Abstract
Beneficial health effects of olive oil and its phenolics are presented in light of the Mediterranean diet (MD), which is characterized by (1) a high intake of cereals, vegetables including leafy greens, legumes, nuts, and fruit; (2) a moderate intake of poultry, fish, eggs, milk and dairy products, as well as a regular but moderate ethanol consumption (generally in the form of wine during meals); and (3) a low intake of red and processed meat and industrial confectionary. Olive oil (OO) is the main fat used in all preparations of the MD. The health benefits of consuming OO have been known since antiquity and were traditionally attributed to its high MUFA content, mainly oleic acid. A large number of epidemiological and laboratory studies suggest beneficial and protective effects of OO in reduced risk of suffering cardiovascular disease (CVD) and cerebrovascular diseases, diabetes mellitus, metabolic syndrome, certain cancers, and neurodegenerative diseases. Potential effects of OO on various diseases-related parameters are discussed in relation to OO and its phenolics.
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1 Introduction
In a number of studies, the Mediterranean diet (MD) has been connected with longevity and a reduced risk of morbidity and mortality. Life-style factors, such as regular physical activity, a healthy diet, and the existing social cohesion in southern European countries have been recognized as candidate protective elements which may explain the Mediterranean paradox. The term MD was coined in the 1960s by Ancel Keys within the framework of the Seven Countries Study. This epidemiological study with more than 12,000 individuals reported that Italian and Greek populations had lower mortality rates, and a reduced incidence of cancer and cardiovascular disease (CVD), compared to those from other European countries, America, and Asia [1]. Such findings led to an exponential increase from 1999 of original articles regarding the MD [2]. High adherence to this diet pattern has been associated with a reduction in the risk of suffering CVD and cerebrovascular diseases, diabetes mellitus, metabolic syndrome, certain cancers, and neurodegenerative diseases [3]. The link between adherence to the MD and a reduction in total mortality has also been confirmed [4, 5].
In general, the MD is characterized by (1) a high intake of cereals, vegetables including leafy greens, legumes, nuts, and fruit; (2) a moderate intake of poultry, fish, eggs, milk and dairy products, as well as a regular but moderate ethanol consumption (generally in the form of wine during meals); and (3) a low intake of red and processed meat and industrial confectionary [4,5,6,7]. Along with some other traits of the Mediterranean diet, the use of olive oil (OO), as the main source of fat (especially dressings), is common in southern European countries. A relatively high fat consumption (up to 40% of total energy intake), mostly from monounsaturated fatty acids (MUFAs) (up to 20% of total energy consumption) is characteristic of this diet [8]. In the Mediterranean area, it is estimated that subjects consume between 25 and 50 mL of OO per day (raw and that used for cooking). Nevertheless, its consumption varies around the Mediterranean countries.
The health benefits of consuming OO have been known since antiquity and were traditionally attributed to its high MUFA content, mainly oleic acid. In this regard, a recent meta-analysis of 32 cohort studies with the aim of studying MUFA (of both plant and animal origin), oleic acid, MUFA/saturated fatty acid (SFA) ratio, and OO intake, indicated that, when comparing the upper to the lower tertile of consumption, OO, but not MUFA, was associated with a reduced risk of all-cause mortality, CVD events, and stroke [9]. Thus, the extra constituents of OO may also have a protective potential [10,11,12].
2 Cancer
Cancer is a multifactorial disease in which several aberrant processes are involved (deregulation of cell cycle, abnormal expression of pro-oncogenes, deregulated angiogenesis, excessive oxidative stress, chronic inflammatory responses, etc.). Several lifestyle factors such as smoking, unhealthy eating, and sedentary habit can increase the predisposition to develop cancer. Thirty to 40% of all cancers could be prevented by appropriate diets, physical activity practice, and maintenance of appropriate body weight [13]. Traditionally, a high consumption of fruit and vegetables has been inversely related to chronic degenerative diseases such as cancer [13, 14]. In the EPIC study, fiber intake from cereals, fruit, and vegetables showed a protective effect on colorectal cancer, and fruit consumption was also associated with lower rates of lung cancer [15]. Among the Mediterranean countries, meta-analyses of ecological and cohort studies found that cancer morbidity and mortality are lower than in other ones [16]. A high adherence to the MD, in which OO is the main source of fat, has been associated with reduced mortality for all type of cancers in prospective studies [5]. Around 25% of colorectal cancer incidence, 15% of breast cancer, and 10% of prostate, pancreas, and endometrial cancer could be prevented by a TMD in the Western countries [17]. Recently, a 4.8-year adherence to a traditional MD (supplemented with virgin olive oil (VOO) or nuts) was found to protect against breast cancer development in an elderly women [18]. In contrast, in Mediterranean cohorts within the framework of the EPIC Study, OO consumption was not linked to lower breast cancer risk in postmenopausal women. Nevertheless, an inverse association between OO intake and the levels of estrogens and progesterone receptor-negative tumors was suggested [19]. Also within the EPIC Study, the adherence to an MD was associated with a decrease in the incidence of gastric adenocarcinoma [20]. In this respect, the antimicrobial activity conferred by OO against Helicobacter pylori (a microorganism related to gastric ulcers and subsequent carcinomas) could play a role in such an observation [21]. Finally, in Caucasian populations in the Mediterranean basin, prostate cancer incidence is lower than that in Caucasian males from other areas. The richness of MUFAs versus SFAs in the MD pattern has been postulated as a possible explanation [22].
