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A–Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance: Part 38
  1. N Cermak1,
  2. T Yamamoto2,
  3. R Meeusen3,
  4. L M Burke4,
  5. S J Stear5,
  6. L M Castell6
  1. 1Department of Human Movement Sciences, Maastricht University Medical Centre, Maastricht, The Netherlands
  2. 2Laboratory of Neurophysiology, Department of Psychology, Tezukayama University, Nara, Japan
  3. 3Department of Human Physiology & Sportsmedicine, Vrije Universiteit Brussel, Brussels, Belgium
  4. 4Australian Institute of Sport, Canberra, Australia
  5. 5Performance Influencers Limited, London, UK
  6. 6Green Templeton College, University of Oxford, Oxford, UK
  1. Correspondence to L M Castell, Green Templeton College, University of Oxford, Oxford OX2 6HG, UK; lindy.castell{at}

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Introductory remarks

Three amino acids are discussed in Part 38, which begins with an essential amino acid, threonine. In animal studies it is important for maintaining gut function, and also has a role in immune function. The amino acid tryptophan is a precursor of serotonin. It was first shown to be instrumental in promoting fatigue in rats, and this has since been confirmed in humans. It has mainly come to prominence in sports studies because of attempts to counteract its fatiguing effects by the use of branched chain amino acids (BCAA). Recently there has been some interest in the soporific effects of tryptophan, which were first observed in the 1960s. The third amino acid discussed is tyrosine: its increase across the blood–brain barrier can promote an increase in dopamine and norepinephrine.


N Cermak

Threonine is one of the nine essential amino acids required by humans. As such, threonine cannot be synthesised endogenously, and thus threonine must be obtained through diet or nutritional supplementation. Foods high in threonine include cottage cheese, poultry, fish, meat, lentils and sesame seeds. In animals, threonine is a primary component of intestinal mucin protein and plasma γ-globulin required for maintaining gut function.1 Threonine supplementation in chickens, pigs and mice has been shown to elevate serum antibodies against various viruses, providing support for a role of dietary threonine in modulating immune function.1 ,2 In rats, threonine deficiency has been found to depress the synthetic rate of phospholipid and nucleoprotein phosphorus fractions in the liver, resulting in an increase in the deposition of liver fat.3 As far as the author is aware, there is no published research to support threonine supplementation in healthy humans, and as such, there is currently no evidence to suggest that additional threonine can improve athletic performance. However, based on the aforementioned animal research, there may be some potential for threonine supplementation to support immune function, which may be beneficial for athletes, particularly during periods of strenuous training when immune function has been shown to be depressed.4


T Yamamoto and LM Castell

Tryptophan (C11H12N2O2) is an essential amino acid which contains an indole functional group and, uniquely among amino acids, binds to albumin in the blood. Mobilisation of fatty acids during exercise leads to an increase in non-esterified fatty acids (NEFA), which compete for the same binding site. The increase in NEFA results in tryptophan becoming unbound. This leads to an increase in the plasma concentration of free tryptophan and thus to an increase in the plasma concentration ratio of free tryptophan : large neutral amino acids, particularly BCAA.5 Tryptophan is a precursor of the neurotransmitter 5-hydroxytryptamine (5-HT, also known as serotonin) which is involved in sleep, mood changes and fatigue. There is evidence that an increase in free and total tryptophan across the blood–brain barrier leads to an increased rate of synthesis of 5-HT and kynurenic acid.6 Central fatigue (emanating from the brain) is an important aspect of exercise-induced fatigue in addition to muscle (peripheral) fatigue. The suppression of voluntary movement due to fatigue is a result of modulation of motor-neuron pathways in both the central and peripheral nervous systems. It has been well documented that this is triggered by tryptophan.5–7

Tryptophan supplementation has been prescribed for many years in the general community to alleviate depression. It has also been investigated in relation to sports performance. Two studies have claimed a beneficial effect of acute tryptophan supplementation on exercise capacity, hypothesising that its mood-enhancing effect might reduce the perception of pain or discomfort during exercise.8 ,9 However, other studies have failed to show this effect.10 In fact, given the known role of tryptophan as a key substance in the initial reactions leading to fatigue and perception of fatigue,5–7 it seems more likely that tryptophan supplementation and a consequent increase in the plasma concentration of tryptophan might lead to premature fatigue in, for example, endurance events. Indeed, this has been shown in rats where suppression of tryptophan uptake in the brain, via pretreatment with 2-amino-2-norbornanecarboxylic acid, has been seen to diminish central fatigue and to improve running performance.11 The effects of BCAA supplementation are described earlier in the A–Z series.12 The availability of tryptophan has been observed to be an important factor in immune system function; however, this has not been studied in the context of exercise. In addition, the potential role of tryptophan as a sleep agent to promote recovery after exercise is a current topic of interest but this has not has not been studied specifically in athletes.

Finally, it is important to be aware that, in the late 1980s, cases of eosinophilia-myalgia syndrome (EMS) occurred, including some deaths, in many people using tryptophan supplements.13 This was generally, but not unanimously,13 attributed to contamination during synthesis by one manufacturer. As a result, the sale of tryptophan as an isolated over-the-counter (OTC) supplement was banned in most countries. However, OTC tryptophan was reintroduced in many countries in the mid-2000s. In summary, there is currently no evidence that tryptophan supplementation has any beneficial effects on athletes. Indeed, as discussed above, tryptophan is known to be a key substance in the initial reactions leading to fatigue and perception of fatigue.


R Meeusen

Tyrosine (4-hydroxyphenylalanine) is an amino acid that can be synthesised in the body from phenylalanine. Tyrosine shares a common transport molecule with large neutral amino acids at the blood–brain barrier; therefore an increase in the tyrosine ratio causes an increase in brain tyrosine that would lead to an increase in brain dopamine (DA) and norepinephrine (NE) concentration. Since both DA and NE play a key role in a variety of stress-related behaviors, it is not surprising that tyrosine has been the focus of considerable military interest for its cognitive ‘antistress’ effects. A series of preclinical, animal studies clearly indicate that tyrosine reduces many of the adverse effects of acute stress on cognitive performance in a wide variety of stressful environments. Although it has been difficult to demonstrate conclusively that tyrosine has beneficial effects in humans, in part due to ethical concerns, most of the evidence suggests that tyrosine has utility as an acute treatment to prevent stress-related declines in cognitive function. Tyrosine affects the same neurotransmitter systems as the amphetamines and related drugs, which are potent performance-enhancing compounds, although they have many side effects.14 Studies examining acute tyrosine supplementation could not show benefits either on prolonged exercise capacity15 or performance16 in temperate conditions. A recent study showed that supplementing tyrosine 1 h pre-exercise is associated with increased exercise capacity in the heat.17 More research is necessary to demonstrate the performance-enhancing effects of tyrosine.

Concluding comments

None of the three amino acids addressed has been shown to be effective as a nutritional supplement in athletes. In addition, some care would need to be taken with tryptophan administration. Tryptophan only became available again a few years ago, having been taken off the market for nearly 20 years due to its role in an outbreak of EMS in 1989. It is now widely used again, although some countries may still have restrictions about its use in amino acid mixes.


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  • Competing interests None.

  • Provenance and peer review Commissioned; not externally peer reviewed.

  • ▸ References to this paper are available online at