Decreased glutathione in patients with anorexia nervosa. Risk factor for toxic liver injury?
OBJECTIVE
To investigate glutathione and amino acids related to glutathione metabolism in patients with anorexia nervosa in order to test the hypothesis that these patients exhibit a deficiency of glutathione and therefore might be at an increased risk of developing toxic liver injury.


METHODS
Controlled observatory study and case report.


METHODS
University Hospital.


METHODS
Subjects included 11 female patients with anorexia nervosa and 12 healthy female controls.


METHODS
Determination of fasting free and total glutathione, homocysteine, vitamins B(6) and B(12) and folic acid in plasma.


RESULTS
A 14-y-old patient with a body mass index of 12.6 kg/m(2) presented with markedly elevated transaminases (ALAT >50 x upper limit of normal), and paracetamol was detected in her blood. Patients with anorexia nervosa exhibited lower circulating concentrations of free cysteine (8.9+/-1.5 vs 12.0+/-1.4 micromol/l) and free and total glutathione (5.0+/-1.3 vs 7.1+/-1.2 and 11.2+/-3.8 vs 16.2+/-5.0 micromol/l, respectively). The plasma concentrations of homocysteine (17.5+/-4.9 vs 12.0+/-3.8 micromol/l) and also of glycine (194+/-37 vs 143+/-41 micromol/l) and glutamine (422+/-51 vs 353+/-51 micromol/l) were significantly higher in patients with anorexia nervosa who were not deficient in folic acid, vitamin B(6) and B(12).


CONCLUSIONS
Lower plasma concentrations of glutathione suggest lower intracellular concentrations of the tripeptide. Higher homocysteine, glycine and glutamine concentrations point to a decreased utilization of these amino acids for glutathione synthesis and an impairment of trans-sulfuration. Consequently, the capacity of patients with anorexia nervosa to detoxify electrophilic metabolites and reactive oxygen species via glutathione may be impaired.
Zenger
F
F
Department of Clinical Pharmacology, University of Bern, Switzerland.
Russmann
S
S
Junker
E
E
Wüthrich
C
C
Bui
M H
MH
Lauterburg
B H
BH
D000082:Acetaminophen / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000596:Amino Acids / Q000097:blood; D000856:Anorexia Nervosa / Q000150:complications / Q000378:metabolism*; D015992:Body Mass Index; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008107:Liver Diseases / Q000209:etiology / Q000378:metabolism*; D008111:Liver Function Tests; D012307:Risk Factors; D013557:Switzerland; D014803:Vitamin B Complex / Q000097:blood
D000596:Amino Acids; D006710:Homocysteine; D014803:Vitamin B Complex; D000082:Acetaminophen; D005978:Glutathione