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Effects of astaxanthin-rich Haematococcus pluvialis extract on cognitive function: a randomised, double-blind, placebo-controlled study

Authors:
  • Shirasawa Anti-Aging Medical Institute

Abstract and Figures

In this study we tried to confirm the effect of an astaxanthin-rich Haematococcus pluvialis extract on cognitive function in 96 subjects by a randomised double-blind placebo-controlled study. Healthy middle-aged and elderly subjects who complained of age-related forgetfulness were recruited. Ninety-six subjects were selected from the initial screen, and ingested a capsule containing astaxanthin-rich Haematococcus pluvialis extract, or a placebo capsule for 12 weeks. Somatometry, haematology, urine screens, and CogHealth and Groton Maze Learning Test were performed before and after every 4 weeks of administration. Changes in cognitive performance and the safety of astaxanthin-rich Haematococcus pluvialis extract administration were evaluated. CogHealth battery scores improved in the high-dosage group (12 mg astaxanthin/day) after 12 weeks. Groton Maze Learning Test scores improved earlier in the low-dosage (6 mg astaxanthin/day) and high-dosage groups than in the placebo group. The sample size, however, was small to show a significant difference in cognitive function between the astaxanthin-rich Haematococcus pluvialis extract and placebo groups. No adverse effect on the subjects was observed throughout this study. In conclusion, the results suggested that astaxanthin-rich Haematococcus pluvialis extract improves cognitive function in the healthy aged individuals.
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Original Article
J. Clin. Biochem. Nutr. | September 2012 | vol. 51 | no. 2 | 102–107doi: 10.3164/jcbn.D-11-00017
©2012 JCBN
JCBNJournal of Clinical Biochemistry and Nutrition0912-00091880-5086the Society for Free Radical Research JapanKyoto, JapanjcbnD-11-0001710.3164/jcbn.11-00017Original Article
Effects of astaxanthin-rich Haematococcus
pluvialis extract on cognitive function:
a randomised, double-blind,
placebo-controlled study
Mikiyuki Katagiri,
1,
* Akira Satoh,
2
Shinji Tsuji
2
and Takuji Shirasawa
1
1
Department of Aging Control, Graduate School of Medicine, Juntendo University, 3-3-10-201 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
2
Technology Center, Yamaha Motor Co., Ltd., 3622-8 Nishikaizuka, Iwata, Shizuoka 438-0026, Japan
*To whom correspondence should be addressed.
E-mail: mkatagi@juntendo.ac.jp
9
(Received 8 November, 2011; Accepted 10 November, 2011; Published online 30 March, 2012)
Copyright © 2012 JCBN2012This is an open access article distributed under the terms of theCreative Commons Attribution License, which permits unre-stricted use, distribution, and reproduction in any medium, pro-vided the original work is properly cited.
In this study we tried to confirm the effect of an astaxanthin-rich
Haematococcus pluvialis extract on cognitive function in 96 sub-
jects by a randomised double-blind placebo-controlled study.
Healthy middle-aged and elderly subjects who complained of age-
related forgetfulness were recruited. Ninety-six subjects were
selected from the initial screen, and ingested a capsule containing
astaxanthin-rich Haematococcus pluvialis extract, or a placebo
capsule for 12 weeks. Somatometry, haematology, urine screens,
and CogHealth and Groton Maze Learning Test were performed
before and after every 4 weeks of administration. Changes in cog-
nitive performance and the safety of astaxanthin-rich Haemato-
coccus pluvialis extract administration were evaluated. CogHealth
battery scores improved in the high-dosage group (12 mg astax-
anthin/day) after 12 weeks. Groton Maze Learning Test scores
improved earlier in the low-dosage (6 mg astaxanthin/day) and
high-dosage groups than in the placebo group. The sample size,
however, was small to show a significant difference in cognitive
function between the astaxanthin-rich Haematococcus pluvialis
extract and placebo groups. No adverse effect on the subjects was
observed throughout this study. In conclusion, the results sug-
gested that astaxanthin-rich Haematococcus pluvialis extract
improves cognitive function in the healthy aged individuals.
Key Words: Astaxanthin, Haematococcus pluvialis,
cognitive function, aging, clinical efficacy
Introduction
I
t is widely accepted that cognitive function decreases with
aging. Moreover, dementia, Alzheimer disease, etc., are
diseases in which cognitive function is drastically reduced.
