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Phenylalanine

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Also listed as: D-phenylalanine, DL-phenylalanine, L-phenylalanine
Related terms
Background
Evidencetable
Tradition
Dosing
Safety
Interactions
Attribution
Bibliography

Related Terms
  • Alpha-aminohydrocinnamic acid, beta-phenyl-alanine, Cari Loder regime, DLPA, D-phenylalanine, DL-phenylalanine, L-phenylalanine.

Background
  • Phenylalanine is available as a dietary supplement in the form of L-phenylalanine, D-phenylalanine, and DL-phenylalanine. L-phenylalanine is an essential amino acid in humans, and proteins contain only this form. The role of D-phenylalanine in humans is unclear. DL-phenylalanine is a manmade product made of 50 percent D-phenylalanine and 50 percent L-phenylalanine.
  • Depression is a common use for L-phenylalanine or DL-phenylalanine. Pain is a common use for D-phenylalanine. However, evidence is lacking to support this use.
  • Studies suggest that L-phenylalanine in combination with exposure to ultraviolet A (UVA) light or sunlight may help treat vitiligo, a condition in which there is a loss of skin pigment. This combination may also be used with a cream or gel of 10 percent phenylalanine, according to European studies.
  • Significant side effects include worsened Parkinson's disease with DL-phenylalanine and worsened movement disorders with L-phenylalanine.
  • People who have with phenylketonuria (PKU, a condition in which the body cannot break down phenylalanine) should follow a strict phenylalanine-restricted diet. Left untreated in mothers, PKU may lead to birth defects and health problems in babies. Higher phenylalanine levels in mothers have been found to increase the risk of birth defects.

Evidence Table

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. GRADE *


DL-phenylalanine has been studied for potential benefits in adults with attention deficit hyperactivity disorder (ADHD). However, there are some conflicting results. Further research is needed in this area to support the use of phenylalanine for this condition.

C


D-phenylalanine in combination with other agents may help reduce symptoms of alcohol withdrawal. However, the effect of D-phenylalanine alone is unclear. Further study is needed before a firm conclusion can be made.

C


D-phenylalanine has been found to increase the pain-relieving effects of acupuncture during tooth removal. More information is needed in this field before the use of phenylalanine as an additional therapy for dental pain can be supported.

C


L-phenylalanine has been found to improve mood in people who have major depression. A combination of L-phenylalanine and selegiline (L-deprenyl) has also been found to benefit those with this condition. DL-phenylalanine and D-phenylalanine have also been studied for depression, although the results are unclear. Further high-quality research is needed in this area.

C


L-phenylalanine has been studied in combination with ultraviolet A (UVA) light or exposure to sunlight for the treatment of vitiligo. European studies report that this combination may be used with a cream or gel of 10 percent phenylalanine. However, these preparations may not be available in the United States. Further study is needed in this area.

C


Levels of phenylalanine have been found to be lower in people with attention deficit disorder (ADD) and attention deficit hyperactivity disorder (ADHD). D-phenylalanine has been studied for people with ADHD. However, it was found to lack benefit. Further high-quality research is needed in this area.

D


D-phenylalanine has been found to lack effect on the enhancement of acupuncture for low back pain. Further high-quality studies are needed.

D


D-phenylalanine has been found to lack benefit for people who have long-term pain. Research is limited in this area, and further study is needed.

D


The Cari Loder regime is a proposed method of treatment for multiple sclerosis (MS) that includes L-phenylalanine, lofepramine, and vitamin B12 injected into the vein. However, this combination has been found to lack effect on symptoms of MS.

F


Phenylalanine has been studied for phenylketonuria, with negative effects reported in terms of mood and brain function. A phenylalanine-restricted diet is advised in people with this disease.

F
* Key to grades

A: Strong scientific evidence for this use
B: Good scientific evidence for this use
C: Unclear scientific evidence for this use
D: Fair scientific evidence for this use (it may not work)
F: Strong scientific evidence against this use (it likley does not work)


Tradition / Theory

The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.

  • Osteoarthritis, Parkinson's disease, rheumatoid arthritis.

