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AMINO ACID SUPPLEMENTS

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) There are about 22 amino acids that are the primary components of protein. Amino acids are the protein source of total parenteral nutrition administered in patients without normal dietary intake. Bodybuilders and other athletes are experimenting with amino acids as pharmacologic agents to release growth hormone.

Specific Substances

    A) ARGININE
    1) L-2-amino-5-guanidinovaleric acid
    2) Guanidine aminovaleric acid
    3) Amino-4-guanidovaleric acid
    4) L-arginine
    5) Argininum
    6) R
    7) Molecular Formula: C6-H14-N4-O2
    8) CAS 74-79-3
    GLUTAMINE
    1) Levoglutamide
    2) Levoglutamine
    3) L-glutamic acid 5-amide
    4) l-glutamine
    5) L-glutamine
    6) L-(+)-2-aminoglutaramic acid
    7) Molecular Formula: C5-H10-N2-O3
    8) CAS 56-85-9
    9) CAS 32640-56-5
    HISTIDINE
    1) L-2-amino-3-(1H-imidazol--4-yl)propionic
    2) acid
    3) His
    4) H
    5) L-histidine
    6) Histidinum
    7) Molecular Formula: C6-H9-N3-O2
    8) CAS 71-00-1 (L-histidine)
    9) CAS 645-35-2 (anhydrous L-histidine hydrochloride)
    LYSINE
    1) Lys
    2) K
    3) L-lysine
    4) L-2,6-diaminohexanoic acid
    5) Molecular Formula: C6-H14-N2-O2
    6) CAS 56-87-1
    LYSINE HYDROCHLORIDE
    1) L-2,6-diaminohexanoic acid hydrochloride
    2) Lys hydrochloride
    3) L-lysine monohydrochloride
    4) Lysini hydrochloridum
    5) Molecular Formula: C6-H14-N2-O2-HCL
    6) CAS 657-27-2
    LEUCINE
    1) L-2-amino-4-methylvaleric acid
    2) Alpha-aminoisocaproic acid
    3) L
    4) Leu
    5) L-leucine
    6) Leucinum
    7) Molecular Formula: C6-H13-N-O2
    8) CAS 61-90-5
    METHIONINE
    1) L-2-amino-4-(methylthio)butyric acid
    2) DL-2-amino-4-(methylthio)butyric acid
    3) M
    4) S-methionine
    5) L-methionine
    6) Methioninum
    7) DL-methioninum
    8) Racemethionine (USAN)
    9) Molecular Formula: C5-H11-N-O2-S
    10) CAS 63-68-3 (Methionine)
    11) CAS 59-51-8 (DL-methionine)
    ORNITHINE
    1) L-2,5-Diaminovaleric acid
    2) A,d-Diaminovaleric Acid
    3) L-Ornithine
    4) Molecular Formula: C5-H12-N2-O2
    5) CAS 70-26-8
    PHENYLALANINE
    1) L-2-amino-3-phenylpropionic acid
    2) alpha-aminohydrocinnamic acid
    3) F
    4) Phe
    5) L-phenylalanine
    6) Phenylalaninum
    7) Molecular Formula: C9-H11-N-O2
    8) CAS 63-91-2
    THREONINE
    1) L-2-amino-3-hydroxybutyric acid
    2) beta-methylserine
    3) T
    4) Thr
    5) L-threonine
    6) Threoninum
    7) Molecular Formula: C4-H9-N-O3
    8) CAS 72-19-5
    VALINE
    1) (S)-2-amino-3-methylbutanoic acid
    2) Alpha-aminoisovaleric acid
    3) V
    4) Val
    5) L-Valine
    6) Valinum
    7) Molecular Formula: C5-H11-N-O2
    8) CAS 72-18-4

