serum)ng/mL Test group 11

0.38 ± 0.19

0.41 ± 0.22

0.204

0.45 ± 0.25

0.003 0.069 0.107 0.075 0.186 0.904 0.618 0.555

8

0.39 ± 0.19

0.36 ± 0.15

0.591

0.40 ± 0.13

0.918

sRAGE –
esRAGE

pg/mL Test group 11 440.45 ± 246.60 495.36 ± 288.13 0.030 523.91 ± 322.55

Skin corneum
CML

μg/mg Test group 11
proteinControl
7

Control
Control
Control

8 687.38 ± 182.28 704.88 ± 142.11 0.861 739.25 ± 173.30

7 354.14 ± 178.69 375.86 ± 100.43 0.783 387.00 ± 121.62

0.324

0.001 0.348 0.341 0.495 0.522 0.436 0.310 0.302
0.588

45.45 ± 32.10

28.95 ± 22.93

0.174

46.31 ± 28.60

34.45 ± 17.24

0.289

0.775

0.829 0.952

0.577

Differences were considered significant for p < 0.05. Dunnett's test was used to compare data obtained before diet intake with those obtained 8 and 12 weeks after dietintake. For CML, the paired t-test was used to compare data obtained before diet intake with those obtained 12 weeks after diet intake. The independent samples t-test(the unpaired t-test on SPSS) was used to compare absolute and percent changes in values from baseline (before diet intake) between groups. SD, standard deviation;
AGEs, advanced glycation end products; 3DG, 3-deoxyglucosone; CML, carboxymethyl lysine; RAGE, receptor for AGE; sRAGE, soluble RAGE; esRAGE,
endogenous secreted RAGE.

_ 92 _Glycative Stress ResearchFig 2- a(a)

2.50
Test diet (n = 12)
Control diet (n = 11)
2.00

Serum CML [μg /mL]*p = 0.047
1.50

1.00

0.50

0.00
0w

8w

12 w

Fig 2- b

( b)

2.50
Test diet (n = 11)
Control diet (n = 8)

Serum CML [μg /mL]2.00

*p = 0.019
1.50

1.00

0.50

0.00
0w

8w

Fig 2. CML change

12 w

a: Total analysis, b: Subclass analysis. Results are expressed as mean ± stndaed deviation. Student t test. CML,
carboxymethyl lysine.

_ 93 _

Anti-Glycation Effect of a Functional Soymilk Beverage Supplemented with Rice Bran/Rice Bran Oil

Table 9. Skin-related parameters
Parameter

Unit

Group

n

0w
Mean

Melanin

Skin color difference (Upper arm)

Index

Hb Index
Hb SO2
Index

(%)

L*
a*

Skin color diffrerence (Cheak)b*

Skin elesticity (Upper arma)

