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Amino Acid Complex is designed
to provide adequate amounts of essential proteins which may be lacking in the diet. 

Amino acids are used in all the body’s chemical reactions, and
play a role in important activities such as lowering cholesterol, preventing the buildup of plaque
in the cardio-vascular system, absorbing and storing vitamins
and minerals, synthesizing and balancing neuro-transmitters, building muscles and bones, maintaining a strong immune
system and metabolism, and promoting overall good health under stressful conditions.

 

(Click for list of ingredients.)

Amino acids are the building blocks of life.  The body uses amino acids to form proteins, diverse chains of amino acids necessary for all chemical reactions in the body.  Amino acids are normally found as proteins in foods. 

The body breaks down these proteins in digestion to acquire the essential amino acids it needs to form other proteins; however, proteins are found in a wide range of forms in different foods, some forms being easier for the body to digest than others, and some providing more of the essential amino acids than other proteins do. 

Thus it is important to eat a variety of foods containing protein, such as milk, meat, and soy, to provide the body with all of the proteins it needs to synthesize all the essential amino acids.  But sometimes a perfect diet is simply not possible.  Therefore, supplementing the diet with a healthy supply of amino acids in readily usable form can help ensure that the body is receiving all the nutrients it needs. 

OTHER FUNCTIONS OF AMINO ACIDS:

Amino acids can be broken down in the liver to make energy.  Some amino acids, called glucogenic amino acids, can be used as a source of glucose, one of the main sources of energy for the muscles during exercise.  Tryptophan is used to make serotonin, an important neurotransmitter.  Arginine is used to make nitric oxide, a hormone and signal molecule.  Each amino acid has a specific biological function.

 

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Click the name of each ingredient to learn more...


LYSINE is an essential amino acid, meaning the body cannot produce it itself so it must be supplied in the diet.  Lysine is required for the synthesis of all proteins.  It plays a major role in the body’s absorption of calcium, in muscle building, recovery from surgery or sports injury, and in the production of hormones, enzymes, and antibodies.  In addition, lysine is used to create carnitine, a nutrient which converts fatty acids into energy and which helps lower cholesterol (University of Maryland Medical center).

HISTIDINE is a conditionally essential amino acid, because in most adults it can be produced by the body.  It is important in the synthesis of two major substances, histamine and carnosine.  Histamine, aside from playing a role in the immune response, is a neurotransmitter that regulates sleep patterns.  In addition, histamine is released during orgasm as a part of the sexual response.  Low histamine levels may cause problems sleeping and weaken the immune system. 

ARGININE is also a conditionally essential amino acid.  It is used in cell division, wound healing, detoxifying the body of ammonia, in the immune system, and in hormone regulation, where it may increase the production of the growth hormone and thereby contribute to muscle building.  Like other amino acids, arginine is required for the synthesis of many important proteins.  Arginine is involved in the production of creatine, an acid which supplies energy to the muscles.  It also helps maintain a healthy vascular system.  Low arginine levels are associated with a weak endothelium, the lining of veins and arteries.  Importantly, arginine is used to create nitric oxide, a highly reactive molecule which acts as a hormone and signaler in the body. 

Arginine is used as part of treatments for male sexual dysfunction.  In clinical trials it has been shown to enhance libido, increase sexual stamina, and treat erectile dysfunction.  Sexual stimulation begins in the brain, where neurotransmitters fire signals down the spinal cord to the genitals.  These signals in turn cause the release of certain chemicals which allow blood to flow to the penis.  The main chemical responsible for this process is called cyclic guanosine monophosphate, or cGMP.  The neurotransmitter responsible for releasing cGMP is nitric oxide, NO.  Because arginine is required in the production of NO, increasing arginine levels may increase NO levels, benefitting men with sexual dysfunctions.

ASPARTIC ACID is a non-essential amino acid, but it is used to synthesize four essential amino acids, methionine, threonine, isoleucine, and lysine.  In addition, aspartic acid contributes to the breakdown of ammonia in the liver and to gluconeogenesis, the process in which glucose is formed from amino acids.  In the brain, aspartic acid acts as an excitatory neurotransmitter which activates NMDA, an important receptor for the healthy function of cells.  Some believe that its actions as a neurotransmitter combat fatigue and increase endurance.

THREONINE is an essential amino acid.  It is found in high amounts in the heart, muscles, and nervous system.  Like other amino acids, threonine is required for the production of important proteins, enzymes, and antibodies.  It may also play a role in producing collagen, an important constituent of skin and other connective tissues.  Threonine can also help the body better absorb and store important nutrients through the metabolic process. 

SERINE is a non-essential amino acid.  Serine is important to metabolism because it is used to produce several enzymes responsible for breaking down and using nutrients from food.  It is particularly important in the synthesis of tryptophan and cysteine.  Like aspartic acid, serine plays a role in activating NMDA receptors in the brain.  Serine is important in the production of the myelin sheath, a protective layer which encases the nerves, promoting the health of the nervous system.

GLUTAMIC ACID is also a non-essential amino acid.  It is vital to cellular metabolism.  As a neurotransmitter, glutamic acid is one of the most available excitatory substances in the brain.  It is believed to play a role in learning and memory.  It is also required to produce GABA, one of the most important inhibitory neurotransmitters.

PROLINE, while not technically an amino acid, belongs to the same biochemical category as the other amino acids in this formula.  It is ordinarily formed by glutamic acid.  Proline is essential for the health of the skin, where it is needed to make collagen, keeps muscles and joints flexible, and reduces sagging and wrinkles.  People who regularly engage in heavy exercise may be at risk for proline deficiency. 

ALANINE, a non-essential amino acid, is one of the most widely used amino acids for protein synthesis.  In addition, the alanine cycle forms glucose from proteins.  Alanine is a component of several nutrients which are essential to health, including tryptophan, vitamin B5, and coenzyme A.  Although its role in the prostate gland is unclear, alanine is present there, and in one trial, men with BPH (benign prostatic hyperplasia) who were treated with alanine supplements experienced a reduction in symptoms.

CYSTINE is technically not an amino acid, but it is formed by a combination of two molecules of cysteine, a non-essential amino acid, and it is a part of many proteins.  It is present in high quantities in the immune system, skeletal system, and in connective tissues.  Cystine is more stable than cysteine, so it is preferred for synthesizing glutathione, an antioxidant which plays a role in the immune system.  Other parts of the body such as neurons, however, do prefer pure cysteine for glutathione synthesis.  Both related substances are included in this formula to provide an optimal source of this important nutrient.

VALINE is an essential amino acid.  Body builders use valine for muscle growth, tissue repair, and for increased energy due to its stimulant effect.  It can be used as energy in place of glucose, increasing the body’s overall store of energy and available forms.  It is also required for proper cognitive function.

METHIONINE is an essential amino acid which plays a role in synthesizing cysteine, carnitine, taurine, lecithin, and phosphatidylcholine.  Methionine is used by the brain to make SAMe (S-adenosyl-methionine), a powerful nutrient which is used to combat depression, fibromyalgia, and liver disorders.  As an anti-inflammatory substance, SAMe may benefit the joints as well.  SAMe supports mood and relieves anxiety by acting as a serotonin regulator.  Serotonin is an important neurotransmitter connected with mental health, and improper serotonin regulation may lead to depression and other conditions.  The essential amino acid methionine is used to create SAMe, but methionine cannot be produced by the body.  It must, therefore, be provided in the diet or in supplements.

ISOLEUCINE is also an amino acid.  Isoleucine is used for muscle recovery, but its primary biological roles are in forming hemoglobin, regulating blood sugar and energy, and in forming blood clots.  Isoleucine is part of a group of amino acids called BCAAs (branched chain amino acids) which also includes leucine and valine.  BCAAs may protect neurons from damage caused by the transmitter glutamate.  This claim was discovered when patients with Lou Gehrig’s disease, a nervous system disorder, found an improvement in their condition when treated with supplemental BCAAs.

TYROSINE is a nonessential amino acid that is often recommended for weight loss, depression, and Parkinson’s disease.  Tyrosine is used to synthesize several essential neurotransmitters, including epinephrine, norepinephrine, serotonin, and dopamine.  It also plays a role in regulating hormones and in producing melanin in the skin and hair.  Importantly, tyrosine exhibits some antioxidant effects.  It has the ability to destroy excess free radicals caused by smoking, radiation, or exposure to toxins.  In alternative medicine, tyrosine is prescribed to relieve stress because it qualifies as an adaptogen.  An adaptogen is a sub-stance which helps the body to cope with stressful conditions by promoting normal, healthy mental function.  Tyrosine’s adaptogen qualities may be related to its ability to regulate neurotransmitters which affect mood and anxiety. 

LEUCINE is an essential amino acid.  Like valine and isoleucine, leucine is part of the group of amino acids called BCAAs, or branched chain amino acids.  BCAAs may play a role in protecting neurons from damage by the transmitter glutamate, an important activity which may promote healthy cognitive function. 

During intense physical exercise, the muscles require larger amounts of glucose for energy.  If glucose is not available, the body will break down important proteins in muscles in order to supply the necessary energy.  To promote muscle building, extra glucose supplies are necessary to protect those proteins.  The body can convert BCAAs into glucose, and of all the BCAAs, leucine is the most effective for muscle building because it is broken down into glucose the fastest. 

With valine and isoleucine, lecuine also helps regulate blood sugar, produce growth hormones, and burn fats.

PHENYLALANINE is an essential amino acid.  The body converts phenylalanine into tyrosine (see above).  Some research suggests that phenylalanine may help relieve chronic pain when used in combination with prescription pain relievers by exciting neurons involved in the control of pain.  In addition, phenylalanine has been included as part of treatments for depression because it may lead to better epinephrine and norepinephrine levels, benefitting mood.

