Phenylalanine as a therapeutic supplement

DEFINITION: Natural substance of the human body used as a supplement to treat specific health conditions.

• PRINCIPAL PROPOSED USE: Depression
• OTHER PROPOSED USES: Attention-deficit/hyperactivity disorder, multiple sclerosis, generalized pain, Parkinson’s disease, rheumatoid arthritis, vitiligo, alcohol withdrawal

Overview

Phenylalanine occurs in two chemical forms: L-phenylalanine, a natural amino acid found in proteins, and its mirror image, D-phenylalanine, a form synthesized in a laboratory. Some studies have involved the L-form, others the D-form, and still others a combination of the two known as DL-phenylalanine.

In the body, phenylalanine is converted into another amino acid called tyrosine. Tyrosine, in turn, is converted into L-dopa, epinephrine, and norepinephrine, three key neurotransmitters (chemicals that transmit signals between nerve cells). Because some antidepressants work by raising levels of norepinephrine, various forms of phenylalanine have been tried as a possible treatment for depression.

D-phenylalanine (but not L-phenylalanine) has been proposed to treat chronic pain. It blocks enkephalinase, an enzyme that may act to increase pain levels in the body. Other proposed natural uses for phenylalanine include the skin condition vitiligo, attention-deficit/hyperactivity disorder (ADHD), alcohol withdrawal, and Parkinson’s disease. 

Requirements and Sources

L-phenylalanine is an essential amino acid, meaning that humans need it for life and the body cannot manufacture it from other chemicals. It is found in protein-rich foods such as meat, fish, poultry, eggs, dairy products, and beans. If people eat enough protein, they are likely to get enough L-phenylalanine for their nutritional needs. There is no nutritional need for D-phenylalanine.

Therapeutic Dosages

D- and DL-phenylalanine are typically taken at a dose of 100 to 200 milligrams (mg) daily for the treatment of depression. For the treatment of chronic pain, studies have used D-phenylalanine in doses as high as 2,500 mg daily. It is best not to take a phenylalanine supplement at the same time as a high-protein meal, as it may not be absorbed well.

Therapeutic Uses

Small double-blind, comparative studies suggest (but do not prove) that both the D- and DL- forms of phenylalanine might be helpful for depression. However, emerging studies have found that low levels of phenylalanine are linked to major depressive disorder. Weak and contradictory evidence has been used to advocate the use of D-phenylalanine as a general analgesic (pain-relieving treatment). Preliminary uncontrolled and double-blind studies found that L-phenylalanine may enhance the effectiveness of ultraviolet for vitiligo.

Highly preliminary evidence suggests that D-phenylalanine may be helpful for multiple sclerosis when combined with transcutaneous electrical nerve stimulation (TENS). D-phenylalanine has also been proposed as a treatment for Parkinson’s disease. Emerging studies appear to support its use for this condition.

Although D- and DL-phenylalanine are marketed as treatments for ADHD, they do not appear to be helpful. Some proponents claim that phenylalanine works better when combined with tyrosine, glutamine, and gamma-aminobutyric acid (GABA), but this has not been proven. Finally, one 2011 study found phenylalanine could have benefits for individuals going through alcohol withdrawal.

Scientific Evidence

Depression. A pair of double-blind comparative studies found that D- or DL-phenylalanine may be as effective as the antidepressant drug imipramine and possibly work more quickly. The larger of the two studies compared the effectiveness of D-phenylalanine at 100 mg daily against the same daily dose of imipramine. Sixty people with depression were randomly assigned to take either imipramine or D-phenylalanine for thirty days. The results in both groups were statistically equivalent, meaning that phenylalanine was about as effective as imipramine. D-phenylalanine worked more rapidly, however, producing significant improvement in only fifteen days. Like most antidepressant drugs, imipramine requires several weeks to take effect.

The other double-blind study followed more than two dozen people, one-half of whom received DL-phenylalanine (150 to 200 mg daily) and the other half imipramine (100 to 150 mg daily). When they were reevaluated after thirty days, both groups had improved by a statistically equal amount. L-phenylalanine has also been tried as a treatment for depression, but not in studies that could provide a scientifically meaningful result.

No double-blind, placebo-controlled studies of phenylalanine for depression have been done. Still, while older studies did not show efficacy, newer studies appeared to indicate that low phenylalanine levels were linked to an increased risk of developing major depressive disorder. These findings warrant further study but fall short of supporting claims.

Chronic pain. The enzyme enkephalinase breaks down enkephalins, naturally occurring substances that reduce pain. D-phenylalanine (but not L-phenylalanine) is thought to block enkephalinase; this could lead to increased enkephalin levels, which, in turn, would tend to reduce pain. On this basis, D-phenylalanine has been proposed as a pain-killing drug.

However, there is no meaningful evidence that it works in this way. A small double-blind, placebo-controlled study reported evidence for the effectiveness of D-phenylalanine in chronic pain, but a careful reexamination of the math involved showed that it proved little. Another small double-blind, placebo-controlled study failed to find any benefits. Another study commonly described as showing D-phenylalanine to be effective suffered from many flaws (including the fact that it lacked a control group) and, therefore, cannot be trusted. While one study did appear to support claims that phenylalanine could provide benefits for patients undergoing alcohol withdrawal, and studies also supported claims of its benefits for vitiligo, other studies could not prove that phenylalanine provided benefits for Parkinson's disease or ADHD.

Safety Issues

The long-term safety of phenylalanine in any of its forms is not known. Both L- and D-phenylalanine must be avoided by those with the rare metabolic disease phenylketonuria (PKU). The maximum safe dosages of phenylalanine have not been established for young children, pregnant or nursing women, or those with severe liver or kidney disease. There are some indications that the combined use of phenylalanine and antipsychotic drugs might increase the risk of developing the long-term side effect known as tardive dyskinesia or worsen symptoms in those who already have it. Like other amino acids, phenylalanine may interfere with the absorption or action of the drug levodopa, which is used for Parkinson’s disease.

Important Interactions

Phenylalanine might interfere with the action of levodopa and other amino acids; those taking amino acids should take phenylalanine only under a physician’s supervision. Persons taking antipsychotic medications should not use phenylalanine.

Bibliography

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