AstaREALAstaREAL®®
Astaxanthin: Astaxanthin: Reducing Eye fatigueReducing Eye fatigue
Clinical SummaryClinical Summary
Summary
• Eye fatigue suffers a global problem.
• Only 50% of sufferers respond to conventional measures e.g. ergonomics
• Astaxanthin alleviates eye fatigue by directly improving the ciliary body function that controls lens refraction.
• Astaxanthin reduces inflammation and improves retinal blood flow.
Eye Fatigue & Accommodation
1.1. Toyama Medical & Toyama Medical & Pharmaceutical UniversityPharmaceutical University
2.2. Fujita Health University Fujita Health University School of MedicineSchool of Medicine
3.3. Hokkaido University Hokkaido University School of Medicine x 2School of Medicine x 2
4.4. Kajita ClinicKajita Clinic
SixSix independent facility (eighteight clinical trials) demonstrated that eye fatigue and accommodation were significantly improved after AstaREAL supplementation.
1-1. 1-1. AccommodationAccommodation
A double masked study
VDT=Visual Display Terminals
5 mg astaxanthin per day or placebo during 4 weeks
0
1
2
3
4
NoSupplementation
After
Astaxanthin 5mg/ day (n=13)
Placebo (n=13)
non-VDT Subjects (n=13)
Acc
om
od
atio
n (
Dio
pte
rs)
Before
p<0.01
1-2. 1-2. Eye FatigueEye Fatigue
0
2
4
6
8
10
12
14
Before After
Astaxanthin5mg/ day Placebo
No.
of
sub
ject
s w
ith
Eye
Fati
gue
p<0.05
A questionnaire
before and after the administration period.
54% 54% reduction reduction
0
1
2
3
4
5
0 mg 2 mg 4 mg 12 mg
Before After
Acc
om
mod
atio
n (
sec.
)
A double blind study
46 eye fatigue subjects
0 mg (placebo, n=10) 2 mg (n=10) 4 mg (n=13)12 mg (n=13)Astaxanthin per day or placebo for 28 days
Dose DependentDose DependentEffect!!Effect!!
2. 2. AccommodationAccommodation
3-1. Dose Finding Study-13-1. Dose Finding Study-1
Sub-objective Accommodation PowerSub-objective Accommodation Power
0
2
4
6
0 mg 6mg 12mg
Start 4w
p<0.05
Obj
ectiv
e A
ccom
mod
atio
n P
ower
(D
)
A double blind study
30 eye fatigue subjects
0 mg (placebo, n=10) 6 mg (n=10)12 mg (n=10)Astaxanthin per day or placebo for 4 weeks
Singificantly increased by 12mg supplementation at week 4 compared to start
0
2
4
6
0 mg 6mg 12mg
Start 4w
*
3-1. Dose Finding Study-23-1. Dose Finding Study-2
Positive Accommodation TimePositive Accommodation Time
- 6mg supplementation; Significantly shortened at week 4 compared to start
- 12mg supplementation;Also significantly shortenedat week 4 comparedto start
* p<0.05
Pos
itive
Acc
omm
odat
ion
Tim
e (D
/s)
*
0
2
4
6
0 mg 6mg 12mg
Start 4wNeg
ativ
e A
ccom
mod
atio
n T
ime
(D/s
)3-1. Dose Finding Study-33-1. Dose Finding Study-3
Negative Accommodation TimeNegative Accommodation Time
- 6mg supplementation; Singificantly shortenend at week 4 compared to start & placbo
P<0.05
Optimal DoseOptimal Dose= 6mg/day= 6mg/day
3-2. Efficacy-Identification 3-2. Efficacy-Identification Study-1Study-1Sub-objective Accommodation PowerSub-objective Accommodation Power
Sub
-obj
ectiv
e A
ccom
mod
atio
n P
ower
R
ate
of C
hang
e (%
)
A double blind study
40 eye fatigue subjects
0 mg (placebo, n=20) 6 mg (n=20)Astaxanthin per day or placebo for 4 weeks
Sigificantly higher at week 2 & 4 compared to start & placebo
0
50
100
150
200
0 mg 6mg
Start 2w 4w
P<0.01
P<0.01
3-2. Efficacy-Identification 3-2. Efficacy-Identification Study-2Study-2
Pos
itive
Acc
omm
odat
ion
Tim
e R
ate
of C
hang
e (%
)
Sigificantly higher at week 2 & 4 compared to start & placebo
0
50
100
150
200
0 mg 6mg
Start 2w 4w
P<0.01
P<0.01
Positive & Negative Accommodation TimePositive & Negative Accommodation Time
Neg
ativ
e A
ccom
mod
atio
n T
ime
Rat
e of
Cha
nge
(%)
0
50
100
150
200
0 mg 6mg
Start 2w 4w
P<0.01
P<0.01
4. Accommodative recovery4. Accommodative recoveryHFC (High Frequency Component in Accommodative Mirco-Fluctuation HFC (High Frequency Component in Accommodative Mirco-Fluctuation of ciliary body)of ciliary body)
10 healthy subjects(Male: 5, Female: 5)
HFC difference was calculated between HFC at VDT (visual display terminal) working for 30min and HFC at 20min rest after VDT. The difference was measured before and after 6 mg astaxanthin/day for 2 weeks.
Increase of HFC after the rest was singificantly restrained by astaxanthin supplementation.
