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ISSN 0037 380X

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201l VOL.48 No.5

 48

5 (2011 5 )

59

(519)

PYRROLOQUINOLINE QUINONE DISODIUM SALT

IMPROVES HIGHER BRAIN FUNCTION
Takashi KOIKEDA'), Masashiko NereNo'), and Kou MASUDA''

the substance to be useful in memory retention in rat water

INTRODUCTION

The number of people suffering dementia is almost

certain to increase as population in Japan ages. Although
the decline in physiological function associated with aging

maze studies, with the effects enhanced when PQQ is

administered with coenzyme Q10 (CoQ10)'o'. Studies in
humans have demonstrated substantial enhancement of
attention and information identification and processing

in the elderly seems largely unavoidable, the added

burden of oxidative stress-which impairs memory,
learning, and other higher brain functions and often

ability as major effects of PQQ, and as in the animal

studies, these effects were enhanced when PQQ was

impacts daily activities even when not causing dementia-

To further investigate the effects of PQQ in humans, we

can be prevented. Demand for preventive measures is

conducted a placebo-controlled, double-blinded study in

high.

brain functions with the antioxidant (i.e., active oxygen-

which 50- to 7}-year-old Japanese subjects with selfidentified forgetfulness or forgetfulness identified by a
family member, colleague, or acquaintance were given

scavenging) effects of functional substances derived from

PQQ alone or with CoQ10 for 24 weeks and underwent

natural sources has been recently demonstrated in a wide

evaluation of higher brain function using the Repeatable

Improvement of impaired memory, learning, and other

array of animal studies'

Pyrroloquinoline quinone (PQQ) is a quinone

identified in 1979 as an oxidoreductase coenzyme in
microorganisms. PQQ is also present in many
vegetables, fermented foods, and other regularly
consumed foods as well as the tissues of humans and
ratsn-'"i. The discovery of the impacts of PQQ deficiency

in mice in 1989'n' suggested the nutritional importance

of PQQ in mammals. PQQ was found to possibly
function as a new vitamin in 2003"'. These findings
drew more attention to the contribution of PQQ to
physiological activity in humans. Research has shown

that PQQ facilitates nerve regeneration with its

administered with CoQ10

Battery for the Assessment of Neuropsychological Status

(RBANS). The interesting findings of the study are

presented in this paper.

METHODS
Study Supplements
Study products (200 mg in no.2 hard capsules) were
PQQ disodium salt, coenzyme Q10, PQQ disodium salt
placebo, and coenzyme Q10 placebo (hereafter referred to

as the study supplements and placebo supplements)

supplied by Mitsubishi Gas Chemical Company Inc. The

primary ingredients in the study supplements and placebo

supplements are shown in Table 1, along with the amounts

neuroprotective actions and enhancement of nerve

growth factorr6 2r; in addition to acting as an

present.

antioxidant"-'o'

Subjects

Having investigated PQQ extensively, we have shown

1)

2)
3)

'u).

A questionnaire was administered during the subject

Shiba Palace Clinic, 6F, Dairva A Hamamatsucho Building, 1-9-10, Hamamatsucho, Minato-ku, Tokyo 105-0013 JAPAN

Mitsubishi GasChemicalCo.,lnc.,MITSUBISHIBuliding,5-2,Marunouchi2-chome,Chiyoda-ku,Tokyo100-8324,JAPAN
SOLfKEN Co., Ltd., 3F, Daiwa A Hamamatsucho Building, 1-9-10, Hamamatsucho, Minato-ku, Tokyo 105-0013 JAPAN
Key words: pyrroloquinoline quinone (PQQ); coenzyme Qi0 (CoQi0); higher brain function improvement;
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS); placebo-controlled double-blinded study

60

(520)

48

5 (2011 5 )

Tatrle

recruitment period. Individuals satisfying inclusion criteria

(l)

A without satisfying the exciusion criteria through selfreporting underwent screening. Sixty-five individuals

Study supplement formulations

PQQ disodium salt

Ingredients

satisfying inclusion criterion B and found to be eligible for

PQQ disodium

study participation by the study center were selected for

Starch

inclusion in the study.