(1)
Astaxanthin (Ax) is a carotenoid found in marine organisms such
as shrimp, crab, krill, salmon, and microalgae.
(2)
It has strong
anti-oxidant properties, as it consumes free radicals such as singlet
oxygen to form stable triplet oxygen. In recent years, the effect of
Ax against aging and against illnesses related to oxidisation stress
has been confirmed by its use in cosmetics and whitening products
and in the treatment of fatigue and cancer.
(3,4)
Ax exhibits immuno-
modulation properties;
(5,6)
alleviates eye fatigue;
(7)
and prevents
Helicobacter pylori infection,
(8)
metabolic syndrome,
(9)
and atopic
dermatitis.
(10)
Due to its high consumption of glucose and oxygen, the brain
tends to produce active oxygen and free radicals even though it
is composed of substances that are easily oxidisable, such as
unsaturated fatty acids and catecholamine. That is, the brain is an
organ that is easily damaged by oxidisation stress. Brain health,
such as that during normal aging and in neurodegenerative condi-
tions such as Alzheimer disease or Parkinson disease, is closely
related to oxidisation stress.
(11,12)
Halliwell reported oxidative
damage in the aging brain, and suggested that anti-oxidants may
play a role in protecting the brain from reactive oxygen species
(ROS).
(13)
Therefore, since Ax is a strong antioxidant, we anticipate that it
will be beneficial for maintaining brain health. Ax improved cell
survival and reduced apoptosis and caspase 3 and 9 activation in
neuroblastoma cells exposed to oxidative stress. Ax also inhibits
oxidation stress-induced apoptosis in nerve cells. Memory and
learning ability, as assessed in the T-maze test, is improved in
immature mice by treatment with Ax. Moreover, when a normal
aging mouse was medicated with Ax, memory improvement was
observed. In Morris water maze examinations in Fischer rats, Ax
treatment improved the memory of both immature (4 months) and
aged rats (18 months). The effect was more remarkable in the old
rats than in the young ones, suggesting that Ax improves cognition
and/or prevents age-related cognitive damage.
We performed a preliminary clinical trial of 12 weeks of
astaxanthin-rich Haematococcus pluvialis extract (Ax-Hp) treat-
ment in 10 healthy men between 50 to 69 years of age, who
complaints of age-related forgetfulness to assess the effects of the
supplements on cognition.
(14)
We reported changes in the P300
brain waves, related to cognitive function, and improvements
in CogHealth scores.
(14)
This randomised double-blind placebo-
controlled study was performed to validate the effects of Ax-Hp
on cognitive function. In the preliminary trial, a 12-mg/day dose of
Ax elicited an effect. In this trial, we employed a 12-mg/day dose
and a 6-mg/day dose to look for the presence of a dose response.
Materials and Methods
Study subjects. Healthy men and women between 45 to 64
years of age, who complaints of age-related forgetfulness were re-
cruited; 138 subjects participated after providing signed informed
consent. The subjects’ height, body weight, body mass index
(BMI), blood pressure, and pulse rate were measured, along with
performing haematological and urinary analyses, the Hachinski
Ischaemic Scale, and tests of cognitive function (Hasegawa
Dementia Scale-Revised [HDS-R], CogHealth, and Groton Maze
Learning Test [GMLT]).
Subjects were excluded if they exhibited signs of dementia
(HDS-R score, 20 points) or cerebrovascular dementia (Hachinski
Ischaemic Score, 7), habitually consumed Ax supplements,
I
J. Clin. Biochem. Nutr. | September 2012 | vol. 51 | no. 2 | 103
©2012 JCBN
M. Katagiri et al.
used games and books designed to improve cognitive function, or
were judged unfit for participation due to the results of their
laboratory analyses. Eventually, 96 subjects (46 men and 50
women, 55.7 ±3.7 years of age) qualified for participation.
Study design. This randomised double-blind placebo-
controlled study consisted of a high-dosage group (12 mg/day of
Ax), low-dosage group (6 mg/day of Ax), and a placebo group.
