title: Plasma choline and betaine correlate with serum folate, plasma S-adenosyl-methionine and S-adenosyl-homocysteine in healthy volunteers.
abstract: BACKGROUND
  Choline is essential for mammalian cell function. It plays a critical role in cell membrane integrity, neurotransmission, cell signaling and lipid metabolism. Moreover, choline is involved in methylation in two ways: a) its synthesis requires methyl groups donated by S-adenosyl-methionine (AdoMet); and b) choline oxidation product betaine methylates homocysteine (Hcy) to methionine (Met) and produces dimethylglycine. This later donates one carbon units to tetrahydrofolate (THF).
  
  
  METHODS
  To evaluate the correlations of choline and betaine with folate, AdoMet, S-anenosyl-homocysteine (AdoHcy), total homocysteine (tHcy), and DNA methylation, choline, betaine and dimethylglycine were measured by LC-MS/MS in plasma of 109 healthy volunteers, in whom folate, AdoMet, AdoHcy, tHcy, and DNA methylation have previously been reported.
  
  
  RESULTS
  Using a bivariate model, choline and betaine showed strong positive correlations with folate (r = 0.346 and r = 0.226), AdoHcy (r = 0.468 and r = 0.296), and correlated negatively with AdoMet/AdoHcy ratio (r = – 0.246 and r = – 0.379). Only choline was positively correlated with AdoMet (r = 0.453). Using a multivariate linear regression model, choline correlated strongly with folate ( β = 17.416), AdoMet ( β = 61.272), and AdoHcy ( β = 9.215). Betaine correlated positively with folate ( β = 0.133) and negatively with tHcy ( β = – 0.194) ratio. Choline is an integral part of folate and methylation pathways.
  
  
  CONCLUSIONS
  Our data highlight the importance of integrating choline in studies concerning addressing pathological conditions related to folate, homocysteine and methylation metabolism.
authors.affiliation: Biochemistry-Hormonology Laboratory, Robert Debré Hospital, 48 Boulevard Serurier, 75019 Paris, France. apolline.imbard@rdb.aphp.fr
authors.forename: Apolline
authors.initials: A
authors.lastname: Imbard
authors.forename: Yvo M
authors.initials: YM
authors.lastname: Smulders
authors.forename: Rob
authors.initials: R
authors.lastname: Barto
authors.forename: Desiree E C
authors.initials: DE
authors.lastname: Smith
authors.forename: Robert M
authors.initials: RM
authors.lastname: Kok
authors.forename: Cornelis
authors.initials: C
authors.lastname: Jakobs
authors.forename: Henk J
authors.initials: HJ
authors.lastname: Blom
mesh_terms: D000293:Adolescent; D000328:Adult; D001622:Betaine / Q000097:blood*; D002794:Choline / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D019175:DNA Methylation; D005260:Female; D005492:Folic Acid / Q000097:blood*; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D012435:S-Adenosylhomocysteine / Q000097:blood*; D012436:S-Adenosylmethionine / Q000097:blood*; D012521:Sarcosine / Q000031:analogs & derivatives / Q000097:blood; D012737:Sex Factors; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D012739:Gonadal Steroid Hormones; D001622:Betaine; C025138:dimethylglycine; D012436:S-Adenosylmethionine; D005492:Folic Acid; D012435:S-Adenosylhomocysteine; D002794:Choline; D012521:Sarcosine