Background

Amino-acid tyrosine (TYR) levels peak between 1 and 2 h after consumption and can remain significantly elevated up to 8 hours. Once it has passed the blood-brain barrier (BBB) and is taken up by the appropriate brain cells, TYR is converted into L-DOPA. L-DOPA is converted into DA, resulting in an increase in DA level. TYR supplementation seems to have a beneficial effect only in situations that stimulate neurotransmitter synthesis, i.e., situations that are sufficiently stressful or challenging. Once the threshold has been passed TYR would be metabolized rather than converted into L-DOPA. Also of influence is that TYR shares a transporter across the BBB with several other large neutral amino-acids such as phenyl- alanine and tryptophan.

TYR supplementation might be preferable over L-DOPA administration, given the characteristic inverted-U profile of DA, it would be easy for L-DOPA administration to push individuals to the lower right end of the curve, whereas the subtle increase from TYR is far less likely to do so.

Consuming TYR, the precursor of dopamine (DA) and norepinephrine (NE), may counteract decrements in neurotransmitter function and cognitive performance. However, reports on the effectiveness of TYR supplementation vary considerably, with some studies finding beneficial effects, whereas others do not. Here we review the available cognitive/behavioral studies on TYR, to elucidate whether and when TYR supplementation can be beneficial for performance.

Review clinical setting

Depression

Not always has the supplementation of TYR been successful. We speculate perhaps those depressed individuals experiencing a lack of motivation, which may result from DA deficiency, are the ones who could benefit most from TYR supplementation. On the other hand, individuals with psychotic depression may have excess DA. Such individuals would be unlikely to benefit from a further boost in DA activity and therefore TYR supplementation may not be recommendable for them.

Schizophrenia

AMP might be beneficial, but research is scarce. It is important to distinguish between striatal areas, often demonstrating a hyperdopaminergic state in schizophrenia, and extrastriatal, prefrontal regions showing, in contrast, a marked reduction in DA activity. More studies are needed in which samples are larger and heterogeneity is kept as small as possible or response to TYR is distinguished between patients. Also should the moment of application be considered (remission, psychosis, etc.).

ADHD

The results are not straightforward; sometimes an effect is found. This might be due to the several different risk factors, which needs to be taken in consideration in future research.

Parkinson

Parkinson is characterized by decreased DA levels in many brain areas. Administering TYR to Parkinson's patients raised levels of DA's metabolite homovanillic acid, suggesting TYR effectively promoted DA function. TYR stimulates neurotransmitter production only in already active neurons, yet Parkinson's is associated with a loss of dopaminergic neurons, thereby reducing TYR's site of action. Therefore it is unlikely that TYR administration would be very successful.

Stress

Stress induces increased catecholamine activity and turnover rates in the brain, leading to depletion of neurotransmitter levels as well as behavioral depression. However, studies that administered TYR to rats prior to stress exposure have shown neurotransmitter depletion and decrements in performance can be reversed. The researchers speculate that consistent evidence has not been found, because physical performance only benefits from TYR supplementation when it places high enough cognitive demands on the individual that induce catecholamine depletion.

Healthy individuals

TYR can enhance working memory performance, but in the absence of an overt exposure to stress. Improvements were only found under particularly challenging conditions, such as when other tasks were performed simultaneously and in a taskswitching paradigm.

Conclusion

The potential of using TYR supplementation to treat clinical disorders seems limited. The cognitive changes mediating performance improvements after TYR supplementation remain unknown and, unfortunately, most of the literature focuses on short rather than long-term settings. Nevertheless, based on this overview of the literature the authors conclude TYR is very promising as an enhancer of cognition and perhaps mood, but only when (healthy) individuals find themselves in stressful or cognitively demanding situations.