Serotonin: The chemistry of Well-Being
Overview and Experiments Update
The Magic Ingredient of Our Success Formula
During the past 25 years, the Pharmaceutical industry
has invested billions of dollars on the marketing of
antidepressants. An indirect results are that the terms
“increase in serotonin level” and “serotonin as a
chemistry of well being” has become part of our
mainstream vocabulary. The industry funding has been
essential for identifying the serotonin/dopamine
transporters as a target for the development of
antidepressants.
Our study shows that in oral form, 100% water soluble
serotonin and dopamine have insignificant absorption
rates. In this case the notion that oral water-soluble
ingredients should work as well as oral bioavailable is
not working.
Optimization of oral bioavailability is a continuing
challenge for the pharmaceutical industry.
We have created such a transporter. The transporter
completely mimics the natural way of serotonin
absorption as well as numerous other ingredients.
The bioavailability of the new natural serotonin is raised
up to 3,000 times.
Under these circumstances it becomes possible to
market an oral supplement (capsules, gel, and chewing
gum) with the brand “Natural serotonin”.
Our R&D are co-operated with 4 Groups of Scientists with 40years experience with serotonin related health problems led by:
Dr. Lubovtseva
Lubov Histological studies
of serotonin in the
tissues
Dr. Moshkin MikhailSeasonal affective disorder
Dr. Simonenkov
Alexey-Use of
serotonin drugs in
clinical practice
Dr. Popova Nina –
Serotonin behavioral
neurogenetics
The second challenge is to exploit well-established use and brand
of serotonin as a chemistry of well-being
The third marketing success challenge is to come in under the radar
with efficacy not only beyond the competition, but ahead of an entire
industry, giving no chance to our competitors to clone it.
Despite a reduction in attrition due to
pharmacokinetics issues, efficacy has not
improved, since 1991.
We discovered an universal
solution for many ingredients,
which mimics existing natural
delivery system of active
substances in the body at the
cellular level. In comparison
with 100% water soluble
Serotonin we increse it efficacy
in oral form by 3000 times!!!
Mannanoligosaccharide (MOS)
Supramollecular with Serotonin
Macrophages envelope Mannan
Oligosaccharides like mycobacteria
Serotonin (Also known as 5-HT, or 5hydroxytryptamine)
• Serotonin is the most ubiquitous
neurotransmitter of all
• It’s found in the central and peripheral
nervous systems, it is located in the GI tract,
platelets, mast cells and macrophages
• ~95% of all serotonin in the body is in the gut
Functions of serotonin
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Happiness
Sociability/boosts self-esteem/overcomes shyness
Social phobias
Makes you full and feel sleepy
Impulsive eating disorders
Impulse control
Helps to control pain pathways
Nausea, vomiting, gastric motility
Generalized anxiety disorder
Aggression
Premenstrual disorders
Migraines
Erections
Prevent bleeding
Immune control
Provide Thermoregulation
Serotonin in skin regulates
thermogenesis
Typical
metabolism
The serotonin and smooth muscle
•
•
•
•
Serotonin is the leading factor responsible for
stimulation of the smooth muscles contraction
The smooth muscles can contract without
conscious control
Serotonin is considered as an “energy” factor the
smooth muscles contraction
Smooth muscle is found within the walls of all
blood vessels, including the smallest arteria, in
lymphatic vessels, the urinary bladder, uterus,
male and female reproductive tracts, GI tract,
respiratory tract, arrector pili, closing up the
skin’s pores, the eye’s ciliary muscle that
controls accommodation for viewing objects at
varying distances, the iris of the eye, which is
responsible to the amount of light entering the
eye
The Second Brain...serotonin and
the gut
• GUT CHECK: A complex, independent nervous system lines
the gastrointestinal tract that has been dubbed the "second
brain” influences Mood and Well-Being
Age related Serotonin decrease
Different serotonin receptors and the serotonin transporter decline with age
coursing that can be treated by Newly developed Serotonin supplement:
• low energy levels
• reduced initiative
• decrease in sex drive
• reduced visual acuity
• development of varicose and spider veins
• uncontrolled weight gain
• reduction of erections in the morning
• depression
• bleeding gums
• reduced thermo genesis
• weather sensitive problems
• low tolerance for alcohol
Serotonin is major factor of Thermoregulation
•
•
•
The vasomotor response and total body
oxygen consumption are clearly
reduced in intensity with age.
