title: Choline deficiency in mice and humans is associated with increased plasma homocysteine concentration after a methionine load.
abstract: BACKGROUND
  Elevated concentrations of homocysteine in blood may be an independent risk factor for the development of atherosclerosis. Elevated homocysteine concentrations can be caused by decreased methylation of homocysteine to form methionine, as occurs in folate deficiency. A parallel pathway exists for methylation of homocysteine, in which choline, by way of betaine, is the methyl donor.
  
  
  OBJECTIVE
  Our goal was to determine whether choline deficiency results in a decreased capacity to methylate homocysteine.
  
  
  METHODS
  C57BL/6J mice were fed diets containing 0, 10, or 35 mmol choline/kg diet for 3 wk. We then administered an oral methionine load to the animals and measured plasma homocysteine concentrations. Also, in a pilot study, we examined 8 men who were fed a diet providing 550 mg choline/d per 70 kg body weight for 10 d, followed by a diet providing almost no choline, until the subjects were clinically judged to be choline deficient or for <or=42 d. A methionine load was administered at the end of each dietary phase.
  
  
  RESULTS
  Two hours after the methionine load, choline-deficient mice had plasma homocysteine concentrations twice those of choline-fed mice. Four hours after the methionine load, clinically choline-depleted men had plasma homocysteine concentrations that were 35% greater than those in men not choline depleted.
  
  
  CONCLUSIONS
  These results suggest that choline, like folate, plays an important role in the metabolism of homocysteine in humans and that response to a methionine load may be useful when assessing choline nutriture.
authors.affiliation: Department of Nutrition, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Kerry-Ann
authors.initials: KA
authors.lastname: da Costa
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Gaffney
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Fischer
authors.forename: Steven H
authors.initials: SH
authors.lastname: Zeisel
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D002794:Choline / Q000008:administration & dosage* / Q000378:metabolism; D002796:Choline Deficiency / Q000097:blood* / Q000378:metabolism; D018592:Cross-Over Studies; D006710:Homocysteine / Q000097:blood* / Q000378:metabolism; D006801:Humans; D008082:Lipotropic Agents / Q000008:administration & dosage; D008099:Liver / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000008:administration & dosage* / Q000378:metabolism; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009752:Nutritional Status; D010865:Pilot Projects
chemical_list: D008082:Lipotropic Agents; D006710:Homocysteine; D008715:Methionine; D002794:Choline