TRYPTOPHAN is an essential amino acid.  Tryptophan is a popular supplement for the treatment of depression.  Tryptophan is used to make 5-HTP, a substance which raises serotonin levels in the brain.  Elevated serotonin levels are associated with improved mood, stress reduction, and optimal cognitive function.  Low levels of serotonin may result in depression, anxiety, and an increase in the symptoms of stress, including an inhibited metabolism, problems sleeping, and immunosuppression. 

Serotonin can also be converted by the body into melatonin, a chemical which regulates the sleep cycle.  For this reason, tryptophan supplements have been used as a sleep aid as well.  Many people report feeling tired or sleepy after eating turkey.  This common experience may be due to the fact that turkey contains tryptophan. 

Tryptophan has been researched to treat a large range of mental health conditions, including manic, addictive, and obsessive compulsive personality disorders.  In the early 1990s, a contaminated batch of tryptophan supplements was linked to a serious disease.  This led to the ban of tryptophan supplements, but when it was discovered that tryptophan itself was not responsible for the outbreak, the ban was lifted.  As a result tryptophan undergoes more rigorous purification processes, increasing its effectiveness and safety above that of other supplements.

CYSTEINE is non essential but it is contains a unique sulfur composition which is a building block for many important proteins.  Cysteine often comes as a pair of molecules called cystine (see above).  It is also an important source of sulfur for metabolism, as well as an antioxidant.  Infants and the elderly are at risk for cysteine deficiency because their bodies are less able to synthesize it on their own. 

Cysteine is required for the formation of glutathione, an important anti-oxidant in the brain.  It is one of many cigarette additives, included because smokers have diminished levels of glutathione and because it increases saliva production.

Cysteine can also be used as part of a hangover remedy because it destroys the toxic substance acetyldehyde, one cause of the symptoms of a hangover.  N-acetyl-L-cysteine (NAC) is an important antioxidant and a derivative of cysteine.  NAC provides support to the immune system and may be used to relieve the symptoms of respiratory illnesses.  One study suggests that NAC may even provide some benefit to those with heart disease.

GLUTAMINE is a nonessential amino acid, but as a supplement it is used by body builders because it helps resupply the body with amino acids depleted during intense physical exercise. Glutamine is stored in skeletal muscles, and exercise overuses the nutrients in skeletal muscle.  For this same reason, older people experiencing muscle pain use glutamine supplements as part of a treatment for their condition.  People who are fasting or recovering from serious illness may also benefit from glutamine supplements. 

Several studies have indicated that glutamine provides benefits to the gastrointestinal tract.  The mechanism for this action is unclear, but glutamine supplements appear to improve the health of the digestive system.

People with cancer have very low glutamine levels, and supplementation is therefore recommended.  Chemotherapy may also deplete nutrient levels.

TAURINE is an important nutrient because it helps maintain cardiovascular health and is present in high concentrations in the muscles, where it protects cell membranes, acts as an anti-oxidant in the lungs, and regulates the flow of calcium near skeletal tissue.  Elsewhere in the body, taurine assists in the reduction of dangerously high collagen levels, a complication associated with diabetes.  Popular energy drinks such as Red Bull® and +Battery® contain taurine because of its positive effects on muscular endurance.

Taurine is one of the most abundant free amino acids in the body. It is not incorporated into proteins, yet taurine is very important in metabolism and is present in particularly high levels in the brain, skeletal muscle, heart, and retina of the eye.  Taurine is regarded as a conditionally-essential amino acid, because it can be synthesized by the body from the other sulfur-containing amino acids, cysteine and methionine, but in some conditions, such as infancy or deficiency, taurine must be supplied by the diet.

Taurine synthesis is vitamin B6 dependent. Taurine is essential for infants where it plays important roles in the development of the nervous system, retina, and muscle tissue.  Taurine is well known for its role in bile salt synthesis and has crucial functions in the liver’s detoxification process. Taurine also appears to have a strengthening effect on cell membranes and is important in maintaining normal distribution of calcium. This in turn has implications on neuron excitability and the regulation of osmosis. In the retina, taurine helps maintain the structure and function of the visual cells.

Dietary taurine is mainly supplied through meat and other animal products.  Vegetarians and vegans are, therefore, at risk for taurine deficiency.  By producing its bile acid in the liver, taurine assists in the absorption of fat, making it a healthy supplement for weight management and good overall metabolism.  According to PDRhealth.com, taurine “has putative

hypocholesterolemic, hypotensive, antiatherogenic and detoxifying activities. It may also have steatorrhea-reducing activity in those with cystic fibrosis and has putative antidiabetic, inotropic and antiseizure activities.”  Extensive research has been performed surrounding these properties of taurine which shows that taurine can be used to support cardiovascular health, prevent retinal damage, and curb the onset of diabetes in some patients.

Bodybuilding.com supports the use of taurine supplements to improve muscular health:

“Taurine is an amino acid like glutamine that is earning more and more respect from bodybuilders and protein scientists.

“While taurine generally is the second most abundant amino acid in muscle, in several metabolic conditions, some muscle biologists like Eric Serrano, M.D., have determined that it, not glutamine, is the most voluminous amino represented in striated type 2 muscle fiber! Taurine has several critical functions and can act similarly to creatine in that it expands your cells by helping the muscle cell itself hold more water, increasing cell volume. For a lifter or bodybuilder, this is significant because expanded muscle cells can boost hydration resulting in a higher rate of protein synthesis and bodybuilders will appreciate the increased appearance of muscle fullness.”

MORE INFORMATION ON THE INGREDIENTS
OF AMINO ACID COMPLEX:

LYSINE:
From the University of Maryland Medical Center:

Overview
Lysine is an essential amino acid, which means that it is essential to human health but cannot be manufactured by the body. For this reason, lysine must be obtained from food. Amino acids are the building blocks of protein. Lysine is important for proper growth and it plays an essential role in the production of carnitine, a nutrient responsible for converting fatty acids into energy and helping to lower cholesterol. Lysine appears to help the body absorb and conserve calcium and it plays an important role in the formation of collagen, a substance important for bones and connective tissues including skin, tendon, and cartilage.

If there is too little lysine in the diet, kidney stones and other health related problems may develop including fatigue, nausea, dizziness, loss of appetite, agitation, bloodshot eyes, slow growth, anemia, and reproductive disorders. It is extremely rare, however, to obtain insufficient amounts of lysine through the diet. Generally, only vegetarians who follow a macrobiotic diet and certain athletes involved in frequent vigorous exercise are at risk for lysine deficiency. For vegetarians, legumes (beans, peas and lentils) are the best sources of lysine.

Lysine is involved in the browning reaction, or carmelization, in foods such as pastries, doughnuts, cookies and cereals. In this process, lysine and sugar become linked together in a way that makes lysine difficult for the body to absorb. As a result, a diet high in cereals and baked goods, especially those that contain a lot of simple sugars, can result in low lysine intake.

Uses

Herpes and Shingles
L-lysine can be used to treat mouth and genital lesions caused by herpes simplex virus as well as shingles caused by herpes zoster viruses. Taking lysine supplements can speed recovery time and reduce the chance of recurrent breakouts of the herpes infection.

Osteoporosis
L-lysine helps improve the absorption of calcium from the digestive tract and prevent loss of calcium in the urine. In so doing, some researchers speculate that L-lysine may help prevent bone loss associated with osteoporosis. In addition, test tube studies suggest that L-lysine in combination with L-arginine (another amino acid) increases the activity of bone-building cells and enhances production of collagen.

Other
Certain forms of lysine and/or lysine bound to anti-inflammatory medications may help alleviate pain following an episiotomy (a procedure performed during labor that involves cutting the vaginal area to enlarge the vaginal opening and facilitate delivery). These forms of lysine may also relieve migraine headaches and painful periods. Whether L-lysine and other readily available lysine supplements also offer these benefits is not known.

Dietary Sources
Good sources of lysine are foods rich in protein including meat (specifically red meat, pork, and poultry), cheese (particularly parmesan), certain fish (such as cod and sardines), nuts, eggs, soybeans (particularly tofu, isolated soy protein, and defatted soybean flour), spirulina, and fenugreek seed.

Available Forms
Lysine is available in tablets, capsules, creams, and liquids, and is usually sold in the L-lysine form.

Precautions
Because of the potential for side effects and interactions with medications, dietary supplements should be taken only under the supervision of a knowledgeable healthcare provider.

Lysine supplements are considered safe and nontoxic. However, one animal study found that chicks fed with L-lysine developed elevated cholesterol and triglyceride levels. For this reason, individuals with cardiovascular disease and those with elevated cholesterol and/or triglyceride levels should consult a healthcare practitioner before taking lysine supplements.

Possible Interactions
There are no reports in the scientific literature to suggest that lysine interacts with any conventional medications.

Supporting Research
Bruzzese N, Sica G, Iacopino F, et al. Growth inhibition of fibroblasts from nasal polyps and normal skin by lysine acetylsalicylate. Allergy . 1998;53:431–434.

Civitelli R, Villareal DT, Agnusdei D, Nardi P, Avioli LV, Gennari C. Dietary L-lysine and calcium metabolism in humans. Nutrition . 1992;8(6):400-405.

De los Santos AR, Marti MI, Espinosa D, Di Girolamo G, Vinacur JC, Casadei A. Lysine clonixinate vs. paracetamol/codeine in postepisiotomy pain. Acta Physiol Pharmacol Ther Latinoam . 1998;48(1):52–58.

Di Girolamo G, Zmijanovich R, de los Santos AR, Marti ML, Terragno A. Lysine clonixinate in the treatment of primary dysmenorrhea. Acta Physiol Pharmacol Ther Latinoam . 1996;46(4):223-232.

Fini M, Torricelli P, Giavaresi G, Carpi A, Nicolini A, Giardino R. Effect of L-lysine and L-arginine osteoblast cultures from normal and osteopenic rats. Biomed Pharmacother. 2001;55(4):213-220.

Flodin NW. The metabolic roles, pharmacology, and toxicology of lysine. J Am Coll Nutr . 1997;16:7–21.

