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L-Phenylalanine
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L-phenylalanine is a protein amino acid. It is classified as an essential amino acid because the body requires a dietary source of the amino acid to meet its physiological demands. L-phenylalanine is found in proteins of all life forms. Dietary sources of the amino acid are principally derived from animal and vegetable proteins. Vegetables and juices contain small amounts of the free amino acid. The free amino acid is also found in fermented foods such as yogurt and miso. The alternative sweetener aspartame is a dipeptide of L-phenylalanine, as is the methyl ester, and L-aspartic acid.
In addition to being involved in protein synthesis, L-phenylalanine is the precursor of L-tyrosine. The conversion of L-phenylalanine to L-tyrosine is via the enzyme L-phenylalanine hydroxylase. It is this enzyme that is virtually absent in those with the inborn error of metabolism phenylketonuria (PKU). L-tyrosine produced from L-phenylalanine is a precursor in the synthesis of the neurotransmitters norepinephrine and dopamine, among other reactions. L-phenylalanine is marketed as a nutritional supplement and used by some for its putative antidepressant activity.
L-phenylalanine is also known as beta-phenylalanine, alpha-aminohydrocinnamic acid, (S)-2-amino-3- phenylpropanoic acid and alpha-amino-beta-phenylpropionic acid. It is abbreviated as either Phe or by its one-letter abbreviation F. The molecular formula of L-phenylalanine is C9H11NO2, and its molecular weight is 165.19 daltons. L-phenylalanine is an aromatic amino acid with the following structural formula:
ACTIONS AND PHARMACOLOGY
ACTIONS
L-phenylalanine has putative antidepressant activity. It may also, when used in conjunction with UVA irradiation, have antivitiligo activity.
MECHANISM OF ACTION
The mechanism of L-phenylalanine's putative antidepressant activity may be accounted for by its precursor role in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated brain norepinephrine and dopamine levels are thought to be associated with antidepressant effects.
The mechanism of L-phenylalanine's possible antivitiligo activity is not well understood. It is thought that L-phenylalanine may stimulate the production of melanin in the affected skin.
PHARMACOKINETICS
Following ingestion, L-phenylalanine is absorbed from the small intestine by a sodium dependent active transport process. L-phenylalanine is transported from the small intestine to the liver via the portal circulation. In the liver, L-phenylalanine is involved in a number of biochemical reactions, including protein synthesis, the formation of L-tyrosine and oxidative catabolic reactions. L-phenylalanine that is not metabolized in the liver is distributed via the systemic circulation to the various tissues of the body, where it undergoes metabolic reactions similar to those that take place in the liver.
INDICATIONS AND USAGE
L-phenylalanine may be helpful in some with depression. It may also be useful in the treatment of vitiligo. There is some evidence that L-phenylalanine may exacerbate tardive dyskinesia in some schizophrenic patients and in some who have used neuroleptic drugs.
RESEARCH SUMMARY
Both oral and intravenous administration of L-deprenyl and L-phenylalanine in doses of 5 to 10 milligrams and 250 milligrams per day, respectively, demonstrated significant antidepressant effects in 155 unipolar depressed patients. In another preliminary study, L-phenylalanine was said to have mood-elevating effects in 31 of 40 depressed subjects. Followup is needed.
Several clinical studies have shown that L-phenylalanine may be helpful in the treatment of vitiligo in both children and adults. L-phenylalanine, in doses up to 100 mg/kg/day significantly improved vitiligo in 200 subjects when combined with UVA/sunlight. Best results were achieved in early-stage disease, but significant repigmentation occurred in some with later-stage disease who used the supplement/sunlight combination for prolonged periods. Another study confirmed these effects but found that no added benefit was derived from doses exceeding 50 mg/kg/day.
Recently, other researchers have reported on their six-year experience in treating vitiligo with L-phenylalanine in combination with daily sun exposure. Subjects treated by these researchers received oral L-phenylalanine 50 or 100 mg/kg/day plus topical 10% phenylalanine gel daily. The total average improvement rate was rated at 83.1%, but the improvement rate limited to those judged to have good response was 56.7%, with a 90.3% rate for the face, 42.8% for the trunk and 37.1% for the limbs. This uncontrolled, retrospective study involved 193 patients, male and female, children and adults, with evolving vitiligo of various types. There was no statistically significant difference in response rates between those who received 50 mg/kg/day versus those receiving 100 mg/kg/day or between children and adults.
On the negative side, there is a report that a loading dose of 100 mg/kg of L-phenylalanine exacerbated symptoms of tardive dyskinesia in some neuroleptic-treated depressives. In another study, the same L-phenylalanine challenge exacerbated tardive dyskinesia symptoms in schizophrenic subjects.