SD

Mean

Inter-group
Inter-group
analysisanalysisby change values by % change

12w

SD

p values

MeanSD

p values

8w

0.70 ± 0.08

0.67 ± 0.10

0.016

0.69 ± 0.08

0.545

0.273 0.438 0.252 0.452

0.197 0.405 0.102

Control

110.64 ± 0.12

0.63 ± 0.12

0.854

0.61 ± 0.13

0.202

Test group 12

0.86 ± 0.19

0.91 ± 0.24

0.547

0.93 ± 0.30

0.335

0.324 0.791 0.535 0.554

0.990 0.348 0.809

Control

110.87 ± 0.18

0.83 ± 0.13

0.845

0.95 ± 0.21

0.357

Test group 12

59.45 ± 4.52

56.05 ± 7.17

0.154

55.70 ± 5.83

0.109

0.591 0.252 0.702 0.270

0.894 0.492 0.220

Control

0.883 0.982 0.841 0.997

0.233 0.226 0.372

0.238 0.694 0.263 0.724

0.608 0.122 0.492

0.063 0.789 0.058 0.685

0.176 0.687 0.269

0.681 0.588 0.638 0.654

0.239 0.257 0.135

0.698 0.953 0.777 0.765

0.351 0.377 0.511

0.359 0.308 0.387 0.367

0.482 0.083 0.176

0.965 0.406 0.983 0.395

0.448 0.505 0.279

0.814 0.474 0.750 0.465

0.916 0.852 0.726

0.323 0.318 0.336 0.339

0.091 0.342 0.341

0.866 0.259 0.869 0.261

0.345 0.639 0.681

0.168 0.281 0.229 0.447

0.181 0.922 0.658

0.165 0.056 0.176 0.069

0.275 0.962 0.843

0.414 0.337 0.408 0.360

0.030 0.328 0.247

0.028 0.839 0.063 0.984

0.023 0.384 0.086

0.112 0.192 0.198 0.277

0.025 0.375 0.214

1159.04 ± 9.03

53.73 ± 8.71

0.054

51.72 ± 9.06

0.008

Test group 12

69.42 ± 1.49

69.57 ± 2.01

0.827

69.42 ± 2.20

1.000

Control

11

70.37 ± 2.18

70.61 ± 1.96

0.855

70.35 ± 2.71

0.999

Test group 12

5.55 ± 0.92

5.47 ± 1.03

0.938

5.51 ± 1.29

0.983

Control

11

5.37 ± 0.70

4.85 ± 0.80

0.182

5.16 ± 1.12

0.713

Test group 12

14.41 ± 1.51

14.10 ± 1.83

0.357

14.67 ± 1.73

0.466

Control

13.78 ± 1.90

0.438

13.81 ± 1.92

0.389

11

Melanin
Index

Test group 12

1.12 ± 0.15

1.09 ± 0.13

0.240

1.10 ± 0.16

0.481

Control

11

1.04 ± 0.14

1.03 ± 0.12

0.671

1.01 ± 0.11

0.171

Hb Index

Test group 12

1.12 ± 0.18

1.17 ± 0.24

0.503

1.20 ± 0.20

0.179

Control

11

1.18 ± 0.14

1.26 ± 0.24

0.171

1.26 ± 0.23

0.159

Test group 12

52.99 ± 4.73

57.17 ± 3.00 ＜0.001

58.82 ± 5.02 ＜0.001

Control

11

51.71 ± 3.79

54.49 ± 4.02

0.019

56.05 ± 4.43 ＜0.001

Test group 12

64.72 ± 1.61

64.86 ± 2.06

0.898

64.74 ± 2.45

0.999

Control

1165.35 ± 2.24

65.47 ± 2.23

0.829

65.80 ± 2.08

0.124

Test group 12

8.86 ± 0.89

9.16 ± 1.60

0.464

9.49 ± 1.35

0.055

Hb SO2
Index
L*
a*

(%)