To ensure the safety and protect the rights of subjects,

the study was conducted in accordance with ethical
principles grounded in the Declaration of Helsinki and with

salt (BioPQQrtr)

Amount
20 1ng
140 5 1ng

Magnesium stearate

75 mg

Starch hydrolysate

82 mg

(2)PQQ disodium salt placebo

Ingredients

the approval of the ethics committee of Shiba Palace Clinic

(Chair: Dr. Touma Suzuki). Subjects were enrolled in the
study only after being fully informed of the objectives and
methods of the study and after providing written consent to

Amount

Starch

187 1ng

Caramel coloring

8.8 mg

Magnesium stearate
Starch hydrolysate

ll mg
13_2 nag

participate.
(3) Coenzyme Q10

Inclusion Criteria A
(1) Japanese men and women 50-70 years old at the time

Coenzyme Q10

of consent.

Saflower oil

(2) Persons with self-identified forgetfulness

Ingredients

or

Beeswax

Emulsifier (glycerol ester)

forgetfulness identified by a close relative or acquaintance.

100 mg
188 mg
6 mg
6 mg

(4) Coenzyme Q10 placebo

Inclusion Criterion B
RBANS result* (relative selection according to score:
persons with total score of 29-52 were selected)

Amount

lngredients

Exclusion Criteria

Amount

Dextrin
Saflower oil

100 mg

Beeswax

13 mg

Emulsifier (glycerol ester)

13 mg

174 mg

(1) Current use of a drug with the potential to affect test

results (antiplatelet drug, anticoagulant, anticonvulsant
(e.g., sodium valproate) , antidepressant, monoamine
oxidase (MAO) inhibitors, thiazide diuretics, warfarin,

similar herb, Korean ginseng, soybean peptide, milk

insulin, dilantin (antiandrogen), acenocoumarol,

peptide

trazodone, drug products metabolized by cytochrome P450

species)

(3) Current regular consumption of any herb

or

supplement with the potential to affect blood glucose

(2) Current regular use or consumption of any of the

drug or food products (including drinks and candies) in

levels

Items 1 or 2 below, which have the potential to affect test

alcohol (sake or shochu: >540 mL; beer: three 500-mL

results:

bottles)

[1]

a-lipoic acid (thiotic aciil. Gingko biloba extract,

carnitine

[2]

Docosahexaenoic acid (DHA), eicosapetaenoic acid

(EPA), arachidonic acid, or another polyunsaturated fatty

acid, r-aminobutyric acid (GABA), phosphatidylserine

(PS), phosphatidylcholine (PC), lycopene, theanine,
caffeine, bacopa, vinca minor, piperine, or any other

(4) Current daily consumption of large volumes of

(5) Potential allergy to any of the study product

ingredients

(6) Current participation in another clinical study

(7) Treatment, hospitalization, or surgery for stroke,
subarachnoid hemorrhage, cerebral infarction, cerebral
hemorrhage, brain contusion, or head trauma

(8) History of serious hepatic, renal, or cardiac

*RBANS: A neuropsychological battery developed by Randolph in the United States"'. The neuropsychological battery questions allow
RBANS has
repeated and quick (-30 min) evaluation of higher brain function disorders with a variety of brain disease complications.
study.
was
used
in
this
RBANS*'
of
version
The
States.
in
the
United
recently attracted attention
Japanese

 48

Table

61 (521)

5 (2011 5 )

Study schedule

Test

First screening

Second screening

Baseline

Veek 8

Week 16

Veek 24

RBANS

No

YeS

Use screening scores

Yes

Yes

Yes

Tatrle
Subject baseline characteristics
Subject baseline characteristics (overall)
Characteristic

Placebo group

PQQ+Q10 grOup

PQQ group

Subjects

22

22

21

Age (years)

553 52

556 43

561 50

Mean

standard deviation
Subject baseline characteristics (males)

Characteristic

Placebo group

Subjects

Age (years)

553 47

Mean

PQQ+Q10 grOup

PQQ group
7

56.1

35

579 52

standard deviation
Subject baseline characteristics (females)

Characteristic

Placebo group

Subjects

15

Age (years)