Dosing

Adults (18 years and older)

  • For ADHD in adults, 50 milligrams of DL-phenylalanine has been taken by mouth three times daily, with a gradual increase to a maximum of 400 milligrams three times daily for 2-4 weeks.
  • For long-term pain, 250 milligrams of D-phenylalanine has been taken by mouth four times daily for four weeks.
  • For dental pain relief during tooth removal, 2-4 grams of D-phenylalanine has been taken by mouth 30 minutes before acupuncture.
  • For depression, 500 milligrams of L-phenylalanine has been taken by mouth twice daily (morning and noon), then increasing up to 14 grams daily. A dose of 250 milligrams of L-phenylalanine has been taken by mouth once daily for 28-96 days. D-phenylalanine has been taken by mouth at doses of 100-600 milligrams daily for 15 days to four weeks. DL-phenylalanine has been taken by mouth at doses of 50-200 milligrams daily for 15-30 days.
  • For low back pain, 1.5 grams of D-phenylalanine has been taken by mouth daily in three divided doses (0.5 grams after the evening meal and at bedtime on the day before acupuncture, and 0.5 grams after breakfast on the day of acupuncture), or four grams has been taken by mouth in a single dose 30 minutes before acupuncture.
  • For phenylketonuria (PKU), phenylalanine has been taken by mouth daily for four weeks at a dose based on sex and weight (4,000 milligrams for males under 60 kilograms; 4,500 milligrams for males 60-94 kilograms; 5,000 milligrams for males over 95 kilograms; 2,500 milligrams for females under 50 kilograms; 3,000 milligrams for females 50-84 kilograms; and 3,500 milligrams for females over 85 kilograms).
  • For vitiligo, 50-100 milligrams of L-phenylalanine per kilogram of body weight has been taken by mouth once daily (with water after or during breakfast with a low amount of protein, such as two slices of brown bread with jam and a cup of tea). L-phenylalanine has been taken by mouth at a dose of 50 milligrams per kilogram three times weekly for up to three months. A gel containing 10 percent phenylalanine has been applied to the skin from April through October. A cream containing 10 percent phenylalanine has been applied to the skin.

Children (under 18 years old)

  • For ADHD in children, 10 milligrams of D-phenylalanine per kilogram of body weight has been taken by mouth daily in four divided doses, with the dose gradually increasing over the first three days to a maximum of 20 milligrams per kilogram of body weight daily in four divided doses.
  • For vitiligo, phenylalanine has been taken by mouth at doses of 50-100 milligrams per kilogram daily.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

  • Avoid in people with known allergy or sensitivity to D-phenylalanine, DL-phenylalanine, or L-phenylalanine.

Side Effects and Warnings

  • Phenylalanine is likely safe in the form of L-phenylalanine, taken by mouth in doses of 50-100 milligrams per kilogram daily for about 1.5 years to treat vitiligo. Phenylalanine is likely safe in the form of D-phenylalanine, taken by mouth in doses of 2-4 grams, 30 minutes before acupuncture, for the treatment of dental pain.
  • Phenylalanine is possibly safe in the form of L-phenylalanine, taken by mouth in doses of up to 14 grams daily plus 100 milligrams pyridoxine, twice a day for three weeks, for the treatment of depression.
  • Phenylalanine may cause abnormal heart rhythms, anxiety, constipation, emotional changes, fatigue, headache, heartburn, nausea, sedation, sleep difficulty, worsened cognitive function and/or quality of life (people with PKU), worsened movement disorder symptoms, worsened Parkinson's disease symptoms, and worsened schizophrenia.
  • Phenylalanine may interfere with the way the body processes certain drugs using the liver's "cytochrome P450" enzyme system.
  • Use cautiously in people who are taking monoamine oxidase inhibitors (MAOIs), and in those who have anxiety or other mental disorders, headaches or migraines, high blood pressure, sleep disorders, and stomach or intestine disorders.
  • Avoid in people who have movement disorders, Parkinson's disease, or phenylketonuria (PKU), and in those who are taking levodopa and/or carbidopa.
  • Avoid in people with known allergy or sensitivity to D-phenylalanine, DL-phenylalanine, or L-phenylalanine.

Pregnancy and Breastfeeding

  • There is a lack of scientific evidence on the use of phenylalanine during pregnancy or breastfeeding.

