Phenylalanine

While some complementary and alternative techniques have been studied scientifically, high-quality data regarding safety, effectiveness, and mechanism of action are limited or controversial for most therapies. Whenever possible, it is recommended that practitioners be licensed by a recognized professional organization that adheres to clearly published standards. In addition, before starting a new technique or engaging a practitioner, it is recommended that patients speak with their primary healthcare provider(s). Potential benefits, risks (including financial costs), and alternatives should be carefully considered. The below monograph is designed to provide historical background and an overview of clinically-oriented research, and neither advocates for or against the use of a particular therapy.

Related Terms

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

Background

  • Phenylalanine is commercially available as a dietary supplement in the forms of L-phenylalanine, D-phenylalanine, and DL-phenylalanine. L-phenylalanine is an essential amino acid in humans, and proteins contain only this form. According to experts, L-phenylalanine likely is likely safe when consumed in amounts that typically occur in food. The role of D-phenylalanine in humans is unclear. DL-phenylalanine is a synthetic product made of 50% D-phenylalanine and 50% L-phenylalanine.

  • Good scientific evidence (reported primarily in the 1970s and 1980s) supports the use of L-phenylalanine or DL-phenylalanine to treat depression. Good scientific evidence also supports the use of L-phenylalanine, in combination with exposure to ultraviolet A light or sunlight, to treat vitiligo, a skin condition characterized by patchy loss of skin pigments.

  • The Cari Loder regime is a treatment for multiple sclerosis (MS) that includes phenylalanine, as well as lofepramine (an antidepressant not available in the United States), and intramuscular injections of vitamin B12. The treatment was developed by Cari Loder, a research scientist and MS patient, and it was described in the popular literature. Subsequent clinical research failed to produce data supporting the use of the regime to treat MS.

  • Areas of current research interest regarding phenylalanine include diagnosis, dietetics, nutrition, and physiology.

Scientific Evidence

Uses

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.

Depression

A number of reports, published primarily in the 1970s and 1980s, provide good evidence for the use of L-phenylalanine or DL-phenylalanine in treating depression. Additional research is needed before a conclusion can be made.

Vitiligo

Several studies suggests that L-phenylalanine, in combination with exposure to ultraviolet A light or sunlight, may help treat vitiligo (patches of unpigmented skin). Additional studies are needed in this area.

Attention deficit hyperactivity disorder (adults)

Limited research suggests that DL-phenylalanine may have positive effects on mood in adults with attention-deficit hyperactivity disorder (ADHD). Additional research is needed before a conclusion can be made

Dental anesthesia

Preliminary research suggests that D-phenylalanine may enhance the effect of acupuncture as anesthesia during tooth extraction. Additional research is necessary before a conclusion can be made.

Attention deficit hyperactivity disorder (children)

Limited research suggests that D-phenylalanine may be ineffective for treating attention-deficit hyperactivity disorder (ADHD) in children. Additional research is needed in this area.

Chronic pain

Limited research suggests that D-phenylalanine may be ineffective for treating various form of chronic pain. Additional research is needed before a conclusion can be made.

Low back pain

Preliminary research suggests that D-phenylalanine may not enhance acupuncture’s effect on low back pain. Additional research is necessary before a conclusion can be made.

Multiple sclerosis

Limited research suggests that Cari Loder’s regime (L-phenylalanine, lofepramine (an antidepressant not available in the United States), and intramuscular vitamin B12) likely lacks an effect on disabilities associated with multiple sclerosis. Additional research is needed before a conclusion can be made.

*Key to grades:

Tradition

The below uses are based on tradition or scientific theories. 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 health care professional.

  • Alcohol withdrawal, osteoarthritis, Parkinson’s disease, rheumatoid arthritis.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older)

  • For attention-deficit hyperactivity disorder (ADHD) in adults, 50 milligrams of DL-phenylalanine has been taken by mouth three times daily, with a gradual increase in dose to a maximum of 400 milligrams three times daily.

  • For chronic pain, 250 milligrams of D-phenylalanine has been taken by mouth four times daily.

  • For dental anesthesia, two or four grams of D-phenylalanine has been taken by mouth 30 minutes before acupuncture for anesthesia during teeth extraction.

  • For depression, 500 milligrams of L-phenylalanine has been taken by mouth twice daily (morning and noon), with the dose gradually increasing daily by 500 milligrams in the morning and at noon until therapeutic effects or adverse effects occur, or to a limit of 2-3 grams over the dose that was taken one week prior), up to 14 grams daily.

  • 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 in a single dose 30 minutes before acupuncture.

  • For multiple sclerosis, 500 milligrams of L-phenylalanine has been taken by mouth twice daily with 70 milligrams of lofepramine (an antidepressant not available in the United States) twice daily, with weekly intramuscular injections of 1,000 micrograms of vitamin B12 (this is known as Cari Loder’s regime).

  • For vitiligo, 50, 70, or 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). In some cases, the 50- and 100-milligram doses have been followed 15 minutes later by application of a gel of 10% phenylalanine (not available in the United States).

Children (under 18 years old)

  • For attention-deficit hyperactivity disorder (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.

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 with known allergy or hypersensitivity to D-phenylalanine, DL-phenylalanine, or L-phenylalanine.

Side Effects and Warnings

  • Phenylalanine may cause abnormal electrocardiogram (EKG) readings, less sunburn (particularly on vitiligo patches), constipation, headache, heartburn, nausea, and fatigue. Phenylalanine may worsen tardive dyskinesia in people with schizophrenia.

  • Phenylalanine may increase blood pressure. Caution is advised in people with blood pressure disorders, or in those taking drugs, herbs, or supplements that affect blood pressure.

