Tyrosine is a nonessential amino acid that was discovered circa 1846. The word “tyrosine” is derived from the Greek word “tyros” which translates roughly to “cheese.” Tyrosine is most commonly cited as “L-tyrosine” or the levorotatory “L” enantiomer due to the fact that L-amino acids are manufactured in cells and used in protein synthesis; dextrorotatory “D” enantiomers are not.
When most people think of L-tyrosine, they associate it with the neurotransmitter dopamine. Upon ingestion, L-tyrosine is efficiently broken down by the body and converted into dopamine; hence being considered a “dopamine precursor.” Thus, most people are able to get sufficient dopamine by eating foods high in tyrosine.
Unfortunately, many individuals are not consuming enough foods with L-tyrosine to attain sufficient levels of dopamine. Should an individual eat unhealthy and/or avoid foods with L-tyrosine, they may end up with low dopamine, and a host of other problems related to dopamine deficiency. There are many benefits associated with L-tyrosine consumption, regardless of whether you’re getting it via foods or supplementation.
L-Tyrosine Mechanisms of Action
The mechanism of action associated with L-tyrosine is to aid in catecholamine synthesis. Catecholamine metabolism begins with the amino acid L-phenylalanine, which is then converted into L-tyrosine via the enzyme phenylalanine hydroxylase. Following the conversion of L-phenylalanine to L-tyrosine, the L-tyrosine is converted into L-DOPA via the enzyme tyrosine hydroxylase.
Decarboxylation of L-DOPA results in synthesis of the neurotransmitter dopamine. Following production of dopamine, an enzyme called “dopamine-beta-hydroxylase” converts it into norepinephrine (noradrenaline) and epinephrine (adrenaline) via PNMT (Phenylethanolamine-N-methyltransferase). The triad of dopamine, norepinephrine, and epinephrine are collectively referred to as “catecholamines.”
Some speculate that the catecholamine synthesis associated with L-tyrosine provides neuroprotective benefit via an antioxidant effect. In other words, the catecholamine production may scavenge free radicals in the brain and help preserve neural health. L-tyrosine has also been suggested to stimulate production of T3 (triiodothyronine) and T4 (thyroxine) hormones, both of which are important for maintenance of physical and mental health.
L-Tyrosine Benefits (Scientific Research)
Below is a list of studies investigating the therapeutic potential of L-tyrosine supplementation. L-tyrosine is an effective supplement when used to maintain cognitive function under stress, and there is preliminary evidence to suggest benefit when using it for conditions like ADHD. However, using it for the treatment of other conditions such as dementia lacks scientific support.
ADHD: There are several studies that have investigated the usage of L-tyrosine for the treatment of ADHD (attention-deficit/hyperactivity disorder). A study published in 2011 suggested that when administered with 5-HTP (a serotonin precursor), L-tyrosine can be an effective intervention for ADHD. In addition, those taking both dopamine precursors (L-tyrosine) and serotonin precursors (5-HTP) may benefit from simultaneous administration of vitamin cofactors to aid in catecholamine synthesis.
This protocol was developed by Neuro Research Clinics and preliminary results suggested equal efficacy to pharmaceutical ADHD medications. Other evidence for using L-tyrosine to treat ADHD comes from a case study suggesting that supplementation significantly benefits individuals with certain genetic polymorphisms that may contribute to ADHD. Moreover, L-tyrosine appears to work in synergy with pharmaceutical drugs like methylphenidate, potentiating increases in extracellular dopamine.
There was one report that suggested L-tyrosine is ineffective for the treatment of ADHD, but this was not a formal study. A study published in the 1980s determined that L-tyrosine administration resulted in short-term therapeutic relief from ADHD symptoms, but eventually resulted in tolerance and a diminished effect. Evidence is mixed, yet favors the idea that L-tyrosine could benefit certain individuals with ADHD when strategically utilized.
2011: A publication in 2011 discussed a pilot study that investigated using amino acid precursors (including L-tyrosine) for the treatment of ADHD (attention-deficit/hyperactivity disorder). The study incorporated precursors of dopamine (L-tyrosine) and serotonin (5-HTP) and sought to determine both safety and efficacy. A total of 85 participants engaged in the study, all of which were between 4 and 18 years of age with a clinical diagnosis of ADHD.
ADHD symptoms were evaluated with the ADHD Rating Scale (ADHD-RS) prior to treatment and then after treatment. Participants were treated for an initial period of 8 to 10 weeks, during which if patients failed to get relief within 3 to 4 weeks of treatment, urinary samples were collected to determine levels of serotonin and dopamine. Researchers determined to get urinary levels of these neurotransmitters within a therapeutic range based on a specific protocol.
Various vitamin cofactors such as: Vitamin C (1000 mg), calcium citrate (220 mg), vitamin B6 (75 mg), folate, L-lysine (500 mg), L-cysteine (4500 mg), and selenium – were also administered to maximize synthesis. Based on the protocol, if patients didn’t respond to initial dosing, they moved on to a “Level 2” dosing, followed by a “Level 3,” until they responded. Results indicated that approximately 67% of individuals experienced significant improvement in ADHD symptoms with just dopamine and serotonin precursors; L-tyrosine and 5-HTP (respectively).
Researchers suggested that the dopamine and serotonin precursors yielded similar results to trials involving Strattera (Atomoxetine) and Ritalin (Methylphenidate). In fact, they suggest that using monoamine precursors may be a superior treatment option due to increased safety and superior tolerability. Moreover, it was noted that both L-tyrosine and 5-HTP have attained GRAS (Generally Recognized As Safe) status by the FDA.
This amino acid precursor protocol may be equal in efficacy to potent, pharmaceutical ADHD medications. That said, this was a mid-size study and first of its kind demonstrating efficacy for treating ADHD with L-tyrosine and 5-HTP. Individuals looking for an Adderall alternative may want to consider testing amino acid precursors.
- Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3035600/
2009: A case report published in 2009 documented a 4 year old boy diagnosed with Phenylketonuria and comorbid ADHD. Phenylketonuria a condition associated with polymorphisms of genes involved in phenylalanine hydroxylase. Those with this condition are unable to properly convert phenylalanine into tyrosine, which inhibits catecholamine synthesis.
Individuals with Phenylketonuria need to eat special diets, restricting them of foods containing phenylalanine due to the fact that they cannot metabolize it. That said, researchers investigated whether supplementation with L-tyrosine would improve this boy’s ADHD severity. After all, his catecholamine levels were likely lower than average.
Upon supplementation with L-tyrosine (100 mg/kg per day) the boy experienced a significant reduction in ADHD symptoms. The reduction was noted to have occurred over a period of 4 weeks, and the L-tyrosine supplementation was well-tolerated. This is a case example of an individual who benefitted significantly from L-tyrosine supplementation.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/19622700
2009: A report published in 2009 suggested that there was no evidence to support the use of L-tyrosine as a therapeutic intervention for ADHD. That said, just because this review points out that there isn’t sufficient evidence to support using L-tyrosine, does not mean that it is automatically an ineffective option. When this report was published, there wasn’t enough past research to draw upon in order to fully elucidate whether L-tyrosine could be useful (as a standalone treatment, with other monoamine precursors, or as an adjunct) for the treatment of ADHD.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/19344299
1991: A study was published in 1991 investigating the administration of L-tyrosine, methylphenidate (Ritalin), and a combination of L-tyrosine plus methylphenidate in a group of rats. The goal of this study was to determine how L-tyrosine and methylphenidate influenced synthesis and release of dopamine. Researchers also sought to understand whether L-tyrosine acted synergistically with methylphenidate for production of dopamine.
It was discovered that administration of methylphenidate plus L-tyrosine lead to significant increases in dopamine levels compared to methylphenidate in isolation. L-tyrosine as a standalone supplement resulted in minor, yet significant increases in dopamine levels; enhancing the firing of dopaminergic neurons. Due to the fact that many individuals with ADHD are thought to have low dopamine and/or dopaminergic dysfunction in various parts of the brain – perhaps L-tyrosine may reverse these abnormalities.
Further, it should be considered that L-tyrosine may provide therapeutic effect for individuals with less severe ADHD. Among those with severe ADHD symptoms, using L-tyrosine as an adjunct to a pharmaceutical medication (e.g. methylphenidate) may provide synergistic benefit, ultimately enhancing the therapeutic effect.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/1760749
1987: An old study published in 1987 investigated the role of catecholamines among individuals diagnosed with ADHD. A group of 12 adults were assigned to receive L-tyrosine over the course of 8 weeks. All of these adults were diagnosed specifically with “residual ADHD,” a specific subtype of ADHD.
Results suggested that 8 of the 12 adults experienced moderate responses to L-tyrosine after 2 weeks of administration. However, it appeared as though by week 6, the same 8 responders became tolerant to the effects of L-tyrosine. Researchers concluded that using L-tyrosine for residual ADHD was not an effective intervention.
It should be noted that in this study, L-tyrosine administration appeared to provide relatively quick relief within 2 weeks. It may provide acute relief of ADHD symptoms when administered on an intermittent or “as-needed” basis. It may be beneficial to investigate whether the substance could be used by individuals with ADHD as a temporary cognitive enhancer and also to understand the mechanisms associated with tolerance development.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/3300376
Blood pressure: Research suggests that L-tyrosine may have an effect on modulation of blood pressure. Some studies have determined that L-tyrosine administration reduces hypertension (high blood pressure), while other evidence suggests that L-tyrosine may promote an increase in blood pressure as a result of catecholamine synthesis. Certain studies have suggested a dose-dependent and administration-dependent relationship between L-tyrosine and blood pressure.
Other evidence suggests that L-tyrosine’s effect on blood pressure can be altered with administration of agents that affect the CNS. Further, some research documents the fact that baseline blood pressure (i.e. prior to taking L-tyrosine) may influence responses; those with hypertension may experience a reduction, while those with normal blood pressure may experience an increase.
1999: A study published in 1999 analyzed the effect of L-tyrosine on 21 military cadets engaged in a combat training course. Three measures were assessed prior to L-tyrosine administration, one of which was blood pressure. Of the 21 participants, 10 were assigned to receive 5 drinks containing L-tyrosine (2 grams) and the other 11 received a carbohydrate rich drink with the same number of calories.
Drinks were administered for 5 days, and participants were reassessed thereafter for blood pressure. Individuals receiving the “L-tyrosine” drinks had significantly lower systolic blood pressure compared to those receiving the placebo. Authors of the study speculate that L-tyrosine supplementation may offset certain aspects of stress, such as acute increases in blood pressure.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/10230711
1995: A study published in 1995 specifically investigated the effect of L-tyrosine on cardiovascular stress in humans. Researchers had noted that in animal trials, L-tyrosine seemed to decrease physiological and behavioral changes associated with acute stress. For this study, researchers recruited 20 participants and assigned them to “LBNP” (Lower Body Negative Pressure) sessions.
Some of the participants received 100 mg/kg L-tyrosine, while the others received a placebo. Results indicated that those taking the L-tyrosine displayed increased pulse pressure, a counterintuitive finding due to the fact that “LBNP” typically decreases blood pressure. This provides some evidence to suggest that L-tyrosine may unfavorably increase blood pressure in certain individuals.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/7716196
1994: A study published in 1994 discovered that L-tyrosine administration decreased blood pressure approximately 15 minutes after ingestion. This study involved assessing task performance following acute stress. Despite reducing diastolic blood pressure within 15 minutes of administration, blood pressure had normalized within 1 hour.
This study suggests that L-tyrosine administration may promote an acute decrease in blood pressure, followed by a return to baseline within 1 hour. It should be noted that this effect was only noted for diastolic blood pressure – systolic blood pressure did not appear to change.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/8293316
1987: Researchers published a study in 1987 noting that the effect of L-tyrosine on blood pressure is unknown due to conflicting reports. The goal of this study was to determine the effects of L-tyrosine on blood pressure among rats with hypertension. Results of the study suggested that L-tyrosine’s effect on blood pressure may be associated with the modality of administration as well as the dosage.