553 56

Mean

-f

PQQ group

13

15

55_3

48

551

4.7

standard deviation

Dosage and Administration

disease

(9) Prior or current hepatitis

Subjects took 4 capsules of the study supplement once

(10) Severe anemia or psychiatric disease

daily after breakfast with about 100-200 mL of plain cold or

(11) History of or current outpatient treatment for any

of the following: seizures; epilepsy; diabetes mellitus;

hot water.

abnormal thyroid function; hemodialysis; uremia; anuria;

Tests

psychiatric disease

Tests were conducted according to the schedule in Table

(12) Found by the investigator to be ineligible for

2. RBANS was administered orally by employees of Souken

at the time of the second screening and at Weeks 8,

participation in the study

(

PQQ+Q10 group

tS) Has taken a detailed (i. e. , >30 min)

16,

and 24 of study supplement use.

neuropsychological battery at a medical institution

Study Design

The study was a placebo-controlled, double-blinded

study (three-group parallel study)

Statistical Analysis
Measurements are expressed as mean + standard
deviation in the tables and mean + standard error in the
figures.

RBANS results at baseline and Weeks 8, 16, and 24

of.

Duration of Study
Subjects took the study supplements over a 24-week
period from May 1 to December 11, 2009. Subjects were

Tukey's test was used for intergroup comparisons. RBANS

instructed to maintain a regular lifestyle, avoid excessive

and Weeks

exercise, eating, and drinking, and maintain the quality and

analyzed with Dunnett's test. The placebo group was

quantity of their regular eating and exercise habits during

compared to the PQQ group and to the PQQ+CoQ10 group

the study.

with an unpaired t test.

study supplement use were analyzed using Dunnett's test.

results and differences for individual subtests at baseline

8, 16, and 24 of study supplement use were

Category

Uni

Baseline

Group
22

Placebo

RBANS

Veek 8

Intergroup P value

1:2P=1000

430 49

P value over time

484 82

P=0002*

PQQ

22

430 59

1:3P=10110

518 86

P 0 1=

PQQ+Q10

21

430 56

2:3P=l lD00

525 72

Nd.: Dumd! rdt m udld b ed'6s

Nd.: T*.yt bd *s u*d ro tuidir!

t@e

rh. Dl@bo

Fup (r).

Faa

s@

O), rid Paa+alo

Fup

RBANS score
(difierence)

Mean

Points

22

532 741

PQQ

22

882 691

PQQttQ10

21

943 761

565 70

543 69

P 0001

Week 16

105 64

P=O lll15

3P=0164
3P=0960

129 89

P=0067
P=0314

PQQ

Immediate

memory

Visuospatial

Unit

Points

P0ints

Language

Attention

Delayed

memory
Mean

Points

Points

Group

Baseline

Intergroup P value

Week 8

112 73

P value over

22

486 73

1:2P=0858

488

PQQ

22

481 89

1:3P=0018*

512

P=0998
P=0292

PQQ+Q10

21

422 9.6

497

P 0001*

Placebo

22

429 120

404 124

PQQ

22

364 107

PQQ Q10

21

418 123

Placebo

22

497 66

PQQ

22

492 81

546 96

P=0554
P'0157
P=0354
P=0522
P=0010**

PQQttQ10

21

514 61

Placebo

22

420 87

PQQ

22

443 104

PQQ+Q10

21

469 102

Placebo

22

447

PQQ

22

448

PQQ+Q10

21

428

2P=0067
3P=0763

408 99
451 88

l12P=0813
113P=0368

518 55
561 76

P=0070

2P=0431

494 81

P 0001* *

3P=0101

529 83

P 0001*

542 101

P=0001**

491= 80
488 98
478 76

P=0031

l:2P=0950
1:3P=0438

P value

over time

543 76

P 0001***

557 74

P 0001*

573 74

P 0001***

Intergroup P value

1:2P=0817
1:3P=0397
2:3P=0761

Weck 24

P value

1:2P=0549
1:3P=0939

116 63

134 81

P=0()34

1:2P=0676
1:3P=0442

2:3P=0765

142 63

P=0002**

2:3P=0919

lntergroup P value

over time

0001**

P<0.05, **: P<0.01, ***: P<0.001

':

RBANS scores (subtest scores)

lime

Placebo

2P=0242
3P=0844
3P=0547

group (2), and PQQ+Ql0 group (il).

