D-phenylalanine

Phenylalanine/Drug Interactions:

  • AnalgesicsAnalgesics: In human research, D-phenylalanine has analgesic effects by inhibition of carboxypeptidase, which degrades enkephalins (10; 29).
  • Antidepressant agentsAntidepressant agents: Hypomania theoretically may occur, given that it happened with L-phenylalanine in two of 40 patients with depression in a human case series (11; 12). In combination with tricyclic antidepressants, constipation may occur, given that there was some constipation with L-phenylalanine in the case series. In combination with bupropion, insomnia may occur, given that several patients noted insomnia in the case series.
  • Antidepressant agents, monoamine oxidase inhibitors (MAOIs)Antidepressant agents, monoamine oxidase inhibitors (MAOIs): There is the theoretical possibility of the hypertensive interaction between monoamine oxidase inhibitors (MAOIs) and tyramine, given that in rabbits with prior treatment with pargyline, there was an increase in the recovery of p-tyramine after intraventricular injection of L-phenylalanine (13). However, with the combination of oral selegiline 5-10mg daily and L-phenylalanine 250mg daily, improvement occurred for unipolar depression in 90% of patients in human research (30).
  • Antipsychotic agentsAntipsychotic agents: Tardive dyskinesia worsened in severity, on the basis of the increase in total score on the Abnormal Involuntary Movement Scale at assessment 90 minutes after consumption of an experimental drink that contained L-phenylalanine 100mg/kg by men with schizophrenia in a randomized controlled trial (19).
  • BaclofenBaclofen: Dietary supplements of phenylalanine theoretically may inhibit absorption of baclofen, given that in an in situ study of the absorption of baclofen from the middle section of the small intestine of rats, when phenylalanine also was present in the solution of baclofen there was indication that baclofen and phenylalanine apparently share some carrier for absorption; as a qualitative description of the effect of the interaction on baclofen, a suitable model was complete competitive inhibition with residual absorption (43).
  • Carbidopa/levodopa (Sinemet?)Carbidopa/levodopa (Sinemet?): In human research, patients with idiopathic Parkinson's Disease who consumed a high-protein formula one time had an elimination of antiparkinson's effects with levodopa/carbidopa; however, recommended daily allowance (RDA) of protein lacked an effect on plasma levodopa levels if administered orally or intravenously (18).
  • Cardiovascular agentsCardiovascular agents: Antihypertensive drugs theoretically may be less effective, given that L-phenylalanine and D-phenylalanine have tyrosine as a metabolite, so these dietary supplements thereby are precursors of catecholamines (11; 12; 44).
  • CefdinirCefdinir: According to animal research, dietary protein and L-phenylalanine supplementation may affect the upregulation of oligopeptide transport activity potentially leading to changes in the pharmacokinetics of cefdinir; however, human research reported unchanged pharmacokinetics with cefdinir when taken after L-phenylalanine supplementation and a high-protein diet (45).
  • CNS StimulantsCNS Stimulants: In human research of D-phenylalanine for adults with ADHD, D-phenylalanine improved mood and mood changes (14). In human research of D-phenylalanine for children with ADHD, D-phenylalanine was chosen as the experimental treatment because of enhancement of action in alteration of central phenylethylamine, which hypothetically mediates the clinical effects of amphetamine and methylphenidate (37).
  • ClobetasolClobetasol: Vitiligo improved in 90.9% of patients with treatment with the combination of oral L-phenylalanine 100mg/kg daily, topical phenylalanine as a 10% gel, sunlight or irradiation with ultraviolet A, and nightly clobetasol propionate 0.025% in human research (46).
  • Cytochrome P450 metabolized agentsCytochrome P450 metabolized agents: Based on secondary sources, phenylalanine may interact with drugs metabolized by cytochrome P450.
  • ImmunomodulatorsImmunomodulators: Interactions hypothetically may occur, given that L-phenylalanine's metabolite, phenylethylamine, may inhibit synthesis of antibodies (9).
  • LevodopaLevodopa: Tremor, rigidity, weakness, and drowsiness developed with ingestion of DL-phenylalanine 4g when a patient still was on effective treatment with levodopa for Parkinson's disease in human research (4). Oral phenylalanine100mg/kg reversed the therapeutic effect from intravenous infusion of levodopa, without reduction of concentrations of levodopa in plasma, in patients with the on/off phenomenon of Parkinson's disease (20). In human research, patients with idiopathic Parkinson's Disease who consumed a high-protein formula one time had an elimination of antiparkinson's effects with levodopa/carbidopa; however, recommended daily allowance (RDA) of protein lacked an effect on plasma levodopa levels if administered orally or intravenously (18).
  • LofepramineLofepramine: A linear model of repeated measures showed a cumulative benefit over 24 weeks in favor of L-phenylalanine 500mg twice daily plus lofepramine 70mg twice daily in human research of Cari Loder's regime for multiple sclerosis; the benefit was a small improvement in score on a scale for measurement of neural disability (47). Note: Lofepramine is a tricyclic antidepressant that is unavailable in the US.
  • Sapropterin dihydrochloride (Medi-Span?)Sapropterin dihydrochloride (Medi-Span?): In human research, sapropterin dihydrochloride significantly increased phenylalanine tolerance in children with phenylketonuria (PKU) while maintaining adequate phenylalanine blood levels (48).
  • SedativesSedatives: Sedation theoretically may increase, given that mild sedation occurred with DL-phenylalanine above 600mg daily in a randomized controlled trial in adults with attention deficit hyperactivity disorder; mild sedation also occurred during the first week of DL-phenylalanine (14).