    1.2.1) MOLECULAR FORMULA
    1) GLUTAMINE: C5H10N2O3

Available Forms Sources

    A) FORMS
    1) Amino acid solutions are available in 10%, 11.4%, 15%, 8%, and 8.5% injections.
    2) ASPARTATE: Aspartate mineral supplements usually contain the following: copper aspartate 2 mg, iron aspartate 18 mg, magnesium aspartate 400 mg, manganese aspartate 7 mg, potassium aspartate 99 mg, and zinc aspartate 15 mg (Jellin et al, 2000).
    B) USES
    1) Amino acids are the protein source of total parenteral nutrition administered in patients without normal dietary intake. Formulations contain approximately 15 amino acids, both essential and nonessential, with a total content ranging between 3% and 15%. Some preparations which contain mostly essential amino acids are designed for renal failure patients needing protein supplementation while others are specific for hepatic dysfunction and metabolic stress (Gilman et al, 1990; AMA, 1986).
    2) Branched-chain amino acid therapy may be effective for the management of hepatic encephalopathy. This type of amino acid therapy is controversial; more investigation is necessary (Eriksson & Conn, 1989; Alexander et al, 1989).
    3) Bodybuilders and other athletes are experimenting with amino acids as pharmacologic agents to release growth hormone (Bucci et al, 1992).
    4) ASPARTATES
    a) Oral: Aspartates is used to increase absorption of mineral supplements, and improve athletic performance (Jellin et al, 2000).
    5) BRANCHED-CHAIN AMINO ACIDS
    a) Oral: Branched-chain amino acids are used to improve exercise performance and reduce protein and muscle breakdown during intense exercise. In addition, they are used for amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), latent portosystemic encephalopathy, and chronic hepatic encephalopathy (Jellin et al, 2000).
    b) Intravenous: Branched-chain amino acids are used for acute hepatic encephalopathy, in conditions of high metabolic stress due to severe trauma or sepsis (Jellin et al, 2000).
    6) GLUTAMINE
    a) Oral: Glutamine is used for depression, moodiness, irritability, anxiety, insomnia, short bowel syndrome, Crohn's disease and enhanced exercise performance. In addition, glutamine is used for HIV wasting, abnormal intestinal permeability in people with HIV, chemotherapy-induced mucositis, protection of immune and gut barrier function in people with esophageal cancer undergoing radiochemotherapy, cystinuria, peptic ulcer, ulcerative colitis, sickle cell anemia, improving recovery after bone marrow transplant, and for alcohol withdrawal support. It is also used orally as enteral nutrition, for preventing morbidity in trauma patients, and preventing infectious complications in critically ill patients (Jellin et al, 2000).
    b) Intravenous: glutamine is used for improving recovery after surgery and after bone marrow transplant, and preventing chemotherapy-induced mucositis (Jellin et al, 2000).
    7) HISTIDINE
    a) Oral: Histidine is used for rheumatoid arthritis, allergic diseases, ulcers, and anemia (Jellin et al, 2000).
    8) L-ARGININE
    a) Oral: L-arginine is used for cardiovascular conditions, including congestive heart failure, angina pectoris and coronary atherosclerosis, intermittent claudication, and erectile dysfunction. In addition, it is used for prevention of the common cold, male infertility, interstitial cystitis, treating cyclosporine nephrotoxicity, and improving athletic performance. L-arginine is also used in combination with ibuprofen for migraine headaches (Jellin et al, 2000).
    b) Topical: It is used as an aid in wound healing, for treating cold hands and feet, and for male and female sexual dysfunction (Jellin et al, 2000).
    c) Arginine administered intravenously is used to test for growth hormone reserve in patients with suspected growth hormone deficiency (Prod Info R-Gene(R) 10 IV injection, 2007). The drug may also be used as an aid to detect growth hormone deficiency in panhypopituitarism, pituitary dwarfism, chromophobe adenoma, postsurgical craniopharyngioma, hypophysectomy, pituitary trauma, acromegaly, gigantism, and problems of growth and stature (Prod Info R-Gene(R) 10 IV injection, 2007; Raiti et al, 1967a; Merimee et al, 1965a).
    9) LYSINE
    a) Oral: Lysine is used to prevent and treat clinical symptoms of recurrent herpes simplex labialis, to treat rheumatoid arthritis, heroin intoxication, and to increase the absorption and decrease the elimination of calcium (Jellin et al, 2000; Tomblin & Lucas, 2001). It is also used as an aid to improve athletic performance. L-lysine monohydrochloride has been used to treat metabolic alkalosis (Lasser, 1960).
    10) METHIONINE
    a) Oral: Methionine is used for liver function support and preventing liver damage in acetaminophen poisoning (Jellin et al, 2000).
    11) ORNITHINE
    a) ORAL: Ornithine is used for improving athletic performance and to heal wounds (Jellin et al, 2000; Bucci et al, 1992). The ornithines (aspartate, hydrochloride, and oxoglurate) have been used to treat hyperammonemia and hepatic encephalopathy (Sweetman, 2001).
    12) PHENYLALANINE
    a) ORAL: Phenylalanine is used to treat depression, Parkinson's disease, chronic pain, osteoarthritis, rheumatoid arthritis, alcohol withdrawal symptoms, and vitiligo (Sweetman, 2001; (Jellin et al, 2000).
    b) TOPICAL: Phenylalanine is used for vitiligo (Sweetman, 2001; (Jellin et al, 2000).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) TOPIC DESCRIPTION: There are about 22 amino acids that are the primary components of protein. Isoleucine (Iso), leucine (Leu), lysine (Lys), methionine (Meth), phenylalanine (Phe), threonine (Thr), tryptophan (Trp), and valine (Val), are considered "essential" because they are not manufactured by the body and must be supplied by foods in the diet. Histidine (His) and arginine (Arg) are "semiessential" or conditionally essential in some clinical states (eg; renal or hepatic insufficiency). Tyrosine (Tyr), glycine (Gly), serine (Ser), glutamine (Glu), aspartate (Asp), cystine (Cys), proline (Pro), alanine (Ala), ornithine (Orn) are considered "nonessential" amino acids.
    B) USES: Amino acids are the protein source of total parenteral nutrition administered in patients without normal dietary intake. Formulations contain approximately 15 amino acids, both essential and nonessential, with a total content ranging between 3% and 15%. Some preparations which contain mostly essential amino acids are designed for renal failure patients needing protein supplementation while others are specific for hepatic dysfunction and metabolic stress. Orally, branched-chain amino acids are used to improve exercise performance and reduce protein and muscle breakdown during intense exercise. In addition, they are used for amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), latent portosystemic encephalopathy, and chronic hepatic encephalopathy. Intravenously, branched-chain amino acids are used for acute hepatic encephalopathy, in conditions of high metabolic stress due to severe trauma or sepsis.
    C) PHARMACOLOGY: Arginine: L-Arginine is a precursor of nitric oxide, which exhibits activity as a vasodilator, platelet-aggregation inhibitor and modulator of immunological processes and epithelial permeability. Arginine also stimulates the release of pituitary growth hormone presumably as a result of effects on the hypothalamus. Glutamine: Produced mainly in skeletal muscle and acts as an inter-organ nitrogen and carbon transporter. It is important for maintaining intestinal function, immune response, and amino acid homeostasis during times of severe stress. Methionine: Potentiates both basal and growth hormone releasing hormone (GHRH) induced growth hormone (GH) secretion. It can increase serum homocysteine levels.
    D) EPIDEMIOLOGY: Overdose is rare.
    E) WITH THERAPEUTIC USE
    1) Diarrhea, nausea, vomiting, abdominal pain, bloating, or gout have been reported with oral administration of arginine, glutamic acid, lysine, and DL-methionine. Intravenous use has been associated with hyperammonemia and intrahepatic cholestasis.
    2) ARGININE: Hypophosphatemia, hyperkalemia, phlebitis, hyperthermia, extravasation injury, and acute allergic reactions (nasal obstruction and discharge, coughing, profuse sweating, severe choking) have occurred during arginine infusions. Rapid arginine infusion rates have reportedly caused local irritation, flushing, nausea, vomiting, numbness, and headache.
    3) LYSINE: Fanconi's syndrome has been reported with chronic L-lysine ingestion.
    4) METHIONINE: Drowsiness and irritability may occur with DL-methionine.
    F) WITH POISONING/EXPOSURE
    1) Toxicity from orally administered amino acids is extremely low. At high doses, administration of IV arginine may cause hypotension. Overdose effects are anticipated to be an extension of adverse effects following therapeutic doses.
    0.2.3) VITAL SIGNS
    A) WITH THERAPEUTIC USE
    1) An elevation in body temperature has occurred with arginine infusions.
    0.2.20) REPRODUCTIVE
    A) PHENYLALANINE - Birth defects most commonly associated with prolonged hyperphenylalaninemia are microcephaly, microsomia, mental retardation, congenital heart disease, strabismus, and hip dislocation.