Table
Category

Irrlergrrrup P value

P value over time

2P=0259

standard deviation

(l),

O lllDl

Veek 24

Intergroup P value
l

Note; Dunnett's test was used to statistically analyzc Week 8 versus Week 16 and Week 8 versus Weck 24 scores in each group.
point, but no significant differences were detected.
Note: The nunbers before the P valucs represent the placebo group

time

P 0001

RBANS scores (differences)

lntergroup P value

Placebo

P value over

531 72

P=0059
P=0015*

lntergroup P value

Week 16

P value over time

1:2P=0432

555 83

P=0001**

1:3P=0749

580 86

537 85

P<0001*

449t106
445 94
440 74

503 93

P=0698
P=0003**
P=0636
P=0417
P=0011*
P=0153
P<0001

550 92

0001

535 95

P=0004

529 77

P 0001***

517 74

P 0001* *

515 75

P 0001 *

1:2P=0904
1:3P=0164
=0235
1 3P=0037*
112

521 81
545 107
554 82

112P=0161
1:3P=0090

2P=0922
3P=0592

o001 **

standard deviation

point
Note: An unDaired t test was used to statistically analyze the placebo group versus the PQQ group and the placebo group versus the PQQ+Q10 group at each observation
Note: The numbers before the P values represent the placebo group (1). PQQ group (2), and PQQ+Q10 group (3).

Intergroup P value

Vc ek 24

f'value over tinle

lntcrgroup P value

87

P 00()1**

l12P=0727

582 101

P 0001 *

113P=0516

554 98

0001**

405 147

P'0587

I:2P=0518

377 136

0903

1:3P 0389

437111 89

P==0734

1:212=0395

538 80

P=0068

1:3P 0195

562 69

P 0001*

78

P 0001*

1:2P=0321
1:3P=0506

112P=0887
1:3P=0763

572

598

1:2P=0100
1:3P=0264
1:2P=0595
1:3P=0539

530 91

P 0001

74
576 85
511 78
495 78

P 0001

487 68

P=0003**

557

=0306
1:3P=0018*
1:2

1:2P=0282
113P=0093

P 0001

P=0001**
P=0023

112P=0503
1:3P'0300

Category

2P=0333
3P=0221
3P=0961

Week 16

(3).

Table
Veek 8

Group

O llKll

lntergroup P value

Table 4 RBANS scores

Table
Category

Immediate menory

(diference)

Points

0roup

Veek 8

Intergroup P value

Veek 16

0245 11323

1:2P=0353

691 770

P 0001

PQQ

312 883

113P=0024

992 748

P=0006**

116 110

PlaccbO

(diference)

Language
(difierence)

ldrfierence.)

Delayed memory
(difierence)

Mean

Points

Points

748 868

-249 1248

1:2P=0059
1:3P=0129

PQQ

436 1082

PQQ+Q10

331 1204

Placebo

210 842

PQQ

548 931

PQQ+Q10

468 952

Placebo

735 714

PQQ

859 963

PQQttQ10

733 1198

Placebo

444 896

PQQ

403 708

PQQ+Q10

506 1012

P value c'ver tinrc

202 959
802 852
230 994

1:2P=0215
1:3P=0352

240 758
539 911
391 766

2P=0631
3P=0993

Week 24

1:2P=0196
113 )=0119

867 820

P=0060

132 79

P=0007

P=0089
P'0252
P=0834
P=0982
P=0998
P=0919
P=0846

-238 957

2P=0034

3P 0926

128 1046
196 1339

112P 0244

415 844

=0520

701 859

1:3

832 838
110 70

1:3P 0605

114 101

112P=0506
1:3P=0842

643 846

688 654

P'0051
P=0238

871 814

P=0044

825 6"

