What is L-tyrosine
L-Tyrosine (C9H11NO3) is a conditionally essential (non-essential) amino acid because L-tyrosine can be synthesized in the body from L-phenylalanine, an essential amino acid 1. If insufficient L-phenylalanine is available, L-tyrosine then becomes essential. Therefore, if L-phenylalanine is present in sufficient quantity in your diet, L-tyrosine is non-essential, which is the normal circumstance. If the conversion of L-phenylalanine to L-tyrosine is compromised, as in phenylketonuria (PKU), or in very young humans, in whom the demand for L-phenylalanine is exceptionally high, additional dietary L-tyrosine may be required for protein synthesis and growth.
L-Tyrosine occurs naturally in foods, mainly as part of proteins. Food sources of tyrosine include fish, soy products, poultry, eggs, dairy products, lima beans, almonds, peanuts, sesame seeds, pumpkin seeds, wheat germ, oats, avocados, and bananas.
Some people have low levels of tyrosine in their bodies because of a hereditary condition called phenylketonuria (PKU). For those with phenylketonuria (PKU), a severe deficiency in the enzyme phenylalanine hydroxylase prevents conversion of phenylalanine to tyrosine, making tyrosine an essential amino acid for this population 2. Tyrosine is given as a supplement to increase tyrosine levels in people with phenylketonuria (PKU).
Tyrosine is incorporated into proteins of all life forms and is a precursor for synthesis of thyroxin, melanin, and the neurotransmitters dopamine and norepinephrine 2.
L-Tyrosine is also a precursor of the biosynthesis of melanin, which contributes to coat color in many animal species. Dietary L-tyrosine is provided by mixed dietary protein intakes from different sources such as meat, fish, eggs, dairy products, beans, nuts, oats, and wheat; it can also be consumed in the form of food supplements. The Joint FAO/WHO expert committee of Food Additives 3 assessed L-tyrosine when used as a flavoring and no concern for consumer safety was identified. The content of L-tyrosine in foods can be measured by established methods.
L-Tyrosine is the starting point for the synthesis of all catecholamines. L-Tyrosine is hydroxylated to form dihydroxy-L-phenylalanine (also known as levodopa or L-dopa) via the enzyme tyrosine hydroxylase 4. In dopaminergic neurons, levodopa is metabolized to dopamine by means of the enzyme dopa decarboxylase. In noradrenergic nerve cells and in the adrenal medulla, dopamine is transformed to noradrenaline via the enzyme dopamine β-hydroxylase. Noradrenaline can then be transformed into adrenaline by the addition of a methyl group through the action of phenylethanolamine-N-methyltransferase 5.
L-Tyrosine is the precursor of the catecholamines; alterations in the availability of L-tyrosine to the brain can influence the synthesis of both dopamine and norepinephrine in experimental animals and probably in humans 6. In animals, stress increases the release of catecholamines, which can result in the depletion of their levels, an effect that can be corrected by giving L-tyrosine. L-Tyrosine does not seem to enhance the release of catecholamines when neurons are firing at their basal rates, but it does when firing rates are increased by stress. This is the basis for studying the effect of L-tyrosine on the stress response of humans.
Patients or healthy people feeling somewhat stressed may read claims that L-tyrosine alleviates the effects of stress. They probably imagine that L-tyrosine will help them to feel less stressed in response to the psychosocial stressors of everyday life. What has been shown is that L-tyrosine prevents some of the cognitive decline in response to physical stressors, an effect of interest to almost noone outside the military. Patients who are already taking L-Tyrosine need to be educated about what it has actually been shown to do and about the lack of evidence for long-term safety 6.
Given that purified L-tyrosine is handled metabolically in a somewhat different way from ingesting it as part of the diet, calling it a dietary or natural supplement is misleading. Effectively, L-tyrosine is being used as a drug. Safety data on long-term L-tyrosine use in healthy people is lacking. In one of the longest studies, 2.5 g L-tyrosine 3 times daily had no beneficial or adverse effects when given to people with mild essential hypertension for 2 weeks. The measures in this study were limited to heart rate and blood pressure.
