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LOGINMental fatigue and physical performance: the tyrosine connection
Andrew Hamilton investigates new research on how mental fatigue can impact physical performance, and asks if tyrosine supplementation could lend a helping hand?
Having family ties to Ireland and living a short hop away across the Irish Sea as I do, I’ve been fortunate enough to visit the beautiful ‘Emerald Isle’ quite a few times. And if you’re a keen cyclist, the friendly people and fantastic scenery makes for a great training destination. However, should you wish to cycle across its green and pleasant landscape, you absolutely need to beware of the abundance of very large and territorial dogs, which emerge without warning from behind garden walls at lightning speed, baring gleaming white teeth while snapping inches away from your heels.
It was during one of these high-speed sprints to escape the snarling jaws of a particularly humongous dog that I stumbled across a truth, which broke all the conventional rules of exercise physiology. Having covered nearly 50 hard, rain-soaked miles into a headwind, I was completely exhausted, almost unable to spin the cranks, when the ‘hound from hell’ gave chase, looking very menacing indeed. As he started snapping inches behind my calves, the primeval instinct of fear took over and I suddenly found myself accelerating at warp factor 9 to outsprint him for the next half-mile, until his bark could be heard no more!
Performance in mind
Here’s a question: if, as is commonly believed, muscular fatigue occurs as a result of physical and chemical changes in muscles - for example running out of ‘fuel’ or a build-up of fatiguing lactate – how was it that a mere change in mental disposition (fear in my case!) enabled me to suddenly summon up phenomenal amounts of extra energy? As seasoned SPB readers may be aware, the reason is that the brain is far more influential in determining how much fatigue an athlete experiences during exercise than was previously thought. In particular, scientists now understand that the brains regulates levels of muscle fatigue in order to ‘always hold something in reserve’ – most likely a throwback our ancient past when humans needed to escape dangerous predators, regardless of whether muscles were tired or not!
This ability of the brain to regulate perceived fatigue and therefore physical performance is the key tenet of something known as ‘Central Governor Theory’, which was developed by the brilliant Professor Tim Noakes(1). Understanding this link between brain function and exercise performance has opened up fascinating possibilities for sports performance. We already know that by a process of mood elevation and distraction, music played during exercise can delay fatigue and enhance performance(2,3).
There’s also robust evidence that you can use deception and expectation techniques to ‘trick’ your brain into believing an exercise task is easier than it really is, resulting in improved performance(4,5). Indeed, deception and expectation play a key role in the placebo effect; athletes typically experience a performance boost from a completely inert pill that they are told is an ergogenic supplement because they believe it will help them. Yet if you tell them that same pill will harm their performance, the expectation of worse performance does actually worsen performance (the so-called nocebo effect).
Brain chemistry and fatigue
The central nervous system (CNS) governs how electrical signals are both generated within the brain and sent down neural pathways to activate muscles with electrical impulses. However, all of these electrical impulses arise from complex brain chemistry and the vital role of chemical messengers. In very (oversimplified) terms, when a nerve cell in the brain receives chemical signals via certain biological molecules known as ‘neurotransmitters’ (eg glutamate or GABA), these molecules cross the gap between nerves (the synapse) and bind to receptors on the receiving neuron, altering the cell membrane’s permeability to sodium and potassium ions.
This shift in chemical concentration alters the nerve cell’s internal charge; if the shift is big enough, it triggers a rapid, self-propagating electrical impulse, which travels down the nerve axon to the next synapse, where the process can be repeated many thousands of times. If that nerve pathway eventually innervates muscle fibers, it can stimulate a contraction, resulting in muscle movement. Although it sounds a complicated process, the key take-home point here is that brain chemistry – in particular, the correct function of chemical neurotransmitters – is intimately involved in CNS and muscle function. It follows therefore that if the balance of chemical neurotransmitters is altered in any way, this could affect how the CNS interfaces with and regulates muscles during exercise.
Dopamine and fatigue during exercise
Given the above, it stands to reason that if brain chemistry can be altered by (eg by ingesting certain drinks or supplements that can cross the blood-brain barrier to enter the brain), it might be possible to lessen fatigue signals generated in the brain and therefore increase exercise performance. Previous research has demonstrated that mental fatigue impairs endurance exercise performance by altering brain neurochemistry – specifically by lowering the concentration and activity of a neurotransmitter called dopamine in a region of the brain known as the ‘anterior cingulate cortex’ (ACC)(6). This lowering of dopamine levels caused by mental fatigue prior to exercise results in an increased in rate of perceived exertion (RPE), reduced motivation and poorer subsequent exercise performance(7).
Athletes frequently encounter mentally fatiguing tasks prior to training or competition, including travelling, work demands or even online tasks. So if mental fatigue prior to exercise depletes the dopamine pathways in the ACC and reduces exercise performance, a pertinent question is whether increasing the activity and availability of dopamine in the ACC can help counter this effect? It turns out that caffeine ingestion has been investigated in this context and at least part of caffeine’s positive effects occurs via the enhancement of dopamine pathways, reducing perceived exertion and increasing the athlete’s tolerance for prolonged physical exertion(8,9).
