Phenylalanine Uses, Side Effects, And Possible Side Effects April 28, 2016


Phenylalanine is classified as an essential amino acid. It means that the body doesn’t produce phenylalanine on its own, but must obtain it from foods or supplements. Amino acids serve as the foundation for the synthesis of proteins in the body. Due to the fact that it can cross the blood-brain barrier, it has a direct impact and effect on the brain chemistry. Inside the body, phenylalanine can be converted into tyrosine, another amino acid that is utilized to synthesize two major neurotransmitters: dopamine and norepinephrine, both of which promote alertness and focus.

Phenylalanine also has a relationship with numerous central nervous system actions as well as an impact on mood, pain perception, and in memory and learning. It also has an influence on appetite suppression. Common uses of phenylalanine include the treatment of arthritis, depression, migraines, Parkinson’s disease, and schizophrenia.

As a point of interest, phenylalanine is a major component of aspartame, which has been perceived to be one of the most dangerous food additives used today (1).Two major components of aspartame (phenylalanine and aspartic acid) are known as chiral components, having two isomers that are non-superimposed double mirror images of each other. Metabolism breaks down aspartame into its specific components: phenylalanine, aspartic acid, and methanol. Concerns regarding too much phenylalanine in the diet are questionable. Actually, extra phenylalanine is broken down into acetoacetate and fumarate, both of which are a part of normal energy metabolism.

Because aspartic acid and phenylalanine are amino acids that occur naturally in foods that contain proteins, a healthy body is capable of processing them. They do not contribute to health issues in most individuals. However, individuals diagnosed with phenylketonuria are advised to avoid aspartame. Anyone diagnosed with such a genetic defect must be vigilant in monitoring intake of phenylalanine.

One article, “Aspartame: by far the most dangerous a substance added to most foods today” (2) defines a number of adverse reactions reported to the FDA regarding food additives. According to Mercola (3)  (see table), just a few adverse reactions associated with aspartame include those in the following table. Actually, over 90 documented symptoms have been linked to aspartame.

Muscle spasmsWeight gainRashesDepressionFatigue
IrritabilityTachycardiaInsomniaVision problemsHearing loss
Heart palpitationsDifficulty breathingAnxiety attacksSlurred speechLoss of taste
TinnitusVertigoMemory lossJoint pain

When it comes to a number of illnesses that have been associated with aspartame (triggered or even made worse by consumption), they are defined in the following table (4[1]:

Brain tumorsMultiple sclerosisEpilepsyChronic fatigue syndromeParkinson’s disease
Alzheimer’sMental retardationLymphomaBirth defectsFibromyalgia

Things to Know 

  • Aspartame – an artificial sweetener (non-saccharine) used as a sugar substitute in a number of beverages and foods. The most common forms of aspartame are sold as Equal® or NutriSweet®. According to the American Cancer Society, it’s composed of two amino acids: phenylalanine and aspartic acid.
  • Phenylalanine is considered an essential amino acid that the body needs, but doesn’t produce by itself. Only one form of phenylalanine (L-phenylalanine) can be ingested from foods.
  • L-phenylalanine’s molecular formula is C9H11NO2. 

The body breaks down aspartame into phenylalanine, methanol, and aspartic acid(5).[2] While many consumers are concerned about the effect of methanol, the amounts of methanol resulting from aspartame breakdown in the body are lower than that found with many natural organic foods. In fact, according to the American Cancer Society, a liter of diet soda involves the consumption of 55 mg of methanol. A liter of fruit juice? 680 mg(6).[3]

As far as consumption is concerned, the US Food and Drug Administration (FDA) recommends no more than 50 mg per kilogram of body weight. The European Food Safety Authority (EFSA) recommends allowable daily intake at 40 mg per kilogram.

What does that mean for consumers? A typical adult weighing about 165 pounds would have to consume more than 3,750 mg of aspartame daily. For example, a 12-ounce diet soda contains approximately 192 mg of aspartame. A packet of sweetener contains 35 mg. Again, according to the American Cancer Society, an adult who weighs 165 pounds would have to drink in excess of 19 cans of diet soda or consume 107 packets of sweetener to go over the recommended daily allowance (7).[4]

Mechanism Of Action

Phenylalanine is transformed into tyrosine by the body. Tyrosine is an amino acid required for the formation of proteins as well as a number of brain chemicals such as epinephrine, norepinephrine, thyroid hormones, and l-dopa(8).[5] It is well-known that norepinephrine has an influence on mood, and therefore, a variety of phenylalanine forms have commonly been suggested in the treatment of depression.

