Tyrosine

Common Name: Tyrosine

Clinical Name: L-Tyrosine

Summary

L-Tyrosine

chemical name: L-tyrosine

overview of interactions:
• nutrients affecting drug performance: L-Dopa

• sympathomimetic substances, including L-tyrosine, affecting drug performance and toxicity: Phenelzine


chemistry/function:
• Tyrosine is a nonessential amino acid. It can be synthesized from phenylalanine.
• Tyrosine is involved with the synthesis of neurotransmitters in the brain. Tyrosine is a precursor to L-dopa, dopamine, norepinephrine and epinephrine. Brain concentrations of these neurotransmitters are dependent upon intake of tyrosine. Tyrosine requires biopterin (a folate derivative), NADPH and NADH (forms of niacin), copper and vitamin C. The conversion of tyrosine into these neurotransmitters requires vitamin B6, folic acid, and copper.
• Tyrosine is a precursor to thyroid hormones and catecholestrogens (compounds that have estrogen- and catecholamine-like effects). Tyrosine is also involved with the synthesis of enkephalins, substances which have pain relieving effects in the body, and melanin, a pigment in the body.
• Tyrosine is a constituent of amino sugars and amino lipids

dietary sources: Dietary sources richest in tyrosine are fish, meat, dairy, eggs, nuts, wheat germ and oats. Average intake in the U.S.: 3.5-5 g per day. Tyrosine can be synthesized from phenylalanine.

deficiency: Since tyrosine is a precursor to thyroid hormones and catecholamines, a deficiency leads to hypothyroidism and low adrenal function. It is also a precursor to melanin, the pigment that gives skin its color. A lack of melanin due to a tyrosine deficiency could predispose a person to cancer. Some research indicates that tyrosine levels may low in some individuals suffering from depression. Anyone experiencing a pattern of protein loss, especially over an extended period of time, for example with kidney disease, may develop a deficiency in tyrosine and other amino acids.

known or potential therapeutic uses: Common uses are depression and alcohol withdrawal support. Individuals with phenylketonuria (PKU) are often treated with tyrosine to compensate for inborn errors of phenylalanine metabolism. Tyrosine has been reported to be of value in the treatment of many other conditions including addictions, Alzheimer’s disease, cardiovascular disease, dementia, excessive appetite, hypotensive crisis, impotence and deficient libido, narcolepsy, Parkinson's disease, schizophrenia and stress disorders.

maintenance dose: RDA: 7.3 mg/pound body wt. /day, approximately 1 g per day. Supplementation is usually not necessary for most individuals. Optimal levels of intake have not been established.

therapeutic dose: 1-8 g per day. 100 mg/kg of body weight/day; this constitutes a large dose. When appropriate, most healthcare providers trained in nutritional therapies would start with 2 g per day and work up. Supplemental use at therapeutic doses would typically be short term.

side effects/toxicity: L-Tyrosine has very low toxicity. There have been very few reports of toxicity.

contraindications: None known to date other than potential interactions as above.



Interactions

nutrients affecting drug performance: L-Dopa

• mechanism: L-Tyrosine is a semi-essential amino acid that converts to L-Dopa. Phenylalanine is a precursor of L-tyrosine.

• nutritional concerns: Supplementation of L-tyrosine, or its precursor phenylalanine, may serve as a valuable adjunctive therapy in the treatment of Parkinson's disease or similar conditions. However, such supplementation by individuals using Levodopa may raise levels of L-Dopa to undesirably high levels. Anyone taking Levodopa should consult the prescribing physician and/or a nutritionally-oriented doctor regarding the issue of supplementation with either of these amino acids. Nutritionally-oriented physicians will want to closely monitor the L-Dopa levels of any individual using these substances together.

sympathomimetic substances, including L-tyrosine, affecting drug performance and toxicity: Phenelzine

• mechanism: The potentiation of sympathomimetic substances and related compounds by MAO inhibitors may result in hypertensive crises. Individuals taking phenelzine should avoid sympathomimetic drugs (including amphetamines, cocaine, methylphenidate, dopamine, epinephrine and norepinephrine), or related compounds (including methyldopa, L-dopa, L-tryptophan, L-tyrosine and phenylalanine).
(Alvine G, et al. J Clin Psychiatry 1990 Jul;51(7):311; Goff DC. Am J Psychiatry 1985 Dec;142(12):1487-1488; Levy AB, et al. Can J Psychiatry 1985 Oct;30(6):434-436; Threlkeld DS. Facts and Comparisons Drug Information, Apr 1997.)


