Title: The Possible Link Between Dieting, Tryptophan And Bulimia Nervosa

Key words: binge eating, serotonin, tryptophan, dieting, depressive symptoms, migraine, satiety responses, hypothalamus, pituitary, neurotransmission

Date: Aug 2000

Category: 7. The Mind

Type: Article

Author: Dr Van Rhijn



Bulimia Nervosa


The Possible Link Between Dieting, Tryptophan And Bulimia Nervosa



The eating disorder bulimia nervosa (BN) is characterised by recurrent episodes of binge eating accompanied by extreme weight control behaviour due to overvalued ideas concerning body image regarding weight and shape1. Although the neurobiological basis is still unclear, there is evidence of abnormalities in serotonin neurotransmission2, indicating a possible link between its precursor tryptophan (TRP), dieting and BN.


Eating and Serotonin

The essential amino acid TRP is a precursor3 of serotonin synthesis4 (a major neurotransmitter) and its depletion is associated with a rapid lowering of mood5, development of depression6, disturbance of impulse control (increased impulsivity)7, obsessionality as well as neuro-endocrine disturbances. Large neutral amino acid (LNAA) levels fall following carbohydrate binging, and produce an increase in the TRP:LNAA ratio8,9, and this relative increase in TRP availability in bulimic patients was associated with a blunting of the normal sensation of hunger and an enhanced rating for nausea10. Thus relative TRP:LNAA levels may be associated with the termination of bingeing and vomiting, perhaps due to TRP’s effects on brain serotonin metabolism11. Oral administration of TRP successfully diminished bingeing behaviour in a normal weight bulimic female12.


In contrast, serotonin receptors appear to influence eating behaviour13, and a reduction in serotonin function results in impaired satiety, increased food intake14 and weight gain15. Dieting can cause a moderate degree of plasma TRP depletion16,17 and thus a decrease in TRP availability18. As most cases of BN evolve from normal dieting19, it could be postulated that reduced brain serotonin transmission has a contributory role in the development of BN in vulnerable individuals20, as found in acutely ill, normal weight bulimics21,22.


To study its neuropsychiatric effects, serotonin neurotransmission can artificially be acutely lowered, with a TRP depleted diet, to induce reduced serotonin synthesis. Studies with clinically recovered BN23, and currently ill BN24 cases indicated that acute TRP depletion results in depressive symptoms and a temporary return of key symptoms of the disorder such as the subjective sense of loss of control over eating, the overvalued ideas regarding weight and body shape as well as fatigue, increased anxiety and indecisiveness25.


Chronic depletion of plasma TRP may therefore contribute to the development of BN in vulnerable individuals who persistently put themselves on restrictive diets26. It has been suggested that BN and migraine sufferers share a common pathophysiological relationship involving postsynaptic 5-HT dysfunction27. Further neuro-endocrine studies found that prolactin responses were blunted following challenges with the postsynaptic 5-HT receptor agonist d,l-fenfluramine28 and m-chlorophenylpiperazine (m-CPP)29, suggesting that postsynaptic 5-HT receptor sensitivity is state dependently altered in BN. M-CPP studies also support a role for serotonin (5-HT) function in the mediation of satiety responses, that are impaired in BN30.



These findings indicate that post-synaptic responsiveness in hypothalamic-pituitary serotonergic pathways is reduced in bulimia. Lowered brain TRP levels and secondary alterations in 5-HT neurotransmission may contribute to the pathophysiology of BN, especially cognitive and mood disturbances, but it remains debatable whether this relationship is causal or a consequence of the disordered eating pattern in vulnerable, predisposed individuals.



1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Washington, D.C. 1994; American Psychiatric Association.


2. Leibowitz, S.F. The role of serotonin in eating disorders. Drugs. 1990; 39: 33 – 48.


3. Fernstrom, J. Dietary amino acids and brain function. J. Am. Diet. Assoc. 1994; 94(1): 71 – 77.


4. Benkelfast, C. et al. Tryptophan depletion markedly reduces the rate of serotonin synthesis in normal healthy volunteers. Am. Coll. Neuropsycho-pharmacology. 1995; 34: 214.


5. Nishizawa, S. et al. Differences between males and females in rates of serotonin synthesis in the human brain, Proc. Nat. Acad. Sci. USA. 1993; 94: 5308 – 5313.


