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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
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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-
Copyright © 2019, Gilad&Gilad LLC, All rights reserved
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
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● 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
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● 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-
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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
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Translating Research Into Practice
‘The Valley of Death’
Where some 99% of treatments fail
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● 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
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Agmatine in Urine Following Oral Intake(2 hr apparent blood half-life)
Arbitrary Units (AU)
Measured by ELISA
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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
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Safety Clinical Trial-Open Label, Dose-Escalating Clinical Study Design-
Keynan et al., Pain Med., 2010;11(3):356–368
Copyright © 2019, Gilad&Gilad LLC, All rights reserved
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.
Copyright © 2019, Gilad&Gilad LLC, All rights reserved
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®
Copyright © 2019, Gilad&Gilad LLC, All rights reserved
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
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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
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“Proof-of-concept”
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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…
Copyright © 2019, Gilad&Gilad LLC, All rights reserved
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.
Copyright © 2019, Gilad&Gilad LLC, All rights reserved
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
Copyright © 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.
Copyright © 2019, Gilad&Gilad LLC, All rights reserved
➢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
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Any Questions ? Call us: (toll-free) 1-888-484-4523, or 1-702-790-2877Contact us via email: info@ForNerveHealth.com .
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