A dietary pattern that lowers oxidative stress increases antibodies to oxidized LDL: Results from a randomized controlled feeding study

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 (Spearmanʹs ρ = 0.46, P < 0.0001), but not with changes in specific carotenoids, tocopherols or with change in LDL cholesterol (each: P > 0.10). Conclusion: 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.