title: Randomized controlled trial of the effect of short-term coadministration of methylcobalamin and folate on serum ADMA concentration in patients receiving long-term hemodialysis.
abstract: BACKGROUND
  Serum asymmetric dimethylarginine (ADMA) levels are increased in maintenance hemodialysis patients, and this abnormality may increase cardiovascular risk. We investigated whether combined administration of oral folate and intravenous methylcobalamin in such patients is more beneficial than oral folate alone at decreasing circulating ADMA levels.
  
  
  METHODS
  Randomized controlled trial.
  
  
  METHODS
  Patients undergoing hemodialysis.
  
  
  METHODS
  40 patients were randomly assigned to 1 of 2 groups. For 3 weeks, they received supplementation with either folate alone (15 mg/d; n = 20; folate group) or coadministered folate (15 mg/d) and methylcobalamin (500 mug after each hemodialysis treatment 3 times weekly; n = 20; methylcobalamin group).
  
  
  RESULTS
  
  
  
  METHODS
  normalization of plasma homocysteine levels (<15 mumol/L), decrease in serum ADMA levels.
  
  
  RESULTS
  change in augmentation index in the carotid artery and ratios of S-adenosylmethionine to S-adenosylhomocysteine (as a transmethylation indicator) and dimethylamine to ADMA (as an indicator of ADMA hydrolysis).
  
  
  METHODS
  Blood samples were collected under fasting conditions during the prehemodialysis procedure.
  
  
  RESULTS
  The proportion showing normalization of plasma homocysteine levels was much greater in the methylcobalamin group (18 of 20 patients; 90%) than in the folate group (6 of 20; 30%; P < 0.001). The percentage of decrease in ADMA levels was greater in the methylcobalamin than folate group (25.4% +/- 10.2% vs 13.2% +/- 11.2%; P < 0.001). The increase in ratio of S-adenosylmethionine to S-adenosylhomocysteine was not different between the 2 groups; however, the ratio of dimethylamine to ADMA was increased in only the methylcobalamin group (P = 0.04). Augmentation index was decreased in only the methylcobalamin group (P = 0.03).
  
  
  CONCLUSIONS
  This study had an open-label nature and did not examine long-term effects of homocysteine-normalizing therapy (no clinical end points).
  
  
  CONCLUSIONS
  Coadministration of intravenous methylcobalamin and oral folate in hemodialysis patients normalized hyperhomocysteinemia and decreased ADMA levels and arterial stiffness. We suggest that this regimen may have greater potential than folate alone to decrease cardiovascular risk in such patients.
authors.affiliation: Department of Nephrology, Kariya-Toyota General Hospital, Kariya, Japan. nephkidedta@do9.enjoy.ne.jp
authors.forename: Katsushi
authors.initials: K
authors.lastname: Koyama
authors.forename: Akinori
authors.initials: A
authors.lastname: Ito
authors.forename: Jun
authors.initials: J
authors.lastname: Yamamoto
authors.forename: Takae
authors.initials: T
authors.lastname: Nishio
authors.forename: Junko
authors.initials: J
authors.lastname: Kajikuri
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Dohi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ohte
authors.forename: Akira
authors.initials: A
authors.lastname: Sano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakamura
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Kumagai
authors.forename: Takeo
authors.initials: T
authors.lastname: Itoh
mesh_terms: D000284:Administration, Oral; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D002318:Cardiovascular Diseases / Q000453:epidemiology; D004359:Drug Therapy, Combination; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000517:prevention & control; D007275:Injections, Intravenous; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D012307:Risk Factors; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D006710:Homocysteine; D014803:Vitamin B Complex; C018524:N,N-dimethylarginine; D005492:Folic Acid; D001120:Arginine; C019476:mecobalamin; D014805:Vitamin B 12