Phenylalanine has a close relationship to tyrosine, which only differs from phenylalanine by one hydroxyl (OH) group (see image at left courtesy Phenylalanine hydroxylase enzymes are found in liver cells and enable the conversion of phenylalanine into tyrosine.

Excessive amounts of phenylalanine in the diet contribute to possible mental disorders. Prompt treatment can reverse some symptoms.

How it’s taken

Phenylalanine is commercially available in L-, D-, and DL-phenylalanine forms. They are not created equal. L-phenylalanine is considered an essential amino acid for humans, and proteins contain this form of phenylalanine.

L- The “L” in front of amino acids or other supplements means that it is in its free form.  In other words, it means that that amino acid is not attached to another amino acid. The L- form of phenylalanine is the most common form in which the amino acid is incorporated into protein synthesis by the body. This is a natural form of the amino acid found in proteins. L-phenylalanine is found in just about any food that contains proteins including meat, poultry, fish, milk and dairy products, soy products, and a number of seeds and nuts. Aspartame, an artificial sweetener, is high in phenylalanine(9)[6].

D- The “D” designates a synthetically created amino acid. The “L” stands for levo (left) and the “D” stand for devo (right). The left or right designation defines the spiral rotation of the molecular chemical structure. For example, some proteins in plant and animal tissues are made with “L” forms of amino acids, which are considered more compatible with human biochemistry. The D- form of phenylalanine performs as a painkiller. Classified as a mirror image of L-phenylalanine made in a laboratory, D-phenylalanine is not found in any food sources but is manufactured in laboratories. The function of D-phenylalanine, at least in regard to humans, remains uncertain(10).[7]

DL- The “DL” stands for a natural form of phenylalanine commonly found in protein-rich foods. DL-phenylalanine contains two different forms of phenylalanine. The L- form is composed of natural substances that are found in foods rich in protein. The D- form defines a synthetically created amino acid. DL-phenylalanine is commonly used to relieve minor depression and as a pain reliever. The DL- form is not only effective in some situations in the control of pain, such as that associated with arthritis, but can function as a foundation for the synthesis of proteins.  This form of phenylalanine is a combination of natural as well as synthetic phenylalanine. DL-phenylalanine is synthetically created with 50% D-phenylalanine and 50% L-phenylalanine.

Brief History Of The Use Of Phenylalanine

Early research (circa 1970s and 1980s) promotes the use of phenylalanine in the treatment of some forms of depression. Phenylalanine supplements have been used, with varying results, for a number of medical conditions and issues. As per the University of Michigan Health System:

Depression: Approximately 3 to 4 g L-phenylalanine OR 150 to 200 mg DL-phenylalanine daily.

Results: Improved mood/attitude in depressed individuals(11).[8]

Pain: Approximately 1,500 mg daily.

Results: Some effectiveness in blocking enzymes that contribute to body-produced pain killers. May be effective in treating some chronic pain(12).[9]

An alternative medical treatment devised by Carl Loder (known as the Carl Loder Regimen) has been used as a natural treatment approach for multiple sclerosis that utilizes and combines phenylalanine with lofepramine (an antidepressant not available in the US) as well as intramuscular (IM) injections of vitamin B12.  However, clinical research has not determined any efficacy or support in the benefits of this alternative medical therapy for the treatment of MS. Research continues in this area(13).[10]

Symptoms Of A Phenylalanine Deficiency

Phenylalanine deficiencies may produce one or more potential symptoms, including but not limited to:


  • Problems with memory and focus
  • Lack of appetite
  • Lack of energy
  • Confusion
  • Decreased awareness/alertness

A person who lacks the necessary phenylalanine hydroxylase enzyme activity to convert phenylalanine to tyrosine is not able to normally metabolize phenylalanine, which results in a condition known as phenylketonuria or PKU. Instead of converting to tyrosine, these excessive amounts of phenylalanine are converted to phenylketonurias that appear in urine. In such cases, non-treatment can contribute to mental retardation(14).[11]

PKU can cause irreversible brain damage in infants if not treated with the first few weeks of birth. Today, at least in the US, newborns are tested for PKU within 48 to 72 hours following their birth. If not treated, children are often diagnosed with hyperactivity, sometimes with autistic behaviors such as rocking or erratic hand movement(15).[12] A person diagnosed with PKU must avoid foods or beverages that contain phenylalanine and is recommended to take tyrosine supplements. This is essential for brain development.

