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Phenylalanine is a hydrophobic essential amino acid with a benzyl side chain; as its name suggests, it is a derivative of alanine, another amino acid. Being an essential amino acid entails that phenylalanine cannot be biosynthesized by our bodies and must be obtained through consumption of food sources rich in it, for example, eggs (especially egg whites), seaweeds, fish, soy flour and soy protein concentrates, tofu, mollusks, milk, and Parmesan, Fontina, Swiss, Romano, and Gruyère cheeses. [1]
Phenylalanine’s physiological importance lies on its being a building block for proteins in the body, like all other amino acids, and being most characteristically the precursor of a variety of vital hormones and neurotransmitters, such as melanin, dopamine, norepinephrine, and thyroxine. Phenylalanine is usually buried within a protein because of its hydrophobic nature where this amino acid’s phenyl ring stacks with other aromatic systems, resulting in added structural stability. [2]
Phenylalanine is interestingly one of few amino acids that exist in both L- and D-forms. D-Phenylalanine is an enantiomer, that is, mirror image, of L-phenylalanine, and although further research is still needed to clearly unravel its functions, D-phenylalanine has been reported to exert pharmacological activity at niacin receptor 2. In contrast, L-phenylalanine is converted by the body into L-tyrosine and is considered a competitive antagonist of NMDA and AMPA receptors. The third form of the amino acid, DL-phenylalanine, can be produced by combining the previously mentioned D- and L-forms. [3]
Phenylalanine and Depression
Because phenylalanine is the precursor of neurotransmitters associated with mood, it comes naturally that manipulating its levels to alter other neurotransmitters’ concentrations would be explored as a possible therapeutic strategy against depression. A clinical study published in the Journal of Clinical Psychiatry demonstrated that phenylalanine elevates mood in 31 out of 40 study participants with depression. [4] Moreover, in the preliminary study of Fischer, Heller, Nachon, and Spatz (1975), 17 study participants of 23 subjects with depression manifested absolute euthymia (i.e., normal or positive mood) between 1 and 13 days of treatment with 50 or 100 mg of orally administered DL- or D-phenylalanine. [5] An open study on DL-phenylalanine in doses of 75-200 mg/day administered on 20 depressed patients for 20 days reported substantial antidepressant properties for the amino acid. Out of the 20 individuals enrolled in the trial, 12 patients were discharged without any further treatment; additionally, anxiety and sleep disturbances were observed to have been moderately affected by DL-phenylalanine treatment, whereas core symptoms such as depressed mood, retardation, and agitation were “preferentially” influenced. [6]
Phenylalanine and Pain
Phenylalanine has been proposed as well to exert analgesic properties and lessen discomfort in chronic pain conditions. In rodent studies, administration of D-phenylalanine results in long-lasting, naloxone-reversible analgesia, with a potency similar to that of inhibitors of met-enkephalin degradation by mouse brain enzymes. [7]
Phenylalanine and Vitiligo
An earlier study by Antoniou et al. (1989) indicated the efficacy and safety of oral administration of phenylalanine at a dose of 100 mg/kg body weight along with ultraviolet A (UVA) exposure in treating vitiligo, a condition chiefly characterized by hypopigmentation and white patches on the skin. [8] Such study finding is similar to that of Cormane et al. (1985), who also reported the effectiveness of phenylalanine treatment with UVA exposure against vitiligo. In this study, 4-month treatment led to repigmentation of hypopigmented macules in skin areas with adipose tissues, with patients displaying tolerance to the sun and absence of sunburn. [9] A comprehensive systematic review by Szczurko and Boon (2008) on published articles about natural vitiligo remedies, including vitamins, herbs, and supplements, identified four clinical trials associating L-phenylalanine with beneficial effects for patients with vitiligo. [10] Additionally, Camacho and Mazuecos (2002) augmented their vitiligo “L-phenylalanine plus phototherapy” treatment approach with 0.025% clobetasol propionate, a very potent topical corticosteroid. Their open trial involved 70 patients diagnosed with evolutive vitiligo and receiving oral and topical L-phenylalanine treatment and 0.025% clobetasol propionate at night while being exposed to sunlight (during spring and summer) or UVA lamps (during autumn and winter). The study results indicated a 90.9% improvement among participants, 68.5% of whom had obtained an improvement equivalent to 75% or more. Such improvement rate (i.e., 75%) was achieved 87.9% of the time on the face, 60.4% on the trunk, and 54.6% on the limbs, although only moderate treatment response was observed among individuals with focal and segmental vitiligo. [11]
References:
[1] Phenylalanine(g). USDA National Nutrient Database for Standard Reference Release 27. https://www.ars.usda.gov/ARSUserFiles/80400525/Data/SR27/sr27_doc.pdf
[2] Phenylalanine. The Biology Project, Department of Biochemistry and Molecular Biophysics, University of Arizona. https://biology.arizona.edu/biochemistry/problem_sets/aa/phenylalanine.html
[3] Phenylalanine. Wikipedia. https://en.wikipedia.org/wiki/Phenylalanine
[4] 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. https://pubmed.ncbi.nlm.nih.gov/3944066
[5] Fischer E., Heller B., Nachon M., Spatz H. (1975). Therapy of depression by phenylalanine. Preliminary note. Arzneimittelforschung. 25(1): 132. https://pubmed.ncbi.nlm.nih.gov/1173765
[6] Beckmann H., Strauss M. A., Ludolph E. (1977). DL-phenylalanine in depressed patients: an open study. Journal of Neural Transmission. 41(2-3): 123-134. https://pubmed.ncbi.nlm.nih.gov/335027
[7] Ehrenpreis S. (1985). Analgesic properties of enkephalinase inhibitors: animal and human studies. Progress in Clinical & Biological Research. 192: 363-370. https://pubmed.ncbi.nlm.nih.gov/2934746
[8] Antoniou C. et al. (1989). Vitiligo therapy with oral and topical phenylalanine with UVA exposure. International Journal of Dermatology. 28(8): 545-547. https://pubmed.ncbi.nlm.nih.gov/2583897
[9] Cormane R. H. et al. (1985). Phenylalanine and UVA light for the treatment of vitiligo. Archives of Dermatological Research. 277(2): 126-130. https://link.springer.com/article/10.1007%2FBF00414110
[10] Szczurko O., Boon H. S. (2008). A systematic review of natural health product treatment for vitiligo. BMC Dermatology. 8:2. doi:10.1186/1471-5945-8-2. https://biomedcentral.com/1471-5945/8/2
[11] Camacho F., Mazuecos J. (2002). Oral and topical L-phenylalanine, clobetasol propionate, and UVA/sunlight–a new study for the treatment of vitiligo. Journal of Drugs in Dermatology. 1(2): 127-131. https://pubmed.ncbi.nlm.nih.gov/12847735
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