Phenylketonuria (PKU) is treated by restricting dietary intake of natural protein and substituting a protein source that lacks phenylalanine but is fortified with tyrosine. This recommendation is because people with PKU are unable to metabolise phenylalanine, the precursor to tyrosine. Unfortunately, tyrosine supplementation has not been shown to consistently improve neuropsychologic function in PKU, which is possibly because increases in plasma tyrosine levels are not sustained and brain influx often remains suboptimal despite tyrosine supplementation. In practice, plasma tyrosine levels are monitored and controlled (normal: 45 micromol/L) before tyrosine supplementation is considered.
Therapeutically, tyrosine supplements are used to enhance levels of its derivatives and, therefore, improve cognitive function.
One randomised, placebo-controlled study investigated the effects of L-tyrosine (1 50 mg/kg) on cognitive performance following one night’s sleep loss. Supplementation was found to significantly reduce performance decline, with cognitive improvements lasting approximately 3 hours.
RCTs comparing the effects of a balanced amino acid drink with one lacking in tyrosine and phenylalanine demonstrated that tyrosine-depleted individuals experienced impaired spatial recognition memory and spatial working memory and an increase in plasma prolactin levels, indicating a decrease in dopamine neurotransmission within the hypothalamus. Although ratings of depression and other aspects of cognitive function were unaffected, subjective feedback indicated that the participants felt better on the balanced drink.
Changes in tyrosine transport may also influence cognitive functioning in schizophrenia via the dopamine system.
As tyrosine is a precursor to both dopamine and noradrenalin, researchers have suggested that tyrosine depletion may play a role in the pathogenesis of depression. To date studies testing this hypothesis have produced mixed results. One study found that tyrosine- and phenylalanine-depleted individuals became less content and more apathetic than those given a balanced amino acid mixture. However, a separate study in individuals with a past history of recurrent depression found that tyrosine depletion did not alter objective or subjective measures of mood, although plasma prolactin levels did increase and performance on a spatial recognition memory task was impaired.
Tyrosine appears to be most effective in treating depression associated with a lack of dopamine. One study involving patients with signs of dopamine-dependent depression (DDD) found that treatment with oral tyrosine (3200 mg/day) caused an immediate improvement in mood, as judged by clinical impression and objective test scores (Montgomery-Asperg Depression Rating Scale) and sleep parameters from day 1 of treatment. Considered ineffective in other types of depression, supplementation with tyrosine should be limited to DDD.
REWARD DEFICIENCY SYNDROME
Tyrosine depletion appears to affect reward-based processing and tests involving reward/punishment processing are affected by dopamine depletion. A lack of D2 receptors and/or dopamine depletion states have been implicated in a number of conditions or destructive behaviours thought to be caused by poorly functioning biochemical reward systems.
Individuals tend to be at risk of multiple addictive, impulsive and compulsive behavioural problems, such as severe alcoholism, cocaine, heroin, marijuana and nicotine addiction, pathological gambling, sex addiction, chronic violence, post-traumatic stress disorder, risk taking behaviours and antisocial behaviour. As such, the use of tyrosine as a precursor to dopamine has a theoretical basis for use in this condition.
Reward deficiency syndrome has also been proposed as a possible mechanism explaining the tendency to drug and alcohol addiction in schizophrenics.
To date, no large controlled studies are available to determine the clinical effects of tyrosine supplementation in this condition.
Tyrosine has been used to aid in the withdrawal of cocaine, caffeine and nicotine. Anecdotal reports suggest it is successful; however, large controlled studies are not available to determine clinical significance.
L-tyrosine supplementation has been considered because chronic cocaine use is believed to cause catecholamine depletion and cocaine withdrawal has been associated with major depression. To date, results from trials using tyrosine as a stand-alone treatment during cocaine withdrawal have produced disappointing results. Although untested as yet, the effects of tyrosine may be of most assistance where a deficiency of dopamine D2 receptors is suspected, such as in reward deficiency syndrome.
Physical and emotional stress can impair performance and memory. In order to reduce the adverse effects of stress on these functions, improvements in stress adaptation are sought, such as with the use of supplements such as tyrosine. Several clinical studies have explored the effects of tyrosine in volunteers exposed to stressful situations, generally producing positive results on some parameters. (See ‘Clinical note: allostatic responses to stress’ in the Siberian ginseng for more information about stress adaptation.)
