title: A dietary pattern that lowers oxidative stress increases antibodies to oxidized LDL: results from a randomized controlled feeding study.
abstract: BACKGROUND
  Oxidation of LDL (oxLDL) is thought to have an important role in early stages of atherogenesis. Antibody to oxLDL (Ab-oxLDL) has been proposed as a biomarker which might be directly associated with oxidative stress. Yet studies designed to test this hypothesis are lacking. We tested the hypothesis that consumption of a healthy diet rich in fruits and vegetables and reduced in saturated fat, total fat, and cholesterol will concomitantly reduce oxidative stress and Ab-oxLDL.
  
  
  METHODS
  One hundred and three healthy individuals were randomly assigned to consume a typical American (control) diet or the DASH diet rich in fruits, vegetables and low-fat dairy products and reduced in fat (27%), saturated fat (7%), and cholesterol (150 mg/day) for 3 months. Outcomes were urinary isoprostanes (in vivo marker of oxidative stress), oxygen radical absorbing capacity (ORAC, an in vitro assay measuring antioxidant activity in serum), and Ab-oxLDL measured at baseline, 1-3 months of feeding.
  
  
  RESULTS
  Compared to the control diet, consumption of the DASH diet significantly lowered urinary isoprostane (-226 pg/ml, 95% CI: -420 to -32, P=0.023). Compared with the control group, change in ORAC was higher in the DASH group, 143 trolox units/ml (95% CI: -23 to 308, P=0.091). In comparison with the control diet, increased titers of Ab-oxLDL (37 mU/ml [95% CI: 16-57, P=0.006]) were seen after consumption of the DASH diet. Higher titers of Ab-oxLDL occurred at month 2 (56 mU/ml, 95% CI: 20-90, P=0.004) and month 3 (41 mU/ml, 95% CI: -6 to 88, P=0.082), after initially small increases at month 1 (20 mU/ml, 95% CI: -10 to 51, P=0.176). End-of-study increases in AB-oxLDL were highly correlated with increased ORAC (Spearman's rho=0.46, P<0.0001), but not with changes in specific carotenoids, tocopherols or with change in LDL cholesterol (each: P>0.10).
  
  
  CONCLUSIONS
  Consumption of a healthy diet replete in antioxidants reduced oxidative stress (urinary isoprostanes) yet increased Ab-oxLDL. This indirect association of Ab-oxLDL with urinary isoprostanes hinders use of Ab-oxLDL as a marker of oxidative damage.
authors.affiliation: Welch Center for Prevention, Epidemiology and Clinical Research, The Johns Hopkins Medical Institutions, 2024 East Monument Street, Suite 2-624, Baltimore, MD 21205-2223, USA. ermiller@jhmi.edu
authors.forename: Edgar R
authors.initials: ER
authors.lastname: Miller
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Erlinger
authors.forename: Frank M
authors.initials: FM
authors.lastname: Sacks
authors.forename: Laura P
authors.initials: LP
authors.lastname: Svetkey
authors.forename: Jeanne
authors.initials: J
authors.lastname: Charleston
authors.forename: Pao-Hwa
authors.initials: PH
authors.lastname: Lin
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Appel
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001323:Autoantibodies / Q000096:biosynthesis* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D015415:Biomarkers; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000494:pharmacology; D018752:Diet, Fat-Restricted; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005638:Fruit; D006801:Humans; D028421:Isoprostanes / Q000652:urine; D008077:Lipoproteins, LDL / Q000276:immunology*; D008297:Male; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D014675:Vegetables
chemical_list: D000975:Antioxidants; D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D002791:Cholesterol, Dietary; D004041:Dietary Fats; D028421:Isoprostanes; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein