Phenylalanine is an essential amino acid that is not synthesized in adequate amounts by the body, so it must be obtained from dietary sources. In healthy individuals, phenylalanine is converted by the body into tyrosine. Tyrosine is the parent compound for the manufacturing of the hormones norepinephrine and epinephrine by the adrenal medulla and of the hormones thyroxine and triiodothyronine by the thyroid gland. In adults, approximately 90% of the recommended dietary allowance (RDA) of phenylalanine is hydroxylated to form tyrosine. The remaining 10% is used for tissue protein synthesis. In children, 60% of the RDA is used for tissue protein synthesis, and the remaining 40% is hydroxylated to form tyrosine.

The inability to convert excess phenylalanine to tyrosine is the underlying cause of phenylketonuria (PKU), the most common metabolic genetic defect. PKU is actually a group of inherited disorders involving phenylalanine metabolism. Patients with PKU have one or more of a number of enzyme defects associated with a corresponding recessive gene. The disease appears in infants 3 to 6 months old. As it must be treated before 3 months of age, PKU screening is done during the first 48 hours of life. The incidence of PKU is approximately 1 in 10,000 Caucasian infants and 1 in 132,000 African-American infants. Mental retardation, usually severe, is the primary manifestation of untreated PKU. Other manifestations may include seizures, muscular hypertonicity, exaggerated tendon reflexes, tremors, and hyperactivity. A skin condition similar to eczema occurs in 15% to 20% of untreated patients.

Treatment for PKU-positive patients is a phenylalanine-restricted, tyrosine-supplemented diet to maintain adequate blood phenylalanine levels for optimum brain development and growth. There is some disagreement about whether these diets can be discontinued without adverse effect and, if so, at what age. Some studies have shown significant differences in mental functioning, in both performance and intelligence, between those who have discontinued the diet and those who have maintained the diet. In adults who have discontinued the diet, severe agoraphobia has been reported, which is reversible with a return to the phenylalanine-restricted diet.

Pregnant women with PKU that is untreated at the time of conception and during gestation give birth to infants with poor intrauterine growth, microcephaly, and congenital abnormalities that are often severe.

Symptoms of phenylalanine deficiency may include confusion, emotional agitation, depression, decreased alertness, decreased memory, behavioral changes, decreased sexual interest, bloodshot eyes, and cataracts. If not corrected by supplemental dietary phenylalanine and tyrosine, the deficiency may lead to restricted weight gain and stunted growth, osteopenia, anemia, alopecia, and even death.

Aspartame (Nutrasweet), the synthetic sweetener, is formed by combining phenylalanine and aspartic acid. The FDA maintains that it is safe; however, there continues to be controversy over its use, and relatively little is known about its effect during pregnancy in the general population.

Generally, phenylalanine is found in cheeses; nuts and seeds; milk chocolate; meat (excluding fat), particularly organ meats; poultry (excluding skin); fish, including shellfish; milk; and eggs. The most concentrated sources are torula yeast, soybean protein isolate, soybean protein concentrate, peanut flour, dried spirulina seaweed, defatted and low-fat soybean flour, dried and salted cod, defatted soy meal, dried and frozen tofu, Parmesan cheese, almond meal, dry roasted soybean nuts, dried watermelon seeds, and fenugreek seeds.

Phenylalanine is an essential amino acid. It is also known as PHA, PHE, amino acid F, and 2-amino-3-phenyl propanoic acid. Its chemical composition is C9H11NO2.

• D-phenylalanine capsules
• L-phenylalanine capsules
• D,L-phenylalanine capsules (50/50 blend of D-phenylalanine and L-phenylalanine)
• Topical creams

• Cancer: Restriction of phenylalanine and tyrosine may help decrease tumor growth and metastasis, particularly in malignant melanoma.
• Depression: L-phenylalanine has been used in treating bipolar disorders with both manic and depressive states combined with vitamins B6 and D.
• Inflammation: Supplementation in the form of D-phenylalanine may be beneficial.
• Multiple sclerosis: Supplementation has been shown to improve bladder control, increase mobility, and ameliorate depression.
• Pain: Supplementation has been effective for chronic pain, particularly for osteoarthritis; use in doses of 250 mg 15 to 30 minutes before meals tid for a period of at least two days and up to three weeks.
• Parkinson's disease: Supplementation in the form of D-phenylalanine may reduce rigidity, walking disabilities, and speech difficulties.
• Rheumatoid arthritis: Supplementation in the form of D,L-phenylalanine was shown to be beneficial in one study.
• Vitiligo: Beneficial effects have been shown given treatment with oral L-phenylalanine, topical cream containing 10% phenylalanine, and ultraviolet A radiation.

