Miller ER 3rd, Erlinger TP, Sacks FM, Svetkey LP, Charleston J, Lin PH, Appel LJ.
A dietary pattern that lowers oxidative stress increases antibodies to oxidized LDL: Results from a
randomized controlled feeding study.
Atherosclerosis. 2005 Nov;183(1):175-82. Epub 2005 Apr 18.
PMID: 16216596
The direct relationship between LDL cholesterol (LDL-c) and risk of atherosclerosis is well established.
Oxidation of LDL-c appears to accelerate this process [1–3]. Hence, measurement
of oxidized LDL-c (oxLDL) has been proposed as a biomarker of cardiovascular disease risk beyond that
which is predicted by LDL-c. While this is an appealing hypothesis, measurement of oxidation of LDL
(oxLDL) has methodological barriers, which limit its use in epidemiological studies.
Instead, non-specific markers of oxidative stress, including assays to determine the susceptibility of lipids
to oxidation (i.e., lag time, thiobarbituric acid substances, malondialdehyde, oxygen radical absorbing
capacity (ORAC) or assays that measure, in vivo, end-product of oxidative damage to lipids (e.g., breath
ethane or urinary isoprostanes)), are commonly used. However, because these assays may not reflect
oxLDL directly, their interpretation is limited. As an alternative, the antibody titer to oxLDL-c (AboxLDL) has been proposed as a more direct estimate of oxLDL antigen in vivo [4,5]. This assay has greater
appeal in part because of its wide commercial availability and better measurement standardization.
While many observational studies have shown direct associations between Ab-oxLDL and established
atherosclerosis [6–14], others have not [15–17]. Uncertainties about the interpretation of Ab-oxLDL, are
based in part, on the finding that titer of Ab-oxLDL is highly dependent on the balance between free radical
activity and antioxidant activity. For example, diabetes is a state of high oxidative stress and is associated
with high Ab-oxLDL [18,19]. However, there is an inverse association between diabetes control
(hemoglobin A–1C) and Ab-oxLDL titer, suggesting that Ab-oxLDL is more rapidly removed from
circulation under conditions of high oxidative stress resulting in lower serum levels. In addition, a low titer
of Ab-oxLDL with poor diabetes control is associated with high levels of circulating immune complex
oxLDL/Ab-oxLDL) [18,20]. Hence, simultaneous measurement of oxidative stress and Ab-oxLDL
may be critical in the interpretation of titers of Ab-oxLDL [21]. We previously documented, in the setting
of a randomized controlled feeding study, that consumption of a healthy diet rich in fruits and vegetables
and reduced in saturated fat, total fat, and cholesterol reduces oxidative stress (i.e., reduces in
vivo oxidation of lipids) and increases antioxidant activity [22]. The objective of this study is to examine
effects of this diet on the response of Ab-oxLDL titers in the setting of a randomized, controlled feeding
trial.
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