Physiological function of DNA-Na

Physiological function of DNA-Na
*What’
s DNA-Na?
DNA (Deoxyribonucleic acid) plays a role of genetic information
in our life. It is also a source of important nutrients along with sugar,
protein, vitamins and minerals for our body, and it is recognized as
“
the 7th essential nutrient”
. Nucleic acid is biosynthesized by de novo
pathways in our body, but this ability is reduced by aging. Therefore it
is important to take DNA as a food ingredient or a supplement for
providing a source of salvaged biosynthesis of DNA.
Our DNA-Na and NUCLEOPROTEIN (mixture of DNA and
gene protein) is purified from high quality natural salmon milt. It is
safe and available for dietary supplements. This report demonstrates
the results of our study of DNA-Na.
*The Effect of taking DNA-Na on Alcohol Metabolism.
It is thought that DNA-Na is able to improve the hepatic function of consuming alcohol. We
studied the effect of taking DNA-Na on alcohol metabolism. And we also tested turmeric extract,
which is expected the same effect on alcohol.
In this study, healthy volunteers (men, n=11, Age: 30y. -50y.) took DNA-Na (2 g) tablets, or
turmeric extract (1.5g : granulated powder containing 30mg of curucumin) 30 min before drinking
beer (633 mL, alcoholicity: 5.5%). Their blood was tested at regular intervals (0,1,2,4hr). At these
points, their blood alcohol level, blood acetaldehyde level, and blood acetic acid level were checked.
As a result of alcohol level, neither the test groups who consumed the DNA-Na supplement nor
who consumed the turmeric extract supplement showed significant difference compared with the
control group.
Fig.1
Change of blood alcohol level
after drinking alcohol
bloo d actealhyde level (mg/ L)
On the other hand, the results of their blood acetaldehyde level and acetic acid level showed a
significant difference between the test groups who consumed the DNA-Na (not only 2000mg taken
group but also 500mg taken group) and the control group. Therefore, DNA-Na suppressed the
elevation of blood acetaldehyde level and accelerated up-tendency of blood acetic acid level.
These results suggested that DNA-Na activated acetaldehydedehydrogenase (ALDH) activity and
it had an improvement effect against bad-feeling of alcohol more than the turmeric extract.
These blood kinetics data were supported by volunteer’
s comments “
DNA-Na didn’
t make them
sick after drinking.”
4
Control
DNA-Na(500mg)
3
DNA-Na(2000mg)
turmeric
extract(1500mg)
2
*
1
0
0
1
2
3
afte r drin kin g alc o h ol (h )
4
Fig2. Change of blood acetaldehyde level after drinking alcohol (*: p<0.005)
Fig3. Change of blood acetic acid level after drinking alcohol (✝:p<0.1)
We tried to clarify the mechanism of alcohol metabolism in vitro on taking DNA-Na. So, ethanol
and the digestive of DNA –Na (deoxyadenosine ; dA, thymine ; dT, deoxyguanosine ; dG,
deoxycytidine ; dC) was added to the homogenate of rat liver, and the mixture was incubated at
37 ℃ for 1.5 h. Then the concentration of alcohol and acetaldehyde in the mixture was measured.
The result showed that the homogenate including the digestive DNA-Na promoted the consumption
of ethanol and acetaldehyde compared with control. Furthermore, interestingly, dA and dG had
stronger effect than dT or dC.
Ethanol is converted into acetaldehyde by alcohol dehydrogenase (ADH) and the acetaldehyde is
changed into aldehyde dehydrogenase (ALDH). These alcohol metabolizing enzyme reactions are
conjugated with the cycle of coenzyme (NAD+/NADH).
According to the promotion effect on both ethanol and acetaldehyde, digestive DNA-Na might be
involved in the cycle of NAD+/NADH.
