ProEndorphin: Energy, Mood and Neurotransmitters
Phenylalanine in PROENDORPHIN
What is Phenylalanine? 
Phenylalanine is an essential amino acid - meaning that the body cannot synthesize it on its own and we must get it from the diet. The primary dietary sources of phenylalanine are high protein foods such as meat, fish, eggs and dairy products. Amino acids come in two forms, designated as "L" and "D" forms. The Lform is the naturally occurring form in foods, whereas the D-form is the synthetic variety. Sometimes the D-form is removed, but in the case of phenylalanine, the combination of the two forms is used to take advantage of the unique characteristics of both forms. The combined form of the supplement is known as DL-phenylalanine or DLPA. [44]
General Functions
DLPA has two distinct fates in the body. The L-form of phenylalanine can be converted in the body to another amino acid - tyrosine. Tyrosine, in turn, can be convelied into one of several neurotransmitter molecules (L-dopa, norepinephrine, and epinephrine), each of which have important functions in brain metabolism. The D-form of phenylalanine cannot be converted to tyrosine, but it can be converted to another compound called phenylethylamine (as can the L-form), which may have effects in elevating mood, treating depression and altering pain sensation. [44]
In addition, phenylalanine teams up with tryptophan, another amino acid, to control the release of cholecystokinin, an intestinal hormone commonly called CCK. It plays an instrumental role in controlling appetite by signaling the brain when the stomach is full, thereby turning off the hunger signals that can lead to overeating. Phenylalanine is capable of passing through the brain's protective blood-brain barrier and acting directly on brain chemistry. It is thought to play roles in memory and alertness. Phenylalanine is also thought to prevent the breakdown of the brain's natural painkillers. [45]
Phenylalanine and Pain Management
Research suggests that DL-phenylalanine has an analgesic (pain relief) effect by way of blocking the degradation of enkephalin by the enzyme carboxypeptidase A. Enkephalins are endorphins in the brain that bind to specific receptor sites, including pain-related opiate receptors. Unlike other substances that target opiate receptors, there has been no data to indicate addiction or withdrawal symptoms associated with phenylalanine. The slow-acting, but long-lasting compound is recommended for chronic pain rather than acute pain.
*In a human trial, patients suffering from chronic pain were given 250 mg phenylalanine orally 3 or 4 times a day for 5 weeks. Significant relief occurred after 4 weeks for the total population (n=43) and after 2 weeks for the subset of arthritic patients (n=30). [46]
*In animal studies, D-phenylalanine decreased chronic pain within 15 minutes of administration and the effects lasted up to six days. [47] It also decreased responses to acute pain. These findings have been independently verified in at least five other studies. [48,49]
*Twenty adult patients with longstanding intractable pain of various conditions, resistant to previous therapy, were admitted to a double-blind, crossover study in which orally administered D-phenylalanine, 250 mg, three times daily was compared with placebo. Assessments were made at two weeks, the crossover time and at four weeks when patients reported whether they had less or more pain or that there was no change. Of the twenty patients, seven showed an improvement of 50% or more while receiving phenylalanine, one patient improved on placebo, two patients withdrew because of lack of analgesia and four patients on D-phenylalanine reported the occurrence of side-effects. It was concluded that D-phenylalanine produced significant analgesia in the patients studied and further investigation of this class of agent was warranted. [50]
Phenylalanine and Mood Enhancement
Mild depression, "the blues" and lack of energy can, often times, be non-specific responses to a wide variety of stressors, hormone imbalances or biochemical abnormalities. There are millions of tired and stressed-out people who can relate to promises of natural products that will enhance their brain function; and the number is continually growing as the worldwide population ages. An important part of maintaining optimal brain function is ensuring that the brain receives an adequate supply of nutrients that promote improvements in mood, emotions, confidence and self-efficacy. Along with the proper nutrients, regular exercise and adequate diet can result in profound changes in the body's own production of mood elevating chemicals such as the endorphins that cause "runner's high" and neurotransmitters such as serotonin that contribute to emotional well-being. Phenylalanine has been associated with improved mental function - particularly under conditions of chronic stress. Phenylalanine is converted to the amino acid, tyrosine, and then in turn converted to the neurotransmitter norepinephrine, which may help elevate mood. [51]
*In a double-blind controlled study, DL-phenylalanine (150-200 mg/24 h) or imipramine, an antidepressant drug, (150-200 mg/24 h) was administered to 40 depressed patients (20 patients in each group) for 30 days. Diagnoses were established according to the International Classification of Diseases. The AMP system, the Hamilton Depression Scale and the Bf- S self-rating questionnaire were used to document psychopathological, neurologic, and somatic changes. Twenty-seven patients (14 on imipramine, 13 on phenylalanine) completed the 30 day trial. No statistical difference could be found between these two drug treatments. It was concluded that DL-phenylalanine might have substantial antidepressant properties. [52]
*Another human study compared the effectiveness ofD-phenylalanine to imipramine, anantidepressant drug. Sixty people with depression were randomly assigned 100 mg daily doses of either DPA or imipramine for 30 days. The results in both groups were statistically significant, with the DPA showing positive effects more quickly than the antidepressant drug.[53]
SAFETY
The amount of phenylalanine needed to produce toxicity in humans remains unknown. Transient headaches and nausea has, however, been reported when persons supplemented with amounts reaching nearly 1500 mg per day. [54]
Phenylalanine should be avoided by persons with phenylketonuria (PKU) and tardive dyskinesia .. Tardive dyskinesia (TD) is characterized by a condition of abnormal, repetitive and uncontrollable movements, resulting from the long-term use of antipsychotic medications (e.g. schizophrenia). These individuals may suffer from an abnormality, which sharply inhibits the processing of phenylalanine. [54]
GUIDELINES FOR USE
The National Research Council has established recommended dietary allowances (RDAs) for phenylalanine. Individuals over 13 years of age should get 14 mg/kg of bodyweight per day.
Some adults may need to tailor intake to an allowance approaching 39 mg/kg of bodyweight to obtain physiological improvement. The median intake of phenylalanine ranges from 750 to 3,000 mg per day for adults. [54]
In addition, the U.S. National Academy of Sciences recommends that healthy people achieve 0.36 grams of highly bioavailable protein for each pound of bodyweight - equaling 0.8 grams of protein, per kilogram of bodyweight per day. [54]
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