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- Stress – 9
- Athletic performance – 7
- Tyrosine supplements should not be taken by those with conditions associated with increased dopamine levels such as mania and schizophrenia.
- Tyrosine should be avoided in patients with melanoma.
- This supplement may increase sensitivity to the effects of CNS stimulants. Caution is advised when taking tyrosine along with stimulants and dosages should be lowered accordingly.
- Other drugs which tyrosine may interact with include monoamine oxidase inhibitors (MAOIs), opiates, and L-DOPA.
Introduction
L-tyrosine is an amino acid found in the diet that is a precursor to numerous important substances in the body, most notably the catecholamines dopamine (DA) and norepinephrine (NE). It is also a precursor to both melanin and thyroxine. Tyrosine is considered to be conditionally essential because it can be synthesized from phenylalanine when there is sufficient dietary phenylalanine [1]. People with phenylketonuria lack the enzyme necessary to convert phenylalanine to tyrosine, and for them tyrosine is an essential amino acid [2]. It is also an essential amino acid in infants, uremic patients, and some malnourished patients [3].
Supplementation with tyrosine results in increased plasma and brain levels of the amino acid [4]. The rate-limiting enzyme for the creation of DA is tyrosine hydroxylase, which converts tyrosine to DOPA [5]. In rats, this enzyme is around 75% saturated, meaning that increasing tyrosine availability should have the ability to increase DA synthesis by approximately 1/3rd [6]. This makes increasing tyrosine availability less effective at increasing DA levels than increasing tryptophan availability is at increasing serotonin levels, but it is still enough to exert measurable effects [7].
Tyrosine depletion through dietary means reliably produces the symptoms of decreased dopamine and norepinephrine levels in both humans and animals. These include reduced response to amphetamines, endocrine changes, decreased mood and spatial memory abilities, and other psychological changes [8-10]. In animals, tyrosine depletion results in lower brain levels of dopamine, and this effect has also been found in humans in a positron emission tomography (PET) study [9].
Studies on the opposite effect, increasing DA and NE by increasing tyrosine availability, produce less reliable results. This may be a function of the dose-response curve and the conditions of the study. Many studies indirectly indicate that tyrosine increases catecholamine levels in humans because of the behavioral changes it produces (see below). Tyrosine supplementation also increases plasma neurotransmitter levels [11]. In the brain, changes in neurotransmitter levels from increased tyrosine availability vary based on brain region and conditions. Some neurons become more sensitive to tyrosine availability when their activity increases [12]. One source indicates increased activation of DA neurons, increased DA synthesis, or rapid or chronic depletion of intraneuronal DA as the most likely situations in which tyrosine availability will have a significant effect in humans [13].
Athletic Performance
Tyrosine supplementation has the potential to increase athletic performance in multiple ways. One of the mechanisms possibly contributing to fatigue during exercise is an increase in central serotonin levels and an increase in the ratio of serotonin to dopamine. Tyrosine may help decrease this ratio and compete with tryptophan (the amino acid precursor to serotonin) at the blood-brain barrier [14-15]. Increased dopaminergic activity may decrease the perception of fatigue. Also, during highly stressful conditions, catecholamine levels can become depleted, and tyrosine may be particularly useful under these conditions [14].
There have only been a few studies examining the effect of tyrosine on exercise performance. One study compared the effects of placebo, tyrosine (25 mg/kg), carbohydrates, and tyrosine plus carbohydrates on a cycling time trial after 90 minutes of submaximal cycling. The tyrosine group performed better than the placebo group (32.64 minutes vs. 34.44 minutes), and the tyrosine plus carbohydrate group completed the time trial sooner than the carbohydrate only group (26.11 minutes vs. 27.17 minutes), but neither of these differences were statistically significant. However, tyrosine did significantly decrease the rating of perceived exertion relative to placebo. The authors also found a different metabolic response to exercise in the tyrosine and carbohydrate group than the carbohydrate group, and suggested that a difference in study design, such as conditions resulting in greater catecholamine depletion, may have demonstrated a significant difference in performance [14].
Another study was conducted by Struder et al. [16]. In this study, subjects were given either placebo, paroxetine (an SSRI), BCAAs, or 20 grams of tyrosine and cycling performance was measured. Tyrosine did not improve performance on any measure. However, the hormonal profile in the subjects consuming tyrosine was indicative of a decrease, rather than an increase in central dopamine levels. This is consistent with animal studies, which indicate that excessive quantities of tyrosine decrease dopamine levels [14].
Supporting the idea that the lack of effect in these studies is due to study design is the fact that tyrosine improves physical performance in animals subjected to stressful conditions. For example, when administered prior to cold stress, tyrosine increased swimming performance in rats, an effect which was further increased by coadministration of amphetamine. This was associated with increased NE in the hippocampus [17].