11

8.91 ± 0.95

9.28 ± 1.45

0.149

9.29 ± 1.32

0.130

Test group 12

18.49 ± 1.49

18.24 ± 1.33

0.437

18.15 ± 1.31

0.242

Control

11

17.42 ± 1.40

17.61 ± 1.73

0.791

17.54 ± 1.65

0.911

Test group 12

0.91 ± 0.02

0.91 ± 0.02

0.998

0.90 ± 0.02

0.031

Control

110.92 ± 0.01

0.92 ± 0.02

0.947

0.90 ± 0.02

0.010

Test group 12

0.26 ± 0.05

0.25 ± 0.03

0.165

0.22 ± 0.04 ＜0.001

Control

Control

R2
R6
R7
R2
R6
R7

11

0.29 ± 0.05

0.25 ± 0.04

0.019

0.23 ± 0.04

0.001

Test group 12

0.71 ± 0.04

0.71 ± 0.05

0.209

0.69 ± 0.05

0.003

Control

110.73 ± 0.02

0.71 ± 0.03

0.015

0.69 ± 0.03 ＜0.001

Test group 12

0.81 ± 0.06

0.78 ± 0.06

0.137

0.78 ± 0.06

0.116

Control

110.86 ± 0.04

0.80 ± 0.05

0.003

0.80 ± 0.04

0.003

Test group 12

0.40 ± 0.07

0.38 ± 0.05

0.384

0.41 ± 0.08

0.922

Control

11

0.34 ± 0.04

0.36 ± 0.05

0.245

0.36 ± 0.06

0.371

Test group 12

0.41 ± 0.05

0.39 ± 0.07

0.334

0.40 ± 0.06

0.972

Control

0.46 ± 0.06

0.41 ± 0.06

0.004

0.44 ± 0.06

0.107

11

12w

8w

12w

Inter-group
analysisby measured values

Test group 12

13.41 ± 1.91b*Skin elesticity (Cheak)

8w

0w

8w

12w

Differences were considered significant for p < 0.05. Dunnett's test was used to compare data obtained before diet intake with those obtained 8 and 12 weeks after dietintake. The independent samples t-test (the unpaired t-test on SPSS) was used to compare absolute and percent changes in values from baseline (before diet intake)between groups. SD, standard deviation.

_ 94 _Glycative Stress Research

Table 10. Skin-related parameters (subclass analysis)
Parameter

Unit

Group

n

0w

Skin color difference (Upper arm)

Mean

SD

p values

MeanSD

p values

8w

Test group 11

0.70 ± 0.08

0.67 ± 0.10

0.020

0.69 ± 0.08

0.542

0.303 0.646 0.323 0.680 0.195 0.400 0.121

Control80.63 ± 0.14

0.63 ± 0.13

0.945

0.61 ± 0.14

0.480

Hb Index

Test group 11

0.85 ± 0.19

0.88 ± 0.23

0.698

0.87 ± 0.24

0.808

Control

80.83 ± 0.11

0.83 ± 0.16

0.998

1.00 ± 0.22

0.063

Test group 11

59.68 ± 4.67

56.85 ± 6.92

0.285

56.72 ± 4.88

0.255

Control

Hb SO2
Index

(%)

L*

Skin color diffrerence (Cheak)

Mean

8

62.66 ± 6.07

55.30 ± 9.83

0.032

53.13 ± 9.79

0.007

Test group 11

69.48 ± 1.55

69.75 ± 2.00

0.400

69.74 ± 1.99

0.442

Control

870.41 ± 2.41

70.33 ± 2.17

0.978

69.78 ± 3.00

0.360

Test group 11

5.51 ± 0.95

5.36 ± 1.00

0.750

5.29 ± 1.08

0.529

Control

85.39 ± 0.79

4.95 ± 0.82

0.387

5.46 ± 1.19

0.976

Test group 11

14.51 ± 1.53

14.26 ± 1.83

0.463

14.94 ± 1.54

0.152

Control

8

13.15 ± 1.95

13.41 ± 2.01

0.781

13.44 ± 1.83

0.742

Melanin
Index

Test group 11

1.12 ± 0.15

1.09 ± 0.14

0.252

1.10 ± 0.16

0.622

Control

8

1.05 ± 0.16

1.03 ± 0.12

0.438

1.01 ± 0.10

0.118

Hb Index

Test group 11

1.11 ± 0.18

1.16 ± 0.25

0.498

1.20 ± 0.21

0.173

Control8

1.14 ± 0.13

1.22 ± 0.26

0.248

1.23 ± 0.23

0.224

Test group 11

53.37 ± 4.77

57.19 ± 3.15

0.001

58.90 ± 5.25 ＜0.001

Control

852.48 ± 4.13

55.12 ± 2.72

0.036

56.85 ± 3.95

0.001

Test group 11

64.85 ± 1.63

64.89 ± 2.15

0.989

64.71 ± 2.57

0.908

Control865.16 ± 2.41

65.43 ± 2.35

0.609

65.70 ± 2.13

0.186

Test group 11

8.85 ± 0.94

9.11 ± 1.67

0.577

9.49 ± 1.42

0.072

a*

Hb SO2
Index
L*
a*

(%)