6. Smith, K.A. et al. Relapse of depression after rapid depletion of tryptophan. Lancet. 1997; 349: 915 – 919.


7. Askenazy, F. et al. Whole blood serotonin content, tryptophan concentrations, and impulsivity in anorexia nervosa. Biol. Psychiatry. 1998; 43(3): 188 – 195.


8. Pijl, H. et al. Plasma amino acid ratios related to brain serotonin synthesis in response to food intake in bulimia nervosa. Biol. Psychiatry. 1995; 38(10): 659 – 668.


9. Schreiber, W. et al. Circadian pattern of large neutral amino acids, glucose, insulin, and food intake in anorexia nervosa and bulimia nervosa. Metabolism. 1991; 40(5): 503 – 507.


10. Turner, M.S. et al. Psychological, hormonal and biochemical changes following carbohydrate bingeing: a placebo controlled study in bulimia nervosa and matched controls. Psychol. Med. 1991; 21(1): 123 – 133.


11. Kaye, W.H. et al. Bingeing behaviour and plasma amino acids: a possible involvement of brain serotonin in bulimia nervosa. Psychiatry Res. 1988; 23(1): 31 – 43.


12. Cole, W. & Lapierre, Y.D. The use of tryptophan in normal-weight bulimia.  Can. J. Psychiatry. 1986; 31(8): 755 – 756.


13. Morley, J.E. et al. Opioid modulation of appetite. Neurosci. Biobehav. Rev. 1983;7: 281 – 305.


14. Weltzin, T.E. et al. Acute tryptophan depletion in bulimia: effects on large neutral amino acids. Biol. Psych. 1994; 35: 388 – 397.


15. Tecott, L.H. et al. Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors. Nature. 1995; 374: 542 – 546.


16. Anderson, I.M. et al. Dieting reduces plasma tryptophan and alters brain 5-HT function in women. Psychol. Med. 1990; 29: 785 – 791.


17. Cowen, P.J. et al. Moderate dieting causes 5-HT2C receptor supersensitivity.  Psychol. Med. 1996. 26(6): 1155 – 1159.


18. Cowen, P.J. & Smith, K.A. Serotonin, dieting, and bulimia nervosa.  Adv. Exp. Med. Biol. 1999; 467: 101 – 104.


19. Hsu, L.K.G. Can dieting cause an eating disorder? Psychol. Med. 1997; 27: 509 – 513.


20. Brewerton, T.D. Toward a unified theory of serotonin dysregulation in eating and related disorders. Psychoneuroendocrinology. 1995; 20: 561 – 590.


21. Kaye, W.H. & Weltzin, T.E. Serotonin activity in anorexia and bulimia nervosa: relationship to the modulation of feeding and mood. J. Clin. Psychiatry. 1991; 52 (Suppl): S41 – S48.


22. Weltzin, T.E. et al. Acute tryptophan depletion and increased food intake and irritability in bulimia nervosa. Am. J. Psychiatry. 1995; 152(11): 1668 – 1671.


23. Smith, K.A. et al. Symptomatic relapse in bulimia nervosa following acute tryptophan depletion.  Arch. Gen. Psychiatry. 1999; 56(2): 171 – 176.


24. Kaye, W.H. et al. Effects of acute tryptophan depletion on mood in bulimia nervosa.  Biol. Psychiatry. 2000; 47(2): 151 – 157.


25. Weltzin, T.E. et al. Acute tryptophan depletion in bulimia: effects on large neutral amino acids. Biol. Psychiatry. 1994; 35(6): 388 – 397.


26. Cowen, P.J. et al. Why is dieting so difficult? Nature. 1995; 376: 557.


27. Brewerton, T.D. & George, M.S. Is migraine related to the eating disorders?  Int. J. Eat. Disord. 1993; 14(1): 75 – 79.


28. Wolfe, B.E. et al. Serotonin function following remission from bulimia nervosa. Neuropsychopharmacology. 2000; 22(3): 257 – 263.


29. Brewerton, T.D. et al. Neuro-endocrine responses to m-chlorophenylpiperazine and L-tryptophan in bulimia. Arch. Gen. Psychiatry. 1992. 49(11): 852 – 861.


30. Brewerton, T.D. et al. Testmeal responses following m-chlorophenylpiperazine and L-tryptophan in bulimics and controls. Neuropsychopharmacology. 1994; 11(1): 63 – 71.