With reference to OO, an inverse association between its intake and the appearance of different types of cancers has been described mainly from case-control studies [23]. In this respect, a meta-analysis of case-control studies assessing the effects of OO and MUFA intake was performed (N = 19, 13,800 cancer patients and 23,340 controls). Subjects in the group with the highest OO consumption presented lower odds of suffering any type of cancer (logOR = −0.41; CI: [−0.53, −0.29]). Considering different cancer origins, the meta-analysis showed that high OO intake is linked to a lesser probability of having cancer of the digestive tract (logOR = −0.36; CI: [−0.50, −0.21]) and breast cancer (logOR = −0.45; CI: [−0.78, −0.12]) [24].
In a clinical trial, patients with advanced cancer received a dietary intervention rich in oleic acid and Gc protein-derived macrophage activating factor (GcMAF) which can inhibit cancer cell proliferation. The diet, which was low in carbohydrates, rich in proteins, fermented milk products (which contains naturally-produced GcMAF), Vitamin D3, and omega-3 fatty acids, enhanced the immune system, and a 25% reduction in tumor volume was observed [25].
3 Neurodegenerative Diseases
Chronic inflammatory status, together with oxidative stress, affects neuron functionality. Oxidation and inflammation processes promote the deposition of a number of proteins inside neurons, consequently, the correct function of the mitochondria becomes impaired. When these processes are perpetuated over a long period of time, the development of several neurodegenerative diseases can occur. In particular, Alzheimer’s disease, which is one of the greatest challenges of any national health system, given the population aging. As there is no curative treatment to date, preventive strategies based on a healthy aging are being promoted. A number of epidemiological studies suggests that several nutrients (such as antioxidants, E and B-vitamins, and polyunsaturated fatty acids) [26], and foods (such as fish, vegetables, fruit, and wine) [27] may decline cognitive impairment, including Alzheimer’s disease [28]. As oxidative stress can play a role in the development of neurodegenerative diseases [29], the intake of phenolic compounds (PCs), with a considerable spectra of bioactivities in vitro and in vivo, has been proposed for their management [30].
Given the association between cardiovascular risk factors and neurodegenerative ones, the cardiovascular health benefits of the MD can also confer protection against neurodegenerative disorders [31]. While diets rich in saturated fats and simple carbohydrates are linked to neurodegenerative diseases [32], the MD is able to enhance cognitive function. An association between MD adherence and delay in cognitive decline was observed in elderly subjects in a prospective cohort study in France [6]. Moreover, in elderly individuals at high cardiovascular risk following the MD, better cognitive efficiency [28] and performance were reported [33]. The majority of these studies have been performed in the Mediterranean areas; nevertheless, other projects have been conducted in non-Mediterranean countries which suggest that the healthy benefits of an MD can be transferred to other populations. In this respect, greater adherence to the MD pattern was linked to a reduced risk of Alzheimer’s disease with approximately 2000 subjects in New York [7].
The reduced vascular comorbidities observed with an MD, together with its richness in compounds with antioxidant and anti-inflammatory effects, can play a role in central nervous system benefits [34,35,36]. In this regard, VOO, one of the key foods of the MD pattern, has been linked to improved cognitive function due to its relevant bioactive compounds [28]. Hydroxytyrosol, oleuropein, and especially oleuropein aglycon have been shown to inhibit Tau aggregation in vitro [37].