The use of L-tyrosine with levodopa may decrease the effectiveness of levodopa because they compete for absorption in the small intestine. If taken concomitantly it is recommended that dosages be separated by at least two hours. In persons taking thyroid hormone medications, tyrosine administration may boost thyroxin levels because it is a thyroid hormone precursor.
Before using tyrosine, talk to your healthcare provider. You may not be able to use tyrosine if you have certain medical conditions, especially:
- overactive thyroid; or
- Graves disease.
It is not known whether tyrosine will harm an unborn baby. Do not use this product without medical advice if you are pregnant.
It is not known whether tyrosine passes into breast milk or if it could harm a nursing baby. Do not use this product without medical advice if you are breast-feeding a baby.
Do not give any herbal/health supplement to a child without medical advice.
Tyrosine is used in animal feeds for dogs and cats (dry and moist food), as well as chickens and piglets. L-Tyrosine is intended to be used in feed and food for all animal species and categories. L-Tyrosine can be added directly to complete or complementary feedingstuffs. The supplementation of animal feed with L-tyrosine is efficacious in cases where high requirements for tyrosine as a melanin precursor occur. This has been demonstrated for cats for intensively coloring the coat. L-Tyrosine may also have the potential to intensify the pigmentation of the coat/plumage of other species, but limited evidence is available.
Tyrosine has also been used in alternative medicine and sold as a herbal supplement as an aid in improving mental performance, alertness, or memory. Tyrosine has also been used to treat depression or attention deficit disorder (ADD or ADHD). However, research has shown that tyrosine may not be effective in treating these conditions. Tyrosine also may not be be effective in improving exercise performance.
Other uses not proven with research have included dementia, high blood pressure, narcolepsy, schizophrenia, weight loss, premenstrual syndrome, Parkinson’s disease, chronic fatigue syndrome, alcoholism, cocaine addiction, and other conditions.
It is not certain whether tyrosine is effective in treating any medical condition. Medicinal use of this product has not been approved by the FDA. Tyrosine should not be used in place of medication prescribed for you by your doctor.
There are no regulated manufacturing standards in place for many herbal compounds and some marketed supplements have been found to be contaminated with toxic metals such as lead, cadmium, mercury and arsenic or other drugs. L-Tyrosine is obtained by acid hydrolysis of natural keratin (poultry feathers). The feathers are dissolved in 20 % hydrochloric acid at 70 °C followed by hydrolysis at 106 °C. L-Tyrosine is eventually separated from L-cystine by crystallization from alkaline solution. Herbal/health supplements should be purchased from a reliable source to minimize the risk of contamination.
Depression, as a mood disorder, is considered a serious problem to human health because of its relatively high prevalence associated with a significant disability 7.
A number of theories were studied to identify the cause of depression, including genes and circadian rhythms 8; however, the monoamine hypothesis was the most influential and widely studied one. This hypothesis suggests that disturbances in the cerebral level of noradrenaline (norepinephrine), dopamine or serotonin play a key role in depression 9.
Several studies have suggested serotonin precursors (tryptophan, 5-hydroxytryptophan) and catecholamines precursors (phenylalanine, tyrosine) as a possible way to manage depression 10.
L-tyrosine is a precursor of adrenaline, dopamine and noradrenaline (norepinephrine), where it may have an impact on depression. Most clinical trials examining tyrosine supplementation in depressed patients have been small in size and yielded mixed results. Two clinical studies on depressed patients and healthy volunteers have shown that treatment with L-tyrosine has a positive role in depression management, mediated by noradrenaline (norepinephrine) and dopamine levels 11, 12.
