L-Tyrosine

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Anecdotally, L-Tyrosine tends to be taken in doses of 500-2000mg approximately 30-60 minutes before any acute stressor (this tends to be exercise)

Studies in humans showing most anti-stress promise for acute supplemental L-Tyrosine use a dosage range of 100-150mg/kg bodyweight which can be taken 60 minutes before exercise; this is a dosage range of 9-13.5g for a 200lb person and 7-10g for a 150lb person.

If using higher doses and finding digestive issues, this may be split into two doses separated by half an hour (30 and 60 minutes prior to acute stress).

The Human Effect Matrix looks at human studies (excluding animal/petri-dish studies) to tell you what effect L-Tyrosine has in your body, and how strong these effects are.

Level of Evidence	Effect	Change	Magnitude of Effect Size	Scientific Consensus	Comments
B	Blood Pressure			66% See all 3 studies	It is possible that Tyrosine can reduce blood pressure during stress, but the one study that noted this also noted a reduction in blood pressure in the stressed placebo;... show other studies have found no influence.
B	Cognition		Minor	100% See all 3 studies	Tyrosine appears to effectively improve cognition during acute stressors (altitude and cold being tested most); this appears reliable if the acute stressor is present,... show but may not be an inherent increase in cognition and it is unsure if it applies to chronic stress and fatigue.
C	Working Memory		Minor	50% See 2 studies	Appears to preserve working memory during acute stressors without inherently having a memory boosting effect
C	Noradrenaline			100% See study	No significant influence on plasma noradrenaline levels (despite increased plasma tyrosine) during rest or during a cold stress test (which increases noradrenaline)
C	Subjective Well-being		Minor	50% See 2 studies	There appears to be an increase in subjective well being during stress when tyrosine is preloaded (perhaps secondary to the antistress effects of tyrosine), although this... show is not overly reliable
C	Stress		Minor	100% See 2 studies	Perceptions of stress during acute stressors, as well as related symptoms of acute stress, appear to be reduced following tyrosine ingestion
C	Heart Rate			100% See study	No significant influences of Tyrosine on heart rate has been noted
C	Depression			100% See study	Depressive symptoms that occur during acute stressors have not been affected by Tyrosine supplementation; chronic depression not yet researched
C	Fatigue			100% See study	No significant influence has been noted on fatigue from L-Tyrosine supplementation during acute stresses

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Edit1. Sources and Structure

1.1. Biological Significance

The catecholamine metabolic pathway in vivo starts with the amino acid L-phenylalanine, which gets converted into L-tyrosine by the enzyme phenylalanine hydroxylase. L-tyrosine then gets converted into the compound L-DOPA via tyrosine hydroxylase. L-DOPA is then decarboxylated via aromatic L-amino acid decarboxylase into Dopamine, which later turns into noradrenaline via oxidation from the enzyme dopamine-beta-hydroxylase and then finally converted to adrenaline via Phenylethanolamine-N-methyl-transferase. The last three compounds (Dopamine, NA, Adrenaline) are collectively referred to as 'Catecholamines'; the rate limiting step in this formula is the enzyme tyrosine hydroxylase.^[1]

Supplementing with any of the prior substrates has the ability to increase adrenaline levels, given that the enzyme between said substrate and adrenalines are not maxed out.

Supplemental L-Tyrosine is converted into L-DOPA and then into active catecholamines (adrenaline/epinephdrine, noradrenaline/norepinephrine, and dopamine). L-Tyrosine forms a pool of substrate that this group of catecholamine neurotransmitters can get substrate from when their production is needed.

1.2. Phenylketuria

Phenylketonuria (PKA) is a genetic disease in which the body fails to properly metabolize the amino acid Phenylalanine, and said amino acid can build up to toxic levels.

Tyrosine has been looked at for possibly alleviating symptoms of PKA (as a reduction of phenylalanine may reduce catecholamines, but this can be attenuated with L-Tyrosine which is what Phenylalanine turns into in order to create catecholamines). Results, however, are preliminary.^[2][3]

Edit2. Pharmacology

2.1. Serum

150mg/kg L-Tyrosine taken in a vessel of apple sauce can elevated plasma Tyrosine concentrations from 56.3nmol/L (baseline and similar to control values) to the range of 140-168nmol/L within 90 minutes, which remained within that concentration until measurements stopped at 150 minutes; a significant difference from placebo existed within 30 minutes and was measured at approximately 80nmol/L.^[4] These changes in plasma Tyrosine concentrations were not matched with increases in plasma norephedrine, which were similar between groups.^[4]

A similar spike in serum Tyrosine levels is noted in rats (serum norepinephrine untested) and the increase in serum Tyrosine appears to return to baseline 4 hours after oral administration.^[5]

Fairly rapidly absorbed from the intestines into the blood, and remains peaked for approximately 2-4 hours after ingestion

Edit3. Neurology

3.1. Mechanisms

Most mechanisms related to L-Tyrosine are due to it being a precursor to catecholamine synthesis, and catecholamine synthesis being somewhat sensitive to a localized substrate pool.^[6][7]

