Antioxidant effect of virgin olive oil in patients with stable coronary heart disease: a randomized, crossover, controlled, clinical trial

Abstract

The Mediterranean diet, in which olive oil is the main source of fat, has been associated with a reduced incidence of coronary heart disease (CHD) and low blood pressure levels. Virgin olive oil (VOO), besides containing monounsaturated fat, is rich in phenolic compounds (PC) with antioxidant properties. The aim of this study was to examine the antioxidant and anti-hypertensive effect of two similar olive oils, but with differences in their PC (refined: 14.7 mg/kg versus virgin: 161.0 mg/kg), in 40 males with stable CHD. The study was a placebo controlled, crossover, randomized trial. A raw daily dose of 50 mL of VOO and refined olive oil (ROO) were sequentially administered over two periods of 3 weeks, preceded by 2-week washout periods in which ROO was used. Lower plasma oxidized LDL (p < 0.001) and lipid peroxide levels (p = 0.003), together with higher activities of glutathione peroxidase (p = 0.033), were observed after VOO intervention. Systolic blood pressure decreased after intake of VOO (p = 0.001) in hypertensive patients. No changes were observed in diastolic blood pressure, glucose, lipids, and antibodies against oxidized LDL. Consumption of VOO, rich in PC, could provide beneficial effects in CHD patients as an additional and complementary intervention to the pharmacological treatment.

Introduction

The Mediterranean diet, in which olive oil is the main source of fat, is associated with a decrease in overall and cardiovascular mortality [1]. Diets rich in monounsaturated fatty acids (MUFA) are used to manage cardiovascular disease risk, provided that they do not exceed the saturated fatty acid (SFA) recommendation and compromise weight control [2]. On the other hand, olive oil-rich diets have shown to reduce low-density lipoprotein (LDL) oxidation [3].

Oxidation of LDL is a hallmark for atherosclerosis and coronary heart disease (CHD) development [4]. One of the earliest steps in the generation of oxidized LDL (oxLDL) is the lipid peroxidation of polyunsaturated fatty acids (PUFA). Tissue membranes that are rich in PUFA are more susceptible to oxidation by free radicals than membranes rich in MUFA [5]. However, lipid peroxidation, and its chain reaction in LDL, can be interrupted if LDL lipids are protected from free radicals by antioxidants.

Olive oil is rich in MUFA and antioxidant compounds. The concentration of antioxidants in olive oils is influenced by the olive oil extraction procedures. Virgin olive oil (VOO), obtained exclusively by physical procedures, is much more than a MUFA fat because it contains relatively high amounts of antioxidants, mainly phenolic compounds (PC). However, PC are lost when the olive oil is refined. The main PC in olive oil are oleuropein and ligstroside aglycones which by hydrolysis both give hydroxytyrosol (OHT) and tyrosol (T) [6]. Both free forms of T, OHT and their secoroid and conjugated forms, represent around 80% of the PC present in a virgin olive oil [7]. Olive oil PC have been shown to protect LDL from lipid peroxidation in in vitro experiments [8]. Animal studies suggest a protective effect of olive oil phenolics on LDL oxidation [9]. However, the information from randomized, crossover, controlled intervention trials in humans, which provides first level of scientific evidence, on the in vivo effects of olive oil rich in PC is scarce and controversial [10], [11], [12], [13].

Compared with a saturated fat diet, the Mediterranean diet has been found to be associated with lower levels of blood pressure [14]. In the few studies concerning the relationship between olive oil consumption and blood pressure levels, olive oil consumption was effective in lowering blood pressure in hypertensive patients [15], [16]. Hypertension is related to endothelial dysfunction which contributes to make the atherosclerotic plaque more unstable, thus increasing the risk of secondary events in CHD patients [17]. On the other hand, a relationship exists between oxidative stress and LDL oxidation with endothelial dysfunction [18].

Thus, the first aim of the present study was to evaluate the effect of both VOO and refined virgin olive oil (ROO) with differences in their PC concentration, on oxidative stress in stable CHD patients. The second aim was to compare the effects of olive oil on blood pressure in hypertensive and stable CHD patients. A randomized, crossover, placebo controlled trial study was designed.