8

8.81 ± 1.09

9.13 ± 1.66

0.394

9.13 ± 1.46

0.394

Test group 11

18.51 ± 1.56

18.22 ± 1.39

0.409

18.14 ± 1.37

0.254

Control

817.28 ± 1.54

17.43 ± 1.78

0.917

17.38 ± 1.51

0.960

Test group 11

0.92 ± 0.02

0.92 ± 0.02

0.993

0.90 ± 0.02

0.059

Control80.92 ± 0.01

0.92 ± 0.02

0.873

0.89 ± 0.02

0.010

Test group 11

0.26 ± 0.04

0.24 ± 0.03

0.207

0.22 ± 0.04

0.001

Control

Controlb*

Skin elesticity (Upper arma)

SD

Inter-group
Inter-group
Inter-group
analysisanalysisanalysisby change values by % change by measured values

12w

MelaninIndexb*Skin elesticity (Cheak)

8w

R2
R6
R7
R2
R6
R7

8

0.29 ± 0.05

0.25 ± 0.05

0.071

0.23 ± 0.04

0.009

Test group 11

0.72 ± 0.04

0.71 ± 0.04

0.229

0.70 ± 0.05

0.007

Control80.73 ± 0.02

0.70 ± 0.03

0.021

0.68 ± 0.03 ＜0.001

Test group 11

0.82 ± 0.06

0.78 ± 0.06

0.097

0.77 ± 0.06

0.071

Control80.87 ± 0.04

0.82 ± 0.04

0.027

0.81 ± 0.04

0.018

Test group 11

0.41 ± 0.08

0.38 ± 0.06

0.428

0.42 ± 0.08

0.875

Control80.33 ± 0.03

0.34 ± 0.05

0.510

0.34 ± 0.06

0.652

Test group 11

0.41 ± 0.05

0.39 ± 0.07

0.274

0.40 ± 0.06

0.726

Control

0.47 ± 0.07

0.43 ± 0.06

0.041

0.45 ± 0.07

0.506

8

12w

8w

12w

0w

8w

12w

0.711 0.125 0.887 0.147 0.759 0.600 0.272
0.263 0.064 0.271 0.070 0.242 0.691 0.307
0.496 0.180 0.522 0.182 0.317 0.560 0.968
0.458 0.528 0.498 0.475 0.777 0.355 0.748
0.212 0.813 0.198 0.967 0.106 0.354 0.070
0.986 0.357 0.886 0.440 0.389 0.314 0.166
0.717 0.976 0.767 0.832 0.653 0.590 0.751
0.422 0.446 0.460 0.512 0.677 0.153 0.366
0.626 0.279 0.602 0.266 0.738 0.613 0.390
0.885 0.431 0.832 0.436 0.934 0.980 0.596
0.420 0.374 0.416 0.372 0.108 0.295 0.273
0.789 0.052 0.794 0.051 0.708 0.913 0.070
0.241 0.357 0.216 0.565 0.110 0.571 0.423
0.207 0.013 0.221 0.016 0.667 0.611 0.213
0.723 0.630 0.733 0.687 0.049 0.141 0.151
0.076 0.983 0.135 0.868 0.011 0.152 0.046
0.335 0.708 0.517 0.892 0.065 0.322 0.145

Differences were considered significant for p < 0.05. Dunnett's test was used to compare data obtained before diet intake with those obtained 8 and 12 weeks after dietintake. The independent samples t-test (the unpaired t-test on SPSS) was used to compare absolute and percent changes in values from baseline (before diet intake)between groups. SD, standard deviation.

