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• 05/01/2014 - Scientific Communication - American Academy of Neurology 66th, Annual Meeting, Philadelphia, PA: Tohidi et al., "Effects of agmatine sulfate in small fiber..." (Abstract # 4082).
    
Aug. 2012 - Article - Michele Cagan, "Breaking news: Pioneer scientists uncover the Holy Grail lifesaver for...". Health Sciences Institute (HSI), 17(2), August 2012 Issue, pp. 4-5,8.
    

Oct. 2011 - Book Chapter about AgmaSet®
- "...Protecting and Strengthening Your Nerve Cells." In: Breakthroughs in Natural Healing - 2012. By: Bill Gottlieb. Bottom Line Publications, page 14.

            
                                                
                       
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Access Clinical Trial Paper
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  Pain Medicine
(11:356-368, 2010),
   Describing
the safety (lack of
   adverse effects) and superior efficacy of
   G - agmatine ®
.         
Access Agmatine Review Paper: 

      Agmatine: clinical applications
   after 100 years in translation. Drug
    Discovery Today
18:880-893, 2013.
 
           
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ENDORSEMENTS**

  
Dr. Gary Young prescribes AgmaSet® since July, 2010 -"I first heard about AgmaSet® back in July 2010 and decided to field test it with some of my patients - people with all kind of health-related nerve functions. And I've been prescribing it ever since that first test patient reported feeling good with healthier nerve functions and a better quality of life."
 
Dr. Gary Young, D.C.
HealthWorld Chiropractic Group
Hartsdale, New York, 10530
http://www.doctorgaryyoung.com/
  
Dr. Neal G. Snyder Recommends
- "I have been a chiropractic doctor for 29 years. I have  excellent results using AgmaSet® for health-related spinal-nerve functions of the upper and lower extremities. I recommend this product highly."

Dr. Neal G. Snyder, D.C.

Chiropractic Health and Wellness Center 
Los Angeles, CA 90064

 http://www.snyderchiro.com/

Dr. Dana Clark Thanks
- "Dr. Gilad, thank you for introducing me to AgmaSet®. I manage a large number of patients with varying levels of health-related nerve functions arising from multiple causes and have found the addition of AgmaSet® to significantly improve my patient outcomes..."

           

Dr. Dana Clark, D.C.
Pacific Coast Spine and Rehab
Los Angeles, CA 90025

www.pacificcoastspine.com

**Endorsements may be edited for length or to meet legal guidelines. They represent individual experience only, with no material connections and are not to be construed as advertisements or claims.

 

 

 
 RESEARCH
   
Learn More - Access the Slide Presentation
(And Check the Links below)

Welcome. This is an introduction to the science and research behind our products for nerve health. The text is edited in compliance with the Food and Drug Administration (FDA) regulations, which disallow certain advantages of dietary supplemenets to be fully expressed.You may contact our scientists with any questions about scientific research related to our products. Please  email us, or call toll free: 1-888-484-4523 (9:00 AM to 5:00 PM Pacific Time, Monday through Friday).

 
NERVOUS SYSTEM STRUCTURE AND FUNCTION

The nervous system is composed of three major divisions: the brain and spinal cord, together called the central nervous system (CNS), and the peripheral nervous system of which peripheral nerves constitute a major part. The nervous system is the ultimate coordinator of all bodily functions and its proper function is of cardinal importance for healthy daily living.


The nerve cells, called neurons are the main players in charge of performing nervous system functions. Neurons are interconnected by their axons, long fiber extensions responsible for transmitting information in the form of electrical signals. Neurons receive signals from organs of the body and sense the environment. After processing that information they coordinate the proper response of the various body organs.

Neurons, both in the CNS and the peripheral nervous system, are vulnerable to alterations in health-related conditions. Neurons may succumb and die as a result of lethal genetic changes or harsh environmental insults resulting in permanent functional alterations or complete loss of functions. In other words, functional recovery ultimately depends on nerve cell resilience and capability to sustain and recover.

Neuroprotection                        
Clearly, maintaining nerve cell resilience is mandatory for healthy nervous system function. One way this may be achieved is by providing fortifying nutrients directed at activating the cell's own molecular mechanisms that underlie the self-healing power and survival capabilities of neurons.

In ground-breaking laboratory experiments, Dr. Gad Gilad and Varda Gilad the founders of our company, discovered in 1994 that the unique molecule agmatine is endowed with neuroprotective properties for nerve cell survival.

Their discovery led to clinical trials, which demonstrated that dietary G-Agmatine® (Gilad&Gilad's trademarked brand of agmatine) is a safe and most effective nutraceutical ingredient leading to resilient nerve functions and a better health-related quality of life (graphic illustration), for which normal peripheral nerve functions are fundamental (Keynan et al., Pain Medicine 11:356-368 2010).

