L-ArginineM2 | L-Arginine | Arginine

Directory of Topics

•	Nanotechnology & L-Arginine	•	How to use L-ArginineM²
•	Safe Forms of L-Arginine	•	L-Arginine Regimens: Usage Directions
•	Unacceptable Forms of L-Arginine	•	Daytime Protocol
•	L-Lysine & L-Arginine	•	Night-Time Protocol
•	Lysine & Herpes Simplex Virus	•	Fat-Burning Protocol
•	L-Arginine M² Legal Claims	•	Athlete’s Protocol
•	L-Arginine M² Claims & Protocols	•	Human Maximum Performance for Athletes
•	Arginine & Blood-Brain-Barrier	•	L-Arginine M² & Anti-Doping Regulations
•	Inventor: About the Inventor and Patent Holder	•	Japanese Version
•	Official L-Arginine Athletes	•	Q & A: Common Questions About L-Arginine M²
•	Dangers of L-Arginine	•	Blind Amino Acid ® Rider

L-Arginine
L-ArginineM2® nanotechnology is directed
at harnessing the benefits of the
amino acid L-Arginine

Miracle Molecule

The amino acid L-arginine is considered the most potent nutraceutical ever discovered, due to its powerful health properties, and is referred to by scientists as the “Miracle Molecule.”

The remarkable properties of L-arginine were validated by the 1998 Nobel Prize in Medicine, and since then have created a frenzy of interest in the pharmaceutical and nutraceutical fields.

Columbia University refers to L-arginine as the “Magic Bullet” in human health. Over 10,000 L-arginine citations have been compiled by Columbia University researchers in their quest to document the benefits of this simple amino acid. It is now taught to medical students at the Columbia University College of Physicians and Surgeons.

The Nobel Prize landmark discovery of the functions of nitric oxide (NO) highlighted the fact that without NO, human life would be impossible. Even more revolutionary was the irrefutable evidence that L-arginine is the sole NO molecule in the human body.

Twenty years ago, the idea that a simple and humble amino acid could change the face of medicine would have been dismissed. Now, physicians, researchers, and scientists are embracing the effectiveness of L-arginine and its use has become mainstream.

Forms of L-Arginine
Creating Safe L-Arginine Formulas

Incorrect ingredients in L-arginine products will block L-arginine’s entry into the body as a free form amino acid. If L-arginine is not properly formulated, it will not elevate serum levels of L-arginine, will not cross the Blood-Brain-Barrier (BBB), and will not provide health benefits. L-arginine products that are founded on metabolic mistakes do not metabolize correctly, and are therefore ineffective.

It is unwise to use any L-arginine product without first ascertaining its length of use (history and use in humans), the formulator of the product, the patent status, the form of L-arginine used, the exclusion of L-arginine antagonists, and its ultimate isoform pathway via inclusion of a “Blind Amino Acid ® Rider.”

Because all forms of L-arginine are Blind Amino Acids, it is mandatory that the form of L-arginine be bound to a Blind Amino Acid ® Rider, and formulated by an L-arginine expert with a background in safe Arginine isoform pathways.

The L-arginine-nitric-oxide signaling pathway is probably the most complicated facet of biochemistry. In creating an effi cacious formula, the form of L-arginine used will dictate the quality of the product. If the form of Arginine used in a formula is not appropriate, the product will not work, and can exhibit
side effects.

The L-form (left-handed) of Arginine is acceptable for human use, while the D-form (right-handed) is not. The D-form of L-arginine is an example of an unacceptable form of L-arginine, though there are many other unacceptable forms, including L-arginine antagonists.

Antagonists are agents that directly compete with L-arginine and:

•	Block L-arginine health benefits
•	Prevent L-arginine metabolism
•	Negate L-arginine’s ability to cross the Blood-Brain-Barrier
•	Cause potential serious health problems (including damage to sperm and mortality)

Forms of L-Arginine
Unacceptable L-Arginine Formulas

Arginine HCL

In studies where the HCL form of L-arginine has been used, metabolic acidosis and alterations in electrolytes have been documented. It is therefore not recommended for human use. Arginine HCL is the form that was used in the tragic Johns Hopkins/JAMA clinical trial that caused mortalities. (www.ArginineAnswers.com).

Arginine Pyroglutamate

Not recommended for human use. Mechanism of action in the body is entirely speculative according to the Physician’s Desk Reference (PDR).

Arginine Ketoglutarate And Alpha-Ketoglutarate (AKG)

Researchers and physicians caution that Alpha-ketoglutarate is not recommended for human use.

High Glycemic L-Arginine

High glycemic L-arginine formulas are not eff ective and are contraindicated for use in humans. High glycemic formulas include those that contain: maltodextrins, glucose, glucose polymers, sugar (sucrose), honey, high fructose corn syrup, fructose corn syrup, flavors made with maltodextrins, sweeteners without caloric impact, and any high glycemic raw material. Any of these ingredients block Arginine transport and metabolism and are contraindicated in L-arginine formulas.

Nutrients & Supplements

Foods, drinks (other than water), nutrients, vitamins, herbs, minerals, and supplements also block L-arginine. Therefore, they must be taken separately from L-arginine formulas.

Capsules, Tablets, Sprays, Liquids

Formulas Containing Less Than 5,000 Mg For Daytime Use, And Less Than 10,000 Mg

For Night-Time Use

Formulas Without A Blind Amino Acid ® Rider

Formulas That Contain Protein Or Any Competing Amino Acid

L-LYSINE & L-ARGININE

Formulas containing L-arginine with L-lysine do not work, and are the result of improper formulating.

