Memory impairments in humans after acute tryptophan depletion using a novel gelatin-based protein drink

J Psychopharmacol. 2009 Jan;23(1):56-64. doi: 10.1177/0269881108089577. Epub 2008 May 30.


Acute tryptophan depletion (ATD) can be used to decrease serotonin levels in the brain. Traditionally, ATD has been established by administering amino acid (AA) mixtures and studies using this method showed that serotonin is involved in learning and memory processes. This study used a recently developed gelatin-based protein drink to examine whether it 1) is superior to the traditional AA method in controlling the tryptophan levels in the placebo condition, 2) impairs long-term memory and 3) differentially affects episodic and spatial memory. Sixteen healthy subjects participated in a double-blind, placebo-controlled study. Memory was assessed using a visual verbal learning test and an object relocation task (spatial memory). Tryptophan ratio significantly decreased after ATD and did not significantly increase in the placebo condition. Delayed recall in the verbal learning test and delayed relocation of objects to positions in the spatial task were impaired after ATD. Spatial short-term memory, however, improved. The current results indicate that the tryptophan levels were essentially neutral in the placebo condition compared with those in the traditional AA mixture. Our study provides further evidence that impairment in long-term episodic and elementary spatial memory after ATD is related to lowered tryptophan levels in plasma.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Affect / physiology
  • Amino Acids, Essential / administration & dosage
  • Amino Acids, Essential / blood
  • Amino Acids, Essential / chemistry
  • Amino Acids, Essential / deficiency*
  • Cross-Over Studies
  • Dietary Proteins / adverse effects*
  • Dietary Proteins / analysis
  • Dietary Supplements
  • Double-Blind Method
  • Drinking
  • Female
  • Gelatin / adverse effects*
  • Gelatin / chemistry
  • Humans
  • Male
  • Memory Disorders / diagnosis*
  • Memory Disorders / etiology
  • Memory, Short-Term / drug effects
  • Mental Recall / drug effects
  • Placebos / administration & dosage
  • Placebos / analysis
  • Placebos / chemistry
  • Surveys and Questionnaires
  • Task Performance and Analysis
  • Tryptophan / administration & dosage*
  • Tryptophan / blood
  • Tryptophan / chemistry
  • Tryptophan / deficiency*
  • Verbal Learning / physiology


  • Amino Acids, Essential
  • Dietary Proteins
  • Placebos
  • Tryptophan
  • Gelatin