Furst P. Dietary L-lysine supplementation: a promising nutritional tool in the prophylaxis and treatment of osteoporosis. Nutrition . 1993;9(1):71-72.

Griffith RS, Walsh DE, Myrmel KH, Thmpson RW, Behforooz A. Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Dermatologica . 1987;175(4):183-190.

Hugues FC, Lacoste JP, Danchot J, Joire JE. Repeated doses of combined oral lysine acetylsalicylate and metoclopramide in the acute treatment of migraine. Headache . 1997;37:452–454.

Krymchantowski AV, Barbosa JS, Cheim C, Alves LA. Oral lysine clonixinate in the acute treatment of migraine: a double-blind placebo-controlled study. Arq Neuropsiquiatr . 2001;59(1):46-49.

Pizzorno JE, Murray MT. Textbook of Natural Medicine . Vol 1. 2nd ed. Edinburgh: Churchill Livingstone; 1999.

Schmeisser DD, Kummerow FA, Baker DH. Effect of excess dietary lysine on plasma lipids of the chick. J Nutr . 1983;113(9):1777-1783.

Shils ME, Olson JA, Shike M, Ross AC. Modern Nutrition in Health and Disease . 9th ed. Baltimore, Md: Williams & Wilkins; 1999:41;1,010.

Tfelf-Hansen P. The effectiveness of combined oral lysine acetylsalicylate and metoclopramide in the treatment of migraine attacks. Comparison with placebo and oral sumatriptan. Funct Neurol . 2000;15(Suppl 3):196-201.

Werbach MR. Nutritional Influences on Illness . 2nd ed. Tarzana, Calif: Third Line Press; 1993:159–160, 384, 434, 494–495, 506, 580, 613–614, 636.

RETURN TO INGREDIENTS LIST

HISTIDINE

PDRHealth.com:
DESCRIPTION
L-histidine is a protein amino acid that is found in the proteins of all life forms. Although most L-histidine is found in proteins, a small amount of free L-histidine does exist in plants and fermented foods. The naturally occurring dipeptides found in muscle, carnosine and anserine are both comprised of L-histidine and beta-alanine.

L-histidine is one of the 10 essential amino acids for infants. It has never been clear if L-histidine is an essential amino acid for adults. At the very least, it is a conditional essential amino acid for adults. That is, even though L-histidine is synthesized in adult human tissues, sufficient quantities may not be made to meet the physiological requirements imposed by certain stress or disease situations.

L-histidine is a solid water-soluble substance. Chemically, it is called (S)-alpha-amino-1H-imidazole-4-propanoic acid; alpha-amino-4 (or 5)-imidazolepropionic acid; L-2-amino-3- (1H-imidazol-4yl) propionic acid, and glyoxaline-5-alanine. Its IUPAC abbreviation is His, and its one-letter abbreviation is H. L-histidine is classified as a basic amino acid.

ACTIONS AND PHARMACOLOGY

ACTIONS
The actions of supplemental L-histidine are entirely unclear. It may have some immunomodulatory as well as antioxidant activity.

MECHANISM OF ACTION
Since the actions of supplemental L-histidine are unclear, any postulated mechanism is entirely speculative. However, some facts are known about L-histidine and some of its metabolites, such as histamine and trans-urocanic acid, which suggest that supplemental L-histidine may one day be shown to have immunomodulatory and/or antioxidant activities. Low free histidine has been found in the serum of some rheumatoid arthritis patients. Serum concentrations of other amino acids have been found to be normal in these patients. L-histidine is an excellent chelating agent for such metals as copper, iron and zinc. Copper and iron participate in a reaction (Fenton reaction) that generates potent reactive oxygen species that could be destructive to tissues, including joints.

L-histidine is the obligate precursor of histamine, which is produced via the decarboxylation of the amino acid. In experimental animals, tissue histamine levels increase as the amount of dietary L-histidine increases. It is likely that this would be the case in humans as well.

Histamine is known to possess immunomodulatory and antioxidant activity. Suppressor T cells have H2 receptors, and histamine activates them. Promotion of suppressor T cell activity could be beneficial in rheumatoid arthritis. Further, histamine has been shown to down-regulate the production of reactive oxygen species in phagocytic cells, such as monocytes, by binding to the H2 receptors on these cells. Decreased reactive oxygen species production by phagocytes could play antioxidant, anti-inflammatory and immunomodulatory roles in such diseases as rheumatoid arthritis.

This latter mechanism is the rationale for the use of histamine itself in several clinical trials studying histamine for the treatment of certain types of cancer and viral diseases. In these trials, down-regulation by histamine of reactive oxygen species formation appears to inhibit the suppression of natural killer (NK) cells and cytotoxic T lymphocytes, allowing these cells to be more effective in attacking cancer cells and virally infected cells.

PHARMACOKINETICS
L-histidine is absorbed from the small intestine via an active transport mechanism requiring the presence of sodium. From the small intestine, L-histidine is transported to the liver by means of the portal circulation, where some is metabolized and from whence some enters the systemic circulation to be distributed to various tissues in the body.

L-histidine is metabolized in several different ways. It is a substrate for protein synthesis; decarboxylation produces histamine; it is converted to trans-urocanate in the skin; it forms the dipeptides carnosine and anserine in muscle; it is a precursor of the thiol antioxidant, L-ergothioneine; and it forms alpha-ketoglutarate.

INDICATIONS AND USAGE
L-histidine may be indicated for use in some with rheumatoid arthritis. It is not indicated for treatment of anemia or uremia or for lowering serum cholesterol.

RESEARCH SUMMARY
It has been reported that rheumatoid arthritis (RA) sufferers have abnormally low blood levels of this amino acid. In a pilot study, RA patients received up to 6 grams of supplemental histidine daily and were said to benefit with as little as 1 gram daily. A subsequent study with 4.5 grams daily in some with more active and prolonged disease found much less benefit—but still enough to warrant further research.

CONTRAINDICATIONS, PRECAUTIONS, ADVERSE REACTIONS

CONTRAINDICATIONS
L-histidine supplementation is contraindicated in anyone hypersensitive to any component of the preparation.

PRECAUTIONS
L-histidine supplements should be avoided by children, pregnant women and nursing mothers. Those with allergies or peptic ulcer disease should only use L-histidine supplements under strict medical supervision. Although there are no reports of adverse events in these groups, increased histamine production from L-histidine might negatively affect those with these conditions.

ADVERSE REACTIONS
Mild gastrointestinal side effects have been reported. L-histidine is generally well tolerated.

INTERACTIONS
Medroxyprogesterone Acetate: L-histidine was observed to enhance (in tissue culture) the effect of medroxyprogesterone acetate in reducing the number of human breast cancer cells that were in the S phase.

H1 and H2 Blockers: Although not reported, L-histidine, via its metabolism to histamine, might decrease the efficacy of H1 and H2 blockers.

No other drug, nutritional supplement, food or herb interaction are known.

OVERDOSAGE
None reported.

DOSAGE AND ADMINISTRATION
Tablets and capsules typically are available in 500 milligram to 1000 milligram dosages. Dosages have ranged from 500 milligrams to 4.5 grams daily.


LITERATURE

Blumenkrantz MJ, Shapiro DJ, Swendseid ME, Kopple JD. Histidine supplementation for treatment of anaemia of uraemia. Br Med J. 1975; 2(5970):530-533.

Gerber DA. Decreased concentration of free histidine in serum in rheumatoid arthritis, an isolated amino acid abnormality not associated with generalized hypoaminoacidemia. J Rheumatol. 1975; 2:384-392.

Gerber DA. Low free serum histidine concentration in rheumatoid arthritis. A measure of disease activity. J Clin Invest. 1975; 55:1124-1173.

Gerber DA, Sklar JE, Niedwiadowiez J. Lack of effect of oral L-histidine on the serum cholesterol in human subjects. Am J Clin Nutr. 1971; 24:1382-1383.

Gerber DA, Tanenbaum L, Ahrens M. Free serum histidine levels in patients with rheumatoid arthritis and control subjects following an oral load of free L-histidine. Metabolism. 1976; 25:655-657.

Ghezzo F, Racca S, Conti G, et al. L-histidine medroxyprogesterone acetate interaction modulates human breast cancer cell growth and progestin receptor expression in vitro. Pharmacy Res. 1997; 35:119-122.

Griswold DE, Alessi S, Badger AM, et al. Inhibitions of T suppressor cell expression by histamine type 2 (H2 ) receptor antagonists. J Immunol. 1984; 132:3054-3057.

Hellstrand K, Dalgren C, Hermodsson S. Histaminergic regulation of NK cells. Role of monocyte-derived reactive oxygen metabolites. J Immunol. 1994; 153:4940-4947.

Lee NS, Fitzpatrick D, Meier E, Fisher H. Influence of dietary histidine on tissue histamine concentration, histidine decorboxylase and histamine methyltransferase activity in the rat. Agents Actions. 1981; 11:307-311.

Pinals RS, Harris ED, Burnett JB, Gerber DA. Treatment of rheumatoid arthritis with L-histidine: a randomized, placebo-controlled, double-blind trial. J Rheumatol. 1977; 4:414-419.

RETURN TO INGREDIENTS LIST




ARGININE

REFERENCES:

Abel T, Knechtle B, Perret C, et al. Influence of chronic supplementation of arginine aspartate in endurance athletes on performance and substrate metabolism - a randomized, double-blind, placebo-controlled study. Int J Sports Med. 2005 Jun;26(5):344-9.

Black P, Max MB, Desjardins P, et al. A randomized, double-blind, placebo-controlled comparison of the analgesic efficacy, onset of action, and tolerability of ibuprofen arginate and ibuprofen in postoperative dental pain. Clin Ther. 2002;24(7):1072-1089.

Carrier, M, Pellerin M, Perrault LP, et al. Cardioplegic arrest with L-arginine improves myocardial protection: results of a prospective randomized clinical trial. Ann.Thorac.Surg. 2002;73(3):837-841.