0 .7
consumption of ethanol
[μmol / tube]
0 .5
0 .4
0 .3
0 .2
0 .1
0
control
0 .1 2 5 m M dNs
1 .2 5 m M dNs
consumption of acetaldehyde
[μmol / tube]
0 .5
0 .6
0 .4
0 .3
0 .2
0 .1
0
control
0 .1 2 5 m M dNs
1 .2 5 m M dNs
Fig.4 The effect of deoxyribonucleosides on ethanol metabolism
(in vitro test, liver homogenate of rat)
(a) consumption of ethanol, (b) consumption of acetaldehyde
0.3
0.3
0.2
0.1
0
1.25mM
dNs
0.313mM
dA
0.313mM
dT
0.313mM
dG
0.313mM
dC
consumption of a ceta ldehy de
[ μmol / tube]
consumption of etha nol
[μmol / tube]
0.4
0.2
0.1
0
1.25mM
dNs
0.313mM
dA
0.313mM
dT
0.313mM
dG
Fig.5 The effect of each deoxyribonucleoside on ethanol metabolism
(in vitro test, liver homogenate of rat)
(a) consumption of ethanol, (b) consumption of acetaldehyde
0.313mM
dC
*The Effect of taking DNA-Na on inhibition of aging.
The shortage of nucleic acids in our body may be contributed to the aging process. Taking high
nucleic acid containing supplements may prevent the aging process. We have studied the anti-aging
function on DNA-Na. In this study, 0.1% of DNA-Na was administrated to senescence-accelerated
mice (SAMP male and female n= 7 respectively) with their feed for 11 months. The results showed
that the mice administrated DNA-Na received better aging scores compared with the control mice.
Agi n g S c o r e
4
3
*
*
*
*
*
*
2
Control
0 . 1 % DNA- Na
*
*
*
*
*
*
*
*
1
*
*
*
*
or
sc
bo
g
ck
ag
in
ba
of
of
e
nd
ag
Be
Av
er
Da
m
e
ne
es
nd
ou
ar
ag
e
Lo
Sk
ss
in
of
tu
ey
m
ha
or
ir
s
en
Ev
ir
es
n
ee
sh
iv
ss
Ha
Re
Pa
ac
ti
vi
ty
i ty
0
Fig.6 Improvement of aging score
(*p<0.05)
In the same experiment, it was found that the abilities of breeding (number of total babies) and
weaning were improved. The rate of weaning success was defined as a number of babies that were
alive for 3 weeks against the number of total babies. Improving of the rate of weaning success means
that parents’physical strength and their brain function were in a good condition. Besides the
concentration and the activity of sperm were improved.
110
0.1%DNA-Na
100
90
80
70
60
Nummber of
Total babies
Fig.7
300
250
200
150
100
Control
0 . 1 % DNA- Na
30%
Activity of sper m
Control
Con c e ntrati on of sperm(×1 000 0 0/m l)
[Collaboration with Prof. S.Yamamoto (Ochanomizu women’
s University) and Providence University in Taiwan]
Control
0 . 1 % DNA- Na
25%
20%
15%
10%
50
5%
0
0%
Rate of weaning
success(%)
Improvement of breeding
and weaning success
Fig.8 Concentration of sperm
Fig.9 Activity of sperm
*The Effect of taking DNA-Na on brain function.
We have studied the effect of taking DNA-Na on brain function. The diet containing 0.1% of
DNA-Na was administrated to senescence-accelerated mice (male and female n= 7 respectively) for
11 months.
① Stimulation(Light, noise)
Dark room
②Avoidance
① Moving
③ Electric Shock
② Electric Shock
Passive Avoidance Test
Mice favor dark atmosphere. If they moved to the dark
room, they were punished by electric shock. In this study,
the tendency staying in bright room was measured.
14
Control
0.1%DNA-Na
12
10
8
6
*
4
*
2
0
1Day
2Day
3Day
4Day
The Time of moving to dark room(min)
Active Avoidance Test
If mice didn’
t move to next room after receiving
the stimulation, they were punished by electric
shock.
16
Number of Failureof avoidance
Light room
100
Control
0.1%DNA-Na
80
60
*
40
*
*
20
0
Trial
1Day
2Day
3Day
7Day
Fig.10 Number of failure of avoidance
Fig.11 Time of moving to dark room
After 3 days, the number of avoiding failure was
decreased on administrating DNA-Na for control.
After 2 days, the staying time in the bright room was tend
to extend against control significantly (p<0.05). Therefore
the abilities of learning and memorizing were improved.
These results suggested that supplementation of DNA-Na may reduce the age-induced
deterioration of certain memory tasks in senescence-accelerated mice.