The subjects were randomly allocated into 3 groups (n= 32 per
group). After confirming that the average age and BMI of each
group were equivalent, the study coordinator named the 3 groups
as the high-dosage group, low-dosage group, and placebo group,
and created the allocation table. The coordinator also labelled
the high-dosage, low-dosage, and placebo supplements with the
subject IDs, according to the allocation table. The coordinator
sealed and stored the allocation table until the study ended. The
demographic characteristics of each group are shown in Table 1.
To minimise the learning effect, the CogHealth battery and
GMLT were repeated 2 weeks after the screening tests; these
scores were set as the baseline. Assessments of subjective
symptoms, somatometry, haematological and urinary tests, and
cognitive function tests (CogHealth and GMLT) were performed
after 4, 8, and 12 weeks of Ax-Hp administration. The subjects
maintained a diary to record their daily Ax-Hp supplement doses
and the subjective symptoms during the 12-week study period
(Fig. 1).
Supplements. Puresta
®
(YAMAHA Motor Co., Ltd.)
(15)
was
used for Ax-rich Haematococcus pluvialis oil. The raw materials
of the supplements were olive oil (K. Kobayashi & Co., Ltd.),
gelatine (porcine in origin), Ax-Hp (6 or 12 mg of Ax dialcohol),
glycerine, vitamin E, and an emulsifier. The placebo capsule had
corn oil (J-OIL MILLS, Inc.) as a substitute for Ax-Hp. The
subjects ingested the supplement after breakfast everyday for 12
weeks. When they could not take the supplement after breakfast,
they were asked to take it after lunch or supper.
Ethics. The study protocol and informed consent documents
were reviewed and approved by the ethics committee of Anti-
Aging Science, Inc. All study subjects provided written informed
consent prior to participation. The protocols were carried out
under the provisions of the Declaration of Helsinki.
Cognitive function tests.
CogHealth battery. The CogHealth battery measures response
time and accuracy with 5 card games played on a personal com-
puter. The card games include tests of ‘simple reaction’, ‘choice
reaction’, ‘working memory’, ‘delayed recall’, and ‘divided atten-
Table 1. Characteristics of study subjects
Characteristic Placebo group Ax-Hp low-dosage group Ax-Hp high-dosage group
Mean ±SD Mean ±SD Mean ±SD
No. of subjects 32 32 32
No. of men/women 15/17 16/16 15/17
Age (years) 51.6 ±5.3 51.1 ±5.9 51.5 ±5.7
Height (cm) 161.6 ±7.0 161.8 ±8.4 161.4 ±8.9
Body weight (kg) 61.1 ±10.1 61.0 ±10.8 62.6 ±11.6
BMI 23.3 ±2.8 23.2 ±2.9 23.9 ±3.3
Fig. 1. Flow diagram of the experimental design and procedure.
doi: 10.3164/jcbn.D-11-00017
©2012 JCBN
104
tion’. The ‘simple reaction’ task requires the subjects to push a
button as quickly as possible when the cards are placed face-up on
a table. The ‘choice reaction’ task requires subjects to identify
whether a card is red or black by pushing a button (labelled YES
or NO) when cards are placed face-up on a table. These tasks
measure the reaction and control in a frontal lobe function. The
‘working memory’ task requires subjects to identify whether a
card is the same or different from the previous card. The ‘delayed
recall’ task requires subjects to identify whether overturned cards
have appeared previously. These 2 tasks measure immediate
memory and episodic memory. The ‘divided attention’ task
requires subjects to identify whether a card touches a line while
moving up and down at random. This task measures spatial
attention.
The response time is measured with a sensitivity of 1/1,000 s.
The CogHealth battery is not influenced by culture, language, or
level of education,
(16)
and is not influenced by the learning effect.
Moreover, it can detect a slight change in cognitive function and
can be used to diagnose mild cognitive impairment.
(17,18)
The CogHealth battery is based on task switching as an
evaluation of high-order cognitive functions (execution function),
such as control of action or reconstruction of information
processing.
(19–21)
Moreover, brain image analysis by fMRI has
revealed frontal lobe activity associated with task switching; thus,
the CogHealth test is also a frontal lobe function test.
(22,23)
Reaction time in a task-switching test is a measure of the
processing time in total cognition and performance processing,
and is widely used as an index of cognitive information-
processing ability.
Although CogHealth battery was developed in Australia, it has
been validated in Japanese subjects.