Cartledge JJ, Davies AM, Eardley I. A randomized double-blind placebo-controlled crossover trial of the efficacy of L-arginine in the treatment of interstitial cystitis. BJU.Int 2000;85(4):421-426.

Garhofer G, Resch H, Lung S, et al. Intravenous administration of L-arginine increases retinal and choroidal blood flow.Am J Ophthalmol. 2005 Jul;140(1):69-76.

Gianotti L, Braga M, Nespoli L, et al. A randomized controlled trial of preoperative oral supplementation with a specialized diet in patients with gastrointestinal cancer. Gastroenterology 2002;122(7):1763-1770.

Hladunewich MA, Derby GC, Lafayette RA, et al. Effect of L-arginine therapy on the glomerular injury of preeclampsia: a randomized controlled trial.Obstet Gynecol. 2006 Apr;107(4):886-95.

Houwing RH, Rozendaal M, Wouters-Wesseling W, et al. A randomised, double-blind assessment of the effect of nutritional supplementation on the prevention of pressure ulcers in hip-fracture patients. Clin Nutr. 2003;22(4):401-405.

Koga Y, Akita Y, Junko N, et al. Endothelial dysfunction in MELAS improved by l-arginine supplementation. Neurology. 2006 Jun 13;66(11):1766-9.

Korting G, Smith S, Wheeler M, et al. A randomized double-blind trial of oral L-arginine for treatment of interstitial cystitis. J Urol. 1999;161(2):558-565.

Lebret T, Herve JM, Gorny P, et al. Efficacy and safety of a novel combination of L-arginine glutamate and yohimbine hydrochloride: a new oral therapy for erectile dysfunction. Eur.Urol. 2002;41(6):608-613.

Miller HI, Dascalu A, Rassin TA, et al. Effects of an acute dose of L-arginine during coronary angiography in patients with chronic renal failure: a randomized, parallel, double-blind clinical trial. Am.J.Nephrol. 2003;23(2):91-95.

Mansoor JK, Morrissey BM, Walby WF, et al. L-arginine supplementation enhances exhaled NO, breath condensate VEGF, and headache at 4,342 m. High Alt Med Biol. 2005 Winter;6(4):289-300.

Polan ML, Hochberg RB, Trant AS, et al. Estrogen bioassay of ginseng extract and ArginMax, a nutritional supplement for the enhancement of female sexual function. J.Womens Health (Larchmt.) 2004;13(4):427-430.

Schulman SP, Becker LC, Kass DA, et al. L-arginine therapy in acute myocardial infarction: the Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) randomized clinical trial. JAMA. 2006 Jan 4;295(1):58-64.

From the MAYO CLINIC:

Background
L-arginine was first isolated in 1886. In 1932, L-arginine was found to be required for the generation of urea, which is necessary for the removal of toxic ammonia from the body. In 1939, L-arginine was also shown to be required for the synthesis of creatine. Creatine degrades to creatinine at a constant rate, and is cleared from the body by the kidney.

Arginine is considered a semi-essential amino acid, because although it is normally synthesized in sufficient amounts by the body, supplementation is sometimes required (for example, due to inborn errors of urea synthesis, protein malnutrition, excess ammonia production, excessive lysine intake, burns, infection, peritoneal dialysis, rapid growth, or sepsis). Symptoms of arginine deficiency include poor wound healing, hair loss, skin rash, constipation, and fatty liver.

Arginine is a precursor of nitric oxide, which causes blood vessel relaxation (vasodilation). Preliminary evidence suggests that arginine may be useful in the treatment of medical conditions that are improved by vasodilation, such as angina, atherosclerosis, coronary artery disease, erectile dysfunction, heart failure, intermittent claudication/peripheral vascular disease, and vascular headache. Arginine also stimulates protein synthesis and has been studied for wound healing, bodybuilding, enhancement of sperm production (sperma-togenesis), and prevention of wasting in people with critical illness.

Arginine hydrochloride contains high chloride content and has been used for the treatment of metabolic alkalosis. This use should be under the supervision of a qualified healthcare professional.

Most people likely do not need to take arginine supplements because the body usually makes sufficient amounts.

Synonyms
Arg, arginine, arginine hydrochloride (intravenous formulation), ibuprofen-arginate (Spedifen®), L-arg, L-arginine, 2-amino-5-guanidinopentanoic acid.

Note : Arginine vasopressin is different from arginine/L-arginine, with an entirely different mechanism. NG-monomethyl-L-arginine is different from arginine/L-arginine, and functions as an inhibitor of nitric oxide synthesis.

Dietary sources of arginine : Walnuts, filberts, pecans, Brazil nuts, sesame and sunflower seeds, brown rice, raisins, coconut, gelatin, buckwheat, almonds, barley, cashews, cereals, chicken, chocolate, corn, dairy products, meats, oats, peanuts.

Evidence
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Uses based on scientific evidence          Grade*

Growth hormone reserve test / pituitary disorder diagnosis
Intravenously administered arginine can be used to evaluate growth hormone reserve in individuals with suspected growth hormone deficiency. For example, in patients with suspected panhypopituitarism, growth/stature abnormalities, gigantism/acromegaly, or pituitary adenoma. This is an FDA labeled indication for arginine. A

Inborn errors of urea synthesis
In patients with inborn errors of urea synthesis, high blood ammonia levels and metabolic alkalosis may occur, particularly in patients with ornithine carbamoyl transferase (OCT) deficiency or carbomoyl phosphate synthetase (CPS) deficiency. Arginine can be a helpful treatment by shifting the way the body processes nitrogen, but should be avoided in patients with hyperargininemia (high arginine levels). Other drugs may have similar benefits, such as citrulline, sodium benzoate, or sodium phenylbutyrate, although dialysis may be necessary initially. This use of arginine should be supervised by a qualified healthcare professional.        A

Adrenoleukodystrophy (ALD)
Adrenoleukodystrophy (ALD) is a rare inherited metabolic disorder characterized by the loss of fatty coverings (myelin sheaths) on nerve fibers in the brain, and progressive destruction of the adrenal gland. ALD is inherited as an x-linked genetic trait that results in dementia and adrenal failure. Injections of arginine have been proposed to help manage this disorder, although most study results are inconclusive. Further research is needed to evaluate the use of arginine in ALD.            C

Burns
A randomized, controlled clinical trial designed to evaluate immune function of patients given 15 milligrams of arginine orally suggests that arginine may help with the recovery of immune function and protein function in partial-thickness burn patients. Further research is necessary in this area before a conclusion can be drawn.            C

Coronary artery disease / angina
There is initial evidence from several studies that arginine taken by mouth or by injection improves exercise tolerance and blood flow in arteries of the heart. Benefits have been shown in some patients with coronary artery disease and angina. A small randomized, controlled clinical trial studied the effects of a medical food bar enriched with L-arginine and a combination of other nutrients in the management of chronic stable angina. The authors found that this arginine-rich medical food, when used with traditional therapy, improves vascular function, exercise capacity and aspects of quality of life in these patients. However, further research is needed to confirm these findings and to establish doses that may be safe and effective.   C

Critical illness
Some studies suggest that arginine may provide benefits when added to nutritional supplements during critical illnesses (for example, in patients being treated in intensive care units). However, it is unclear what the specific role of arginine may be in improving recovery. A randomized, controlled clinical trial was designed to study the effects of a high-protein formula enriched with arginine, fiber, and antioxidants in early nutrition therapy of critically ill patients. The study measured infections in the hospital intensive care unit (ICU), length of hospital stay, and death rates. Patients fed the high-protein diet enriched with arginine, fiber and antioxidants developed fewer hospital infections than patients fed a standard high-protein diet. There was no difference in length of ICU hospital stay or death rate. Overall the scientific data to date does not show benefit for only L-arginine supplementation, nor does it show harm. At this time there is no rationale for the routine supplementation of arginine alone to enhance recovery from serious illness. Because of the potential for harm, this amino acid should only be administered to critically ill patients in large doses under carefully monitored study conditions.      C

Dental pain (ibuprofen arginate)
A well-designed multicenter, randomized, controlled clinical trial found that ibuprofen-arginate (Spedifen®) reduced pain faster after dental surgery compared to conventional ibuprofen alone. The study included 498 patients who were given ibuprofen-arginate, ibuprofen, or placebo after dental surgery. The degree of pain relief, onset of action, and tolerability of both ibuprofen-arginate and ibuprofen were compared. It was found that ibuprofen arginate relieved pain faster and adverse events with ibuprofen-arginate were similar to those seen with ibuprofen alone. Another similar trial concluded that patients treated with ibuprofen-arginate rated its overall effectiveness higher than those treated with ibuprofen alone. Adverse event profiles were similar across all treatment groups. Further research is merited in this area.   C

MELAS syndrome
One study found that two years of supplementation with oral L-arginine significantly improved endothelial function in patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke). Further research is merited in this area.    C

Erectile dysfunction
Early studies propose that men with low nitrate levels in their blood or urine may find arginine supplements to be useful for managing erectile dysfunction (ED). A randomized, controlled clinical trial reported improvements in patients with mild-to-moderate ED following use of a combination of L-arginine, glutamate and yohimbine hydrochloride. Notably, yohimbine hydrochloride is an FDA-approved therapy for this condition, and the effects caused by arginine alone in this combination therapy are difficult to determine. It is not clear what doses of arginine may be safe or effective in treating this condition, and comparisons have not been made with other agents used for ED.            C

Gastrointestinal cancer surgery
Supplementation with an oral combination of arginine and omega-3 fatty acids may reduce length of hospital stay and infections after surgery in gastrointestinal cancer patients. There is conflicting evidence as to when to give the combination (either before or after surgery). Both strategies have been reported as superior to conventional treatment (no artificial nutrition) at reducing infections after surgery and reducing hospital stay. In a large, randomized, controlled clinical trial, malnourished cancer patients were given oral enteral nutrition supplemented by arginine, omega-3 fatty acids and RNA before surgery. It was found that supplementation with the combination before surgery reduced complications after surgery and hospital stay. A different randomized, controlled clinical trial in patients with gastrointestinal cancer studied the effects of an enteral diet supplemented with arginine, omega-3 fatty acids and glutamine (administered after surgery) on immune function and inflammatory response. This study reported the supplement to be well-tolerated with positive effects on immune and inflammatory response. Further research is needed to determine the possible effects of arginine alone.C