The following are the recommended dietary allowances for phenylalanine plus tyrosine, according to the National Research Council.

• Birth to 4 months: 125 mg/kg/day
• 5 months to 2 years: 69 mg/kg/day
• 3 to 12 years: 22 mg/kg/day
• Adults and teenagers: 14 mg/kg/day

Based on obligatory amino acid losses (including data from amino acid tracer studies), it has been suggested that adults need 39 mg/kg/day.

Nutritional doses are 0.75 to 2 g per day; therapeutic doses are 2 to 3 g per day; experimental doses are 4 to 5 g per day.

See "Warnings/Contraindications/Precautions"

• Anxiety, headaches, and hypertension are possible side effects of supplementation.
• Individuals with PKU and women who are lactating or pregnant should avoid supplementation.
• L-dopa competes with phenylalanine and should not be taken at the same time of day.
• Little is known about the use of aspartame (Nutrasweet) during pregnancy.

In situ, phenylalanine (up to 100 mM) decreased the absorption of isotonic perfusion solutions of baclofen (0.5 mM) in the rat small intestine by 67% (Cejudo-Ferragud et al. 1996). To maximize absorption of the drug, baclofen should not be administered with meals, especially meals high in protein content.

Infusion of L-phenylalanine prior to administration of 3-O-methyl-6-[18F]fluoro-L-DOPA (18F-DOPA) prevented 18F-DOPA uptake in the brain (Doudet et al. 1992). L-phenylalanine improved specific-to-non-specific contrast images of 18F-DOPA during positron emission tomography (PET) scanning.

Administration of levodopa (1 mg/kg/hour IV) following administration of phenylalanine (100 or 200 mg/kg po) in two patients with advanced Parkinson's disease altered the clinical effects of the drug (Woodward, et al. 1998). The therapeutic response to levodopa could be diminished when administered at the same time as phenylalanine.

Bugard P, Bremer HJ, Buhrdel P, et al. Rationale for the German recommendations for phenylalanine level control in phenylketonuria 1997. Eur J Pediatr. 1999;158:46-54.

Cejudo-Ferragud E, Nacher A, Polache A, Cercos-Fortea T, Merino M, Casabo VG. Evidence of competitive inhibition for the intestinal absorption of baclofen by phenylalanine, Int J of Pharm (Amsterdam). 1996;132:63-69.

Doudet D, McLellan CA, Aigner TG, Wyatt RJ, Cohen RM. Delayed L-phenylalanine infusion allows for simultaneous kinetic analysis and improved evaluation of specific-to-non-specific fluorine-18-DOPA uptake in brain. J of Nucl Med. 1992;33(7):1383-1389.

Ensminger AH, Ensminger ME, Konlande JE, Robson JRK. Foods & Nutrition Encyclopedia. 2nd ed. Boca Raton, Fla: CRC Press, Inc; 1994:60-64, 1748.

Garrison RH Jr, Somer E. The Nutrition Desk Reference. 3rd ed. New Canaan, Conn: Keats Publishing, Inc; 1995:39-52.

Haas EM. Staying Healthy with Nutrition. Berkeley, Calif: Celestial Arts Publishing; 1992.

Herbert V, Subak-Sharpe GJ, eds. Total Nutrition (Mount Sinai School of Medicine). New York, NY: St. Martin's Press; 1995:318-320.

Newstrom H. Nutrients Catalog. Jefferson, NC: McFarland & Co; 1993:303-312.

Pietz J. Neurological aspects of adult phenylketonuria. Curr Opin Neurol. 1998;11:679-688.

Pietz J, Dunckelmann R, Rupp A, et al. Neurological outcome in adult patients with early-treated phenylketonuria. Eur J Pediatr. 1998;157:824-830.

Shils ME, Olson JA, Shike M, Ross AC. Modern Nutrition in Health and Disease. 9th ed. Baltimore, Md: Williams & Wilkins; 1999:41, 1010.

Start K. Treating phenylketonuria by a phenylalanine-free diet. Prof Care Mother Child. 1998;8:109-110.

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.

Woodward, WR, Olanow CW, Beckner Rm et al. The effect of L-dopa infusions with and without phenylalanine challenges in parkinsonian patients. Neurol. 1998;48:1704-1708.