_ 95 _

Anti-Glycation Effect of a Functional Soymilk Beverage Supplemented with Rice Bran/Rice Bran Oil
Fig 3- a

(a)

0.10

Test diet (n = 12)

0.08

Control diet (n = 11)

0.06

R6

0.04
0.02

*p = 0.028

0.00- 0.02

0w

12 w

8w

- 0.04- 0.06- 0.08- 0.10

Fig 3- b

( b)

0.02

Test diet (n = 11)

0.01

Control diet ( n = 8)

**

0.00
0w

8w

12 w

R7

- 0.01- 0.02- 0.03*p = 0.013- 0.04- 0.05*- 0.06**- 0.07

Fig 3- c(c )*p <0.05**p <0.01

104.00
Test diet (n = 11)
Control diet ( n = 8)

%Change of R 7

102.00**100.0098.00
96.00*p = 0.016
94.00

*

92.00

**

90.00
0w

8w

Fig 3. Skin viscoelasticity change*p <0.05**p <0.01

12 w

a: Difference in R6 by total analysis (Cheak), b: Difference in R7 by subclass analysis (Upper arm), c: % change of R7 by subclassanalysis (Upper arm). Results are expressed as mean ± stndaed deviation. *p < 0.05, **p < 0.01, intra-group analysis vs.0w by
Dunnett’s test, inter-group analysis by Student’s t test.

_ 96 _Glycative Stress Research

Safety evaluation

Safety evaluation was based on the FAS (n = 25). No
serious adverse event was observed during the study period(from September 10 to December 18, 2013). One subject
in the control group had a skin rash after the completion ofassessments at week 8 and was prematurely withdrawn fromthe study at the investigator’s discretion.

Discussion

Data summary
The objective of this study was to evaluate the antiglycation effect of the test diet. Individuals with highglycation stress were selected by screening and assigned toreceive either a functional soymilk beverage, the test diet, ora control beverage for 12 weeks in a randomized controlled
trial (RCT). The results showed that the following parameters
were significantly improved in the test group comparedto the control group: increased exercise as determined bya questionnaire survey, decreased CML (an AGE), andimproved skin elasticity index R6. A subclass analysis in
the subjects with a BMI of ≥ 25 showed a slower increase inplasma glucose level and a slower decrease in skin elasticity
index R7 in the test group. Moreover, HbA1c, a marker of
glucose metabolism, sRAGE, esRAGE, [sRAGE - esRAGE],
and melanin index for skin color difference in the upper arm
was significantly improved after diet intake only in the test
group, with no significant difference between groups.