(24)
A Japanese version of the
CogHealth battery and the GMLT were offered with the coopera-
tion of Health Solution, Inc. (Tokyo).
The subjects performed the CogHealth battery with a keypad
that consists of only 2 keys to exclude the influence of computer
Tab l e 2 . Comparison of the 3 groups of CogHealth at the time of Ax-Hp
administration
Dropouts were excluded from the data analysis. Data were analyzed by
2-way factorial ANOVA adjusted for age and sex.
Tas k p value
Time Group Interaction
Response time
Simple reaction 0.376 0.249 0.817
Choice reaction 0.601 0.770 0.826
Working memory 0.220 0.636 0.436
Delayed recall 0.174 0.552 0.423
Divided attention 0.621 0.467 0.810
Accuracy
Working memory 0.074 0.892 0.178
Delayed recall 0.343 0.344 0.635
Tab l e 3 . Mean response times and accuracies (±SD) on CogHealth tasks at baseline, and after 4, 8, and 12 weeks of Ax treatment
Dropouts were excluded from the data analysys.
p<0.1, *p<0.05, **p<0.01 (vs baseline). Data were analyzed by one-way repeated measure ANOVA,
adjusted for age and sex. Multiple comparisons of 4, 8, and 12 weeks with baseline were performed using Bonferroni correction.
Group/Task
Baseline 4 weeks 8 weeks 12 weeks
Mean ±SD Mean ±SD p
(vs baseline) Mean ±SD p
(vs baseline) Mean ±SD p
(vs baseline)
Placebo group (n= 31)
Response time (ms)
Simple reaction 288.7 ±59.1 271.5 ±38.2 0.789 267.8 ±40.6 0.345 265.0 ±36.9 0.123
Choice reaction 467.5 ±70.9 446.4 ±53.1 0.506 453.1 ±56.5 1.000 440.9 ±52.8 0.124
Working memory 686.0 ±148.9 647.7 ±100.4 0.194 670.6 ±151.5 1.000 644.6 ±124.7 0.071
Delayed recall 909.7 ±218.1 875.3 ±217.8 1.000 887.8 ±243.1 1.000 903.8 ±270.1 1.000
Divided attention 413.0 ±103.3 390.0 ±75.2 0.597 379.6 ±82.0 0.153 388.7 ±73.9 0.397
Accuracy (%)
Working memory 95.1 ±5.3 96.2 ±3.8 1.000 95.2 ±5.5 1.000 94.9 ±8.3 1.000
Delayed recall 66.9 ±10.3 68.8 ±8.6 1.000 71.1 ±10.4 0.355 69.2 ±9.4 1.000
AX low-dosage group (n= 29)
Response time (ms)
Simple reaction 303.4 ±81.7 284.3 ±46.2 0.660 274.8 ±39.4 0.077 285.0 ±48.0 0.608
Choice reaction 468.0 ±82.6 448.8 ±60.4 0.558 440.2 ±52.9 0.080 446.7 ±44.0 0.393
Working memory 661.9 ±120.2 651.4 ±94.2 1.000 629.6 ±96.4 0.352 641.6 ±91.8 1.000
Delayed recall 912.2 ±145.6 882.3 ±139.5 1.000 844.4 ±103.8 0.051
878.4 ±131.4 1.000
Divided attention 428.8 ±72.4 411.9 ±85.7 1.000 406.7 ±71.9 0.960 405.3 ±81.6 0.483
Accuracy (%)
Working memory 94.1 ±5.0 95.3 ±4.4 1.000 96.4 ±5.3 0.159 96.7 ±3.7 0.186
Delayed recall 70.7 ±6.7 72.4 ±11.0 1.000 72.9 ±8.8 1.000 71.0 ±7.9 1.000
AX high-dosage group (n=29)
Response time (ms)
Simple reaction 302.9 ±71.2 292.2 ±49.7 1.000 284.5 ±56.7 0.626 280.6 ±47.3 0.242
Choice reaction 480.1 ±77.5 454.7 ±64.1 0.207 453.1 ±67.2 0.104 451.1 ±56.7 0.083
Working memory 655.9 ±136.5 638.6 ±130.2 1.000 624.5 ±132.1 0.319 609.2 ±123.5 0.044*
Delayed recall 880.1 ±189.4 843.9 ±182.8 0.852 829.4 ±209.8 0.302 818.3 ±195.9 0.097
Divided attention 419.4 ±79.6 415.4 ±104.9 1.000 392.3 ±86.9 0.483 385.3 ±72.5 0.074
Accuracy (%)
