Phenylalanine

Phenylalanine is a nutrient belonging to the essential amino acid class.

Phenylalanine is also known as Phe, 2-amino-3-phenyl-propanoic acid and L-phenylalanine.

Phenylalanine is vital for producing neurotransmitters, protein synthesis, and normal brain function. It is a precursor for several significant molecules necessary for the body's growth and function.

Phenylalanine deficiency can lead to genetic disorders like phenylketonuria (PKU). It occurs when the body cannot adequately metabolise phenylalanine, resulting in reduced quantities in circulation. Signs and symptoms include intellectual and developmental difficulties, delayed growth, and other neurological disorders.

Phenylalanine can be obtained naturally in various protein-rich meals derived from plant and animal sources. Plant sources include oats, lentils, pea beans, spirulina, peanuts, and seeds. In contrast, chicken, pork, steak, tuna fish, salmon fish and cottage cheese are excellent sources of animal sources of phenylalanine.

The small intestine absorbs phenylalanine and gets distributed throughout the human body. Tyrosine is produced from it, or it can be destroyed via the phenylalanine hydroxylase pathway. Urine is the primary route for eliminating excess phenylalanine.

The common side effects of phenylalanine include anxiety, headache, and constipation.

Phenylalanine is available in tablets, capsules and oral powders.

Biochemical action of Phenylalanine

Phenylalanine, belonging to the essential amino acid class, acts in several biochemical processes. It works via the phenylalanine-to-tyrosine conversion pathway.

The primary role of phenylalanine involves enzymatic transformations that result in the production of tyrosine. Tyrosine is the building block for several essential substances, including neurotransmitters and pigments. Synthesis of neurotransmitters, including dopamine, norepinephrine, and epinephrine, occurs by converting phenylalanine to tyrosine. The effects of phenylalanine on neurology and mental health are shown by the neurotransmitters, which seriously impact mood, cognitive ability, and stress reaction.

Tyrosine, synthesized from phenylalanine, is essential for melanin formation, which determines the skin, hair, and eye colour. Phenylalanine and skin health are related because melanin protects skin cells from UV radiation damage and supports skin cell protection.

Additionally, phenylalanine helps produce nitric oxide (NO), a signalling molecule that regulates various physiological processes. Tyrosine and L-DOPA are made as a result of the conversion of phenylalanine to tyrosine, which also controls immunological responses, blood vessel dilatation, and neurotransmission.

Phenylalanine is available in tablets, capsules and oral powders.

• Tablets: To be swallowed whole with water/liquid, as applicable.
• Capsules: To be swallowed whole with water/liquid, as applicable.
• Powders, oral: Powders must be mixed thoroughly with the appropriate amount of liquid and stirred well to dissolve the powder, as applicable.

Phenylalanine can be used as a supplement when the amount of phenylalanine taken through diet is insufficient.

Taking leucine supplements effectively treats phenylalanine deficiency caused by specific genetic diseases or other disorders.

Phenylalanine supplements help produce melanin, which affects the colour of the skin, hair, and eyes.

Supplements containing phenylalanine may help in the production of dopamine while alleviating the symptoms of depression.

Phenylalanine supplement may potentially help treat vitiligo when combined with UV light therapy.

Vitamins and natural supplements should not replace a balanced diet.

This product is not intended to diagnose, treat or prevent any disease(s).

Phenylalanine can help to support as a supplement for the following health benefits:

• Vitiligo: Loss of skin pigmentation in vitiligo is caused by autoimmune factors. Phenylalanine combined with UV light treatment has shown potential in symptom relief. A skin gel, sunshine exposure, and 50 mg of phenylalanine per 50 pounds of BW (Body weight) were all used in clinical investigations to show a significant improvement in skin colour. Participants in Spain who used this method reported an improvement in the appearance of their vitiligo by 75%.
• ADHD: Attention-deficit/hyperactivity disorder (ADHDP), a brain disorder affecting children and adults, prevents normal development by causing chronic inattention and hyperactivity. Even though there is no cure, there are therapeutic choices. Given that ADHD patients frequently have low phenylalanine levels, phenylalanine supplementation may be helpful for symptom alleviation. It may help lessen withdrawal symptoms if used together with conventional ADHD drugs.
• Mood: Phenylalanine helps produce dopamine, which can potentially improve mood and lessen depressive symptoms. It helps to make "feel-good" hormones by converting them to tyrosine. Phenylalanine supplementation has been linked to better depression symptoms, but it's still necessary to consult a doctor, especially if one tries to control the condition.