Serotonin controls the vasomotor
mechanism, how you blood vessels
dilate and constrict.
Internal body temperature is controlled
through sweat production and the rate
of blood flowing through the network
of blood vessels within the skin.
Serotonin supplements is the Natural
Way to Improve Thermo genesis.
Serotonin treatment of Meteo-dependent People
Increased sensitivity to weather
changes affected primarily the elderly
and vegetatively unstable people. They
respond not only to changes in weather,
but the high humidity, temperature
fluctuations, low pressure, electrical
voltage in the atmosphere of various
ailments: headaches, migraines, sleep
disorders, anxiety states, depression,
insomnia.
Serotonin improve skin via blood
circulation
Improves Skin
The pores of the skin through which sweat is excreted get
clogged due to the use of creams, deodorants and dead skin
cells. These clogged pores cause skin problems like acne,
pimple and blackheads. The serotonin supplement opens up
these pores, and the sweat flushes out of them, thus carrying
poisonous substances out of the body.
Improves Blood Circulation
The serotonin supplement activates the blood vessels that
ensures that there is proper supply of blood even by the
thinnest of the capillaries. Proper blood supply brings fresh
nutrients to the cells and ensures complete removal of waste
out of them.
Serotonin expelling toxins in the
blood
Serotonin prevent bleeding. The
natural chemistry to treat
bleeding gums
Serotonin increases visual acuity in
the 0.2-0.3 units per course of
treatment (10-20 capsules of 10 mg)
mg)
Serotonin removes varicose and
spider veins
Serotonin may rank people
10 mg
200 mg
Morning wood is a good indicator of healthy
serotonin levels
Team spirit
Here we have a solitary and lonely
creature, the desert locust. But just
give them a little serotonin, and they
go and join a gang
Serotonin linked to estrogen and
menstrual migraines
Serotonin and depression
What do women do when we’re depressed? We
eat!
In addition to
increasing serotonin
in the brain,
chocolates (boost)
anandamide—a
substance that
closely resembles
marijuana
Weight loss
The weight loss drugs
target the satiety center
in the hypothalamus—
boost serotonin that tells
you – “stop eating,
you’re full”
The SRI’s (serotonin reuptake inhibitors)
1987—the first selective serotonin reuptake inhibitor marketed Prozac
The SRIs—side effects
• Increasing serotonin may result in
decreased dopamine
• Dopamine gives you some zip to
your doo-dah in the bedroom
• SRIs may result in anorgasmia, loss
of libido and premature ejaculation
• Inhibit platelets
• Course bleeding gums
Serotonin syndrome
Overdose of SSRIs Drugs associated
with serotonin syndrome
Experimental part
Membrane potential is the
difference in electrical potencial
between the interior and the
exterior of a biological cell with
synthetic serotonin (green) and
Sea-backthorn extract (red).
Serotonin from sea-backtorn
Serotonin content 1-2%
- Neurotransmitter
Serotonin
Melatonin
- “Happiness“ Hormone
- Increase Activity
- Awakening from sleep
Triptophan
Dietary sourses
Serotonin
Melatonin
-Circadian rhythm
- Sleep
- Seasonal
affective disorders
- Depression
- Decrease in
activity
The comparitive study of the natural (ОбП) and
synthetic serotonin (Сер). Morphological and
neurochemical benefits of its consumption for
Djungarian hamster
Dosage:
synthetic serotonin – 28.5 mg/per hamster*per day;
natural serotonin – 300 mg - equivalent for 28.5 mg of synthetic serotonin/per hamster*per
day
Duration : A) 02.11.2010-15.01.2011
B) 02.11.2011 – 15.01.2012
Djungarian
hamster :
seasonal
changes
•Seasonal colour changes
•Weight reduction
•Motion activity reduction
•Temperature regulation changes
• Immune response suppression
Research objectives:
A comparison study of morphofunctional changes for two groups of
animals:
•Screening group (K) и
•Group fed with serotonin enhanced supplement (ССВО)
All the tests were carried out in shorter daylight hours.