Cognitive Performance and Stress
Tyrosine is particularly useful at combating the decrements in cognitive performance associated with stress and fatigue. Various stressors result in increased catecholamine synthesis and release and consequently increased precursor demand, and many stress-related changes in behavior and cognition are associated with catecholamine depletion [18]. Norepinephrine depletion is associated with behavioral depression and decreased exploration and motor behavior in animals and lowered attention span in humans, and dopamine is important for learning and memory processes [19]. Since stress results in increased catecholamine synthesis and depletion, it is likely that the impact of tyrosine supplementation will become more pronounced in this state.
In a number of experimental paradigms, tyrosine reduces or prevents impairments in cognition and other negative effects caused by stressors. One study found tyrosine restored maze performance to normal in mice fed a 40% restricted diet [15]. In other rodent studies, tyrosine has protected from behavioral and neurochemical changes associated with hypoxia, restraint stress, and tail-shock. Some of the effects prevented were an increase in corticosterone and NE depletion [17]. Treatment of sheep subjected to stress with large amounts of tyrosine reduced many of the physiological changes, including the increase in cortisol [20]. Tyrosine has also been reported to increase the survival rate in rats stressed by sepsis and acute hemmorhagic shock [7].
In humans subjected to stressful conditions, tyrosine not only improves working memory and attention but may also improve mood and well-being [14, 18]. Tyrosine has been reported to alleviate some of the negative consequences of cold, high altitudes, fatigue, military training, and sleep deprivation [21-22]. It has also been postulated to decrease stress under conditions of aging, anorexia, and obesity [21].
One study in healthy young men compared the effects of 150 mg/kg tyrosine, caffeine, phentermine, and D-amphetamine on cognitive performance in sleep deprived subjects. Tyrosine improved performance on several tests, but was not as effective as D-amphetamine [22]. Another study found that tyrosine did not affect sleep related measures such as sleep quantity and quality after sleep deprivation, while the other psychostimulants did [23]. In subjects exposed to cold and hypoxia, tyrosine reduced the incidence of headache, tension, fatigue, and psychomotor impairments. In another study in healthy subjects subjected to 90 dB noise, tyrosine improved mental performance and reduced blood pressure relative to placebo [19].
Because most of the research has focused on highly stressful conditions that are not commonly encountered in real life, a study was conducted to see if tyrosine was still effective under conditions of relatively mild stress. This was measured by the ability to perform multiple simple tasks simultaneously. When subjects were given simple tasks, such as arithmetic, auditory monitoring, visual monitoring, and a memory task, tyrosine did not improve performance. When asked to perform multiple simple tasks at the same time, performance on the memory task was significantly better in subjects receiving tyrosine. This study demonstrated that tyrosine can improve cognitive performance even in the absence of significant stress-related biological changes [18].
Dosage and Side Effects
Toxicological studies indicate that tyrosine is quite safe. In mice and rats, no toxic signs were observed after both IM and subcutaneous injection of up to 2500 mg/kg, at which point some edema was noted in rats. The LD50 is not established, but is greater than 5000 mg/kg. After 28 days of 10, 25, or 50 mg/kg injections to rats, the primary noted effect was some immune system stimulation at 25 mg/kg or more. In beagle dogs, the effects were similar. Also, in vitro studies indicated no mutagenic effect. A review of the studies from 1976-2001 found that they reflected "a lack of toxicity" [36].
Because tyrosine primarily increases DA and NE levels in situations of increased demand or depletion, side effects are less common and severe than with most stimulants. Taken before bed, it may result in insomnia. It should also be noted that, although animal toxicology studies indicate a high degree of safety, long-term safety of tyrosine supplements has yet to be established in humans.
The daily dosage of tyrosine supported in the majority of the literature is 100 mg/kg [4, 19]. Therefore, the daily dosage for most will probably fall in the 3-12 g range. Exceeding this amount is not recommended, and the dosage should be started on the lower end of this range to determine personal tolerance, especially if one is taking stimulants or antidepressants. The dosage should be divided among 3 or more doses daily. Around 2 g prior to exercise may be used to improve athletic performance.
N-acetyl-L-tyrosine has been proposed as a "better" form of tyrosine. While the present research is limited, it indicates that if anything N-acetyl-L-tyrosine is inferior. When orally administered to mice, N-acetyl-L-tyrosine was less bioavailable than tyrosine and two other prodrugs [37]. When given parentally, N-acetyl-tyrosine has inferior bioavailability compared to tyrosine in piglets and human newborns [38].
Certain supplements may improve the results from tyrosine supplementation, depending on the purpose it is being used for. Vitamin B6 is sometimes recommended because it is involved in the conversion of tyrosine into dopamine, although there is not yet scientific support for the contention that it will increase the effects of tyrosine supplementation. Tyrosine is commonly used along with D,L-phenylalanine for a stimulant effect. The combination of tyrosine with 5-HTP may also be useful for some. Finally, tyrosine may also be used to potentiate the appetite suppressing effects of stimulants.
Recommended products
- 1Fast400 L-Tyrosine Powder is the most economical way to go for those consuming large amounts of tyrosine.
- Now Tyrosine capsules are another convenient option.
No part of this article may be reproduced in any form without the permission of David Tolson or Mike McCandless.