Specifically, low-dose intravenous injections of L-tyrosine resulted in high blood pressure, whereas high-dose intravenous injections resulted in low blood pressure. When given to the rats via diet, no overt effect on blood pressure was noted. While it cannot be assumed that these results would hold true in humans, it is evident that the method of administration and dosage of L-tyrosine may influence blood pressure.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/3691650
1983: A study published in 1983 determined how a group of spontaneously hypertensive rats (SHR) responded to dietary supplementation L-tyrosine for 15 weeks. It was noted that dietary supplementation with L-tyrosine resulted in slower increases in blood pressure than rats fed a standard diet (without L-tyrosine). That said, the difference between the two groups of rats wasn’t considered statistically significant.
It was noted that the initial few days of L-tyrosine supplementation decreased blood pressure. Despite small reductions in blood pressure, removal of L-tyrosine from the diet mitigated any small decreases associated with supplementation. Results from this study suggest that no major change in blood pressure is associated with dietary consumption of L-tyrosine.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/6845771
1983: Another study published in 1983 involved administration of L-tyrosine to dogs. The goal of this study was to determine how L-tyrosine would affect the dogs’ blood pressure. Researchers induced hypotension (low blood pressure) among the dogs via bleeding one hour prior to administration.
It was noted that the dogs with normal blood pressure prior to hypotension experienced an increase in blood pressure following L-tyrosine administration; this increase was dose-dependent. Dogs that were hypertensive prior to bleeding experienced decreases in blood pressure following L-tyrosine administration. This provides some evidence to suggest that baseline blood pressure status may predetermine responses to administration of L-tyrosine.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/6655468
1979: An early study from 1979 demonstrated that L-tyrosine administration among rats with hypertension reduced blood pressure. The reduction in blood pressure peaked within 2 hours of L-tyrosine injections. The mechanism by which L-tyrosine lowers blood pressure appears to be via the CNS (central nervous system).
Specifically, the antihypertensive effect of L-tyrosine is associated with expedited release of catecholamines such as norepinephrine and epinephrine. This is among the first reports suggesting that L-tyrosine administration is significantly reducing blood pressure through its effect on the CNS.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/291018
Cognitive performance: L-tyrosine appears to enhance cognitive function (i.e. act as a nootropic) in normal, healthy individuals when exposed to stress. Research has demonstrated that L-tyrosine improves cognitive performance in scenarios of abnormally “warm” or “cold” weather. In addition, it appears to buffer against stress-induced cognitive impairment and cognitive deficits associated with sleep deprivation.
Further, those exposed to acute stressors (e.g. combat training or loud noise) demonstrate significantly better cognitive task performance with L-tyrosine than without it. Many studies suggest that L-tyrosine inhibits stress-induced catecholamine depletion and normalizes suboptimal catecholamine reserves. There is also evidence that L-tyrosine increases cognitive flexibility under normative (non-stressful) circumstances.
2015: A review of evidence was conducted analyzing the effects of L-tyrosine on behavior and cognitive function. Researchers included a total of 15 studies within their review, and evidence indicated that L-tyrosine is able to improve working memory and information processing in demanding scenarios such as extreme weather. Authors suggest that L-tyrosine may enhance cognitive performance by increasing suboptimal levels of catecholamines.
Evidence is most robust for using L-tyrosine as a cognitive enhancer in demanding scenarios such as extreme weather and/or under acute stress. These conditions may deplete your catecholamine reserves, but administration of L-tyrosine seems to increase them to preserve optimal cognition. It remains unclear as to whether L-tyrosine enhances cognitive function in normative conditions.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/25797188
2015: It was reported that L-tyrosine is able to increase levels of dopamine within the brain. A study published in 2015 investigated whether L-tyrosine could increase cognitive flexibility. Cognitive flexibility refers to the ability to switch between tasks or modalities of thought; the quicker a person can switch tasks, the greater the cognitive flexibility.
The study design was double-blind, placebo-controlled, and randomized. A total of 22 participants were assigned to receive either: L-tyrosine or a placebo during “proactive” and “reactive” tasks. Results indicated that L-tyrosine significantly increased cognitive flexibility. Authors suggested that supplementation of L-tyrosine maximized cognitive resources, which resulted in superior performance.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/25598314
2015: A study published in 2015 sought to determine the effect of L-tyrosine on cognitive performance during exercise associated with a sport. In this case, researchers recruited 8 soccer players and had them complete a 90 minute soccer-simulation performance test on a non-motorized treadmill in an environmental chamber set to 77 degrees Fahrenheit. The participants were given either: L-tyrosine in a drink prior to their exercise (5 hours before and 1 hour before) or a placebo.
The study was considered double-blind and randomized in design. Cognitive performance was measured prior to the exercise task, at “half time” (45 minutes), following half time, and following the entire simulation (after 90 minutes). The cognitive performance task assessed dual-task and vigilance.
Outcomes revealed that cognitive vigilance and reaction time among soccer players significantly improved following administration of L-tyrosine in a warm (77 degree) setting. Results suggest that in warm-weather conditions, L-tyrosine may enhance cognitive function and/or inhibit cognitive impairment associated with exercise and/or heat.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/25326727
2014: A report published in 2014 suggests that L-tyrosine supplementation may have different effects on cognitive performance based on the individual. Authors hypothesize that responses to L-tyrosine supplementation may be related to individual differences in the neurotransmission of dopamine. Individuals with certain genetic polymorphisms that alter concentrations of dopamine in certain regions may benefit more (or less) from supplementation of L-tyrosine than others.
Authors specifically noted that the Val allele of the COMT polymorphism leads to low levels of dopamine within the prefrontal regions of the brain. Further, they suggest that those with this particular polymorphism and the “T allele” (of the TH gene) may derive substantial benefit from L-tyrosine supplementation due to the fact that greater quantities of L-tyrosine can be converted into dopamine.