Dietary disproportions of amino acids are counterproductive and can alter serum levels and flux of specific amino acids across the Blood-Brain-Barrier (BBB). The Lysine/Arginine antagonism is an example of this alteration. A plethora of definitive clinical studies have proven that L-arginine and L-lysine are antagonistic in humans, IE Johns Hopkins University.

One of the most prominent formulating mistakes related to L-arginine antagonism is the inclusion of Lysine. Though L-lysine is a direct antagonist of L-arginine, it is frequently seen in L-arginine formulas. L-lysine should never be combined with L-arginine, but is often seen in L-arginine products with the purpose of mitigating the herpes reaction. This combining technique is a result of bad science, as it negates the benefits of L-arginine.

L-LYSINE& HERPES SIMPLEX VIRUS

The human Herpes Simplex Virus (HSV) is a recurrent viral infection that is caused by Herpes virus hominis (HVH), a widespread infectious agent. The human herpes viruses are multipotential, and inclu+de HSV types 1 and 2, human cytomegalovirus, Varicella-Zoster virus, and the Epstein-Barr Virus. These viruses are transmitted by respiratory and oral secretions and commonly produce fever blisters, cold sores, flu-like symptoms, headache, swollen glands, and may also infect the urethra causing burning sensations during urination. There is currently no cure for HSV, but there are measures that can be taken to reduce manifestations.

Increased levels of lysine over arginine suppress viral replication and inhibit cytopathogenicity of herpes simplex virus (HSV). This interaction between the amino acids lysine and arginine can be mitigated by taking L-lysine supplements about 2 hours separately from L-arginine

The L-ARGININE M² patent and formula have been bioengineered to reduce the effects of herpes simplex as stimulated by lack of L-lysine, but symptom triggers in humans are also caused by lack of sleep and stress. Eight hours of sleep per night is required to reduce activation of HSV. During human sleep cycles, immune function is activated, which affects the herpes simplex virus, as well as all viruses. Additionally, if sleep cycles and nutrient intake is not balanced, HSV will become prominent with manifestations such as cold sores and lethargy.

L-LYSINE DOSAGE & HSV

Lysine has been used effectively as an agent for reduction of occurrence, severity and healing time for recurrent HSV infection. Supplementation with free-form L-lysine has shown to be beneficial in controlling herpes symptoms.

The amount of Lysine required to control herpes varies from case to case, but a typical dose to maintain remission (as stated in most trials) is 500-1000 milligrams (mg), and for active herpes, 1000 mg (1 gram) to 6000 mg (6 grams) taken daily.

Clinical trials suggested that persons with the herpes simplex virus take 1000 mg of oral L-lysine in capsule form, a few times per day (1-3), taken 2 hours apart from the L-arginine (as they compete with each other).

In terms of controlling HSV outbreaks, UCLA School of Medicine (Dr. Griffith, Dr. Kagan, Dr. Norins) found that there is a 96% success rate in patients taking 1500 mg of supplemental L-lysine daily.

Lysine supplements in capsule form can be found in most health food stores. When selecting a Lysine supplement, Lysine should be the only ingredient listed on the label, as the addition of any other amino acid or ingredient can negate its benefit. Tablets are to be avoided. The most advanced and efficacious form of Lysine supplementation is NanoGel technology.

Lysine/Arginine
Copyright © 1983-2007

Aspirin

Aspirin is a known antagonist to Arginine, and cannot be taken within 2 hours of taking L-arginine. Aspirin can be beneficial and is frequently recommended by a physician. If your physician has recommended aspirin, take it separately from L-arginine.

L-Ornithine

L-ornithine has been clinically proven to be an antagonist of L-arginine and disrupts Larginine transport. L-ornithine is contraindicated in any L-arginine formulas, and specifically in products geared to the athlete. L-ornithine should be avoided by bodybuilders, powerlifters, and all other athletes, as well as persons desiring to increase muscle mass, because Ornithine is a non-protein amino acid. Ornithine is not anabolic and is not used to make protein in the human body, whereas Arginine does make protein and is anabolic.

L-Citrulline

According to multiple independent studies, L-citrulline is not an appropriate ingredient in an L-arginine formulation. The use of Citrulline in an L-arginine formulation can cause inherent problems, including depletion of L-arginine.

•	Endogenous NOS inhibitors reduce the enzyme sensitivity to L-arginine. These inhibitors include, NG, NG-dimethyl-L-arginine, L-citrulline, argininosuccinic acid and agmatine.

•	Intracellular L-citrulline, an NOS product, is a potent inhibitor of NOS so that the cells may need extra L-arginine to compete with L-citrulline inhibition.

The Arginine Paradox (Folia Pharmacol. Japan Vol. 119 7-14:2002 Department of Pharmacology, Teikyo University School of Medicine):

Lee J, Ryu H, Ferrante RJ, Morris SM Jr, Ratan RR. Translational control of inducible nitric oxide synthase expression by Arginine can explain the Arginine paradox. Proc Natl Acad Sci U S A 2003;100:4843-8.

P. Roy. Recent trends in the nitrergic nervous system.2005. In. Journal of Pharmacology; P. Roy, G. Venkat Ramana, M. Naidu, P. Usha Rani

Thomas G, Ramwell PW. Nitric oxide, donors and inhibitors. In: Bertram G Katzung, editor. Basic and Clinical Pharmacology. United States: McGraw Hill; 2004.p.313-8.

