Phenylalanine: benefits, dosage, contraindications

Updated on 19 March 2025

Phenylalanine is an essential amino acid that the human body cannot synthesize and must therefore be obtained through the diet. It is naturally found in many protein-rich foods, such as meats, eggs, dairy products, legumes, and certain algae. Phenylalanine is the precursor of several essential biologically active molecules, including tyrosine, which is the source of neurotransmitters like dopamine, norepinephrine, and adrenaline. This amino acid exists in two main forms: L-phenylalanine, present in foods, and D-phenylalanine, produced synthetically and used for therapeutic purposes. A version called DL-phenylalanine (DLPA) combines both forms and is often offered as a dietary supplement. Phenylalanine plays a key role in protein synthesis and mood regulation. In fact, L-phenylalanine is metabolized into tyrosine, which contributes to the production of neurotransmitters related to alertness and well-being. D-phenylalanine appears to modulate natural opioid systems, which can have an impact on pain management. However, for individuals with phenylketonuria (PKU), a genetic disorder that prevents the metabolism of phenylalanine, the accumulation of this amino acid can lead to toxic effects, including neurological damage. In these cases, a strictly controlled and low-phenylalanine diet is essential. When used in supplementation, phenylalanine is sometimes studied for its effects on vitiligo, depression, and pain management.

Other name(s)

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Amino acids

Indications

Rating methodology

EFSA approval.

Several clinical trials (> 2) randomized controlled with double blind, including a significant number of patients (>100) with consistently positive outcomes for the indication.

Several clinical trials (> 2) randomized controlled with double blind, and including a significant number of patients (>100) with positive outcomes for the indication.

One or more randomized studies or multiple cohorts or epidemiological studies with positive outcomes for the indication.

Clinical studies exist but are uncontrolled, with conclusions that may be positive or contradictory.

Lack of clinical studies to date that can demonstrate the indication.

Skin health
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In the treatment of vitiligo, oral administration of L-phenylalanine at doses ranging from 50 to 100 mg/kg per day, combined with UVA exposure, has shown promising results for restoring skin pigmentation. Treatment duration varies from 3 to 6 months. Topical application of cream containing 10% L-phenylalanine combined with phototherapy also improves symptoms in children and adults. Moreover, a cream containing 2% undecylenoyl phenylalanine applied twice a day for 12 weeks effectively reduces pigmentation of age spots, confirming phenylalanine's benefit in skin health.

Posologie

Topical

cream

Oral phenylalanine loading and sunlight as source of UVA irradiation in vitiligo on the Caribbean island of Curacao NA
A randomized, double-blind, vehicle-controlled study of a preparation containing undecylenoyl phenylalanine 2% in the treatment of solar lentigines

Depression
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Preliminary clinical studies indicate that L-phenylalanine could be beneficial in treating depression. This mechanism is based on its role as a precursor to neurotransmitters such as dopamine and norepinephrine, essential for mood regulation. A study showed that a supplementation of 250 mg per day of L-phenylalanine, in combination with standard treatment, significantly improves depressive symptoms in 80 to 90% of patients. However, most studies are old and require further research to confirm these results and optimize dosages.

Posologie

Oral

250 mg

Dl-phenylalanine in depressed patients: an open study

Properties

Antidepressant

Phenylalanine, particularly L-phenylalanine, acts as a precursor to neurotransmitters such as dopamine and norepinephrine, whose increased levels are known to improve mood. It also promotes the production of 2-phenylethylamine, a neuromodulator associated with stimulating effects on attention and well-being. These mechanisms explain its potential role in treating depressive symptoms, although clinical data remain limited.

Usages associés

Depression

The subjective and cognitive effects of acute phenylalanine and tyrosine depletion in patients recovered from depression

Analgesic

D-phenylalanine works by inhibiting carboxypeptidase, an enzyme that normally degrades enkephalins, natural opioids involved in pain control. This action would prolong the analgesic effect of enkephalins, thus increasing the pain tolerance threshold. The effects observed in humans are, however, variable and require further study.

Analgesic effectiveness of D-phenylalanine in chronic pain patients

Safety dosage

Adult:

L-phenylalanine: Doses ranging from 250 mg to 100 mg/kg per day, used for a maximum of 3 months. D-phenylalanine: Doses of 50 mg to 1 g per day, administered over a period of 2 to 4 weeks. DL-phenylalanine: Doses of 50 to 200 mg per day, over a period of 2 to 4 weeks. Topical route: Cream containing 10% L-phenylalanine or 2% undecylenoyl phenylalanine, applied to the skin.

Interactions

Médicaments

Levodopa: strong interaction

Phenylalanine competes with levodopa for transport into the brain.

Precautions

Pregnant woman: avoid

Pregnant women with elevated phenylalanine levels in the blood should avoid L-phenylalanine, as high levels increase the risk of congenital malformations.

Breastfeeding woman: avoid

Avoid medicinal doses of L- or D-phenylalanine, in the absence of reliable information on their safety during breastfeeding.

Contraindications

Phenylketonuria: prohibited

Individuals with hereditary metabolic disorders should avoid phenylalanine supplements due to the toxic accumulation of this amino acid, which can lead to developmental delays, hypertension, and a risk of stroke.

Schizophrenia: prohibited

L-phenylalanine may worsen tardive dyskinesias in schizophrenic individuals. Special caution is needed in this case.

Conseil scientifique