This was an interesting report highlighting the potential complexities in responses to L-tyrosine supplementation. Further research needs to be conducted to determine how certain genetic polymorphisms may predict responses to L-tyrosine. Perhaps a company like GeneSight may be useful in predicting individuals likely to derive significant cognitive benefit from L-tyrosine.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/25339925
2013: A study published in 2013 determined whether L-tyrosine would bolster cognitive resources associated with cognitive control. To assess L-tyrosine’s effect on cognitive control, they performed assessments designed to measure “working memory” representations. The specific working memory assessment utilized in the study was the “N-Back” test.
All participants were assigned to engage in a “1-back” condition of “easy” difficulty and then in a 2-back condition of “tougher” difficulty. Individuals administered L-tyrosine demonstrated superior performance in the 2-back condition, but not the 1-back condition. Authors suggest that L-tyrosine provides greater cognitive enhancement when cognitive demand increases. (In other words, supplementation of L-tyrosine may help you increase your IQ score due to maximizing catecholamine reserve).
- Source: http://www.ncbi.nlm.nih.gov/pubmed/24379768
2007: Researchers noted that in rat studies, L-tyrosine attenuated catecholamine reduction associated with acute forms of environmental stress. They speculated that this effect may be similar in humans exposed to environmental stressors. A study published in 2007 investigated whether severe cold temperatures could impair cognitive function in humans, and whether L-tyrosine could mitigate temperature-induced impairment.
A total of 19 participants were recruited for the experiment, and were assigned to take 3 tests on separate days. The first day included taking a placebo and testing at 95 degrees Fahrenheit, the second involved a placebo and testing at 50 degrees Fahrenheit, and the third involved taking L-tyrosine (150 mg/kg) at 50 degrees Fahrenheit. The test sessions involved 90 minute water immersions, and cognitive performance was assessed.
The cold conditions resulted in poorer responses on memory and reaction time, with increased errors on another test. Upon ingestion of L-tyrosine (150 mg/kg), responses associated with memory improved, and information processing was quicker (as evidenced by decreased study time). Results demonstrated that cold temperatures impair cognitive function, but administration of L-tyrosine significantly attenuates some of the impairment.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/17585971
2001: A study published in 2001 determined the effects of L-tyrosine administration on mice. Researchers focused specifically on measures of behavior, exercise tolerance, and neurochemistry. They used an 8-arm maze to evaluate cognitive function in the mice after one week of L-tyrosine administration.
Results indicated that L-tyrosine improved cognitive function as evidenced by enhanced maze navigation. This may have been a result of increases in the neurotransmission of dopamine and serotonin, specifically within the hippocampal region. While cognitive function wasn’t a primary measure in this study, L-tyrosine appeared to enhance cognition.
- Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2631648/
1999: A study published in 1999 evaluated the effect of L-tyrosine on cognitive task performance among a group of 21 participants. The participants were considered “military cadets” and were set to undergo a combat training course. Prior to the combat training course, individuals were divided into 2 groups: one received a drink with L-tyrosine (2 grams) and the other received drink with carbohydrates serving as a placebo; both drinks contained an equal number of calories.
A baseline cognitive assessment was conducted prior to the combat course. After 5 days of combat course training, another cognitive assessment was recorded. Researchers noted that the individuals receiving L-tyrosine in their drinks performed significantly better on memory and tracking tasks than those receiving the placebo drinks.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/10230711
1995: A study from 1995 determined whether L-tyrosine could improve work performance among sleep-deprived individuals. Participants in the study had lost one full-night’s worth of sleep and cognitive function was assessed with a variety of performance tasks. Approximately 6 hours after the start of the experiment, half of the participants received L-tyrosine while the remaining half were given a placebo.
Researchers discovered that L-tyrosine administration significantly reduced cognitive-performance impairment associated with sleep deprivation as evidenced by a psychomotor task and vigilance task. Performance enhancement from L-tyrosine was noted to have lasted 3 hours. Authors speculate that L-tyrosine may attenuate cognitive performance impairment associated with sleep deprivation.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/7794222
1994: A study published in 1994 analyzed the effect of L-tyrosine on mental performance in 16 participants exposed to acute stress. All participants were noted as “healthy” and “young” and were tested twice over 2 days. One of the tests was conducted following administration of L-tyrosine (100 mg/kg), while the other was conducted following administration of a placebo.
During task assessments, researchers exposed participants to an acute stressor (90 decibels of noise). It was discovered that L-tyrosine significantly improved cognitive performance under stress compared to the placebo. This suggests that when faced with stress-sensitive tasks, catecholamine synthesis as a result of L-tyrosine may inhibit stress-induced cognitive impairment.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/8293316
Dementia: Those diagnosed with dementia often develop a host of neurophysiological symptoms. In 1977, researchers investigated whether treatment with amino acid precursors could offer therapeutic benefit to those with dementia. For this study, researchers recruited 10 individuals diagnosed with severe Alzheimer’s disease or multi-infarct dementia.
The treatment protocol for these individuals included daily administration of L-tyrosine (4 grams), 5-HTP (800 mg), and carbidopa (100 mg). Assessments were conducted to determine whether the individuals experienced significant improvement in aspects of neuropsychological functioning. Various side effects were reported from the amino acid precursor treatment, including: diarrhea, drowsiness, vomiting, agitation, and nausea.
Among the 10 participants, 2 patients showed significant improvement based on neuropsychological assessments; the remaining 8 showed no improvement. Results suggest that improvement in dementia from amino acid precursors is unlikely, and side effects may be unpleasant. That said, it may be beneficial to understand the mechanisms associated with favorable responses in the 2 responders and whether the L-tyrosine or 5-HTP provided more benefit than the other.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/301148
Depression: There isn’t significant evidence to suggest using L-tyrosine for depression. That said, many of the studies are flawed in that they emphasize acute tyrosine (and phenylalanine) depletion and fail to investigate the administration of L-tyrosine. Most individuals with depression are not going to derive substantial benefit from supplementing with L-tyrosine.