• Parkinson’s Disease: It is a neurological disease that typically affects people over 40 and damages the brain's dopamine-producing neurons. It causes difficulties with motor coordination, depression, sleep problems, and cognitive decline. Although D-phenylalanine has demonstrated promise in decreasing tremors, care is advised since it may interact with the Parkinson's drug Levodopa.
• Pain relief: The involvement of phenylalanine in synthesising neurotransmitters like endorphins and dopamine, which impact pain modulation, is related to its potential advantages in the treatment of pain. According to some research, phenylalanine supplementation can reduce pain, including migraines and chronic pain, by modulating these neurotransmitter pathways. However, seeing a healthcare provider before using is essential, especially if one is on medication or has a health issue.
• Alcohol withdrawal: Due to its effect on the generation of neurotransmitters, phenylalanine supplementation may help to ease the symptoms of alcohol withdrawal. It may help reduce the mood swings, anxiety, and depression that frequently accompany alcohol withdrawal by promoting the production of dopamine and norepinephrine.

Phenylalanine supplementation may be administered orally.

Orally: Phenylalanine supplements are available as tablets, capsules and powders that can be taken orally. Phenylalanine supplements should be taken on an empty stomach for at least 30 minutes in the morning or between meals. To increase absorption, it should be taken in the absence of other protein-containing foods. Phenylalanine supplements should also be taken before bed to promote overnight muscle repair and development.

The dosage and duration of treatment should be as per the clinical judgment of the treating healthcare professional).

Vitamins and natural supplements should not replace a balanced diet

This product is not intended to diagnose, treat or prevent any disease(s).

• Tablets: 500 mg
• Capsules: 500mg, 550mg, 1000mg
• Powder, oral: 500 mg, 1000 mg

Dosage Adjustment for Adult Patients

FROM MOUTH:

Adults with vitiligo, a skin condition that causes white, unpigmented patches, often take 50–100 mg/kg of L-phenylalanine daily, combined with UV exposure.

Phenylalanine is available in tablets, capsules and oral powders.

Phenylalanine should be a supplement that helps in several biochemical processes and appropriate dietary restrictions.

• Avoid alcoholic beverages.

• Stay within your daily calorie needs.

• Artificial sweeteners like aspartame

• Keep away from food, especially those that include other amino acids, since these may hinder absorption.

• While taking leucine supplements, limit the consumption of phenylalanine-rich foods to avoid excessive intake.

Recommended Daily Allowance (RDA)

As per FSSAI, the estimated RDA of phenylalanine is 33 mg/kg body weight per day.

Upper Tolerable Intake (UTL):

The UTL of phenylalanine is not established.

Phenylalanine supplementation may be contraindicated in the following conditions:

• Hypersensitivity: sensitive to phenylalanine
• Chronic liver disease
• Chronic kidney disease (CKD)
• Kidney failure
• Schizophrenia
• Phenylketonuria (PKU)
• Tardive dyskinesia

High-dose supplements should be avoided in children and older people unless advised to do so by a healthcare professional.

Before taking phenylalanine, individuals with renal or liver disorders should see a physician since the dosage may need to be adjusted to prevent adverse effects.

Supplements containing phenylalanine should be given with caution to people with a history of hypertension or other mental conditions.

Individuals taking medications like (MAOIs), antipsychotic drugs, and levodopa may use phenylalanine supplements cautiously as they can cause unwanted interactions.

To avoid potential interactions, it is recommended to use only one amino acid supplement or dietary supplements.

Caution is advised when consuming alcohol with phenylalanine.

While taking phenylalanine supplements, limit the consumption of artificial sweeteners and phenylalanine-rich foods to avoid excessive intake.

The adverse reactions related to phenylalanine can be categorised as:

• Common: GI disturbances, high blood pressure and headaches
• Less common: Allergic Reactions (Skin rashes, itching, or swelling)
• Rare: Tachycardia and neurological symptoms.

The clinically relevant drug interactions of phenylalanine are summarized here:

• Levodopa: Levodopa is commonly used for the treatment of Parkinson's disease. Levodopa and phenylalanine may worsen Parkinson's disease, so avoiding this supplement while taking levodopa is advised.
• Monoamine oxidase inhibitors (MAOIs): Tyramine, a molecule found in the body, can be elevated by phenylalanine. Tyramine, in large doses, can raise blood pressure. Some MAOIs, including phenelzine, selegiline, and tranylcypromine, are used to treat depression and can prevent the body from metabolising tyramine. Tyramine levels may become excessive, which might put your blood pressure at risk.
• Baclofen: Phenylalanine may reduce the amount of baclofen absorbed by the body. This might lessen the effect of the drug baclofen.
• Antipsychotic drugs: Haloperidol, olanzapine, perphenazine, fluphenazine, and other medications used to treat mental disorders, such as chlorpromazine, clozapine, and fluphenazine may produce jerky muscular movements. The risk of jerky athletic movements may rise if phenylalanine is combined with several drugs for mental problems.