Chandran S, Sridhar N, Veeranjaneyulu A. Nitric oxide: concepts, current perspectives and future therapeutic implications. Indian J Pharmacol 1998;30:351-66.

Legal Claims
For L-ArginineM2®

“Legal Claims” herein stated (1-15) are solely related to the L-ArginineM² Patent, as awarded to Dr. Ann de Wees Allen, the exclusive inventor and Patent-holder of L-ArginineM².

Each of the fifteen (15) claims for L-ArginineM² have been submitted and analyzed by FDA and FTC regulatory attorneys and are allowed under the Dietary Supplement Health and Education Act of 1994.

Said claims have been determined to meet the legal requirements of “Dietary Supplement Structure/Function” claims per government regulations, as related to Dr. Allen’s Patent for L-arginine, and upon review of the Patent’s documentary evidence and clinical substantiation spanning a two-decade period of more than 23 years, including broad use of safety in humans.

The following claims are unique to the L-ArginineM² Patent and evidential documents submitted since 1983, and may not be used for any other product or patent, under penalty of law.

Basis for Claims:

•	2 Decades of L-Arginine Research
•	Safe Use by Over 250,000 Human Subjects
•	Safe Use in Humans Over A Longer Period Than Any Other L-Arginine Product (Since 1983)
•	Over 100,000 Pages of Documentation
•	Only L-Arginine That Contains a Rider for Blind Amino Acids
•	Only Certified Low Glycemic L-Arginine Product

LEGAL CLAIMS
As related to L-ArginineM2® Patent

1.	Enhances Muscle Mass
2.	Supports Muscle Growth
3.	Stimulates Muscle Development
4.	Supports Hypothalamic Response
5.	Aids In Decreasing Body Fat
6.	Is An Antioxidant
7.	Helps Maintain Healthy Blood Sugar Levels
8.	Is More Well Tolerated Than L-Arginine Alone
9.	Helps Boost Energy
10.	Is Rejuvenative
11.	Helps Promote Healthy Sexual Performance
12.	Is An Adaptogen
13.	Growth Hormone: Helps Provide The Building Blocks Necessary For The Body To Maintain Its Own Healthy Growth Hormone Levels
14.	Helps Produce Nitric Oxide (NO)
15.	Stimulates Production Of Human Anti-Aging Mechanisms In Persons Over 23

* See explanation at www.ArginineAnswers.com

L-ArginineM2®
Claims and Protocols

The L-ArginineM2® Protocols align the claims (1-15)
with the appropriate method of use.

	Claim	Protocol
1.	Enhances Muscle Mass	Night Time
2.	Supports Muscle Growth	Night Time
3.	Stimulates Muscle Development	Night Time
4.	Supports Hypothalamic Response	Night Time
5.	Aids In Decreasing Body Fat	Night Time/Fat Burning
6.	Is An Antioxidant	All
7.	Helps Maintain Healthy Blood Sugar Levels	All
8.	Is More Well Tolerated Than L-Arginine Alone	All
9.	Helps Boost Energy	All
10.	Is Rejuvenative	All
11.	Helps Promote Healthy Sexual Performance	All
12.	Is An Adaptogen	All
13.	Growth Hormone: Helps Provide The Building Blocks Necessary For The Body To Maintain Its Own Healthy Growth Hormone Levels	Night Time
14.	Helps Produce Nitric Oxide (NO)	All
15.	Stimulates Production Of Human Anti-Aging Mechanisms In Persons Over 23	Night Time

How To Use L-ArginineM2®

L-ArginineM2®
Regimens

Since L-arginine is both Dose-Dependant and Timing-Dependent, the benefits derived from taking L-ArginineM²are based on the amount taken (Dose-Dependent) and the time it is taken (Timing-Dependent).

Therefore, there are four (4) diff erent Protocols for achieving dose-related and time-related benefits from L-ArginineM². Each of the four (4) Protocols is attained by following a specific Regimen as follows:

•	*DAYTIME*
•	*NIGHT-TIME*
•	*FAT-BURNING*
•	*ATHLETES*

DAYTIME
Protocol & Regimen

The Daytime Protocol is appropriate for the following claims:

6.	Is An Antioxidant
7.	Helps Maintain Healthy Blood Sugar Levels
8.	Is More Well Tolerated Than L-Arginine Alone
9.	Helps Boost Energy
10.	Is Rejuvenative
11.	Helps Promote Healthy Sexual Performance
12.	Is An Adaptogen
14.	Helps Produce Nitric Oxide (NO)

Directions for the Daytime Regimen

Amount: One level scoop of L-ArginineM² contains 5 grams (5,000 mg) of Elemental L-arginine, the therapeutic dose required for daytime use. Use one (1) level scoop of L-ArginineM² mixed with 4-8 ounces of water. Do not use flavored or enhanced water, do not use juice, use only plain water, either tap water or bottled water.

Timing: Take 1 scoop (mixed in water) in-between meals. Do not take with meals or within ½ hour of meals or snacks. May be taken 1-3 times per day as desired or as directed by a physician.

Contraindications: L-arginine products may NOT be used by persons under age 23 without express instruction from an attending physician. Pregnant and nursing women may not use any L-arginine product. Do not take L-arginine with L-citrulline or any other amino acid or protein.