Working memory 95.4 ±5.8 93.8 ±6.6 0.433 95.4 ±5.5 1.000 95.6 ±7.4 1.000
Delayed recall 67.3 ±11.8 71.3 ±9.0 0.361 71.5 ±7.3 0.320 72.9 ±7.5 0.028*
J. Clin. Biochem. Nutr. | September 2012 | vol. 51 | no. 2 | 105
©2012 JCBN
M. Katagiri et al.
skills. Prior to performing each task, the subjects received a full
explanation of the task and were permitted to practice.
GMLT. The ‘maze’ of the GMLT was specified at random on a
personal computer in a 10 ×10 layout requiring 28 steps to move
from the upper left to the lower right goal.
(25)
The subjects worked
through the same hidden maze 5 times, and then performed 5
CogHealth tasks. The same maze was performed once again at the
end of testing, to provide a measure of spatial working memory.
The GMLT indicates a learning effect, while the CogHealth is not
affected by learning.
In order to exclude the influence of computer skills, the subjects
performed the test on a touch screen. The subjects received
instructions for all tasks of CogHealth battery and GMLT, were
asked to ‘Please push a button quickly and correctly’, and were
guided so that maximum performance might be demonstrated.
(26)
Analysis of the results of CogHealth battery included mean
response time (ms) for every task, mean accuracy (%) of ‘working
memory’ and ‘delayed recall’, and those of the results of the
GMLT included mean total duration (s) and total errors after
performing a maze 6 times.
Somatometry. Somatometry data included height, body
weight, BMI, blood pressure (systolic/diastolic), and pulse rate.
Haematological and urinary tests. Haematological para-
meters, including white blood cell count, red blood cell count,
haemoglobin level, haematocrit, platelet count, MCV, MCH, and
MCHC; biochemical parameters, including levels of total protein,
albumin, total bilirubin, triglycerides, total cholesterol, HDL
cholesterol, LDL cholesterol, BUN, creatinine, AST, ALT,
γ
-GTP
,
LDH, ALP, uric acid, serum electrolytes (Na, K, and Cl), and
fasting blood sugar and A/G ratio; and qualitative urinalysis
parameters, including protein, glucose, occult blood, pH, and
urobilinogen, were determined.
Statistical analysis. All cognitive parameters of CogHealth
and GMLT were compared between groups with 2-way factorial
ANOVA adjusted for age and sex. One-way repeated measure
ANOVA, adjusted for age and sex, was used to compare scores at
baseline and at after 4, 8, and 12 weeks; multiple comparisons
were performed using Bonferroni correction.
All statistical analysis was performed using SPSS 16.0J for
Windows (SPSS Japan Inc., Tokyo, Japan).
Results
The effectiveness and safety of Ax-Hp were evaluated in 89
subjects who participated in all tests (high-dosage group, 29;
low-dosage group, 29; and placebo, 31). The subjects ingested
80% or more of the provided Ax-Hp supplements.
Improvement of CogHealth score. Table 2 shows the
comparison of 3 groups at the time of Ax-Hp administration, and
Table 3 shows the mean response time of all 5 CogHealth tasks
and the mean accuracy of 2 tasks—‘working memory’ and
‘delayed recall’—at baseline and at 4, 8, and 12 weeks of Ax-Hp
administration. The 3 groups did not significantly differ. However,
the changes in response time were as follows: in the high-dosage
group, improvement trends were observed for ‘choice reaction’
(451.1
±
56.7 vs 480.1
±
77.5), ‘delayed recall’ (818.3
±
195.9
vs 880.1
±
189.4), and ‘divided attention’ (385.3
±
72.5 vs 419.4
±
79.6), each p values <0.1 at 12 weeks, and ‘working memory’ was
significantly improved (609.2
±
123.5 vs 655.9
±
136.5; p<0.05)
at 12 weeks; improvement trends were observed for ‘working
memory’ (644.6
±
124.7 vs 686.0
±
148.9; p<0.1) at 12 weeks
in the placebo group and ‘delayed recall’ (844.4
±
103.8 vs
912.2
±
145.6; p<0.1) at 8 weeks in the low-dosage group.