Interactions

Interactions with Drugs

  • Phenylalanine may interfere with the way the body processes certain drugs using the liver's "cytochrome P450" enzyme system. As a result, the levels of these drugs may be altered in the blood, and may cause altered effects or potentially serious adverse reactions. People using any medications should check the package insert, and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.
  • Phenylalanine may also interact with agents for the heart, agents for mental disorders, agents that affect the immune system, antidepressants (monoamine oxidase inhibitors [MAOIs]), baclofen, carbidopa/levodopa (Sinemet®), cefdinir, central nervous system (CNS) stimulants, clobetasol, levodopa, lofepramine, pain relievers, sapropterin dihydrochloride (Medi-Span®), and sedatives.

Interactions with Herbs and Dietary Supplements

  • Phenylalanine may interfere with the way the body processes certain herbs or supplements using the liver's "cytochrome P450" enzyme system. As a result, the levels of other herbs or supplements may be altered in the blood. It may also alter the effects that other herbs or supplements possibly have on the P450 system.
  • Phenylalanine may also interact with acupuncture, amino acids, antidepressants (monoamine oxidase inhibitors [MAOIs]), herbs and supplements for the heart, herbs and supplements for mental disorders, herbs and supplements that affect the immune system, pain relievers, sedatives, and vitamin B12.

Attribution
  • This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
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  2. Currell K, Moore DR, Peeling P, et al. A-Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance - part 28. Br.J Sports Med. 2012;46(1):75-76.
  3. Deutz NE, Safar A, Schutzler S, et al. Muscle protein synthesis in cancer patients can be stimulated with a specially formulated medical food. Clin Nutr 2011;30(6):759-768.
  4. Feillet F and Agostoni C. Nutritional issues in treating phenylketonuria. J Inherit.Metab Dis. 2010;33(6):659-664.
  5. Huang L, Hogewind-Schoonenboom JE, van Dongen MJ, et al. Methionine requirement of the enterally fed term infant in the first month of life in the presence of cysteine. Am J Clin Nutr 2012;95(5):1048-1054.
  6. Jukic T, Rojc B, Boben-Bardutzky D, et al. The use of a food supplementation with D-phenylalanine, L-glutamine and L-5-hydroxytriptophan in the alleviation of alcohol withdrawal symptoms. Coll.Antropol. 2011;35(4):1225-1230.
  7. MacDonald A, Evans S, Cochrane B, et al. Weaning infants with phenylketonuria: a review. J Hum.Nutr Diet. 2012;25(2):103-110.
  8. Pasiakos SM, McClung HL, McClung JP, et al. Leucine-enriched essential amino acid supplementation during moderate steady state exercise enhances postexercise muscle protein synthesis. Am J Clin Nutr 2011;94(3):809-818.
  9. Rocha JC and Martel F. Large neutral amino acids supplementation in phenylketonuric patients. J Inherit.Metab Dis. 2009;32(4):472-480.
  10. Rocha JC and Martins MJ. Oxidative stress in phenylketonuria: future directions. J Inherit.Metab Dis. 2012;35(3):381-398.
  11. Rucklidge JJ, Johnstone J, and Kaplan BJ. Nutrient supplementation approaches in the treatment of ADHD. Expert.Rev.Neurother. 2009;9(4):461-476.
  12. Tang JE, Lysecki PJ, Manolakos JJ, et al. Bolus arginine supplementation affects neither muscle blood flow nor muscle protein synthesis in young men at rest or after resistance exercise. J Nutr 2011;141(2):195-200.
  13. ten Hoedt AE, de Sonneville LM, Francois B, et al. High phenylalanine levels directly affect mood and sustained attention in adults with phenylketonuria: a randomised, double-blind, placebo-controlled, crossover trial. J Inherit.Metab Dis. 2011;34(1):165-171.
  14. van Spronsen FJ, de Groot MJ, Hoeksma M, et al. Large neutral amino acids in the treatment of PKU: from theory to practice. J Inherit.Metab Dis. 2010;33(6):671-676.
  15. Webster D and Wildgoose J. Tyrosine supplementation for phenylketonuria. Cochrane.Database.Syst.Rev. 2010;(8):CD001507.

Copyright © 2011 Natural Standard (www.naturalstandard.com)


The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

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