Incorporation of L-tyrosine into the Alpha BRAIN™ Source formula: A review of available scientific knowledge and observed benefits to humans.

Abstract

L-tyrosine is a non-essential amino acid that serves as substrate precursor for the synthesis of catecholamine neurotransmitters, which include dopamine, epinephrine and norepinephrine. In contrast to other neurotransmitter systems, the production of catecholamines is sensitive to local substrate concentrations. Increased tyrosine availability positively affects the rate of dopamine synthesis in neuronal cells. Current findings on the functional effects of this tyrosine-induced dopamine elevation indicate that supplementation can produce significant cognitive results under stressed conditions. This includes improving working memory, improved exercise capacity in stressed conditions, alertness and elevated mood.

Background

L-tyrosine is a non-essential amino acid synthesized in the liver through the conversion of an essential amino acid phenylalanine (Phe). Approximately 15% of Phe is enzymatically converted to L-tryosine and deposited into the blood stream (Fig 1). Circulating L-tyrosine in blood serum is able to cross the blood-brain barrier by the Large Neutral Amino Acid (LNAA) carrier system that exists in the brain capillaries (Fig. 2). The transport of tyrosine across the membrane requires no expenditure of energy and is largely driven by a concentration gradient (a tendency for molecule to flow from high to low concentrations). Thus, concentration of available tyrosine and competition among similar amino acids for the carrier are the two factors that regulate tyrosine crossing the blood-brain barrier[1]. Once taken up by the neuron, tyrosine is first converted to L-DOPA and is further modified to produce dopamine. Dopamine itself is used as a neurotransmitter or subjected to additional modifications to produce norepinephrine and epinephrine (Fig 2). The conversion of tyrosine to L-DOPA is the rate-limiting step for dopamine synthesis, meaning dopamine production is only dependent the concentration of available tyrosine and turnover rate of the enzyme tyrosine hydroxylase. This might lead to the conclusion that more tyrosine results in increased dopamine; however, during normal physiological conditions, enough tyrosine is available in the bloodstream to maximize the capacity of the enzyme[2]. The caveat to this model is that acute stress results in depletion of norepineprhine and dopamine neurotransmitters in catecholaminergic neurons. In particular, neurons in the locus coeruleus respond specifically to stress by modulating attention, alertness, motor activity, and anxiety. Thus tyrosine supplementation may protect against the adverse behavioral effects of acute stress by preventing the depletion of neurotransmitter in such neurons[3].

Significant Findings

Treatment with tyrosine reduces environmental stress
A military study evaluated the effects of tyrosine treatment on mood states, cognitive performance and reaction time in stressed healthy males. A double blind, placebo-controlled study compared the effects of a tyrosine supplement (100 mg/kg) to a placebo in subjects exposed to 4.5 hour of cold temperature and hypoxia (decreased oxygen levels mimicking high altitude). Subjects were exposed to twice the level of environmental stressors (15° C and ½ atmospheric pressure). The results indicate tyrosine, compared to placebo, significantly reduced the physical symptoms of headache, coldness, distress, fatigue, muscular discomfort and sleepiness among those subjects who responded adversely to the environmental stressors[4]. In addition, tyrosine effectively reduced adverse emotional responses to increased stress, evaluated by the Clyde Mood Scale. Statistically significant reductions in dizziness, confusion, fatigue and unhappiness were observed with tyrosine supplementation. A majority of subjects also reported that they could think more clearly when given the active supplement.

Tyrosine supplementation increases exercise capacity in highly stressed conditions

Previous studies have suggested that increasing dopamine through pharmacological reuptake inhibitors can significantly enhance human exercise performance in warm conditions[5]. A clear link between dopamine and central nervous system fatigue is highlighted by the enhancement of exercise capacity and attention with amphetamines, which stimulate dopamine release[6]. Prior to 2011, no studies had shown that an increase in tyrosine could effect similar improvements. A recent study reported increased exercise capacity during hot conditions (30°C, 60% humidity) in moderately trained, healthy adults. In comparison to adults who drank a placebo, those who consumed 150 mg/kg tyrosine, 1 hour prior to exercise significantly increased their time before exhaustion [3]. The study concluded that tyrosine availability increases exercise capacity in stressful conditions, citing an increased tolerance to central nervous system fatigue as a possible mechanism.

