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L-Phenylalanine May Improve Mood

Phenylalanine is a unique amino acid and one of the few amino acids with both the L- and D- forms active. Because it serves as precursor to the neurotransmitters involved in the elevation of mood, this amino acid supplement has been investigated for its antidepressant effects. This article discusses the efficacy of L-phenylalanine as an antidepressant, how to take it to improve mood and possible dangers involved in combining the amino acid with other drugs.
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What is L-Phenylalanine?

Phenylalanine is an essential, alpha amino acid. There are 3 forms of the amino acid: the natural L-phenylalanine, the synthetic try-phenylalanine-for-depression-and-anxiety and DL-phenylalanine, a combination of the first two forms.

The primary use of L-phenylalanine in the body is in the production of tyrosine, another amino acid.

Tyrosine is the precursor of monoamine neurotransmitters such as dopamine, epinephrine and norepinephrine. Given the importance of these brain chemicals, phenylalanine is important to maintain adequate levels of monoamine neurotransmitters in the brain.

When L-phenylalanine crosses into the brain, it is converted to L-tyrosine and then to L-dopa which is further converted into the three neurotransmitters mentioned above.

However, to cross the blood-brain barrier, L-phenylalanine shares the same transport mechanism with tryptophan.

Tryptophan is another amino acid essential for the synthesis of serotonin, a neurotransmitter important to mood. When phenylalanine is ingested in large amounts, it can reduce the absorption of tryptophan into the brain and, by extension, reduce the production of serotonin.

On the other hand, phenylalanine deficiency can cause mental confusion, reduced alertness, lethargy, depression, memory impairment and loss of appetite.

Side Effects, Toxicity and Phenylketonuria

Side effects of phenylalanine include anxiety, restlessness and hyperactivity especially in children.

Although phenylalanine supplements are mostly well-tolerated, they can cause nausea, headaches and heartburn in high doses. At doses higher than 5,000 mg per day, phenylalanine becomes toxic and can damage the nerves.

Another peculiar form of phenylalanine toxicity has also been reported. It affects people who have a metabolic disorder known as phenylketonuria.

Phenylketonuria is a rare disorder in which the enzyme required to properly utilize phenylalanine is missing. This results in the accumulation of phenylalanine and low levels of the neurotransmitters that are produced from this amino acid.

In an even rarer form of phenylketonuria, it is biopterin, a coenzyme, which is missing.

Because phenylalanine is naturally found in breast milk, phenylketonuria must be caught early on in newborns. If left untreated, this disorder can cause permanent mental retardation within 3 weeks in affected babies.

Children and adults with phenylketonuria are advised to avoid foods and supplements rich in phenylalanine. Excellent dietary sources of phenylalanine include proteins such as eggs, meat, fish, cheese and milk.

To ensure optimal levels of neurotransmitters made from this amino acid, phenylketonurics are advised to take tyrosine supplements instead.

Care should also be taken with packaged foods containing phenylalanine or products that can increase phenylalanine in the body. For example, aspartame, a popular artificial sweetener can increase phenylalanine levels.

Although, phenylalanine is only a metabolite of aspartame and the sweetener’s potential of increasing phenylalanine levels is moderate, the risk is high enough for regulatory bodies to mandate warnings on labels of products containing aspartame and similar products.

Because of its ability to change the levels and activities of neurotransmitters, phenylalanine can interact with drugs that share similar mechanisms of action.

Such drugs include MAOI (monoamine oxidase inhibitor) antidepressants, levodopa and antipsychotics.

Phenylalanine As A Supplement

Phenylalanine supplements are available in three different forms: L-phenylalanine, D-phenylalanine and DL-phenylalanine (a 50/50 mixture of both the D- and L- forms of the amino acids).

These forms of phenylalanine are available as tablets, capsules, powders and topical creams.

These supplements are used for treating a number of medical conditions including chronic pain, depression, attention-deficit hyperactivity disorder (ADHD), osteoarthritis, rheumatoid arthritis, Parkinson’s disease, symptoms of alcohol withdrawal and vitiligo.

Phenylalanine is useful in the treatment of vitiligo because it is also a precursor of melanin, the chief pigment molecule in the skin.

D- and L-Phenylalanine

The amino acid is also recommended in the treatment of chronic pain and different forms of arthritis because of its analgesic properties. The form of phenylalanine with analgesic benefits is D-phenylalanine.

D-phenylalanine is one of the few D-amino acids with known therapeutic benefits.

To function as an analgesic, D-phenylalanine blocks the enzyme responsible for breaking down endorphins. Since endorphins are natural painkillers produced in the body, prolonging their activities can produce relief from pain.