Heart failure (CHF)
Studies of arginine in patients with chronic heart failure have shown mixed results. Some studies report improved exercise tolerance. Additional studies are needed to confirm these findings before a firm conclusion can be drawn.            C

Heart protection during coronary artery bypass grafting (CABG)
Arginine-supplemented "blood cardioplegic solution" is proposed to have protective properties for the heart. A randomized, controlled clinical trial using this solution in patients undergoing heart surgery (coronary artery bypass grafting) reports improved heart protection. Further research is needed before a firm conclusion can be drawn.            C

High blood pressure
A small study suggests that arginine taken by mouth may dilate the arteries and temporarily reduce blood pressure in hypertensive patients with type 2 diabetes. Larger, high-quality studies are needed before a recommendation can be made.        C

Immunomodulator
Preliminary study results suggest that arginine supplementation may enhance the immune response elicited by the pneumococcal vaccine in older people. More studies are needed to confirm these results.   C

Migraine headache
Preliminary studies suggest that adding arginine to ibuprofen therapy may decrease migraine headache pain.       C

Myocardial infarction
Study results of arginine supplementation after myocardial infarction (heart attack) are mixed. Further research is needed before a recommendation can be made. A cardiologist and pharmacist should be consulted prior to initiation of arginine therapy.           C

Peripheral vascular disease / claudication
Intermittent claudication is a condition characterized by leg pain and fatigue due to buildup of cholesterol plaques or clots in leg arteries. A small number of studies report that arginine therapy may improve walking distance in patients with claudication. Further research is needed before a firm conclusion can be drawn.            C

Pre-eclampsia (high blood pressure in pregnancy)
Early study suggests that prolonged dietary supplementation with L-arginine may decrease blood pressure that is too high in pregnant women. Further research is needed to confirm these results. C

Pressure ulcers
Studies of arginine for pressure ulcers show mixed results. Further research is needed before a conclusion can be drawn.            C

Recovery after surgery
One study suggests that arginine may provide benefits when used as a supplement after surgery. It is not clear what the specific role of arginine may be in improving immune function, or what dose is safe or effective.             C

Transplants
Dietary supplementation with L-arginine and canola oil has been associated with decreased rejection rates after the first month in renal transplant patients. Due to reductions in cardiac events, long-term benefits for patient survival may be particularly important. Further research is needed to confirm these results.            C

Wound healing
Arginine has been suggested to improve the rate of wound healing in elderly individuals. A randomized, controlled clinical trial reported improved wound healing after surgery in head and neck cancer patients, following the use of an enteral diet supplemented with arginine and fiber. Arginine has also been used topically (on the skin) to attempt to improve wound healing. Further research is necessary in this area before a firm conclusion can be drawn.        C

Key to grades
A Strong scientific evidence for this use
B Good scientific evidence for this use
C Unclear scientific evidence for this use
D Fair scientific evidence against this use (it may not work)
F Strong scientific evidence against this use (it likely does not work)

Uses based on tradition or theory
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

AIDS/HIV, ammonia toxicity, anti-aging, beta-hemoglobinopathies, cancer, cardiac syndrome X, cold prevention, cystic fibrosis, dementia, diabetes, glaucoma, growth hormone stimulation, hemolytic uremic syndrome (HUS), hepatic encephalopathy, high cholesterol, increased muscle mass, infantile necrotizing enterocolitis, infection, inflammatory bowel disease, ischemic stroke, liver disease, lower esophageal sphincter relaxation, low sperm count, metabolic acidosis, obesity, osteoporosis, pain, peritonitis, pre-term labor contractions, pulmonary hypertension (high blood pressure in the lungs), Raynaud's phenomenon, sepsis, sexual function in women, sickle cell anemia, stomach motility disorders, stomach ulcer, stroke, supplementation to a low protein diet, thrombotic thrombocytopenic purpura (TTP), tumors.

Safety
The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies
Anaphylaxis (severe allergic reaction) has occurred after arginine injections. People with a known allergy should avoid arginine. Signs of allergy may include rash, itching or shortness of breath.

Side Effects and Warnings
Arginine has been well tolerated by most people in studies lasting for up to six months, although there is a possibility of serious adverse effects in some individuals.
Stomach discomfort, including nausea, stomach cramps or an increased number of stools, may occur. People with asthma may experience a worsening of symptoms if arginine is inhaled, which may be related to allergy. Headache has also been reported.

Other potential side effects include low blood pressure and changes in numerous chemicals and electrolytes in the blood. Examples include high potassium, high chloride, low sodium, low phosphate, high blood urea nitrogen and high creatinine levels. People with liver or kidney disease may be especially sensitive to these complications and should avoid using arginine except under medical supervision. After injections of arginine, low back pain, flushing, headache, numbness, restless legs, venous irritation and death of surrounding tissues have been reported.

In theory, arginine may increase the risk of bleeding. Patients using anticoagulants (blood thinners) or antiplatelet drugs, or with underlying bleeding disorders, should speak with a qualified healthcare provider before using arginine and should be monitored.

Arginine may increase blood sugar levels. Caution is advised in patients taking prescription drugs to control sugar levels.

Pregnancy and Breastfeeding
Arginine cannot be recommended as a supplement during pregnancy and breast-feeding because there is not enough scientific information available.

L-arginine has been used in women with preeclampsia until day 10 postpartum but should not be used without supervision of an OB/GYN and pharmacist.

Methodology
This patient information is based on a professional level monograph edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Selected references

1. Abel T, Knechtle B, Perret C, et al. Influence of chronic supplementation of arginine aspartate in endurance athletes on performance and substrate metabolism - a randomized, double-blind, placebo-controlled study. Int J Sports Med. 2005 Jun;26(5):344-9.

2. Black P, Max MB, Desjardins P, et al. A randomized, double-blind, placebo-controlled comparison of the analgesic efficacy, onset of action, and tolerability of ibuprofen arginate and ibuprofen in postoperative dental pain. Clin Ther. 2002;24(7):1072-1089.

3. Carrier, M, Pellerin M, Perrault LP, et al. Cardioplegic arrest with L-arginine improves myocardial protection: results of a prospective randomized clinical trial. Ann.Thorac.Surg. 2002;73(3):837-841.

4. Cartledge JJ, Davies AM, Eardley I. A randomized double-blind placebo-controlled crossover trial of the efficacy of L-arginine in the treatment of interstitial cystitis. BJU.Int 2000;85(4):421-426.

5. Garhofer G, Resch H, Lung S, et al. Intravenous administration of L-arginine increases retinal and choroidal blood flow.Am J Ophthalmol. 2005 Jul;140(1):69-76.

6. Gianotti L, Braga M, Nespoli L, et al. A randomized controlled trial of preoperative oral supplementation with a specialized diet in patients with gastrointestinal cancer. Gastroenterology 2002;122(7):1763-1770.

7. Hladunewich MA, Derby GC, Lafayette RA, et al. Effect of L-arginine therapy on the glomerular injury of preeclampsia: a randomized controlled trial.Obstet Gynecol. 2006 Apr;107(4):886-95.

8. Houwing RH, Rozendaal M, Wouters-Wesseling W, et al. A randomised, double-blind assessment of the effect of nutritional supplementation on the prevention of pressure ulcers in hip-fracture patients. Clin Nutr. 2003;22(4):401-405.

9. Koga Y, Akita Y, Junko N, et al. Endothelial dysfunction in MELAS improved by l-arginine supplementation. Neurology. 2006 Jun 13;66(11):1766-9.

10. Korting G, Smith S, Wheeler M, et al. A randomized double-blind trial of oral L-arginine for treatment of interstitial cystitis. J Urol. 1999;161(2):558-565.

11. Lebret T, Herve JM, Gorny P, et al. Efficacy and safety of a novel combination of L-arginine glutamate and yohimbine hydrochloride: a new oral therapy for erectile dysfunction. Eur.Urol. 2002;41(6):608-613.

12. Miller HI, Dascalu A, Rassin TA, et al. Effects of an acute dose of L-arginine during coronary angiography in patients with chronic renal failure: a randomized, parallel, double-blind clinical trial. Am.J.Nephrol. 2003;23(2):91-95.

13. Mansoor JK, Morrissey BM, Walby WF, et al. L-arginine supplementation enhances exhaled NO, breath condensate VEGF, and headache at 4,342 m. High Alt Med Biol. 2005 Winter;6(4):289-300.

14. Polan ML, Hochberg RB, Trant AS, et al. Estrogen bioassay of ginseng extract and ArginMax, a nutritional supplement for the enhancement of female sexual function. J.Womens Health (Larchmt.) 2004;13(4):427-430.

15. Schulman SP, Becker LC, Kass DA, et al. L-arginine therapy in acute myocardial infarction: the Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) randomized clinical trial. JAMA. 2006 Jan 4;295(1):58-64.

