title: Effects of antioxidant supplementation on postprandial oxidative stress and endothelial dysfunction: a single-blind, 15-day clinical trial in patients with untreated type 2 diabetes, subjects with impaired glucose tolerance, and healthy controls.
abstract: BACKGROUND
  Increased generation of reactive oxygen species (ROS) and oxidative stress may be of crucial importance in the pathogenesis of endothelial damage. Furthermore, there is understood to be a relationship between endothelial damage, glycemic control, disorders of lipid metabolism, and coagulative hemostatic disorders.
  
  
  OBJECTIVE
  This study investigated within- and between-group changes in various circulating markers of oxidation-reduction balance and endothelial function after a balanced moderate-fat meal with and without antioxidant supplementation in patients with early-stage, untreated type 2 diabetes mellitus; subjects with impaired glucose tolerance (IGT); and healthy controls.
  
  
  METHODS
  In this single-blind, controlled clinical study, groups of patients with type 2 diabetes and subjects with IGT were identified and compared with a group of healthy controls. All groups followed a controlled, well-balanced diet for 10 days before and throughout the study. Before and after consumption of a standardized moderate-fat meal, plasma levels of oxidants (malondialdehyde, 4-hydroxynonenal, oxidized low-density lipoprotein), the antioxidant glutathione peroxidase, and markers of endothelial function (NO, endothelin-1, von Willebrand factor [vWF], vascular cell adhesion molecule-1 [VCAM-1]) were determined. These measures were then reassessed after 15 days of standard antioxidant treatment consisting of a thiol-containing antioxidant (N-acetylcysteine 600 g/d), a bound antioxidant (vitamin E 300 g/d), and an aqueous phase antioxidant (vitamin C 250 mg/d). The efficacy of antioxidant treatment in reversing abnormalities in oxidation-reduction balance after a moderate-fat meal was assessed by evaluating changes in plasma levels of ROS on the morning of the 16th day following an overnight fast. Safety was monitored in terms of adverse events, vital signs, physical findings, and laboratory values.
  
  
  RESULTS
  The study included 46 patients with type 2 diabetes (23 men, 23 women; mean [SD] age, 41 [3] years; mean body mass index [BMI], 24 [2] kg/m(2)), 46 with IGT (23 men, 23 women; mean age, 39 [3] years; mean BMI, 23 [3] kg/m(2)), and 46 control subjects (23 men, 23 women; mean age, 40 [1] years; mean BMI, 22 [1] kg/m(2)). Before supplementation, all 3 groups had significantly increased levels of oxidants, vWF, and VCAM-1 (all, P < 0.001) and significantly decreased levels of antioxidants and NO (both, P < 0.001) after consumption of a moderate-fat meal. After 15 days of antioxidant treatment, significant improvements in these measures were seen in all groups (P < 0.05).
  
  
  CONCLUSIONS
  This study showed changes in oxidation-reduction balance, NO bioavailability, and nonthrombogenic endothelial factors after a moderate-fat meal in patients with type 2 diabetes and those with IGT, but these postprandial changes were reverse in all subjects after 15 days of standard antioxidant supplementation. These findings suggest that the use of anti-oxidants may have decreased oxidative stress in these subjects.
authors.affiliation: Department of Internal Medicine and Systemic Disease, University of Catania, Via S. Sofia 86, 95123 Catania, Italy. sergio.neri4@tin.it
authors.forename: Sergio
authors.initials: S
authors.lastname: Neri
authors.forename: Salvatore S
authors.initials: SS
authors.lastname: Signorelli
authors.forename: Benedetto
authors.initials: B
authors.lastname: Torrisi
authors.forename: Davide
authors.initials: D
authors.lastname: Pulvirenti
authors.forename: Barbara
authors.initials: B
authors.lastname: Mauceri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Abate
authors.forename: Luca
authors.initials: L
authors.lastname: Ignaccolo
authors.forename: Fabio
authors.initials: F
authors.lastname: Bordonaro
authors.forename: Danila
authors.initials: D
authors.lastname: Cilio
authors.forename: Stefano
authors.initials: S
authors.lastname: Calvagno
authors.forename: Carmelo
authors.initials: C
authors.lastname: Leotta
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use; D000328:Adult; D000975:Antioxidants / Q000032:analysis / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D018149:Glucose Intolerance / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008297:Male; D016877:Oxidants / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D019518:Postprandial Period; D016037:Single-Blind Method; D014810:Vitamin E / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D001786:Blood Glucose; D016877:Oxidants; D014810:Vitamin E; D001205:Ascorbic Acid; D000111:Acetylcysteine