PKU typically presents itself with numerous manifestations and symptoms(16)[13] including:

  • Mental retardation
  • Odd posture
  • Awkward gait
  • Epilepsy
  • Eczema
  • Cataracts
  • Brain calcification

Scientific studies lacking

There is a lack of scientific studies and interest in phenylalanine as far its potential treatment in a number of medical scenarios, such as treatment for Parkinson’s disease symptoms, chronic pain, and depression. After the initial flurry of excitement in the 1970s, 1980s, and early 1990s, few explorations into such use have been conducted.

Chronic Pain

D-phenylalanine has undergone quite a bit of focused research as a treatment for chronic pain. Very few studies have verified the efficacy of D-phenylalanine to provide verifiable and positive results. The small number of studies that have been done lack in detail, results, and, possibly, oversight. In the past 20 years, no controlled and randomized clinical trials have pursued the benefits of phenylalanine in dealing with chronic pain. More research is required regarding the efficacy as well as safety for this use. However, the few limited studies of the use of D-phenylalanine in reducing chronic pain were reported to provide no beneficial effects over the administration of a placebo.

Phenylalanine As An Antidepressant 

Since the 1970s, a number of studies have been performed regarding the use of phenylalanine as a reliable form of treatment for depression. As with studies regarding its use for treating chronic pain, the lack of studies have failed to yet produce verifiable results concerning its effect on mood, although some individuals have reported improvement in mood when taking phenylalanine. The mechanism of action of phenylalanine on the brain chemical production (including norepinephrine and dopamine) is thought to be a major force behind elevated mood, but again, additional research is required to verify the efficacy.

Phenylalanine and pyroxene have been used with varying results for schizophrenia, but its use as a treatment for depression, anxiety, or bipolar disorders requires further research. A study conducted in 2009 (“Convergent patterns of association between phenylalanine hydroxylase variants and schizophrenia in four independent samples”)(17)[14] explored the potential link between phenylalanine hydroxylase gene mutations and schizophrenia, but the lack of follow-up to the study has stalled the research.

Early studies have shown definite improvement of mood in groups of people diagnosed with varying degrees of depression. One study, published in 1975, tested the use of DL-phenylalanine in a group of 23 patients who had not responded to traditional MAOIs. They were given between 50 and 100 mg phenylalanine daily for 15 days. Results showed that 13 of the patients showed improvement after 13 days of treatment(18).[15]

In 1977, a study published in the Journal of Neural Transmission tested 20 patients diagnosed with depression. They were given 75 mg to 200 mg phenylalanine daily for 20 days. “Significant” improvements in mood were noted in four patients, eight were ‘cured’, and four had a mild or moderate response to the treatment. The last four showed no improvement.(19)[16]

In 1984, a study was conducted combining phenylalanine with selegiline, an antidepressant. The study involved 155 patients diagnosed with depression. Nearly 90% of the outpatients involved in the study showed effective results, while 81% of inpatients showed positive results. The same results were reported in 1991 in an article published in the Journal of Clinical Psychiatry.(20)[17]

Limited double-blind and comparative studies have determined that L-phenylalanine and DL-phenylalanine may be effective in its use as an antidepressant, similar to that of imipramine. One older (1970s) study determined the efficacy of D-phenylalanine at 100 mg daily against the same daily dose of imipramine(21).[18]

Therapeutic Dosages And Uses Of Phenylalanine For Depression 

A therapeutic dosage recommendation for D-phenylalanine averages 100 to 200 mg daily when treating depression(22)[19]. Nevertheless, the study testing this dosage was quite small and short-term (60 people for 30 days) while both resulted in similar effects. For most, the phenylalanine worked relatively quickly, at approximately 15 days for noticeable improvements.

Another small study (double-blind) engaged another small group of people (27), who received between 150 and 200 mg of DL-phenylalanine daily. The other group received 100 to 150 mg imipramine daily. Results after 30 days showed similar statistical results(23).[20]

Additional studies involving the therapeutic use of phenylalanine for the treatment of depressive disorders continued into the 1980s, with a few scientifically verifiable and meaningful results. As such, continuing studies involving placebo-controlled as well as double-blind studies regarding the use of phenylalanine for depression are required.

