Phenylalanine

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Latest Edit: Hector 2014-03-17 (EDT)

See Also Amino Acids

Phenylalanine is an essential amino acid which can be converted into other amino acids, most notably tyrosine. Through this pathway of conversion, important neurotransmitters and hormones are synthesized such as L-dopa, dopamine, epinephrine, norepinephrine, thyroxine, and melanin. Via another pathway phenylalanine is also converted into phenylethylamine which is a substance in the brain which acts as a stimulant and mood lifter and is therefore often used in the treatment of depression. Furthermore, phenylalanine is also involved in the synthesis of other important brain neuropeptides and intestinal hormones [1].

Food Sources

  • D-phenylalanine does not occur naturally in foods.
  • Aspartame (also known as NutraSweet and Equal) contains phenylalanine.

Uses

The following is a list of the primary uses for phenylalanine. [1]

Deficiency Symptoms

Phenylalanine deficiency in and of itself is quite rare; it is primarily associated with overall low protein intake. Signs and symptoms of phenylalanine deficiency may include:[1]

  • fatigue
  • confusion
  • behavioural changes
  • decreased alertness
  • impaired memory
  • poor vascular health
  • eye disorders (e.g., bloodshot eyes, cataracts)
  • changes in appetite
  • weight gain

Prescribing Considerations

  • Supplemental L-phenylalanine and DL-phenylalanine are both available.
  • Phenylalanine is available as capsules, powder, and tablets.
  • The recommended dosages varies based on age and health status. To determine what your specific requirements are talk to your naturopathic doctor or other trained medical professional.
  • Child: 125mg/kg (birth to 4 months); 69mg/kg (5 months-2 years); 22mg/kg (3-12 years)
  • Adolescent (14-18 years): 14mg/kg
  • Adult: 14mg/kg body weight (or 1g for a 70kg adult)

Safety

  • L-phenylalanine and DL-phenylalanine are generally considered safe in most individuals at typical doses. Some caution the use of DL-phenylalanine due to its affect on neurotransmitters, mood, and CNS function. Doses >1500mg/day should only be done under medical supervision.
  • Children: Testing for phenylketonuria is essential before administering phenylalanine. Sufficient research outlining the safety in children and infants is lacking.
  • Adults: The maximum safe dose is unknown and high doses may potentially be toxic. Some adverse effects may include occasional anxiety, nausea, dyspepsia, and transient headaches.
  • Pregnancy and Breastfeeding: Phenylalanine is generally contraindicated during both pregnancy and nursing.
  • Adverse Effects in Specific Populations: Phenylketonuria (PKU) is an inherited disorder which results in an error in the metabolism of phenylalanine due to a deficiency in a key enzyme. Without this enzyme, these individuals cannot convert phenylalanine into tyrosine and therefore cannot properly synthesize dopamine. This results in mental retardation, organ damage, unusual posture, and can compromise pregnancy in a woman with maternal PKU. All of this is a result of build up phenylalanine and its neurotoxic metabolites. Phenylalanine-free diets are essential to prevent the negative consequences of this condition. Individuals with severe liver disease should also be cautious and high blood levels of phenylalanine and tyrosine should be avoided.
  • Contraindications: individuals with phenylketonuria, pregnancy and nursing, cancer (especially pigmented melanoma; tyrosine) is also contraindicated), hyperthyroidism or schizophrenia.
  • Precautions: L-phenylalanine should not be taken with other foods high in protein; the use of phenylalanine-containing aspartame is generally contraindicated in individuals with PKU and also may be contraindicated in Parkinson's disease.

Drug Interactions

Drug interactions include:[1]

Supportive or Beneficial:
  • Levodopa (L-dopa) - Phenylalanine is the precursor to L-dopa and therefore may be beneficial. However, separate intake is necessary as phenylalanine and levodopa compete for CNS transport when taken simultaneously. Separate intake by several hours.
  • Methadone, Morphine and Related Oral Narcotic Analgesics (Opiates) - D-phenylalanine may increase circulating enkephalins by inhibiting breakdown thereby enhancing the analgesic effect. Close monitoring and active management necessary.
  • Selegiline, Phenylethylamine, and Monoamine Oxidase (MAO-B) Inhibitors - Preliminary research indicates that co-administration of selegiline and phenylalanine (in the D or combined DL forms) may reduce necessary therapeutic dosage of the MAO inhibitor, thereby decreasing the risk of drug-induced adverse effects. Medical supervision and active management is necessary.
Contraindicated:
  • Naloxone - Drug may inhibit D-phenylalanine's analgesic effect. Avoid concomitant use.
  • Phenothiazine and Butyrophenone Typical Antipsychotic (Neuroleptic) Medications - Concomitant use with neuroleptics might increase risk of drug-induced tardive dyskinesia. Avoid concomitant intake.
Separate Intake:
  • Baclofen - Avoid simultaneous intake of phenylalanine and high-protein meals due to impaired drug absorption. Separate intake by 2-4 hours.

Nutrient Interactions

Nutrient interactions include:[1]

  • Branched-Chain Amino Acids: Isoleucine, leucine, and valine - Branched-chain amino acids compete with phenylalanine for transport across the blood-brain barrier. Separate intake of phenylalanine and branched-chaine amino acids/high-protein meals by at least 2 hours.
  • Vitamin B6 - L-phenylalanine activity is enhanced by simultaneous administration of B6 especially in treatment of depression.
  • Tyrosine - Because of the possible additive effect, avoid unmonitored concomitant administration in the treatment of depression. Food sources containing both are generally considered safe at usual levels of intake.

References

  1. 1.0 1.1 1.2 1.3 1.4 Stargrove Mitchell Bebell, Treasure Jonathan, McKee Dwight L (2008) Herb, Nutrient, and Drug Interactions, Clinical Implications and Therapeutic Strategies. Mosby