The common side of Phenylalanine include the following:

• Anxiety
• Headache
• Constipation
• Gastrointestinal Distress like nausea, vomiting, or stomach pain
• Increased Blood Pressure
• Heartburn
• Fatigue
• Nausea
• Constipation
• Dizziness
• Headache
• Sedation
• Trouble sleeping

Phenylalanine should be prudent in the following group of special populations.

• Pregnancy:

When taken by pregnant women with normal phenylalanine levels in amounts typically found in food, phenylalanine is LIKELY SAFE. However, a mother's excessive phenylalanine intake during pregnancy might raise her risk of birth abnormalities. Even regular meal portions are unsafe for women who have high phenylalanine levels. Additionally, healthcare professionals advise avoiding phenylalanine for at least 20 weeks before pregnancy. This should lower the chance of birth abnormalities.

Avoid phenylalanine supplements unless advised to do so by a healthcare professional while pregnant.

• Paediatrics:

Without specific health recommendations, phenylalanine supplements are typically not advised for children. There is no sufficient scientific evidence traceable regarding the use and safety of phenylalanine for paediatric populations.

Dosage Adjustment for Paediatric Patients

There are no specific dosage adjustments provided.

• Geriatrics:

There is no sufficient scientific evidence traceable regarding the use and safety of phenylalanine for geriatric populations. Avoid phenylalanine supplements unless advised to do so by a healthcare professional.

• Lactating mothers:

There is no sufficient scientific evidence traceable regarding the use and safety of phenylalanine for lactating mothers populations. Avoid phenylalanine supplements unless advised by a healthcare professional while lactating.

Dosage Adjustment in Kidney Impairment

There are no specific dosage adjustments provided.

Dosage Adjustment in Hepatic Impairment

There are no specific dosage adjustments provided

The physician should be vigilant about the knowledge pertaining to identifying and treating overdosage of phenylalanine. Overconsumption of phenylalanine may lead to adverse effects like nausea, heartburn, and headaches.

There is no specific antidote or treatment for excessive intake of supplemental phenylalanine. Intake of phenylalanine-rich foods and supplements should be immediately reduced or stopped when an overdose is suspected or experience any unusual symptoms after phenylalanine supplement use or dietary intake. Supportive therapy should also be given, addressing any symptoms that persist or worsen. Physical treatment might be added if necessary.

Biochemistry profile of Phenylalanine

Phenylalanine is an α-amino acid with a benzene ring as its primary structure. It consists of a central carbon atom bound to an amino group, a carboxyl group, with a side chain that contains a phenyl group.

Phenylalanine is one of the essential amino acids that is required for many metabolic reactions is phenylalanine. It is a precursor for synthesising tyrosine, necessary for producing neurotransmitters, including dopamine, norepinephrine, and epinephrine. These neurotransmitters are crucial for controlling mood, cognitive ability, and stress response. In addition, melanin, a pigment that controls the colour of skin, hair, and eyes, is contributed by phenylalanine. It also helps produce nitric oxide (NO), a signalling molecule that controls immunological responses, neurotransmission, and blood vessel dilation. Thus,

phenylalanine is involved in various complex pathways, which are essential for maintaining skin health, protecting the nervous system, and maintaining good physiological health.

Kinetic profile:

• Absorption: Phenylalanine is absorbed from the small intestine by a sodium-dependent active transport process, where it is then circulated throughout the body to different tissues.
• Distribution: Phenylalanine is transported by the bloodstream throughout the body after absorption. It enters the central nervous system after crossing the blood-brain barrier and is essential for producing neurotransmitters.
• Metabolism: Tyrosine, an essential amino acid, and the phenylalanine hydroxylase pathway are both used in phenylalanine metabolism. Tyrosine is produced as a result, and it then participates in several metabolic activities.
• Elimination: Excess phenylalanine is predominantly metabolised and eliminated when not utilised in protein synthesis or other metabolic pathways. The breakdown byproducts, which comprise metabolites like phenylpyruvate, phenyl lactate, and phenylacetate, are ultimately eliminated from the body through urine.

2. National Institute of Nutrition. 2011.Dietary guidelines for Indians; 2nd Edition. Hyderabad. India

3. https://pubchem.ncbi.nlm.nih.gov/compound/Phenylalanine

4. Tessari P. 2019. Nonessential amino acid usage for protein replenishment in humans: a method of estimation; American Society for Nutrition. Department of Medicine, University of Padova, Padova, Italy