‘Delayed recall’, a measure of accuracy, significantly improved in
the high-dosage group at 12 weeks (72.9
±
7.5 vs 67.3
±
11.8;
p<0.05). The results of the CogHealth test suggest that 12 weeks
of high-dose Ax-Hp administration improved cognitive function.
Improvement of GMLT score. Table 4 shows the com-
parison of 3 groups at the time of Ax-Hp administration, and
Table 5 shows the total durations and errors of the 6 trials of
GMLT at baseline and at 4, 8, and 12 weeks of Ax-Hp administra-
tion. There was no significant difference in the 3 groups. In each
group, the total duration was significantly shortened at 8 weeks,
but there was no difference between the groups.
However, the total errors in each group were as follows: the
low-dose group showed significant improvement after 4 weeks
(63.3
±
24.5 at Week 4, 61.3
±
21.6 at Week 8, and 57.3
±
20.7 at
Week 12, each p<0.01 vs baseline; 79.9
±
31.0); the high-dose
group also showed significant improvement after 4 weeks
(68.9
±
33.9; p<0.05 at Week 4, and 60.8
±
24.5; p<0.01 at Week
8 and 60.6
±
25.1; p<0.01 at Week 12, each p values vs baseline;
83.0
±
36.9), whereas the placebo group showed significant
improvement at 12 weeks (60.7
±
25.6 vs 74.3
±
22.9, p<0.01).
On the basis of these results, we conclude that short-term spatial
working memory was improved by ingestion of 6 mg of Ax.
Safety evaluation of Ax-Hp. Somatometry, haematological
and urinary tests, and an oral consultation after 12 weeks of Ax-Hp
Tab l e 4 . Comparison of the 3 groups of GMLT at the time of Ax-Hp
administration
Dropouts were excluded from the data analysys. Data were analyzed by
2-way factorial ANOVA adjusted for age and sex.
Tas k p value
Time Group Interaction
Total duration 0.185 0.850 0.870
Total errors 0.724 0.905 0.278
Tab l e 5 . Mean total duration and total errors (±SD) on GMLT tasks at baseline, and after 4, 8, and 12 weeks of Ax treatment
Dropouts were excluded from the data analysys. *p<0.05, **p<0.01 (vs baseline). Data were analyzed by one-way repeated measure ANOVA,
adjusted for age and sex. Multiple comparisons of 4, 8, and 12 weeks with baseline were performed using Bonferroni correction.
Group/Task
Baseline 4 weeks 8 weeks 12 weeks
Mean ±SD Mean ±SD p
(vs baseline) Mean ±SD p
(vs baseline) Mean ±SD p
(vs baseline)
Placebo group (n=31)
Total duration (s) 158.8 ±36.0 148.7 ±35.6 0.193 143.0 ±34.9 0.017* 134.4 ±33.2 <0.001**
Total errors 74.3 ±22.9 67.8 ±23.3 0.925 65.1 ±23.0 0.258 60.7 ±25.6 0.003**
Ax low-dosage group (n=29)
Total duration (s) 157.8 ±25.9 147.3 ±21.5 0.322 137.2 ±23.8 0.002** 127.8 ±16.2 <0.001**
Total errors 79.9 ±31.0 63.3 ±24.5 0.005** 61.3 ±21.6 0.001** 57.3 ±20.7 <0.001**
Ax high-dosage group (n=29)
Total duration (s) 162.0 ±44.8 153.2 ±43.0 0.517 139.5 ±34.3 <0.001** 135.4 ±33.2 <0.001**
Total errors 83.0 ±36.9 68.9 ±33.9 0.024* 60.8 ±24.5 <0.001** 60.6 ±25.1 <0.001**
doi: 10.3164/jcbn.D-11-00017
©2012 JCBN
106
administration revealed no confirmed adverse effects, indicating
that Ax-Hp supplementation is safe.
Discussion
There have been many reports of research on cognitive func-
tional improvement in the fields of medicine, psychology, and
exercise physiology. The aging population and the medical
issues that accompany aging have raised concerns about cognitive
function improvement. And it is hoped that prevention may be
achieved via specific dietary changes; there have been promising
reports on the effectiveness of docosahexaenoic acid,
(27)
arachidonic acid,
(28)
Ginkgo biloba
,
(29)
Pinus radiata
bark extract,
(30)
and acetic acid bacteria
(31)
in retarding cognitive function loss.
