Anxiolytic effects of acute tryptophan depletion in anorexia nervosa

Int J Eat Disord. 2003 Apr;33(3):257-67; discussion 268-70. doi: 10.1002/eat.10135.


Objective: Recent studies have raised the question as to whether a dysregulation of the neurotransmitter serotonin may contribute to the alterations in mood seen in anorexia nervosa (AN). People with AN tend to be anxious, obsessional, perfectionistic, and harm avoidant. These traits are premorbid and persist after recovery. It has been suggested that increased activity of brain serotonin systems could contribute to this pathologic condition. Dieting in AN, which serves to reduce plasma levels of tryptophan (TRP), may serve to reduce symptoms of dysphoric mood.

Method: Fourteen women currently symptomatic with AN (ILL AN), 14 women recovered from AN (REC AN), and 15 healthy control women (CW) underwent acute tryptophan depletion (ATD). Measures of psychological state were self-assessed at baseline and hourly after ATD to determine whether ATD would reduce negative mood.

Results: ILL AN and REC AN had significantly higher mean baseline TRP/LNAA (tryptophan/large neutral amino acids) ratios compared with CW. In contrast to placebo, the ATD challenge demonstrated a significantly greater reduction in the TRP/LNAA ratio for ILL AN (-95%) and REC AN (-84%) compared with CW (-70 %). Both the ILL AN and REC AN had a significant reduction in anxiety on the ATD day compared with the placebo day.

Discussion: These data demonstrate that a dietary-induced reduction of TRP, the precursor of serotonin, is associated with decreased anxiety in people with AN. Restricting dietary intake may represent a mechanism through which individuals with AN modulate a dysphoric mood.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Affect*
  • Anorexia Nervosa / physiopathology*
  • Anorexia Nervosa / psychology*
  • Anxiety / physiopathology*
  • Diet*
  • Diet, Reducing*
  • Double-Blind Method
  • Female
  • Humans
  • Tryptophan / metabolism*


  • Tryptophan