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An In-Depth Analysis Of L-Tyrosine.

Dr. Di takes a scientific look into claims that tyrosine can do wonders for sports performance and weight loss, and for anything else that may ail you.

By: Mauro Di Pasquale

9/27/2002 - Dr. Di takes a scientific look into claims that tyrosine can do wonders for sports performance and weight loss, and for anything else that may ail you.

Introduction

Tyrosine is considered a non-essential amino acid and is formed from phenylalanine in the body. While the body can convert phenylalanine to tyrosine, it cannot convert tyrosine to phenylalanine. Tyrosine is the parent compound and thus essential for the manufacture of the catecholamine hormones/neurotransmitters including: dopamine, dihydroxyphenyalanine (DOPA), norepinephrine, and epinephrine, in the central and peripheral nervous system and adrenal medulla, and thyroxine and triiodothyronine by the thyroid gland. Also, the pigment melanin (which occurs in the skin, hair, and choroid lining of the eye) forms from the enzymatic conversion of tyrosine.

Although tyrosine is classified as a non-essential amino acid since it can be synthesized from phenylalanine, there are special considerations that may make it a conditionally-essential amino acid. That's because while man can synthesize most of the non-essential amino acids from glucose and ammonia, tyrosine synthesis requires the availability of phenylalanine, just as cysteine requires the availability of methionine.

Both phenylalanine and methionine are essential amino acids, and if they are available in the diet below minimal requirement levels, tyrosine and cysteine can become essential amino acids. That's because the lack of precursor amino acids decreases the ability of the body to produce these normally non-essential amino acids and they then become rate limiting for protein synthesis.

For example, in some patients with liver disease, the hepatic conversion of phenylalanine to tyrosine, and methionine to cystine, is inadequate, and unless sufficient cystine/tyrosine is administered, repletion of lean tissue (net protein synthesis) will be substantially limited and body function will be impaired.

Thus, tyrosine and phenylalanine (which can be converted to tyrosine) are precursors for the neurotransmitters dopamine, epinephrine and norepinephrine. Since variations in neurotransmitter concentrations have been shown to result in a variety of physiological and psychological changes (such as depression and memory deficits), and studies have shown that the use of exogenous tyrosine can transiently increase plasma and CNS catecholamines. The use of tyrosine may potentially be useful as an anti-depressant, as well as for its stimulating and anorexiant properties.

As well, the lack of tyrosine has been shown to have serious repercussions. For example, individuals not able to convert phenylalanine to tyrosine, due to a hereditary lack of phenylalanine hydroxylase secondary to an inborn error of metabolism known as phenylketonuria, develop serious mental and physical sequelae.

Tyrosine Metabolism

The catecholamine hormones, epinephrine (E) and norepinephrine (NE) are synthesized through various steps from the amino acid, tyrosine. In fact, the hydroxylation of tyrosine by the enzyme tyrosine hydroxylase is the rate-limiting step in the synthesis of the catecholamines. In other words, if an individual lacks sufficient tyrosine or enough tyrosine hydroxylase required to convert tyrosine to the next metabolite in the pathway, the catecholamines may become deficient. This is, however, a rare occurrence except for certain diseases or induced by specific medications.

Tyrosine hydroxylase is activated by stimulation of the adrenergic neurons or the adrenal medulla. After nerve stimulation, there is a delayed increase in tyrosine hydroxylase gene expression. This mechanism maintains the content of catecholamines in response to increased release of these transmitters. Additionally, tyrosine hydroxylase is controlled by feedback inhibition by catechol compounds.

Tyrosine is metabolized into the catecholamines in various tissues. Norepinephrine is synthesized from tyrosine in the postganglionic sympathetic nerves. Although more so for E than NE, both catecholamines are synthesized from tyrosine in the adrenal medulla. In the adult human, approximately 80% of the catecholamines in the adrenal medulla are comprised of E. Both catecholamines are stored in vesicles within cells to ensure their regulated release from adrenergic nerves and the adrenal medulla.

Some hormones, such as glucocorticoids, can stimulate secretion of E from the adrenal medulla. Certain drugs, such as ephedrine, can displace NE from their binding sites on nerve endings, essentially sending them into the extracellular fluid. The released NE can then act at other receptor sites on effector cells. Also, some of these amine drugs mobilize NE stored in the vesicles by competing for the uptake process in the neurons. This mechanism explains the indirect actions of several sympathomimetic drugs, such as ephedrine and tyramine.

Adrenergic nerves can maintain the output of NE during long periods of stimulation without exhausting the reserve supply as long as synthesis and uptake of the transmitter are not impaired. To meet increased demand, regulatory mechanisms help to activate tyrosine hydroxylase and the other enzymes involved in synthesis.