Beneficial effects of rice bran extracts

Rice bran extracts contain a variety of substances andhave various biological activities, such as anti-oxidative 5, 21-23),
anti-inflammatory 24), cholesterol-lowering 4, 25, 26) and glucose
metabolism-improving 27) actions, as well as providing dietaryfibers that inhibit absorption and promote the excretion ofintestinal toxins 1, 28, 29).
The ethanol-soluble fraction of the hot water extract ofrice bran contains phenols that have a strong antioxidative
capability, such as protocatechuic acid, caffeic acid, ferulic acidand gentisic acid 5), as well as dietary fiber, glucosylceramide
and arabinoxylan. We have also demonstrated that rice bran
extracts inhibit AGE production in an in vitro model of thehuman serum albumin-glucose reaction 8).
Extracts and processed products of rice bran have beentested in animals. The oral administration of rice branderived dietary fiber in rats pretreated with polychlorinatedbiphenyl (PCB) has been shown to inhibit the absorption ofpolychlorinated dibenzofuran (PCDF) and polychlorinateddibenzo-para-dioxin (PCDD) by the small intestine andpromote their excretion in feces 1, 28, 29). This effect has also
been demonstrated in humans; a combination of rice branfiber and cholestyramine has been shown to promote theexcretion of PCDF and PCB in Taiwanese Yu-Chengpatients 30). Rice bran oil has been shown to reduce the serum
cholesterol level in rats 4). Rice bran oil extracts fermented
with Saccharomyces cerevisiae (IFO2346) have demonstrated
anti-stress and anti-fatigue activities when administered orally
in rats and mice 31). Rice bran fluid treated with enzymes
and Bifidobacterium bifidum has been shown to reduce thearea of stress-induced gastric ulcers and ameliorate elevatedserum levels of GOT and GPT 32). Hairless mice (HR-AD)
fed a diet containing rice bran-derived glucosylceramide(GluCer) showed better preservation and restoration of skinbarrier function chronically or acutely disrupted by repeatedtape stripping, as compared to control mice 33). Furthermore,
modified arabinoxylan extracted from rice bran (MGN-3) and
its fractions have been shown to suppress D-galactosamine(D-GalN)-induced liver damage and IL-18 expression in rats 34).
In cell culture systems, the methanol extract of rice bran
has been shown to significantly suppress the proliferation ofmouse splenic lymphocytes stimulated with concanavalin
A (ConA) or lipopolysaccharide (LPS) and suppress ConAinduced interferon-gamma production and LPS-induced
interleukin-6 (IL-6) production 35). The extract has also beenshown to suppress the production of IL-1-alpha and tumor
necrosis factor (TNF)-alpha from LPS-stimulated mouse
macrophage lineage cells 35).
Interesting results have been reported regarding theeffect of rice bran on glucose metabolism 36, 37). Treatment of
26 patients with type 1 diabetes with the soluble fraction ofrice bran for 60 days resulted in decreased HbA1c (11%),decreased FPG (29%) and increased insulin (4%) levels 36).
When the same treatment was given to 31 patients with type2 diabetes, the results showed decreased HbA1c (15%),decreased FPG (33%) and increased serum insulin (4%). In
that study, the fiber fraction of rice bran was also administered
to 26 patients with type 2 diabetes and decreases in totalcholesterol (12%), LDL-cholesterol (15%) and tryglyceride(8%) were reported 36). In a double-blind study in which 28
patients with type 2 diabetes were divided into 2 groups
and treated with stabilized rice bran extract at a dosage of
20 g/day for 12 weeks, the treatment resulted in a decreased
peak postprandial plasma glucose level (14.4%), decreased
area under the glucose level-time curve (15.7%), decreased
HbA1c, decreased total cholesterol (9.2%), decreased LDLcholesterol (13.7%), increased free fatty acid (20%) andincreased adiponectin (40%) levels 37). These findings suggestthat rice bran contains ingredients that have beneficial effects
on glycolipid metabolism, with its soluble and fiber fractions
contributing to its effects on glucose and lipid metabolism,
respectively.
Clinical experience with BioBran, a rice branarabinoxylan derivative, has been reported from casereports 38, 39), non-controlled open-label studies 40 - 42) and
RCTs 43, 44).
A case report has been published in which a 62-year-old
female patient with umbilical metastasis of recurrent coloncancer (Sister Mary Joseph’s Nodule, SMJN) was treatedwith BioBran in a combination therapy; she achieved a longterm survival of at least 2 years and 1 month 38). In anothercase report, a 64-year-old male patient with surgicallyuntreatable terminal pancreatic cancer with distant metastasis
was treated with BioBran in combination with a low-toxicity
chemotherapy; he exhibited temporary relief of ascites,
increased appetite, increased body weight, and reduced tumor
markers; he was able to engage in a normal social life forabout 17 months after the discovery of cancer 39).
In an uncontrolled open-label study, 8 patients withchronic rheumatoid arthritis were treated with BioBran
as a supportive treatment to steroids, analgesics and othermedications for 6 to 12 months, and 3 of them showed
evidence of improvement in symptoms and QOL 40). In thatstudy, 5 of the 8 patients used steroids and analgesics andthe remaining 3 patients used analgesics and Chinese herbal
medicines as well as heat therapy. No rice bran-related_ 97 _