The tyrosine connection
Caffeine however is not the only nutrient that can boost dopamine pathways in the brain. L-tyrosine is an amino acid (a building block of protein – see figure 1), which when taken in isolation can cross the blood-brain barrier, where it can be converted into dopamine (and another neurotransmitter called norepinephrine). Since mentally fatiguing and/or demanding tasks accelerates the turnover of dopamine, the demand for tyrosine (from which dopamine is synthesized) rises. If that extra tyrosine is not supplied, the available tyrosine pool may become depleted, which can them limit dopamine synthesis. In theory at least, this could have a negative knock-on effect for subsequent exercise performance.
Figure 1: The chemical structure of L-tyrosine
When it comes to mental fatigue alone (ie not the effects of that fatigue on exercise performance), there’s solid evidence that L-tyrosine supplementation (100–300mgs per kilo of bodyweight) helps to maintain executive function (working memory and mental flexibility when problem solving) and cognitive processing performance under stressful conditions such as sleep deprivation, demanding multi-tasking and extreme hot/cold temperatures(10). But would extra tyrosine also translate into improved exercise performance?
A recent meta-study (a combined analysis of all the previous research on this topic) found that supplementing L-tyrosine did not improve endurance exercise performance(11). However, the studies analyzed in this meta-study did not test the performance of the study participants under conditions of mental fatigue. Because tyrosine’s mechanism of action relies on enhancing dopamine synthesis specifically when the dopaminergic system is challenged (ie under conditions of mental fatigue), it’s not surprising that testing endurance performance in those who were mentally fresh drew a blank! Instead, what’s needed is a study looking into tyrosine supplementation and exercise performance in subjects who undertake that exercise in a mentally fatigued state, and for that, we can turn to new research.
New research
Published in the ‘European Journal of Sport Science’, this study investigated mentally fatigued recreational cyclists, and whether giving them pre-task L-tyrosine supplementation was able to stem the normally observed mental fatigue-induced performance declines during ‘time-to-exhaustion’ cycling at their 80% maximal power output(12). To carry out this study, twelve recreational cyclists were recruited and firstly underwent baseline testing to determine key fitness parameters such as maximal power output and to familiarize themselves with the study protocol.
One of the familiarization tasks was to practice what is known as a ’Stoop Test’ (see below). This test requires participants to rapidly identify incongruent words and colors – eg identify the font color when the words reads “green” but is written in red font. This has been shown to be a difficult mental task and one which induces significant mental fatigue after a few minutes. The point of practising the Stroop test during the familiarization visit was that it was this test that was to be used to induce mental fatigue before the exercise trials.
Test procedure
After a few days, the cyclists then performed two time-to-exhaustion cycling tests at 80% of their maximum power output (after performing mentally fatiguing Stroop testing) on two separate occasions. These trials were identical in design apart from what the cyclists consumed five minutes before trial began. The two trials (performed in a random order and separated by seven days) were as follows:
Experimental
· Consumption of 300mgs per kilo of L-tyrosine as powder dissolved in a sugar-free lemon drink.
· 60 minutes of Stroop testing.
· Cycle to exhaustion at 80% of maximum power output (hard!).
Placebo
· Consumption of the same volume of a sugar-free lemon drink containing no L-tyrosine (placebo).
· 60 minutes of Stroop testing.
· Cycle to exhaustion at 80% of maximum power output.
Using a randomized, double-blind, crossover design helped the researchers to generate more robust evidence. In particular, employing a crossover design meant that all the cyclists underwent both trials, meaning they each served as their own control – thus reducing individual variability. The high dose of L-tyrosine was chosen because (as mentioned above) previous research has shown that it maximizes blood tyrosine concentrations and supports brain executive functions under stress.
For the time-to-exhaustion cycling test, the participants first performed a standardized warm-up consisting of 5 minutes of cycling at 40% of their maximum power. After this, the power output corresponding to 80% of maximum power was set, and participants were instructed to maintain a pedal cadence between 60 and 70rpm. The time to exhaustion was measured from the beginning of this workload until the pedal cadence dropped below 60 rpm for more than six seconds despite them receiving verbal encouragement from the researchers. Throughout the cycle testing, the researchers tracked the cyclists’ oxygen uptakes (to see if the L-tyrosine was producing any physiological effect) and perceived exertion (to track how hard the athletes felt they were working).
What they found
When the data from all the trial was analyzed, there were three key findings:
· Longer time to exhaustion – when the cyclists ingested the L-tyrosine drink, there was a very significant increase in the time they managed to cycle at 80% of maximum power; an average of 460 seconds in the tyrosine trial vs. 399 seconds in the placebo trial – over 15% improvement (see figure 2).
