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Tyrosine

Nutrient Name: Tyrosine.
Synonym:L-Tyrosine
Related Substance:L-Phenylalanine.

Summary Table
nutrient description

Physiology and Function

Tyrosine is a conditionally essential amino acid normally synthesized from phenylalanine, which is an essential amino acid. Hepatic conversion ofL-phenylalanine toL-tyrosine can be impaired during infection, trauma, chronic illness, liver disease, or other forms of severe stress, thus making tyrosine a conditionally essential amino acid.

L-Tyrosine plays a critical role in the synthesis of neurotransmitters within the central nervous system (CNS). In particular, it serves as a precursor toL-dopa, dopamine, norepinephrine, and epinephrine, the brain concentrations of which depend on intake of tyrosine. The conversion ofL- tyrosine into these neurotransmitters requires vitamin B6, folic acid, and copper. Tyrosine also requires biopterin (a folate derivative), NADPH and NADH (metabolites of niacin), copper, and vitamin C. Tyrosine acts as an adaptogen through its role as a precursor of norepinephrine and epinephrine.

Several other key activities are among the known functions of tyrosine. Tyrosine is a precursor to thyroid hormones and catecholestrogens, compounds that have estrogen-like and catecholamine-like effects, as well as a constituent of amino sugars and amino lipids. It is also involved in the synthesis of enkephalins, important endogenous analgesic peptides in the endorphin family, and melanin, a pigment responsible for hair and skin color. Lastly, tyrosine binds free radicals and is considered a mild antioxidant.

nutrient in clinical practice

Known or Potential Therapeutic Uses

Common uses include depression, thyroid nutriture, and alcohol withdrawal support. Individuals with phenylketonuria (PKU) are often treated with tyrosine to compensate for inborn errors of phenylalanine metabolism and resultant tendency to tyrosine deficiency.

Historical/Ethnomedicine Precedent

Tyrosine has not been used historically as an isolated nutrient.

Possible Uses

Addictions, alcohol withdrawal support, Alzheimer's disease, attention deficit disorder, cardiovascular disease, chronic fatigue, cocaine abuse and withdrawal, cognitive enhancement, dementia, depression, excessive appetite, fatigue, hypotensive crisis, hypothyroidism, impotence, jet lag, low libido, narcolepsy, Parkinson's disease, premenstrual syndrome, schizophrenia, stress disorders, weight loss.

Deficiency Symptoms

Because tyrosine is a precursor to thyroid hormones and catecholamines, a deficiency may lead to impaired thyroid function as well as low adrenal function. Some research indicates that tyrosine levels may be low in some individuals with depression. A lack of melanin caused by a tyrosine deficiency could predispose a person to skin cancer. Anyone experiencing a pattern of protein loss, especially over an extended period (e.g., with nephrotic syndrome), may develop a deficiency in tyrosine and other amino acids.

Dietary Sources

Dietary sources richest in tyrosine are fish, meat, dairy, eggs, nuts, wheat germ, and oats. Normally, tyrosine can be synthesized endogenously fromL-phenylalanine.

Source of Supplemental Form

MostL-tyrosine in nutraceuticals is produced by bacterial fermentation processes in a growth medium, from which the amino acid is then purified.

Supplemental Form

Capsule, powder, tablet; solution, oral.

Tyrosine is best absorbed when ingested at least 30 minutes before meals, divided into three daily doses. Some manufacturers have claimed that acetyl-L-tyrosine (ALT) affects the brain more rapidly than any other form.

It is often recommended that tyrosine be taken together with a multivitamin-mineral complex because vitamins B6, folate, and copper participate in the conversion ofL-tyrosine into neurotransmitters.

Dosage Range

Adult

Dietary:

  • Recommended dietary intake (RDA): 7.3 mg/pound body weight/day, approximately 1 g/day
  • Average daily intake in United States: 3.5 to 5 g
  • Supplemental/Maintenance:   Supplementation is usually not necessary for most individuals. Optimal levels of intake have not been established.
  • Pharmacological/Therapeutic:   1 to 8 g/day.

Clinical trials have used 100 mg/kg body weight/day, which constitutes a large dose. When indicated, many health care providers experienced in nutritional therapeutics initiate treatment with 2 g per day and gradually increase the dose as appropriate. Use at therapeutic doses would typically be short term. The most common recommended dose is 500 to 1000 mg three times daily (before each of the three meals).

  • Toxic:   Usually not to exceed 12 g per day, the highest known safe level.

Pediatric (<18 Years)

Dietary: No specific dietary recommendation has been established for tyrosine in children.

Supplemental/Maintenance: Not currently recommended for children.

