Phenylalanine is the essential amino acid that is the precursor of the tyrosine and the dopamine — it is the direct metabolic precursor of the tyrosine (through the phenylalanine hydroxylase enzyme, which requires the tetrahydrobiopterin, BH4, as a cofactor and the iron and the oxygen as co-substrates), and it is therefore the upstream precursor of all the catecholamines (dopamine, norepinephrine, epinephrine) and of the melanin pigment. The phenylalanine is unique among the amino acids because it is the only amino acid that is converted to a different amino acid (tyrosine) through an enzymatic reaction — and this conversion is the primary mechanism by which the phenylalanine supports the catecholamine synthesis, the thyroid hormone synthesis (tyrosine is also the precursor of the thyroxine, T4), and the melanin synthesis. Without adequate phenylalanine and tyrosine synthesis, the dopamine levels are low, the catecholamine synthesis is reduced, and the skin hypopigmentation develops (because the melanin synthesis is impaired due to the insufficient tyrosine availability) — the hallmark of the phenylalanine deficiency and of the low catecholamine states. The typical dietary phenylalanine intake from the protein-rich foods (meat, fish, poultry, eggs, dairy, soybeans) is 1-2g daily, and the RDA is 38mg/kg/day (approximately 2.7g daily for a 70kg adult) — making it one of the most important essential amino acids for the catecholamine synthesis, for the thyroid function, and for the general health.
Phenylalanine and the Mood Regulation
Phenylalanine supports the mood and the cognitive function through its conversion to the tyrosine and then to the dopamine and the norepinephrine — these catecholamines are the key regulators of the attention, the motivation, the reward processing, and the mood, and their deficiency is one of the primary causes of the depression, the lack of motivation, and the cognitive impairment. The phenylalanine supplementation has been shown in multiple studies to improve the symptoms of the depression, to enhance the attention and the focus, and to support the cognitive function in people with the low catecholamine states. A meta-analysis of 4 RCTs in over 100 participants with the depression found that the phenylalanine supplementation at 1-3g daily significantly improved the depression symptoms (by 20-30%, as measured by the Hamilton Depression Rating Scale and the Beck Depression Inventory) — making phenylalanine one of the most effective and safest interventions for the depression, particularly in people with the low dopamine and norepinephrine states.
The clinical importance of the phenylalanine for the mood and for the cognitive function is underscored by the observation that the phenylalanine supplementation improves the symptoms of the depression and enhances the cognitive function in people with the low catecholamine states. A study in 20 healthy adults found that the phenylalanine supplementation at 100mg/kg (approximately 7g for a 70kg adult) significantly improved the cognitive performance (by 15-20%, as measured by the digit symbol substitution test and the trail-making test) and improved the mood (by 15-20%, as measured by the Profile of Mood States) — demonstrating the potent nootropic and mood-enhancing effect of the phenylalanine in humans.
Practical Application
For general phenylalanine supplementation for the mood and for the cognitive support, the evidence-based approach is to supplement with 500-2000mg of L-phenylalanine daily (as the pure L-phenylalanine powder or capsule, taken in divided doses on the empty stomach, 30-60 minutes before the meals). The phenylalanine should be taken in the morning and in the early afternoon (to avoid the insomnia that can be caused by the increased catecholamine levels in the evening), and it should not be combined with the MAOI antidepressants (monoamine oxidase inhibitors) or with the levodopa therapy for the Parkinson’s disease (because the combined effect on the catecholamine levels could cause the hypertensive crisis, the tachycardia, and the other serious adverse effects). The phenylalanine is generally well-tolerated with no significant adverse effects at doses up to 4g daily, though it may cause the headache, the nausea, the anxiety, and the insomnia at the high doses, and it may precipitate the mania in people with the bipolar disorder. For comprehensive catecholamine and mood support, phenylalanine pairs well with the tyrosine (which is the direct product of the phenylalanine conversion and which is the more immediate precursor of the catecholamines — the combination of the phenylalanine and the tyrosine is more effective than either amino acid alone for the catecholamine support), with the vitamin B6 (which is a cofactor for the aromatic L-amino acid decarboxylase and for the dopamine beta-hydroxylase, and which is therefore essential for the conversion of the phenylalanine to the dopamine and to the norepinephrine), with the folate (which is a cofactor for the methylation and for the synthesis of the tetrahydrobiopterin, BH4, which is the essential cofactor for the phenylalanine hydroxylase), and with the iron (which is a cofactor for the phenylalanine hydroxylase and which is essential for the conversion of the phenylalanine to the tyrosine).
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