Animal’s weight
1
30
Масса тела, г
Duration, days
-1
-2
At the end of experiment
* - p=0.04
20
-3
К
-4
ССВО
-5
10
-6
0
1
3
5
7
К
9
ССВО
Groups of animals
4
Animal’s fatness
3
Индекс
Changes in body weight
0
Weight
2
1
0
К
ССВО
Groups of animals
Spontaneous motion activity
before the experiment and within 1st -3rd weeks of experiment
500
450
400
ССВО
350
300
250
200
150
100
50
19
19
20
20
21
21
21
22
22
23
23
24
24
25
25
26
26
26
27
27
28
28
29
29
30
30
31
31
32
32
32
33
33
34
34
35
35
36
36
37
37
37
38
38
39
39
40
40
41
41
42
42
43
43
0
0
3
1
2
Test equipment to register
the spontaneous motion
activity
Spontaneous motion activity
250
Average nightly activity changes, per week
Motion activity dynamics (average nightly per week)
200
К
150
ССВО
100
50
0
0
-50
1
2
3
4
Duration, weeks
5
6
7
9
Oxygen intake dynamics
15 minutes animals exposure to cold, into the helium oxygen environment (HELOX)
Oxygen intake, ml*
18
15
12
Контроль
ССВО
9
1
2
3
4
5
6
7
8
9
Test duration, minutes
10
11
12
13
14
15
An equipment to
register the oxygen
intake
Oxygen intake
15 minutes animals exposure to cold, into the helium oxygen environment (HELOX)
К
200
17
Ml/g weight
Ml/g weight
ССВО
100
11
0
5
Суммарное
* p= 0.03
Mаксимальное
Mинимальное
Energy loss
15 minutes animals exposure to cold, into the helium oxygen environment (HELOX)
Total energy loss during
the test
Body thermal
conductivity
90
3.0
* р = 0.005
J/weight, g/temperature 0С
* p =0.001
J/weight, g
60
2.0
1.0
30
Контроль
ССВО
Контроль
ССВО
38
Body temperature before and
after exposure to cold in HELOX
К
*
Body temperature , C
ССВО
36
34
* - p = 0.018
32
До теста
К
После теста
ССВО
Scatterplot: S_MOC vs. dTb (Casewise MD deletion)
dTb
= 4.3391 - .0295 * S_MOC
Correlation: r = -.2581
1
Scatterplot:
dTb
S_MOC
vs.
dTb
(Casewise MD deletion)
= -20.20 + .08914 * S_MOC
Correlation: r = .95259
1
0
0
-2
-1
-3
dTb
dTb
Temperature changes
-1
-2
-4
-5
-3
-6
-4
155
160
165
170
Total oxygen intake
175
180
S_MOC
185
190
195
200
205
95% confidence
-7
160
170
180
190
200
S_MOC
210
220
230
240
95% confidence
Erythrocytes
Type
Erythrocytes
RBC/HCT
Haematocrite
Haemoglobin
HGB/RBC
HGB/HCT
Контроль
×1012 c/l
9,54±0,20
фл
46,14±0,55
%
43,84±0,65
g/l
16,84±0,37
17,64±0,22
38,40±0,32
СВВО
9,23±0,19
45,90±0,55
42,33±0,97
16,56±0,33
17,98±0,18
39,17±0,35
Leukocytes
Type
Leukocytes
Lymphocytes
Контроль
9,89±1,20
×109/l
6,24±0,71
СВВО
7,90±0,80
5,32±0,41
MID#
1,97±0,54
1,08±0,15
Granular
leukocytes
Thrombocytes
Thrombocryte
1,64±0,26
×109 c/l
225,0±7,0
%
0,21±0,01
1,56±0,25
226,7±11,4
0,21±0,01
Visceral organs weight
Animals
group
Name, weight, mg
Suprarenal
capsule
5,10±0,38
Brown fat
Thymus gland
Spleen
К
Android
glands
56,0±16,5
140,7±20,9
20,3±5,4
61,1±10,7
ССВО
34,0±2,54
4,43±0,43
107,0±20,8
17,3±5,1
40,0±3,5
1400
50
Spontaneous motion
Immune response
25
Number of АОК/spleen weight, mg
Energy changes, (average per night per week, sec/hour)
Immune response to the antigen intake (sheep red
blood cell)
0
К
-25
ССВО
-50
-75
1050
*
700
350
-100
0
-125
0
1
2
3
4
Time after antigen intake, days
5
6
К
ССВО
Группы животных
* - р=0,0509 (Mann-Whitney U тест)
Serotonin enhanced supplement consumption:
1.Considerably reduced weight
2. Increased spontaneous motion activity within first four weeks of
the experiment
3. Kept summer type of thermal regulation it means that more
energy wasted to compensate exposure to cold.
