Key Takeaways (expand)
- Phenylalanine is one of the nine essential amino acids that our bodies can’t make on their own, and one of 20 amino acids used to create protein.
- Phenylalanine can be biologically converted into another amino acid, tyrosine, via the enzyme phenylalanine hydroxylase.
- Through its conversion to tyrosine, phenylananine contributes to the production of the neurotransmitters dopamine, epinephrine, and norepinephrine (collectively known as the catecholamines).
- Phenylalanine also serves as a precursor for phenethylamine, which acts as a central nervous system stimulant.
- Due to its role in producing neurotransmitters that influence mood, phenylalanine may have a protective effect against depression; more research is needed.
- Some evidence suggests phenylalanine has analgesic (pain-reducing) properties, although studies in humans have been inconsistent.
- Phenylalanine helps produce the skin pigment melanin, and supplementation can be helpful for reducing symptoms of vitiligo— a condition where white patches appear on skin due to irregular depigmentation.
- A handful of trials have found phenylalanine to be helpful for ADHD and Parkinson’s disease, but more studies are needed to replicate these findings.
- Insufficient intake of phenylalanine can cause symptoms related to altered neurotransmitter production—including confusion, depression, loss of appetite, reduced alertness, memory problems, and lack of energy.
- Good sources of phenylalanine include most high-protein foods, including beef, pork, poultry, fish, dairy products, eggs, nuts, and seeds.
Table of Contents[Hide][Show]
Phenylalanine (symbol Phe) is one of the nine nutritionally indispensable amino acids that our bodies can’t make on their own; hence, we must consume it from our diet! It was first synthesized in the year 1882.
Phenylalanine supports the structure and function of different proteins and enzymes within the body. It’s also involved in synthesizing certain neurotransmitters (dopamine, epinephrine, and norepinephrine), helps produce the skin pigment melanin, and can be converted into another amino acid, tyrosine.
Phenylalanine is found in most high-protein foods, including beef, pork, poultry, fish, dairy products, eggs, nuts, and seeds. The body also receives phenylalanine from diet foods and drinks containing the artificial sweetener aspartame, which produces phenylalanine as a metabolite.
The Biological Roles of Phenylalanine
Broadly, amino acids are molecules with the molecular formula of R-CH(NH2)-COOH-NH2, where -NH2 is the basic amino group, COOH is an acidic carboxyl group, and R represents a molecular unit called a side chain. That side chain is unique for each amino acid, and its chemical properties create different classes of amino acids: nonpolar and neutral, polar and neutral, polar and acidic, and polar and basic.
Although hundreds of amino acids exist, only 20 of them are used for what amino acids are arguably most known for: forming the building blocks of proteins. Proteins are not only an essential macronutrient in the human diet; they’re molecules that perform most of the various functions of life. In addition to being major structural components of cells and tissues, proteins have incredibly diverse roles that range from driving chemical reactions (e.g., enzymes) to signaling (e.g., some types of hormones) to transporting and storing nutrients. Proteins are synthesized within cells through a two-phase process of transcription and translation, during which amino acids get linked together to form long chains (spanning anywhere from 20 to over 2,000 amino acids in length!).
So, while all proteins are made of amino acids, not all amino acids are used for making proteins! We use the term proteinogenic amino acids to refer specifically to the amino acids that get encoded into our DNA and incorporated into proteins. Meanwhile, non-proteinogenic amino acids do neither of these things (although they still have some very important biological roles!).
Amino acids can be further classified based on whether we can create them in our bodies, or need them from our diet. Essential amino acids are amino acids that can only be obtained from foods; these include histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. Non-essential amino acids are amino acids our bodies can synthesize metabolically from other molecules; these include alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, proline, serine, and tyrosine. And, some amino acids are conditionally essential, meaning our bodies can normally make them, but some circumstances (like illness or stress) can limit their synthesis and create a dietary requirement. These include arginine, cysteine, glutamine, tyrosine, glycine, ornithine, proline, and serine.
As an essential amino acid, we need a dietary source of phenylalanine in order to meet our body’s requirements. And as a proteinogenic amino acid, it’s used for the construction of proteins!
