Phenylalanine

Common Names: L-Phenylalanine; D,L-Phenylalanine, DLPA; Phenylethylamine

Clinical Name: Phenylalanine

Summary

Phenylalanine

forms: L-Phenylalanine, D,L-Phenylalanine (DLPA); Phenylethylamine

overview of interactions:

• nutrient affecting drug performance: L-Dopa

• nutrient affecting drug performance: Phenylethylamine and Selegiline (Deprenyl®)

chemistry/function:
• L-phenylalanine is an essential amino acid that plays a key role in the biosynthesis of other amino acids, including L-tyrosine, and related biochemical processes involving the synthesis of several important neurotransmitters, principally L-dopa, dopamine, epinephrine and norepinephrine. Through a different metabolic pathway, L-phenylalanine can also be converted to phenylethylamine. Phenylethylamine is a naturally occurring substance in the brain that appears to elevate mood. Along with another amino acid, tryptophan, phenylalanine also governs the release of cholecystokinin, an intestinal hormone also known as CCK.
• D-phenylalanine, the mirror image of L-phenylalanine, does not occur naturally in the body. Further, it does not feed into the process of synthesizing L-tyrosine, L-dopa, or norepinephrine.
• DLPA is a mixture of the essential amino acid L-phenylalanine and its mirror image D-phenylalanine. DLPA does not occur naturally in the body.

dietary sources: Cheese and meats are the richest dietary sources of phenylalanine with most foods containing proteins providing some L-phenylalanine. D-phenylalanine does not normally appear in foods.

deficiency: there is some potential for deficiency in individuals with very low in protein. However, this is considered to be very uncommon. Deficiency is reported to cause bloodshot eyes, cataracts and behavioral changes.

known or potential therapeutic uses:
• L-phenylalanine: Appetite suppression, depression, vitiligo.
• D-phenylalanine: Osteoarthritis, Parkinson’s disease, rheumatoid arthritis, and pain from a variety of causes, such as chronic back pain, dental pain, menstrual cramps and migraines.
• DLPA: Alcohol withdrawal, depression, rheumatoid arthritis, and pain from a variety of causes (due to the action of D-phenylalanine).

mechanism: L-phenylalanine plays a key role in the synthesis of several neurotransmitters, principally L-dopa, dopamine, epinephrine and norepinephrine. D-phenylalanine is a non-nutrient amino acid that has been shown to inhibit the breakdown of enkephalins, opiate-like substances in the brain. The analgesic effect of D-phenylalanine is inhibited by nalaxone.

maintenance dose: Usually not necessary. Optimal levels of intake have not been established.

therapeutic dose:
• L-phenylalanine is commonly provided in doses of 500 mg, typically taken 1-3 times daily,
preferably between meals.
• DLPA is the most commonly used form of phenylalanine used as a supplement, typically in dosages ranging from 75 mg to 1,500 mg per day. DLPA generally comes in capsules containing 375-750 mg with 50% D-phenylalanine and 50% L-phenylalanine. One to two capsules are usually taken in the morning upon waking, preferably on an empty stomach. Doses used in research on pain relief were 4 g before an acute painful episode, such as surgery, or 500 mg three times daily for chronic pain.
(Bucci LR. 43-44, 1994.)

Note: L-phenylalanine activity is enhanced by simultaneous consumption of 20 -30 mg of vitamin B6, especially in the treatment of depression.

side effects: DLPA has been reported to cause anxiety, occasional heartburn, nausea, and transient headaches in some individuals. L-phenylalanine should not be taken with foods high in protein since it competes with other amino acids for a position on the same amino acid carrier.

toxicity: No toxicities have been reported or suspected as being associated with phenylalanine.
Experienced practitioners of nutritional medicine generally caution that supplemental dosages of various forms of phenylalanine should never exceed 2400 mg per day. Concern has also been raised that prolonged use of any D isomer amino acid may eventually exert a toxic effect.

contraindications:
• Contraindicated during pregnancy or while nursing.
• Phenylalanine should not be taken by phenylketonurics as they lack the enzyme necessary to metabolize phenylalanine.
• Phenylalanine should be used with caution by people with hypertension, as it may raise blood pressure in some individuals.
• Phenylalanine should be avoided by individuals with cancer, especially pigmented melanoma.
• Use of phenylalanine may be contraindicated for individuals with hyperthyroidism or schizophrenia.
• Some sources suggest that phenylalanine should be avoided by individuals taking MAO inhibitors, presumably due to L-phenylalanine's role in synthesis of dopamine, norepinephrine and epinephrine. However, this potential for an adverse interaction has not been substantiated by clinical studies and, in fact, some research points to synergistic value of such a combination.