time

101 100

P=0410
P=0882

107 106

P value over

0001***
P=0004

1:2P=0448

828 1005
666 1027

112P=0867
1:3P=0832

Intergroup P vrlue

107

95

470 807
599 826

Intergroup P value

112P=0602
113P=0074

1:2P=0233
1:3P=0227

P=0998
P=0365
P=0730
P=0461
P=0561
P=0195
P=O H4
P=0212
P=0070

1:2P=0272
1:3P=0112

112P=0877
1:3P=0921

P=0390
P=0914
P=0778

112P=0490
1:3P=0862

standard deviation

Note: Dunnett's test was used to statistically analyze Week 8 versus Week 16 and Week 8 versus Week 24 scores in each group. t: P<0.05, '*: P<0.01, *'*: P<0.001 '
Note: An unpaired t test was used to statistically analyze the placebo group versus the PQQ group and the placebo group versus the PQQ+Q10 group at each observation poinl
Note: The numbers before the P values represent the placebo group (1), PQQ group (2), and PQQ+Q10 group (3).

Table
Category

lmmediate memory

(higher-scoring tier)

Group

Veek 8

Placebo

215 984

PQQ

228 995

PQQ Q10

200 660

PlacebO

Imnediate memory
(lower-scoring tier)
Mean

Points

-165 128

PQQ

414 767

PQQ+Q10

1250 740

RBANS immediate memorv scores with subiects stratified

lntergroup P value
1

2
3

=0975
=0969

=0230
1:3P=00060

112

Week 16

P value over

timc

Intergroup P value

816 894

=0072

1:2P'0930

845 629

=0100

li3

687 971

P=0088

566

=0754

Veek 24

P value over time

Intergroup P value

971 934

P=0022

l:2P=0639

806 722

P=0128

1:3P=0421

126 590

P 0001**

=0014*

1 2P=0085

764 719

=0002

117 870

P=0050

1:3P=0016

126 124

P=0028

158 108

P=0324

138 970

=0823

64()

Attention

Points

RBANS scores (subtest score diffcrences)

P:acebO

PQQ+Q10
Visuospatial

1:2P=0289
1:3P=0106

standard deviation

Note: Dunnett's test was used k) statistically anaiyze Week 8 versus Week 16 and Week 8 versus Week 24 scores in each group. *: P<0.05, **; P<0.0I, ***: P<0.001
Nole: Nunbers before P values rcpresent the placebo group (1), Pt;Q group (2), and PQQ+Q10 group (iJ).

 48

(524)

Statistical analyses were performed using Dr. SPSS II

5 (2011 5

scoring tier,the PQQttCoQ10 grOup in the low

for Windows software (SPSS Japan,). A two-sided level of

significance of less than 5% was used for all statistical

scoring tier sho ved a significantly better score at

tests.

This finding shows that individuals with lower RBANS

Veek

8 and Veek 16 than the placebo group (Fig 3).

scores may achieve a better degree of improvement in

RESULTS

response to PQQ use than individuals

Subjects

vith

higher

scores

Baseline characteristics of subiects are shown in Table

Adverse Events

3.

The placebo group contained 22 subjects (7 men,

15

women) with a mean age of 55.3 + 5.2 years (men, 55.3

+ 4.7 years; women, 55.3 r- 5.6 years). The PQQ group
also contained 22 subjects (7 men, 15 women) with a
mean age of 55.6 + 4.3 years (men, 56.1 + 3.5 years;

women, 55.3

4.8 years). The PQQ+CoQ10 group

No adverse events M ere encountered in the study_

S S"0 r

vas
A placebo controHed, d9uble blinded study
conducted with the participatiOn Of 65 apaneSe subiects
bet veen

5o and 70 years old with self

identified

contained 21 subjects (8 men, 13 women) with a mean age

forgetfuinesS or forgetfulncss identified by a fanlily

+ 5.0 years (men,57.9 + 5.2 years; women,55.1

member,colleague,or acquaintance SubieCtS Were

given PQQ alone Or with CoQ10 fOr 24 weeks to

of 56.1

4.7 years).

demonstrate the ability of these regilnens to improve

higher brain function.Filthough no substantial difference

RBANS Results
Time courses of absolute total RBANS scores are shown

relative to placebo was seen in total RBF NS scores

in Table 4, and score differences are shown in Table 5 and

Figure 1. Absolute subtest scores (immediate memory,

either for PQQ alone Or with CoQ10,the PQQ+CoQ10

group achieved improvement in inlmediate memory.

visuospatial/constructional, language, attention, delayed

memory) are shown in Table 6, and score differences are

This improvement was more pronounced in subiectS With

shown in Table 7.

ver baseline RBANS scores, vho also achieved

significant improvement in the visuospatia1/
lo

Although the PQQ and PQQ+CoQ10 groups showed

significantly better total scores over time, a similar

constructional subt st The results suggest that PQQ

improvement over time was seen in the placebo group.

brain function.