Laboratory Monitoring

    A) Monitor vital signs, renal function, and liver enzymes in symptomatic patients.
    B) Monitor fluid and electrolyte status in patients with significant vomiting and/or diarrhea.
    C) Plasma concentrations are not readily available or clinically useful in the management of overdose.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. Correct any significant fluid and/or electrolyte abnormalities in patients with severe diarrhea and/or vomiting. In high doses, intravenous L-arginine can cause hypotension due to peripheral vasodilatation. Generally, if the rate of infusion is slowed or stopped, hypotension is transient. Manage mild hypotension with IV fluids.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Treat severe hypotension with IV 0.9% NaCl at 10 to 20 mL/kg. Add dopamine or norepinephrine if unresponsive to fluids. In patients with acute allergic reaction, oxygen therapy, bronchodilators, diphenhydramine, corticosteroids, vasopressors and epinephrine may be required.
    C) DECONTAMINATION
    1) Toxicity after ingestion is unlikely and generally only expected with chronic use. Gastrointestinal decontamination is generally unnecessary.
    D) AIRWAY MANAGEMENT
    1) Ensure adequate ventilation and perform endotracheal intubation early in patients with severe allergic reactions.
    E) ANTIDOTE
    1) None
    F) EXTRAVASATION INJURY
    1) Extravasation injury has been reported infrequently following IV arginine infusion. If extravasation occurs, stop the infusion. Disconnect the IV tubing, but leave the cannula or needle in place. Attempt to aspirate the extravasated drug from the needle or cannula. If possible, withdraw 3 to 5 mL of blood and/or fluids through the needle/cannula. Elevate the affected area. No information is available regarding the application of warm or cold compresses following extravasation of arginine. Administer analgesia for severe pain. If pain persists, there is concern for compartment syndrome, or injury is apparent, an early surgical consult should be considered. Close observation of the extravasated area is suggested. If tissue sloughing, necrosis or blistering occurs, treat as a chemical burn (ie, antiseptic dressings, silver sulfadiazine, antibiotics when applicable). Surgical or enzymatic debridement may be required. Risk of infection is increased in chemotherapy patients with reduced neutrophil count following extravasation. Consider culturing any open wounds. Monitor the site for the development of cellulitis, which may require antibiotic therapy.
    2) GAULT TECHNIQUE (SALINE FLUSH-OUT TECHNIQUE): Prepare around the area of extravasation and inject 1% lidocaine subQ. Inject 1500 Units of hyaluronidase subcutaneously to the affected area. Make 4 small stab incisions around the periphery of the lesion. Pass a blunt tipped catheter or Veress needle attached to a saline-filled syringe into the first stab incision and irrigate the fluid through the subcutaneous tissue, flowing out of the other 3 incisions. Repeat the procedure while injecting through the other incisions. Approximately 500 mL fluid total is recommended. Saline should be actively flowing out the other incisions and not accumulating, which can cause an iatrogenic compartment syndrome. Cover the wound with a dry sterile dressing and monitor it daily.
    G) ENHANCED ELIMINATION
    1) There is no information regarding the effectiveness of hemodialysis or hemoperfusion for the removal of amino acid supplements from plasma.
    H) PATIENT DISPOSITION
    1) HOME CRITERIA: A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    2) OBSERVATION CRITERIA: Patients with a deliberate overdose, and those who are symptomatic, need to be monitored until they are clearly improving and clinically stable.
    3) ADMISSION CRITERIA: Patients with severe symptoms despite treatment should be admitted.
    4) CONSULT CRITERIA: Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    I) PITFALLS
    1) When managing a suspected overdose, the possibility of multidrug involvement should be considered. Consider another etiology, if a patient has severe toxicity.
    J) PHARMACOKINETICS
    1) ARGININE: L-arginine is moderately absorbed from the gastrointestinal tract, producing peak plasma levels after 1 hour following a 10 mg oral administration. Bioavailability is approximately 20% following ingestion. Metabolized in the liver secondary to hydrolytic cleavage of the guanidino group by arginase, resulting in formation of urea and ornithine. Ornithine may ultimately be utilized for the production of glucose. Elimination half-life was approximately 42 minutes following 30 grams intravenously.
    K) DIFFERENTIAL DIAGNOSIS
    1) Other agents that cause extravasation injury or other infusion-related symptoms (eg, hypotension, irritation, flushing, headache, nausea and vomiting.)

Range Of Toxicity

    A) TOXICITY: A minimum toxic dose has not been established. GLUTAMINE: Doses up to 40 mg daily have been well-tolerated. HISTIDINE: Doses up to 4 g daily have been well-tolerated. LYSINE: Diarrhea and abdominal discomfort were reported following ingestion of 10 g daily for 5 days. Fanconi's syndrome occurred in a 44-year-old woman following the oral ingestion of L-lysine 3000 mg daily for 5 years.
    B) THERAPEUTIC DOSES: Varies with agent.

Clinical Effects

Summary Of Exposure

    A) TOPIC DESCRIPTION: There are about 22 amino acids that are the primary components of protein. Isoleucine (Iso), leucine (Leu), lysine (Lys), methionine (Meth), phenylalanine (Phe), threonine (Thr), tryptophan (Trp), and valine (Val), are considered "essential" because they are not manufactured by the body and must be supplied by foods in the diet. Histidine (His) and arginine (Arg) are "semiessential" or conditionally essential in some clinical states (eg; renal or hepatic insufficiency). Tyrosine (Tyr), glycine (Gly), serine (Ser), glutamine (Glu), aspartate (Asp), cystine (Cys), proline (Pro), alanine (Ala), ornithine (Orn) are considered "nonessential" amino acids.
    B) USES: Amino acids are the protein source of total parenteral nutrition administered in patients without normal dietary intake. Formulations contain approximately 15 amino acids, both essential and nonessential, with a total content ranging between 3% and 15%. Some preparations which contain mostly essential amino acids are designed for renal failure patients needing protein supplementation while others are specific for hepatic dysfunction and metabolic stress. Orally, branched-chain amino acids are used to improve exercise performance and reduce protein and muscle breakdown during intense exercise. In addition, they are used for amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), latent portosystemic encephalopathy, and chronic hepatic encephalopathy. Intravenously, branched-chain amino acids are used for acute hepatic encephalopathy, in conditions of high metabolic stress due to severe trauma or sepsis.
    C) PHARMACOLOGY: Arginine: L-Arginine is a precursor of nitric oxide, which exhibits activity as a vasodilator, platelet-aggregation inhibitor and modulator of immunological processes and epithelial permeability. Arginine also stimulates the release of pituitary growth hormone presumably as a result of effects on the hypothalamus. Glutamine: Produced mainly in skeletal muscle and acts as an inter-organ nitrogen and carbon transporter. It is important for maintaining intestinal function, immune response, and amino acid homeostasis during times of severe stress. Methionine: Potentiates both basal and growth hormone releasing hormone (GHRH) induced growth hormone (GH) secretion. It can increase serum homocysteine levels.
    D) EPIDEMIOLOGY: Overdose is rare.
    E) WITH THERAPEUTIC USE
    1) Diarrhea, nausea, vomiting, abdominal pain, bloating, or gout have been reported with oral administration of arginine, glutamic acid, lysine, and DL-methionine. Intravenous use has been associated with hyperammonemia and intrahepatic cholestasis.
    2) ARGININE: Hypophosphatemia, hyperkalemia, phlebitis, hyperthermia, extravasation injury, and acute allergic reactions (nasal obstruction and discharge, coughing, profuse sweating, severe choking) have occurred during arginine infusions. Rapid arginine infusion rates have reportedly caused local irritation, flushing, nausea, vomiting, numbness, and headache.
    3) LYSINE: Fanconi's syndrome has been reported with chronic L-lysine ingestion.
    4) METHIONINE: Drowsiness and irritability may occur with DL-methionine.
    F) WITH POISONING/EXPOSURE
    1) Toxicity from orally administered amino acids is extremely low. At high doses, administration of IV arginine may cause hypotension. Overdose effects are anticipated to be an extension of adverse effects following therapeutic doses.