NIGHT-TIME
Protocol & Regimen

The Night-Time Protocol is strictly for use by persons over age 23. You cannot use any L-arginine product at bedtime or night-time in persons who are under age 23, as they are still producing growth hormone (GH), and growth factors. Using L-ArginineM², or any other L-arginine product to increase height will not work, as total height is genetically controlled and cannot be altered.

For persons over age 23, the Night-Time Protocol is appropriate for the following claims:

1.	Enhances Muscle Mass
2.	Supports Muscle Growth
3.	Stimulates Muscle Development
4.	Supports Hypothalamic Response
5.	Aids In Decreasing Body Fat
6.	Is An Antioxidant
7.	Helps Maintain Healthy Blood Sugar Levels
8.	Is More Well Tolerated Than L-Arginine Alone
9.	Helps Boost Energy
10.	Is Rejuvenative
11.	Helps Promote Healthy Sexual Performance
12.	Is An Adaptogen
13.	Growth Hormone: Helps Provide The Building Blocks Necessary For The Body To Maintain Its Own Healthy Growth Hormone Levels
14.	Helps Produce Nitric Oxide (NO)
15.	Stimulates Production Of Human Anti-Aging Mechanisms In Persons Over 23

Directions for the Night-Time Regimen

Amount: Two level scoops of L-ArginineM² contain 10 grams (10,000 mg) of Elemental L-arginine, the therapeutic dose required for Night-Time use. 25 total grams of L-ArginineM² contain 10 grams of pure L-arginine.

Two (2) level scoops of L-ArginineM² mixed with 8 ounces of water or any preferred amount of water. Some people wish to use a smaller amount of water at bedtime to avoid night-time urination. The amount of water used is not important, as long as the 2 scoops are mixed thoroughly. Do not pre-mix L-ArginineM² with water and let it sit for more than 10 minutes.

Do not use flavored or enhanced water, do not use juice, use only plain water, either tap water or bottled water.

Timing: Take 2 scoops (mixed in water) 30 minutes prior to SLEEP. Example: Dinner 8 PM, take L-ArginineM² 11 PM, go to sleep at 11:30 PM.

L-ArginineM² Night-Time Regimen must be taken on an empty stomach. You cannot eat for 2-3 hours prior to taking the Night-Time dose, or the product will not work (accessing the BBB and Delta sleep cycle is mandatory).

Do not take within 2-3 hours of meals or snacks or drinks other than water. May be taken only one (1) time per day at bedtime.

Contraindications: L-arginine products may NOT be used by persons under age 23 without express instruction from an attending physician. Pregnant and nursing women may not use any L-arginine product. Do not take L-arginine with L-citrulline or any other amino acid or protein.

FAT-BURNING
Protocol & Regimen

The Preferential Fat-Burning Protocol is primarily for persons who wish to use L-ArginineM² as an adjunct to reducing excess adipose body fat and is appropriate for the following claims:

5.	Aids In Decreasing Body Fat
6.	Is An Antioxidant
8.	Is More Well Tolerated Than L-Arginine Alone
9.	Helps Boost Energy
12.	Is An Adaptogen

Mechanism for Preferential Fat-Burning

When L-ArginineM² is used as a drink prior to and during exercise, it triggers a relative shift in substrate utilization from carbohydrate to FAT.

The biochemical mechanism by which L-ArginineM² preferentially triggers Adipose Tissue Fat-Burning (ATFB) is a result of the unique combination of Trutina Dulcem bonded to the Elemental
L-arginine molecules in a low glycemic matrix.

No other Arginine product worldwide can produce Preferential Fat Burning.

L-ArginineM² taken as a drink prior to and during exercise reduces the weight of abdominal
(retroperitoneal) and epididynal adipose tissue fat tissues (45 and 25% respectively).

L-ArginineM² increases adipose tissue fat expression of genes aligned with glucose oxidation and fatty acid oxidation by 120 % to 800 % via Heme Oxygenase-3, PPARC-1, NOs- 1, and AMP-A Protein Kinase.

An ideal exercise for this mechanism is using a treadmill @ 70% VO2max. Alternatively, fast walking or light jogging will also trigger the appropriate VO2max.

Directions for the Preferential Fat-Burning Regimen

Amount: One level scoop of L-ArginineM² contains 5 grams (5,000 mg) of Elemental L-arginine, the therapeutic dose required for the Fat-Burning Regimen.

Use one (1) level scoop of L-ArginineM² mixed with 8-12 ounces of water.

Do not use flavored or enhanced water, do not use juice, use only plain water, either tap water or bottled water.

Timing: Take 1 scoop L-ArginineM² and mix in 8-12 ounces of water. You may place 1 scoop in your sports bottle, add water, and shake to dissolve. Drink the entire contents prior to and during exercise.

Do not take with meals or within ½ hour of meals or snacks. Do not use any sports drink within 2 hours of using the Fat-Burning Regimen – water only.

May be taken 1-2 times per day prior to exercise.

Contraindications: L-arginine products may NOT be used by persons under age 23 without express instruction from an attending physician. Pregnant and nursing women may not use any L-arginine product. Do not take L-arginine with L-citrulline or any other amino acid or protein.

ATHLETES
Protocol & Regimen

The Protocol for Athletes is designed for the professional, competing, world-class, and/or serious athlete. Persons under age 23 may not use this regimen.

This regimen is designed to increase muscle mass and muscle mitochondria, increase strength, reduce adipose tissue body fat, and to shorten recuperation time. Benefits of specific interest to athletes are bolded.

