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
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
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
- D-phenylalanine capsules
- L-phenylalanine capsules
- D,L-phenylalanine capsules (50/50 blend of D-phenylalanine and
- 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
- Inflammation: Supplementation in the form of D-phenylalanine may be
- 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.
|Dosage Ranges and Duration of
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.
- Anxiety, headaches, and hypertension are possible side effects of
- Individuals with PKU and women who are lactating or pregnant should
- 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
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)
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.
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Haas EM. Staying Healthy with Nutrition. Berkeley, Calif: Celestial
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Pietz J. Neurological aspects of adult phenylketonuria. Curr Opin Neurol.
Pietz J, Dunckelmann R, Rupp A, et al. Neurological outcome in adult patients
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Shils ME, Olson JA, Shike M, Ross AC. Modern Nutrition in Health and
Disease. 9th ed. Baltimore, Md: Williams & Wilkins; 1999:41, 1010.
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with and without phenylalanine challenges in parkinsonian patients.
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