Agmaset and AgmaVet - Gilad & Gilad...Magic Bullet (Paul Ehrlich) Firing Squad (Polypharmacy) Ion...

Neuroscientists - 1977

Donated to – Dr. Donald J. Reis’s

Laboratory of Neurobiology, Cornell

University Medical College.

(oil pastel on paper)

Agmaset® and AgmaVet ®

Science Leading to Product

Copyright © 2019, Gilad&Gilad LLC, All rights reserved

Agmaset® and AgmaVet ® -Nutraceuticals containing the neuroprotective ingredient G-Agmatine®.

G-Agmatine® -Gilad&Gilad’s proprietary brand of agmatine.

https://ForNerveHealth.com

Agmatine*A Novel Neuroprotective Dietary Ingredient**

*Discovered in 1910 (Albrecht Kossel) **Neuroprotection Discovery 1994 (Gilad et al.)

H2N-C-NH-(CH2)4-NH2

║

NH


Structural Formula

Molecular Formula

C5H14N4

Chemical Formula

2D

3D

Metabolic Pathways-Agmatine is a metabolite of the amino acid arginine-

-But agmatine exerts different effects than arginine-


Adapted from Halaris and Plietz

(CNS Drugs 21, 855-900, 2007)

NO Synthase

Ornithine

ArginineDecarboxylation

Decarboxylase

Agmatine

Diamine Oxidase

Agmatinase

Agmatine

Arginine

Polyamines

Agmatine is a Naturally Occurring Compound with

Broad Distribution in the Body

● Brain: 300 ng/mg

● Blood: 47 ng/ml

● Intestine: 55 ng/mg

● Fecal: 3,290 ng/g


● Commonly found in foodstuff derived from plants,

fish and animals (usual range: 0.1 – 10 mg/kg).

● High levels are found in certain fish products (200

and up to 650 mg/kg).

● Intestinal microbial production is considered a

major source of agmatine.

Agmatine is a Ubiquitous Compound Present in

Many Plant- and Animal-Derived Foodstuff


● Neuroprotection.

● Healthy pain-free nerve functions.

● Healthy mood functions.

● Healthy coping with Stress .

● Learning and memory enhancement.

● Healthy blood glucose regulation.

● Healthy blood flow.

● Protection of healthy kidney functions.

● Healthy control of cell growth.

Agmatine Exerts Multiple Effects-Animal Model Experiments-


NMDA

Insulin &Glucose

IR

PAs

Nicotine

UNIQUE MECHANISM OF ACTION

‘The Molecular Shotgun Concept’

Agmatine Modulates

Multiple Molecular Targets

Magic Bullet

(Paul Ehrlich)

Firing Squad

(Polypharmacy)

Ion Channels

Transporters

MMPs AGEs


Translating Research Into Practice

‘The Valley of Death’

Where some 99% of treatments fail


● Oral agmatine is absorbed by the gastrointestinal

tract.

●Agmatine is distributed throughout the body. It

crosses the blood-brain-barrier.

●Agmatine is mostly converted to putrescine,

precursor for polyamine synthesis, and urea. Some

may be oxidized.

●Agmatine is excreted by the kidneys.

Absorption, Distribution, Metabolism and

Elimination


Agmatine in Urine Following Oral Intake(2 hr apparent blood half-life)

Arbitrary Units (AU)

Measured by ELISA


Adapted from Huisman et al.(Anal. Chem. 82, 6526-33, 2010)

Translation of Research into Treatment-Clinical Studies Focus on Sciatic Nerve-

Adapted from WebMD Slideshow:

‘A Visual Guide to Sciatica’

sciatic nerve


Safety Clinical Trial-Open Label, Dose-Escalating Clinical Study Design-

Keynan et al., Pain Med., 2010;11(3):356–368


Treatment RegimenParticipants

[Male] [Female]Cohort

1 capsule 3 times daily (1.335 g agmatine sulfate/day)

- 10 day treatment

5

[3] [2]1st Cohort

2 capsules 3 times daily (2.670 g/day) - 10 day

treatment

5

[1] [4]2nd Cohort

8 daily capsules (2 in the morning, 3 at noontime and 3

in the evening) (3.560 g/day) - 10 day treatment

12

[7] [5]3rd Cohort

8 daily capsules (2 in the morning, 3 at noontime and 3

in the evening) (3.560 g/day) - 21 day treatment

12

[8] [4]4th Cohort

Adverse Effects

During 7 month Follow-up1st Cohort 2nd Cohort 3rd Cohort 4th Cohort

Mild Diarrhea 1 2

Discontinuations – Due to the above Adverse

Effects1

Free Will Discontinuations 1

Clinical Studies➢About 1.5% of the population cope everyday with circumstances

that challenge healthy sciatic nerve functions.

➢ Sciatic nerve functions can be clearly defined and measured.