For persons over age 23, the Athlete’s Regimen is appropriate for the Following Claims:

1.	Enhances Muscle Mass
2.	Supports Muscle Growth
3.	Stimulates Muscle Development
4.	Supports Hypothalamic Response
5.	Aids In Decreasing Body Fat
6.	Is An Antioxidant
7.	Helps Maintain Healthy Blood Sugar Levels
8.	Is More Well Tolerated Than L-Arginine Alone
9.	Helps Boost Energy
10.	Is Rejuvenative
11.	Helps Promote Healthy Sexual Performance
12.	Is An Adaptogen
13.	Growth Hormone: Helps Provide The Building Blocks Necessary For The Body To Maintain Its Own Healthy Growth Hormone Levels
14.	Helps Produce Nitric Oxide (NO)
15.	Stimulates Production Of Human Anti-Aging Mechanisms In Persons Over 23

Directions For The
Athlete's Regimen

Human Sports Performance

Serious Results for Serious Athletes

Directions for Athletes taking L-ArginineM2 are very precise, and must be followed to the letter in order to obtain maximum benefits.

After two decades of working with hundreds of World-Class athletes, our advanced L-arginine research and protocols have been finely-tuned, and are considered the most successful in the entire sports industry.

Reaching Human Maximum Performance in sports requires that an athlete maximize his/ her genetic and individual physical potential. This requires working one-on-one with:

•	A skilled nutritional/biochemical expert trained in State-of-the-Art methodologies in sports performance.

•	A trainer that is highly skilled in sports physiology.

Parameters directly tied to athletic ability:

1.	Genetics/Heredity
2.	Somatotype
3.	Individual Biochemistry
4.	Food Program
5.	Nutritional Supplementation
6.	Age
7.	Focus & Drive (Mental/Brain/Physical)
8.	Training
9.	Performance Hormone Levels

GAINING ‘THE EDGE”

Without an “Edge” the athlete is doomed to mediocrity. The “Edge” is gained by going beyond the barriers required of normal persons, and achieving Human Maximum Performance. All of the nine (9) of the parameters directly tied to athletic ability must be addressed in order to reach Human Maximum Performance. Trial and error do not work in the highly competitive field of sports.

The utilization of L-ArginineM² in a Human Maximum Sports Performance Program addresses numbers 5 and 9 of the parameters specifically:

1.	Genetics/Heredity
2.	Somatotype
3.	Individual Biochemistry
4.	Food Program
5.	Nutritional Supplementation
6.	Age
7.	Focus & Drive (Mental/Brain/Physical)
8.	Training
9.	Performance Hormone Levels

Performance Hormone Levels

An athlete’s ability to perform is largely dependent on his/her hormone levels. The most important sports performance hormones (in males and females) are testosterone and growth hormone.

Athletes with genetically low testosterone or growth hormone (GH) levels will not be able to compete at a high level. Sub-optimal levels of performance hormones result in ultimate failure in the professional and competitive sports arena.

In humans, the primary function of performance hormones is to provide:

•	Generation Of Natural Anabolic Hormones
•	Increased Muscle Mass
•	Decreased Adipose Tissue Body Fat
•	Increased Internal Thermogenesis
•	Increased Strength & Stamina
•	Reduced Incidence Of Injury
•	Improved Healing Time

Many athletes turn to illegal steroids, and synthetic testosterone and GH to increase their performance abilities. These drugs are illegal and dangerous, and reduce lifespan. They are also unnecessary. There are legal and safe methods for naturally and legally increasing performance hormones in humans.

Normal humans produce very high amounts of performance hormones, such as testosterone and GH, during ages 15-18. After age 23, production of these hormones decrease, and continue to descend as age progresses. At age 30, the decline begins to aff ect sports performance.

Though the brain (via the hypothalamus/pituitary axis) “turns off ” its production of performance hormones as age progresses (beginning at age 23), this axis can be re-instated in a natural and legal methodology in humans.

The brain is completely able and capable of reinstating the same performance hormones as those found in a teenager. It requires precise dosing and timing, and the ability of L-arginine to cross the Blood-Brain-Barrier (BBB). If L-arginine does not cross the BBB, there is no reinstation or release of performance hormones.

Therefore, athletes cannot take L-arginine in a form that is incapable of crossing the Blood-Brain-Barrier (BBB).

Forms Of L-Arginine That Do
Not Cross The Blood-Brain-Barrier

(For complete list see: Unacceptable L-Arginine Formulas)

•	Capsules Or Tablets
•	Sprays Or Liquid
•	High Glycemic Formulas (Any Formula That Contains Glucose, Glucose Polymers, Sugar, Sucrose, Maltodextrins, Honey)
•	Less Than 10,000 Mg (10 G) Of Elemental L-Arginine
•	Formulas Without A Blind Amino Acid ® Rider
•	Formula That Contain Protein Or Competing Amino Acids
•	Formulas With No/Low Carbohydrates
•	HCL Arginine Or
•	Formulas Taken At Incorrect BBB Access-Times
•	Formulas Taken With Or Near Food/Drink (Other Than Water)
•	Formulas That Contain High Glycemic Flavor Systems
•	L-Lysine: Unlike L-arginine, L-lysine does not improve whole muscle strength or size, and is therefore a substandard amino acid for athletes and persons desiring to increase size and power output from muscle tissue and muscle mitochondria.

Amount For Athletes

In order to elicit any performance hormone response from the brain, including growth hormone and testosterone, a minimum of 10,000 mg (10 grams) of Elemental L-arginine is required. Anabolic, anti-aging and sports performance benefits only occurs when 10 grams of pure elemental L-arginine is ingested in a low glycemic format with no competing proteins, amino acids, maltodextrins, or sugars.

