title: Choline deficiency causes reversible hepatic abnormalities in patients receiving parenteral nutrition: proof of a human choline requirement: a placebo-controlled trial.
abstract: BACKGROUND
  Previous studies have shown that plasma free choline concentrations are significantly decreased in many long-term home total parenteral nutrition (TPN) patients. Furthermore, low choline status has been associated with both hepatic morphologic and hepatic aminotransferase abnormalities. A preliminary pilot study suggested choline-supplemented TPN may be useful in reversal of these hepatic abnormalities.
  
  
  METHODS
  Fifteen patients (10 M, 5 F) who had required TPN for > or =80% of their nutritional needs were randomized to receive their usual TPN (n = 8), or TPN to which 2 g choline chloride had been added (n = 7) for 24 weeks. Baseline demographic data were similar between groups. Patients had CT scans of the liver and spleen, and blood for plasma free and phospholipid-bound choline, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, gamma glutamyl transferase (GGT), bilirubin, serum lipids, complete blood count (CBC), and chemistry profile obtained at baseline, and weeks 2, 4, 6, 12, 16, 20, 24, and 34. CT scans were analyzed for Hounsfield unit (HU) densities.
  
  
  RESULTS
  There were no significant differences in any measured parameters after 2 weeks. However, at 4 weeks, a significant difference in liver HU between groups was observed (13.3+/-5.0 HU [choline] vs 5.8+/-5.2 HU [placebo], p = .04). This significant trend continued through week 24. Recurrent hepatic steatosis and decreased HU were observed at week 34, 10 weeks after choline supplementation had been discontinued. A significant increase in the liver-spleen differential HU was also observed in the choline group (10.6+/-6.2 HU [choline] vs 1.3+/-3.3 HU [placebo], p = .01). Serum ALT decreased significantly (p = .01 to .05) in the choline group vs placebo at weeks 6,12, 20, and 24. Serum AST was significantly decreased in the choline group by week 24 (p = .02). The serum alkaline phosphatase was significantly reduced in the choline group at weeks 2, 12, 20, 24, and 34 (p = .02 to 0.07). Total bilirubin was normal in these patients and remained unchanged during the study. Serum GGT tended to decrease more in the choline group, but the greater decrease was not statistically significant.
  
  
  CONCLUSIONS
  Choline deficiency is a significant contributor to the development of TPN-associated liver disease. The data suggest choline is a required nutrient for long-term home TPN patients.
authors.affiliation: Division of Gastroenterology, Northwestern University Medical School, Chicago, IL 60611, USA. a-buchman@northwestern.edu
authors.forename: A L
authors.initials: AL
authors.lastname: Buchman
authors.forename: M E
authors.initials: ME
authors.lastname: Ament
authors.forename: M
authors.initials: M
authors.lastname: Sohel
authors.forename: M
authors.initials: M
authors.lastname: Dubin
authors.forename: D J
authors.initials: DJ
authors.lastname: Jenden
authors.forename: M
authors.initials: M
authors.lastname: Roch
authors.forename: H
authors.initials: H
authors.lastname: Pownall
authors.forename: W
authors.initials: W
authors.lastname: Farley
authors.forename: M
authors.initials: M
authors.lastname: Awal
authors.forename: C
authors.initials: C
authors.lastname: Ahn
mesh_terms: D000328:Adult; D002794:Choline / Q000008:administration & dosage* / Q000097:blood; D002796:Choline Deficiency / Q000628:therapy*; D019587:Dietary Supplements; D005217:Fat Emulsions, Intravenous; D005260:Female; D006801:Humans; D008082:Lipotropic Agents / Q000008:administration & dosage* / Q000097:blood; D008099:Liver / Q000201:enzymology / Q000473:pathology*; D008297:Male; D009751:Nutritional Requirements; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D013154:Spleen / Q000473:pathology; D014057:Tomography, X-Ray Computed; D000637:Transaminases / Q000378:metabolism
chemical_list: D005217:Fat Emulsions, Intravenous; D008082:Lipotropic Agents; D000637:Transaminases; D002794:Choline