Vital Signs

    3.3.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) An elevation in body temperature has occurred with arginine infusions.
    3.3.3) TEMPERATURE
    A) ARGININE: Elevation in body temperature was reported in 2 of 25 patients at the end of arginine infusions during treatment of cirrhosis (Tissot-Favre & Brette, 1970).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) ARGININE: In high doses, intravenous L-arginine can cause hypotension due to peripheral vasodilatation (Calver, 1990).
    B) THROMBOPHLEBITIS
    1) ARGININE: Phlebitis has occurred during arginine infusions (Imler et al, 1973). Rare instances of thrombophlebitis have occurred during administration of amino acids (AMA, 1986).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM FINDING
    1) ARGININE: Numbness and headache can occur during intravenous IV infusion of arginine (Prod Info R-Gene(R) 10 IV injection, 2007).
    2) DL-METHIONINE: Drowsiness and irritability may occur with therapeutic use (Sweetman, 2001).
    B) COMA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 27-year-old bodybuilder was admitted comatose (Glasgow Coma Scale of 5), tachycardic and hypotensive. Seven days prior to presentation, the patient had taken approximately 14,000 mg of taurine along with insulin. Neurological examination was unremarkable. A tox screen was positive for anabolic steroids. Taurine can significantly decrease blood glucose levels, therefore it was suggested that the patient may have had a severe hypoglycemic episode due to the combined effects of taurine and insulin (Obermann et al, 2006).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) ARGININE: Nausea and vomiting occur in approximately 3% of patients receiving arginine infusion (Prod Info R-Gene(R) 10 IV injection, 2007).
    2) GLUTAMIC ACID: Nausea may occur as a result of transient acetylcholinosis in patients taking glutamic acid (Ghadimi, 1973).
    3) DL-METHIONINE: Nausea and vomiting may occur with oral use (Sweetman, 2001).
    B) DRUG-INDUCED GASTROINTESTINAL DISTURBANCE
    1) ARGININE: Abdominal cramps and bloating were reported following oral administration of arginine in cystic fibrosis patients (Kattwinkel et al, 1972). In these patients, significant weight loss was also observed.
    2) ARGININE: Diarrhea, abdominal pain, bloating, or gout may occur with therapeutic use (Jellin et al, 2000).
    3) L-LYSINE MONOHYDROCHLORIDE: Diarrhea and abdominal discomfort were reported with L-lysine 10 g daily for 5 days (Lasser, 1960).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) ABNORMAL LIVER FUNCTION
    1) AMINO ACID SOLUTIONS: Hyperammonemia has been seen in patients receiving total parenteral nutrition with amino acids (AMA, 1986; Johnson et al, 1972; Heird et al, 1972; Akpolat, 1993).
    2) AMINO ACID SOLUTIONS: INTRAHEPATIC CHOLESTASIS has been reported as a complication of total parenteral nutrition (Rodgers et al, 1976).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) ABNORMAL RENAL FUNCTION
    1) L-LYSINE: A case of Fanconi's syndrome developed in a 44-year-old woman, following the chronic ingestion of L-lysine (3000 mg daily for 5 years). The patient developed severe tubulointerstitial nephritis progressing to chronic renal failure (Lo et al, 1996).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) THROMBOCYTOPENIC DISORDER
    1) ARGININE: Thrombocytopenia has reportedly occurred in one patient receiving arginine (Prod Info R-Gene(R) 10 IV injection, 2007). A cause-and-effect relationship is unclear.

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) FLUSHING
    1) ARGININE: Intravenous infusion of arginine, particularly rapid infusion, has produced nausea, vomiting, headache, flushing, numbness and local venous irritation in approximately 3% of patients treated (Prod Info R-Gene(R) 10 IV injection, 2007).
    B) SKIN NECROSIS
    1) ARGININE: Four hours post infusion, edema and redness developed in association with pain in a 7-year-old. At 48 hours the traumatized area closely resembled a full-thickness burn and a skin graft was required. Various authors recommend that arginine should be diluted to a 10% concentration to prevent tissue injury (Elanjian, 1992).
    2) ARGININE: Extravasation may cause necrosis and superficial phlebitis (Jellin et al, 2000).
    3) ARGININE: A 3-year-old girl developed extravasation in the distal forearm and skin necrosis after an arginine IV infusion. She was treated with supportive care, including Gault flush-out technique, but required wide debridement and a combination of groin flap and later a split-thickness skin graft (Salameh & Shoufani, 2004).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) ACUTE ALLERGIC REACTION
    1) ARGININE: An anaphylactic reaction to arginine was reported in a 10 1/2-year-old boy following an IV infusion of 100 mL (10% solution) at a rate of 8 mL/minute for 15 minutes. Within 5 minutes of initiation of the infusion, the patient developed nasal obstruction and discharge, with coughing and severe choking, followed by profuse sweating. Signs and symptoms disappeared within 2 hours. The authors suspect an allergic reaction to arginine, possibly secondary to polymerization of the drug, resulting in a unit with antigenic capabilities (Tiwary et al, 1973).
    2) ARGININE: Allergic reaction, including macular rash with hand and facial swelling and redness, nasal obstruction, increased pulse, sweating, and choking have been reported (Jellin et al, 2000).