The appropriate dose for most athletes is 2 scoops of L-ArginineM².

10 grams of L-arginine = 2 level scoops of L-ArginineM²

2 level scoops of L-ArginineM² contain 10 grams (10,000 mg) of Elemental L-arginine.

3 level scoops contain 15 grams (15,000 mg) of Elemental L-arginine.

2-3 level scoops are the therapeutic doses required for the athlete, depending on the size of the individual.

When mixing L-ArginineM², do not use flavored or enhanced water, do not use juice, use only plain water, either tap water or bottled water. Biochemically speaking, de-ionized water is the best form of water available (not distilled or spring water).

Selecting Appropriate Serving Size: Athletes can decide how many servings to take depending on personal goals and overall size. Start by taking 1 serving the first night and then increase to 2-3 servings, if desired, over a period of a few days.

See Contraindications for exemptions.

Athletes Timing:

Take L-ArginineM2 30 minutes prior to sleep on a totally empty stomach. A totally empty stomach means nothing taken but water 2-3 hours prior to taking L-ArginineM². You must take L-ArginineM² thirty (30) minutes prior to sleep because L-arginine must cross the Blood Brain Barrier (BBB) during Delta Sleep.

In athletes, if you have anything in your stomach for two hours prior taking L-ArginineM², it is not going to work, and will be a waste of time, money and effort.

Athletes only produce significant amounts of growth hormone (GH) two times in a 24-hour period:

•	During specific sleep cycles
•	During intense exercise (not aerobics), such as lifting weights and resistance exercise

Therefore, athletes can take L-ArginineM² (at GH doses/2+ scoops) twice per day, while the non-athlete should not.

Timing For 1) Sleep Cycle

Take 2-3 scoops L-ArginineM² and mix in ½ - 1 cup water. Use enough water for the powder to go into solution. If the water is cold, it may take a minute for solubility.

Take at bedtime (on a totally empty stomach) 30 minutes prior to sleep. Do not pre-mix the product and let it sit for more than 10-15 minutes.

Do not take with meals or within ½ hour of meals or snacks. Do not use any sports drink within 2 hours of using the Athletes Regimen – water only. Ingesting food, amino acids, or proteins with or near this product is not in any way harmful, it simply will negate the benefits.

Timing For 2) Intense Exercise

Athletes may take an optional 1-2 servings 30 minutes prior to intense exercise on an empty stomach. Intense exercise is defined as lifting weights or resistance exercise (not aerobic exercise). If taking
L-ArginineM² 30 minutes prior to sleep is problematic, the athlete may instead utilize Timing # 2 (Intense Exercise). In general, athletes should not eat close to bedtime, as it interferes with the body’s natural cycles and production of anabolic muscle building.

Athletes Suggestions:

If an athlete is not accustomed to taking large doses of L-arginine, a slow-start program may be acceptable. In persons not accustomed to taking large doses of L-arginine, soft stools or mild diarrhea may occur. This is a normal reaction to high-dose L-arginine. In said cases, reduce the amount taken until normal stools return.

Start off the first night with one scoop which is 5 grams of L-arginine. For 2-3 nights just take one scoop. Then go up to 2 scoops, which is 10 grams of elemental L-arginine. Take 10 grams per night at bed time for about 3 weeks to a month. The body should then be accustomed to large doses of L-arginine.

Increased Doses: Directions for male athletes electing to use more than 10 grams of L-arginine at bedtime:

After working up to 10 grams (without diarrhea), athletes may elect to start taking 15 grams
(3 scoops) per night at bed time.

•	Stay at 3 scoops for one month.
•	Compare the results with those of the 10 gram dose. If the athlete is getting better results at 10 grams per night versus 15 grams per night, stay at 10 grams per night.
•	More is not always better - If you’re not getting better results at 15 grams go back to 10 grams.

Female athletes should stay at 10 grams.

Contraindications: L-arginine products may NOT be used by persons under age 23 without express instruction from an attending physician. Pregnant and nursing women may not use any L-arginine product. Do not take L-arginine with L-citrulline or any other amino acid or protein. Non-athletes should not take more than 10 grams of L-arginine at one time.

Long-Term Safety of
L-Arginine In Humans
January 2006

Media Warns of L-Arginine Dangers

On January 4, 2006 the Wall Street Journal reported “Heart Patients Urged to Avoid L-Arginine.” The article stated that the dietary supplement L-arginine “May harm heart patients” and that “Heart attack patients should avoid the dietary supplement L-arginine, based on a study that was scuttled after six volunteers taking the over-the-counter supplement died.”

The Wall Street Journal announcement was triggered by the clinical study reported in the January 2006 issue of the Journal of the American Medical Association (JAMA) entitled L-Arginine Therapy in Acute Myocardial Infarction (1).

The L-arginine double-blind, placebo-controlled clinical trial was headed by Dr. Steven Schulman, M.D. of Johns Hopkins Medical Institutions, and involved administering various doses of the amino acid L-arginine orally to subjects who had experienced cardiac events (myocardial infarction).

The clinical trial was abruptly stopped when death occurred (within six months) in 6 patients (8.6%) in the L-arginine group and none (-0-) in the placebo group (P = .01). After six months of a planned two-year study, the researchers became alarmed at the mortality rate in the group taking L-arginine, as compared to those taking a placebo. None of the subjects in the placebo (non-arginine) group died.