Please read the disclaimer concerning the intent and limitations of the information provided here.
Do not rely solely on the information in this article.

The information presented in Interactions is for informational and educational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, case reports, and/or traditional usage with sources as cited in each topic. The results reported may not necessarily occur in all individuals and different individuals with the same medical conditions with the same symptoms will often require differing treatments. For many of the conditions discussed, treatment with conventional medical therapies, including prescription drugs or over-the-counter medications, is also available. Consult your physician, an appropriately trained healthcare practitioner, and/or pharmacist for any health concern or medical problem before using any herbal products or nutritional supplements or before making any changes in prescribed medications and/or before attempting to independently treat a medical condition using supplements, herbs, remedies, or other forms of self-care.



References

Alvestrand A, Ahlberg M, Forst P, Bergstrom J. Clinical results of long-term treatment with a low protein diet and a new amino acid preparation in patients with chronic uremia. Clin Nephrol 1983 Feb;19(2):67-73.
Abstract: 15 patients with severe uremia (mean serum creatinine concentration 965, range 568-1383 mumoles/l) were treated with an unselected protein restricted (16-20 g protein/day) diet and a new amino acid preparation, containing the essential amino acids in proportions which differed from those recommended by Rose for normal man and which contained in addition histidine and tyrosine, for an average period of 224 (range 33-737) days. Plasma urea concentration decreased and the uremic symptoms disappeared. Ten nitrogen balance studies were performed in 6 patients after a mean treatment time of 151 days. The mean nitrogen balance, corrected for changes in total urea pool, was + 0.4 +/- 0.22 g N/day. In 4 patients, in whom progression of the renal insufficiency was assessed by plots of the reciprocal of serum creatinine concentration versus time, retardation of progression was observed after institution of the regimen. The results show that nitrogen equilibrium can be maintained during long-term treatment with this regimen and suggest that better nitrogen utilization is achieved with the new amino acid preparation than when essential amino acids are given to uremic patients in the proportions considered optimal for normal man. It is further shown that the progression of renal insufficiency may be retarded by this regimen.

Alvine G, Black DW, Tsuang D. Case of delirium secondary to phenelzine/L-tryptophan combination. J Clin Psychiatry 1990 Jul;51(7):311. (Letter)

Banderet LE, Lieberman HR. Treatment with tyrosine, a neurotransmitter precursor, reduces environmental stress in humans. Brain Res Bull 1989 Apr;22(4):759-762.
Abstract: Acutely stressful situations can disrupt behavior and deplete brain norepinephrine and dopamine, catecholaminergic neurotransmitters. In animals, administration of tyrosine, a food constituent and precursor of the catecholamines, reduces these behavioral and neurochemical deficits. Using a double-blind, placebo-controlled crossover design we investigated whether tyrosine (100 mg/kg) would protect humans from some of the adverse consequences of a 4.5 hour exposure to cold and hypoxia. Tyrosine significantly decreased symptoms, adverse moods, and performance impairments in subjects who exhibited average or greater responses to these environmental conditions. These results suggest that tyrosine should be evaluated in a variety of acutely stressful situations.

Chiaroni P, Azorin JM, Bovier P, Widmer J, Jeanningros R, Barre A, Dufour H, Tatossian A, Tissot R. A multivariate analysis of red blood cell membrane transports and plasma levels of L-tyrosine and L-tryptophan in depressed patients before treatment and after clinical improvement. Neuropsychobiol 1990;23(1):1-7.
Abstract: The purpose of this study was to examine whether biological variables, such as erythrocyte membrane transports and plasma levels of monoamine precursor amino acids (tyrosine, tryptophan and phenylalanine), exhibit a particular pattern relatively to DSM-III depressive subgroups (dysthymic disorders, major recurrent depression and biopolar depression), when they are treated synthetically by a stepwise discriminant analysis. We conducted two tests in 97 subjects (64 depressed patients vs. 33 controls): the first before any antidepressant treatment, and the second after pharmacotherapy and clinical improvement. Our results clearly indicate a satisfying homogeneity for the controls and bipolar depressed patients as opposed to dysthymic disorders and major recurrent depression in both tests. The most informative biological variables are the erythrocyte membrane transports before treatment, tryptophan parameters after clinical improvement. Evidence is provided that multivariate analysis constitutes an interesting approach in biological psychiatry.