Tyrosine mitigates working memory decrements during cold exposure.

Cold exposure elicits a stress response through increased levels of coritsol and can adversely affect human cognition and decision making. Healthy volunteers were submerged in cold water (35° C) for two, 90-minute sessions and evaluated on mood responses and decision making. Using double blind, within-subject testing, either tyrosine (150 mg/kg) or a placebo was administered 30 minutes prior to immersion. Those subjects who received tyrosine performed better on a memory-matching task. They had more correct responses and decreased reaction time during decision making. Furthermore, there were no changes in body temperature or cortisol levels between the two groups, ruling out the possibility of tyrosine directly interfering with the physiological changes that impair behavior during stress. This study affirms that tyrosine supplementation not only protects against stress-induced memory deficits, but also facilitates faster processing[7].

Tyrosine helps overcome performance deficits due to prolonged sleep deprivation.
Sleep deprivation produces well-studied performance failures in cognitive alertness, memory formation and retrieval, visual vigilance, response time, and frequency of correct responses. A recent study evaluated these parameters with administration of tyrosine, amphetamine, caffeine, or placebo after one night without sleep (35 hours awake). Tyrosine administration of 150 mg/kg prior to testing improved running memory recall tasks, logical reasoning, and visual vigilance as compared to the placebo group[8]. Amphetamine and caffeine supplements were most effective in immediately overcoming sleep deprivation cognitive deficits. However, the addictive qualities and diminishing margins of return of these substances may have negative long-term consequences that were not evaluated in this study[8]. The researchers concluded that tyrosine supplement could aid in overcoming the cognitive impairments due to acute sleep deprivation.

Conclusion

The peer reviewed, scientific studies on human subjects cited in this report show direct evidence that tyrosine supplementation can improve mood, memory, cognitive and physical performance during times of increased stress or sleep deprivation. These studies are representative of a larger body of scientific work on the effects of tyrosine supplementation on cognition, and give credence to the incorporation into the AlphaBRAIN formula. Increasing the availability of tyrosine appears be most beneficial during times of elevated stress, when the turnover rate of catecholamine neurotransmitters is exceedingly high. This suggests that tyrosine will mediate a resorting balance of dopamine production, rather than pervasive increase in neurotransmitters.

Currently, no studies directly compare effects of L-DOPA and tyrosine supplementation. However, one should predict differences in the cognitive effects of replacing mucuna extract (where L-DOPA is an active ingredient) with tyrosine in the AlphaBRAIN formula. Administration of L-DOPA provides more immediate effects on elevating catecholamine neurotransmitters by bypassing the rate-limiting step of dopamine production. Replacement of mucuna with tyrosine may diminish the immediate cognitive benefits, yet will contribute a positive impact nonetheless. Furthermore, tyrosine is a much safer compound and does not elicit the negative side effects associated with L-DOPA. In conclusion, the modification of AlphaBRAIN formula by replacing mucuca extract with tyrosine, may shift the cognitive impact from more immediate effects towards less pronounced but longer, neuroprotective enhancements.

Dosage and Warnings

The standard dosage in most human trials is 150 mg/kg. No toxicity was noted in any studies with this dosage, although people with high blood pressure should avoid taking excess tyrosine. Individuals prescribed monoamine oxidase inhibitors (MAOIs) to treat depression should consult their physicians before taking tyrosine.

Ingredient Summary

L-tyrosine is an amino acid precursor to the excitatory neurotransmitters dopamine, norepinephrine, and epinephrine. Proper synthesis of these neurotransmitters is essential for mood, alertness, memory and motivation. The available L-tyrosine in our body is directly related to our brain’s efficiency in producing these key neurotransmitters. Increased stress can alter utilization of neurotransmitters and lead to impairments of cognitive function. Supplemental L-tyrosine has proven to combat the effects of stress on our mental health.

Reference

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