RESEARCH:

The role of NO synthases in arginine-dependent small intestinal and colonic carcinogenesis.
Author:           Yerushalmi,-H-F; Besselsen,-D-G; Ignatenko,-N-A; Blohm-Mangone,-K-A; Padilla-Torres,-J-L; Stringer,-D-E; Cui,-H; Holubec,-H; Payne,-C-M; Gerner,-E-W
Citation: Mol-Carcinog. 2006 Feb; 45(2): 93-105

Abstract:  Arginine is catabolized by NOS2 and other nitric oxide synthases to form nitric oxide. We evaluated the roles of dietary arginine and Nos2 in Apc-dependent intestinal tumorigenesis in Min mice with and without a functional Nos2 gene. NOS2 protein was expressed only in intestinal tissues of Apc(Min/+) Nos2+/+ mice. NOS3 expression was higher in intestinal tissues of mice lacking Nos2, mainly in the small intestine. When diet was supplemented with arginine (0.2% and 2% in drinking water), lack of Nos2 results in decreased tumorigenesis in both small intestine and colon. In Nos2 knockout mice, supplemental arginine (up to 2%) caused a decrease in small intestinal tumor number and size. The arginine-dependent decrease was associated with an increase in nitrotyrosine formation and apoptosis in the region of intestinal stem cells. Mice expressing Nos2 did not show these changes. These mice did, however, show an arginine-dependent increase in colon tumor number and incidence, while no effect on apoptosis was seen. These changes were associated with increased nitrotyrosine formation in epithelial cells. Mice lacking Nos2 did not show changes in tumorigenesis or nitrotyrosine formation, while demonstrating an arginine-dependent increase in apoptosis. These data suggest that Nos2 and dietary arginine have significant effects on intestinal and colonic tumorigenesis in Min mice. In both tissues, loss of Nos2 is associated with decreased tumorigenesis when mice are supplemented with dietary arginine. In the small intestine, Nos2 prevents the arginine-induced decrease in tumor number and size, which is associated with NOS3 expression and increased apoptosis. In the colon, Nos2 is required for the arginine-induced increase in tumor number and incidence. Copyright 2005 Wiley-Liss, Inc.


The effects of sustained-release-L-arginine formulation on blood pressure and vascular compliance in 29 healthy individuals.
Author:           Miller,-A-L
Citation: Altern-Med-Rev. 2006 Mar; 11(1): 23-9

Abstract: Vascular endothelial function is crucial to cardiovascular function and thus to blood perfusion to the heart and throughout the body. A number of substances are produced and secreted by vascular endothelial cells, the most important of which is nitric oxide, a potent regulator of vascular function. Nitric oxide diffuses from endothelial cells into underlying smooth muscle, causing relaxation, which results in vasodilation. When this process is inhibited or inadequate the arteries cannot dilate as necessary, resulting in hypertonicity and reduced blood flow. Such endothelial dysfunction also causes increased platelet and monocyte adhesiveness and smooth muscle proliferation, processes thought to be at the genesis of atherosclerotic plaque formation. Since L-arginine is the body's only substrate for nitric oxide synthesis, adequate L-arginine must be present for proper nitric oxide production. In this open label trial, a group of 29 asymptomatic individuals were given L-arginine (1,050 mg, as Perfusia-SR, a sustained-release preparation) twice daily (total 2.1 g daily) for one week. Systolic blood pressure was reduced in 62 percent of participants compared to baseline, with a non-significant mean decrease in all patients of 4 mm Hg. Diastolic blood pressure was reduced in 69 percent of participants, with a mean reduction of 3.7 mm Hg (p = 0.005). In the 10 individuals who were borderline or hypertensive (systolic > 130 or diastolic > 85), there was a mean systolic reduction of 11 mm Hg (p = 0.05), while normotensives (n = 19) had a mean systolic decrease of only 0.22 mm Hg. Diastolic blood pressure was decreased a non-significant 4.9 mm Hg in borderline or hypertensives and 4.5 mm Hg in normotensives (p = 0.026). Vascular elasticity relates to endothelial function, and can be measured non-invasively. At baseline and follow-up, vascular compliance was assessed via digital pulse wave analysis (DPA; Meridian Medical). After one week, pulse wave analysis showed a significant increase in large artery compliance (mean 23% improvement; p = 0.02) and a non-significant increase in small artery compliance (mean 23% improvement; p = 0.15). This study demonstrates blood pressure reductions, especially in patients with borderline or frank hypertension, as well as improved vascular compliance - an indicator of improved endothelial function and perfusion - after a one-week trial of sustained-release L-arginine. Poor endothelial function due to inadequate endothelial nitric oxide production is present in hypertension, as well as in numerous other aspects of cardiovascular disease, including angina, erectile dysfunction, cerebrovascular disease, and peripheral vascular disease. This is the first study showing a moderate dose of sustained-release L-arginine can improve endothelial function and blood pressure.


L-arginine supplementation causes additional effects on exercise-induced angiogenesis and VEGF expression in the heart and hind-leg muscles of middle-aged rats.
Author:           Suzuki,-J
Citation: J-Physiol-Sci. 2006 Feb; 56(1): 39-44

Abstract: The effects of dietary L-arginine supplementation on exercise-induced angiogenesis and VEGF expression were examined in male middle-aged (12 months old) Wistar rats. Exercise training lasted for six weeks at 20 m/min on a 0% gradient for 10-60 min/day. Rats in the L-arginine-treated groups drank water containing 2.5% L-arginine. According to histochemical identification of the capillary profile, in the soleus muscle the capillary-to-fiber (C:F) ratio showed a significantly greater value in the L-arginine-treated training group than in both the sedentary control and training groups. Training with L-arginine significantly increased the C:F ratio in the subendocardium of the left ventricle, whereas training alone did not. In the plantaris muscle, training with or without L-arginine significantly increased the capillary density, but it did not affect the C:F ratio. A Western blot analysis showed that training with L-arginine significantly increased VEGF protein expression by 2.9-fold in the soleus muscle and by 1.7-fold in the left ventricle, but the increase with training alone was insignificant. The tissue endothelial nitric oxide synthase protein levels were significantly increased in both the soleus (by 1.3-fold) and the left ventricle (by 1.4-fold) only after training with L-arginine supplementation. In the plantaris muscle, these protein levels did not change after either training or L-arginine treatment. The present results suggest that in middle-aged rats, L-arginine administration caused additional effects on exercise-induced angiogenesis by presumably promoting VEGF expression in the hind-leg muscle as well as in the left ventricle.


Dietary L-arginine supplementation reduces fat mass in Zucker diabetic fatty rats.
Author:           Fu,-W-J; Haynes,-T-E; Kohli,-R; Hu,-J; Shi,-W; Spencer,-T-E; Carroll,-R-J; Meininger,-C-J; Wu,-G
Citation: J-Nutr. 2005 Apr; 135(4): 714-21

Abstract: This study was conducted to test the hypothesis that dietary supplementation of arginine, the physiologic precursor of nitric oxide (NO), reduces fat mass in the Zucker diabetic fatty (ZDF) rat, a genetically obese animal model of type-II diabetes mellitus. Male ZDF rats, 9 wk old, were pair-fed Purina 5008 diet and received drinking water containing arginine-HCl (1.51%) or alanine (2.55%, isonitrogenous control) for 10 wk. Serum concentrations of arginine and NO(x) (oxidation products of NO) were 261 and 70% higher, respectively, in arginine-supplemented rats than in control rats. The body weights of arginine-treated rats were 6, 10, and 16% lower at wk 4, 7, and 10 after the treatment initiation, respectively, compared with control rats. Arginine supplementation reduced the weight of abdominal (retroperitoneal) and epididymal adipose tissues (45 and 25%, respectively) as well as serum concentrations of glucose (25%), triglycerides (23%), FFA (27%), homocysteine (26%), dimethylarginines (18-21%), and leptin (32%). The arginine treatment enhanced NO production (71-85%), lipolysis (22-24%), and the oxidation of glucose (34-36%) and octanoate (40-43%) in abdominal and epididymal adipose tissues. Results of the microarray analysis indicated that arginine supplementation increased adipose tissue expression of key genes responsible for fatty acid and glucose oxidation: NO synthase-1 (145%), heme oxygenase-3 (789%), AMP-activated protein kinase (123%), and peroxisome proliferator-activated receptor gamma coactivator-1alpha (500%). The induction of these genes was verified by real-time RT-PCR analysis. In sum, arginine treatment may provide a potentially novel and useful means to enhance NO synthesis and reduce fat mass in obese subjects with type-II diabetes mellitus.

Arginine supplementation does not enhance serum nitric oxide levels in elderly nursing home residents with pressure ulcers.
Author: Stechmiller,-J-K; Langkamp-Henken,-B; Childress,-B; Herrlinger-Garcia,-K-A; Hudgens,-J; Tian,-L; Percival,-S-S; Steele,-R
Citation: Biol-Res-Nurs. 2005 Apr; 6(4): 289-99

Abstract: The purpose of this study was to determine whether arginine supplementation enhances in vitro (neutrophil burst and mitogen-induced lymphocyte proliferation) and in vivo (delayed-type hypersensitivity [DTH] and serum nitric oxide) measures of immune function in nursing home elders with pressure ulcers. Twenty-six elders, 65 years of age or older, with one or more pressure ulcers, were randomized to receive 8.5 g of arginine or an isonitrogenous supplement for 4 weeks. Immune function studies and serum arginine, ornithine, citrulline, and nitric oxide were measured at baseline, 4 weeks postsupplementation (Week 4) and after a 6-week washout (Week 10). At Week 4, serum ornithine increased (p = .01) and arginine trended to increase (p = .055), but there was no increase in citrulline or nitric oxide with arginine supplementation. There were no differences in neutrophil burst or DTH responses between groups. Whole blood mitogen-induced proliferation decreased significantly at Week 10 in the isonitrogenous but not in the arginine-supplemented group. There is mounting concern that arginine supplementation during an inflammatory state could be detrimental due to overwhelming nitric oxide production. A key finding of this study is that arginine supplementation did not increase serum nitric oxide levels over that observed in elders with pressure ulcers given an isonitrogenous supplement.