For a selective reference list of scientific articles click here.

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FOCUS ON PERIPHERAL NERVE HEALTH

For further health-related information, please refer to the LINKS section

Peripheral nerves - the motor, sensory and autonomic nerves, connect the brain and spinal cord (i.e., the cental nervous system) to muscles, skin and internal organs. Normal peripheral nerve activity is critical for proper pain sensitivity, sensory activity and motor (muscle) performance.

                         
The structure of peripheral nerves may be compared to a cable containing numerous axons. Signals propagate from the body organs to the spinal cord and brain and then back along these axons.


Protecting Healthy Nerve Functions - Clearly, protecting normal activity of axons (termed axonoprotection), and their parent neurons (i.e., neuroprotection) is fundamental for healthy bodily functions. Further information may be found at: http://www.ninds.nih.gov.

For example, pain sensations are often the consequence of direct damage to either the central or the peripheral nervous system, but are more common when the peripheral nervous system is involved.

Various health-related factors can jeopardize peripheral nerve function. Some are more localized or focal, affecting only few nerves, but other factors are more pervasive, influencing nerves throughout the body.

An example of focal factors' importance, is proper spine-nerve structure/function relationships, which are critical for healthy sciatic nerve functions. Challenges to proper functions of this nerve, which innervates the leg and foot, are highly prevalent, affecting 2% to 3% of the population. An interesting anecdote is the description by the novelist and Nobel laureate Hermann Hesse of coping with his own sciatic nerve functions in his novel Kurgast (1925). Another common example is proper structure of the carpal tunnel in the wrist for healthy functions of the median nerve of the forearm and hand. Yet another example is proper function of the facial nerve (the 7th cranial nerve), which controls the tongue's sensory functions and the muscles in charge of facial expressions. Further information may be found at: http://www.acatoday.org.


An image of information flow in the nervous system (Rene Descartes 17th century) 
Health-related predicaments carrying widespread threats to healthy nerve functions throughout the body include: • Metabolic functions such as: glucose or amino acid metabolism. • Nutritional requirements such as: low vitamin B12 intake or vitamin B6 surplus. • Infections. • Toxic drugs. • Heredity. • Environmental toxins. Further information may be found at: http://www.aan.com/ and http://www.painfoundation.org.

Overweight is a pertinent example of a widespread predicament that precipitates not only focal changes, such as spine-nerve structure/function relationships, but also general metabolic functions, such as control of glucose metabolism, thus posing a direct threat to proper nerve functions throughout the body.

Maintaining healthy metabolism -Healthy metabolism is critical for proper nerve functions. 
Maintaining healthy metabolism is a dynamic process regulated according to varying energy demands of organs throughout the body in response to changes in the external and internal environments. This fundamental process, termed homeostasis, was discovered in the mid 1800s by Claud Bernard, the father of modern physiology. For example, imbalance of glucose (sugar) homeostasis can lead to dire changes in healthy nerve functions.

Such changes in health-related circumstances have characteristic effects on nerve functions including changes in pain, temperature and touch sensations and in nerve-dependent muscle strengthFurther information may be found at: http://www.painfoundation.org and http://www.painmed.org/patientcenter/main.aspx.




Unfortunately, more than 20 million people in the United States alone cope everyday with circumstances that pose great challenges to normal peripheral nerve functions. The Gilad's findings, therefore, have wide implications for a multitude of people worldwide whose need for an  effective neuroprotective dietary supplement to support their nerve resilience remained unmet until now.

Note: Animals are also susceptible to various harsh circumstances that challenge healthy nerve functions. These are common in companion animals such as dogs, cats and horses. 
 
Gilad&Gilad's
exclusive For-Nerve-HealthTM nutraceutical supplements contain G-Agmatine® and present first-of-a-kind products now available to fulfill these unmet needs.


For a selective reference list of scientific articles click here.


 
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AGMATINE - A MULTIFUNCTIONAL COMPOUND
(Learn More - Access the Slide Presentation)
                       
Discovery - Agmatine is a metabolite of the amino acid arginine, discovered in 1910 by the Nobel laureate Albrecht Kossel. It is naturally produced by decarboxylation of arginine and therefore, sometimes termed decarboxylated arginine. Agmatine is widespread in nature and is found in microbial organisms, plants and animals.

Presence in Foodstuff - Agmatine is present in foodstuff derived from plants, fish, and meat. It is found in relatively high levels in the gut and production by gut-dwelling bacteria (microbiota) is considered an important agmatine source. Agmatine sulfate, the commonly used salt form of agmatine, is absorbed by the gut and distributed in the body including the nervous system. Like with arginine, which is a semi-essential or conditionally essential amino acid, depending on their health status, individuals who have poor nutrition or poor metabolic conditions may be advised to increase their intake of agmatine.

