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J Nutr Sci Vitaminol
,
54
, 511–514, 2008
Note
Acute
D
-Psicose Administration Decreases the Glycemic Responses
to an Oral Maltodextrin Tolerance Test in Normal Adults
Tetsuo I
IDA
1
, Yuka K
ISHIMOTO
1
, Yuko Y
OSHIKAWA
1
, Noriko H
AYASHI
1
, Kazuhiro O
KUMA
1
,
Mikiko T
OHI
2
, Kanako Y
AGI
3
, Tatsuhiro M
ATSUO
2
and Ken I
ZUMORI
3
2
Research Institute, Matsutani Chemical Industry Co., Ltd., 5–3, Kita-Itami, Itami 664–8508, Japan
Faculty of Agriculture, Kagawa University, 2393 Ikenobe, Miki-cho, Kita-gun, Kagawa 761–0795, Japan
3
Rare Sugar Research Center, Kagawa University, 2393 Ikenobe, Miki-cho, Kita-gun,
Kagawa 761–0795, Japan
(Received June 5, 2008)
1
Summary
An examination was conducted to verify
D
-psicose suppressed the elevation of
blood glucose and insulin concentration in a dose-dependent manner under the concurrent
administration of maltodextrin and
D
-psicose to healthy humans. Twenty subjects aged 20–
39 y, 11 males and 9 females were recruited. A load test of oral maltodextrin was conducted
as a randomized single blind study. The subjects took one of five test beverages (7.5 g
D
-psi-
cose alone, 75 g maltodextrin alone, 75 g maltodextrin 2.5, 5 or 7.5 g
D
-psicose). Blood
was collected before an intake and at 30, 60, 90 and 120 min after an intake. Intervals of
administration were at least 1 wk. The load test with 75 g maltodextrin showed significant
suppressions of the elevation of blood glucose and insulin concentration under the doses of
5 g or more
D
-psicose with dose dependency. An independent administration of 7.5 g
D
-psi-
cose had no influence on blood glucose or insulin concentration.
D
-Psicose is considered effi-
cacious in the suppression of the elevation of blood glucose concentration after eating in
humans.
Key Words
D
-psicose, insulin, sweetening agent, blood glucose, humans
The method of mass-producing
D
-psicose (
D
-ribo-2-
hexulose; CAS registration number: 551–68–8; molec-
ular formula: C
6
H
12
O
6
; molecular weight: 180.156),
which is a C-3 epimer of
D
-fructose, has recently been
developed using
D
-tagatose 3-epimerase (
1
). This has
enabled investigations of
D
-psicose to be conducted into
various fields. With respect to safety from a clinical
study, maximum non-effective levels of
D
-psicose in
causing diarrhea in human subjects were estimated as
0.55 g per kg body weight (
2
). Looking at uses in food,
D
-psicose, corresponding to about 70% of the sweet
taste of sucrose, was formed from fructose during cook-
ing and was included in fruit juice, Worcestershire
sauce and so on (
3
,
4
).
One of the effects
D
-psicose indicated is the suppres-
sion of the elevation of plasma glucose after feeding in
rats (
5
), which fact is of assistance in reducing the risk
of lifestyle-related diseases such as diabetes. In this
study, we investigated the effect of
D
-psicose on post-
prandial plasma glucose concentration in healthy
adults and confirmed the effective doses of an intake.
Materials and Methods
Subjects and study design.
Table 1 summarizes the
backgrounds of 20 healthy Japanese male and female
volunteers, who were recruited from the employees of
Matsutani Chemical Industry Co., Ltd. and the students
E-mail: tetsuo-iida@matsutani.co.jp
of the Faculty of Agriculture, Kagawa University. The
inclusion criteria were as follows: Volunteers were
recruited if he or she was a healthy male or female adult
showing a fasting plasma glucose concentration of
110 mg/100 mL or less as defined in the diabetes diag-
nosis standard prescribed by the Japan Diabetes Society.
Volunteers were excluded if he or she was being treated
for diabetes, had any notable systemic disease that was
problematic in the performance of the study, had a
hepatic function disorder or a renal function disorder or
was judged as inappropriate by a physician.
A load test with oral maltodextrin was conducted
under a randomized single blind study design. The
experimental methods used in the current study have
been referred to in a previous report (
6
). After over 12 h
fasting, blood was first collected in the early morning.
Soon after the first blood collection, subjects took
D
-psi-
cose of differing doses including 75 g maltodextrin
(300 mL) within 1 min. Blood (180 L) was collected at
30, 60, 90 and 120 min after an intake. We set four
doses of
D
-psicose (0, 2.5, 5 and 7.5 g). Administration
was conducted at intervals of at least 1 wk. The intake
order of the four beverages was randomly determined
with respect to each subject. Life conditions for the sub-
jects in the experimental period are indicated in Fig. 1.