Reproductive

    3.20.1) SUMMARY
    A) PHENYLALANINE - Birth defects most commonly associated with prolonged hyperphenylalaninemia are microcephaly, microsomia, mental retardation, congenital heart disease, strabismus, and hip dislocation.
    3.20.2) TERATOGENICITY
    A) HUMAN
    1) PHENYLALANINE - Birth defects most commonly associated with prolonged hyperphenylalaninemia are microcephaly, microsomia, mental retardation, congenital heart disease, strabismus, and hip dislocation (REPROTOX(R) , 2001). This is generally seen in offspring of mothers with phenylketonuria.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs, renal function, and liver enzymes in symptomatic patients.
    B) Monitor fluid and electrolyte status in patients with significant vomiting and/or diarrhea.
    C) Plasma concentrations are not readily available or clinically useful in the management of overdose.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with severe symptoms despite treatment should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with a deliberate overdose, and those who are symptomatic, need to be monitored until they are clearly improving and clinically stable.

Monitoring

    A) Monitor vital signs, renal function, and liver enzymes in symptomatic patients.
    B) Monitor fluid and electrolyte status in patients with significant vomiting and/or diarrhea.
    C) Plasma concentrations are not readily available or clinically useful in the management of overdose.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) Toxicity after ingestion is unlikely and generally only expected with chronic use. Gastrointestinal decontamination is generally unnecessary.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Toxicity after ingestion is unlikely and generally only expected with chronic use. Gastrointestinal decontamination is generally unnecessary.
    6.5.3) TREATMENT
    A) SUPPORT
    1) MANAGEMENT OF MILD TO MODERATE TOXICITY
    a) Treatment is symptomatic and supportive. Correct any significant fluid and/or electrolyte abnormalities in patients with severe diarrhea and/or vomiting.
    2) MANAGEMENT OF SEVERE TOXICITY
    a) Treatment is symptomatic and supportive. In patients with acute allergic reaction, oxygen therapy, bronchodilators, diphenhydramine, corticosteroids, vasopressors and epinephrine may be required.
    B) MONITORING OF PATIENT
    1) Monitor vital signs, renal function, and liver enzymes in symptomatic patients.
    2) Monitor fluid and electrolyte status in patients with significant vomiting and/or diarrhea.
    3) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    C) ACUTE ALLERGIC REACTION
    1) SUMMARY
    a) Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta adrenergic agonists, corticosteroids or epinephrine. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.
    2) BRONCHOSPASM
    a) ALBUTEROL
    1) ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007). CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 mg/kg (up to 10 mg) every 1 to 4 hours as needed, or 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    3) CORTICOSTEROIDS
    a) Consider systemic corticosteroids in patients with significant bronchospasm.
    b) PREDNISONE: ADULT: 40 to 80 milligrams/day. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 to 2 divided doses divided twice daily (National Heart,Lung,and Blood Institute, 2007).
    4) MILD CASES
    a) DIPHENHYDRAMINE
    1) SUMMARY: Oral diphenhydramine, as well as other H1 antihistamines can be used as indicated (Lieberman et al, 2010).
    2) ADULT: 50 milligrams orally, or 10 to 50 mg intravenously at a rate not to exceed 25 mg/min or may be given by deep intramuscular injection. A total of 100 mg may be administered if needed. Maximum daily dosage is 400 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    3) CHILD: 5 mg/kg/24 hours or 150 mg/m(2)/24 hours. Divided into 4 doses, administered intravenously at a rate not exceeding 25 mg/min or by deep intramuscular injection. Maximum daily dosage is 300 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    5) MODERATE CASES
    a) EPINEPHRINE: INJECTABLE SOLUTION: It should be administered early in patients by IM injection. Using a 1:1000 (1 mg/mL) solution of epinephrine. Initial Dose: 0.01 mg/kg intramuscularly with a maximum dose of 0.5 mg in adults and 0.3 mg in children. The dose may be repeated every 5 to 15 minutes, if no clinical improvement. Most patients respond to 1 or 2 doses (Nowak & Macias, 2014).
    6) SEVERE CASES
    a) EPINEPHRINE
    1) INTRAVENOUS BOLUS: ADULT: 1 mg intravenously as a 1:10,000 (0.1 mg/mL) solution; CHILD: 0.01 mL/kg intravenously to a maximum single dose of 1 mg given as a 1:10,000 (0.1 mg/mL) solution. It can be repeated every 3 to 5 minutes as needed. The dose can also be given by the intraosseous route if IV access cannot be established (Lieberman et al, 2015). ALTERNATIVE ROUTE: ENDOTRACHEAL ADMINISTRATION: If IV/IO access is unavailable. DOSE: ADULT: Administer 2 to 2.5 mg of 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube. CHILD: DOSE: 0.1 mg/kg to a maximum of 2.5 mg administered as a 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube (Lieberman et al, 2015).
    2) INTRAVENOUS INFUSION: Intravenous administration may be considered in patients poorly responsive to IM or SubQ epinephrine. An epinephrine infusion may be prepared by adding 1 mg (1 mL of 1:1000 (1 mg/mL) solution) to 250 mL D5W, yielding a concentration of 4 mcg/mL, and infuse this solution IV at a rate of 1 mcg/min to 10 mcg/min (maximum rate). CHILD: A dosage of 0.01 mg/kg (0.1 mL/kg of a 1:10,000 (0.1 mg/mL) solution up to 10 mcg/min (maximum dose 0.3 mg) is recommended for children (Lieberman et al, 2010). Careful titration of a continuous infusion of IV epinephrine, based on the severity of the reaction, along with a crystalloid infusion can be considered in the treatment of anaphylactic shock. It appears to be a reasonable alternative to IV boluses, if the patient is not in cardiac arrest (Vanden Hoek,TL,et al).
    7) AIRWAY MANAGEMENT
    a) OXYGEN: 5 to 10 liters/minute via high flow mask.
    b) INTUBATION: Perform early if any stridor or signs of airway obstruction.
    c) CRICOTHYROTOMY: Use if unable to intubate with complete airway obstruction (Vanden Hoek,TL,et al).
    d) BRONCHODILATORS are recommended for mild to severe bronchospasm.
    e) ALBUTEROL: ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007).
    f) ALBUTEROL: CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    8) MONITORING
    a) CARDIAC MONITOR: All complicated cases.
    b) IV ACCESS: Routine in all complicated cases.
    9) HYPOTENSION
    a) If hypotensive give 500 to 2000 milliliters crystalloid initially (20 milliliters/kilogram in children) and titrate to desired effect (stabilization of vital signs, mentation, urine output); adults may require up to 6 to 10 L/24 hours. Central venous or pulmonary artery pressure monitoring is recommended in patients with persistent hypotension.
    1) VASOPRESSORS: Should be used in refractory cases unresponsive to repeated doses of epinephrine and after vigorous intravenous crystalloid rehydration (Lieberman et al, 2010).
    2) DOPAMINE: Initial Dose: 2 to 20 micrograms/kilogram/minute intravenously; titrate to maintain systolic blood pressure greater than 90 mm Hg (Lieberman et al, 2010).
    10) H1 and H2 ANTIHISTAMINES
    a) SUMMARY: Antihistamines are second-line therapy and are used as supportive therapy and should not be used in place of epinephrine (Lieberman et al, 2010).
    1) DIPHENHYDRAMINE: ADULT: 25 to 50 milligrams via a slow intravenous infusion or IM. PEDIATRIC: 1 milligram/kilogram via slow intravenous infusion or IM up to 50 mg in children (Lieberman et al, 2010).
    b) RANITIDINE: ADULT: 1 mg/kg parenterally; CHILD: 12.5 to 50 mg parenterally. If the intravenous route is used, ranitidine should be infused over 10 to 15 minutes or diluted in 5% dextrose to a volume of 20 mL and injected over 5 minutes (Lieberman et al, 2010).
    c) Oral diphenhydramine, as well as other H1 antihistamines, can also be used as indicated (Lieberman et al, 2010).
    11) DYSRHYTHMIAS
    a) Dysrhythmias and cardiac dysfunction may occur primarily or iatrogenically as a result of pharmacologic treatment (epinephrine) (Vanden Hoek,TL,et al). Monitor and correct serum electrolytes, oxygenation and tissue perfusion. Treat with antiarrhythmic agents as indicated.
    12) OTHER THERAPIES
    a) There have been a few reports of patients with anaphylaxis, with or without cardiac arrest, that have responded to vasopressin therapy that did not respond to standard therapy. Although there are no randomized controlled trials, other alternative vasoactive therapies (ie, vasopressin, norepinephrine, methoxamine, and metaraminol) may be considered in patients in cardiac arrest secondary to anaphylaxis that do not respond to epinephrine (Vanden Hoek,TL,et al).
    D) GLYCINE
    1) Glycine has been used to detoxify excessive methionine. Methionine supplementation may place a competitive demand on the availability of glycine for other metabolic processes (Meakins et al, 1998).