Phenylalanine can be biologically converted into another amino acid, tyrosine, via the enzyme phenylalanine hydroxylase. Like phenylalanine, tyrosine is proteinogenic, but it also serves the very important role of being a precursor for three neurotransmitters. First, tyrosine is converted into L-DOPA (also called dihydroxyphenylalanine), which mediates neurotrophic factor release by the brain and central nervous system. From there, L-DOPA is further converted into the neurotransmitters dopamine, epinephrine (adrenaline), and norepinephrine (noradrenaline)—which are collectively known as the catecholamines. Dopamine plays a role in regulating pleasurable reward and motivation, as well as memory, attention, and body movements. Meanwhile, epinephrine and norepinephrine are involved in the body’s “fight or flight” (AKA acute stress) response, working together to elevate heart rate, blood sugar, focus, attention, and excitement.
Phenylalanine also serves as a precursor for phenethylamine, which acts as a central nervous system stimulant. It’s produced from phenylalanine by enzymatic decarboxylation, with the the enzyme aromatic L-amino acid decarboxylase. Phenethylamine regulates monoamine neurotransmission in the brain, and can also serve as a neurotransmitter itself.
Phenylalanine can have important drug interactions to be aware of. For example, in people taking antipsychotic medications, phenylalanine supplements can cause a movement disorder called tardive dyskinesia. Likewise, phenylalanine can interact with some antidepressants (particularly monoamine oxidase inhibitors, or MAOIs) and cause insomnia, hypomania, elevated blood pressure, and constipation. Phenylalanine can also potentiate the effects of sedatives, and reduce the effectiveness of drugs for high blood pressure.
Want to Know ALL the Easy Steps to Nutrivore?
Get it Directly in Your Inbox!
The Nutrivore Newsletter is a weekly email that delivers bite-size fun facts, practical tips, recipes and resources. Sign up now and get 5 free guides directly to your inbox:
- Easy Steps to Nutrivore 4-page guide
- Nutrivore Foundational Foods 6-page guide
- Nutrivore Score Guide to Food Groups 3-page guide
- Nutrivore Meal Map
- Top 100 Nutrivore Score Foods
Phenylalanine in Health and Disease
Higher intakes of phenylalanine from food and supplements may be protective for certain health conditions, particularly ones with neurological components!
Phenylalanine and Depression
Due to its role in producing neurotransmitters that influence mood, phenylalanine has been studied for its potential effects on depression. Studies tend to show a correlation between low blood levels of phenylalanine and the occurrence of major depressive disorder, suggesting that either low intake or altered amino acid metabolism could contribute to this condition. And, several small studies from the 1970s found that supplementation with 50 to 200 mg of phenylalanine daily, for a duration of 15 to 30 days, was able to substantially improve symptoms in patients with depression. However, larger studies with more rigorous designs are needed to confirm these results!
Phenylalanine and Pain
Some research has also explored whether phenylalanine has analgesic (pain-reducing) properties, potentially by blocking enzymes that break down endorphins and enkephalins (peptides involved in pain perception). Animal models have shown that phenylalanine (specifically in the synthetic isoform D-phenylalanine) can decrease chronic pain within 15 minutes of administration, with effects lasting up to six days, as well as reduce animals’ responses to acute pain. However, the evidence in humans is less compelling: several trials have shown a pain-reducing effect of D-phenylalanine (including as an adjunct to acupuncture), but had poor designs and unreliable results; other studies failed to find any benefit of D-phenylalanine over a placebo. It’s possible that only certain individuals, and/or only specific types of pain (chronic versus acute), may be responsive to phenylalanine supplementation. So, while an analgesic effect of this amino acid would make sense from a mechanistic angle, the evidence for its impact on pain in humans is inconclusive.
Phenylalanine and Vitiligo
Vitiligo—a condition where white patches appear on skin due to irregular depigmentation—may be responsive to phenylalanine supplementation. In preliminary studies, phenylalanine (in both oral and topical forms) was able to strengthen the skin-repigmenting effect of UVA treatment in patients with vitiligo. For some people, phenylalanine on its own was able to modestly induce skin repigmentation.
Phenylalanine and ADHD
One trial showed that in patients with ADHD, the isomer DL-phenylalanine (but not L-phenylalanine or D-phenylalanine) could improve some symptoms on a short-term basis. However, much more research is needed to replicate this finding!
