title: Hyperhomocysteinemia and endothelial function in young subjects: effects of vitamin supplementation.
abstract: BACKGROUND
  The relationship between hyperhomocysteinemia and cardiovascular disease has not been totally elucidated.
  
  
  OBJECTIVE
  The study aimed to verify the association between hyperhomocysteinemia and endothelial dysfunction before and after modification of total homocysteine (tHcy) serum levels with vitamin supplementation in young male subjects devoid of any other cardiovascular risk factor.
  
  
  METHODS
  Twenty hyperhomocysteinemic (tHcy > 15 [micromol/l) male volunteers (< or = 40 years) and 20 age-matched subjects with normal tHcy levels (tHcy < 13 micromol/l) were included. Exclusion criteria were smoking, hypertension, diabetes, vitamin ingestion, obesity, hypercholesterolemia, renal failure, and positive antiphospholipid antibodies. Serum tHcy, folate, vitamin B12 levels, activated protein C and S, protein C resistance, fibrinogen, prothrombin, thrombin, antithrombin III, and in vitro oxidation of low-density lipoprotein (LDL) particles were measured. Noninvasive ultrasound measurements of endothelium-dependent (EDD) and -independent dilatation (EID) of the brachial artery were performed. Each pair was then randomly assigned to receive a vitamin capsule (0.6 mg folic acid, 0.8 mg B12. and 2.0 mg B6) oran identical placebo during 8 weeks, in a double-blind study design. After the treatment phase, blood samples and vascular reactivity were repeated.
  
  
  RESULTS
  Nine pairs of volunteers received vitamins and 11 received placebo. Hyperhomocysteinemic subjects had lower baseline serum levels of vitamin B12. Serum folate levels, antithrombotic function, in vitro LDL oxidation, and EDD were similar in all groups. After the vitamin supplementation, serum folic acid levels increased significantly both in normo- and hyperhomocysteinemic subjects, unlike vitamin B12, which increased only in the hyperhomocysteinemic individuals. Plasma tHcy decreased significantly in the supplemented groups. Treatment with vitamins was not associated with improvement in EDD or antithrombotic function.
  
  
  CONCLUSIONS
  Mild hyperhomocysteinemia is not associated with endothelial dysfunction in young male subjects with no additional cardiovascular risk factors, and reduction of tHcy by vitamin supplementation does not modify EDD in this age group. In this sample, tHcy was more related to vitamin B12 than to folic acid status.
authors.affiliation: Institute of Nutrition and Food Technology, University of Chile, Santiago. shirsch@uec.inta.uchile.cl
authors.forename: Sandra
authors.initials: S
authors.lastname: Hirsch
authors.forename: M
authors.initials: M
authors.lastname: Pia De la Maza
authors.forename: Paulina
authors.initials: P
authors.lastname: Yañez
authors.forename: Andrea
authors.initials: A
authors.lastname: Glasinovic
authors.forename: Margarita
authors.initials: M
authors.lastname: Petermann
authors.forename: Gladys
authors.initials: G
authors.lastname: Barrera
authors.forename: Vivian
authors.initials: V
authors.lastname: Gattas
authors.forename: Edgardo
authors.initials: E
authors.lastname: Escobar
authors.forename: Daniel
authors.initials: D
authors.lastname: Bunout
mesh_terms: D000293:Adolescent; D000328:Adult; D019587:Dietary Supplements; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects*; D005492:Folic Acid / Q000097:blood / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000188:drug therapy*; D008297:Male; D014805:Vitamin B 12 / Q000097:blood / Q000627:therapeutic use*; D025101:Vitamin B 6 / Q000097:blood / Q000627:therapeutic use*
chemical_list: D006710:Homocysteine; D025101:Vitamin B 6; D005492:Folic Acid; D014805:Vitamin B 12