Ax is a strong anti-oxidant. Nakagawa et al.
(32)
reported the anti-
oxidant effect of Ax-Hp on phospholipid peroxidation in human
erythrocytes. Iwabayashi et al.
(33)
reported that Ax-Hp increases
the biological anti-oxidants potential (BAP) in human. It is clear
that the anti-oxidant activity of Ax-Hp is effective in human
and animal studies. This study lets expect that Ax-Hp reduces
oxidisation in the brain, leading to improved scores in tests of
cognitive function.
Flavonoids are strong natural anti-oxidants like Ax, and they
were thought to improve age-related cognitive decline. Youdim
et al.
(34)
reported on the neuroprotective effects of dietary flavo-
noids in vivo. Pipingas et al.
(30)
reported that flavonoid-rich P.
radiata bark extract improved cognitive function in tests of
immediate recognition and spatial working memory. It is thought
that the brain and nervous oxidisation are improved by the anti-
oxidant activity of flavonoids, as is the case with Ax-Hp.
We performed a preliminary clinical trial of Ax-Hp and
cognitive function improvement in 10 healthy men between 50 to
69 years of age, who complained of age-related forgetfulness.
We reported that the response time of 5 CogHealth tasks was
significantly improved (p<0.05) and that the amplitude of P300
brain waves, which are related to cognitive function, tended to
increase (p<0.1) after 12 weeks of Ax-Hp treatment.
This randomised double-blind placebo-controlled study was
performed to validate the beneficial effects of Ax-Hp on cognitive
function in human subjects. Based on the results of the preliminary
study, the high dosage was set at 12 mg/day, and 6 mg/day was
set as the low dosage in order to confirm the presence of a dose
response. The administration period was set to 12 weeks as in
the preliminary study. Brain function was assessed with the
CogHealth test and GMLT, both of which can perform objective
measures in a large number of subjects.
We failed to show a significant difference between groups in
the CogHealth test. No differences were observed at any of the
assessments (4, 8, or 12 weeks). In addition, there were no
differences between the high-dosage, low-dosage, and placebo
groups in the reaction time and accuracy of the task-switching test.
However, we observed significant improvements in the high-dose
group in the response time for 1 task and in the accuracy of 1 task,
and improvement trends was observed in 3 tasks. We conclude
that these significant differences and trends are indicative of the
Ax-induced improvement in cognitive function.
GMLT also revealed no significant differences between groups.
The total duration did not change between groups or over time.
However, total error improved significantly by 4 weeks in the
low-dosage and high-dosage groups in contrast to the placebo
group, which showed significant improvement only at 12 weeks.
These results also suggest the Ax-induced improvement in cogni-
tive function.
Although improvements in the CogHealth test were observed
only with a dose of 12 mg/day, GMLT scores were improved at
6 mg/day. This difference may be because the methods of
measuring cognitive performance differ. The GMLT includes a
test of spatial working memory that is highly sensitive, can be used
to measure age-related reductions in cognitive function, and can
detect the effect of a supplement or remedy. Further verification is
required.
Although the tests employed by Pipingas et al.
(30)
differ from the
tests used in this study, immediate recognition is evaluated by the
CogHealth test and spatial working memory is evaluated by the
GMLT. The combination of these tasks may be useful to verify
other supplements or remedies.
The CogHealth test revealed improvements in cognitive func-
tion with 12 mg/day Ax-Hp for 12 weeks. This supports the results
of our preliminary clinical study. In particular, the improvement
in response time, which is a measure of short-term memory, and
in the accuracy of the ‘delayed recall’ task was remarkable.
Moreover, total errors in the GMLT, which is also associated with
memory, showed significant improvement with 6 and 12 mg/day
Ax-Hp.
However, significant differences between groups were not
observed, possibly due to the small sample size. Moreover, the
average age may have been too young to observe age-related
cognitive decline. We plan to investigate this issue further.
We observed no adverse effects to express any concerns
regarding the safety of Ax-Hp.
Conflicts of Interests
This work was supported by a grant from Yamaha Motor Co.,
Ltd.