Dyck LE, Dewar KM. Inhibition of aromatic L-amino acid decarboxylase and tyrosine aminotransferase by the monoamine oxidase inhibitor phenelzine. J Neurochem 1986 Jun;46(6):1899-1903.
Abstract: The concentration of p-tyramine in the rat striatum was increased significantly by intraperitoneal injection of phenelzine (5 or 100 mg/kg). Unlike other monoamine oxidase (MAO) inhibitors, phenelzine had no effect on p-tyramine levels in the first 1-2 h following injection. The high dose of phenelzine increased the p-tyramine levels much more than the low dose. In addition, the high dose of phenelzine increased striatal p-tyrosine levels significantly 12 h after injection. Further studies showed that phenelzine inhibited the tyrosine aminotransferase activity of rat liver homogenates; the IC50 was 50 microM. Phenelzine also inhibited the aromatic L-amino acid decarboxylase activity of rat brain homogenate with an IC50 of 25 microM. Following intraperitoneal injection of 100 mg/kg phenelzine, the initial concentration of phenelzine in the striatum appears to be high enough to inhibit aromatic L-amino acid decarboxylase. It is suggested that the multiple enzyme inhibition caused by administration of high doses of phenelzine accounts for its unusual effects on striatal p-tyramine levels compared with other MAO inhibitors, i.e., its initial lack of effect on p-tyramine levels followed later by very large increases in p-tyramine levels.

Gelenberg AJ, Gibson CJ, Wojcik JD. Neurotransmitter precursors for the treatment of depression. Psychopharmacol Bull 1982 Jan;18(1):7-18. (Review)

Gelenberg AJ, Wojcik JD, Gibson CJ, Wurtman RJ.  Tyrosine for depression. J Psychiatr Res. 1982-83;17(2):175-80. (Review)
Abstract: The catecholamine hypothesis of affective disorders postulates that depression reflects inadequate norepinephrine activity at unspecified brain centers that regulate mood. In light of experimental data showing that the oral administration of tyrosine, precursor of the catecholamine series of neurotransmitters, can increase brain norepinephrine concentrations and activity, we have conducted preliminary trials of tyrosine in depressed outpatients. Initial results are encouraging, and we are now conducting a double-blind, parallel-group trial comparing tyrosine to the tricyclic antidepressant imipramine and to placebo in non-bipolar outpatients with major depression.

Goff DC. Two cases of hypomania following the addition of L-tryptophan to a monoamine oxidase inhibitor. Am J Psychiatry 1985 Dec;142(12):1487-1488.
Abstract: The combination of L-tryptophan and a monoamine oxidase inhibitor (MAOI) has been reported to be an effective antidepressant regimen. Neurotoxicity has previously been associated with this combination. The author presents two cases of hypomania following the addition of L-tryptophan to an MAOI.

Haavik J. L-DOPA is a substrate for tyrosine hydroxylase. J Neurochem 1997 Oct;69(4):1720-1728.
Abstract: In the presence of thiols, tyrosine hydroxylase (TH) oxidizes L-dihydroxyphenylalanine (L-DOPA) with a specific activity of up to 140 nmol min(-1) mg(-1) at 37 degrees C and pH 7.0, which is approximately 12-50% of its TH activity under similar experimental conditions. Using assay conditions that are optimal for measuring TH activity, the specific DOPA oxidase activity of human TH is similar to that of mushroom tyrosinase, but the two enzymes are clearly different in terms of substrate specificities, cofactor dependencies, and selectivity with respect to the effects of metal chelators and other inhibitors. In the presence of an excess of dithiothreitol, 2-mercaptoethanol, cysteine, or reduced glutathione, the reaction products of the two enzymes are identical and have been identified tentatively as thioether derivatives of DOPA. Theoretically, the oxidation of L-DOPA by TH may contribute to the formation of neuromelanin (pheomelanin) in catecholaminergic neurons and in the metabolism of DOPA to reactive intermediates that can react with free thiol groups in cellular proteins. The DOPA oxidase activity of TH can lead to errors in the estimation of in vivo or in vitro TH activity, and currently used assay protocols may have to be modified to avoid interference from this activity.

