The direct relationship between traditional CVD risk factors and risk of atherosclerosis is well established. Dietary modifications which lower blood pressure and lipids provide a likely explanation for much of the risk reduction. However, oxidative stress, including oxidation of LDL-c (oxLDL) appears to be an important, if not obligatory step in the pathogenesis of atherosclerosis and may accelerate this process.26 Hence, measurement of oxidative stress using biomarkers may offer insight into mechanisms of CVD risk reduction beyond that which is predicted by lipids or other CVD risk factors alone.
Oxidative stress markers commonly used, including nonspecific in vitro 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). Formation of these oxidation products is dependant on free radical activity (i.e. metabolic rate), substrate concentration (i.e. lipids), and antioxidant activity (both endogenous and dietary). Hence, alterations in dietary patterns can give important insight into the benefit or harm of nutrients when linked to subsequent changes in markers of oxidative stress.
In the DASH trial, consumption of the DASH diet reduced breath ethane exhalation (an in vivo marker of oxidized n-3 polyunsaturated acids)17 and reduced urinary isoprostanes (an in vivo degradation product of arachidonic acid). These findings provide indirect evidence for reduced oxLDL in vivo. In addition, consumption of the DASH diet was previously shown to prevent an expected rise in urinary isoprostanes induced by acute hyperlipidemia.15 Consumption of the DASH diet resulted in increasing serum antioxidants and the ORAC of serum (Fig. 2.2).
A limitation of the ORAC assay is the inability to determine which component(s) of the diet provides the greatest activity in protecting against oxidative stress. However, consumption of the DASH diet resulted in increased serum levels of several carotenoids including lutein, cryptoxanthin, zeaxanthin and P-carotene,
important lipid soluble antioxidants. A proportionate increase in lipid peroxidation products derived from a higher polyunsaturated fat intake, can be diminished by supplementation of diet with plant-based sources of antioxidants such as flavenoids.11 In addition, supplementation of diet with carotenoid-rich vegetable products has been shown to enhance lipoprotein carotenoid concentrations and reduce lipid peroxidation in healthy men consuming a diet controlled for fat intake.4 Consumption of a diet high in fruit and vegetable has also been shown to increase endogenous enzymatic antioxidant activity (erythrocyte glutathionione peroxidase activity) and resistance of plasma lipoproteins to oxidation.9 Finally, reduced oxidative stress observed in the DASH trial may, in part, be explained by the higher serum content of these dietary antioxidants and enhanced antioxidant enzymatic activity.
Additional benefits of consumption of the Mediterranean diet may be related to a predominance of monounsaturated fat in the diet. Monounsaturated fats are more resistant to oxidation than polyunsaturated fats.1914 A higher proportional polyunsatu-rated fatty acid intake results in an increased number of double bonds (targets of oxidation) which has previously been linked to greater oxidation in vitro.7 The Mediterranean diet, compared with the typical US diet, is greatly reduced in polyunsaturated fatty acids. Hence, enrichment of diet with monounsaturated fatty acids will reduce the rate of oxidized lipids.27 Finally, olive oil is enriched with several compounds that constitute the unsaponified fraction of the oil, (hydrocarbons, sterols, and polyphenols), that prevent the oil from oxidation and underlie its exceptional stability.19
Collectively, these studies suggest that the consumption of the Mediterranean style diet may lower risk of CVD, independent of traditional CVD risk factors, via the increased antioxidants and reduced oxidative stress.
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