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Phenylalanine promotes alertness and vitality, elevates mood, decreases pain, aids memory and learning, and is used to treat arthritis and depression. Phenylalanine is used by the brain to produce norepinephrine, a neurotransmitter that transmits signals between nerve cells. Phenylalanine uses an active transport channel to cross the blood-brain barrier and, in large quantities, interferes with the production of serotonin, another neurotransmitter. Phenylalanine plays a key role in the biosynthesis of other amino acids. Measurement of phenylalanine is included in the Amino Acids, Plasma and Amino Acids, Urine tests along with 23 other amino acids.

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Phenylalanine (Phe/F) is an amino acid found in mother’s milk and a number of foods, including meat, poultry, fish, cottage cheese, lentils, peanuts, and sesame seeds. Phenylalanine is an essential nutrient, but some individuals are born with a genetic disorder, phenylketonuria.

Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism, about one case per 10.000 live births in Europe, caused by absent or virtually absent phenylalanine hydroxylase (PAH) enzyme activity. This enzyme normally converts phenylalanine to tyrosine and the absence of PAH enzyme activity leads to abnormally high levels of phenylalanine and its metabolites (phenylpyruvate) in the blood, which is toxic, particularly to the brain. If not detected early and treated by dietary means (a low- phenylalanine diet) hyperphenylalaninemia causes irreversible mental retardation, delays in motor development, autism, seizures, and other symptoms, even endocrine abnormalities. Fortunately, PKU may be detected by modern newborn screening programs.

Structurally, phenylalanine is closely related to dopamine, epinephrine (adrenaline), and tyrosine. Phenylalanine is converted into tyrosine, which then becomes converted into catecholamine neurotransmitters. Consequently, supplementation with phenylalanine has been presumed to have antidepressant effects. Phenylalanine is classified as a nonpolar amino acid because of the hydrophobic nature of its benzyl side chain. Phenylalanine is part of the composition of aspartame, a common sweetener used in prepared foods as a sugar replacement.

Phenylethylamine (PEA) is metabolized from phenylalanine. It is a neurotransmitter and a hormone and may act as a neuromodulator for catecholamines. Phenylethylamine increases extracellular levels of dopamine and modulates noradrenergic transmission. Phenylethylamine also antagonizes GABA(B) receptors, suppressing their inhibitory effects. Thus, along with phenylalanine, supplementation with phenylethylamine has been presumed to have antidepressant effects.

Supplementation with phenylalanine has been recommended for decades, although few controlled studies exist to investigate claims of effectiveness. It has also been presumed to be beneficial in the pediatric population. After reviewing several studies, researchers concluded that the antidepressant effect of phenylalanine was weak but potentially useful, especially as an adjunct to prescription antidepressants.

Supplementation with phenylethylamine has also been shown to be effective in a few studies and was shown to be effective even in patients who failed to respond to prescription antidepressants.

In research studies, phenylalanine and phenylethylamine have been well tolerated with very few adverse effects, and no effects of nausea, fatigue, sleep changes, or cardiovascular effects have been observed. Both phenylethylamine and phenylalanine have been found to be activating and the supplements should generally be given in the morning.

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