Effects of dietary tryptophan and phenylalaninetyrosine depletion on phasic alertness in healthy adults - A pilot study

  • Patricia Hildebrand
  • Werner Königschulte
  • Tilman Jakob Gaber
  • Sarah Bubenzer-Busch
  • Katrin Helmbold
  • Caroline Sarah Biskup
  • Karl-Josef Langen
  • Gereon Rudolf Fink
  • Florian Daniel Zepf The University of Western Australia (UWA), Perth
Keywords: Dietary challenge procedures, amino acids, acute tryptophan depletion, phenylalanine tyrosine depletion, serotonin, dopamine, phasic alertness


Background: The synthesis of the neurotransmitters serotonin (5-HT) and dopamine (DA) in the brain can be directly altered by dietary manipulation of their relevant precursor amino acids (AA). There is evidence that altered serotonergic and dopaminergic neurotransmission are both associated with impaired attentional control. Specifically, phasic alertness is one specific aspect of attention that has been linked to changes in 5-HT and DA availability in different neurocircuitries related to attentional processes. The present study investigated the impact of short-term reductions in central nervous system 5-HT and DA synthesis, which was achieved by dietary depletion of the relevant precursor AA, on phasic alertness in healthy adult volunteers; body weight–adapted dietary tryptophan and phenylalanine–tyrosine depletion (PTD) techniques were used.

Methods: The study employed a double-blind between-subject design. Fifty healthy male and female subjects were allocated to three groups in a randomized and counterbalanced manner and received three different dietary challenge conditions: acute tryptophan depletion (ATD, for the depletion of 5-HT; N=16), PTD (for the depletion of DA; N=17), and a balanced AA load (BAL; N=17), which served as a control condition. Three hours after challenge intake (ATD/PTD/BAL), phasic alertness was assessed using a standardized test battery for attentional performance (TAP). Blood samples for AA level analyses were obtained at baseline and 360 min after the challenge intake.

Results: Overall, there were no significant differences in phasic alertness for the different challenge conditions. Regarding PTD administration, a positive correlation between the reaction times and the DA-related depletion magnitude was detected via the lower plasma tyrosine levels and the slow reaction times of the first run of the task. In contrast, higher tryptophan concentrations were associated with slower reaction times in the fourth run of the task in the same challenge group.

Conclusion: The present study is the first to demonstrate preliminary data that support an association between decreased central nervous system DA synthesis, which was achieved by dietary depletion strategies, and slower reaction times in specific runs of a task designed to assess phasic alertness in healthy adult volunteers; these findings are consistent with previous evidence that links phasic alertness with dopaminergic neurotransmission. A lack of significant differences between the three groups could be due to compensatory mechanisms and the limited sample size, as well as the dietary challenge procedures administered to healthy participants and the strict exclusion criteria used. The potential underlying neurochemical processes related to phasic alertness should be the subject of further investigations.

Keywords: dietary challenge procedures; amino acids; acute tryptophan depletion; phenylalanine–tyrosine depletion; serotonin; dopamine; phasic alertness

(Published: 29 April 2015)

Responsible Editor: Seppo Salminen, University of Turku, Finland.

Citation: Food & Nutrition Research 2015, 59: 26407 - http://dx.doi.org/10.3402/fnr.v59.26407


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Author Biography

Florian Daniel Zepf, The University of Western Australia (UWA), Perth
Prof. Dr. Florian D. Zepf is the Chair and Winthrop Professor of Child and Adolescent Psychiatry at the University of Western Australia, and the Clinical Director / Head of Department of the Specialised Child and Adolescent Mental Health Services in Western Australia.

He is the recipient of prestigious research awards, including the "Young Minds in Psychiatry Award" (awarded by the American Psychiatric Association and the American Psychiatric Institute for Research and Education), the Donald J. Cohen Fellowship Award (granted by the International Association of Child and Adolescent Psychiatry and Allied Professions) and the Raine Visiting Professorship of the University of Western Australia.

He has published several papers and book chapters on a variety of topics related to different aspects of mental health in children and adolescents, and is an internationally highly recognized clinician and researcher in the field of paediatric neuropsychopharmacology. His main research interests are neurochemical aspects of brain function and their development in neuropsychiatric disorders, neuroimaging, neurofeedback, eating disorders as well as attention and affective disorders.

He is a member of the American Academy of Child and Adolescent Psychiatry (AACAP), the American Psychiatric Association (APA), the German Society of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy (DGKJP), the Society of Biological Psychiatry (SOBP), the International College of Neuropsychopharmacology (CINP), the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP), the International Society fo Serotonin Research, and the International Society for Tryptophan Research (ISTRY).

How to Cite
Hildebrand P., Königschulte W., Gaber T. J., Bubenzer-Busch S., Helmbold K., Biskup C. S., Langen K.-J., Fink G. R., & Zepf F. D. (2015). Effects of dietary tryptophan and phenylalaninetyrosine depletion on phasic alertness in healthy adults - A pilot study. Food & Nutrition Research, 59. https://doi.org/10.3402/fnr.v59.26407
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