3.2. Memory

L-Tyrosine (200-400mg/kg) can acutely increase norephedrine (NE) concentrations in the hippocampus and prevent an acute stress-induced reduction of NE concentrations in rats subject to cold stress.^[8] This may precede the ability of L-Tyrosine administration to reverse losses of memory induced by cold stress in humans.^[4] This study (n=8) noted that 150mg/kg L-Tyrosine (dissolved in apple sauce that placebo ingested solely) taken before cognitive testing in a room where the temperature was reduced from 22°C to 4°C was able to reduce the time taken to answer a delayed Matching-to-Sample test and increase the amount of correct answers relative to cold placebo, but was unable to fully preserve performance seen in warm control periods (where L-Tyrosine did not appear to further improve performance).^[4]

Currently no evidence that L-Tyrosine supplementation can improve memory function from baseline, but may be able to attenuate a decrease in memory formation associated with acute stressors

3.3. Wakefulness

One study has combined supplemental L-Tyrosine and 'extended wakefulness' and noted that 150mg/kg of L-Tyrosine was able to attenuate the decrease in cognitive performance that was associated with sleep deprivation.^[9]

May improve cognitive performance during sleep deprivation without significantly affecting sleep function

3.4. Stress

Acute uncontrollable stress is a phenomena that is able to deplete norephinephrine (NE) concentrations in neural tissue, particularly the hypothalamus and brainstem (containing the locus coeruleus)^[10] and behavioural alterations associated with NE depletion in research animals have been shown to be avoidance/escape,^[11] spontaneous motor activity,^[12] aggressive behaviors,^[13] and swimming.^[14] Ingestion of L-Tyrosine can attenuate the development of behavioural abnormalities associated with acute uncontrollable stressors in research animals in the range of 200-400mg/kg (oral or intravenous) 30-60 minutes prior to the acute stressor.^{[10][15][16][8]}

Appears to mitigate some overt symptoms of acute and uncontrollable stress (this is in contrast to the Adaptogen class of molecules, which may be effective against chronic and manageable stress); the two stress respones being mediated by different mechanisms

Some studies have been conducted specifically as it applies to cold stress (the goal of Cold Exposure therapy) have noted decrease immobility time in a dose-dependent manner in mice given 200-400mg/kg L-Tyrosine injections to a similar magnitude of 5-20mg/kg Phenylpropanolamine; Tyrosine appeared to synergistically reduce immobility time when paired with either Phenylpropanolamine or Amphetamines.^[8] These effects correlated with hippocampal norephedrine concentrations, which were preserved with L-Tyrosine.^[8] These protective effects have been noted in human subjects, albeit a small sample size.^[4]

May reduce the adverse effects of cold stress, has some human evidence of doing so (as it pertains to memory function)

One study in humans subjected to high altitudes has noted protective effects against acute stress due to lessened symptoms of acute stress, where 100mg/kg L-tyrosine (divided into two doses taken an hour apart) was associated with less headaches, stress, fatigue, distress, sleepiness, muscular soreness, and coldness due to the acute stressor as assessed by the Environmental Symptoms Questionnaire.^[17] This study also noted improvements (relative to placebo) on global ratings of mood and happiness (assessed by Clyde Mood Scale and Profile of Mood states) and cognitive function (various cognitive tests).^[17] Similar results are noted with the same oral dose after acute noise stressor^[18] and some of these effects are noted after acute physical lower body stressors.^[19]

Protection against acute stress has also been noted during a week-long combat training session, where 42g of protein (of which 2g were Tyrosine) was compared to placebo and associated with a preservation of cognitive performance, although this study failed to find significant improvements in mood between groups.^[20]

3.5. Neural Aging

Increasing levels of L-tyrosine in the brain is being looked at as a pharmaceutical method of alleviating neurological decline as catecholamines are typically decreased in states of dementia.

Surprisingly, catecholamines may act as anti-oxidants in the brain and be neuroprotective.^[21]

Edit4. Cardiovascular Health

4.1. Blood Pressure

150mg/kg L-Tyrosine taken prior to a cognitive test (with acute stressor) failed to significnatly influence blood pressure inherently or the spike in blood pressure induced by the acute stressor (which L-Tyrosine did not modify, spiking in both control and L-Tyrosine condition).^[4]

One study conducted in cadets undergoing combat training who consumed 42g protein (2g tyrosine, confounded with other amino acids) noted that supplementation was associated with a decrease in systolic blood pressure by 10.4% from baseline, with placebo experiencing a lesser and nonsignificant decrease in blood pressure; no significant change noted in diastolic in this study although a trend towards reduction was noted^[20] and another study under acute noise stress noted that L-Tyrosine ingestion was associated with a reduction in diastolic blood pressure within 15 minutes of ingestion of 100mg/kg.^[18] This reduction in diastolic blood pressure has been noted previously in research animals.^[22][23]

Although there isn't much reliability in the evidence currently, supplemental L-Tyrosine appears to either be ineffective or slightly reduce blood pressure; studies are confounded with the inclusion of stressors (which increase blood pressure) and effects of L-Tyrosine per se cannot be easily separated from the effects of an L-Tyrosine and stress interactions

Edit5. Interactions with Physical Performance

L-tyrosine is typically supplemented with to alleviate the decline in neurological performance associated with moderate to long term mental exertion (which can be through study or exercise).