Protective Effects - Laboratory experiments showed that treatment with agmatine exerts beneficial effects on various bodily functions. Seminal studies in the early 1920s demonstrated the mild reduction of blood glucose by agmatine. Further scientific research however, was renewed only years later. Of specific interest, is the substantial body of evidence beginning in the 1990s, demonstrating the beneficial effects of agmatine on the nervous system. These include the breakthrough discovery of neuroprotection by the Gilads and discoveries by others including proper control of pain sensations and of behavioral response to stress.

Mild reductions in blood glucose and in blood pressure and heart rate, are additional beneficial effects that may be contributory to agmatine's salutary effects on the nervous system. Additionally, agmatine may exert cardio-protective and kidney protective effects.

Importantly, results of our clinical trials, published in Pain Medicine (Kaynan et al., Pain Med. 11:356-368 2010) demonstrated that dietary G-Agmatine® (Gilad&Gilad's  brand of agmatine) is safe (lacking adverse side effects) and most effective for proper sciatic nerve functions and for healthy spine-nerve structure/function interactions, thus affording a better health-related quality of life. --Remarkably, the 2010 publication of the clinical trials coincided with the centennial of agmatine discovery by Albrecht Kossel in 1910, and established G-Agmatine® as a safe and most effective nutraceutical.

Molecular Mechanisms of Action - The beneficial effects of agmatine occur by its interaction with and modulation of multiple molecular targets of specific importance for nervous system function. These include: (A) modulation of several neurotransmitters - molecules that transmit nerve signals [notably: nicotine, glutamate (NMDA), and adrenaline]; (B) blockade of membrane channels that transport key salts into cells (notably: potassium and calcium); (C) regulation of nitric oxide (NO) production, a ubiquitous regulatory molecule; (D) modulation of polyamines metabolism, known neuroprotective molecules; (E) inhibition of processes that destroy extracellular proteins.

                            
--Agmatine acts as a molecular shotgun targeting multiple molecular mechanisms involved in promoting healthy nervous system functions and is considered the ultimate neuro-modulator.

Present Reserach Efforts - Gilad&Gilad is presently engaged in conducting more clinical trials to substantiate the effectiveness of G-Agmatine® in other indications associated with maintenance of healthier nerve functions.
 
---For further information on potential clinical applications see http://en.wikipedia.org/wiki/Agmatine and
Piletz et al., Drug Discovery Today, 2013; 18:880-893.


For a selective reference list of scientific articles click here.

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 REFERENCES - A Selective List of Peer-Reviewed Research Publications
Nerve Functions
  • Cajal SRY. ... The Nervous System (Translated Ed. May RM). Oxford University Press. 1928. (Classic Principles).
Peripheral Nerve Health
  • Cranford CS, Ho JY, Kalainov, DN, Hartigan BJ, Carpal Tunnel. J Am Acad Orthop Surg 2007; 15:537-548.
  • Frymor JW. N Engl J Med 1988; 318:291-300.
  • Raj PP, Intervertebral Disc: Anatomy-Physiology-. Pain Practice 2008; 8(1): 18–44.
  • O’connor AB, Robert A, Dworkin H, ..: An Overview of Recent Guidelines. Am J Med 2009;122: S22–S32.
  • Park SB, Krishnan AV, Lin CS-V, Goldstein D, Friedlander M, Kiernan MC, Mechanisms ... Curr Medicinal Chem 2008; 15: 3081-3094.
  • Said GR, ...-A Review. Nature Clin Practice Neurol 2007; 3(6): 331-340
Agmatine

Overview

Discovery

  • Kossel A, Über das Agmatin. Zeitschrift für Physiologische Chemie 1910; 66: 257-26.
Presence in Foodstuff
  • Izquierdopulido M, Hernandezjover T, Marinefont A, Vidalcarou MC. Biogenic amines in European bears. J Agric Food Chem 1996; 44:3159-3163.
  • Morris B. Bio-functional legumes with nutraceutical, pharmaceutical, and industrial uses. Economic Botany 2003;57:254–261.
  • Kawabata T, Obshima H, Ino M. Occurrence of methylguanidine and agmatine in foods. IARC Sci Publ 1978; 19:414-423.
Functional Effects
  • Frank E, Nothmann M, Wagner A, Uber synthetisch dargestellte korper mit insulinartiger wirkung auf den normalen und .... organismus. Klin Wchschr 1926;5(45):2100-2107.
  • Weitzel, G., Pfeiffer, B., Stock., W. ...effects of agmatine derivatives in adipocytes, H.-S. Z. Physiol. Chem 1980; 361:51-60.