4 Diabetes Mellitus
4.1 Type-II Diabetes and Impaired Glucose Tolerance
Impaired glucose tolerance is defined as high blood glucose levels after eating, whereas impaired fasting glucose is defined as high blood glucose after a period of fasting. People with impaired glucose tolerance are at high risk of developing DM2. Unsurprisingly, impaired glucose tolerance shares many characteristics with DM2 and is associated with obesity, advancing age, and the inability of the body to use the insulin it produces. Not everyone with impaired glucose tolerance goes on to develop DM2 [38]. DM2 is a chronic disease that occurs either when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces. Hyperglycemia is a common effect of uncontrolled diabetes and over time leads to serious damage to many of the body's systems, especially the nerves and blood vessels [39]. Some 382 million people worldwide, or 8.3% of adults, are estimated to have diabetes. According to International Diabetes Federation, the causes are still unclear but people with overweight, poor diet, lack of physical activity, and family story of diabetes are at high risk of DM2 [38].
Several studies have found a link between MD and glucose metabolism. The ATTICA study observed that adherence to MD was related to better homoeostasis factors related to fasting glucose (fasting plasma glucose, insulin levels and the insulin resistance index: HOMA) in normoglycemic people [40]. Moreover, PREDIMED study found that a long-term intervention with a high-quality dietary pattern based on traditional MD and rich in EVOO could reduce the incidence of DM2 in older people at high cardiovascular risk. This beneficial effect was mainly due to the overall composition of the dietary pattern and not to calorie restriction, increased physical activity, or weight loss [41]. A couple of meta-analysis [42, 43] also found a significant association between adherence to dietary patterns and decreased risk of DM2. One of the previous meta-analysis specifically concluded that adherence to a MD is associated with a decreased risk of becoming diabetic at a reasonable magnitude (19%) [43]. Other systematic review of eight meta-analyses and five randomized controlled trials studied the effect of MD on the treatment of DM2 and prediabetic states. This review indicated that in DM2 patients, the adherence to MD was associated with lower glycated hemoglobin (HbA1c) levels and improved cardiovascular risk factors, as compared with control diets, mainly lower fat diets [44]. Thus, it is suggested that the Mediterranean diet is not only suitable for prevention but it is also an appropriate dietary pattern for the management of DM2.
Another meta-analysis of prospective cohort studies to assess the association between different diets and prevention of DM2 found that although the diets associated with prevention of DM2 may vary in their composition, nonetheless they shared several common components, including whole grains, fruit, vegetables, nuts, legumes, protein sources such as white meat and seafood, little or moderate alcohol, and reduced intake of red and processed meats and sugar-sweetened beverages, and noteworthy healthy table oils (i.e., olive oil) [45]. MD covers all of the above being one of its emblematic characteristics is the use of olive oil.
One of olive oil’s characteristics is its high content in monounsaturated fatty acids (MUFA). Evidence suggests that diets enriched in MUFAS from OO have a positive effect in glycemic control. A study examining intakes of MUFA through the increased consumption of olive oil found an association with lower fasting plasma glucose concentration [46, 47]. Another cohort study of women found a similar result after a 22 years follow-up. The published results showed that higher olive oil intake was associated with modestly lower risk of DM2 and that hypothetically substituting other types of fats and salad dressings (stick margarine, butter, and mayonnaise) with olive oil was inversely associated with the onset of DM2 [48]. In another cross-sectional study in Spain (Pizarra study), it was found that insulin resistance was significantly lower in people who consumed OO than in those who consumed sunflower oil or a mixture [167].
Furthermore, a randomized trial with two groups of DM2 patients, following a MD using OO or a control low-fat diet presented that the MD with OO can improve endothelial dysfunction, inflammation, and oxidative in DM2 patients compared to a control diet [49]. The PREDIMED trial also provides strong evidence that long-term adherence to a MD supplemented with EVOO, which is high in MUFAS and bioactive polyphenols, results in a substantial reduction in the risk for DM2 among older people with high cardiovascular risk [41].
Oleic acid (cis C18:1 n-9), the predominant MUFA on OO, has been related to a lower insulin resistance as well. A study addressing [50] the relationship between changes in membrane fatty acid composition and glucose transport as an index of insulin sensitivity found a reduction in insulin resistance when a polyunsaturated (linoleic acid; C18:2 n-6) rich diet was changed to an oleic acid (C18:1 n-9) rich diet. This improvement was related to the change in membrane fluidity, as an oleic acid-rich membrane would be less fluid to its linoleic acid-rich equivalent [46]. Similar results were found in another study [51] where changes in membrane fatty acids and signaling proteins induced by VOO consumption in elderly persons with DM2 compared to a control group were analyzed. The long-term consumption of VOO induced changes in the fatty acid content of erythrocyte membranes from elderly DM2 participants. These changes were due to an increase amount of oleic acid in the membranes and in consequence biochemical changes in the amount of signaling proteins (G proteins and protein kinase C). The above could explain the mechanisms of glycemic homeostasis after consumption of olive oil.