Pharmacological/Therapeutic: Indicated when amino acid imbalance demonstrated by laboratory assessment. In particular, tyrosine is administered in patients with PKU once plasma tyrosine levels have been controlled. Otherwise, specific treatment recommendations have not been established.

Toxic: No toxic dosage level established specifically for infants and children.

Laboratory Values

Range of normal plasma tyrosine levels:

  • Children: 26 to 110 µmol/L
  • Adults: 45 to 74 µmol/L

safety profile

Overview

L-Tyrosine is usually tolerated well by most adults and generally considered to be free of adverse effects for most individuals at usual dosage levels of 2 to 3 g daily.L-Tyrosine has very low toxicity.

Nutrient Adverse Effects

General Adverse Effects

Nausea, diarrhea, vomiting, and nervousness are the primary effects associated with intake of high dosage levels of tyrosine in some reports. Migraine headache, elevated blood pressure, and mild gastric upset may also result from excessive levels of tyrosine (or tyrosine-derived neurotransmitters such as dopamine).

Adverse Effects Among Specific Populations

Use of tyrosine may be contraindicated for individuals with hyperthyroidism, Tourette's syndrome, or schizophrenia, particularly when high brain dopamine levels are present. Exogenous tyrosine (or phenylalanine) administration could theoretically result in elevated brain dopamine levels and symptom aggravation.

Exogenous tyrosine could theoretically promote cancer cell division in susceptible individuals. Many tumor cells overexpress tyrosine kinase enzymes; phosphorylated tyrosine functions as a cell-signaling molecule that drives DNA synthesis, cell growth, and division in these tumors.

Pregnancy and Nursing

Evidence is lacking within the scientific literature to suggest or confirm any adverse effects related to fetal development during pregnancy or to infants who are breast-fed associated with tyrosine administration. Caution still advised regarding supplementation with free-formL-tyrosine.

Infants and Children

No adverse effects have been reported. However, sufficient research-based evidence is lacking to guarantee the safety of tyrosine in infants and children.

Contraindications

  • Migraine.
  • L-Tyrosine is contraindicated in those with the inborn errors of metabolism, alkaptonuria and tyrosinemia types I and II.
  • Tyrosine (and phenylalanine) should be avoided by individuals with cancer, especially pigmented melanoma.
  • Tyrosine should be avoided by individuals taking monoamine oxidase (MAO) inhibitors because of its role in synthesis of dopamine, norepinephrine, and epinephrine.
  • L-Tyrosine is contraindicated in those hypersensitive to any component of anL-tyrosine-containing supplement.

Precautions and Warnings

Concomitant administration of phenylalanine and tyrosine at high dosage levels should be avoided outside of professional supervision due to potential additive effects. Food sources may contain both nutrients but typically would be considered safe at usual levels of intake.

interactions review

Strategic Considerations

Tyrosine from direct dietary sources as well as that synthesized endogenously from phenylalanine provides adequate quantities for normal physiological functions in most healthy individuals with reasonable nutriture. Administration of tyrosine is uncommon in conventional medicine apart from prevention and treatment of tyrosine deficiency in individuals with PKU and occasionally as an adjunctive agent for individuals with Parkinson's disease. Oral dosage levels of 19.2 mg/kg daily, divided equally in meals, and 100 mg/kg daily in three divided doses are typical for PKU and Parkinson's patients, respectively. Prudent clinical management requires establishing controlled plasma tyrosine levels approximating the norm of 45 µmol/L before considering tyrosine administration. Furthermore, concomitant use of tyrosine and levodopa should be discouraged outside the context of medical supervision because levodopa may interfere with the absorption of tyrosine.

Although supportive evidence is largely inconclusive, many practitioners experienced in nutritional therapeutics routinely prescribeL-tyrosine, with other nutrients and botanicals, as part of a comprehensive strategy to support thyroxine, dopamine, and other neurotransmitters in the treatment of fatigue, depression, suboptimal thyroid function, and other conditions. Methods for establishing clinical indications and determining therapeutic response are largely anecdotal and unsystematic, with clinical research data limited and preliminary.

A review of the collective body of available evidence reveals several medications that may interact with tyrosine to produce clinically significant effects in certain patients. The potentially severe interaction with MAO inhibitors, including the risk of a hypertensive crisis and catastrophic sequelae, warrants a general contraindication of concomitant use. Physicians prescribing any of these medications should ask patients about supplemental use of tyrosine and advise that they be avoided or discontinued, except possibly under close supervision. However, most interactions involving tyrosine and conventional medications can be beneficial in appropriate circumstances, but usually warrant supervision, monitoring, and periodic adjustments. Thus, coadministration of tyrosine can often enhance clinical outcomes when used in conjunction with levodopa, levothyroxine, and oral contraceptives within an integrative strategy. Concomitant use with imipramine, mixed amphetamines, appetite suppressants, or opioid analgesics may be appropriate in some cases but requires close supervision and regular monitoring by health care providers trained and experienced in both conventional pharmacology and nutritional therapeutics. In many cases, tyrosine administration can work more effectively when complemented by folic acid, B vitamins, and other nutrients typically at suboptimal levels in the target patient populations, compromised with the primary pathology or comorbid conditions, depleted by typical medications, or otherwise supportive of the therapeutic intervention.