*The Effect of taking DNA-Na on endurance running capacity.
We researched the effect of taking DNA-Na on endurance running capacity. In this study, 0.1%
of DNA-Na containing diet was administrated to mice (5 week-age, n=7- 10) for 12 weeks, and their
endurance running capacity was measured with treadmill. As the results, mice ran a significant
longer distance in the DNA group than the control group (p<0.05). After the running exercise, their
blood sugar level was measured. The blood glucose level was significantly higher in the DNA group
(p<0.05). These results suggested that dietary DNA activated the glucose metabolism and
consequently enhances the running capacity in mice. [Collaboration with Kagawa Nutrition University]
1500
1000
500
0
グルコース濃度 (g/l)
3
*
Blood glucose level (g/L)
Running distance (m)
走行距離 (m)
2000
対照群 DNA-Na
DNA投与群
Control
group
( n= 7)
Fig.12 Running distance
(n= 8)
(*p<0.05)
対照群
Control
2.5
*
2
1.5
1
0.5
0
非運動群
Non-Exercise
運動群-1
Exercise
(n=10)
(n=9)
Fig.13 Blood glucose level
DNA-Na
DNA投与群
Promotion activity
on producing hyaluronic acid
*The effect of DNA-Na on the production of hyaluronic acid using human cell.
Hyaluronic acid, which is a content of extracellar matrix, is able to hold a lot of moisture and it
contributes to our skin moisture. Therefore promoting the produce of hyaluronic acid is expected to
improve our skin conditions (moisture, elasticity, tension and sleek etc). We evaluated the promoting
effect of DNA-Na on the production of hyaluronic acid using human normal dermal fibroblast
(SF-TY cell). The results showed that DNA-Na has the promoting effect of hyaluronic acid
production on the fibroblast (Fig.14). This data suggested that DNA-Na would improve skin
conditions.
150%
134%
109%
100%
100%
50%
Control
50 µg/mL
DNA-Na
additive
100 µg/mL
DNA-Na
additive
Fig.14 Promotion activity of DNA-Na on producing hyaluronic acid
<Improving effect of DNA-Na on skin care>
We investigated the effect of rubbing and taking the DNA-Na from salmon milt on human skin.
*Effect of the DNA-Na cream on skin (human study)
At first, we investigated the effect of the DNA-Na on skin. The cream containing DNA-Na (3%)
or the control cream was rubbed to the male subjects (n=10 each group) for 12 weeks. The result
showed that the DNA cream improved the skin-elasticity more than the control after the fourth week.
The change of skin-elasticity was improved significantly (Fig.15). Rubbing of the DNA cream
tended to decrease transepithelial water loss (TEWL) and to increase water content in the face skin at
12th week. (Fig.16, 17).
140%
Control
3%DNA-Na
<Summary of the protocol>
Test method:
Each cream was rubbed to the subject's face.
Skin-Elasticity was measured by Cutometer.
○ Measurement method and Definition of
Skin-Elasticity
Put the probe of Cutometer on the skin and
pull it by constant negative pressure.
We measured the height (Uf) that skin was
drawn into the probe.
Releasing the constant negative pressure, we
measured the restored height (Ur).
Skin-Elasticity was defined in Ur/Uf.
130%
Change of skin-elastisity
Subjects:
healthy adult men(Age:30∼59)
Ten people / each group
**
**
*
120%
110%
100%
90%
80%
4
Fig.15
8
12 weeks
Effect of rubbing DNA-Na Cream on
Skin-Elasticity.
(n = 10, means±S.E., Student’
s t-test * p<0.05, **<0.01)
120%
Control
†
3%DNA-Na
110%
120%
†
Changes of water content
in the face skin
Changes of TEWL(%)
Control
3%DNA-Na
100%
90%
80%
70%
4
8
110%
100%
90%
12 weeks
4
Fig.16 Effect of rubbing DNA-Na Cream on TEWL.
(n = 10, means ± S.E., Student’
s t-test †p<0.10)
8
12weeks
Fig.17 Changes of water content in the face
skin.