  • Gilad GM, Salame K, Rabey JM, Gilad VH. Agmatine is (effective) in rodent... models. Life Sci 1996; 58:PL41-PL46.
  • Lortie MJ, Novotny WF, Peterson OW, Vallon V, Malvey K, Mendonca M, Satriano J, Insel P, Thompson SC, Blantz RC. Agmatine, a bioactive metabolite of arginine. Production, degradation and functional effects in the kidney of the rat. J Clin Invest 1996;97:413-420.
  • Gilad GM, Gilad VH. ...(effects of) agmatine (in) spinal cord ... in rats. Neurosci Lett 2000;296:97-100.
  • Zomkowski AD, Hammes L, Lin J, Calixto JB, Santos AR, Rodrigues AL. Agmatine produces ... effects in two models ....(of) mice. Neuroreport 2002;13:387-391.
  • Berenholz L, Segal S, Gilad VH, Klein C, Yehezkeli E, Eviatar E, Kessler A, Gilad GM. Agmatine ...(effects)... (in) facial nerve ... J Periph Nervous Sys 2005; 10:319-328.
  • Steer H. The source of carbon dioxide for gastric acid production. Anat Rec 2009; 292:79-86.
  • Halaris A, Plietz J, Agmatine: metabolic pathway and spectrum of activity in brain. CNS Drugs 2007; 21(11):885-900. (Review).
  • Keynan O, Mirovsky Y, Dekel S, Gilad VH, Gilad GM. Safety and efficacy of dietary agmatine sulfate.... An open label, dose-escalating study followed by a randomized, double-blind, placebo-controlled trial. Pain Med 2010; 11:356-368.
Mechanisms of Action
  • Komori Y, Guillermo CW, Fukuto JM. Inhibition of purified nitric oxide synthase from rat cerebellum and macrophage by L-arginine analogs. Arch Biochem Biophys 1994;315:213-218.
  • Raasch,W, Schafer U, Chun J, Dominiak P. Biological significance of agmatine, and endogenous ligand at imidazoline binding sites. J Pharmacol 2001; 133:755-780. (Review).
  • Haenisch B, von Kügelgen I, Bönisch H, Göthert M, Sauerbruch T, Schepke M, Marklein G, Höfling K, Schröder D, Molderings GJ,Regulatory mechanisms underlying agmatine homeostasis in humans. Am J Physiol Gastrointest Liver Physiol 2008; 295(5):G1104-1110. (Review). 

    Nutraceuticals 

  • Zeisel SH. Regulation of “nutraceuticals.” Science. 1999;285:1853-1855

     

     

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G-Agmatine®
- The Gilad&Gilad's Brand of Agmatine
- In a Class-Of-Its-Own for Neuroprotection and Resilient Nerve Functions -
                 
Featured Advantages:

  • G-Agmatine® is Gilad&Gilad's brand name for the multifunctional ingredient agmatine. A natural amino acid metabolite present in low amounts in plant, fish and meat foodstuff.
  • G-Agmatine® is a safe nutraceutical dietary ingredient as proven by clinical trials.
  • G-Agmatine® is effective for nerve resilience and healthier nerve functions and for a better quality of life at the required fortified dose range of 1.335 to 2.760 gram per day as evidenced by clinical trials.
  • G-Agmatine® Additional benefits extend to healthier glucose metabolism and to kidney and cardiovascular health as amply indicated by experimental scientific studies.
  • G-Agmatine® is a high quality product, manufactured for Gilad&Gilad under cGMP (current Good Manufacturing Practice) conditions in accordance with the highest quality standards and regulations governing our industry.
  • G-Agmatine® is protected by patents.
LINKS
Agmatine - Wikipedia The Free Encyclopedia
AmAmhttp://en.wikipedia.org/wiki/Agmatine

FDA "Tips For The Savvy Supplement User"
http://www.fda.gov...

 Albrecht Kossel
(From Wikipedia, the free encyclopedia):
http://en.wikipedia.org...
                       
NIH Neurological Institute
P.O. Box 5801
Bethesda, MD 20824
Tel: 800-352-9424 or 301-496-5751
http://www.ninds.nih.gov...

American Academy of Orthopaedic Surgeons and  American Association of Orthopedic Surgeons
6300 North River Road
Rosemont, Illinois 60018-4262
Tel: 847-823-7186

http://www.aaos.org/

American Chiropractic Association (ACA)
1701 Clarendon Boulevard
Arlington, VA 22209
Tel: 703-276-8800

http://www.acatoday.org

American Academy of Neurology
1080 Montreal Avenue
St. Paul, MN 55116
Tel: 651-695-2810

www.aan.com

American Pain Foundation
201 North Charles Street
Suite 710
Baltimore, MD 21201-4111
Tel: 888-615-7246
http://www.painfoundation.org


                       

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Last update: August 1, 2014

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