Secondhand tobacco smoke impairs neurogenic and endothelium-dependent relaxation of rabbit corpus cavernosum smooth muscle: improvement with chronic oral administration of L-arginine.
Author:           Gocmez,-S-S; Utkan,-T; Duman,-C; Yildiz,-F; Ulak,-G; Gacar,-M-N; Erden,-F
Citation: Int-J-Impot-Res. 2005 Sep-Oct; 17(5): 437-44

Abstract: The first goal of this study was to examine the effect of secondhand smoking on neurogenic, endothelium- and cGMP-dependent relaxant responses of rabbit corpus cavernosum smooth muscle. Our second goal was to determine whether such an effect can be prevented by oral administration of L-arginine. Male New Zealand rabbits were divided into control, chronic passive cigarette smoking and L-arginine treatment groups. Relaxant or contractile responses in isolated corpus cavernosum smooth muscle strips were determined by using in vitro muscle technique. There was no significant difference in the relaxant response of the strips to papaverine, sodium nitroprusside and contractile response to KCl among the groups. Relaxant responses to acetylcholine and electrical field stimulation and contractile response to phenylephrine were significantly decreased in the strips of the smoking group than that of the control group. The impaired relaxations of strips were markedly improved by treatment of L-arginine, but the contractile responses to phenylephrine were not affected. These data indicate that secondhand smoking may impair both neurogenic and endothelium-dependent relaxation of corpus cavernosum smooth muscle, and may contribute to the etiology of impotence. Chronic dietary supplementation with L-arginine offsets the impairment of neurogenic and endothelial relaxation. Therefore, we suggest that secondhand smoking exposure to cigarette produces selective impairment of neurogenic and endothelium-dependent relaxation of corpus cavernosum smooth muscle via a mechanism related to the decreased production and/or availability of nitric oxide.

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ASPARTIC ACID

From Bodybuilding.com

A Non-Essential Amino Acid
Aspartic Acid is a non-essential amino acid, which means that it can be manufactured by the body with proper nutrition. It can be found in animals and plants, especially sugar cane and sugar beets.

Aspartic Acid is good for helping the body get rid of harmful ammonia. When ammonia enters the bodies circulatory system, it acts like a highly toxic substance which can harm the central nervous system. Recent studies show that Aspartic Acid may increase resistance to fatigue and increase endurance.

Even though Aspartic Acid is considered a non-essential amino acid, it does play a major role in metabolism. During the citric acid cycle Aspartic acid aids in the construction and synthesis of other amino acids and biochemicals. Among these biochemicals are asparagine, arginine, lysine, methionine, threonine, isoleucine, and several nucleotides.

Aspartic acid increases stamina making it good for fatigue. Low levels of aspartic acid can cause chronic fatigue, because it can lead to lowered cellular energy.

Aspartic acid is one of the key components in all living things. Proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA.

PDRhealth:

L-Aspartate

TRADE NAMES
L-Aspartate is available as magnesium, potassium, calcium and zinc salts from numerous manufacturers. It is available in the base form as L-aspartic acid (Tyson).

DESCRIPTION
L-aspartate is a protein amino acid naturally found in all life forms. L-aspartate is a dicarboxylic amino acid. Although most L-aspartate is in proteins, small amounts of free L-aspartate are found in body fluids and in plants. The normal diet contains about 2 grams of L-aspartate daily. L-aspartate is also in the alternative dipeptide sweetener aspartame; the amount of L-aspartate from the sweetener is a small fraction of total L-aspartate consumed.

L-aspartate is considered a non-essential amino acid, meaning that, under normal physiological conditions, sufficient amounts of the amino acid are synthesized in the body to meet the body's requirements. L-aspartate is formed by the transamination of the Krebs cycle intermediate oxaloacetate. The amino acid serves as a precursor for synthesis of proteins, oligopeptides, purines, pyrimidines, nucleic acids and L-arginine. L-aspartate is a glycogenic amino acid, and it can also promote energy production via its metabolism in the Krebs cycle. These latter activities were the rationale for the claim that supplemental aspartate has an anti-fatigue effect on skeletal muscle, a claim that was never confirmed.

L-aspartate is also known as L-amino succinate. Its IUPAC abbreviation is Asp. Its one-letter abbreviation, used when spelling out protein structures, is D. It is a solid, with an acid form that is slightly soluble in water, and with salt forms that are more water-soluble. Available salts include magnesium, calcium, potassium, zinc and combinations thereof. L-aspartate is used interchangeably with the term aspartic acid. The biological form of this substance, however, is the anion of aspartic acid, L-aspartate.

ACTIONS AND PHARMACOLOGY

ACTIONS
L-aspartate salts are delivery forms for cations such as magnesium, potassium, calcium and zinc.

MECHANISM OF ACTION
L-aspartates can form salts with cations such as magnesium, potassium, calcium and zinc.

PHARMACOKINETICS
Following ingestion, L-aspartate is absorbed from the small intestine by an active transport process. Following absorption, L-aspartate enters the portal circulation and from there is transported to the liver, where much of it is metabolized to protein, purines, pyrimidines and L-arginine, and is catabolized as well. L-aspartate is not metabolized in the liver; it enters the systemic circulation, which distributes it to various tissues of the body. The cations associated with L-aspartate independently interact with various substances in the body and participate in various physiological processes.

INDICATIONS AND USAGE
There is no support for the claim that aspartates are exercise performance enhancers, i.e. ergogenic aids.

RESEARCH SUMMARY
There are claims that L-aspartate is a special type of mineral transporter for cations, such as magnesium, into cells. Magnesium aspartate has not been found to be more biologically effective when compared with other magnesium salts.

There are also claims that L-aspartate has ergogenic effects, that it enhances performance in both prolonged exercise and short intensive exercise. It is hypothesized that L-aspartate, especially the potassium magnesium aspartate salt, spares stores of muscle glycogen and/or promotes a faster rate of glycogen resynthesis during exercise. It has also been hypothesized that L-aspartate can enhance short intensive exercise by serving as a substrate for energy production in the Krebs cycle and for stimulating the purine nucleotide cycle.

An animal study using injected aspartate failed to find any evidence of a glycogen-sparing effect or any ergogenic effects whatsoever. A more recent double-blind human study of male weight trainers similarly found aspartate supplementation to have no effect, and another study of the effect of aspartate on short intensive exercise again found no effect.

CONTRAINDICATIONS, PRECAUTIONS, ADVERSE REACTIONS

CONTRAINDICATIONS
L-aspartate supplementation is contraindicated in those hypersensitive to any component of the preparation.

PRECAUTIONS
Because of lack of long-term safety studies, L-aspartate salts should be avoided by children, pregnant women and lactating women.

ADVERSE REACTIONS
Mild gastrointestinal side effects including diarrhea have been reported.

INTERACTIONS
No drug, nutritional supplement, food or herb interactions are known.

OVERDOSAGE
Overdosage has not been reported.DOSAGE AND ADMINISTRATION

L-aspartate salts of potassium, magnesium, calcium and zinc are available, as well as mixed salts of magnesium potassium aspartate and calcium magnesium aspartate. See Calcium, Magnesium, Potassium and Zinc for dose recommendations of these minerals.


LITERATURE

Bac P, Pages N, Herrenknecht CLA, Teste JF. Inhibition of mouse-killing behavior in magnesium-deficient rats: effect of pharmacological doses of magnesium pidolate, magnesium aspartate, magnesium lactate, magnesium gluconate and magnesium chloride. Magnes Res. 1995; 8:37-45.

de Haan A, van Doorn JE, Westra HG. Effects of potassium + magnesium aspartate on muscle metabolism and force development during short static exercise. Int J Sports Med. 1985; 6:44-49.

Hagan RD, Upton SJ, Duncan JJ, et al. Absence of effect of potassium- magnesium aspartate on physiologic responses to prolonged work in aerobically trained men. Int J Sports Med. 1982; 3:177-181.

Hicks JT. Treatment of fatigue in general practice: a double-blind study. Clinical Medicine. 1964; 71:85-90.

Maughan RJ, Sadler DJ. The effects of oral administration of salts of aspartic acid on the metabolic response to prolonged exhausting exercise in man. Int J Sports Med. 1983; 4:119-123.

Trudeau F, Murphy R. Effects of potassium-aspartate salt administration on glycogen use in the rat during a swimming stress. Physiol Behav. 1993; 54:7-12.

Tuttle JL, Potteiger JA, Evans BW, Ozmun JC. Effects of acute potassium-magnesium aspartate supplementation on ammonia concentrations during and after resistance training. Int J Sport Nutr. 1995; 5:102-109.

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THREONINE

Vitamins-supplements.org:
Threonine is one of the 20 most common natural amino acids. Threonine is another hydroxyl-containing amino acid. It differs from serine by having a methyl substituent in place of one of the hydrogens on the β carbon and it differs from valine by replacement of a methyl substituent with a hydroxyl group. The hydroxyl group is fairly reactive, being able to form hydrogen bonds with a variety of polar substrates. Threonine is an important component in the formation of protein, collagen, elastin and tooth enamel. It is also important for production of neurotransmitters and health of the nervous system. Nutritionally, in humans, threonine is also an essential amino acid. Human beings cannot synthesize it from simpler metabolites. Threonine is must be obtained through the diet.
 
Threonine functions, uses, and health benefits
Threonine is an important part of many proteins in the body and is necessary for the formation of tooth enamel and elastin and collagen which are needed for both healthy skin and wound healing. Threonine has a mild glucose-sparing effect and is useful in the stabilization of blood sugar because it can be converted into glucose in the liver by the process of gluconeogenesis. Threonine is one of the immune-stimulating nutrients (cysteine, lysine, alanine, and aspartic acid are others), as it promotes thymus growth and activity. Threonine may enhance immunity by assisting in the production of agents that fight viral infections. It also can probably promote cell immune defense function. Threonine is important in the formation of collagen and elastin. When combined with aspartic acid, methionine aids liver and lipotropic function. Threonine is used to treat indigestion and intestinal malfunctions. Threonine may prevent fat from accumulating in the liver. A fatty liver can affect liver function and is associated with diseases of the liver such as cirrhosis. Threonine is an immunostimulant which promotes the growth of thymus gland.
 
Dietary sources of threonine
Threonine is found in most meats and fish, dairy foods, eggs, wheatgerm, bananas, carrots, nuts, beans and seeds. Rich sources of threonine include meats, dairy foods and eggs. Wheat germ, many nuts, beans, and seeds, and vegetables contains some small level of threonine.