Phenylalanine and Parkinson’s Disease
One older trial also showed that phenylalanine (as D-phenylalanine) was able to improve tremors and motor control in people with Parkinson’s disease. Here, too, these findings still need to be replicated and further explored with more studies.
Didn’t know phenylalanine was this intriguing? Maybe your friends will enjoy this too!
Health Effects of Phenylalanine Deficiency
Insufficient intake of phenylalanine can cause symptoms related to altered neurotransmitter production, including confusion, depression, loss of appetite, reduced alertness, memory problems, and lack of energy.
Problems From Too Much Phenylalanine
Although dietary supplements containing phenylalanine are generally safe in moderate doses, excessive intakes (typically over 5,000 mg) can have adverse side effects and potentially induce nerve damage. High phenylalanine levels can also compete with the amino acid tryptophan, which uses the same active transport channel as phenylalanine to cross the blood-brain barrier. As a result, excessive quantities can interfere with serotonin production (for which tryptophan is a precursor). Due to lack of safety research, phenylalanine supplements aren’t advised for people who are pregnant or breastfeeding.
For some people, even normal intakes of phenylalanine can be problematic. A hereditary genetic disorder called phenylketonuria (often referred to as PKU) impairs the body’s ability to metabolize phenylalanine, leading to a buildup of this amino acid that can cause brain damage and severe intellectual disability. For people with PKU, a strict low-protein diet is often needed for life in order to prevent dangerously high levels.
Everything You Need to Jump into Nutrivore TODAY!
Guide to Nutrivore
The Guide to Nutrivore e-book explains why and how to eat a Nutrivore diet, introduces the Nutrivore Score, gives a comprehensive tour of the full range of essential and important nutrients!
Plus, you’ll find the Top 100 Nutrivore Score Foods, analysis of food groups, practical tips to increase the nutrient density of your diet, and look-up tables for the Nutrivore Score of over 700 foods.
How Much Phenylalanine Do We Need?
The recommended intake for phenylalanine is 33 mg per kg (or 15 mg per lb) of body weight daily. People with PKU need to consume 25% or less of this amount in order to keep blood levels within 120 to 360 μmol/L.
Expand to see all scientific references for this article.
Beckmann H, Athen D, Olteanu M, Zimmer R. DL-phenylalanine versus imipramine: a double-blind controlled study. Arch Psychiatr Nervenkr (1970). 1979 Jul 4;227(1):49-58. doi: 10.1007/BF00585677.
Beckmann H, Strauss MA, Ludolph E. Dl-phenylalanine in depressed patients: an open study. J Neural Transm. 1977;41(2-3):123-34. doi: 10.1007/BF01670277.
Cormane RH, Siddiqui AH, Westerhof W, Schutgens RB. Phenylalanine and UVA light for the treatment of vitiligo. Arch Dermatol Res. 1985;277(2):126-30. doi: 10.1007/BF00414110.
Couce ML, Sánchez-Pintos P, Vitoria I, De Castro MJ, Aldámiz-Echevarría L, Correcher P, Fernández-Marmiesse A, Roca I, Hermida A, Martínez-Olmos M, Leis R. Carbohydrate status in patients with phenylketonuria. Orphanet J Rare Dis. 2018 Jun 27;13(1):103. doi: 10.1186/s13023-018-0847-x.
Farishian RA, Whittaker JR. Phenylalanine lowers melanin synthesis in mammalian melanocytes by reducing tyrosine uptake: implications for pigment reduction in phenylketonuria. J Invest Dermatol. 1980 Feb;74(2):85-9. doi: 10.1111/1523-1747.ep12519975.
Fischer E, Heller B, Nachon M, Spatz H. Therapy of depression by phenylalanine. Preliminary note. Arzneimittelforschung. 1975 Jan;25(1):132.
Islam MR, Ali S, Karmoker JR, Kadir MF, Ahmed MU, Nahar Z, Islam SMA, Islam MS, Hasnat A, Islam MS. Evaluation of serum amino acids and non-enzymatic antioxidants in drug-naïve first-episode major depressive disorder. BMC Psychiatry. 2020 Jun 24;20(1):333. doi: 10.1186/s12888-020-02738-2.