Researchers conducting the clinical trial stated that instead of the expected benefits from L-arginine, increased risk of death was seen, leading to early termination of the study. As reported in JAMA, “Because of the safety concerns, the data and safety monitoring committee closed enrollment.”

News Media Seeks
Dr. Ann de Wees Allen's Opinion

On December 30, 2005, Bloomberg News called Dr. Ann de Wees Allen’s office and requested an immediate live interview. Bloomberg is the leading global provider of data, news and analytics.

The Bloomberg Terminal and Bloomberg's Media Services provide real-time and archived financial and market data, pricing, trading, news and communications tools in a single, integrated package to corporations, news organizations, financial and legal professionals and individuals around the world.

As the leading worldwide L-arginine researcher and expert (2), Dr. Allen was asked to provide Bloomberg Media Services (BMS) with an expert opinion on the JAMA L-arginine study and subsequent deaths.

Dr. Allen had spoken at length with Dr. Steven Schulman regarding the JAMA publication, and has publicly defended Dr. Schulman, Lead Researcher of the clinical trial, stating that:

“Dr. Steven Schulman is a well-respected doctor and researcher, who focused on the best interests of his patients and the subjects in the study” and that “Dr. Schulman is a kind and caring man, who would never risk human lives in any format. Further, Dr. Schulman conducted a responsible and humane clinical study, with no knowledge of the unfortunate outcome.”

Mortality Related to
Ingestion of L-Arginine

Learned scientists can speculate on the cause of the high mortality rate in the L-arginine JAMA/Johns Hopkins clinical trial, but to do so one must possess intricate knowledge of L-arginine biochemistry as well as cardiovascular medicine, and clinical trial variables.

There are thousands of published clinical trials utilizing L-arginine that have not resulted in mortalities. In terms of future L-arginine clinical trials, it is recommended that the form of L-arginine be bound to a Blind Amino Acid Rider, and formulated by an L-arginine expert with a background in safe arginine Isoform pathways.

Two Decades of L-Arginine Research

Dr. Ann de Wees Allen has been researching L-arginine since 1983, longer than any other arginine researcher, and has tracked oral ingestion of specific L-arginine compounds in over 250,000 human subjects over a 25-year period. Due to Dr. Allen’s discovery that L-arginine has the capacity to access different Isoform pathways, L-arginine was named a “Blind Amino Acid.”

Dr. Allen has spent the past two decades researching efficacious L-arginine protocols in humans, and designing glycoside Riders for the safe transport of oral L-arginine in humans (3). Her research and resulting Patents (4) have been named "Breakthrough Product of the Year" by Success magazine and have been featured on the front page of the Wall Street Journal.

Dr. Allen’s long-standing reputation as the leading expert in the field of L-arginine, as well as the Glycemic Index, is evidenced by 23 years of accolades and accomplishments:

•	Who's Who of American Inventors
•	Association of Clinical Research Professionals
•	American Diabetes Association Council on Nutritional Science & Metabolism
•	Who’s Who in Diabetes Education and Research, American Diabetes Association
•	Received first Glycemic Patent ever awarded worldwide
•	Filed the first Patent on Safe L-arginine Biochemical Pathways
•	Discovered the first Isoform Pathway for L-arginine that Circumvents Disregulated Arginine Metabolism

Generating Safe Forms of L-Arginine

The scientific community only accepts proven and quantified Protocols for the safe and efficacious administration of L-arginine in humans.

L-arginine M² is the result of the entire body of work conducted by Dr. Ann de Wees Allen, with a documented 25-year proven history of safe L-arginine in humans.

L-arginine M² represents the First Generation of safe and effective L-arginine, as the first L-arginine product proven to be safe in humans long-term. L-arginine M² is also the only L-arginine product to be used safely in humans over a 25-year period.

Examining the Safety of L-Arginine

Prior to using any L-arginine product, one must examine the history of its availability on the market. The length of its use in humans must be ascertained in order to determine long-term safety in humans.

Consumers must also be allowed to examine the Patents on any L-arginine product, and the name of the scientist (s) who formulated the product. If the formulator is not named, or is not a proven L-arginine specialist, caution is dictated. Once the formulator’s name is provided, do a “Google” search on their name to make sure this person is recognized as an L-arginine expert. Professional corporations will openly display the name of the formulator. If the formulator is not named, or is not a proven L-arginine specialist, and Patent-holder, caution is dictated.

Many L-arginine products claim to have Patents, when they do not, despite the fact that it is a Federal offense to say “Patent or Patent-Pending” on a label if there is no Patent filed with the United States Federal government (www.USPTO.gov).

The most important aspect in selecting a safe L-arginine product is the addition of a “Blind Amino Acid” Rider. Without this essential facet, L-arginine cannot take a safe Isoform pathway.

Since the JAMA article was published, consumers have become extremely cautious about using L-arginine. It is unwise to use any L-arginine product without first ascertaining its history, use in humans, formulator, Patent-status, and Isoform pathway.

Dosages

Subjects in the study started taking L-arginine HCL, 1 g three times daily for 1 week, increasing to 2 g three times daily in week 2, followed by 3 g three times daily in week 3. Patients were maintained at this dose for 6 months. Dosages of L-arginine are clearly not the culprit in the high mortality rate evidenced during the JAMA Johns Hopkins study, as the subjects in the upper-limit doses only consumed 9 grams of L-arginine per day.