Parkinson’s Disease

Some research has been performed regarding the potential of phenylalanine as part of a treatment plan to reduce the symptoms of Parkinson’s disease. Animal studies suggest a potential for phenylalanine to improve walking, balance, reduced rigidity, depression, as well as speech difficulties commonly linked with Parkinson’s disease conditions. Till date, no studies on humans have been conducted.

When it comes to the therapeutic uses of phenylalanine in the treatment of Parkinson’s symptoms, safety issues have been noted. Older studies (mid-1970s) have shown that use of amino acids like D-phenylalanine and L-methionine may cause more harm than good, according to two studies reported in journals dating in the mid-1980s.

A more recent article published in Neurology in 1993, “Aspartame use in Parkinson’s disease“(24)[21] determined that in a very small study group (18 patients diagnosed with Parkinson’s disease with protein sensitive motor fluctuations) were given 600 to 1,200 mg of aspartame (or a placebo) in a single crossover, double-blind study. The 600 mg of aspartame was reported not to have any effect on motor status or plasma PA. On the other hand, the 1,200 mg doses of aspartame increased the plasma PA, and while no benefits in motor performance were perceived, they did not decline either. As a result, it was determined that heavy use of products containing aspartame sweeteners did not have any negative effect on Parkinson’s disease patients.

Side Effects And Contraindications For Use 

Supplemental forms of phenylalanine and other products containing artificial sweeteners like aspartame are not recommended for pregnant women or any individual diagnosed with diabetes, anxiety attacks, pre-existing pigmented melanoma, high blood pressure, or phenylketonuria.

In pregnant women, phenylalanine may negatively alter brain growth in the developing fetus. That applies to sweeteners such as aspartame that also contain high levels of phenylalanine.


Phenylalanine has the potential to interact and interfere with a number of drugs. It is important for anyone being treated with medication to always verify with a physician regarding the safety of using phenylalanine supplements or any products containing it. A handful of medications with possible interactions with phenylalanine include:

Antipsychotics (including neuroleptic drugs) – L-phenylalanine may interact with drugs prescribed in the treatment of tardive dyskinesia, which is a relatively common and serious side effect that can occur when individuals are taking neuroleptics. Tardive dyskinesia is a neurological disorder that causes involuntary and often irreversible, delayed, and abnormal movements of facial features, and sometimes, involves the extremities or the torso.

A few neuroleptic drugs that phenylalanine may interact or interfere with include, but are not limited to:

  • Haloperidol
  • Chlorpromazine
  • Fluphenazine
  • Trifluoperazine
  • Phenytoin (Dilantin)
  • Valproic acid (Depakote and Depakene)
  • Carbamazepine (Tegretol)

MAOIs (monoamine oxidase inhibitors) – More commonly known as antidepressants, MAOIs are older forms of drugs that, though not commonly used now, are still on the market. Some of the most common monoamine oxidase inhibitors that interfere with phenylalanine include:

  • Phenelzine (Nardil)
  • Isocarboxazid (Marplan)
  • Tranylcypromine sulfate (Parnate)

Be aware that taking any of the above-listed MAOIs with phenylalanine can initiate a severe hypertensive crisis that can lead to stroke or heart attack.

Note – Anyone taking MAOIs should avoid any supplements and foods that contain phenylalanine.

Levodopa – Commonly prescribed in the treatment of Parkinson’s disease to reduce symptoms, a few reports have noted that phenylalanine may contribute to a reduction in the efficacy of levodopa (brand name Sinemet). It is believed that the phenylalanine restricts the absorption of levodopa and can actually worsen Parkinson’s conditions(25).[22]

Baclofen – The absorption of baclofen (brand name Lioresal) may be interrupted with the use of phenylalanine. Commonly prescribed to reduce and provide relief of muscle spasms often associated with Parkinson’s disease or seizure disorders, patients are cautioned to avoid taking baclofen with meals, and especially those that are high in protein content, as well as with any supplements or products containing phenylalanine.

Selegiline – A selective MAO inhibitor, Selegiline (brand names Eldepryl or Deprenyl), combined with L-phenylalanine, can enhance the antidepressant effects of phenylalanine, and they should be avoided being taken together.


Phenylalanine plays an important role in numerous processes in the body. However, too much of anything can give rise to problems. While considering taking supplements or using artificial sweeteners, be aware of your current health status. If you have been diagnosed with any medical condition, confer with a physician or pharmacist regarding potential interaction of phenylalanine with any currently prescribed drugs, over-the-counter products, and even herbal supplements.