However, it appears as though individuals with a catecholamine depression, characterized by insufficient levels of: dopamine, norepinephrine, and/or epinephrine – may attain significant benefit from supplementation. For more information, read the article, “Depression: Dopamine vs. Serotonin.” One study noted that among individuals with dopamine-dependent depression, L-tyrosine (3200 mg) provided clinically significant benefit.
It may be interesting to investigate the potential of using L-tyrosine as an antidepressant augmentation strategy. It may prevent certain symptoms of depression and/or elicit synergistic antidepressant effects when co-administered with other supplemental or pharmaceutical agents.
2005: A study published in 2005 suggested that dopamine and depression may be linked. While most reports at the time suggested that serotonin was the primary culprit for depressive feelings, researchers wanted to investigate the role of dopamine. In this study, researchers recruited 20 participants who underwent temporary depletion of tyrosine and phenylalanine.
The depletion of these amino acids would help researchers determine how low dopamine may influence depressive symptoms among individuals recovered from unipolar depression. To assess depression at a baseline and following the amino acid depletion, the Hamilton Depression Rating Scale (HDRS) was administered. Secondary measures included a battery of computerized tests evaluating cognitive function.
Depletion of tyrosine and phenylalanine reduced plasma levels significantly, but patients did not relapse in depressive symptoms. The only significant effect was that the depletion in these amino acids resulted in altered decision making and reward sensitivity. Researchers speculate that only when a variety of neurotransmitters are simultaneously low (e.g. serotonin and catecholamines) will depressive symptoms emerge.
While this study didn’t investigate the administration of L-tyrosine, acute depletion of tyrosine didn’t seem to cause depression. This suggests that administration of L-tyrosine for additional dopamine is unlikely to improve depressive symptoms.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/15688090
2005: A study published in 2005 concluded that L-tyrosine doesn’t appear to influence mood. Similar to the aforementioned other 2005 study involving acute depletion of tyrosine, this study manipulated dietary intake to reduce levels of tyrosine. Researchers speculated that reductions in tyrosine may affect neurotransmission of dopamine and may contribute to symptoms such as psychomotor slowing, anhedonia, and energy reduction.
This study involved a total of 15 women with a history of recurrent depression. These women were assigned to receive a drink without amino acids (tyrosine / phenylalanine) and a balanced amino acid drink on 2 different occasions. The drink lacking the dopamine precursors resulted in poorer performance on a spatial recognition memory task.
That said, there appeared to be no significant influence of these drinks on mood. Reduction of dopamine precursors via dietary manipulation does not appear to influence mood, even among those with a history of depression. Despite the small-scale nature of this study, it appears as though dopamine doesn’t play as significant of a role in depression as some may suspect.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/15702140
2004: Another study investigated the effect of acute tyrosine depletion among healthy individuals. Researchers speculated that depletion of tyrosine (and phenylalanine) may alter transmission of dopamine, ultimately contributing to specific depressive symptoms. This study was both double-blind, placebo-controlled, and involved half the participants receiving a balanced mix of amino acids and the other half receiving a mix without dopamine precursors (tyrosine / phenylalanine).
A neuropsychological assessment was then administered to determine the effects. This study suggested that individuals depleted of tyrosine demonstrated increased apathy and felt less content. In addition, the group with tyrosine depletion were said to have exhibited a “sad latency bias” and had poorer performance on decision-making tasks.
Authors of this study suggested that clinical depression may be influenced by disruptions in emotion and reward processing associated with dopamine dysfunction. This evidence differs from newer studies suggesting less of a dopaminergic influence. It could be inferred that administration of L-tyrosine would quickly correct acute depletions and ultimately improve mood and decision making.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12955284
1990: In 1990, researchers noted that reduced levels of norepinephrine in the brains of rats result in behavioral depression. When rats are exposed to cold temperatures, norepinephrine neurons fire at a rapid rate, ultimately depleting norepinephrine in these areas of the brain. Researchers tested this theory by lowering the core body temperature of rats.
Reduction of core body temperature resulted in behavioral depression, likely as a result of norepinephrine depletion. As a second experiment, they determined whether administration of L-tyrosine (a precursor to norepinephrine) could inhibit behavioral depression associated with cold temperatures. Results indicated that administration of L-tyrosine 30 minutes before cold temperature exposure inhibited behavioral depression.
This suggests that among individuals experiencing depression as a result of acute catecholamine depletion, administration of L-tyrosine may provide therapeutic benefit. It is unclear as to whether this application would yield similar attenuation of depression in humans.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/2310942
1990: A study published in 1990 investigated the effect of L-tyrosine (100 mg/kg), imipramine (2.5 mg/kg), and a placebo for the treatment of depression. In other words, an amino acid precursor (L-tyrosine) is being compared to a tricyclic antidepressant (imipramine). This study was considered double-blind and randomized, and occurred for a period of 4 weeks.
Results suggested that L-tyrosine provided no substantial antidepressant effect. While this was an early study, it appears as though using an amino acid precursor of dopamine to treat depression doesn’t offer clinical benefit.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/2142699
1988: In 1998, researchers published a study documenting the effects of oral L-tyrosine among 12 individuals with dopamine-dependent depression. Dopamine-dependent depression is classified as a diagnosis of depression that is thought to result primarily from dopamine dysfunction (rather than serotonin). After a short-term trial with the dopamine agonist Piribedil, these individuals were administered a high dose of L-tyrosine (3200 mg per day).
It was noted that on the first day of treatment, mood improved significantly as evidenced by scores on the MADRS (Montgomery Asberg Depression Rating Scale). Further, sleep evaluations discovered significant improvement in sleep quality. Authors of this study note that over 50 individuals have been successfully treated for dopamine-dependent depression with L-tyrosine ranging from a period of several months to 2 years.