Throughout the study, absolute scores and score

differences relative to baseline in the PQQ group and
PQQ+CoQiO group did not differ significantly from the
placebo group. In the language subtest, absolute scores
at Weeks 8 and 24 were significantly higher in the
PQQ+CoQ10 group than in the placebo group.
Differences in immediate memory scores at Week 8
were significantly better in the PQQ+CoQ10 group than
in the placebo group (Fig. 2). Differences in visuospatial/
constructional scores at Week 16 were significantly
better in the PQQ group than in the placebo group.
Differences in language, attention, and delayed
memory scores did not differ significantly among

alone or with CoQ10 may be useful for improving higher

Ve have previously demonstrated the usefuiness of PQQ

vith the
in mernory retention in rat vater maze studies,

effects enhanced when PQQ was administered with

coQ102' studies in humans have shown PQQ to imprOve
the higher brain functions of attention and information
identiflcation and prOcessing ability as well as ilnlllediate

memory(vocabulary memory)and stroop test

performance,albeit in a limited manner26).The
improvement in immediate memory shown in the present
study,
vhich used RBAl S, providcs credible support for
previous indings. Although no distinct direrenccs in total
scores were identined relative to the placebo group,spatial

awareness(visuO,patial)imprOved in addition to inllnediate

groups.

memory

For analysis of immediate memory, subjects were

stratified into 2 tiers according to baseline total scores

must be evaluated further, the results of this study show

(Table 8): a high-scoring

the potential of PQQ used a10ne or with CoQ10 in

tier

(33 subjects); and a low-

scoring tier (32 subjects). Although no significant

difference was present between groups in the high-

Although brain function and assessment inethodologies

preventing or reversing the decline in higher brain function

caused by aging and oxidative stress based on the

 48

65

5 (2011 5 )

(525)

(Points)
18

134 142

112

Placebo(n=22)
PQQ(n=22)
PQQ+Q10(n=21)

88 9:4
Note: Dunnett's test was used to statistically analyze
Week 8 versus Week 16 and Week 8 versus Week 24
scores in each group.

*: P<0.05, **: P<0.01,8**: P<0.001.

Mean

Veek 24

Veek 16

Week 8
standard error

Note: Tukey's test was used to statistically analyze the

placebo group versus the PQQ group, the placebo group
versus the PQQ+QiO group, and the PQQ group versus
the PQQ+Qi0 group at each observation point, but no
significant differences were detected.

Figure

RBANS scores (differences)

(Points)
16

Placebo:PQQ+Q10*

14

101

12

748

Placebo(n=22)
PQQ(n=22)
PQQ+Q10(n=21)

867

Note: Dunnett's test rvas used to statistically analyze

025

Week 8 versus Week 16 and Week 8 versus Week 24

scores in each group.

*: P<0.05, **: P<0.01, ***: P<0.001.

Note: An unpaired t test was used to statistically

-2
-4

analyze the placebo group versus the PQQ group and

Week 24

Veek 16

Veek 8

the placebo group versus the PQQ+Q10 group at each

observation point.

Mean tt standard errOr

Figure

RBANS scores (immediate memory (differences)

(Points)
(

Veek 16)

Placebo:PQQ+Q10** Placebo:PQQ+Q10
117

12 6 138

Placebo(n=11)

M PQQ(n=lo)

PQQ+Q10(n=11)
Note:Dunnett's test vas used to statistically analyze

Veek 8 versus Veek 16 and Veek 8 versus Veek 24

scores in each group

*:P<005,**:P<001,***:P<0001

-5

Note: An unpaired t testvas used to statisticaHy

analyze the placebo group Versus the PQQ grOup and

-10

Veek 16

Week 8
Mean
standard error

Figure

Veek 24

the placebo group versus the PQQ+Q10 grOup at each

observation point

RBANS scores (immediate memory (differences) lower 32 scorers)

66

(526)

48

antioxidant, neuroprotective, and other cell- and neuralactivating aclions of these regimens.
The lack of any reported adverse events during the long
24-week (6-month) period of use indicates that the study
supplements pose no safety problems.