In addition to MUFA, extra virgin olive oil contains also other bioactive components, some of them are called the phenolic compounds such as oleuropein and hydroxytyrosol, flavonoids, specially flavones, and lignans. Apart from PREDIMED, other clinical trials have evaluated the effect of EVOO rich in polyphenols on glycemic biomarkers [52]. Daily consumption of polyphenol-rich EVOO (25 mL/day, 577 mg of phenolic compounds/kg) for 8 weeks significantly reduced fasting plasma glucose and HbA1c, as well as other circulating inflammatory adipokines (visfatin), in overweight patients with DM2 [53], in a crossover randomized trial.
Mediterranean-type dietary patterns are known to improve several parameters of the postprandial state with high atherogenic potential, such as the glycemic load and the secretion and clearance of chylomicrons [54]. The consumption of OOPCs has been able to decrease oxidative stress (as observed in several biomarkers related to oxidative modifications of plasma lipids, proteins, and DNA) in healthy volunteers after meals [10] and in long-term interventions [11]. Concretely, a single dose of 25 mL of OO does not promote postprandial oxidative stress whereas doses equal or superior to 40 mL do [10, 55]. In addition, phenolic compounds from OO have been able to modulate postprandial oxidative stress in healthy volunteers [10]. The glycemic load of a meal can depend on the bioavailability of carbohydrates and food preparation. In this regard, in a study with 12 women with obesity and insulin resistance, food fried in VOO improved both insulin and C peptide responses after a meal [56]. VOO may additionally contribute, within the context of a traditional MD, to the long-term improvement of the glycemic load and the dietary glycemic index [57].
In conclusion, there is already widespread experience of the benefits of olive oil in glucose metabolism, both in a medium- and long-term period and in the postprandial phase, in the context of dietary patterns, of olive oil by itself, and the bioactive compounds of olive oil.
5 Cardiovascular Diseases
The development of an atherosclerotic plaque in the endothelium of blood vessels is common to CVDs. The plaque is formed by the accumulation of cholesterol inside the macrophages and other cells, such as the smooth muscle ones, located in the intima media. This generates an inflammatory chronic response that eventually can trigger acute thrombotic vascular disease, including myocardial infarction, stroke, and sudden cardiac death [58]. Atherosclerotic plaques are linked to the coexistence of several processes related to inflammation, lipid oxidation, dysfunction of the vascular endothelium, exacerbated activation of immune cells, and migration of vascular smooth muscle cells, among others [59].
Since Ancel Keys presented the MD as a health protecting one [1], there have been many studies supporting this link [5, 7, 16, 60]. The most impressive benefits of this diet, however, have been related to reductions in cardiovascular morbidity and mortality [61]. In general, countries from southern Europe present the lowest values of accumulated incidence and mortality rate of coronary heart disease [62, 63]. The paradox of the Mediterranean countries with a low incidence rate of cardiovascular disease [64,65,66], in spite of a marked prevalence of classical cardiovascular risk factors [67, 68], is attributed in part to a high degree of adherence to the MD. Nevertheless, most studies were observational so that any causal inference was hindered by residual confounding among other biases. Thus, large-scale randomized trials using dietary patterns, and assessing clinical end-points, are needed to provide a high level of scientific evidence. In this regard, very few randomized trials have been performed. On one hand, the Lyon Diet Heart Study, a secondary prevention trial, showed a large reduction in rates of coronary heart disease events with a modified MD enriched with alpha-linolenic acid [69]. On the other hand, the PREDIMED study, a multicenter, randomization, intervention trial with the MD, reported the protection of the traditional Mediterranean Diet (TMD) on incident CVD in high cardiovascular risk individuals, in primary prevention [70]. In addition, the PREDIMED Study has also provided evidence of the efficacy of the TMD on primary prevention for stroke [70], atrial fibrillation [71], type-2 diabetes (DM2) [72], and peripheral vascular disease [73].
Nowadays, the relevance of overall high-quality diet patterns, rather than focusing on single nutrients and foods, has highlighted the need to address the complexity of dietary exposures. Nevertheless, it is well-known that OO plays a pivotal role in this diet pattern. Data from EPIC cohorts showed an inverse relationship between OO consumption and coronary heart disease mortality and incidence [74,75,76]. Also, results from the Three-City Study reported an inverse relationship between OO consumption and stroke risk in women [77]. Finally, results of the PREDIMED Study showed that consumption of OO, specifically the extra-virgin variety, within the framework of the Mediterranean diet, reduces the risk of CVD and mortality in elderly high cardiovascular risk individuals [78].