They emphasize the fact that L-tyrosine does not provide substantial benefit to those diagnosed with other types of depression. Therefore, if dopamine is the basis for your depressive symptoms, it may be worth investigating whether you are able to derive benefit from L-tyrosine. If your depression is not caused by low dopamine, it’s probably not worth trying.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/3126995
1984: A report published in 1984 attempted to understand how MAOIs (monoamine oxidase inhibitors) worked. In this report, the author discussed the fact that 5-HTP has antidepressant properties due to its transformation into serotonin within the brain. It was also noted that L-tyrosine converts into dopamine and norepinephrine within the brain.
The author noted that the effects of 5-HTP as an antidepressant are enhanced with administration of L-tyrosine. It was suggested to further investigate the potential antidepressant effect of 5-HTP and L-tyrosine. This provides some early evidence to suggest that when administered with other monoamine precursors, L-tyrosine may contribute to an antidepressant effect.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/6380226
1984: Another report published in 1984 suggests potential benefit from administration of L-tyrosine to depressed patients. The author notes that most early antidepressants targeted both catecholamine (CA) and indoleamine (IA) levels. Catecholamines refer to dopamine, norepinephrine, and epinephrine – whereas indoleamines refers mostly to serotonin.
In this report, it is suggested that administration of both L-tyrosine and 5-HTP may increase levels of norepinephrine and serotonin enough to decrease depression. He describes administration of these precursors as being analogous to performing “organic gardening in the brain.” This provides more evidence to suggest potential benefit from using L-tyrosine as part of a precursor cocktail for targeting depression.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/6443584
1982: In the early 1980s, it was hypothesized that catecholamine dysfunction may contribute to clinical depression. A report published in 1982 suggested that insufficient levels of norepinephrine in regions of the brain responsible for mood regulation may cause depression. Since L-tyrosine administration is known to increase concentrations of norepinephrine, those with depression may derive benefit from supplementation.
It was suggested that preliminary results associated with L-tyrosine supplementation for depression were promising. The author suspected that L-tyrosine may provide relief from all types of depression. That said, we now know that L-tyrosine is most likely to benefit those with depression caused primarily from catecholamine dysfunction (e.g. norepinephrine) as was hypothesized in this study.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/6764934
Skin health: L-tyrosine stimulates a process called melanogensis, or the production of cells called melanocytes. Melanocytes are responsible for generating melanin on the outer layers of the skin, giving the skin its pigment. Some speculate that supplementation of L-tyrosine may improve skin color and provide skin protection.
Generally insufficient melanin is a byproduct of genetic abnormalities rather than lack of dietary L-tyrosine. However, it should be hypothesized that sufficient L-tyrosine intake may be beneficial for skin health. Those with an albino complexion lack the enzyme “tyrosinase” which aids in production of melanocytes via ingestion of L-tyrosine.
2013: A study published in 2013 indicated that L-tyrosine is involved in melanogenesis, or the production of melanin. Melanin is a pigment found within the skin, eyes, and hair and produced by melanocytes. Suggesting that L-tyrosine influences melanogenesis means that it could pay an important role in the health of skin and color. The extent to which supplementation of L-tyrosine affects pigment and skin health remains unknown, but is believed to be complex.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/21834848
1990: An older report from 1990 indicated that L-tyrosine is a precursor to melanin, also influencing MSH receptors. It is assumed that sufficient dietary consumption of L-tyrosine may aid in certain pigmentation processes. In addition, researchers noted that L-tyrosine could aid in bioregulation of mammals upon metabolism.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/2359315
Stress: There remains insufficient evidence to recommend the usage of L-tyrosine for the treatment of psychological stress and/or anxiety in humans. In mouse models, administration of L-tyrosine can reverse cognitive impairment and neurotransmitter alterations caused by stress. Those that will knowingly be exposed to a stressful situation may derive cognitive benefit from supplementation of L-tyrosine.
Individuals with suspected stress-induced catecholamine depletion may benefit more substantially from supplementation of L-tyrosine. While L-tyrosine may buffer certain cognitive deficits associated with stress, it doesn’t seem to produce an anxiolytic (anti-anxiety) effect that most people seek for stress relief.
2012: In a study of adult mice, 9 stressors were administered for a 4 week period to stimulate the effects of “chronic stress.” Among the mice experiencing chronic stress, a variety of unwanted effects were noted. The mice were significantly slower in escaping from a maze, locomotor activity was decreased, hormone levels were altered, brain volumes were reduced, and catecholamine levels (dopamine and norepinephrine) were abnormally low.
Administration of an L-tyrosine supplement was able to inhibit all of these unwanted changes associated with chronic stress. This suggests that supplementation of L-tyrosine may buffer a variety of unwanted changes associated with chronic stress.
- Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4308793/
2009: Another study published in 2009 investigated the effect of L-tyrosine on mice exposed to chronic stress. For the study, researchers altered dietary consumption of L-tyrosine among socially isolated mice. Social isolation resulted in increased locomotor activity at a “home cage” and in an “open field,” indicative of increased stress.
Dietary L-tyrosine was capable of inhibiting locomotor increases associated with chronic stress. It was also noted that metabolites of norepinephrine significantly increased with dietary L-tyrosine, indicating that catecholamines may influence stress. It could be inferred that adequate dietary consumption of L-tyrosine could mitigate certain aspects of stress.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/19712729
2007: A 2007 publication reported that sources such as the U.S. military and Dutch military suggest benefit from L-tyrosine for stress reduction. The author of this publication noted that among animal models, stress stimulates the release of catecholamines (norepinephrine and dopamine) – ultimately reducing their levels; this is likely similar among humans. In these animal models, catecholamine levels can be restored via administration of L-tyrosine.
The author notes that L-tyrosine does not enhance neural firing in normative, non-stressed states – but it does in stressful situations. It was highlighted that L-tyrosine administration in humans buffers against cognitive deficits associated with physical stress. The publication also emphasized that L-tyrosine is different than dietary tyrosine in that it has a greater effect on catecholamine levels.