  • Use cautiously in people taking monoamine oxidase inhibitors (MAOIs), given the theoretical possibility of a severe increase in blood pressure.

  • Use cautiously in people with anxiety disorders, other psychiatric disorders, or sleep disorders, as phenylalanine has been associated with anxiety, hypomania (a condition similar to, but less severe than, mania), and insomnia.

  • Avoid in people with Parkinson’s disease or tardive dyskinesia, as symptoms may worsen.

  • Avoid in people with phenylketonuria (PKU).

  • Avoid with known allergy or hypersensitivity to D-phenylalanine, DL-phenylalanine, or L-phenylalanine.

Pregnancy and Breastfeeding

  • There is currently a lack of available scientific evidence on the use of phenylalanine in pregnant or breastfeeding women.

Interactions

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. 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.

Interactions with Drugs

  • Phenylalanine may raise blood pressure. Caution is advised in people taking drugs that affect blood pressure.

  • Phenylalanine may increase the amount of drowsiness caused by some drugs. Examples include benzodiazepines such as lorazepam (Ativan®) or diazepam (Valium®), barbiturates such as phenobarbital, narcotics such as codeine, some antidepressants, and alcohol. Caution is advised while driving or operating machinery.

  • 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 change in the blood and may cause increased or decreased effects or potentially serious adverse reactions. Those taking any medication should check the package insert and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.

  • Phenylalanine may also interact with antidepressants (including bupropion, monoamine oxidase inhibitors, and tricyclic antidepressants), antipsychotics, baclofen, clobetasol, drugs that affect the immune system, levodopa, or lofepramine.

Interactions with Herbs and Dietary Supplements

  • Phenylalanine may raise blood pressure. Caution is advised in people taking herbs or supplements that lower blood pressure.

  • Phenylalanine may increase the amount of drowsiness caused by some herbs or 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 change in the blood. It may also alter the effects that other herbs or supplements potentially may have on the P450 system.

  • Phenylalanine may also interact with acupuncture, amino acids, antidepressants (including monoamine oxidase inhibitors (MAOIs), antipsychotics, herbs and supplements that affect the immune system, or vitamin B12.

Author Information

  • 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).

References

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

  1. Boirie Y, Albright R, Bigelow M, et al. Impairment of phenylalanine conversion to tyrosine in end-stage renal disease causing tyrosine deficiency. Kidney Int 2004;66(2):591-596. View Abstract
  2. Camacho F, Mazuecos J. Treatment of vitiligo with oral and topical phenylalanine: 6 years of experience. Arch Dermatol 1999;135(2):216-217. View Abstract
  3. Camacho F, Mazuecos J. Oral and topical L-phenylalanine, clobetasol propionate, and UVA/sunlight–a new study for the treatment of vitiligo. J Drugs Dermatol 2002;1(2):127-131. View Abstract
  4. Darling PB, Dunn M, Gilani GS, et al. Phenylalanine kinetics differ between formula-fed and human milk-fed preterm infants. J Nutr 2004;134(10):2540-2545. View Abstract
  5. Durham WJ, Miller SL, Yeckel CW, et al. Leg glucose and protein metabolism during an acute bout of resistance exercise in humans. J Appl Physiol 2004;97(4):1379-1386. View Abstract
  6. Fernstrom JD, Fernstrom MH. Tyrosine, phenylalanine, and catecholamine synthesis and function in the brain. J Nutr 2007;137(6 Suppl 1):1539S-1547S. View Abstract
  7. Festi D, Capodicasa S, Sandri L, et al. Measurement of hepatic functional mass by means of 13C-methacetin and 13C-phenylalanine breath tests in chronic liver disease: comparison with Child-Pugh score and serum bile acid levels. World J Gastroenterol 2005;11(1):142-148. View Abstract
  8. Koch R, Hanley W, Levy H, et al. The Maternal Phenylketonuria International Study: 1984-2002. Pediatrics 2003;112(6 Pt 2):1523-1529. View Abstract
  9. Levy HL, Waisbren SE, Guttler F, et al. Pregnancy experiences in the woman with mild hyperphenylalaninemia. Pediatrics 2003;112(6 Pt 2):1548-1552. View Abstract
  10. Moats RA, Moseley KD, Koch R, et al. Brain phenylalanine concentrations in phenylketonuria: research and treatment of adults. Pediatrics 2003;112(6 Pt 2):1575-1579. View Abstract
  11. Mosnik DM, Spring B, Rogers K, et al. Tardive dyskinesia exacerbated after ingestion of phenylalanine by schizophrenic patients. Neuropsychopharmacology 1997;16(2):136-146. View Abstract
  12. Okano Y, Hase Y, Kawajiri M, et al. In vivo studies of phenylalanine hydroxylase by phenylalanine breath test: diagnosis of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency. Pediatr Res 2004;56(5):714-719. View Abstract
  13. Thompson P, Balis F, Serabe BM, et al. Pharmacokinetics of phenylacetate administered as a 30-min infusion in children with refractory cancer. Cancer Chemother Pharmacol 2003;52(5):417-423. View Abstract
  14. Wade DT, Young CA, Chaudhuri KR, et al. A randomised placebo controlled exploratory study of vitamin B-12, lofepramine, and L-phenylalanine (the “Cari Loder regime”) in the treatment of multiple sclerosis. J Neurol Neurosurg Psychiatry 2002;73(3):246-249. View Abstract
  15. Widaman KF, Azen C. Relation of prenatal phenylalanine exposure to infant and childhood cognitive outcomes: results from the International Maternal PKU Collaborative Study. Pediatrics 2003;112(6 Pt 2):1537-1543. View Abstract

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.