As another experiment for examining the effect of
D
-
psicose administration alone on plasma glucose and
insulin concentration, a beverage (100 mL) containing
7.5 g
D
-psicose without containing maltodextrin was
511
512
Table 1.
I
IDA
T et al.
Characteristics of the subjects in this clinical trial.
Male (
n
11)
Female (
n
9)
26.1
50.1
19.9
91.7
119.0
3.1
0.7
4.8
3.7
1.6
6.2
15.3
1.5
0.3
Total (
n
20)
28.2
57.9
20.7
92.1
110.9
3.1
0.7
6.2
8.6
1.8
7.4
21.9
1.6
0.3
Age (y)
Weight (kg)
BMI
Fasting plasma glucose (mg/100 mL)
Plasma glucose at 2 h after intake of carbohydrate (mg/100 mL)
Basal insulin ( U/mL)
HOMA-R
29.8
64.3
21.5
92.3
104.3
3.2
0.7
6.9
5.3
1.7
8.6
24.8
1.7
0.4
Values are expressed as means SD. Blood for the measurement of fasting plasma glucose and basal insulin concentration
was collected in the early morning after over 12 h fasting. Blood for the measurement of plasma glucose concentration at
2 h after an intake of carbohydrate was collected at 2 h after oral administration of 75 g maltodextrin. HOMA-R was calcu-
lated by the following equation: (fasting plasma glucose concentration fasting plasma insulin concentration) /405.
Fig. 1.
Life conditions for the subjects in the experimental period.
independently administered to eight subjects.
Study beverage.
D
-Psicose (purity of over 98%) was
provided by Rare Sugar Research Center, Kagawa Uni-
versity. The used maltodextrin manufactured by Matsu-
tani Chemical Industry Co., Ltd., was composed of 2.5%
D
-glucose, 7.0% maltose and the rest dextrin. This mal-
todextrin has a sweet taste corresponding to about 16%
of sucrose. Each beverage included small amounts of
citric acid, carbonate and flavor to make it palatable for
the subjects, and to mask differences in the sweetness of
the four beverages. Intake intervals, masking effects of
maltodextrin and these additives played a role in the
blinding of this experiment.
Blood collection and measurements of plasma glucose and
insulin concentration.
Blood was collected in heparin-
ized hematocrit tubes after a finger was pricked with
a puncture device used in the testing of diabetes. The
collected blood was centrifuged with a centrifuge
(1,200 rpm) in a hematocrit tube for 5 min. The plasma
was extracted and refrigerated or frozen until measure-
ments. The plasma glucose concentration was deter-
mined in the glucose oxidase technique (Glucose C II-
Test Wako; Wako Pure Chemical Industries, Ltd.,
Osaka, Japan). Insulin concentration was determined
using the ELISA method (Human Insulin ELISA Kit
EZHI-14K; LINCO Research, Missouri, United States).
Ethical committee.
Volunteers were fully informed of
the objective of the study, the test methods, expected
adverse reactions and other related matters. Before the
study started, written consent was obtained from the
subjects. The study protocol and the implementation
complied with the spirit of the Declaration of Helsinki in
1983 under the approval of the ethical committee of
Matsutani Chemical Industry Co., Ltd. (Approval num-
ber: 060707), under the direction of which committee
all operations of this trial was carried out.
Statistical analysis.
Plasma glucose and insulin con-
centration were statistically analyzed. For these signifi-
cant tests, male and female subject data were com-
bined. The values for analysis were determined before
the intake point as well as at the 30, 60, 90 and
120 min point after intakes for each dose and at the
AUC (area under the curve), which was calculated by
the trapezoidal method, for each dose. All measure-
ments were expressed as average standard deviation.
To examine significant differences, repeated measures
of ANOVA and Dunnett’s multiple comparison tests as a
post hoc analysis were employed with a level of signifi-
cance of 5% or less. For software for statistical process-
ing, we used SPSS 13.0 J (SPSS Inc.).
Decrease of Glycemic Responses with
D
-Psicose
513
Fig. 2. Decreases of plasma glucose (a) and insulin (b)
concentration after taking 5 g or more
D
-psicose in
healthy adults during 2 h after 75 g oral maltodextrin
tolerance tests. Values are expressed as average SD.
Significantly different from a non-intake of
D
-psicose at
*
p
0.05, **
p
0.01 and ***
p
0.001 as determined by
Dunnett’s multiple comparison test for independent
samples. , non-intake of
D
-psicose (n 20); , 2.5 g
D
-
psicose intake (n 20); , 5 g
D
-psicose intake (n 20);
, 7.5 g
D
-psicose intake (n 20).