-4
-2
0
2
4
6
8
10
12
HF
C D
iffer
ence
Before After
P<0.05
Visual Acuity for Sports Performance
Sawaki,K. Sawaki,K. et alet al. 2002, Journal of Clinical. 2002, Journal of Clinical Therapeutics & Medicines, 18:(9) 73-88.Therapeutics & Medicines, 18:(9) 73-88.
- Double blind placebo controlled studies on male handball atheletes
- 6 mg (n=9) astaxanthin vs placebo (n=9) for 4 weeks
- Improving of depth perception & critical flicker fusion
- improved ciliary muscle function for visual acuity
Visual Acuity-1-Depth Perception-
Before Before Ex.Ex.After After Ex.Ex.
** * * p<0.05p<0.05
****
**
**
0.00.0
10.010.0
20.020.0
30.030.0
40.040.0
50.050.0
60.060.0(mm)(mm)
Before After
Treated
Before After
Placebo
Visual Acuity-2-Critical Flicker Fusion -
Before After
Treated
Before After
Placebo
30.030.030.030.0
35.035.035.035.0
40.040.040.040.0
45.045.045.045.0
**
**
Before Before Ex.Ex.After After Ex.Ex.
** p<0.05p<0.05
Photoreceptors processed light better in astaxanthin group.
Why Astaxanthin Reduces Eye Fatigue?Why Astaxanthin Reduces Eye Fatigue?
1. Retinal Blood Flow1. Retinal Blood Flow
100
150
200
250
300
Placebo Treated
0W R 4W R 0W L 4W L
p<0.01
p<0.01
Ret
inal
Blo
od F
low
A double blind study
36 healthy subjects
0 mg (placebo, n=18) 6 mg (n=18)Astaxanthin per day or placebo for 4 weeks
Singificantly increased in the astaxanthin supplemented group at week 4 in both eyes
Nagaki,Y. et al. 2005, J. Clinical Therapeutics & Medicines 21(5):537(73)-542(78).
Why Astaxanthin Reduces Eye Fatigue?Why Astaxanthin Reduces Eye Fatigue?2. Anti-Inflammation2. Anti-Inflammation
0
10
20
30
40
cont. 0 1 10 100 pred.
Infi
ltra
tin
g c
ells (
×1
05 /
ml)
p<0.01p<0.01
mg/kg
[Cellular Infiltration]
0
10
20
30
cont. 0 1 10 100 pred.
Pro
tein
Con
c.
(m
g /
ml)
p<0.01
p<0.01
mg/kg
p<0.05
[Protein]
0
50
100
150
cont. 0 1 10 100 pred.
NO
Con
c.
(μM
)
p<0.01p<0.01
mg/kg
p<0.01
p<0.01
[NO]
0
200
400
600
800
1000
cont. 0 1 10 100 pred.
TN
F-α
(
pg
/m
l)
p<0.01p<0.0
1
p<0.01
p<0.01
mg/kg
[TNF-alpha]
Ohgami,K. et al. 2003, Invest Ophthalmol Vis Sci. 44(6):2694-2701. New publication 2006 also available.
0
3
6
9
12
15
cont. 0 1 10 100 pred.
PG
E2
Con
c.
(n
g /
ml)
p<0.01
p<0.01
p<0.01p<0.01
[PGE2]
mg/kgAstaxanthin suppressed the development of endotoxin-induced uveitis in rats.
The anti-inflammatory effect of 100 mg/kg Ax was as strong as that of 10 mg/kg prednisolone.
Measured in the aqueous humor
The aqueous humor was collected 24hr after LPS treatment.
Pred.=10mg/kg Prednisolone by iv as a positive control
Eye Health -rat model-
0
10
20
30
40
cont. 0 1 10 100 pred.
Infi
ltra
tin
g c
ells (
×1
05 /
ml)
p<0.01p<0.01
mg/kg
[Cellular Infiltration]
0
10
20
30
cont. 0 1 10 100 pred.
Pro
tein
Con
c.
(m
g /
ml)
p<0.01
p<0.01
mg/kg
p<0.05
[Protein]
0
50
100
150
cont. 0 1 10 100 pred.
NO
Con
c.
(μM
)
p<0.01p<0.01
mg/kg
p<0.01
p<0.01
[NO]
0
200
400
600
800
1000
cont. 0 1 10 100 pred.
TN
F-α
(
pg
/m
l)
p<0.01p<0.0
1
p<0.01
p<0.01
mg/kg
[TNF-alpha]
K. Ohgami et al., Invest Ophthalmol Vis Sci. 44(6), 2694-2701 (2003).
Astaxanthin suppressed the development of endotoxin-induced uveitis in rats
Measured in the aqueous humor
The aqueous humor was collected 24hr after LPS treatment.
Pred.=10mg/kg Prednisolone by iv as a positive control
0
3
6
9
12
15
cont. 0 1 10 100 pred.
PG
E2
Con
c.
(n
g /
ml)
p<0.01
p<0.01
p<0.01p<0.01
[PGE2]
mg/kg
Astaxanthin suppresses NF-kB activation
Experimental Eye Reaseach, in press
Normal iris-ciliary body LPS administration LPS + Astaxanthin
↑ NF-kB positive cells** p<0.01
NF-kB p65 were immunostained with antibodies
Green: normal nuclei Red: NF-kB p65