Serotonin: The chemistry of Well-BeingOverview and Experiments Update

The Magic Ingredient of Our Success FormulaDuring 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 40-years experience with serotonin related health problems led by:

Dr. Moshkin Mikhail- Seasonal affective disorder

Dr. Popova Nina – Serotonin behavioral neurogenetics

Dr. Lubovtseva Lubov - Histological studies of serotonin in the tissues

Dr. Simonenkov Alexey-Use of serotonin drugs in clinical practice

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 5-hydroxytryptamine)

• 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 SkinThe 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

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%

SerotoninSerotonin Melatonin

Serotonin Melatonin

TriptophanDietary sourses

- Neurotransmitter- “Happiness“ Hormone - Increase Activity - Awakening from sleep

-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 hamsterDosage:

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

•Seasonal colour changes•Weight reduction•Motion activity reduction•Temperature regulation changes • Immune response suppression

Djungarian hamster :: seasonal seasonal changeschanges

Research objectives:Research objectives:

A comparison study of morphofunctional changes for two groups of animals:•Screening group (K) и •Group fed with serotonin enhanced supplement (ССВОССВО)

All the tests were carried out in shorter daylight hours.

Animal’s weightAnimal’s weight

Spontaneous motion activity Spontaneous motion activity before the experiment and within 1before the experiment and within 1stst -3-3rd weeks of experimentrd weeks of experiment

Test equipment to register the spontaneous motion activity

ССВО

Spontaneous motion activity Spontaneous motion activity

OOxygen intake dynamics xygen intake dynamics 15 minutes animals exposure to cold, into the helium oxygen environment15 minutes animals exposure to cold, into the helium oxygen environment ( (HELOXHELOX))

An equipment to register the oxygen intake

OOxygen intakexygen intake 15 minutes animals exposure to cold, into the helium oxygen environment15 minutes animals exposure to cold, into the helium oxygen environment ( (HELOXHELOX))

Total energy loss during the test Body thermal

conductivity

Energy lossEnergy loss15 minutes animals exposure to cold, into the helium oxygen environment 15 minutes animals exposure to cold, into the helium oxygen environment ((HELOXHELOX))

* - p = 0.018

Body temperature before and Body temperature before and after exposure to cold in after exposure to cold in

HELOXHELOX*

S ca tte rp lo t: S _MOC vs. dTb (Ca se wise M D d e le ti o n )dTb = 4 .3 3 9 1 - .0 2 9 5 * S _MOC

Co rre la ti o n : r = -.2 5 8 1

1 5 5 1 6 0 1 6 5 1 7 0 1 7 5 1 8 0 1 8 5 1 9 0 1 9 5 2 0 0 2 0 5

S _MOC

-4

-3

-2

-1

0

1

dTb

9 5 % co n fi d e n ce

S ca tte rp lo t: S _MOC vs. dTb (Ca se wise M D d e le ti o n )dTb = -2 0 .2 0 + .0 8 9 1 4 * S _MOC

Co rre la ti o n : r = .9 5 2 5 9

1 6 0 1 7 0 1 8 0 1 9 0 2 0 0 2 1 0 2 2 0 2 3 0 2 4 0

S _MOC

-7

-6

-5

-4

-3

-2

-1

0

1

dTb

9 5 % co n fi d e n ce

ССВОССВОКК

Total oxygen intake

Type Erythrocytes RBC/HCT Haematocrite Haemoglobin HGB/RBC HGB/HCT

×1012 c/l фл % g/lКонтроль 9,54±0,20 46,14±0,55 43,84±0,65 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

ErythrocytesErythrocytes

Type Leukocytes Lymphocytes MID# Granular leukocytes

Thrombocytes Thrombocryte

×109/l ×109 c/l %Контроль 9,89±1,20 6,24±0,71 1,97±0,54 1,64±0,26 225,0±7,0 0,21±0,01

СВВО 7,90±0,80 5,32±0,41 1,08±0,15 1,56±0,25 226,7±11,4 0,21±0,01

LLeukocytes eukocytes

Animals group

Name, weight, mg

Android glands

Suprarenal capsule

Brown fat Thymus gland Spleen

К К 56,0±16,5 5,10±0,38 140,7±20,9 20,3±5,4 61,1±10,7

ССВО ССВО 34,0±2,54 4,43±0,43 107,0±20,8 17,3±5,1 40,0±3,5

Visceral organs weightVisceral organs weight

* - р=0,0509 (Mann-Whitney U тест)

Immune response to the antigen intake (sheep red Immune response to the antigen intake (sheep red blood cell) blood cell)

Spontaneous motion

Serotonin enhanced supplement consumptionSerotonin 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.

Recording area 17,5 мм3 (2 х 3,5 х 2,5) :

sagittal

axial

Cr. + Pcr

Glutamine GlutamateTaurine

Lactate/Cr.

*

*

**

Контр ОбП Сер

Контр ОбП Сер Контр ОбП Сер

Контр ОбП Сер Контр ОбП Сер

Nuclear Magnetic Resonance Spectroscopy of cerebrum

metabolites

Biological energy

Antidepressants

Colour seasonal change of Djungarian hamsters

Colour change: 0- 3 нед

H=8.6, p=0.014, Kruskal-Wallis H=2.9, p=0.24, Kruskal-Wallis

Colour change: 0- 9 нед

Colour and brown fat seasonal change

Контр ОбП Сер02.11.2011 – 0 week

28.11.2011 – 3rd week 10.01.2012 – 9th week

P=0.057, LSD тест

*

Контр ОбП СерКонтр ОбП СерКонтр ОбП Сер

Tissue distribution of SEROTONIN-3H and DOPAMINE-3Hin male mice ICR

* - p<0.05 in comparison with serotonin -3Н

(test Mann-Whitney)