(n = 10, means ± S.E., Student’
s t-test†p<0.10)
In addition, according to the answer of questionnaire, more than 90 percent of the subjects who
used DNA cream felt improving roughness of the skin (Fig.18). Furthermore, the subjects using the
DNA cream had a good impression. The DNA Cream could be expected an improvement effect on
the tension of the skin.
Improvement rate
(Collaboration with Ochanomizu University, Professor Shigeru Yamamoto and Providence University (Taiwan))
100%
Control
3%DNA-Na
80%
60%
40%
20%
0%
1
4
8
12
Roughness of face skin
1
4
8
12
Color and glossy of the face skin
1
4
8
12 weeks
Roughness of the hand
Fig.18 Result of questionnaire (n = 10).
○Impression when the subjects used DNA-Na 3% cream
Suppressing the drying of the skin. Cream was immediately absorbed into the skin.
*Effect of taking DNA-Na on human skin conditions.
We investigated the effect of taking DNA-Na on human skin conditions. In this study, the male
subjects (n = 7, Age:40-60 years) took DNA-Na (1 g/day) for 4 weeks and their skin conditions were
inspected. After 4 weeks, taking DNA-Na tended to improve the face skin conditions (spots, pores,
wrinkle, evenness), and to increase water content in the face skin (Fig.19, 20). In conclusion, these
results showed that their skin conditions were improved by taking DNA-Na.
[Collaboration with Providence University in Taiwan]
spots
pores
wrinkle
100%
90%
80%
70%
60%
50%
100%
90%
80%
70%
60%
50%
before
before
4 weeks
evenness
100%
90%
80%
70%
60%
50%
100%
90%
80%
70%
60%
50%
4 weeks
prophyrins
100%
90%
80%
70%
60%
50%
before
Fig.19
before
4 weeks
UV spots
100%
90%
80%
70%
60%
50%
4 weeks
before
4 weeks
before
Improvement of skin conditions.(n = 7, means ± S.E.)
4 weeks
Measurement equipment:VISIA II Complexion Analysis
TEWL
water content
120%
110%
100%
90%
80%
70%
100%
90%
80%
70%
60%
50%
before
4 weeks
sebum content
120%
110%
100%
90%
80%
70%
before
4 weeks
before
Fig.20 Effect of taking DNA-Na on TEWL, water content and sebum content
(n = 7, means ± S.E.)
Measurement equipment
(All of the equipment are manufactured by Courage + Khazaka electronic GmbH, Germany)
TEWL
: Tewameter(TM300)
Water content
: Corneometer(CM825)
Sebum content
: Sebumeter(SM815)
4 weeks
It was shown the images which measured the same part of subject’
s face with VISIA II. The
original image for VISIA II analysis data was shown in Fig.21, and high-contrast image of pores and
spots in face was shown in Fig.22. Taking DNA-Na for 4 weeks (1g / day), pores and spots were
decreased. These results suggested that taking DNA-Na improved complexion and skin-condition.
Before taking
After 4 weeks
Fig.21 Original image of VISIA II data analysis
Before taking
After 4 weeks
Fig.22 High-contrast image of pores and spots (Color revision image ※)
※Software:Zoom Browser EX (Canon)
*The effect of blood uric acid level by taking DNA-Na.
Gout (metabolic arthritis) is a disease due to a congenital disorder of the uric acid metabolism.
In this condition monosodium urate crystals are deposited on the articular cartilage of joints and in
particular tissues like tendons. Previously it was thought that the uric acid in our body is generated
from nucleic acids which have purine base structures. However, recent study revealed that drinking
alcohol and obesity have a negative effect on our uric metabolism.
Blood uric acid(mg/dL)
10
Hyperuricemia
8
6
4
2
0
0
2
4
6
8
week
Fig.23 Change of blood uric acid level
(n=7,
mean±SE)
We researched the effect of blood uric acid level by taking DNA-Na for healthy 9 volunteers
(men, n=9, Age: 40y. -60y.). They took DNA-Na (2g) wrapped with cachet everyday for 8 weeks.
The result showed that their uric acid level didn’
t increase. Therefore, taking DNA-Na is not related
to rising uric acid levels. It is important that we take care to ingest purine base and have a good
eating habit.
Reference
(1)T.Takeda et al., Mechanisms of Aging and development, 17,183-194, (1981).