title: Selenium deficiency occurs in some patients with moderate-to-severe cirrhosis and can be corrected by administration of selenate but not selenomethionine: a randomized controlled trial.
abstract: BACKGROUND
  Selenomethionine, which is the principal dietary form of selenium, is metabolized by the liver to selenide, which is the form of the element required for the synthesis of selenoproteins. The liver synthesizes selenium-rich selenoprotein P (SEPP1) and secretes it into the plasma to supply extrahepatic tissues with selenium.
  
  
  OBJECTIVE
  We conducted a randomized controlled trial to determine whether cirrhosis is associated with functional selenium deficiency (the lack of selenium for the process of selenoprotein synthesis even though selenium intake is not limited) and, if it is, whether the deficiency is associated with impairment of selenomethionine metabolism.
  
  
  METHODS
  Patients with Child-Pugh (C-P) classes A, B, and C (mild, moderate, and severe, respectively) cirrhosis were supplemented with a placebo or supranutritional amounts of selenium as selenate (200 or 400 μg/d) or as selenomethionine (200 μg/d) for 4 wk. Plasma SEPP1 concentration and glutathione peroxidase (GPX) activity, the latter due largely to the selenoprotein GPX3 secreted by the kidneys, were measured before and after supplementation.
  
  
  RESULTS
  GPX activity was increased more by both doses of selenate than by the placebo in C-P class B patients. The activity was not increased more by selenomethionine supplementation than by the placebo in C-P class B patients. Plasma selenium was increased more by 400 μg Se as selenate than by the placebo in C-P class C patients. Within the groups who responded to selenate, there was a considerable variation in responses.
  
  
  CONCLUSIONS
  These results indicate that severe cirrhosis causes mild functional selenium deficiency in some patients that is associated with impaired metabolism of selenomethionine. This trial was registered at clinicaltrials.gov as NCT00271245.
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, and raymond.burk@vanderbilt.edu.
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Burk
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, and.
authors.forename: Kristina E
authors.initials: KE
authors.lastname: Hill
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, and.
authors.forename: Amy K
authors.initials: AK
authors.lastname: Motley
authors.affiliation: Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Byrne
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, and.
authors.forename: Brooke K
authors.initials: BK
authors.lastname: Norsworthy
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D003677:Deficiency Diseases / Q000097:blood / Q000178:diet therapy* / Q000453:epidemiology / Q000209:etiology; D019587:Dietary Supplements / Q000009:adverse effects; D005260:Female; D005979:Glutathione Peroxidase / Q000097:blood; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000503:physiopathology*; D008297:Male; D008715:Methionine / Q000097:blood; D008875:Middle Aged; D009752:Nutritional Status; D010865:Pilot Projects; D064586:Selenic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012643:Selenium / Q000008:administration & dosage / Q000097:blood / Q000172:deficiency* / Q000627:therapeutic use; D012645:Selenomethionine / Q000009:adverse effects / Q000627:therapeutic use; D051149:Selenoprotein P / Q000097:blood; D012720:Severity of Illness Index; D013714:Tennessee / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D051149:Selenoprotein P; D012645:Selenomethionine; D008715:Methionine; C486484:GPX3 protein, human; D005979:Glutathione Peroxidase; D012643:Selenium; D064586:Selenic Acid
keywords: functional selenium deficiency; inorganic selenium metabolism; selenium biomarkers; selenium metabolism by the liver; selenium requirement