The same researchers 13 conducted a subsequent double-blind, placebo-controlled trial involving 14 patients suffering from major depression (five or more symptoms of depression present for at least two weeks) of at least moderate severity. Six patients received 100 mg/kg oral tyrosine daily and eight received placebo for four weeks. Four of six patients (67%) receiving tyrosine achieved scores of 10 or less (lack of clinically significant depression) on the Hamilton Depression Scale (HAM-D), indicating improvement in depressive symptoms. Only three of eight patients (38%) in the placebo group reported improvement. The patient sample size was too small to warrant an analysis of statistical significance 13.
A larger randomized, prospective, double blind trial 14, including 65 patients (ages 18-75) with major depression, compared the efficacy of tyrosine to imipramine or placebo for four weeks. Patients in the tyrosine group (n=21) received 100 mg/kg daily, the imipramine group (n=22) received 2.5 mg/kg daily, and the control group (n=22) received a placebo. Although patients taking tyrosine had increased fasting plasma tyrosine levels as well as increased urinary excretion of a norepinephrine metabolite, no statistically significant improvement in HAM-D scores was noted in the tyrosine group. This may have been a result of the 26-percent dropout rate (17 of 65 patients dropped out – four in the tyrosine group, eight in the imipramine group, and five in the placebo group) and the resulting small patient sample size 14.
In a laboratory mice study, treatment with L-tyrosine-loaded nanoparticles, through behavioral tests, showed positive results which are probably attributed to restorating the basal levels of the cerebral noradrenaline 15. Rauch and Lieberman 16 and Lieberman et al. 17 have also reported that treatment of stressed rats with L-tyrosine reversed the depressive behavior induced by cold exposure or hyperthermia.
The effects of L-tyrosine administration on the cerebral levels of tyrosine hydroxylase and corticotropin-releasing factor should be further investigated.
L-tyrosine effects on stress
Several clinical trials have demonstrated tyrosine administration ameliorates some effects of stress, including hypertension. Some studies were conducted by the U.S. military to identify agents that would help military personnel cope with combat stress. In one double-blind, placebo-controlled, crossover trial, 23 male military personnel (ages 18-20) were given 50 mg/kg tyrosine or placebo and then exposed to three levels of environmental stress – exposure to 58°F/15°C and either 4,200 or 4,700 meters simulated altitude or exposure to 71°F/22°C and 550 meters simulated altitude (normal control) for 4.5 hours. Forty minutes after
stress initiation subjects received a second 50 mg/kg dose of tyrosine or placebo. At the end of the stress period, tyrosine administration had significantly reduced headache, coldness, stress, fatigue, muscle aches, and sleepiness compared to controls, regardless of which simulated high altitude subjects were exposed to. Improvements were noted in mood/mental states (happiness, mental clarity, hostility, and tension) and cognitive tests (math skills, coding map compass, and pattern recognition) in the tyrosine group 18.
A second study conducted by Massachusetts Institute of Technology and U.S. Air Force researchers demonstrated a similar affect when subjects were exposed to -50 mm Hg lower body negative pressure (LBNP) for 30 minutes. LBNP is a technique used to induce cardiovascular stress via application of a simulated gravitational load to the lower body. Tyrosine was administered in 50 mg/kg doses an hour before and after initial stressor exposure. Improvements were noted in pressure tolerance, pulse pressure, and feelings of “vigor”19.
In a study of 16 healthy young adults (mean age=27), 100 mg/kg tyrosine given prior to auditory stressor exposure resulted in significant improvement in the Stroop color-identification test and the Digit Span test evaluating short-term memory. In addition, a significant decrease in diastolic blood pressure was observed in the tyrosine group compared to placebo 20. Other studies have also noted decreased blood pressure in stressed subjects receiving tyrosine therapy 21.