In conclusion, PQQ (alone and with CoQ10) was shown

to be a safe supplement that helps to improve higher brain
function.
CONCLUSIONS
A placebo-controlled, double-blinded study using RBANS

was conducted with the participation of 65 Japanese

subjects between 50 and 70 years old who presented with
self-identified forgetfulness or forgetfulness identified by a
family member, colleague, or acquaintance. Subjects were
given PQQ alone or with CoQ10 for an extended 24-week

period to investigate the ability of these regimens to

improve higher brain function.
PQQ was found to improve not only immediate memory,

but also other higher brain functions such as spatial

awareness. The effects of PQQ were enhanced when the

substance was used with CoQ10. Effects were more

pronounced in subjects with poorer baseline total RBANS
scores. With no adverse events reported during the study,
no safety problems were identified.

5 (2011 5 )

neurobehavioural, neurochemical and immunohistochemical

evidences J Neurochem,93,94-104(2005)
8)Tchantchou F,Chan A,Kine L,Ortiz D,Shea TB:Apple juice
concentrate prevents oxidative damage and impaired ,aze
performance in aged mice J Alzheimers Dis,8,283-287(2

5)

9)Salisbury SA,Forrest HS,Cruse WB,Kennard O:A novel

coenzyme from bacterial primary alcohol dehydrOgenases

Nature,280,Aug 30 843-844(1979)
10)Duine A,Frank J,Van zeeland JK:Glucose dehydrogenase
from Acinetobacter calcoaceticusi a `quinoprotein'

FEBS

Lett,108,443-446(1979)
11)Smidt CR,Steinberg FM,Rucker RB:Physio10gic impOrtance
of pyrroloquinoline quinone PrOc Soc ExP Biol

led,197, 19-

26(1991)
12)Stites TE,Mitchell AE,Rucker RB:Physiological importance
of quinoenzymes and O quinone mil,Of COfactors J Nutr,

130,719-727(2000)

13)Rucker R,Cho"anadisai W,Nakano n4:Potential

physiological impOrtanc of pyrroloquinoline quinone Altern
Ied Rev,14,268-277(2009)

14)Killgore ,Smidt c,Duich L,Romero Chapman N,Tinker D,

Reiser K,Melko M,Hyde D,Rucker RB:Nutritional

impOrtance of pyrr010quin01ine quinone Science,245,Aug 25

850-852(1989)
15)Kasahara T,Kato T:Nutritional biochemistry:A new redox
cofactor tamin fOr malllmals Nature,422,Apr 24 832(2X103)

16)Murase K,Hattori A,Kohno M,Hayashi K:StimulatiOn Of

nerve gro vth factOr synthesis/secretion in mouse astroglial

cens by COenzymes Blochem Mol Biollnt,30,615-621(1993)

17)Urakami T,Tanaka A,Yamaguchi K,Tsuji T,Niki E:

Synthesis Of esters of coenzyme PQQ and IPQ,and
stilnulation of nerve growth factor production Blofactors,5,

139-146(1995/96)

18)Yamaguchi K,SasanO A,Urakami T,Tsuji T,Kondo K:

Stimulation of nerve gro vth factor production by

REFERENCES

1) Urano S, Sato Y, Otonari T, Makabe S, Suzuki S, Ogata M,

Endo T : Aging and oxidative stress in neurodegeneration.

2)

Biofactors, 7, 103-1f2 (1998)

Onodera K, Omoi NO, Fukui K, Hayasaka T, Shinkai T,
Suzuki S, Abe K, Urano S : Oxidative damage ofrat cerebral
cortex and hippocampus, and changes in antioxidative defense
systems caused by hyperoxia. Free Radic Res, 37, 367-372
(2003)

3) McDonald SR, Sohal RS, Forster MJ:Concurrent

administraion of coenzyme Q10 and a-tocopherol improves
learning in aged mice. Free Radic Biol Med, 38, 729-736
(2005)

4)

5)

Bickford PC, Gould T, Briederick L, Chadman K, Pollock A.