Enhanced Elimination

    A) LACK OF INFORMATION
    1) There is no information regarding the effectiveness of hemodialysis or hemoperfusion for the removal of amino acid supplements from plasma.

Range Of Toxicity

Summary

    A) TOXICITY: A minimum toxic dose has not been established. GLUTAMINE: Doses up to 40 mg daily have been well-tolerated. HISTIDINE: Doses up to 4 g daily have been well-tolerated. LYSINE: Diarrhea and abdominal discomfort were reported following ingestion of 10 g daily for 5 days. Fanconi's syndrome occurred in a 44-year-old woman following the oral ingestion of L-lysine 3000 mg daily for 5 years.
    B) THERAPEUTIC DOSES: Varies with agent.

Therapeutic Dose

    7.2.1) ADULT
    A) GENERAL
    1) GLUTAMINE: The following doses have been used:
    a) ORAL
    1) CANCER, oral: 30 grams daily usually given in 3 divided doses (Yoshida et al, 1998).
    2) CHEMOPROTECTIVE, oral: 10 grams orally three times daily or 0.5 gram/kilogram/day (Savarese et al, 1998; Rubio et al, 1998).
    3) INTESTINAL PERMEABILITY, oral: 7 to 21 grams daily in single or divided doses (Den Hond et al, 1999; Den Hond et al, 1999a).
    4) SHORT BOWEL SYNDROME, oral: 0.4 to 0.63 gram/kilogram/day (Cukier et al, 1999; Scolapio, 1999).
    5) STOMATITIS, oral solution: 2 grams twice daily used as a mouthwash and then swallowed (Anderson et al, 1998).
    b) INTRAVENOUS
    1) IMMUNE SYSTEM ENHANCEMENT, parenteral: 0.18 gram/kilogram/day in a total parenteral nutrition solution (O'Riordain et al, 1994).
    2) CANCER, intravenous: 50 grams glycl-L-GLUTAMINE daily or GLUTAMINE 0.57 gram/kilogram/day (Brown et al, 1998; Schloerb & Skikne, 1999).
    c) ENTERAL
    1) CRITICAL ILLNESS, enteral: 5 grams per each 500 milliliters of enteral feeding solution (Jones et al, 1999).
    2) INFECTION, enteral: 12 to 30.5 grams in an enteral feeding solution (Houdijk et al, 1998).
    2) L-ARGININE
    a) ENDOTHELIAL DYSFUNCTION-RELATED CONDITIONS, oral: 6 to 8 grams daily (Tenenbaum et al, 1998).
    b) IMMUNE ENHANCEMENT, oral: 30 grams daily (Marz, 1997).
    c) INTRACTABLE ANGINA PECTORIS, oral: 9 grams daily for 3 months (Blum et al, 1999).
    3) LYSINE
    a) L-lysine for recurrent herpes simplex labialis infections, 1 to 3 grams daily (Lo et al, 1996).
    b) In one study, patients were given lysine 1000 milligrams at the onset of symptoms and 500 milligrams each morning and evening (total of 11 500-milligram tablets) (Tomblin & Lucas, 2001).
    c) Lysine 10 grams daily in divided doses for up to 5 days have been used to treat metabolic alkalosis (Lasser, 1960).
    4) AMINO ACID SOLUTIONS
    a) TOTAL PARENTERAL NUTRITION
    1) The following are recommended protein requirements in adult patients requiring nutritional support (Anon, 1993; Teasley-Strausburg et al, 1992):
    PATIENT CONDITIONPROTEIN REQUIREMENT(gram/kilogram of body weight per day)
    Unstressed0.8 to 1.0
    Low stress1.0 to 1.7
    Critically ill1.5 to 2.0
    Sever burn injury2.0 to 3.0

