**11. Olive oil**

mannite, ellagic acid and gallic acid and the bark and rind contain various tannins. The pol‐ yphenols in pomegranate are believed to provide the anti-oxidant activity and protect LDL against cell-mediated oxidation directly by interaction with the LDL [49]. In fact, the supple‐ mentation of pomegranate juice revealed a significant reduction in the atherosclerotic lesion area compared to the water-treated group reporting significant anti-oxidant capacities of all

The principal mechanisms of action of pomegranate juice may include: increased serum an‐ ti-oxidant capacity, decreased plasma lipids and lipid peroxidation, decreased ox-LDL up‐ take by macrophages, decreased intima-media thickness, decreased atherosclerotic lesion areas, decreased inflammation and decreased systolic blood pressure, thereby reducing/ inhibiting the progression of atherosclerosis and the subsequent potential development of

On the basis of limited safety data, high doses of pomegranate polyphenol extracts may have some deleterious effects: gastric irritation, allergic reactions, including pruritus, urtica‐ ria, angioedema, rhinorrhea, bronchospasm, dyspnea and red itchy eyes. Moreover, dried pomegranate peel may contain aflatoxin, a potent hepatocarcinogen; thus, it should be used cautiously by patients who have hepatic dysfunction or who are taking other hepatotoxic agents. Pomegranate may also increase the risk for rhabdomyolysis during statin therapy, as

a result of intestinal CYP3A4 inhibition and increased absorption of active drugs [49].

The last two decades have seen renewed interest in the health benefits of wine, as documented by increasing research and several epidemiologic observations showing that moderate wine drinkers have lower cardiovascular mortality rates than heavy drinkers or teetotalers. Most of the beneficial effects of wine against CVDs have been attributed to the presence in red wine of resveratrol and other polyphenols. Wines contain polyphenolic compounds that can be rough‐ ly classified in flavonoid and non flavonoid compounds; both classes of compounds have been implicated in the protective effects of wine on the cardiovascular system. Resveratrol is one of

Moderate wine intake reduces cardiovascular risk [51]. In addition, it is known that alcohol favourably modifies the lipid pattern by decreasing total plasma cholesterol, in particular LDL, and by increasing HDL. Cardiovascular risk reduction seems to be linked largely to the effect of non-alcoholic components, mainly resveratrol and other polyphenols, on the vascular wall and blood cells and a great part of the beneficial effects of resveratrol on vas‐

The effect of resveratrol and other wine polyphenols on oxidative stress has been scarcely explored in humans and only a few studies have analyzed the effects of wine supplementa‐

the most biologically active polyphenols contained in wine.

cular function are due to its anti-oxidant effects.

tion on indexes of oxidation *in vivo* [36].

pomegranate extracts.

14 Current Trends in Atherogenesis

CVDs [30,50].

**10. Wine**

A high intake of some unsaturated fatty acid and/or anti-oxidant compounds can both re‐ duce pro-atherogenic risk factors and the susceptibility of the vascular wall to pro-inflam‐ matory and pro-atherogenic triggers.

Many Authors started to recognize olive oil as one of the key elements in the cardioprotec‐ tion and longevity of inhabitants of Mediterranean regions. The healthful properties of olive oil have been often attributed to its high content of monounsaturated fatty acids, namely oleic acid [7]. However, it should be underlined that olive oil, unlike other vegetable oils, contains high amounts of several micronutrient constituents, including polyphenolic com‐ pounds (100– 1000 mg/kg) [10].

The major phenolic compounds in olive oil are: simple phenols (*i.e.*, hydroxytyrosol, tyro‐ sol); polyphenols (oleuropein glucoside); secoiridoids, dialdehydic form of oleuropein and ligstroside lacking a carboxymethyl group and the aglycone form of oleuropein glucoside and ligstroside and lignans. Around 80% or more of the olive oil phenolic compounds are lost in the refination process, thus, their content is higher in virgin olive oil (around 230 mg/ kg) than in other olive oils.

Olive oil supplementation (50 mg/day) to the diet enriched LDL with oleic acid and signifi‐ cantly reduced human LDL susceptibility to *in vitro* oxidation, thus making them signifi‐ cantly less atherogenic. In part, this reflects the lesser susceptibility of monounsaturated fatty acids to lipid peroxidation compared with that of polyunsaturated fatty acids, which are particularly prone to peroxidation due to the greater number of double bonds [10,52].