Safe doses of L-arginine taken with a Blind Amino Acid Rider range up to 50 grams of elemental L-arginine taken daily in humans for over a 20-year period. Since dosages were not responsible for the deaths in the JAMA study, that aspect can be disregarded.

Education

The layperson cannot be expected to possess scientific knowledge of the intricacies of L-arginine and its man.comy forms and functions. To this end, www.ArgM2.com has been designed to educate the public on safety issues, Protocols, contraindications, and other issues related to ingestion of L-arginine.

References

*(1)*	JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (JAMA) Vol. 295 No 1, January 4, 2006 L-Arginine Therapy in Acute Myocardial Infarction The Vascular Interaction With Age in Myocardial Infarction Steven P. Schulman, MD et al Johns Hopkins Hospital
(2)	Dr. Ann de Wees Allen Chief L-Arginine Researcher Medical Advisory Board

Circulation. 2000;101:2126. American Heart Association; What We Know and Don’t Know About L-Arginine and NO

The American Society for Nutritional Sciences. J. Nutr. 134:2820S-2825S, October 2004. Arginine Metabolic Enzymes, Nitric Oxide and Infection

2001. Regulatory role of arginase I and II in nitric oxide, polyamine, and praline syntheses in endothelial cells. Am. J. Physiol. 280:E75-E82.

Wiesinger H. Arginine metabolism and the synthesis of nitric oxide in the nervous system. Prog Neurobiol 2001;64:365-91.

Thomas G, Ramwell PW. Nitric oxide, donors and inhibitors. In: Bertram G Katzung, editor. Basic and Clinical Pharmacology. United States: McGraw Hill; 2004.p.313-8.

Prog Neurobiol. 2001 Jul;64(4):365-91. Arginine metabolism and the synthesis of nitric oxide in the nervous system.

Official Document

L-ArginineM² has met all the legal requirements as set forth by the World Anti-Doping Agency (WADA) and the Human Maximum Performance committee.

L-ArginineM² has been analyzed per all legal standards and has been deemed to be a LEGAL SUBSTANCE for athletes and is NOT A BANNED SUBSTANCE according to the Official Guidelines of the WORLD ANTI-DOPING AGENCY (WADA), and the WORLD ANTI-DOPING CODE.

L-ArginineM², as based on the specific L-arginine formula submitted and tested from 1983 to 2006, qualifies to use the Human Maximum Performance ® Seal of Approval designating safe substances used by professional, Olympic, and competing athletes worldwide.

Per the guidelines of HMP, and each committee below,
L-ArginineM² is allowed for use in athletes by:

•	WORLD ANTI-DOPING AGENCY
•	UNITED STATES ANTI-DOPING AGENCY
•	UNITED STATES OLYMPIC COMMITTEE
•	INTERNATIONAL OLYMPIC COMMITTEE
•	JAPAN OLYMPIC COMMITTEE
•	JAPAN ANTI-DOPING AGENCY
•	USA TRIATHLON AND PROFESSIONAL SPORTS TEAMS
•	AUSTRALIAN SPORTS ANTI-DOPING AUTHORITY

www.HumanMaximumPerformance.com

References & Bibliography

(1) NIH Announces Nanomedicine Development Center Awards. www.Nano.gov

(2) J Cell Biochem.2006 Jan 26; Engineered nanoparticles as precise drug delivery systems. Wikipedia. 2006

Angew Chem Int Ed Engl.2005 Feb 11;44(8):1166-81; DNA CODES FOR NANOSCIENCE Samori B, et al

Nano Lett.,6(4),587-591,2006.American Chemical Society.Covalently Linked Au Nanoparticles to a Viral Vector: Potential for Combined Photothermal and Gene Cancer Therapy.Maaike Everts et al

Pascual et al. May 2004. “GLUT1 deficiency and other glucose transporter diseases”. European journal of endocrinology 150 (5): 627-33.

Liu, X.; Tu, M.; Kelly, R. S.; Chen, C.; Smith, B. J. Development of a computational approach to predict blood-brain barrier permeability. Drug Metab. Dispos. 2004, 32, 132-9.

Klepper, J, Voit T (June 2002). “Facilitated glucose transporter protein type 1 (GLUT1) deficiency syndrome: impaired glucose transport into brain-- a review”. European journal of pediatrics 161 (6): 295-304.

Reichel, A.; Begley, D. J.; Abbott, N. J. An overview of in vitro techniques for blood-brain barrier studies. Methods Mol. Med. 2003, 89, 307-24.

Abbott Joan, N. Prediction of blood-brain barrier permeation in drug discovery from in vivo, in vitro and in silico models. Drug Discovery Today: Technol. 2004, 1, 407-416.

Crivori, P.; Cruciani, G.; Carrupt, P. A.; Testa, B. Predicting blood-brain barrier permeation from three-dimensional molecular structure. J. Med. Chem. 2000, 43, 2204-16.

Basak, S.; Gute, B. D.; Drewes, L. R. Predicting blood-brain transport of drugs: a computational approach. Pharm. Res. 1996, 13, 775-8.

Keseru, G. M.; Molnar, L. High-throughput prediction of blood-brain partitioning: a thermodynamic approach. J. Chem. Inf. Comput. Sci. 2001, 41, 120-8.

Hutter, M. C. Prediction of blood-brain barrier permeation using quantum chemically derived information. J. Comput.-Aided Mol. Des. 2003, 17, 415-33.

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Copyright © 2006-2009

No copies of this material may be made in any format whatsoever (including electronic) without express prior written permission from the authors.

These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure or prevent any disease.