L-phenylalanine

Synonym(s): phenylalanine

Nutrient group: Amino acids

Sources and physiological effects

Dietary sources
The essential, aromatic amino acid L-phenylalanine is required for protein synthesis in humans and hydroxylated to L-tyrosine in the liver. L-phenylalanine is not found in its free in the diet, but occurs exclusively in bound form as a component of proteins or peptides. Pumpkin seeds, walnuts and wholemeal wheat flour are considered good vegetable sources of L-phenylalanine. Animal sources of L-phenylalanine are meat, salmon, milk and chicken eggs.
Physiological effects
Protein synthesis	Preliminary stage of the amino acid L-tyrosine
Thyroid	Hormone synthesis of thyroxine and triiodothyronine
Nervous system	Neurotransmitter synthesis (dopamine, noradrenalin and adrenalin)
Skin	Pre-cursor for the skin pigment melanin

Recommended intake

Requirement
Recommended intake	Adults: 13.7 mg/kg bw daily Infants: 68 mg/kg bw daily
Increased demands	Newborn, Vitiligo

Detailed information

L-phenylalanine – precursor for catecholamines and thyroid hormones

L-tyrosine is the precursor of the excitatory neurotransmitters dopamine, norepinephrine and adrenaline (catecholamines) as well as the thyroid hormones thyroxine and triiodothyronine and is thus involved in neurovegetative processes as well as in all metabolic processes (1). Phenylethylamine (PEA) can also be synthesized from phenylalanine by means of a one-step metabolic pathway alternative to catecholamines. PEA itself is not a catecholamine, but acts as a stimulatory neurotransmitter. It increases attention and mental activity, has a stimulating and mood-lifting effect.
The synthetically produced D-form of phenylalanine cannot be used for metabolism. Racemic mixtures of D- and L-phenylalanine are used in the treatment of pain and are also administered in depression (2).

L-phenylalanine as an adjuvant in depression and fatigue

In recent medical research, a number of health disorders are known to be due to acquired misregulation of neurotransmitter systems. Excess or deficiency of one or more neurotransmitters leads to permanent imbalances between excitatory and inhibitory activity.
In an experimental nutritively generated depletion of phenylalanine (or tyrosine), there was a demonstrated reduction of the release of the neurotransmitter dopamine in the brain (3). In healthy women whose phenylalanin/tyrosine levels were strongly reduced through diet, a decline in mood could be observed, especially when they were confronted with psychological challenges (4).
Laboratory diagnostic studies show that the PEA blood level in chronic fatigue syndrome (CFS) and depression is often greatly reduced, which is why patients can benefit from L-phenylalanine supplementation (5) (6).

Regulation of appetite and satiety in weight control

L-phenylalanine can be used as an adjuvant in comprehensive obesity treatment. L-phenylalanine supports the production of the peptide cholecystokinin (CCK), which is involved in triggering the feeling of satiety. The intake of 10 g L-phenylalanine, D-phenylalanine or a placebo 20 min before a standard meal with a known number of calories led to an increase in basal cholecystokinin levels in a human study. Participants who received L-phenylalanine consumed almost 500 kcal less than people taking placebo. In addition, the L-PA group reported a significantly higher feeling of satiety (7). In addition to regulatory mechanisms that control food intake, phenylalanine can also have a regulating effect on the basal metabolic rate (via thyroid metabolism).

Deficiency symptoms

Impact on	Symptoms
General well-being	Diminished stress resistance, depressive moods, weakness
Skin	Pigmentation disorder (vitiligo)
Nervous system	Disturbed neurotransmitter synthesis (dopamine), reduced cognitive performance
Metabolism	Negative nitrogen balance

Indications

Effect	Indication	Dosage
Physiological effects at a low intake	For dietary treatment of depressions and dates of exhaustion like chronic fatigue syndrome (CFS)	1500 - 3000 mg/d
	In individuals with lowered levels of dopamine or beta-phenylethylamine (PEA)	1500 - 3000 mg/d
	For the natural control of appetite in therapy and for obesity	1500 - 3000 mg/d
	Complementary therapy for vitiligo	1500 – 3000 mg/d mg/kg BW

Administration

General mode of administration
When	L-phenylalanine should be taken between meals
	Notes: In Phenylketonuria the body lacks a liver enzyme (phenylalanine hydroxalase) that converts phenylalanine into the amino acid tyrosine. Since phenylalanine cannot be broken down in the body, very high levels of the amino acid accumulate in the blood (>400 times higher than normal), which eventually lead to poisoning. The skin, hair and brain are particularly affected. The disease leads to a slowed mental development, it can cause brain damage, seizures and skin disorders.
Side effects
In rare cases sleep disturbances can occur.
Contraindications
Phenylketonuria, pregnancy and lactation

Interactions

Drug interactions
MAO inhibitor	An increased intake of L-phenylalanine can lead to dangerous blood pressure levels.
Antidepressants (tricyclic)	An intake of L-phenylalanine may lead to increased levels of dopamine, norepinephrine and epinephrine and should be avoided.
Opioid antagonists (naloxone)	L-phenylalanine cancels the analgesic effect of naloxone.
Nutrient interactions
Vitamins	Sufficient vitamin B₆ – levels are necessary for phenylalanine metabolism.
Amino acids	L-tryptophan, tyrosine, phenylalanine, valine, leucine and isoleucine hinder transport through the blood-brain barrier.

Description and related substances

Description

Proteinogenic, essential amino acid

Related substances

L-phenylalanine (natural form) D-phenylalanine (synthetic form)
DL-phenylalanine (racemate in drugs)

References

1) Gröber, U. 2008. Orthomolekulare Medizin. Ein Leitfaden für Apotheker und Ärzte.
2) Russell, A. L., McCarty, M.F. 2000. DL-phenylalanine markedly potentiates opiate analgesia - an example of nutrient/pharmaceutical up-regulation of the endogenous analgesia system. Med Hypotheses. 55(4):283-8.
3) Montgomery, A. J., McTavish, S. F. B. 2003. Reduction of Brain Dopamine Concentration With Dietary Tyrosine Plus Phenylalanine Depletion: An [11C]Raclopride PET Study. Am J Psychiatry 160:1887-1889.
4) Leyton, M. et al. 2000. Effects on mood of acute phenylalanine/tyrosine depletion in healthy women. Neuropsychopharmacology. 22(1):52-63.
5) Stresshormone und Neurotransmitter. Fachbroschüre 0028. GANZIMMUN - Labor für funktionelle Medizin AG, Mainz.
6) Sabelli, H. C. et al. 1986. Clinical studies on the phenylethylamine hypothesis of affective disorder: Urine and blood phenylacetic acid and phenylalanine dietary supplements. Journal of Clinical Psychiatry, 47(2):66-70.
7) Ballinger, A. B, Clark, M.L. 1994. L-phenylalanine releases cholecystokinin (CCK) and is associated with reduced food intake in humans: evidence for a physiological role of CCK in control of eating. Metabolism. 43(6):735-8.

References Interactions
Stargrove, M. B. et al. Herb, Nutrient and Drug Interactions: Clinical Implications and Therapeutic Strategies, 1. Auflage. St. Louis, Missouri: Elsevier Health Sciences, 2008.
Gröber, U. Mikronährstoffe: Metabolic Tuning –Prävention –Therapie, 3. Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2011.
Gröber, U. Arzneimittel und Mikronährstoffe: Medikationsorientierte Supplementierung, 3. aktualisierte und erweiterte Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2014.