Interactions

nutrients affecting drug performance: L-Dopa

• mechanism: L-Tyrosine is a semi-essential amino acid that converts to L-Dopa. Phenylalanine is a precursor of L-tyrosine.

• nutritional concerns: Supplementation of L-tyrosine, or its precursor phenylalanine, may serve as a valuable adjunctive therapy in the treatment of Parkinson's disease or similar conditions. However, such supplementation by individuals using Levodopa may raise levels of L-Dopa to undesirably high levels. Anyone taking Levodopa should consult the prescribing physician and/or a nutritionally-oriented doctor regarding the issue of supplementation with either of these amino acids. Nutritionally-oriented physicians will want to closely monitor the L-Dopa levels of any individual using these substances together.

• nutrient affecting drug performance: Phenylethylamine and Selegiline (Deprenyl®)

research: Sabelli and Javaid have suggested that administration of phenylethylamine or of its precursor L-phenylalanine improves mood in depressed patients treated with a selective monoamine oxidase B inhibitor.
(Sabelli HC, Javaid JI. Neuropsychiatry Clin Neurosci. 1995 Winter;7(1):6-14; Sabelli HC. J Clin Psychiatry. 1991 Mar;52(3):137.)

Please read the disclaimer concerning the intent and limitations of the information provided here.
Do not rely solely on the information in this article.

The information presented in Interactions is for informational and educational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, case reports, and/or traditional usage with sources as cited in each topic. The results reported may not necessarily occur in all individuals and different individuals with the same medical conditions with the same symptoms will often require differing treatments. For many of the conditions discussed, treatment with conventional medical therapies, including prescription drugs or over-the-counter medications, is also available. Consult your physician, an appropriately trained healthcare practitioner, and/or pharmacist for any health concern or medical problem before using any herbal products or nutritional supplements or before making any changes in prescribed medications and/or before attempting to independently treat a medical condition using supplements, herbs, remedies, or other forms of self-care.


References

Anonymous. Phenylalanine fails to help chronic back pain patients. Family Pract News 1987;17(3):37.

Boulton AA. Phenylethylaminergic modulation of catecholaminergic neurotransmission. Prog Neuropsychopharmacol Biol Psychiatry. 1991;15(2):139-156. (Review)

Bucci LR. Nutrition Applied to Injury Rehabilitation and Sports Medicine. CRC Press, 43-44, 1994.

Budd K. Use of D-phenylalanine, an enkephalinase inhibitor, in the treatment of intractable pain. Adv Pain Res Ther 1983;5:305-308.

Fischer E, Heller B, Nachon M, Spatz H. Therapy of depression by phenylalanine. Preliminary note. Arzneimittelforschung. 1975 Jan;25(1):132.
Abstract: To 23 subjects with endogenous depression after a previous unsuccessful treatment with common antidepressive drugs (imipramine-like or MAO inhibitors) dl- or d-phenylalanine was given in dialy oral doses of 50 or 100 mg during 15 days. A complete euthymia was obtained in 17 subjects between one and 13 days of treatment. No important adverse reaction was observed.

Haavik J. L-DOPA is a substrate for tyrosine hydroxylase. J Neurochem 1997 Oct;69(4):1720-1728.
Abstract: In the presence of thiols, tyrosine hydroxylase (TH) oxidizes L-dihydroxyphenylalanine (L-DOPA) with a specific activity of up to 140 nmol min(-1) mg(-1) at 37 degrees C and pH 7.0, which is approximately 12-50% of its TH activity under similar experimental conditions. Using assay conditions that are optimal for measuring TH activity, the specific DOPA oxidase activity of human TH is similar to that of mushroom tyrosinase, but the two enzymes are clearly different in terms of substrate specificities, cofactor dependencies, and selectivity with respect to the effects of metal chelators and other inhibitors. In the presence of an excess of dithiothreitol, 2-mercaptoethanol, cysteine, or reduced glutathione, the reaction products of the two enzymes are identical and have been identified tentatively as thioether derivatives of DOPA. Theoretically, the oxidation of L-DOPA by TH may contribute to the formation of neuromelanin (pheomelanin) in catecholaminergic neurons and in the metabolism of DOPA to reactive intermediates that can react with free thiol groups in cellular proteins. The DOPA oxidase activity of TH can lead to errors in the estimation of in vivo or in vitro TH activity, and currently used assay protocols may have to be modified to avoid interference from this activity.