    7.2.2) PEDIATRIC
    A) GENERAL
    1) CHILDREN -
    a) GLUTAMINE
    1) STOMATITIS, oral solution: 2 grams twice daily used as a mouthwash and then swallowed (Anderson et al, 1998).
    b) L-ARGININE
    1) GROWTH HORMONE DEFICIENCY, oral: 10 grams arginine chlorhydrate (Loche et al, 1993).
    c) AMINO ACID SOLUTIONS
    1) TOTAL PARENTERAL NUTRITION
    a) CHILDREN: The following are recommended protein requirements for children aged 1 to 10 years requiring nutritional support (Anon, 1993; Teasley-Strausburg et al, 1992):
    PATIENT CONDITIONPROTEIN REQUIREMENT (grams/kilogram of body weight per day)
    Unstressed1.0 to 1.2
    Low stress maintenance anabolism 2.0 to 2.5 2.5 to 3.0
    Critically ill2.5 to 3.5
    Severe burn injury2.5 to 3.5

    b) INFANTS: The following are recommended protein requirements in infants aged 0 to 1 year requiring nutritional support (Anon, 1993; Teasley-Strausburg et al, 1992):
    PATIENT CONDITIONPROTEIN REQUIREMENT (grams/kilogram of body weight per day)
    Unstressed1.6 to 2.2
    Low stress maintenance anabolism 2.0 to 2.5 2.5 to 3.0
    Critically ill2.5 to 3.5
    Severe burn injury2.5 to 3.5

    c) In low birth weight infants, the recommended dose of amino acids for adequate growth and nitrogen utilization is 3 grams per kilogram per day (Anon, 1993). Different amino acids are also required in the low birth weight infant. Because of enzyme immaturity, cysteine, taurine, tyrosine and histidine become essential amino acids in this patient population and must be provided in sufficient quantities (Anon, 1993).

Maximum Tolerated Exposure

    A) GENERAL
    1) GLUTAMINE: Doses up to 40 milligrams daily have been well-tolerated (Jellin et al, 2000).
    2) HISTIDINE: Doses up to 4 grams daily have been well-tolerated (Jellin et al, 2000).
    B) CASE REPORTS
    1) L-LYSINE: A case of Fanconi's syndrome in a 44-year-old woman, following the oral ingestion of L-lysine (3000 mg daily for 5 years) has been reported. The patient developed severe tubulointerstitial nephritis progressing to chronic renal failure (Lo et al, 1996).
    2) L-LYSINE MONOHYDROCHLORIDE: Diarrhea and abdominal discomfort were reported with L-lysine 10 g daily for 5 days (Lasser, 1960).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) L-ARGININE MONOHYDROCHLORIDE
    1) LD50- (INTRAPERITONEAL)RAT:
    a) 3793 mg/kg (RTECS , 2000)
    2) LD50- (ORAL)RAT:
    a) 12 g/kg (RTECS , 2000)
    B) L-GLUTAMINE
    1) LD50- (ORAL)MOUSE:
    a) 21700 mg/kg (RTECS , 2000)
    2) LD50- (ORAL)RAT:
    a) 7500 mg/kg (RTECS , 2000)
    C) L-HISTIDINE
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) >10 g/kg (RTECS , 2000)
    2) LD50- (ORAL)MOUSE:
    a) >15 g/kg (RTECS , 2000)
    3) LD50- (INTRAPERITONEAL)RAT:
    a) >8 g/kg (RTECS , 2000)
    4) LD50- (ORAL)RAT:
    a) >15 g/kg (RTECS , 2000)
    D) L-PHENYLALANINE
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) >1322 mg/kg (RTECS , 2000)
    2) LD50- (INTRAPERITONEAL)RAT:
    a) 5287 mg/kg (RTECS , 2000)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) ARGININE
    1) L-Arginine is a precursor of nitric oxide, which exhibits activity as a vasodilator, platelet-aggregation inhibitor and modulator of immunological processes and epithelial permeability (Smith et al, 1997; Smulders et al, 1997). Arginine also stimulates the release of pituitary growth hormone presumably as a result of effects on the hypothalamus (Cryer et al, 1973).
    2) In patients with normal pituitary function, increases in plasma human growth hormone concentrations occur following IV arginine administration, whereas in patients with impaired pituitary function (hypopituitarism), minimal or no increases in plasma growth hormone are observed (Merimee et al, 1965; Raiti et al, 1967; Merimee et al, 1967). Arginine has a number of actions in respect to metabolic and cellular function, though its precise mechanism of immunomodulation remains unclear (Sigal et al, 1992).
    3) L-Arginine is a precursor of nitric oxide, which exhibits activity as a vasodilator, platelet-aggregation inhibitor and modulator of immunological processes and epithelial permeability (Smith et al, 1997a; Smulders et al, 1997a). These pharmacologic properties led investigators to study L-arginine with variable results in preclinical pilot studies involving patients with peripheral vascular disease (Schellong et al, 1997), hypercholesterolemia and platelet reactivity (Wolf et al, 1997), colorectal cancer (Heys et al, 1997), cardiac transplant (Paulus et al, 1997), and insulin resistance (Wascher et al, 1997). The therapeutic use of L-arginine in these disease states has not been determined.
    4) Arginine significantly increases prolactin (PRL) secretion. The mechanism is not age-dependent (Nair et al, 1985). Increased survival postinfection was exhibited in animal studies when arginine was used as a dietary supplement. The benefit of arginine appears to be mediated by improved bactericidal mechanisms via the arginine-nitric oxide pathway (Gianotti et al, 1993).
    5) ARGININE CHLORHYDATE (10 g) administered orally before an intravenous injection of growth hormone releasing hormone (1 mcg/kg) has been shown to significantly enhance the release of the growth hormone (GH) in short prepubertal children (Loche et al, 1993). The authors postulate that the mechanism of action responsible for the augmentation of GH release may be mediated by inhibition of endogenous release of somatostatin.
    6) Arginine may improve T-lymphocyte responses to mitogens by optimizing nutritional supplementation, 7% of maximum caloric intake, in cancer patients (Dudrick & Souba, 1991).
    B) BRANCHED-CHAIN AMINO ACIDS - The oral administration before exercises increases serum ammonia levels and decreases muscle breakdown (Jellin et al, 2000).
    C) GLUTAMINE
    1) Glutamine is the most abundant amino acid in the body (60% of the free amino acid pool)(DiPiro et al, 1997). Glutamine, traditionally classified as a non-essential amino acid, is produced mainly in skeletal muscle and acts as an inter-organ nitrogen and carbon transporter. It is important for maintaining intestinal function, immune response, and amino acid homeostasis during times of severe stress (Jellin et al, 2000).
    2) In addition, it is an important metabolic fuel for lymphocytes, macrophages, fibroblasts, and small intestine enterocytes. It promotes carbohydrate storage after exhaustive exercise and is a precursor of other amino acids, glucose, purines, and pyrimidines, and glutathione (Jellin et al, 2000; DiPiro et al, 1997).
    D) LYSINE - Lysine is essential for collagen synthesis and antagonizes herpes simplex virus (HSV) growth in vitro (Jellin et al, 2000) 2001).
    E) METHIONINE
    1) Methionine can potentiate growth hormone and its releasing hormone secretion. It can increase serum homocysteine levels (Jellin et al, 2000).
    2) Glycine has been used to detoxify excessive methionine. Methionine supplementation may place a competitive demand on the availability of glycine for other metabolic processes (Meakins et al, 1998).
    F) PHENYLALANINE
    1) D-phenylalanine and L-phenylalanine are two enantiomers with DL-phenylalanine being a mixture of these two forms. D-phenylalanine is not an essential human amino acid. L-phenylalanine is an essential amino acid and is metabolized to tyrosine (Jellin et al, 2000).