It is increasingly accepted that chronic degenerative diseases, such as CVD, cancer, and neurodegenerative ones, share common risk factors. Besides the classical cardiovascular risk factors (diabetes, hypertension, lipid profile, tobacco, and obesity), perpetuated molecular dysregulation with respect to oxidation, low-grade inflammation, LDL atherogenicity, HDL function, and endothelial dysfunction, among others, may be behind their onset.
5.1 Arterial Hypertension and Endothelial Dysfunction
OO has also been linked to an improvement of endothelial dysfunction and blood pressure state. In a meta-analysis of randomized controlled assays (N = 12, with a duration of 6 months or longer) high- versus low-MUFA intake (low MUFA intake was considered a MUFA consumption below 12% of total daily energy consumption) was compared, and MUFA-rich diets decreased systolic (mean effect: −2.26 mmHg; CI: [−4.28, −0.25]; p = 0.03) and diastolic blood pressure (mean effect: −1.15 mmHg; CI: [−1.96, −0.34]; p = 0.005]. In addition, an improvement of the fat mass −1.94 kg, CI: [−3.72, −0.17], p = 0.03] was additionally reported [79]. MUFA intake also has effects on doses of antihypertensive drugs prescribed to patients. A MUFA-rich diet (17.2% of total daily energy intake by MUFAs, 3.8% by PUFAs) was able to decrease blood pressure relative to a polyunsaturated fatty acid (PUFA)-rich one (10.5% of total daily energy intake, 10.5% by PUFAs) and, moreover, decreased the daily dosage of hypertensive agents [80]. A decrease of diastolic blood pressure in hypertensive women was observed after an MD intervention, enriched with VOO or nuts, within the context of the PREDIMED Study [81]. Nitric oxide and endothelin-1 levels, together with endothelin-1 receptor gene expression, could play a role in blood pressure improvement [82].
Regarding OOPCs, in a meta-analysis with 13 studies concerning the effects of high phenolic OO oil on cardiovascular risk factors, medium effects for lowering systolic blood pressure (n = 69; mean effect: −0.52; CI: [−0.77, −0.27]; p<0.01) were described; however, no effects for improving diastolic blood pressure were reported (mean effect: −0.20; CI: [−1.01, 0.62]; p = 0.64) [83].
Endothelial function improved in hypercholesterolemic patients at postprandial state with phenol-rich OOs and OOPC-enriched functional OO intake [84, 85], after a 4-month intervention of a daily intake of VOO in patients with incipient atherosclerosis [86], and after 2 months in women with high-normal blood pressure or stage-1 essential hypertension [87].
Endothelial homeostasis can be disturbed by oxidative stress and chronic inflammatory processes and finally lead to endothelial dysfunction [58]. An increase in nitric oxide metabolites was observed after a phenol-rich OO postprandial intake versus a low-phenolic OO [84]. Also, a decrease in systolic blood pressure after the intake of VOO was described, with a decrease in lipid oxidation markers, in hypertensive stable patients [88]. Finally, in two randomized crossover studies, a 50 mL intake of phenol-rich OO decreased the postprandial leukotriene B4 (a pro-inflammatory eicosanoid) and thromboxane B2 (a vasoconstrictor eicosanoid) levels in comparison to refined OO in healthy [169] and mildly dyslipidemic subjects [89].
5.2 Haemostasis and Platelet Aggregation
Olive oil has been shown to improve the production of coagulation factors and biomarkers linked to platelet aggregation, thus improving the thrombogenetic profile [90].
With regard to monounsaturated fats, a MUFA-rich diet such as the MD decreases postprandial levels of coagulation factor VIIc [91]. In addition, oleic acid (75% of OO fatty acids) attenuates the prothrombotic state in the postprandial phase [91,92,93].
Regarding OOPCs, the consumption of phenol-rich OOs improved the postprandial prothrombotic state (activated coagulation factor VII, tissue factor, tissue plasminogen activator, plasminogen activator inhibitor type-1, and fibrinogen) in a number of randomized controlled trials in both healthy [94] and hypercholesterolemic subjects [90]. In long-term interventions, a decrease in plasma fibrinogen in women with high baseline fibrinogen concentrations has been reported after OO consumption, in a randomized crossover trial [95].