Ultimately this publication notes that L-tyrosine is unlikely to be an effective intervention for what most people consider “stress.” It does buffer against certain cognitive deficits associated with heightened stress, but there is insufficient evidence to recommend L-tyrosine as a therapeutic intervention for everyday stressors.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/17476368
Working memory: There is significant evidence to support the usage of L-tyrosine for optimization of working memory in stressful situations. For example, studies have determined that when faced with a stressor (e.g. cold temperature), working memory is subject to significant impairment. However, administration of L-tyrosine prior to the cold temperature exposure can significantly offset memory impairment.
There is also evidence to suggest that suboptimal catecholamine levels may impair working memory. Maintenance of catecholamines during cognitively demanding tasks promotes optimal performance. Those engaged in cognitively demanding tasks without supplementation of L-tyrosine may experience deficits in working memory and/or other cognitive functions.
2015: In a review of 15 studies, researchers noted that (2 week) “loading” of L-tyrosine significantly inhibits stress-induced working memory impairments. In other words, when exposed to stress, those that had been taking L-tyrosine for a period of time didn’t experience any working memory deficits. Authors suggested that L-tyrosine benefits working memory in stressful situations due to the stabilization of (potentially depleted) catecholamine levels (norepinephrine and dopamine).
- Source: http://www.ncbi.nlm.nih.gov/pubmed/25797188
2013: Another study was conducted to determine whether supplementation of L-tyrosine aids in cognitive-control during cognitively demanding tasks. For the study, they used a test called “N-Back” which specifically evaluates working memory. The study involved using an easy 1-N-back task (remembering 1 number back from the previous) or a more challenging 2-N-back task (remembering 2 numbers back from the previous).
Results indicated that those receiving L-tyrosine performed better at the more demanding 2-N-back task. It was suggested that L-tyrosine may provide benefit to working memory by ensuring optimal catecholamine levels during cognitively demanding tasks. Deficits in dopamine and norepinephrine may lead to impaired performance on more challenging tasks such as 2-N-Back due to greater usage of cognitive resources.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/24379768
2007: Among rats, it has been noted that acute environmental stress results in catecholamine depletion. In other words, levels of neurotransmitters norepinephrine and dopamine plummet as a result. However, when the amino acid precursor L-tyrosine is administered, it prevents catecholamine depletion in rat models.
A study published in 2007 sought to determine the effect of L-tyrosine in humans exposed to acute stressors. Researchers specifically analyzed whether L-tyrosine prevented catecholamine depletion and cognitive deficits associated with acute stress. A total of 19 participants were assigned to three 90-minute water immersion tasks, one per day over a 3 day span.
One test was taken at a 95 degree Fahrenheit temperature and a placebo was given. The next two tests were administered at 50 degrees Fahrenheit, one with a placebo and the other with L-tyrosine. Results suggested that administration of L-tyrosine offset cold weather-induced working memory impairment. This was evidenced by increased accuracy on a Match-to-Sample memory task.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/17585971
2005: A study conducted in the 2000s analyzed whether acute tyrosine depletion may cause depression among a group of 15 women with histories of recurrent depression. Tyrosine depletion was accomplished via administration of a drink lacking both Tyrosine and Phenylalanine; catecholamine precursors. A control group received a drink balanced with various amino acids and was compared to the tyrosine-depleted group.
The findings indicated that performance on spatial recognition memory tasks were impaired among those exposed to acute tyrosine depletion. This suggests that sufficient dietary dopamine precursors (e.g. L-tyrosine) may aid in various memory tasks. Reductions in catecholamine levels as a result of depletion may impair working memory.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/15702140
1999: A study conducted in the 1990s investigated the effect of L-tyrosine on working memory in a group of 10 men and 10 women. All participants were given either L-tyrosine (150 mg/kg) or a placebo, followed by a working memory test. The working memory test incorporated a “Multiple Task” and a “Simple Task” – the former being more difficult than the latter.
Researchers discovered that the individuals receiving L-tyrosine improved significantly on working memory retrieval measures during the “Multiple Task” of the working memory assessment compared to the placebo. No other significant differences were noted between the L-tyrosine group and the placebo group. Authors suggested that L-tyrosine maintains working memory in cognitively demanding scenarios.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/10548261
1994: A study published in 1994 suggested that cold temperature can induce stress which impairs working memory. Researchers suspected that the working memory impairment was a direct result of catecholamine release under stress, resulting in suboptimal levels. They speculated that administration of L-tyrosine as a catecholamine precursor may be able to offset cold temperature induced memory impairment.
In this study, researchers investigated whether L-tyrosine administration (150 mg/kg) would inhibit working memory deficits stemming from cold temperatures. A total of 8 participants engaged in a computer-based delayed matching-to-sample (DMTS) working memory assessment. This assessment was taken at either a cold temperature or a comfortable temperature following ingestion of L-tyrosine or a placebo.
Memory deficits were prominent in the cold temperature, but L-tyrosine significantly improved working memory accuracy in the cold condition compared to the placebo. No significant differences were noted between L-tyrosine and placebo at a comfortable temperature. This suggests that L-tyrosine offsets acute working memory decline in stressful situations.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/8029265
What are the most prominent benefits of taking L-tyrosine?
Based on the scientific research, there aren’t substantial benefits associated with L-tyrosine supplementation under normative, homeostatic conditions. Significant benefits can be derived from L-tyrosine under physically or psychologically stressful conditions. L-tyrosine supplementation prior to exposure to an acute stressor (in the form of abnormally cold, abnormally hot, or physically-demanding conditions) preserves cognitive function.
Perhaps most notably is L-tyrosine’s ability to preserve working memory function upon exposure to an acute stressor. Research suggests that cognition and working memory plummet during exposure to an acute stressor as a result of catecholamine depletion. When faced with stress, excess neural firing depletes some of the catecholamine reserve, leading to diminished levels of dopamine, norepinephrine, and epinephrine.
L-tyrosine administration maintains catecholamine reserves, meaning your dopamine, norepinephrine, and epinephrine levels aren’t subject to significant decline. Since catecholamine levels don’t significantly decline, cognitive function is maintained rather than impaired. In addition, it appears as though L-tyrosine supplementation can enhance cognitive flexibility and performance on advanced tasks that require significant cognitive horsepower (e.g. multi-N-back).
