title: Six-year effect of combined vitamin C and E supplementation on atherosclerotic progression: the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) Study.
abstract: BACKGROUND
  Self-selected supplementation of vitamin E has been associated with reduced coronary events and atherosclerotic progression, but the evidence from clinical trials is controversial. In the first 3 years of the ASAP trial, the supplementation with 136 IU of vitamin E plus 250 mg of slow-release vitamin C twice daily slowed down the progression of carotid atherosclerosis in men but not women. This article examines the 6-year effect of supplementation on common carotid artery (CCA) intima-media thickness (IMT).
  
  
  RESULTS
  The subjects were 520 smoking and nonsmoking men and postmenopausal women aged 45 to 69 years with serum cholesterol > or =5.0 mmol/L (193 mg/dL), 440 (84.6%) of whom completed the study. Atherosclerotic progression was assessed ultrasonographically. In covariance analysis in both sexes, supplementation reduced the main study outcome, the slope of mean CCA-IMT, by 26% (95% CI, 5 to 46, P=0.014), in men by 33% (95% CI, 4 to 62, P=0.024) and in women by 14% (not significant). In both sexes combined, the average annual increase of the mean CCA-IMT was 0.014 mm in the unsupplemented and 0.010 mm in the supplemented group (25% treatment effect, 95% CI, 2 to 49, P=0.034). In men, this treatment effect was 37% (95 CI, 4 to 69, P=0.028). The effect was larger in subjects with either low baseline plasma vitamin C levels or CCA plaques. Vitamin E had no effect on HDL cholesterol.
  
  
  CONCLUSIONS
  These data replicate our 3-year findings confirming that the supplementation with combination of vitamin E and slow-release vitamin C slows down atherosclerotic progression in hypercholesterolemic persons.
authors.affiliation: Research Institute of Public Health, University of Kuopio, Finland. jukka.salonen@uku.fi
authors.forename: Riitta M
authors.initials: RM
authors.lastname: Salonen
authors.forename: Kristiina
authors.initials: K
authors.lastname: Nyyssönen
authors.forename: Jari
authors.initials: J
authors.lastname: Kaikkonen
authors.forename: Elina
authors.initials: E
authors.lastname: Porkkala-Sarataho
authors.forename: Sari
authors.initials: S
authors.lastname: Voutilainen
authors.forename: Tiina H
authors.initials: TH
authors.lastname: Rissanen
authors.forename: Tomi-Pekka
authors.initials: TP
authors.lastname: Tuomainen
authors.forename: Veli-Pekka
authors.initials: VP
authors.lastname: Valkonen
authors.forename: Ulla
authors.initials: U
authors.lastname: Ristonmaa
authors.forename: Hanna-Maaria
authors.initials: HM
authors.lastname: Lakka
authors.forename: Meri
authors.initials: M
authors.lastname: Vanharanta
authors.forename: Jukka T
authors.initials: JT
authors.lastname: Salonen
authors.forename: Henrik E
authors.initials: HE
authors.lastname: Poulsen
mesh_terms: D000368:Aged; D000975:Antioxidants / Q000009:adverse effects / Q000627:therapeutic use*; D001161:Arteriosclerosis / Q000097:blood / Q000000981:diagnostic imaging / Q000517:prevention & control*; D001205:Ascorbic Acid / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D002340:Carotid Artery Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000517:prevention & control*; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging; D008076:Cholesterol, HDL / Q000097:blood; D003692:Delayed-Action Preparations; D019587:Dietary Supplements; D018450:Disease Progression; D004359:Drug Therapy, Combination; D028441:F2-Isoprostanes / Q000097:blood; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D013997:Time Factors; D014463:Ultrasonography; D014810:Vitamin E / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D008076:Cholesterol, HDL; D003692:Delayed-Action Preparations; D028441:F2-Isoprostanes; D014810:Vitamin E; D001205:Ascorbic Acid