5.3 Lipid Profile
Improved dietary fat quality, achieved through a replacement of SFA by unsaturated fat, enhances the lipid profile by reducing low density lipoprotein (LDL) cholesterol and increasing high-density lipoprotein (HDL) cholesterol [96]. Olive oil intake assures an increase of MUFA, without a significant rise of SFA, and guarantees an appropriate intake of (PUFA). As a consequence, the MUFA/SFA ratio is much higher in areas where an MD is followed [97]. An updated review suggested a small, but potentially relevant, reduction in cardiovascular risk with low saturated fat intake [98]. The replacement of energy from saturated fat with polyunsaturated fat provides more healthy benefits than with carbohydrate. Regarding the substitution of SFAs for MUFAs, although the benefits are more modest, some positive effects on lipid profile have been observed. The reduction of dietary saturated fat, and partial replacement by unsaturated fats, has been proposed to achieve maximum health benefits although the ideal type of unsaturated fat is still unclear [98].
Schwingshackl et al. published a meta-analysis including 32 studies with overweight and obese patients. On one hand, decreases in total cholesterol (weighted mean difference −0.12 mmol/L, 95% CI: [−0.28 to −0.03]; P = 0.01) and LDL cholesterol (−0.08 mmol/L, 95% CI: [−0.12 to −0.04]; P<0.0001) were more marked after low-fat diets. On the other hand, a rise in HDL cholesterol (0.06 mmol/L, 95% CI: [0.03, 0.09]; P<0.0001) and a reduction in triglyceride (−0.095 mmol/L, 95% CI: [−0.15, −0.04]; P = 0.001) were more pronounced after the high-fat diet groups [99].
Regarding OO, in a recent meta-analysis about the effects of PC-rich OO on cardiovascular risk factors, no significant effects in improving lipid profile were observed (total cholesterol N = 400; mean effect: −0.05; CI: [−0.16, 0.05]; p = 0.33); HDL cholesterol (N = 400; mean effect: −0.03; CI: [−0.14, 0.08]; p = 0.62); LDL cholesterol (N = 400; mean effect: −0.03; CI: [−0.15, 0.09]; p = 0.61); and triglycerides (N = 360; mean effect: 0.02; CI: [−0.22, 0.25]; p = 0.90). Nevertheless, the small number of studies (N = 8) is a limitation [83]. Specifically, the beneficial effects of OO polyphenols on blood HDL cholesterol concentrations were evaluated by the European Food Safety Authority (EFSA) and they concluded that evidence was insufficient to establish a cause-effect relationship [100]. A recent review indicated that the intake of PC-rich OO induced no significant increases in HDL cholesterol levels [83], while several high-quality randomized controlled trials have pointed to a dose-dependent increment in HDL cholesterol after the consumption of OOPCs [11, 12, 101].
5.4 Lipid Oxidation
In November 2004, the USA Federal Drug Administration [102] permitted a claim on OO labels regarding “the benefits on the risk of coronary heart disease of taking 2 tablespoons (23 grams) of OO daily, due to monounsaturated fat.” However, if the effect of OO is only attributed to its MUFA content, any type of MUFA-rich food (such as rapeseed oil, canola oil, or MUFA-enriched fats) would provide the same beneficial effects for health. The minor components of OO (1–2% of the total content) are classified in two groups: (1) the unsaponifiable: squalene and other triterpenes, sterols, tocopherol, carotenoids, and pigments and (2) the soluble fraction which includes the PCs [168]. In this respect, the EFSA released a health claim concerning the protection of OOPC (5 mg/day) against LDL oxidation [103]. Based on well-designed intervention trials, a cause-effect relationship was established by the EFSA between the consumption of VOO and the protection of LDL particles from oxidative damage [103].
Not only changes in LDL cholesterol are involved in cardiovascular risk, oxidation modifications of the LDL particle may play a major role in atherosclerosis [58, 104, 105]. Several OO components contribute to decreasing LDL oxidizability. On the one hand, MUFAs are less prone to becoming oxidized when compared to other unsaturated fats [106]. On the other hand, OO antioxidants (vitamin E, carotenoids, and OOPCs) can bind to the LDL particle and protect it from oxidative modifications.
A recent meta-analysis (N = 13) reported that oxidized LDL levels decrease significantly after the consumption of high-phenolic OO (N = 300; mean effect: −0.25; CI: [−0.50, 0.00]; p = 0.05) [83]. In the EUROLIVE Study, 200 volunteers were given 25 mL/day of raw OO with high (366 mg/kg), medium (164 mg/kg), and low (3 mg/kg) phenolic content in a randomized, crossover, and controlled trial [11]. Covas et al. reported a decrease of the in vivo lipid oxidative damage (concretely in oxidized LDL, uninduced conjugated dienes, and hydroxy fatty acids) in a linear manner with the phenolic content of the OO administered [11]. As potential mechanisms to explain this benefit, we could consider an increase in the content of vitamin E and OOPC in LDL that may counteract locally oxidative modifications [107, 108]. In addition, the reductive effect of the OOPC on oxidized LDL could be due to the generation of antibodies [109]. Vázquez-Velasco et al. observed, in healthy volunteers, a decrease in the concentration of oxidized LDL when hydroxytyrosol-enriched sunflower oil (45–50 mg/d) was administered during 3 weeks [110]. In 40 males suffering from stable coronary heart disease, VOO was able to decrease the oxidized LDL in plasma compared with another olive oil with a smaller amount of PC in a randomized crossover trial [88]. Finally, LDL oxidizability has also been evaluated in vitro, and it decreased after the consumption of MUFAs [111, 112] and phenol-rich OOs [11, 101, 113, 114].