· Reduced perceived effort – while the cyclists experienced exhaustion in both tests, the rate of increase in perceived exertion as the test progressed was less when they had consumed tyrosine (figure 2). This meant that at equivalent time points, the cyclists experienced less fatigue in the tyrosine trial compared to the placebo trial (or to put it another way, the exact same physical workload felt easier for longer).
· No change in physiological parameters – the third important finding was that there were no changes in physiological markers between the two trials. The cardiovascular function of the cyclists was the same in both trials, which meant that the performance improvements observed and reduced perceived effort arose purely as a result of different brain/nervous system processing.
Figure 2: Time to exhaustion and perceived effort with and without L-tyrosine
Implications for endurance athletes
The key take-home message from this new research is that it provides solid evidence that mental fatigue can significantly harm exercise performance via accelerated neurotransmitter turnover, leading to dopamine depletion in brain structures like the anterior cingulate cortex. When these dopamine stores become depleted because of mental fatigue, the perception of physical effort increases, leading to poorer motivation to push hard and (in this study) causing athletes to quit earlier. By contrast, the effects of mental fatigue appear to be reduced when a large amount of L-tyrosine (300 mg/kg) is ingested because this tyrosine crosses the blood-brain barrier, and sustains dopamine synthesis during mental effort, thus helping to prevent the premature rise in perceived exertion during exercise.
In terms of practical application, there are a number of points. Firstly, athletes should never underestimate the impact of mental fatigue on performance potential. Therefore, it makes sense to try and schedule your hardest training sessions and any races for times when you are least likely to be suffering from mental fatigue or stress. This means trying to avoid scheduling these big physical efforts at times when you may be facing unusual mental demands such as exams, a big work project, starting a new job, moving house, tackling family issues etc. Being burdened with more mental demands and fatigue than normal will undoubtedly harm your performance.
Secondly, be aware that even if you schedule races at a ‘good time of year’, you will still face mental demands that can induce fatigue and reduce performance – eg long-distance travelling to the event, dealing with race logistics, poor sleep, excessive pre-race screen time (social media, video games) or even just worries about the race in general. Therefore try to plan ahead as much as possible and avoid some of these factors if you can (eg reducing screen time or travelling ahead of the event and staying nearby locally for a couple of days beforehand).
Thirdly, this research suggests that where pre-exercise mental fatigue cannot be avoided, ingestion of 300mgs/kg of L-tyrosine 60 minutes before exercise may significantly boost performance by serving as an insurance policy, protecting against reduced physical performance from a ‘tired’ brain. Note that for an 80kg athlete, this amounts to a large dose of 24 grams; the smaller doses (1 to 2 grams) typically used in commercial ‘pre-workout’ products may not replicate these central nervous system benefits. Bear in mind too, that the benefits observed in the above study were seen over very hard and sustained efforts for 6-7 minutes. If your event includes demands like maintaining a steady, aggressive time-trial pace, staying in a breakaway group, or tackling long, sustained climbs, tyrosine is worth considering. For sprint-type events, or very long-duration, lower intensity efforts, it’s less likely to help.
If you want to try the tyrosine supplementation approach, be aware that the cheapest form of L-tyrosine is not capsules, but in the form of a pure powder, which tastes quite bitter and not especially pleasant. Therefore, your best strategy is to shake up the powder with a tart or citrus-flavored drink such as tart cherry juice, cranberry juice, grapefruit juice, or a strong citrus electrolyte powder (lemon, lime, or orange). Don’t blend it into a protein drink because then you’ll be ingesting a slug of other amino acids. Since amino acids compete with each other to cross the blood-brain barrier, these other amino acids will inhibit tyrosine absorption. For the same reason, you should try and take any supplemental tyrosine on an empty stomach. Needless to say, consuming 20 grams or more of a single amino acid on an empty stomach may cause gastrointestinal distress in certain individuals so you must thoroughly test out this dosage during less important training session before trying it in a race environment. Indeed, this a golden rule for ANY new supplement you try!
References
1. Front Physiol. 2012 Apr 11:3:82. doi: 10.3389/fphys.2012.00082
2. J. Strength Cond. Res. 2018 doi: 10.1519/JSC.0000000000002981
3. Percept. Mot. Skills. 2010;110:257–264
4. J Sports Med Phys Fitness. 2018 May;58(5):744-749
5. Int J Sports Med. 2016 May;37(5):341-6
6. Sports Med. 2018 Sep;48(9):2041-2051
7. Frontiers in Physiology 2018. 9: 227
8. Physiology and Behavior 2019. 204: 41–48
9. European Journal of Applied Physiology 2016. 116, no. 11–12: 2293–2303
10. Journal of Psychiatric Research 2015. 70: 50–57
11. Journal of Sports Sciences 2023. 41, no. 22: 2045–2053
12. Eur J Sport Sci. 2026 Apr;26(4):e70150. doi: 10.1002/ejsc.70150
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