Janicki PK, Gumułka SW, Szreniawski Z, Paulo EA, Arnold Z. The effects of D-phenylalanine and its derivatives on enkephalin degradation in vitro: relation to analgesia and attenuation of the morphine withdrawal syndrome. Pol J Pharmacol Pharm. 1986 Jan-Feb;38(1):41-9.
Joanny P, Natali JP, Hillman H, Corriol J. The uptake and efflux of L-phenylalanine and L-tyrosine from rat brain cerebral cortex slices. Biochem J. 1973 Sep;136(1):77-82. doi: 10.1042/bj1360077.
Lopez MJ, Mohiuddin SS. Biochemistry, Essential Amino Acids. [Updated 2022 Mar 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan.
MacDonald A, van Wegberg AMJ, Ahring K, Beblo S, Bélanger-Quintana A, Burlina A, Campistol J, Coşkun T, Feillet F, Giżewska M, Huijbregts SC, Leuzzi V, Maillot F, Muntau AC, Rocha JC, Romani C, Trefz F, van Spronsen FJ. PKU dietary handbook to accompany PKU guidelines. Orphanet J Rare Dis. 2020 Jun 30;15(1):171. doi: 10.1186/s13023-020-01391-y. Erratum in: Orphanet J Rare Dis. 2020 Sep 1;15(1):230.
Ogawa S, Koga N, Hattori K, Matsuo J, Ota M, Hori H, Sasayama D, Teraishi T, Ishida I, Yoshida F, Yoshida S, Noda T, Higuchi T, Kunugi H. Plasma amino acid profile in major depressive disorder: Analyses in two independent case-control sample sets. J Psychiatr Res. 2018 Jan;96:23-32. doi: 10.1016/j.jpsychires.2017.09.014.
Okusaga O, Muravitskaja O, Fuchs D, Ashraf A, Hinman S, Giegling I, Hartmann AM, Konte B, Friedl M, Schiffman J, Hong E, Reeves G, Groer M, Dantzer R, Rujescu D, Postolache TT. Elevated levels of plasma phenylalanine in schizophrenia: a guanosine triphosphate cyclohydrolase-1 metabolic pathway abnormality? PLoS One. 2014 Jan 21;9(1):e85945. doi: 10.1371/journal.pone.0085945.
Pencharz PB, Hsu JW, Ball RO. Aromatic amino acid requirements in healthy human subjects. J Nutr. 2007 Jun;137(6 Suppl 1):1576S-1578S; discussion 1597S-1598S. doi: 10.1093/jn/137.6.1576S.
Roiser JP, McLean A, Ogilvie AD, Blackwell AD, Bamber DJ, Goodyer I, Jones PB, Sahakian BJ. The subjective and cognitive effects of acute phenylalanine and tyrosine depletion in patients recovered from depression. Neuropsychopharmacology. 2005 Apr;30(4):775-85. doi: 10.1038/sj.npp.1300659.
Russell AL, McCarty MF. DL-phenylalanine markedly potentiates opiate analgesia – an example of nutrient/pharmaceutical up-regulation of the endogenous analgesia system. Med Hypotheses. 2000 Oct;55(4):283-8. doi: 10.1054/mehy.1999.1031.
Strasser B, Sperner-Unterweger B, Fuchs D, Gostner JM. Mechanisms of Inflammation-Associated Depression: Immune Influences on Tryptophan and Phenylalanine Metabolisms. Curr Top Behav Neurosci. 2017;31:95-115. doi: 10.1007/7854_2016_23.
Tollefson L, Barnard RJ. An analysis of FDA passive surveillance reports of seizures associated with consumption of aspartame. J Am Diet Assoc. 1992 May;92(5):598-601.
Walsh NE, Ramamurthy S, Schoenfeld L, Hoffman J. Analgesic effectiveness of D-phenylalanine in chronic pain patients. Arch Phys Med Rehabil. 1986 Jul;67(7):436-9.
Wood DR, Reimherr FW, Wender PH. Treatment of attention deficit disorder with DL-phenylalanine. Psychiatry Res. 1985 Sep;16(1):21-6. doi: 10.1016/0165-1781(85)90024-1.
Checklists and Planning Tools
Make Nutrivore simple and easy with these handy-dandy planning tools and checklists.