Results and Discussion
There were no dropouts among the 20 subjects par-
ticipating in this trial.
The time course of plasma glucose and insulin con-
centration after an exclusive intake of
D
-psicose was not
affected except the values declined within the range of
physiological deviation. To ease the burden for the sub-
jects in this experiment, the used beverage was prepared
to only 100 mL, which was sufficient to solve 7.5 g
D
-
psicose, and only eight subjects participated, which
subjects were also sufficient to investigate the fluctuat-
ing trends of glucose and insulin concentration.
The effect of
D
-psicose intakes on plasma glucose con-
centration after maltodextrin loading is presented in
Fig. 2a. The results of repeated measures of ANOVA
among intake doses indicated significant differences at
30 min (
p
0.001), 60 min (
p
0.001), 90 min (
p
0.035) and AUC (
p
0.001). Increases of plasma glu-
cose concentration after maltodextrin loading were sig-
nificantly suppressed with 5 g or more
D
-psicose intake
(Dunnett’s multiple comparison tests). The lower values
almost recovered to a concentration similar to the value
in a non-intake of
D
-psicose at 120 min.
The effect of
D
-psicose intakes on plasma insulin con-
centration after maltodextrin loading is presented in
Fig. 2b. The results of repeated measures of ANOVA
among intake doses indicated significant differences at
60 min (
p
0.007) and AUC (
p
0.004). Increases of
insulin concentration after maltodextrin loading were
also significantly suppressed with 5 g or more
D
-psicose
intake.
An animal study on the suppression of increase in
plasma glucose concentration with
D
-psicose found sig-
nificant drops in plasma glucose concentration when
maltose and sucrose were used as substrates, but no sig-
nificant drops when glucose and soluble starch were
used as substrates (
5
). Another animal study proposed
that
D
-psicose inhibited the hydrolysis of maltose with
-glucosidase, which was prepared from the membrane
of rat small intestines (
7
). It follows from these facts that
one of the suppressive mechanisms of
D
-psicose on the
elevation of plasma glucose concentration of rats after
carbohydrate administration is attributable to the inhi-
bition of -glucosidase. The suppression of the elevation
of plasma glucose concentration in humans with
D
-psi-
cose was accordingly expected when two or more types
of sugars were used as a carbohydrate source. Moreover,
maltodextrin, which is a starch hydrolysate, is used as
the carbohydrate source in the oral glucose tolerance
test for the diagnosis of diabetes in Japan. Not glucose,
but maltodextrin, was hence used as a carbohydrate
source in this study.
As another hypothetical mechanism for the suppres-
sion of increase in plasma glucose concentration,
absorbed
D
-psicose in small intestine, in which
D
-psicose
was estimated to absorb at about 25% (
8
,
9
), has the
effect of promoting the uptake of glucose in the liver. It
has been reported that fructose activated glucokinase
and reduced plasma glucose concentration after being
phosphorylated into fructose 1-phosphate by fructoki-
nase in the liver (
10
,
11
). A similar mechanism of
reducing plasma glucose concentration is also pre-
sumed for
D
-tagatose, an isometric form of
D
-psicose
(
12
). The same biochemical path as fructose and taga-
tose could accordingly enhance glucose tolerance.
The doses of
D
-psicose at 5 g (around 1/15 of a carbo-
hydrate intake) would be the minimum effective doses
for suppressing the elevation of plasma glucose and
insulin concentration for 75 g of maltodextrin. This
suggests that about 5 g
D
-psicose, a practical amount
for an intake, is suitable for suppressing the elevation of
plasma glucose concentration from eating one meal
such as a slice of toast (about 50 g carbohydrate).
As this study confirmed the improving effect of glu-
cose tolerance,
D
-psicose is expected to serve as a food
material with a low glycemic index. In the light of appli-
cations of
D
-psicose for food intended to prevent life-
style-related diseases, this report is insufficient to eluci-
date
D
-psicose influences on glucose tolerance under a
continued intake, eaten with many food materials and
other hypoglycemic food materials such as
L
-arabinose,
514
I
IDA
T et al.
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58:
27–32.
Whistler RL, Singh PP, Lake WC. 1974.
D
-Psicose
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34:
200–202.
Matsuo T, Tanaka T, Hashiguchi M, Izumori K, Suzuki
H. 2003. Metabolic effects of
D
-psicose in rats: studies
on faecal and urinary excretion and caecal fermenta-
tion.
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12:
225–231.
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85:
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research is thus required for the elucidation of these
points.
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