It is suspected in increasing performance from neurally intensive activites, as it does not appear to enhance performance systemically.^[24]

Edit6. Forms of L-Tyrosine

6.1. N-Acetyl-L-Tyrosine (NALT)

N-Acetyl-L-Tyrosine is a more soluble form of L-Tyrosine that appears to be relatively heat stable in solution^[25] that can be deacetylated to L-Tyrosine in the kidneys.^[25]

N-Acetyl-L-Tyrosine appears to be able to contribute free L-Tyrosine in vivo after administration IV administration, but only able to increase L-Tyrosine concentrated 20% despite much larger increases in serum NALT.^[25] 56% of the adminstered dose of NALT is excreted in 4 hours^[25] and another study suggests that, overall, 35% of the total NALT dose (administered parentally) is excreted via the urine as NALT and not L-Tyrosine.^[26]

Limited practical evidence on NALT as an alternative to L-Tyrosine

References

1. Nakashima A, et al. Role of N-terminus of tyrosine hydroxylase in the biosynthesis of catecholamines. J Neural Transm. (2009)
2. Webster D, Wildgoose J. Tyrosine supplementation for phenylketonuria. Cochrane Database Syst Rev. (2010)
3. Poustie VJ, Rutherford P. Tyrosine supplementation for phenylketonuria. Cochrane Database Syst Rev. (2000)
4. Shurtleff D, et al. Tyrosine reverses a cold-induced working memory deficit in humans. Pharmacol Biochem Behav. (1994)
5. Topall G, Laborit H. Brain tyrosine increases after treating with prodrugs: comparison with tyrosine. J Pharm Pharmacol. (1989)
6. Fernstrom JD, Fernstrom MH. Tyrosine, phenylalanine, and catecholamine synthesis and function in the brain. J Nutr. (2007)
7. Lehnert H, Wurtman RJ. Amino acid control of neurotransmitter synthesis and release: physiological and clinical implications. Psychother Psychosom. (1993)
8. Yeghiayan SK, et al. Tyrosine improves behavioral and neurochemical deficits caused by cold exposure. Physiol Behav. (2001)
9. Neri DF, et al. The effects of tyrosine on cognitive performance during extended wakefulness. Aviat Space Environ Med. (1995)
10. Lehnert H, et al. Neurochemical and behavioral consequences of acute, uncontrollable stress: effects of dietary tyrosine. Brain Res. (1984)
11. Irwin J, Suissa A, Anisman H. Differential effects of inescapable shock on escape performance and discrimination learning in a water escape task. J Exp Psychol Anim Behav Process. (1980)
12. Weiss JM. Effects of coping behavior in different warning signal conditions on stress pathology in rats. J Comp Physiol Psychol. (1971)
13. Brady K, Brown JW, Thurmond JB. Behavioral and neurochemical effects of dietary tyrosine in young and aged mice following cold-swim stress. Pharmacol Biochem Behav. (1980)
14. Behavioral Depression Produced by An Uncontrollable Stressor: Relationship to Norepinephrine, Dopamine, and Serotonin Levels in Various Regions of Rat Brain
15. Tyrosine Pretreatment Reverses HypothermiaInduced Behavioral Depression
16. Tyrosine and Stress: Human and Animal Studies
17. Banderet LE, Lieberman HR. Treatment with tyrosine, a neurotransmitter precursor, reduces environmental stress in humans. Brain Res Bull. (1989)
18. Deijen JB, Orlebeke JF. Effect of tyrosine on cognitive function and blood pressure under stress. Brain Res Bull. (1994)
19. Dollins AB, et al. L-tyrosine ameliorates some effects of lower body negative pressure stress. Physiol Behav. (1995)
20. Deijen JB, et al. Tyrosine improves cognitive performance and reduces blood pressure in cadets after one week of a combat training course. Brain Res Bull. (1999)
21. Jodko K, Litwinienko G. Oxidative stress in the neurodegenerative diseases--potential antioxidant activity of catecholamines. Postepy Biochem. (2010)
22. Yamori Y, et al. The hypotensive effect of centrally administered tyrosine. Eur J Pharmacol. (1980)
23. Tyrosine administration reduces blood pressure and enhances brain norepinephrine release in spontaneously hypertensive rats
24. Meeusen R, Watson P, Dvorak J. The brain and fatigue: new opportunities for nutritional interventions. J Sports Sci. (2006)
25. Magnusson I, et al. N-acetyl-L-tyrosine and N-acetyl-L-cysteine as tyrosine and cysteine precursors during intravenous infusion in humans. Metabolism. (1989)
26. Hoffer LJ, et al. N-acetyl-L-tyrosine as a tyrosine source in adult parenteral nutrition. JPEN J Parenter Enteral Nutr. (2003)

(Common misspellings for L-Tyrosine include tyrsine, tyrosin, tyosine, tyosin)

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