When tyrosine hydroxylase is activated by stimulated sympathetic neurons for sustained periods of time, catecholamine synthesis is believed to become dependent upon the concentration of its substrate, tyrosine. Although tyrosine is supplied by the diet, supplementing with L-tyrosine may increase the synthesis and release of NE during prolonged sympathetic nerve stimulation.

Tyrosine As A Nutritional Supplement

Tyrosine seems to have become one of the new darlings of the supplement world. The reason seems to be mainly because it is the precursor to some neurotransmitters such as norepinephrine and dopamine and it has been shown that that tyrosine administration can accelerate catecholamine synthesis in the human sympathoadrenal system.

The latest information on tyrosine contains claims that the use of tyrosine will do wonders for sports performance and weight loss, and for anything else that may ail you. The properties and effects of tyrosine, according to the information and ads, include:

The Properties & Effects Of Tyrosine Are:

  • Relieving stress, both from life situations and secondary to exercise

  • Relieving depression, burnout, anxiety, and mental fatigue. Often tyrosine is recommended for use with St. John's Wort, an herbal preparation that is believed to aid mild depression, for maximum effect against stress.

  • Improving alertness and enhance cognitive performance.

  • Improving workout intensity, increase recuperation and prevent overtraining - secondary to its ability to influence peripheral and CNS levels of neurotransmitters.

  • Increasing thermogenesis, lipolysis and maximizes body composition

  • Effective in the treatment of cocaine addiction, caffeine withdrawal and other drug (addictions).

  • Useful for ameliorating premenstrual syndrome (PMS)

While many of these claims may be pie in the sky and outright fabrications, the research on tyrosine substantiates some of them. Animal studies have shown that norepinephrine agonists reduce age-related declines in memory. In a recent study, tyrosine (100 and 200 mg per kg of body weight were used 15 minutes prior to challenge) significantly improved memory-dependant performance. Tyrosine has been found to minimize or reverse stress-induced performance decrement by increasing depleted pools of brain norepinephrine.

But studies have also shown the beneficial effects of tyrosine supplementation in humans. For example various studies in the past two decades have shown that tyrosine:

The Benefits Of Tyrosine Supplementation:

  1. Modulated the effects of acute stress. In one study acutely stressed rats on tyrosine supplementation displayed neither the stress-induced depletion of NE nor the behavioral depression. These preventive effects of tyrosine were abolished by co-administration of valine, a large neutral amino acid that competes with tyrosine for transport across the blood-brain barrier.

    Since tyrosine alone, in animals not subjected to stress, did not change NE turnover nor the behaviors studied, our observations affirm that catecholaminergic neurons respond to the precursor amino acid only when they are physiologically active. Supplementary tyrosine may be useful therapeutically in people exposed chronically to stress.

    In another study pre-treatment with supplemental tyrosine not only prevented the behavioral depression and hypothalamic NE depletion observed after an acute stress, but also suppressed the rise in plasma corticosterone. A few studies have shown that pretreatment with tyrosine reversed or prevented hypothermia-induced behavioral depression.8,9

    The results of these studies, and others,10 support a role for brain NE in stress and in stress-induced corticosterone secretion, and demonstrate that supplemental tyrosine can protect against several adverse consequences of such stress, and can enhance the synthesis of norepinephrine in stressed animals, thereby preventing both the neurochemical and the behavioral deficits seen with acute stress.11

  2. May be useful for weight loss. A recent study has shown that tyrosine improves some of the neurobiological disturbances of dietary restrictions without causing an increase in body weight.12

  3. Improves cognitive performance under stressful conditions. A study looking at the effects of the amino acid tyrosine on cognitive task performance found that supplementation with tyrosine may, under operational circumstances characterized by psychosocial and physical stress, reduce the effects of stress and fatigue on cognitive task performance.13 Another study found that tyrosine supplementation may sustain working memory when competing requirements to perform other tasks simultaneously degrade performance, and that supplemental tyrosine may be appropriate for maintaining performance when mild to severe decrements are anticipated.14,15

  4. Several studies have also shown that tyrosine supplementation may be effective in altering body composition.

Tyrosine As A Potential Weight & Fat Loss Aid

One of the main mechanisms of most fat loss aids is the increase in stimulation of the sympathetic nervous (SNS) and central nervous (CNS) systems. Stimulation of these systems generally increases release of two hormones, called the catecholamines, and which are the primary mediators of lipolysis and thermogenesis in the body. The importance of this for dieters is a reduction of body fat.

Studies suggest that the pharmacological potency or duration of action of several sympathomimetics may be limited by the amount of endogenous substrate available for synthesis of the catecholamines. Therefore, supplemental tyrosine may prolong the appetite-reducing effects of anorexiants. For instance, one study demonstrated that supplementing with L-tyrosine overcame a tolerance to the appetite-reducing effects of phenylpropanolamine (PPA).16

Another study determined if the activity of mixed-acting sympathomimetic drugs could be restricted by the sympathetic neurons' ability to synthesis catecholamines.17 Researchers coadministered L-tyrosine with various mixed-acting anorexiants, including ephedrine, in hyperphagic rats. The addition of L-tyrosine potentiated the anorectic activity in a dose-dependent manner suggesting increased catecholamine synthesis in stimulated neurons.