Heller B, Fischer E, Martin R. Therapeutic action of D-phenylalanine in Parkinson’s disease. Arzneimittelforschung. 1976 Apr;26(4):577-579.

Lehmann WD, Theobald N, Fischer R, Heinrich HC. Stereospecificity of phenylalanine plasma kinetics and hydroxylation in man following oral application of a stable isotope-labelled pseudo-racemic mixture of L- and D-phenylalanine. Clin Chim Acta. 1983 Mar 14;128(2-3):181-198.
Abstract: L-[15N]Phenylalanine and D-[2H5]phenylalanine have been administered orally to two healthy adult volunteers as a pseudo-racemic mixture at a dose of 25 mg/kg each. After oral application, the plasma kinetics of phenylalanine and tyrosine have been followed by the combined use of high pressure liquid chromatography and field desorption mass spectrometry. Additional incubation with D-amino acid oxidase was used to determine the enantiomeric composition of the differently labelled species of phenylalanine and tyrosine. D-Phenylalanine plasma levels show a faster rise to higher maximum values compared to L-phenylalanine (D/L ratio at maximum 3.19, 3.26). L-Phenylalanine is efficiently hydroxylated to L-tyrosine. In contrast, conversion of D-phenylalanine to the L-form with subsequent hydroxylation to L-tyrosine was observed. From the plasma kinetics it is estimated that about 1/3 of the applied dose of 25 mg/kg of D-phenylalanine is converted to the L-isomer. Of the administered dose of L-phenylalanine only very small amounts are excreted into urine as such (0.25%, 0.8%), whereas a substantial amount of the D-phenylalanine dose is found in urine (27.4%, 38.0%).

Marz, Russell. Medical Nutrition From Marz. Second Edition. Portland, OR. 1997.

Sabelli HC, Fawcett J, Gusovsky F, Javaid JI, Wynn P, Edwards J, Jeffriess H, Kravitz H. Clinical studies on the phenylethylamine hypothesis of affective disorder: urine and blood phenylacetic acid and phenylalanine dietary supplements. J Clin Psychiatry 1986 Feb;47(2):66-70.
Abstract: To test the hypothesis that 2-phenylethylamine (PEA) modulates affect, plasma levels and urinary excretion of its main metabolite, phenylacetic acid (PAA), were studied in depressed and manic subjects, and the mood-elevating effects of its precursor, L-phenylalanine, were studied in depressed subjects. Mean total plasma PAA concentrations were 491.83 +/- 232.84 ng/ml in 12 healthy volunteers and 300.33 +/- 197.44 ng/ml in 23 drug-free patients with major depression. The 24-hour urinary PAA excretion was also measured in 48 healthy volunteers (141.1 +/- 10.2 mg PAA/24 hr) and in 144 patients with major depression (78.2 +/- 41.0 mg PAA/24 hr). The results suggest that low plasma and urinary PAA may be state markers for depression and are compatible with the PEA hypothesis. In further support, phenylalanine elevated mood in 31 of 40 depressives.

Sabelli HC, Javaid JI. Phenylethylamine modulation of affect: therapeutic and diagnostic implications. J Neuropsychiatry Clin Neurosci. 1995 Winter;7(1):6-14. (Review)
Abstract: A review of the literature indicates that brain phenylethylamine (PEA) may be a neuromodulator of aminergic synapses and that it promotes energy, elevates mood, and favors aggression. Phenylacetic acid, the main metabolite of PEA, is decreased in the biological fluids of depressed subjects and schizophrenic subjects and is increased in schizoaffective subjects. The administration of PEA or of its precursor L-phenylalanine improves mood in depressed patients treated with a selective monoamine oxidase B inhibitor. The authors speculate that studies of PEA metabolism may have diagnostic value and that PEA administration may be therapeutic in selected depressed patients.

Sabelli HC. Rapid treatment of depression with selegiline-phenylalanine combination. J Clin Psychiatry. 1991 Mar;52(3):137.

Schulpis CH, Antoniou C, Michas T, Strarigos J. Phenylalanine plus ultraviolet light: preliminary report of a promising treatment for childhood vitiligo. Pediatr Dermatol 1989;6:332-335.

Siddiqui AH, Stolk LM, Bhaggoe R, Hu R, Schutgens RB, Westerhof W. L-phenylalanine and UVA irradiation in the treatment of vitiligo. Dermatology 1994;188(3):215-218.

Werbach MR. Foundations of Nutritional Medicine. Tarzana, CA: Third Line Press, 1997. (Review).