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SERINE

From www.serine.org

Overview of serine deficiency
Serine deficiency is a rare, inherited, metabolic disorder that interferes with normal growth and development, particularly in the central nervous system. Unlike similar neurodevelopmental disorders, serine deficiency can be treated. Treatment benefits all children identified with serine deficiency. Early diagnosis and treatment are the key elements for the greatest success.
What are the clinical signs and symptoms of serine deficiency?

Nearly all children with serine deficiency are born with an abnormally small head (called microcephaly) that is congenital (i.e.: present at birth). Other predominant characteristics include: spastic quadriplegia (the muscles are stiff and contract in an uncontrolled way in both the arms and legs), seizures (abnormal nerve conduction that results in a broad array of symptoms from odd sensations of smell and taste to abnormal muscle movement and loss of consciousness), and severe psychomotor retardation (slowed mental and physical activity).
How does a child develop serine deficiency?

Serine deficiency is inherited. Serine deficiency is a recessive disorder, which means that two copies of the affected gene (one from each parent) are necessary for the signs and symptoms of the disorder to be present. The parents have a 25% chance of having a child with serine deficiency. Both boys and girls have an equal chance of developing serine deficiency if the affected gene is present.

How is serine deficiency treated?
As reported in the literature, children diagnosed with serine deficiency have been given serine (and in some cases glycine) orally. The outcome of treatment with oral serine ranges from improvement of seizure control and well being in older children to normal psychomotor (mental and physical) development in a child who was diagnosed and treated prenatally (the mother was treated with oral serine during pregnancy).

How is the diagnosis of serine deficiency confirmed?
Following clinical examination, confirmation of the diagnosis of serine deficiency can be made by measuring serine levels. Serine levels can be measured in the plasma (following a period of fasting) and in the cerebral spinal fluid (CSF). CSF levels are the most reliable as the levels of serine and glycine remain low independent of meal.

In addition, the activity of the 3-PGDH enzyme can be measured in cultured skin fibroblasts. Skin samples (biopsies) are generally, but not exclusively, collected from the forearm and can be then cultured in the laboratory. The fibroblasts (or cells that are involved in wound healing) divide readily in culture and are useful for testing of metabolic and/or chromosomal disorders.

What is Serine?
Serine is an amino acid. Amino acids are the building blocks of proteins. In addition, some amino acids act as messengers between nerve cells or are used by the body to make other complex molecules.

There are 20 different (alpha) amino acids and all of these are important for the normal function of our bodies. We get the amino acids we need through two sources: our bodies can make them from other molecules or we can get them from our diet. Amino acids that we have to get from our diets because our bodies can’t make them are called “essential” amino acids. All other amino acids are considered “non-essential” to the diet but are still important for normal body function.

Serine is called a non-essential amino acid. Although we do get some serine from the diet, the major sources of serine are through metabolic pathways (the way we use food molecules for energy) in our organs and tissues. One significant source of serine in the brain is via a three-step process that begins with a common substance produced during the normal metabolism (or breakdown) of sugars and ends with serine. Each step in this process is facilitated or accelerated (catalyzed) by an enzyme.

Serine is used in the body in several ways. First, serine plays a central role in the production of the “myelin sheath.” Myelin acts as insulation for nerve cells and speeds the conduction of nerve impulses. The parts of the brain and spinal cord that contain large amounts of myelin appear white and are called the “white matter” of the brain. Breakdown or absence of myelin interferes with nerve impulses. Second, serine is important in the growth and development of cells by acting as the starting material for the building blocks of our genetic material (DNA and RNA). Serine also acts as the starting material for the body’s production of nerve messengers (neurotransmitters) and lipid messenger molecules, which play an important role in the normal development of the nervous system.

Some specifics about the biology of serine deficiency
Children who have serine deficiency have low levels of serine in their bodies. This is caused by a defect in one of the enzymes in the three-step process described above. All but one of the children reported so far in the literature have a defect in the enzyme 3-phosphoglycerate dehydrogenase (3-PGDH). 

With few exceptions, enzymes are proteins and are therefore made up of a chain of amino acids that is folded into a 3-dimensional structure. The order of these amino acids is determined by the body’s genetic code or the DNA. In children with serine deficiency scientists have found a change in one amino acid in the 3-PGDH enzyme that results in a decrease in the activity of that enzyme. This decrease in activity slows down the production of serine that ultimately results in less serine in the body.

Background for doctors

What is L-serine?
L-Serine is classified as a nutritionally non-essential amino acid. While the main source of essential amino acids is from the diet, non-essential amino acids are normally synthesize by humans and other mammals from common intermediates. As shown below, L-serine is biosynthesized from a glycolytic intermediate, 3-phosphoglycerate (3-PG), in a three-step process involving the enzymes: 3-phosphoglycerate dehydrogenase (3-PGDH), phosphoserine aminotransferase (PSAT), and phosphoserine phosphatase (PSP).

L-Serine can also be derived in a reversible reaction from glycine; through degradation of protein and phospholipids; and through dietary intake. The primary pathway maintaining adequate serine concentrations is likely to depend on tissue type and stage of development (de Koning et al., 2003).

What is the role of L-serine?
L-Serine plays a role in cell growth and development (cellular proliferation). The conversion of L-serine to glycine by serine hydroxymethyltransferase results in the formation of the one-carbon units necessary for the synthesis of the purine bases, adenine and guanine. These bases when linked to the phosphate ester of pentose sugars are essential components of DNA and RNA and the end products of energy producing metabolic pathways, ATP and GTP. In addition, L-serine conversion to glycine via this same enzyme provides the one-carbon units necessary for production of the pyrimidine nucleotide, deoxythymidine monophosphate, also an essential component of DNA.

L-Serine is a precursor for the neurotransmitters glycine and D-serine, and indirectly through L-cysteine, for the neurotransmitter taurine.
•          As described above, glycine can be synthesized from L-serine and is an inhibitory neurotransmitter.
•          Glycine acts alone by binding to the glycine receptor on the post-synaptic membrane or together with glutamate as a co-agonist.
•          L-Serine can also be converted to D-serine through a serine racemase. D-serine is an endogenous agonist of the NMDA receptor. 
•          L-Cysteine, which can be formed from L-serine through the trans-sulfuration pathway, is the precursor for proteins, glutathione, taurine, coenzyme A and inorganic sulfate.
•          Taurine is an inhibitory neurotransmitter and is likely to play a role in pre- and post-natal development of the central nervous system.
L-Serine derived phospholipids play a central role in the production of myelin and act as lipid messenger molecules. 
•          The condensation of serine with palmitoyl-CoA is the first step in the synthesis of sphingosine. Sphingosine serves as the core of sphingolipids, which include the sphingomyelins (primarily in brain and other nervous tissue) and glycosphingolipids. Sphingolipids are abundant in the myelin sheath and are present in all membranes. 
•          Phosphatidylserine, which is derived from L-serine, is an important messenger for apoptosis. Apoptosis, or programmed cell death, plays a critical role in the normal development of the nervous system. 

For a comprehensive and recent review of the role of serine in disease and development please see de Koning et al, 2003.

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GLUTAMIC ACID

“Intestinal glutamate metabolism.”
Reeds PJ, Burrin DG, Stoll B, Jahoor F.  U.S. Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.  J Nutr. 2000 Apr;130(4S Suppl):978S-82S.

Although it is well known that the intestinal tract has a high metabolic rate, the substrates that are used to generate the necessary energy remain poorly established, especially in fed animals. Under fed conditions, the quantification of substrate used by the gut is complicated by the fact that potential oxidative precursors are supplied from both the diet and the arterial circulation. To circumvent this problem, and to approach the question of the compounds used to generate ATP in the gut, we combined measurements of portal nutrient balance with enteral and intravenous infusions of [U-(13)C]substrates.

We studied rapidly growing piglets that were consuming diets based on whole-milk proteins. The results revealed that 95% of the dietary glutamate presented to the mucosa was metabolized in first pass and that of this, 50% was metabolized to CO(2). Dietary glucose was oxidized to a very limited extent, and arterial glutamine supplied no >15% of the CO(2) production by the portal-drained viscera. Glutamate was the single largest contributor to intestinal energy generation. The results also suggested that dietary glutamate appeared to be a specific precursor for the biosynthesis of glutathione, arginine and proline by the small intestinal mucosa. These studies imply that dietary glutamate has an important functional role in the gut. Furthermore, these functions are apparently different from those of arterial glutamine, the substrate that has received the most attention.
PMID: 10736365 [PubMed - indexed for MEDLINE]

Anyvitamins.com:

Glutamic acid amino acid information page
Glutamic acid, a non-essential amino acid and is synthesized from a number of amino acids including ornithine and arginine.

Glutamic acid is required for
It is an important excitatory neurotransmitter, and glutamic acid is also important in the metabolism of sugars and fats.

It helps with the transportation of potassium across the blood-brain barrier, although itself does not pass this barrier that easily. It also shows promise in the future treatment of neurological conditions, ulcers, hypoglycemic come, muscular dystrophy, epilepsy, Parkinson's, and mental retardation.

Glutamic acid can be used as fuel in the brain, and can attach itself to nitrogen atoms in the process of forming glutamine, and this action also detoxifies the body of ammonia. This action is the only way in which the brain can be detoxified from ammonia.

The fluid produced by the prostate gland also contains amounts of glutamic acid, and may play a role in the normal function of the prostate.

Toxicity and symptoms of high intake
High dosages of glutamic acid may include symptoms such as headaches and neurological problems.

Although no major side effects are reported on supplementation of this nutrient, people with kidney or liver disease should not consume high intakes of amino acids without first consulting a medical professional.

People suffering from personality disorders as well as child behavior disorders may find benefit from this nutrient.

Food sources of glutamic acid

Excellent sources of glutamic acid include meat, poultry, fish, eggs, and dairy products, as well as some protein-rich