Anti-Glycation Effect of a Functional Soymilk Beverage Supplemented with Rice Bran/Rice Bran Oiladverse event was reported. A 6-month treatment with
BioBran in 16 patients with advanced cancer treated withstandard cancer therapies resulted in increased body weight in
10 (63%) patients, increased white blood cell count in 9 (56%),
increased activity of natural killer (NK) cells in all patients,
and reduced tumor markers in 10 (63%) 41). No adverse
event was observed. Another study in which BioBran was
administered in combination with other therapies to 5 cancer
patients also reported no adverse event 42).
Two controlled trials of rice bran-containing products
have been reported. In a double-blind cross-over study inwhich hydrolyzed rice bran (HRB) extract, prepared bypartially hydrolyzing soluble dietary fiber extracted fromrice bran (main ingredient: arabinoxylan) with a shiitakederived carbohydrate-degrading enzyme, was administered
to 36 elderly subjects (aged 70-95 years, including 9 males)for 6 weeks to evaluate its effect on preventing common
cold symptoms, the treatment shortened the duration ofcommon cold symptoms, reduced the worsening of symptoms
and the need for symptomatic treatment, and relieved thephysical burden of acute-phase respiratory infection 43). In a
RCT in which 152 patients with stage IIIb to IV cancer who
experienced metastasis after undergoing surgery or failed tohave their tumor completely resected were treated with (96patients; combination group) or without (56 patients; control
group) BioBran in addition to a standard alternative/supportive
treatment, the 18-month survival rates in the combinationand control groups were 54.2% and 35.8%, respectively 44).
Moreover, many of the patients in the combination group
showed unchanged or increased NK cell activity. Among the
subjective symptoms evaluated (i.e. pain, malaise, queasy anddecreased appetite), a particularly notable improvement inappetite was observed in the combination group.
Potential benefits of topically applied rice bran oil on
atopic dermatitis have also been reported. Topical applicationof a milky bath agent comprised mainly of rice bran oil in
18 patients with relatively mild atopic dermatitis that mainly
manifests as dry skin either every day or every other day for
2-7 weeks resulted in improvement of dry skin in 14 of 18
patients, as well as resolution or improvement of itching in
87.5% and improvement of scales in 83.3% of patients 45). The
treatment caused no adverse reaction and was highly satisfied
by patients.

Interpretation of data

An increased physical activity as indicated by thequestionnaire survey in this study is consistent with theprevious observation of a prolonged swimming time and antifatigue effect in rats treated with rice bran extracts 31). With nosignificant change in any of the lipid metabolism parameters
tested, the present study failed to verify in humans thepreviously-reported cholesterol-lowering action of rice bran.
The observed decrease in plasma CML level, a measureof glycation stress, may suggest that an AGE productioninhibitory action of the test diet, which has been demonstrated
in vitro, was also exerted in vivo. Given that CML is abundantin the skin, this might have led to an improvement in skinelasticity index R6.
Significant increases were observed in sRAGE, esRAGE,
and [sRAGE - esRAGE] only in the test group, with nosignificant difference between groups. sRAGE and esRAGE
are decoy receptors that bind to AGEs in blood and interstitial
fluid and promote their degradation and excretion. The
difference between sRAGE and esRAGE reflects the levelof sRAGE in a narrow sense (an enzyme-cleaved fragmentof transmembrane RAGE). The present data suggest that
there was no difference between the behavior of sRAGE
in a narrow sense and that of sRAGE. Thus, the increases
in sRAGE, esRAGE and the difference between sRAGE
and esRAGE indicate increased functioning of these decoy
receptors. Although no factor has been identified that affects
soluble RAGE levels, our results provide an interesting
implication that rice bran contains functional ingredients that
affect soluble RAGE levels.