nutrient-drug interactions
Amphetamines and Related Stimulant Medications
Amphetamine (amphetamine aspartate monohydrate, amphetamine sulfate), dextroamphetamine (dextroamphetamine saccharate, dextroamphetamine sulfate, D-amphetamine, Dexedrine). Methylphenidate (Metadate, Methylin, Ritalin, Ritalin-SR; Concerta). Combination drug: Mixed amphetamines: amphetamine and dextroamphetamine (Adderall; dexamphetamine). Extrapolated, based on similar properties: Modafinil (Provigil). Related but no longer on market: Pemoline (Cylert). See also Appetite-Suppressant Medications in Theoretical, Speculative, and Preliminary Interactions Research.
Beneficial or Supportive Interaction, with Professional Management
Drug-Induced Nutrient Depletion, Supplementation Therapeutic, with Professional Management
Prevention or Reduction of Drug Adverse Effect

Probability: 4. Plausible
Evidence Base: Preliminary

Effect and Mechanism of Action

Both adrenergic stimulants and tyrosine have been used in the treatment of narcolepsy and attention deficit disorder (ADD) with hyperactivity. An increase in the availability of tyrosine, under certain conditions, may influence the synthesis and release of dopamine.

Research

Animal research indicates that tyrosine depletion attenuates the release of dopamine produced by amphetamine but not the release of noradrenaline. In a rodent model, Geis et al. 1 observed that rats exposed to amphetamines for 4 to 6 months, but not 35 days or less, reduced amphetamine self-administration after receiving tyrosine. These investigators hypothesized that tyrosine may be useful in certain individuals depending on their history of substance abuse. In an experiment using male rats, Woods and Meyer 2 reported that exogenous tyrosine potentiates the methylphenidate-induced increase in extracellular dopamine in the nucleus accumbens.

A dietary deficiency of tyrosine may impair the therapeutic activity of amphetamines by depleting the available reserves of neurotransmitters. In an experiment involving 15 healthy volunteers, McTavish et al. 3 administered D-amphetamine (20 mg orally) 2 hours after they had ingested either a nutritionally balanced amino acid mixture or one lacking tyrosine and phenylalanine, the catecholamine precursors. These researchers observed that plasma tyrosine levels were significantly lower in subjects who received the nutrient-depleted mixture, but that mean plasma amphetamine levels were higher. Nevertheless, subjects reported that the nutrient-depleted mixture decreased the subjective psychostimulant effects of amphetamine, as indicated by visual analog scales. However, the nutrient-depleted mixture failed to reduce the subjective anorectic effect of amphetamine. This attenuation of some subjective effects of amphetamine after tyrosine depletion suggests that adequate tyrosine intake from dietary protein or nutraceuticals is essential to achieve full therapeutic effect in individuals administered amphetamines. Further research through large, well-designed clinical trials may be warranted.

Nutritional Therapeutics, Clinical Concerns, and Adaptations

Physicians prescribing mixed amphetamines or related stimulants may consider coadministering L-tyrosine as part of an integrative therapeutic strategy. The potential therapeutic efficacy of either therapy may be enhanced by concomitant use, especially in individuals susceptible to or exhibiting a tyrosine deficiency. Prudent clinical management warrants supervision and regular monitoring within the context of collaborative care by health care professionals trained and experienced in both conventional pharmacology and nutritional therapeutics.

Imipramine and Related Tricyclic Antidepressants (TCAs)
Levodopa and Related Antiparkinsonian Medications
Levothyroxine and Related Thyroid Hormones
Monoamine Oxidase (MAO) Inhibitors
Oral Contraceptives: Monophasic, Biphasic, and Triphasic Estrogen Preparations (Synthetic Estrogen and Progesterone Analogs)
theoretical, speculative, and preliminary interactions research, including overstated interactions claims
Appetite-Suppressant Medications, Including Amphetamine, Ephedrine, and Phenylpropanolamine
Codeine, Methadone, Morphine, and Related Oral Narcotic Analgesics (Opiates)
nutrient-nutrient interactions
5-Hydroxytryptophan (5-HTP)
Branched-Chain Amino Acids: Isoleucine, Leucine, Valine
Iodine
Phenylalanine
Citations and Reference Literature
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