In addition to (-)-ephedrine, L-tyrosine potentiated the appetite-reducing effects of several ephedrine isomers such as (-)-norephedrine, and (+)-pseudoephedrine. These substances are found in the most commonly used herbal source of ephedrine, Ma Huang.

In the same study, the coadministration of L-tyrosine to direct-acting beta2-adrenoceptor agonists, such as salbutamol, did not potentiate their anorectic activity. Because their mode of action is by direct stimulation of the beta2-adrenoceptors and not the release of stored catecholamines, L-tyrosine appears to specifically enhance activity of those drugs that preferentially release the catecholamines.

The lowest dose of anorexiant coadministered with L-tyrosine was as effective in appetite suppression as was the highest dose of the anorexiant alone. Thus, supplementing with L-tyrosine may allow for a significantly lower dose of anorexiant and still maintain a therapeutic response. Another response to several sympathomimetics is increased thermogenesis in brown adipose tissue (BAT). This additional mechanism is thought to enhance the weight loss induced by several sympathomimetics. While the potentiation of sympathomimetics by L-tyrosine appears to be centrally located, the response to prolonged sympathetic neuron stimulation in the periphery might be expected to be influenced by the concentrations of peripheral tyrosine and respond similarly.

However, although thermogenesis in BAT was induced by the sympathomimetics, supplementation with L-tyrosine failed to potentiate this effect in rats with the dosages used.18 The potentiation by L-tyrosine on the effects of several mixed-acting sympathomimetics appears to be largely relegated to centrally mediated effects in the brain. Aside from lack of potentiation of peripheral effects induced by sympathomimetics, 19,20 the potentiation by L-tyrosine is attenuated when L-valine is coadministered.21 A large neutral amino acid, L-valine competes with L-tyrosine for uptake into the brain and therefore reduces the effectiveness of L-tyrosine.

Although this may suggest that L-tyrosine be administered with no food in the stomach, there appears to be little if any antagonism between supplementation and food ingestion. Increased plasma tyrosine levels were measured in human subjects who were administered L-tyrosine (100 mg/kg/day) in three equally divided doses before meals containing a total daily intake of 113 grams of protein.22 Plasma tyrosine levels rose significantly after L-tyrosine ingestion and did not appear to affect plasma concentrations of the other neutral amino acids that compete with tyrosine for brain entry.

The former studies were conducted in murine models and may have limited applicability to humans. Unfortunately, no similar studies have been conducted in humans. However, some evidence suggests that supplementation with L-tyrosine may increase human catecholamine synthesis.23,24 A single dose of L-tyrosine (100-150 mg/kg) significantly increased urinary levels of NE, E, dopamine, and 3-methoxy-4-hydroxyphenylglycol (MHPG) within two hours after ingestion.25 The urinary catecholamines are derived from peripheral sources in the body, whereas urinary catecholamine metabolites reflect catecholamine status both peripherally and in the central nervous system (brain). Thus, increased urinary catecholamines and their metabolites may indicate that L-tyrosine supplementation may increase catecholamine synthesis and release from cells in the human body.

In all, coadministration of L-tyrosine has been shown in rats to potentiate the appetite-reducing effects of several sympathomimetics. This mechanism appears to be increased synthesis and release of the catecholamines in the brain. Although tyrosine is a substrate for the peripheral synthesis of catecholamines, supplementation of L-tyrosine was not shown to potentiate the sympathomimetic-induced thermogenesis in BAT of rats.

While studies show that administration of L-tyrosine in humans increases urinary catecholamines and their metabolites, no studies exist that examine potentiation of sympathomimetic-induced thermogenesis in humans. However, evidence of increased catecholamine synthesis and release after L-tyrosine administration in humans may substantiate the hypothesis that it may increase the thermogenesis induced by mixed-acting sympathomimetics. This response may be dosage dependent and larger doses than those given to the study rats may be required for humans.

Adverse Effects

While the use of supplemental tyrosine is usually innocuous, it can be dangerous under some circumstances. The most obvious ones are in cases of phenylketonuria and in those taking antidepressant medication that act by inhibiting monoamine oxidase, the enzyme that is responsible for the breakdown and inactivation of the catecholamines. In the latter case a buildup of the catecholamines, including tyramine, which can be found in certain foods and formed from exogenous tyrosine in the gut by certain bacteria in some foods, can result in dangerous increases in blood pressure.

The bottom line is that in some cases tyrosine supplementation may act as an effective ergogenic and weigh/fat loss aid.