In The Netherlands, 21 Royal Military Academy cadets were given tyrosine and evaluated on computerized memory and tracking tasks, mood questionnaire, and blood pressure during an extremely demanding two-week combat course. In double-blind fashion the tyrosine group (n=10) received 2 g tyrosine in a 500-mL protein-rich orange juice drink daily, and the placebo group (n=11) received a 500-mL carbohydrate rich orange juice drink daily for the first six days of the combat training. Testing was conducted before combat training and the post-test commenced on the sixth day of training. The tyrosine group performed better on memory comparison and tracking tasks and had lower blood pressure readings than the placebo group. Mood questionnaires did not reveal statistically significant improvement in the tyrosine group, although only 13 of 21 participants completed the questionnaire 22.
Another double-blind study 21 similar in sample size investigated the effects of tyrosine on cognitive performance in U.S. Marines during periods of extended nighttime wakefulness. Results demonstrated 150 mg/kg oral tyrosine given in the middle of the testing period resulted in improved performance (smaller performance decline) during the sleep deprivation period. Better performance was observed on tracking tasks and running memory tasks, and subjects also reported reductions in sleepiness and fatigue intensity. No side effects were noted in those taking tyrosine. Two additional small studies conducted by other branches of the U.S. military indicate tyrosine administration at doses of 150 mg/kg prior to exposure to prolonged cold temperatures mitigates working memory deficits 23.
L-tyrosine and increased attention
In the double-blind placebo-controlled study by Banderet and Liebermann 24, 23 males (18-20 years) underwent two stressor conditions (15°C/4200 m altitude pressure and 15°C/4700 m altitude pressure) and a control condition (22°C/550 m altitude) after ingesting either tyrosine (2 doses of 50 mg/kg body weight) or placebo (not described). Stressors and control condition were applied for 4.5 hours each with a minimum of 48 hours between sessions. Test sessions started at 7.00 am and the treatment was provided at 7.20 am and 8.00 am. Behavioral testing, which started 1 h 20 min after tyrosine/placebo ingestions, included a range of cognitive tests assessing vigilance (choice reaction time task) and attention (sustained attention task, dual vigilance task) along with multiple other endpoints. Analysis was restricted to participants who showed an effect of the stressor (i.e. if differences in scores under stressor conditions and placebo condition were greater than group mean difference). However, no information was available on the number of participants who entered the analysis. The European Food Safety Authority Panel notes that the placebo was not described and that insufficient information was available on the statistical analyses performed. The European Food Safety Authority Panel considers that no conclusions can be drawn from this reference for the scientific substantiation of the claim 4.
In another randomized, double-blind, placebo-controlled, parallel study by Neri et al. 25, the effect of tyrosine was assessed in 20 male subjects during an episode of continuous night time work (13 h test duration during the night, from 19.30 pm to 8.20 am). Subjects were submitted to nine experimental blocks of 90 min, separated by 40 min breaks during which they were provided with caffeine-free snacks (composition not described). At 1.30 am and 3.00 am, tyrosine (2 doses of 75 mg/kg body weight, n=10) or placebo (corn starch, 2 doses of 75 mg/kg body weight, n=10) were provided with approximately 113 g of banana yogurt. The testing consisted of a selective attention task (dichotic listening) along with other cognitive endpoints. As an additional stressor, subjects were exposed to a low-frequency 70 dB noise during the tests. Performance on all tasks deteriorated steadily through the night. Differences between groups were not statistically significant for the dichotic listening task. The European Food Safety Authority Panel notes that this study does not show an effect of the consumption of L-tyrosine on attention endpoints 4.
In a cross-over, double-blind study, Thomas et al. 26 administered, in a random order, L-crystalline tyrosine (150 mg/kg body weight) and placebo (7 g microcrystalline cellulose) with 70 g apple sauce to 20 young healthy male and female subjects (age range 20-38 years) to investigate the effects of tyrosine ingestion on performance under mild stress conditions. Cognitive testing began 60 minutes post-ingestion and was administered either in a multi-tasking environment (mild stress condition) or in a simple task environment. In the multi-tasking environment subjects were required to simultaneously perform a Sternberg Memory Task (working memory task), an arithmetic task (addition of numbers), a visual monitoring task and an auditory monitoring task (both sustained attention tasks). In the simple task environment, participants were given the Sternberg task and the visual monitoring task only. Differences between groups were not statistically significant for the visual monitoring task and the auditory monitoring task. The European Food Safety Authority Panel notes that this study does not show an effect of the consumption of L-tyrosine on attention endpoints 4.