Koch R. Tyrosine supplementation for phenylketonuria treatment. Am J Clin Nutr 1996 Dec;64(6):974-975. (Comment/Editorial)

Lenke RR, Koch R, Fishler K, Platt LD. Tyrosine supplementation during pregnancy in a woman with classical phenylketonuria. A case report. J Reprod Med. 1983 Jun;28(6):411-414.
Abstract: A woman with classical phenylketonuria (PKU) adhered poorly to a phenylalanine-restricted diet but did receive tyrosine supplementation from the 14th week of gestation until delivery. At birth the infant demonstrated a head circumference more than two standard deviations below the mean but at 2 years of age had a development quotient (DQ) of 94. This case illustrates the fact that while single case reports may be of value in disproving a theory, they are not sufficient to prove an association because biologic variation may explain one's results. Thus, while tyrosine supplementation may explain the relatively normal DQ, the results are also compatible with the moderate degree of phenylalanine restriction obtained. Current evidence favors the elevated maternal phenylalanine level as the cause of defects in offspring of women with PKU, but tyrosine supplementation should be considered if the level is subnormal.

Levy AB, Bucher P, Votolato N. Myoclonus, hyperreflexia and diaphoresis in patients on phenelzine-tryptophan combination treatment. Can J Psychiatry 1985 Oct;30(6):434-436.
Abstract: Three cases are presented on patients on an MAOI who developed a transient syndrome of myoclonus, hyperreflexia, jaw quivering, teeth chattering and diaphoresis after L-Tryptophan was added. Caution is advised when considering the addition of a serotonergic agent to MAOI's.

Marz, Russell. Medical Nutrition From Marz. Second Edition. Portland, OR. 1997.

McTavish SF, McPherson MH, Sharp T, Cowen PJ. Attenuation of some subjective effects of amphetamine following tyrosine depletion. J Psychopharmacol (Oxf). 1999;13(2):144-147.
Abstract: Fifteen healthy volunteers received d-amphetamine (20 mg orally) 2 h after ingesting either a nutritionally balanced amino acid mixture or one lacking the catecholamine precursors, tyrosine and phenylalanine (TYR-free). Plasma tyrosine levels were significantly lowered in subjects who received the TYR-free mixture but mean plasma amphetamine levels were higher. Despite this, the TYR-free mixture appeared to decrease the subjective psychostimulant effects of amphetamine, as determined by visual analogue scales. In contrast, the TYR-free mixture failed to lower the subjective anorectic effect of amphetamine. These findings are consistent with animal experimental studies indicating that tyrosine depletion attenuates the release of dopamine produced by amphetamine but not the release of noradrenaline.

Meyer JS, Welch KM, Deshmukh VD, Perez FI, Jacob RH, Haufrect DB, Mathew NT, Morrell RM. Neurotransmitter precursor amino acids in the treatment of multi-infarct dementia and Alzheimer’s disease. J Am Ger Soc 1977 Jul;25(7):289-298.
Abstract: Ten patients with severe dementia due to Alzheimer's disease (AD) or multi-infarct dementia (MID) or both, were treated with the precursor amino acids of the neurotransmitters serotonin and dopamine. The precursor amino acids (PAA) were given orally in a preparation that included tyrosine (4 gm daily) and 5-hydroxy-tryptophan (5-HTP) (800 mg daily), plus carbidopa (100 mg daily) as an aromatic amino-acid decarboxylase inhibitor. Diagnosis was established by an electroencephalogram, brain scan, computerized axial tomographic scan, and in one case by necropsy findings. Serial clinical evaluations and measurements of neuropsychologic function were performed. Levels of homovanillic acid (HVA) and 5-hydroxyindole-acetic acid (5-HIAA) were determined before and after administration of probenecid. Side effects of the PAA therapy were diarrhea, drowsiness, nausea, vomiting and agitation, all of which were controlled by reducing the dosage. One patient with MID and one with AD+MID showed clinical and psychologic improvement, but the others did not improve. Analysis of the cerebrospinal fluid for HVA and 5-HIAA before and after the probenecid test indicated some improvement in the metabolic turnover of these acid metabolites of serotonin and dopamine after administration of their precursor amino acids.

Threlkeld DS, ed. Central nervous system drugs, antidepressants, monoamine oxidase inhibitors. In: Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Apr 1997.

Werbach MR. Foundations of Nutritional Medicine. Tarzana, CA: Third Line Press, 1997. (Review).