Olive oil consumption could reduce oxidative damage, on one hand, due to its richness in oleic acid and, on the other hand, due to its minor components of the olive oil particularly the phenolic compounds. The phenolic content in virgin olive oil could reduce the lipid oxi‐ dation and inhibit platelet-induced aggregation [53].

of CVD onset. On the other hand, elements like cadmium, lead, silver, mercury and thallium

Atherosclerosis and Current Anti-Oxidant Strategies for Atheroprotection

http://dx.doi.org/10.5772/53035

17

Magnesium deficiency is considered to be a risk factor of CVDs, in fact its supplementation delays the onset of atherosclerosis or hinders its development. On the other hand, silicon is a major trace element in animal diets and humans ingest between 20-50 mg/day of silicon with the Western diet [59]. Main dietary sources are whole grain cereals and their products (including beer), rice, some fruits and vegetables and drinking water, especially bottled min‐ eral waters with geothermal and volcanic origin [60]. Numerous studies showed that silicon has a role in maintaining the integrity, the stability and the elastic properties of arterial walls [61,62] and postulated silicon as a protective factor against the development of age-linked

In addition, vanadium is considered to have anti-atherosclerotic properties; lithium can also inhibit the synthesis of cholesterol, but has an atherogenous activity that can be inhibited by supplementation with appropriate quantities of calcium. A copper-deficient diet can induce hypercholesterolemia and hypertriglyceridemia that is, in turn, intensified by high levels of

On the basis of these limited data, intakes of silicon, magnesium and vanadium in water and avoiding exposure to cadmium and lead are important elements of the prophylaxis of CVDs, so hard water has positive health effects and should not be replaced by drinking wa‐ ter with insufficient amounts of beneficial elements [58]. It is important to remember also that water has small contribution of mineral trace respect to total dietary intake (7% from

Melatonin, an endogenously produced indoleamine, is a remarkably functionally pleiotropic molecule [66] which functions as a highly effective anti-oxidant and free radical scavenger [67,68]. Endogenously produced and exogenously administered melatonin has beneficial ac‐

Exogenously administered melatonin is quickly distributed throughout the organism; it may cross all morphophysiological barriers and it enters cardiac and vascular cells easily. High‐ est intracellular concentration of melatonin seem to be in the mitochondria; this is especially important as the mitochondria are a major site of free radicals and oxidative stress genera‐ tion. Moreover, melatonin administration in a broad range of concentration, both by the oral

Melatonin itself appears to have an atheroprotective activity during LDL oxidation and also melatonin's precursors and breakdown products inhibit LDL oxidation, comparable to vita‐ min E. Because of its lipophilic and nonionized nature, melatonin should enter the lipid phase of the LDL particles and prevent lipid peroxidation [9] and may also augments en‐

and intravenous routes, has proven to be safe for human studies [72,73].

vascular diseases, such as atherosclerosis and hypertension [62,63].

are considered to be harmful [58].

dietary zinc [58,64].

liquid vs 93% from solid food) [58,65].

**13. Melatonin supplementation**

tions on the cardiovascular system [69,70,71].

dogenous cholesterol clearance.

Moreover, olive oil minor components have also been involved in the anti-oxidant activity of olive oil. Some components of the unsaponifiable fraction, such as squalene, β-sitosterol or triterpenes, have been shown to display anti-oxidant and chemopreventive activities and capacity to improve endothelial function decreasing the expression of cell adhesion mole‐ cules and increasing vasorelaxation [54].

Olive oil phenolic compounds are able to bind the LDL lipoprotein and to protect other phe‐ nolic compounds bound to LDL from oxidation. The role of phenolic compounds from olive oil on DNA oxidative damage remains controversial and perhaps more sensitive methods would be required to detect differences among the types of olive oil consumed. Further studies are required to establish the potential benefits of olive oil and those of its minor com‐ ponents on DNA oxidative damage.

One of the most well known and important characteristic of the Mediterranean diet is the presence of virgin olive oil as the principal source of energy from fat. In contrast to other edible oils with a similar fatty composition, like sunflower, soybean and rapeseed canola oils, virgin olive oil is a natural juice, while the seed oils must be refined before consump‐ tion, thus changing its original composition during this process. Virgin olive oils are those obtained from the olives solely by mechanical or other physical means under conditions that do not lead alteration in the oil. The olives have not undergone any treatment other than washing, decantation, centrifugation or filtration [53].

Virgin olive oil is a source of healthy unsaturated fatty acids and hundreds of micronu‐ trients, especially anti-oxidants, as phenol compounds, vitamin E and carotenes.

Results of the randomized cross-over clinical trials performed in humans on the anti-oxidant effects of olive oil phenolic compounds are controversial. The protective effects on lipid oxi‐ dation in these trials have been better displayed in oxidative stress conditions, i.e. males, submitted to a very strict anti-oxidant diet, hyperlipidaemic or peripheral vascular disease patients. Carefully controlled studies in appropriate populations, or with a large sample size, are urgently required to definitively establish the *in vivo* anti-oxidant properties of the active components of virgin olive oil [55].