In weighing the evidence, the European Food Safety Authority Panel took into account that the two studies from which conclusions could be drawn for the scientific substantiation of the claim showed no effects of L-tyrosine, compared to placebo on attention endpoints 4. The European Food Safety Authority Panel concludes that a cause and effect relationship has not been established between the consumption of L-tyrosine and increased attention.
L-tyrosine has been studied as a potential therapeutic agent for attention deficit disorder (ADD) based on evidence suggesting dopaminergic central nervous system malfunctioning in individuals with ADD. In two studies 27, 28 of 34 and 12 patients with tyrosine dosages ranging from 30-150 mg/kg daily, significant symptomatic improvement in ADD symptoms was initially noted. However, tolerance to tyrosine developed after 6-10 weeks and symptoms returned, indicating no long-term benefit to tyrosine supplementation in this patient population.
L-tyrosine and narcolepsy
In a small, six-month pilot trial in eight narcoleptic patients an average daily dose of 100 mg/kg tyrosine resulted in complete elimination of daytime sleep attacks and cataplexy. The open-label design with lack of a control group limits this study’s value 29. A randomized double-blind, placebo-controlled trial of L-tyrosine in 10 narcoleptic patients with cataplexy (mean age=42) yielded different results. Patients were randomized to receive either 3 g tyrosine three times daily (~125 mg/kg daily for 160-lb adult) or placebo for four weeks and then switched to the other treatment with no washout period. Measurements included a multiple sleep latency test, patient symptom assessment, and psychometric tests. Three subjects in the tyrosine group reported improvement and rated themselves less drowsy, less tired, and more alert when on tyrosine; but improvement was mild and not clinically significant. No significant differences were reported on other assessments compared to the placebo group 30.
The typical daily dosage of oral tyrosine is 100-150 mg/kg body weight.
L-tyrosine side effects
L-Tyrosine is usually absorbed in the proximal small intestine. Any L-tyrosine reaching the large intestine is decarboxylated to tyramine, a biogenic amine, in the human gut. Inadequate degradation (detoxification) of formed tyramine by the gut monoamine oxidases can lead to tyramine entering the systemic circulation. Tyramine acts as a vasopressor 31; it is known to be a cause of migraine headaches in humans 32. Very recently, for a single oral administration in healthy individuals, a no observed adverse effect level (NOAEL) of 200 mg tyramine/person has been proposed, based on a literature survey 33. In contrast, individuals with reduced monoamine oxidase activity may suffer hypertension after ingestion of < 5 mg tyramine 34. Intellectual deficit problems seem to occur when human neonates receive abnormally high quantities of L-tyrosine 35.
Patients with Grave’s disease (hyperthyroidism) should use caution when supplementing with tyrosine because it can boost thyroid hormone levels.
Common side effects may include:
- nausea, heartburn;
- joint pain; or
- feeling tired.
Occasional nausea, diarrhea, headaches, vomiting, or insomnia are reported by those taking higher doses of tyrosine (>150 mg/kg daily). Insomnia can be prevented by avoiding supplementation in the evening.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.References
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- JECFA (Joint FAO/WHO Expert Committee on Food Additives), 2005. Evaluation of certain food additives. WHO Technical Report Series 928, Sixty-third report of the JECFA. ISBN 9241209283, 157 p.
- Scientific Opinion on the substantiation of health claims related to L‐tyrosine and contribution to normal synthesis of catecholamines (ID 1928), increased attention (ID 440, 1672, 1930), and contribution to normal muscle function (ID 1929) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2011.2270
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