Tyrosine supplementation was found to reduce the effects of stress and fatigue on cognitive task performance in a study conducted with a group of 21 cadets during a demanding military combat training course. Subjects received a protein-rich drink containing (2 g) tyrosine five times daily or a carbohydrate-rich drink with the same amount of calories (255 kcal). Assessments on day 6 of the course showed that the tyrosine group performed better on a memory and a tracking task than the control group and further experienced a decrease in systolic blood pressure; however, no effects on mood were observed.
Other studies indicate that high-dose tyrosine (1 50 mg/kg) may also improve some aspects of performance and help sustain working memory when multi-tasking in stressful situations. One placebo-controlled trial involving 20 people found that administration of tyrosine significantly enhanced accuracy and working memory during the multiple task battery 1 hour after ingestion. However, tyrosine did not significantly alter performance on the arithmetic, visual, or auditory tasks during the multiple task, or modify any performance measures during the simple task battery.
Cold stress Similar results were obtained in another controlled trial that investigated the effects of tyrosine (1 50 mg/kg) on memory tasks in cold (4°C) conditions. Two hours after ingesting L-tyrosine, matching accuracy significantly improved in the cold and was at the same level as administration of either tyrosine or placebo at a comfortable 22°C.
Other beneficial effects have been obtained with tyrosine supplementation in volunteers exposed to cold stress. A double-blind, placebo-controlled, crossover study found that tyrosine (100 mg/kg) could protect humans from some of the adverse consequences of a 4.5 hour exposure to cold and hypoxia. Tyrosine significantly decreased symptoms, adverse moods and performance impairment in subjects who exhibited average or greater responses to these environmental conditions.
Tyrosine: Other Uses
Although tyrosine is used to reduce symptoms of irritability, depression, and fatigue associated with PMS, this is largely based on theoretical considerations and the observation that a significant reduction in tyrosine levels occurs during the premenstrual period according to one study.
This study further found that tryptophan depletion caused a significant aggravation of premenstrual symptoms, particularly irritability, and symptom magnitude was correlated with reduction in tryptophan relative to other amino acids.
Although no controlled studies are available, tyrosine is sometimes used for this indication as it indirectly increases testosterone and dopamine levels, both factors important in libido.
Administration of tyrosine has been shown to increase dopamine production in the CNS of patients with Parkinson’s disease.
Tyrosine is thought to potentially suppress appetite and stimulate brown adipose tissue due to its enhancement of noradrenaline synthesis. Additionally, as a precursor for thyroid hormones it may also increase the basal metabolic rate.
CHRONIC FATIGUE SYNDROME
Low tyrosine levels have been identified in subjects with chronic fatigue syndrome, suggesting a possible role for supplementation in this condition.
Abnormalities of the dopaminergic system are thought to be part of the underlying aetiology of this disorder, therefore tyrosine is used on the theoretical basis that an increase in dopamine levels will produce an improvement.
A randomised, double-blind placebo-controlled study of L-tyrosine (9 g/day for 4 weeks) has been conducted in 10 subjects with narcolepsy and cataplexy that tests this theory. While receiving tyrosine, subjects reported feeling less tired, less drowsy and more alert; however, ratings of daytime drowsiness, cataplexy, sleep paralysis, night-time sleep, overall clinical response, and measurements of multiple sleep latency and tests of speed and attention did not detect a significant difference with placebo. An earlier trial of longer duration, however, reported that within 6 months all eight participants were free from daytime sleep attacks and cataplexy.
Tyrosine: Dosage Range
• As tyrosine is considered to be a non-essential amino acid there is no specific recommended daily intake. The typical dose in clinical trials appears to be 100-1 50 mg/kg.
• Depression, PMS and chronic fatigue: 500-1000 mg before meals three times daily.
• Stress: 1 500 mg/day in divided doses.
• Decreased libido, Parkinson’s disease, drug detoxification, and weight loss: 1-2 g/day in divided doses.
• Natural stimulant: 500-1000 mg on an empty stomach first thing in the morning.
• Alertness following sleep deprivation: 1 50 mg/kg/day.
• As individual sensitivity to tyrosine can vary, it is recommended to start at 100 mg/day and gradually increase dose.