Physicochemical

Physical Characteristics

    A) Arginine is a white or white crystalline powder, or colorless crystals, practically odorless, and freely soluble in water, (Sweetman, 2001).
    B) Glutamine is a white crystalline powder (Prod Info NUTRESTORE(R) oral powder for solution, 2011).
    C) Histidine is an odorless, colorless crystals or a white crystalline powder, and freely soluble in water (Sweetman, 2001).
    D) Leucine is a white or almost white, odorless crystalline powder or shiny flakes, and sparingly soluble in water (Sweetman, 2001).
    E) Lysine chloride is a white crystalline powder or colorless crystals, odorless and freely soluble in water (Sweetman, 2001).
    F) Methionine is a white or almost white, crystalline powder or colorless crystals, with a characteristic odor; soluble in water (Sweetman, 2001).
    G) Phenylalanine is a white or almost white, odorless, crystalline powder, or shiny, white flakes; sparingly soluble in water (Sweetman, 2001).
    H) Threonine is a white, odorless crystalline powder or colorless crystals; soluble in water (Sweetman, 2001).
    I) Tryptophan is a white or almost white (slightly yellowish-white) crystalline or amorphous powder, and sparingly soluble in water (Sweetman, 2001).
    J) Valine is a white or almost white, odorless crystalline powder or colorless crystals, and soluble in water (Sweetman, 2001).

Molecular Weight

    A) ARGININE: 174.2 (Sweetman, 2001)
    B) GLUTAMINE: 146.15 daltons (Prod Info NUTRESTORE(R) oral powder for solution, 2011)
    C) HISTIDINE: 155.2 (Sweetman, 2001)
    D) LEUCINE: 131.2 (Sweetman, 2001)
    E) LYSINE: 146.2 (Sweetman, 2001)
    F) LYSINE HYDROCHLORIDE: 182.6 (Sweetman, 2001)
    G) METHIONINE: 149.2 (Sweetman, 2001)
    H) ORNITHINE: 132.2 (Sweetman, 2001)
    I) PHENYLALANINE: 165.2 (Sweetman, 2001)
    J) THREONINE: 119.1 (Sweetman, 2001)
    K) TRYPTOPHAN: 204.2 (Sweetman, 2001)
    L) VALINE: 117.1 (Sweetman, 2001)

Animal Toxicology

Clinical Effects

    11.1.3) CANINE/DOG
    A) Methionine is often found in veterinary urinary acidifiers. Because the formulation is often very palatable, animals may ingest these medications in great quantity.
    B) CASE REPORT - Suspected methionine toxicosis associated with a portacaval shunt has been reported in a dog (Branam, 1982).
    1) A dog developed hyperactivity, excessive drooling, mild disorientation and restlessness 4 days after receiving methionine (110 mg three times daily). In addition, elevated levels of alkaline phosphatase and SGPT, as well as hypoalbuminemia and hypoproteinemia with an abnormally low BUN value were observed. Urinalysis revealed microscopic hematuria (Branam, 1982).
    C) Motor disturbances (ataxia, circling, head pressing, and aimless pacing), abnormal aggressive or somnolent behavior have been reported following oral methionine administration to dogs. In addition, vomiting, blindness, seizures, metabolic disturbances, hepatic encephalopathy, stupor, coma and death have been reported (Branam, 1982).
    D) Toxicity is usually worse in animals with underlying hepatic insufficiency. If methionine is used in animals with hepatic insufficiency, it can cause increased production of methyl mercaptans and can precipitate clinical signs consistent with hepatoencephalopathy (Branam, 1982).
    E) CASE REPORT - After ingesting 500 dL-methionine tablets, a dog developed metabolic acidosis, seizure and coma (Personal Communication, 2002).
    11.1.6) FELINE/CAT
    A) Severe hemolytic anemia with marked increase of methemoglobin concentration and Heinz-body formation were reported in cats given dl-methionine (1 g/kg of body weight/day) for 6 to 10 days (Maede et al, 1987).

Treatment

    11.2.1) SUMMARY
    A) GENERAL TREATMENT
    1) Treatment is mainly symptomatic and supportive.
    2) ANIMAL POISON CONTROL CENTER
    a) ASPCA Animal Poison Control Center, An Allied Agency of the University of Illinois, 1717 S. Philo Rd, Suite 36, Urbana, IL 61802, website www.aspca.org/apcc
    b) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
    c) The following 24-hour phone number is available: (888) 426-4435. A fee may apply. Please inquire with the poison center. The agency will make follow-up calls as needed in critical cases at no extra charge.

Continuing Care

    11.4.1) SUMMARY
    11.4.1.2) DECONTAMINATION/TREATMENT
    A) GENERAL TREATMENT
    1) Treatment is mainly symptomatic and supportive.
    2) ANIMAL POISON CONTROL CENTER
    a) ASPCA Animal Poison Control Center, An Allied Agency of the University of Illinois, 1717 S. Philo Rd, Suite 36, Urbana, IL 61802, website www.aspca.org/apcc
    b) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
    c) The following 24-hour phone number is available: (888) 426-4435. A fee may apply. Please inquire with the poison center. The agency will make follow-up calls as needed in critical cases at no extra charge.

References

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