Lumbar Disc

Nerve Root

2-5 days 14 days 61 days

Day 1 Clinical Assessment (days)

(Screening) (15 - 20) (45) (75)

RandomizationScreening Treatment Follow-up

Efficacy Study – Sciatic Nerve Functions

Randomized, Double-Blind, Placebo-Controlled Trial (RCT)Keynan et al., Pain Med., 2010;11(3):356–368

-Study Design-2.67 g/day G-agmatine®


CategoryGroup .

Placebo (n = 30) GVG-1 (n = 31)

Age (years) *Range

44.8±13.822–75

44.1±12.725–73

Gender *Female

Male14 (46.7 %)16 (53.3 %)

13 (41.9 %)18 (58.1 %)

Body Mass Index () ‡ * 25.4±3.5 27.2±5.6

Current Smoking * 7 (25.9 %) 6 (20.7 %)

Symptom Duration (weeks) *Range

7.9±4.51–16

11.7±15.41–48

Herniation Level *L3–4L4–5

L5–S1L3–4 + L5–S1L4–5 + L5–S1

2 (6.7 %)13 (43.3 %)14 (46.7 %)

1 (3.3 %)

3 (9.7 %)10 (32.3 %)11 (35.5 %)

2 (6.4 %)5 (16.1 %)

Herniation Type *ProtrusionExtrusion

Protrusion + Extrusion

2 (6.7 %)27 (90.0 %)

1 (3.3 %)

1 (3.2 %)23 (74.2 %)7 (22.6 %)

Pain Location *Back Pain OnlyBack + Leg pain

3 (10.0 %)27 (90.0 %)

1 (3.2 %)30 (96.8 %)

Pain Measures *Visual Analogue Scale

McGill Pain QuestionnaireOswestry Disability Index

6.5±2.321.9±9.428.2±8.2

6.9±2.122.6±9.8

25.7±11.9Quality of Life Assessment – SF-36 Score *

Total ScorePhysical Health ScoreMental Health Score

33.8±15.534.7±13.340.2±18.9

37.3±21.435.0±19.543.0±22.9

Neurological Deficits †Sensory – Unilateral Decrease

Motor (Force/Reflex) – Unilateral Weakness7 (23.3 %)

16 (53.3 %)20 (64.5 %)25 (80.6 %)

Baseline Demographics and Clinical Data

Copyright © 2019, Gilad&Gilad LLC,

All rights reserved

Keynan et al., Pain Med.,

2010;11(3):356–368

Neurological Functions †

0

1

2

3

4

5

6

7

8

Baseline 15-20 45-50 75-80

VA

S S

core

Time Interval (Days)

VAS Agmatine

VAS Placebo

0

10

20

30

40

50

60

70

80

90

100

Baseline 15-20 45-50 75-80

SF

-36

Tota

l S

core

Time Interval (Days)

SF-36 Placebo

SF-36 Agmatine

-Treatment- -Treatment-

*

**

Efficacy of G-Agmatine®

Pain Quality of Life


“Proof-of-concept”


The clinical studies serve a “Proof-of-concept” indicating the

beneficial use of G-agmatine® in harsh circumstances that challenge healthy nerve

functions.

Addressed Conditions

More than 20 million people in the

United States alone cope everyday with

circumstances that challenge healthy

nerve functions…


Recommended Effective Regimen

➢ 2 to 3 capsules twice a day with or after meals for

as-long-as needed (each capsule contains 445mg of

G-Agmatine®).

➢ Time to effect -

- In acute circumstances: 2 - 4 days in most, but

may be as-long-as 2 to 4 weeks.

- Chronic conditions: 3 - 6 weeks.

➢ After the effect is established – dosage may be

gradually reduced for maintenance regimen.


AgmaSet®

First-of-its-Kind Dietary Supplement Containing G-Agmatine®

For Nervous System Health and Proper Nerve Functions

Copyright © 2010-2014 Gilad&Gilad LLC, All rights reservedCopyright © 2019, Gilad&Gilad LLC, All rights reserved


AgmaVet®

For Your Animal's Daily DietContaining G-Agmatine®

For Nerve Health

Safety of AgmaSet® (NeurofencineTM)

2009 - 2015

Ongoing surveillance of people who take AgmaSet®

-No adverse effects were reported since surveillance began in 2009. -May rarely cause soft stool or mild diarrhea.


➢All alternative products containing agmatine sulfate are

based on borrowed science. All clinical studies are

borrowed from Gilad&Gilad.

➢ Products targeting the bodybuilding field are all touted

based on scientifically unsubstantiated claims and often

on downright erroneous scientific information.

❖ No evidence for enhanced Growth Hormone

functions.

❖ Agmatine may modulate Nitric Oxide (NO) synthesis,

but does not enhance NO content.

❖ No evidence for enhanced muscle protein synthesis.

Agmatine Sulfate Alternative Products


THANK YOU!PLEASE SPREAD THE GOOD NEWS


https://ForNerveHealth.com

Any Questions ? Call us: (toll-free) 1-888-484-4523, or 1-702-790-2877Contact us via email: [email protected] .

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Agmaset and AgmaVet - Gilad & Gilad...Magic Bullet (Paul Ehrlich) Firing Squad (Polypharmacy) Ion...

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