Considerations for soy allergy

There are multiple types of soy allergy, including class
1 allergy, oral allergy syndrome (OAS = class 2 allergy)
that occurs in association with pollinosis, and inhalation
asthma 46-48). Children are commonly affected by class 1 soyallergy, which is sensitized via the gastrointestinal tract 48).
A recent increase in health consciousness and subsequent
increase in consumption of soy food have led to an increasing
prevalence of soy allergy among adults. Young adults are
increasingly affected by OAS, i.e. class 2 food allergy,
primarily to soymilk and other soy products. By comparison,many of the soy-allergic adults experience pollinosis
during the spring season. This is considered to be due tocross reactivity between soy allergens and alder pollens, asevidenced by the fact that many of the soy-allergic patientsare tested positive for alder pollen-specific IgE 48).
Known soy allergens, i.e. class 1 food allergy-related
antigens include beta-conglycinin (the major antigen),
Glycinin A3 subunit, Gly mBd 30K, and Gly mBd 28K 46, 48).
Kunitz soybean trypsin inhibitor (KSIT: 18-20 kDa) has been
identified as a class 1 inhalation allergy-related allergen 46).
Class 2 allergens that have been identified include Gly m4, a
homologue of major antigen PR-10, and Gly m3, a profilin.
The oil body-binding protein, oleosin (23-24 kDa), hasrecently been identified as a novel allergen 47).
Increasing attention has been paid to food allergythat mainly manifests with gastrointestinal symptoms andcommonly affects infants, especially newborns 49). This
type of allergy is characterized by a low incidence of IgE
antibody positivity and the absence of immediate-type allergic
reaction, suggesting the involvement of a cell-dependent
allergy reaction. In fact, many of these patients test positivein an allergen-specific lymphocyte stimulation test aimed
at evaluating cellular immunity. A majority of the cases arecaused by milk, in particular formulated powdered milk, withfewer cases caused by breast milk and soymilk. Nearly halfof these cases manifest allergic symptoms within 1 week
after birth. Some post-weaning cases are caused by solid
food, such as rice and soybeans. Eosinophilic gastroenteritislike pathological features are observed in some cases, suchas marked increase in eosinophils. There also are subtypes
characterized by septicemia-like features, such as C-reactive
protein positive, increased white blood cell count and collapse.
In the present study, 1 subject in the control groupexperienced skin rash, which was considered to have beencaused by soymilk. Although class 1 allergy was suspected,
no IgE test was performed. Soy allergy is characterized by
the manifestation of diverse reactions depending on themechanism of sensitization and the type of responsibleallergens. Consistent with the fact that soybeans cancause not only class 1 but also class 2 allergy, cases havealso been reported in which the ingestion of soymilk by
pollinosis patients resulted in the manifestation of OAS and_ 98 _Glycative Stress Researchanaphylaxis, among other cases of OAS caused by fruits 50).
However, the clinical symptoms and sensitization pathway
have not been well characterized. There is an ongoing needfor characterizing the sensitization mechanisms, pathogenesis
and responsible allergens, as well as an increasing demand for
low-allergic soy food taking into account the diversity of soy
allergens and specific immunotherapies. It should always be
kept in mind that any test diet that contains soymilk, even at a
low volume, can evoke soy allergy.

SafetyRice bran and rice bran oil are considered safe foodingredients as they have long been consumed by people andthe safety assessment information supports its safety. Residual
pesticide testing has also detected none of the following
nitrogen-containing pesticides from rice bran oil: eptam
knoxweed torbin, metolachlor, thiobencarb, diethofencarb,
pendimethalin, flutolanil, lenacil, alachlor, bitertanol, fenarimoland chlorpropham 51). No serious adverse event suspected tobe related to rice bran or rice bran oil has been reported in thepresent study, two pilot studies (13 subjects treated with thetest diet at 16 g/day for 12 weeks, and 8 subjects treated at 20g/day for 8 weeks, respectively), or the literature 36-42). Given
these considerations, we conclude that there is no concern
about the safety of the test diet.

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In the present RCT in female subjects with high glycationstress, the ingestion of a test diet composed mainly of ricebran, which had demonstrated an AGE production inhibitory
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Acknowledgements

We would like to thank Dr. Yasuhiko Yamamoto at
Kanazawa University for his advice on measuring soluble
RAGE content.

Conflict of interest

A-Kit Corporation (Ogaki, Gifu, Japan) served as theclinical research coordinator in this study under a researchfund commissioned by Sunstar Inc. (Takatsuki, Osaka, Japan).

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