Title: Dieting, tryptophan and bulimia nervosa.

Key words: serotonin, carbohydrate intake, satiety, 5HT dysfunction, hypothalamus, gender differences, dieting, stress

Date: Jan 2001

Category: Specific conditions

Type: Article

Author: Kate Neil (NS3)

 

 

Dieting, tryptophan and bulimia nervosa.

The availability of tryptophan for brain function can be altered by diet1. Normally, dietary tryptophan is transported across the blood-brain barrier and distributed in 5-HT neurons1. Tryptophan is then converted by a hydroxylase enzyme to 5-hydroxytryptophan, which is then decarboxylated to form serotonin1 (5HT).

Dieting lowers plasma tryptophan levels, decreasing 5-HT transmission2. Decreasing hypothalamic 5-HT leads to increased carbohydrate intake and impairment of usual levels of satiety1. Bulimia Nervosa BN sufferers binge on excessive amounts of carbohydrates and total calories with a documented lower level of satiety than controls in response to normal meals1.

Central 5-HT dysfunction has been implicated in the pathophysiology of depression, suicide, anxiety, alcoholism, aggression, impulsivity, and the regulation of satiety and macronutrient selection3. The incidence of these disorders is higher than expected in the families of bulimic patients1.

The effect of decreasing calorie intake on neuroendocrine 5-HT parameters is different in males to females4. The gender specific biological difference suggests a particular sensitivity of the hypothalamic activity in women to the effects of dieting4. BN is significantly more common in women2 as is dieting5.

Animal and human studies suggest that serotonin is involved in the control of feeding5. Artificially reducing serotonin function leads to impaired satiety and weight gain in animals1. D,l-fenfluramine hydrochloride is a 5HT releasing agent that increases plasma prolactin, a marker of 5HT function6. Acutely ill BN subjects show blunted prolactin responses to this releasing agent, which is consistent with the proposal that the condition is associated with lowered brain serotonin function6.

The synthesis of serotonin in the brain is dependent on the availability of its amino acid precursor tryptophan from plasma7. Centrally, functional underactivity of 5-HT has been postulated as a perpetuating mechanism in BN3.

The paradigm that acute tryptophan depletion reduces brain serotonin synthesis is based on animal data showing that the ingestion of a tryptophan depleted amino acid mixture markedly reduces plasma tryptophan concentrations and 5-HA1AA8.

Blood platelets actively take up 5-HT2. This process is sluggish in depressives. If uptake mirrors synaptosomal uptake, then an increased uptake rate would effectively diminish the amount of 5-HT available for activity on postsynaptic receptors at a hypothalamic level, resulting in decreased satiety signals and possible increased preference for carbohydrate, both significant features of BN3.

Indirect evidence suggests that biological predisposition, acting in concert with recurrent dieting behaviour and psychosocial stressors, contributes to the pathophysiology of BN9.

A functional effect of dieting is to lower neurotransmission at post-synaptic 5HT-2C receptors2. There are an increased number of 5HT-2C receptors after dieting, which is a signal that there has been low 5-HT neurotransmission to that synapse2. Drugs that block 5-HT-2C receptors cause weight gain2. Normally, when these receptors are activated by 5-HT it sends a satiety signal2. If this receptor is blocked, people frequently feel hungry2.

Dieting lowers 5-HT in all its various synapses. And, from the point of view of eating, this will lower 5HT-2C receptor function in the hypothalamus, leading to feeling hungry all the time and so potentiating binge eating2. In BN there are recurrent episodes of binge eating and a subjective sense of loss of control2. Those affected eat and then feel bad and take compensatory measures to avoid weight gain like making themselves sick2.

Stress elevates cortisol. Cortisol elevation lowers plasma tryptophan and impairs serotonin transmission2. Dieting and stress compound the decrease in 5-HT function and serotonin transmission in the brain2.

Only a small sub-set of dieters develop BN, suggesting a vulnerability to this disorder2. Most people cope with dieting and stressful lifestyles without developing BN2. Diet induced reductions in plasma tryptophan and brain 5-HT over-time maybe a biological trigger for diet-induced eating disorders in vulnerable individuals2. Dieting is extremely difficult for most people2. Reductions in plasma tryptophan make you hungry, so perhaps it is an evolutionary design to stop you dieting2.

References

  1. Goldbloom D, Garfinkel P, The Serotonin Hypothesis of Bulimia Nervosa: Theory and Evidence, Can.J.Psychiatry Vol 35, Dec 1990
  2. Cowan P, MSc lecture notes, Surrey University, July 2000
  3. Goldbloom D, Hicks L, Garfinkel P, Platelet Serotonin Uptake in Bulimia Nervosa, Biol.Psychiatry, 1990;28:644-647
  4. Goodwin G, Fairburn C, Cowen P, Dieting changes serotonergic function in women, not men: implications for the etiology of anorexia nervosa? Psychol Med 1987: 17:839-842
  5. Galla J, Stewart C, Fehr L, Paola J, Hyman-Dollar M, Serotonin Reuptake Inhibitors and the Treatment of Bulimia Nervosa A comprehensive review, 1995m Widener University, Paper presented April 6, 1995, National Social Science Association Conference, San Diego, CA
  6. Smith K, Fairburn C, Cowen P, Symptomatic Relapse in Bulimia Nervosa Following Acute Tryptophan Depletion, Arch Gen Psychiatry, Vol 56, Feb 1999
  7. Smith K, Fairburn C, Cowen P, Relapse of depression after rapid depletion of tryptophan, The Lancet, Vol 349, Mar 29, 1997
  8. Weltzin T, Ferstrom M, Ferstrom J, Neuberger S, Kaye W, Acute Tryptophan Depletion and Increased Food intake and Irritability in Bulimia Nervosa, Am J Psychiatry 152:11, Nov 1995
  9. Jimerson D, Wolfe B, Metzger E, Finkelstein D, Cooper T, Jeffrey M, Levine M, Decreased Serotonin Function in Bulimia Nervosa, Arch Gen Osychiatry Vol 54, June 1997