    • Phenylalanine/Herb/Supplement Interactions:

  • AcupunctureAcupuncture: D-phenylalanine enhanced the effect of acupuncture as anesthesia during extraction of a tooth in human research (10). There were 35% more patients who stated that they lacked pain (excellent result) or that they had slight pain (good result) with D-phenylalanine 2 or 4g 30 minutes before acupuncture for anesthesia.
  • Amino acidsAmino acids: Theoretically, phenylalanine and other amino acids may have additive effects when taken concomitantly. In human research, large neutral amino acid (LNAA) supplementation decreases plasma phenylalanine (49).
  • AnalgesicsAnalgesics: In human research, D-phenylalanine has analgesic effects by inhibition of carboxypeptidase, which degrades enkephalins (10; 29).
  • Antidepressant agentsAntidepressant agents: Hypomania theoretically may occur, given that it happened with L-phenylalanine in two of 40 patients with depression in human research (11; 12).
  • Antidepressant agents, monoamine oxidase inhibitors (MAOIs)Antidepressant agents, monoamine oxidase inhibitors (MAOIs): Hypomania theoretically may occur, given that it occurred with L-phenylalanine in two of 40 patients with depression in human research (11; 12).
  • AntipsychoticsAntipsychotics: Tardive dyskinesia worsened in severity, on the basis of the increase in total score on the Abnormal Involuntary Movement Scale at assessment 90 minutes after consumption of an experimental drink that contained L-phenylalanine 100mg/kg by men with schizophrenia in a randomized controlled trial (19).
  • B-12B-12: A linear model of repeated measures showed a cumulative benefit over 24 weeks in favor of Cari Loder's regimen (L-phenylalanine 500mg twice daily plus lofepramine 70mg twice daily plus weekly intramuscular vitamin B-12) in a randomized controlled trial in patients with multiple sclerosis; the benefit was a small improvement in score on a scale for measurement of neural disability (47).
  • Cardiovascular agentsCardiovascular agents: Antihypertensive agents theoretically may be less effective, given that L-phenylalanine and D-phenylalanine have tyrosine as a metabolite, so these dietary supplements thereby are precursors of catecholamines (11; 12; 44).
  • Cytochrome P450 metabolized agentsCytochrome P450 metabolized agents: Based on secondary sources, phenylalanine may interact with herbs/supplements metabolized by cytochrome P450.
  • ImmunomodulatorsImmunomodulators: According to human research, interactions hypothetically may occur, given that L-phenylalanine's metabolite, phenylethylamine, may inhibit synthesis of antibodies (9).
  • SedativesSedatives: Sedation theoretically may increase, given that mild sedation occurred with DL-phenylalanine above 600mg daily in a randomized controlled trial in adults with attention deficit hyperactivity disorder; mild sedation also occurred during the first week of DL-phenylalanine (14).

    • Phenylalanine/Food Interactions:

  • B-12B-12: A linear model of repeated measures showed a cumulative benefit over 24 weeks in favor of Cari Loder's regimen (L-phenylalanine 500mg twice daily plus lofepramine 70mg twice daily plus weekly intramuscular vitamin B-12) in a randomized controlled trial in patients with multiple sclerosis; the benefit was a small improvement in score on a scale for measurement of neural disability (47).

    • Phenylalanine/Lab Interactions:

  • CD4 countCD4 count: In human research, a combination of D-phenylalanine, L-glutamine, and L-5-hydroxytriptophan significantly increased CD4 lymphocyte count in patients with alcohol withdrawal symptoms (50).