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.
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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.
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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.
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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.
Citations
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