CONTRAINDICATIONS, PRECAUTIONS, ADVERSE REACTIONS
CONTRAINDICATIONS
L-phenylalanine is contraindicated in those with phenylketonuria. It is also contraindicated in those taking non-selective monoamine oxidase (MAO) inhibitors. L-phenylalanine is contraindicated in those hypersensitive to any component of an L-phenylalanine-containing supplement.
PRECAUTIONS
Pregnant women and nursing mothers should avoid supplementation with L-phenylalanine.
Tardive dyskinesia has been reported to be exacerbated after ingestion of L-phenylalanine by schizophrenics. Therefore, those with schizophrenia should exercise extreme caution in the use of supplemental L-phenylalanine.
Use of L-phenylalanine for vitiligo must be done under medical supervision.
Those with hypertension should exercise caution in the use of L-phenylalanine.
ADVERSE REACTIONS
L-phenylalanine will exacerbate symptoms of phenylketonuria if used by phenylketonurics. L-phenylalanine was reported to exacerbate tardive dyskinesia when used by some with schizophrenia.
INTERACTIONS
DRUGS
Non-selective monoamine oxidase (MAO) inhibitors: including phenelzine sulfate, tranylcypromine sulfate and pargyline HC1 ?Concomitant use of L-phenylalanine and non-selective MAO inhibitors may cause hypertension.
Selegiline: L-phenylalanine and the selective MAO inhibitor selegiline may have synergistic antidepressant activity if used concomitantly.
Neuroleptic Drugs: L-phenylalanine may potentiate the tardive dyskinesia side reactions of neuroleptic drugs if used concomitantly with them.
OVERDOSAGE
There are no reports of Phenylalanine overdosage in the literature.
DOSAGE AND ADMINISTRATION.
L-phenylalanine supplements as well as DL-phenylalanine (see DL-Phenylalanine) supplements are available in the nutritional supplement marketplace. Those who use L-phenylalanine supplements typically use 500 milligrams to 1.5 grams daily.
HOW SUPPLIED
Capsules ?200 mg, 500 mg, 600 mg
Powder
Tablets ?500 mg
LITERATURE
Birkmayer W, Riederer P, Linauer W, Knoll J. L-deprenyl plus L-phenylalanine in the treatment of depression. J Neural Transm. 1984; 59:81-87.
Camacho F, Mazuecos J. Treatment of vitiligo with oral and topical phenylalanine: 6 years of experience. Arch Dermatol. 1999; 135:216-217.
Gardos G, Cole JO, Matthews JD, et al. The acute effects of a loading dose of phenylalanine in unipolar depressed patients with and without tardive dyskinesia. Neuropsychopharmacology. 1992; 6:241-247.
Gibbs J, Falasco JD, McHugh PR. Cholecystokinin-decreased food intake in rhesus monkeys. Am J Physiol. 1976; 230:15-18.
Kostiuk PG, Martyniuk AE. [Possible molecular mechanisms of brain dysfunction in phenylketonuria.] [Article in Russian.] Patol Fiziol Eksp Ter. 1992; Jul-Aug(4):34-36.
Kuiters GR, Hup JM, Siddiqui AH, Cormane RH. Oral phenylalanine loading and sunlight as source of UVA irradiation in vitiligo on the Caribbean island of Curacao. J Trop Med Hyg. 1986; 89:149-155.
Mosnik DM, Spring B, Rogers K, Baruah S. Tardive dyskinesia exacerbated after ingestion of phenylalanine by schizophrenic patients. Neuropsycopharmacology. 1997; 16:136-146.
Sabelli HC, Fawcett J, Gusovsky F, et al. Clinical studies on the phenylalanine hypothesis of affective disorder: urine and blood phenylacetic acid and phenylalanine dietary supplements. J Clin Psychiatry. 1986; 47:66-70.
Schulpis CH, Antoniou C, Michas T, Starigos J. Phenylalanine plus ultraviolet light: preliminary report of a promising treatment for childhood vitiligo. Pediatr Dermatol. 1989; 6:332-335.
Siddiqui AH, Stolk LM, Bhaggoe R, et al. L-phenylalanine and UVA irradiation in the treatment of vitiligo. Dermatology. 1994; 188:215-218.
Zhao G. [Inherited metabolic aberration of phenylalanine in the family members of patients with essential hypertension and stroke]. [Article in Chinese]. Chung Hua I Hsueh Tsa Chih. 1991; 71:388-390.
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