4. Increased immune response to the sheep red blood cells intake.
Nuclear Magnetic Resonance
Spectroscopy of cerebrum
metabolites
Recording area 17,5 мм3
(2 х 3,5 х 2,5) :
Categ. Box & Whisker Plot:
Cr+Pcr
Categ. Box & Whisker Plot: Lactate/Cr
30
28
1,6
Cr. + Pcr
Lactate/Cr.
1,4
sagittal
26
1,2
Lactate/Cr
Cr+Pcr
24
22
20
18
1,0
*
0,8
axial
16
*
14
12
0,6
Контр
1
2ОбП
Mean
±SE
±SD
Сер
3
Контр
1
0,4
Gr_mod
ОбП
2
Mean
±SE
±SD
Сер
3
Gr_mod
Biological energy
Categ. Box & W hisker Plot: Taurine
C ateg. Box & W hisker Plot: Glutam ate
C ateg. Box & W hisker Plot: Glutam ine
3,2
14
46
3,4
44
Glutamine
3,0
42
2,8
40
2,6
Glutamate
12
Taurine
10
38
2,4
Glutamate
Glutamine
2,0
1,8
1,6
34
32
8
6
30
1,4
28
1,2
*
1,0
0,8
0,6
0,4
Taurine
36
2,2
Контр
1
ОбП
2
Gr_m od
Сер
3
*
4
26
24
22
Mean
20
±SE
±SD
2
Контр
1
ОбП
2
Сер
3
Gr_m od
Antidepressants
Mean
0
±SE
±SD
Контр
1
ОбП
2
Gr_mod
Сер3
Me
±S
±S
Colour and brown fat
seasonal change
Colour seasonal change of Djungarian
hamsters
масса при забое
Categ. Box & Whisker Plot:
26
25
24
масса при забое
23
22
21
20
19
02.11.2011 – 0 week
28.11.2011 – 3rd week
10.01.2012 – 9th week
18
Контр
1
ОбП
Сер
3
2
Me
±SE
±SD
Группа
бурый жир, мг
Categ. Box & Whisker Plot:
200
Colour
change: 0- 3 нед
Categ. Box & Whisker Plot:
2.0
P=0.057, LSD тест
Colour
change: 0- 9 нед
Categ. Box & Whisker Plot:
ИзмОкр9_0
ИзмОкр3_0
2.2
180
3.5
H=8.6, p=0.014, Kruskal-Wallis
H=2.9, p=0.24, Kruskal-Wallis
160
3.0
1.8
1.6
бурый жир, мг
1.2
2.0
1.0
ИзмОкр9_0
ИзмОкр3_0
140
2.5
1.4
0.8
0.6
1.5
120
100
1.0
0.4
*
80
0.2
0.5
0.0
60
-0.2
0.0
-0.4
-0.6
Контр
1
2
ОбП
Группа
3
Сер
Mean
±SE
±SD
40
-0.5
Контр
1
ОбП
2
Группа
Сер
3
Mean
±SE
±SD
1
Контр
2
ОбП
Группа
3
Сер
Mea
±SE
±SD
Tissue distribution of SEROTONIN-3H and DOPAMINE-3H
in male mice ICR
* - p<0.05 in comparison with serotonin -3Н
(test Mann-Whitney)