References

1. Rudman D, Kutner M, Ansley J, et al. Hypotyrosinemia, hypocystinemia and failure to retain nitrogen during total parenteral nutrition of cirrhotic patients. Gastroenterology 1981; 81: 1025-35.
2. Rasmussen D. Effects of tyrosine and tryptophan ingestion on plasma catechloamine concentrations. J Clin Endo Metab 1983; 57(4):760-763.
3. Agharanya JC, Alonso R, Wurtman RJ. Changes in catecholamine excretion after short-term tyrosine ingestion in normally fed human subjects. Am J Clin Nutr 1981 Jan;34(1):82-7
4. Shurtleff D, Thomas JR, Shlers ST, et al. Tyrosine ameliorates a cold-induced delayed matching-to sample performance decrements in rats. Psychopharmacology 1993; 112:228-232, .
5. Owasoyo JO, Neri DF, Lamberth JG. Tyrosine and its potential use as a countermeasure to performance decrement in military sustained operations. Aviation Space and Enviromental Medicine 1992; 63:364-369.
6. Lehnert H, Reinstein DK, Strowbridge BW et al. Neurochemical and behavioral consequences of acute, uncontrollable stress: effects of dietary tyrosine. Brain Res 1984 Jun 15;303(2):215-23
7. Reinstein DK, Lehnert H, Wurtman RJ. Dietary tyrosine suppresses the rise in plasma corticosterone following acute stress in rats. Life Sci 1985 Dec 9;37(23):2157-63.
8. Rauch TM, Lieberman HR. Tyrosine pretreatment reverses hypothermia-induced behavioral depression. Brain Res Bull 1990 Jan;24(1):147-50.
9. Shurtleff D, Thomas JR, Schrot J, et al. Tyrosine reverses a cold-induced working memory deficit in humans. Pharmacol Biochem Behav 1994 Apr;47(4):935-41.
10. Reinstein DK, Lehnert H, Scott NA, et al. Tyrosine prevents behavioral and neurochemical correlates of an acute stress in rats. Life Sci 1984 Jun 4;34(23):2225-31.
11. Banderet LE, Lieberman HR. Treatment with tyrosine, a neurotransmitter precursor, reduces environmental stress in humans. Brain Res Bull 1989 Apr;22(4):759-62.
12. Avraham Y, Bonne O, Berry EM. Behavioral and neurochemical alterations caused by diet restriction--the effect of tyrosine administration in mice. Brain Res 1996 Sep 2;732(1-2):133-44.
13. Deijen JB, Wientjes CJ, Vullinghs HF et al. Tyrosine improves cognitive performance and reduces blood pressure in cadets after one week of a combat training course. Brain Res Bull 1999 Jan 15;48(2):203-9.
14. Thomas JR, Lockwood PA, Singh A, et al. Tyrosine improves working memory in a multitasking environment. Pharmacol Biochem Behav 1999 Nov;64(3):495-500.
15. Shukitt-Hale B, Stillman MJ, Lieberman HR. Tyrosine administration prevents hypoxia-induced decrements in learning and memory. Physiol Behav 1996 Apr-May;59(4-5):867-71.
16. Lehnert H, Wurtman RJ. Amino acid control of neurotransmitter synthesis and release: physiological and clinical implications. Psychotherapy and Psychosomatics 1993, 60:18-32.
17. Hull KM, Maher TJ. L-Tyrosine potentiates the anorexia induced by mixed-acting sympathomimetic drugs in hyperphagic rats. J Pharm Exp Ther 1990, 255:403-409.
18. Hull KM, Maher TJ. L-Tyrosine fails to potentiate several peripheral actions of the sympathomimetics. Pharm Biochem Behav 1991, 39:755-759.
19. Hull and Maher. Pharm Biochem Behav 1991. *** repeat citation - see #18
20. Hull KM, Maher TJ. Effects of L-tyrosine on mixed-acting sympathomimetic-induced pressor actions. Pharm Biochem Behav 1992, 43:1047-1052.
21. Hull and Maher. J Pharm Exp Therapeutics 1990. *** Repeat citation - see #17
22. Melamed E, Glaeser B, Growdon JH et al. Plasma tyrosine in normal humans: effects of oral tyrosine and protein-containing meals. J Neural Transm 1980, 47:299-306.
23. Agharanya JC, Alonso R, Wurtman RJ. *** repeat citation - see #3
24. Melamed E, Glaeser B, Growdon JH et al. *** repeat citation - see #22
25. Alonso R, Gibson CJ, Wurtman RJ, et al. Elevation of urinary catecholamines and their metabolites following tyrosine administration in humans. Biol Psychiatry 1982, 17:781-790.

An In-Depth Analysis Of L-Tyrosine.
mauro@metabolicdiet.com

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