Finally, Fitó et al. reported an improvement of circulating oxidized LDL after a 3-month MD intervention in high cardiovascular risk patients [115].
5.5 HDL Functionality
Although low levels of HDL cholesterol are considered an independent cardiovascular risk factor [116], it has been recently observed that presenting high HDL cholesterol levels does not always lead to a decrease in cardiovascular risk [117,118,119]. An increase in HDL cholesterol is one of the goals of clinical management of cardiovascular diseases [117]. In this regard, recent studies have shown that the functionality of HDL can be of greater relevance than its amount [120]. Decreased values of the most relevant HDL function have been reported to be related to a high incidence of subclinical atherosclerosis [121] and coronary events [122].
The functionality of the HDL particle involves the promotion of cholesterol efflux from macrophages and peripheral cells, which constitutes part of the so-called “reverse cholesterol transport” [123]. Furthermore, HDLs play a crucial role in inhibiting the oxidation of plasma lipids (mainly, the ones in LDLs) and also present anti-inflammatory and vasoprotective capacities [124]. Oxidative modifications of the HDL can additionally affect the lipid and/or protein of the lipoprotein and alter its physiological properties [120, 124,125,126] and, in this regard, antioxidants linked to the particle could be able, direct or indirectly, to counteract such oxidation. An increment in HDL fluidity, enhanced HDL composition, and better HDL size distribution could also mediate improvements in HDL function [127,128,129].
Regarding OO, the consumption of a MUFA-rich diet improved the cholesterol efflux capacity of HDLs in a linear trial [130]. This functional improvement could be due to a lower degree of oxidative modifications of the lipoprotein after increasing its MUFA content [131]. Regarding OOPCs, Hernáez et al. reported for the first time an increase in cholesterol efflux after the daily intake of 25 mL of VOO (366 mg/kg) in healthy volunteers within the framework of the EUROLIVE Study [132]. In parallel, biological metabolites of OOPC bound to the HDLs (hydroxytyrosol sulfate, and homovanillic acid sulfate, and glucuronate) were determined. The improvement of HDL fluidity and a triglyceride-poor core can also result in a more functional HDL particle [132]. In this respect, functional VOO supplemented with olive and thyme phenols versus a VOO intervention produced an increase in the lecithin-cholesterol acyl-transferase concentration which esterifies free cholesterol and mediates its migration into the particle core [133]. The consumption of OOPCs has also been shown to be able to increase the levels of the main HDL antioxidant enzyme, paraoxonase-1, as well as HDL anti-inflammatory ability, in a noncontrolled trial [134]. Besides the direct antioxidant effect of OOPCs on HDL particles, these compounds have also been observed to be able to improve the gene expression related to HDL function [135].
Finally, a TMD, especially when supplemented with real-life doses VOO, was able to improve HDL functionality [136]. Concretely, a 1-year intervention with an MD increased cholesterol efflux capacity and, in particular, the VOO-rich MD enhanced nitric oxide synthesis by endothelial cells promoted by HDLs, decreased cholesteryl ester transfer protein activity, and increased HDL ability to esterify cholesterol and paraoxonase-1 arylesterase activity [136].
5.6 Inflammatory Processes and Systemic Oxidative Status
Oxidation and inflammation are intertwined processes which, when sustained for a long period, may induce the onset of a number of chronic degenerative diseases, such as CVD, diabetes, neurodegenerative diseases, and cancer. The increased circulating concentrations of pro-inflammatory analytes (tumor necrosis factor-α, monocyte chemotactic protein-1, soluble vascular cell adhesion molecule 1, and soluble intercellular adhesion molecule-1) perpetuate the inflammatory response in the subendothelial space and establish endothelial dysfunction.