In addition to using L-tyrosine to preserve cognition under stress, some research suggests that it could be effective for those with a catecholamine-based (e.g. low dopamine) depression. Administration of L-tyrosine for dopamine-dependent depression was found to be a highly effective intervention. Moreover, there is evidence that when administered with other amino acid precursors (e.g. 5-HTP) and vitamin cofactors, it may be therapeutically effective for the treatment of ADHD.
Are there any conditions for which L-tyrosine is ineffective?
There is insignificant evidence to suggest that L-tyrosine is an effective cognitive enhancer under normal conditions. Studies suggest that when compared with a placebo in a non-stressful scenario, no significant differences were documented. Further, there remains insignificant evidence to recommend L-tyrosine supplementation for the treatment of neurodegenerative diseases like dementia and/or Alzheimer’s; additional research is warranted to elucidate the therapeutic potential in this area.
A majority of individuals with depression will not attain any significant benefit from supplementation of L-tyrosine. And while L-tyrosine can help prevent catecholamine and cognitive decline associated with stress, it is not an effective anxiolytic or anti-stress supplement. Research does not support the idea that L-tyrosine treats anxiety, and using it is unlikely to result in increased relaxation.
Limitations associated with L-Tyrosine research
As with any dietary supplement, there are significant limitations associated with L-tyrosine research. Most studies to date have been small-scale and focused primarily on evaluating its effect on cognitive function under stress. There is an increasing need for more large-scale, long-term human trials to better understand the therapeutic potential and possible dangers associated with L-tyrosine supplementation.
- Dosage: The dosing guidelines for L-tyrosine are relatively unclear for humans. Some studies involve giving higher doses of L-tyrosine (over 3 grams per day), while others administer an amount based on body weight like 100 mg/kg per day. It is unknown as to whether higher doses are more likely to treat certain conditions or whether lower doses can be equally as effective. Researchers should attempt to elucidate the influence of L-tyrosine dosing on therapeutic outcomes.
- Evaluation criteria: The evaluation criteria used to understand the effects of L-tyrosine is subject to variation based on the study. For example, some studies specifically focus on testing working memory functions, while others focus more on spatial memory. The assessments used to evaluate these measures are generally subject to variation based on the study. Researchers should focus on using similar evaluation criteria to that used in past trials to support or deny older claims.
- Lack of human trials: Most studies highlight subtle differences in L-tyrosine administration in humans compared to rats and mice. There are numerous published studies investigating the effect of L-tyrosine in animals, but there aren’t enough evaluating its effects in humans. Since L-tyrosine appears to be safe over the short-term, more human trials are warranted.
- Participants: There is a need for an increased number of human participants in trials. In addition, the sample should be diverse – including all ages, sexes, and ethnicities. Most studies are limited in that they have a small number of human participants, and the sample is not always diversified.
- Short-term research: Due to the fact that most research involving L-tyrosine has been conducted over a short-term (e.g. hours, days, or weeks), the long-term effects remain a mystery. Although it is believed that L-tyrosine is safe over a long-term, its safety isn’t fully understood – especially when administered at high daily doses for a period of months or years. Researchers should attempt to extend their research to longer-term trials.
- Small-scale trials: The biggest limitation of L-tyrosine research is that the trials are generally small-scale. Since this isn’t a pharmaceutical drug, it is difficult to get funding to conduct research of L-tyrosine. The trials are small-scale in that none incorporate triple-digit numbers of participants. Due to the small-scale nature of the published studies, it is unclear as to whether the results are subject to inaccuracies.
- Study designs: Most of the research conducted with L-tyrosine does not incorporate a placebo-controlled, double-blind, randomized design. Studies that do not incorporate a strict placebo-controlled, double-blind, randomized design may be subject to inaccuracies based on the design alone. In future research of L-tyrosine, there is an increasing need for more robust designs with a greater number of participants.
Further research of L-Tyrosine is warranted
Although there are several benefits that can be derived from L-tyrosine supplementation, the significance of these benefits are unclear for many reasons. The aforementioned limitations such as: small samples, lack of sample diversity, poor study designs, and short-term administration – all may contribute to a skewing of the results. Further research of L-tyrosine should involve large, diverse samples of humans and should be well-designed.
In addition, it would be beneficial to understand the intricacies of dosing such as optimal dosing for certain conditions, and determine whether unwanted long-term effects may occur with frequent supplementation. It would also be interesting to investigate how individuals with genetic polymorphisms affecting catecholamine synthesis and receptors may influence responses to L-tyrosine and other precursors.
Researchers may want to expand upon the large body of research investigating L-tyrosine as a cognitive preservative when faced with stress. However, there are other potential uses of L-tyrosine such as for: ADHD (as part of a protocol), dementia, depression (catecholamine-based), and even skin health – that warrant further investigation. Moreover, the synergistic effects of L-tyrosine remain unclear, particularly when administered with another dopaminergic drug
Co-administration of L-tyrosine with a pharmaceutical agent or another supplement may help us better understand its synergistic potential. There are many potential avenues of investigation for L-tyrosine researchers. The biggest key is to focus on recruiting large enough samples to confirm or dismiss evidence in small-scale preliminary studies.
Have you noticed any benefits from taking L-tyrosine?
If you’ve noticed any significant benefits from supplementation of L-tyrosine, be sure to mention them in the comments section below. Document the brand of L-tyrosine you had been taking, the dosage, as well as the specific formulation (e.g. N-Acetyl L-Tyrosine vs. L-Tyrosine). Discuss how long you’ve been taking L-tyrosine, how often you take it (e.g. daily), and whether it is part of a supplement “stack” or administered in isolation.
Mention on a scale of 1 to 10 how effective L-tyrosine is for your condition and/or purpose of usage. Note how long it took before you noticed L-tyrosine started working and whether you’ve noticed diminished efficacy over time (as a result of tolerance). Is there a way you can tell you’ve benefitted from L-tyrosine? How can you dismiss the possibility of a placebo effect?