Dietary tryptophan depletion in humans using a simplified two amino acid formula - a pilot study

  • Maike Linden
  • Katrin Helmbold
  • Janina Kempf
  • Shabnam Sippas
  • Christian Filss
  • Karl-Josef Langen
  • Albrecht Eisert
  • Florian Daniel Zepf Department of Child and Adolescent Psychiatry, The University of Western Australia (UWA), Perth, Australia


Background: Acute tryptophan depletion (ATD) is a well-established dietary method in translational brain research used to briefly lower central nervous serotonin (5-hydroxytryptamine (5-HT)) synthesis. A simplified two amino acid ATD formula (ATDPHE/LEU) was developed while reducing the overall amount of amino acids (AAs), with the objective of administration especially in children and adolescents in future studies.

Objective: This study investigated tryptophan (TRP) influx rates across the blood-brain barrier (BBB) after dietary ATDPHE/LEU administration relative to the ATD Moja-De protocol that has been established for use in children and adolescents.

Design: Seventy-two healthy adults (50% females) were randomized into four groups and administered ATD Moja-De, its TRP-balanced control condition (BAL), ATDPHE/LEU, or its respective control mixture (BALPHE/LEU) in a counterbalanced, double-blind, between-subjects design. Blood samples were collected at baseline and at hourly intervals for 6 h after AA intake. Questionnaires about mood, taste, and challenge tolerance were completed at fixed time points.

Results: Both challenge mixtures significantly reduced central nervous TRP influx as calculated by Michaelis–Menten kinetics relative to baseline and the respective control conditions with only mild and comparable side effects. A greater decline in TRP influx over the BBB after ATDPHE/LEU administration when compared with ATD Moja-De was detected without group effects for taste, challenge tolerance, and mood. There was unintended initial short increase in plasma TRP concentrations observed after ATDPHE/LEU intake, and a possible redistribution between free and protein-bound TRP triggered by protein synthesis stimulated by the ingested AAs may account for this finding. Moreover, a decline in TRP influx after BALPHE/LEU administration over a 6-h period was observed, and the large amount of PHE in the BALPHE/LEU mixture may be a possible explanation for this particular phenomenon, which could have led to an unexpected increase in displacement of TRP at the BBB in this control condition.

Conclusions: This pilot study provides preliminary evidence for the possibility of lowering TRP influx as calculated by Michaelis–Menten kinetics into the brain by using a simplified ATD protocol in humans. The simplified composition of only two AAs, the lower overall AA amount, and the appropriate tolerance are characteristics of the newly developed ATDPHE/LEU protocol. Future studies focusing on the effects of the ATDPHE/LEU protocol and its respective control condition on CSF 5-HIAA concentrations, as well as neurochemical studies in rodents, are needed to further validate this newly developed AA mixture before definite conclusions about its usability in ATD-related research in humans, its specificity, and additional effects can be made.

Keywords: serotonin; amino acids; dietary tryptophan depletion; influx rate; Michaelis–Menten kinetics; humans

(Published: 16 December 2016)

Citation: Food & Nutrition Research 2016, 60: 29272 -


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Author Biography

Florian Daniel Zepf, Department of Child and Adolescent Psychiatry, The University of Western Australia (UWA), Perth, Australia
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
Linden M., Helmbold K., Kempf J., Sippas S., Filss C., Langen K.-J., Eisert A., & Zepf F. D. (2016). Dietary tryptophan depletion in humans using a simplified two amino acid formula - a pilot study. Food & Nutrition Research, 60.
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