Young D, Shukitt-Hale B, Joseph J: Antioxidant-rich diets
improve cerebellar physiology and motor learning in aged
rats. Brain Res,866, 2ll-277 Q000)
Sharma M,Gupta YK:Effect of alpha lipoic acid on
intracerebroventricular streptozotocin model of cognitive
impairment in rats. Eur Neuropsychopharmacol, t3, 24I-247
(2003)

6)

7)

N, AEikgoz O, Kayatekin BM, Stinmez A,

Kiray M,Aksu I, Giileqer B, TopEu A, Semin I:Effects of
G6neng S, Uysal

melatonin on oxidative stress and spatial memory impairment

induced by acute ethanol treatment in rats. Physiol Res, 54,
341-348 (2005)
Ahmad M, Saleem S, Ahmad AS,Yousuf S, Ansari MA, Khan
MB, Ishrat T, Chaturvedi RK, Agrawal AK, Islam F: Ginkgo

biloba affords dose-dependent protection against

6-hydroxydopamine-induced parkinsonism in rats:

pyrroloquinoline quinone and its derivatives in vitro and in

vivo Biosci Biotechnol Biochem,57,1231-1233(1993)

19)Yamaguchi K,TsuJi T,Uemura D,Kondo K:Cyclooxygenase

induction is essential for NGF synthesis enhancement by NGF
inducers in L NI cens Biosci Biotechnol Biochem,60,92-94

(1996)

20)Liu S, Li H, Ou Yang , Peng H, Vu K, Liu Y, Yang J:

Enhanced rat sciatic nerve regeheration through slicon tubes
lled with pyrroloquinoline quinone
Iicrosurgery, 25, 329-

337(2005)

21)Li HH,Liu SQ,Peng H,Zhang N:Pyrroloquinoline quinone

enhances regeneration of transected sciatic nerve in rats.Clin

J Traumat01,8225229(2005)
22)Miyatchi K,Urakami T,Abeta H,Shi H,Noguchi N,Niki E:
Action of pyrroloquinolinequinol as an antioxidant against lipid

peroxidation in sOlution Antioxid Redox Signal, 1, 547-554

(1999)

23)Ouchi A,Nakano

I,Nagaoka S,Mukai K:Kinetic study of

the antioxidant activity of pyrroloquinolinequinol(PQQH2, a

reduced form of pyrro10quin01inequinone)in micellar solution

J Agnc Food Chem,57,450-456(2009)

24)He K,Nukada H,Urakami T,Murphy MP:Antioxidant and

pro oxidant

properties Of pyrroloquinoline quinone (PQQ) :

implicatiOns for its function in biological systems Biochem

Pharlnacol,65,67-74(2003)

25)Ohwada K,Takeda H,Yamazaki M,Isogai H,Nakano M,

Shilnomura l, Fukui K, Urano S: Pyrroloquinoline quinone
(PQQ)prevents cognitive dencit caused by oxidative stress in
FatS_

Clin Blochem Nutr,42,2934(2008)

26)Nakano M, Ubukata K,YamamotO T,Yamaguchi H:

Contributed articles: Effect of pyrroloquinoline quinone

 48
(PQQ)On mental status of middle aged and elderly persons

F00D STYLE 21,13,50-53(2009)

Randolph C,Tierney Mc,MOhr E,Chase TN:The

Repeatable Battery for the Assessment of Neuropsychological

Status(RBANS):preliminary clinical validity_J Clin Exp

Ncuropsych01,20,310-319(1998)

Yamashima T,Yoshida M,Kumahashi K,Matsui M,Koshino

5 (2011 5 )

67

(527)

Y, Higashima M, Nagasawa T, Ueki A, Ohtsuka M, Aoki S,

Imuro S, Mori N, Takei N, Hoshino R, Minabe Y, Nanba Y,
Nanba M, Kira J, Ohyagi Y, Haraoka J, Akimoto J, Miura N,
Kimura S, Matsushita M: The Japanese version of RBANS

(Repeatable Battery for the Assessment of

Neuropsychological Status. No to Shinkei, 54, 463-471

\2002)