In the treatment of depression, ADHD, Parkinson’s disease and alcohol withdrawal symptoms, L-phenylalanine is the active form of the amino acid. L-phenylalanine is effective in management of these conditions because it serves as a precursor to neurotransmitters such as dopamine and norepinephrine.

Therefore, the DL-form of phenylalanine has both an analgesic and antidepressant properties.

D-phenylalanine can also contribute to the antidepressant effect of DL-phenylalanine through its inhibition of endorphin breakdown. When the D-amino acid prevents the breakdown of endorphins, it blocks the release of GABA (gamma aminobutyric acid) in the midbrain while increasing the release of dopamine.

Furthermore, some D-phenylalanine is converted into L-phenylalanine in the body. Therefore, part of the antidepressant properties of the D-amino acid is due to L-phenylalanine.

Medical Uses of L-Phenylalanine

Overall, L-phenylalanine is the more active form of the amino acid in the brain because it crosses the blood-brain barrier more easily than the D-form.

At high doses, L-phenylalanine can actually serve as both an analgesic and an antidepressant. It achieves this feat by blocking a subgroup of calcium channels in the brain.

Other effects of L-phenylalanine in the brain include the antagonism of glycine and glutamate at specific receptors in the cortex and hippocampus. These antagonism of inhibitory neurotransmitters can also contribute to the antidepressant effect of the amino acid.

Studies on L-Phenylalanine and Depression

Phenylalanine as an Antidepressant

In a 1975 study published in the journal, Arzneimittel-Forschung, the usefulness of DL-phenylalanine was investigated in a small group of patients who had failed to respond to popular antidepressants such as MAOIs.

In that study, 23 patients suffering from depression and who had been unsuccessfully treated with standard antidepressants were given 50 or 100 mg of phenylalanine daily for 15 days. The result of the study showed that phenylalanine completely improved mood (became euthymic or non-depressed) in 13 of the patients within 13 days of treatment.

In another study published in the Journal of Neural Transmission in 1977, 20 depressed patients were given 75 – 200 mg/day of DL-phenylalanine for 20 days.

At the end of the study, 8 patients completely recovered while 4 patients experienced significant improvements in mood. Another 4 patients experienced mild to moderate improvements and the other 4 patients did not respond.

This study demonstrates that phenylalanine possesses considerable antidepressant properties and that it is effective for the majority of patients experiencing depression.

Phenylalanine with Standard Antidepressants

A 1984 study published in the same journal studied the efficacy of the combination of phenylalanine and selegiline, an antidepressant drug.

Selegiline is a monoamine oxidase inhibitor used in the treatment of depression, dementia and Parkinson’s disease.

The brand of selegiline used was L-deprenyl. 5 – 10 mg/day of this drug was combined with 250 mg/day of L-phenylalanine and given to 155 depressed patients. The results showed that this combination was effective for 90% of outpatients and 81% of inpatients suffering from depression.

Another study published in the Journal of Clinical Psychiatry in 1991 also reached the same conclusions.

In that study, the combination of selegiline and phenylalanine significantly improved mood in 9 out of the 10 patients recruited for the study. The improvement in mood occurred within hours of taking the combination and 6 of the patients experienced complete relief after 3 days.

Phenylalanine vs. Standard Antidepressants

A 1979 study published in the Archives of Psychiatry and Neurological Sciences compared the efficacy of DL-phenylalanine and imipramine.

Imipramine is a tricyclic antidepressant used in the treatment of major depression and panic disorders.

In this double-blind, placebo-controlled study, 150 – 200 mg/day of either drug was given to each of the 40 participants. After 30 days of treatment, the scores of both groups on the Hamilton Depression Scale and other clinical measures of depression showed that DL-phenylalanine was just as effective as imipramine.

Taking L-Phenylalanine for Depression

Although researchers have used doses as high as 2,500 mg/day of L-phenylalanine, such high doses are not recommended for long-term use unless recommended by a physician.

In treating depression, the usually recommended dose of DL-phenylalanine supplement is 100 – 200 mg/day.

Phenylalanine supplement should not be taken with meals with high protein content. This is because the absorption of phenylalanine will be reduced when there are more amino acids present and competing for absorption sites.

This is all the more important at the blood-brain barrier. Since phenylalanine shares the same transport mechanism with other amino acids such as tryptophan, crossing into the brain becomes even more difficult when the concentrations of these competing amino acids are high.

In addition, care should be taken when combining phenylalanine with other antidepressants.

While such combinations have been shown to be more effective, they are potentially dangerous if they abnormally raise the levels and/or activities of certain neurotransmitters in the brain.

Lastly, phenylalanine supplementation may worsen tardive dyskinesia in depressed patients already suffering from the disorder. Tardive dyskinesia is a neurological disorder characterized by sudden, involuntary and repetitive movements.





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