Acknowledgments
We thank Dr. Y. Koga (Department of Neuropsychiatry, Kyorin
University School of medicine) for planning the study design; R.
Sakurai (Tokyo Metropolitan Institute of Gerontology) for data
analysis.
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The present treatise, written from an eclectic systematic point of view, stays close to experimental findings and the immediate theories arising therefrom. Primary emphasis is placed upon contributions made by psychologists. The fields covered and the relative space allotted to each may be indicated as follows: memory, 45 pages; retention, 19; memory for form, 23; conditioned response, 32; maze learning, 32; practice and skill, 20; transfer of training, 32; economy and interference, 26; feeling, 8; expression of emotions, 15; bodily changes in emotion, 19; "psychogalvanic reflex," 22; reaction time, 42; association, 28; experimental esthetics, 24; psychophysical methods, 36; results in psychophysics, 22; skin senses, 27; smell and taste, 24; hearing, 38; sight, 37; eye movements, 19; perception of color, 28; perception of form, 28; visual space, 33; attention, 29; reading, 33; problem solving behavior, 37; and thinking, 42 pages. There is a bibliography of 35 pages. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
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rights: 本文データは和漢医薬学会の許諾に基づき複製したものである We evaluated the effects of astaxanthin, a red carotenoid, on accommodation, critical flicker fusion (CFF), and pattern visual evoked potential (PVEP) in visual display terminal (VDT) workers. As controls, 13 non-VDT workers received no supplementation (Group A). Twenty-six VDT workers were randomized into 2 groups: Group B consisted of 13 subjects who received oral astaxanthin, 5 mg/day, for 4 weeks, and Group C consisted of 13 subjects who received an oral placebo, 5 mg/day, for 4 weeks. No significant difference in age was noted among the 3 groups. A double-masked study was designed in Groups B and C. Accommodation amplitude in Group A was 3.7± 1.5 diopters. Accommodation amplitudes (2.3±1.4 and 2.2±1.0 diopters) in Groups B and C before supplementation were significantly (p<0.05) lower than in Group A. Accommodation amplitude (2.8±1.6 diopters) in Group B after astaxanthin treatment was significantly (p<0.01) larger than before supplementation, while accommodation amplitude (2.3±1.1 diopters) in Group C after placebo supplementation was unchanged. The CFFs and amplitude and latency of P100 in PVEP in Group A were 45.0±4.2 Hz, 6.5±1.8μV, and 101.3±6.5 msec, respectively. The CFFs in Groups B and C before supplementation were significantly (p<0.05) lower than in Group A. The CCFs in Groups B and C did not change after supplementation. Amplitudes and latencies of P100 in PVEP in Groups B and C before supplementation were similar to those in Group A and did not change after supplementation. Findings of the present study indicated that accommodation amplitude improved after astaxanthin supplementation in VDT workers. 赤色カロチノイドの一種であるアスタキサンチンのvisual display terminal(VDT)作業者の調節力,中心フリッカー値,パターン視覚誘発電位に及ぼす影響を調べた。VDT作業を行わない13人をコントロールとした(Group A)。26人のVDT作業者を2群に無作為に分けた。Group Bはアスタキサンチン一日5mg 4週間内服した13人で,Group Cはアスタキサンチンを含有しないカプセルを4週間内服した13人とした。外見上同じカプセルでの内服投与を行った。結果:Group AはGroup B及びGroup Cと比較して,調節力,中心フリッカー値は有意に高い値であったが,パターン視覚誘発電位検査結果は,Group B,Cと有意差はなかった。Group Bでは,アスタキサンチンの投与前後で有意な調節力の改善がみられた(p<0.01)。しかし,中心フリッカー値,パターン視覚誘発電位に変化はみられなかった。Group Cでは,投与前後で,調節力,中心フリッカー値,パターン視覚誘発電位に変化はみられなかった。考察:VDT作業者では,非作業者と比べ調節力,中心フリッカー値が低下していることは以前より報告されており,今回の我々の研究でも同様の結果であった。VDT作業者で,アスタキサンチン非内服群では,調節力は投与前後で変化がなかったが,アスタキサンチンの内服群で,有意に調節力が改善した。VDT作業者の調節力の改善には,アスタキサンチンの内服が有効と考えられた。