Traditionally, the health benefits of the MD have been attributed to its richness in antioxidants. Among the approximately 230 chemical compounds of OO, the main antioxidants are carotenes and phenolic compounds, including lipophilic and hydrophilic phenols [137]. Current evidence points to oxidative damage as a promoter of pathophysiological processes in oxidative stress-related diseases such as coronary heart disease, cancer, neurodegenerative pathologies, and, in addition, aging [138,139,140]. Although phenolic compounds are good antioxidants in vitro, their in vivo effects can be indirectly mediated through the activation of several nutrigenomic pathways and not only by their intrinsic antioxidant activity [141, 170]. Benefits of olive oil on lipid oxidation have been extensively explained in the Sect. 5.4 apart.
Several benefits on the levels of pro-inflammatory biomarkers have been proven in human trials with OO or MUFA-rich diets. A daily intake of real-life doses of OO has been shown to produce a decrease of the C-reactive protein (mean effect: −0.64 mg/L; CI: [−0.96, −0.31]; p<0.0001) and IL-6 (mean effect: −0.29; CI: [−0.70, −0.02]; p<0.04) in a recent systematic review [43]. Nevertheless, the heterogeneity of design among studies makes further research necessary. With regard to other MUFA-rich diets, a randomized controlled trial with 28 hypertriglyceridemic and 14 healthy males who followed a diet rich in refined OO (high-oleic acid diet) or a diet rich in high-palmitic sunflower oil, revealed a postprandial decrease of the soluble adhesion molecules (VCAM-1, ICAM-1) after the high-oleic intervention [142]. And in another randomized controlled trial, a 2-month MUFA-rich diet decreased the expression by peripheral blood mononuclear cells of ICAM-1 in healthy males [143]. In contrast, a randomized crossover trial in healthy subjects regarding the effect of three Malaysian diets: palm olein, coconut oil, and OO (the fat source providing approximately 20% of total energy intake in each case), the postprandial and 2-week fasting circulating concentrations of a number of inflammatory biomarkers (tumor necrosis factor-α, IL-1β, IL-6, IL-8, CRP, and interferon-γ) were not affected [144].
The consumption of OO, which provides oleic acid as the main fatty acid, also yields a moderate intake of PUFA (mainly omega-6 linoleic acid and omega-3 alpha-linolenic acid) without a noticeable increase in the intake of SFA. Omega-6 fatty acids, in which PUFAs are predominant (especially in the Western diets), are precursors of pro-inflammatory eicosanoids (2-prostaglandins, tromboxanes, and 4-leukotrienes) [145]. In this regard, omega-3 fatty acids in OO may play a role in the inhibition of the inflammatory process boosted by omega-6 fatty acids [146]. It has been reported that a low incidence of coronary heart disease is related to a diet rich in omega-3 fatty acids [147].
The OOPCs have also shown effects on pro-inflammatory biomarkers. Surprisingly, Beauchamp et al. described oleocanthal anti-inflammatory properties that were similar to those of ibuprofen (cyclooxygenase-2 inhibition and nuclear factor kappa beta counteract) [148]. Moreover, the intake of phenol-enriched OO (50 mL/day) decreased C-reactive protein (CRP) levels at postprandial state relative to refined olive or corn oils in healthy individuals, in a randomized controlled trial. In this regard, a regular intake of OO at long term can contribute to controlling the postprandial inflammatory burden [149]. Also, a combined consumption of white wine (2–3 glasses/daily) and extra VOO (ad libitum) for a 2-week period decreased the levels of CRP and IL-6 in both patients with chronic kidney disease and healthy subjects [150]. Finally, a raw real-life daily dose of 50 mL of VOO for 3 weeks decreased the IL-6 and CRP concentrations (versus refined OO) in a randomized controlled trial with stable coronary heart disease patients [151].
Within the context of a traditional MD, supplementation with VOO or nuts decreased the systemic levels of CRP, IL-6, sVCAM1, and sICAM1 in high cardiovascular risk volunteers within the framework of the PREDIMED Study [81]. In addition, the traditional MD (supplemented with VOO or nuts) was able after 3 months of intervention to decrease the expression of CD49d (an adhesion molecule) and CD40 (a pro-inflammatory ligand) in monocytes isolated from the blood of high cardiovascular risk volunteers [152].
The MD participants had lower plasma concentrations of atherosclerosis-related inflammatory markers (IL-6, IL-8, MCP-1, and MIP-1β) after 3 and 5 years of an MD intervention versus a low-fat diet control group. In addition, IL-1β, IL-5, IL-7, IL-12p70, IL-18, TNF-α, IFN-γ, GCSF, GMCSF, and ENA78 decreased especially after an MD supplemented with VOO [153]. Finally, the reduction in CD49d and CD40 expressions in T lymphocytes and monocytes at 3 years were greater in the MD group than in the low-fat diet control one [154].
5.7 Immune System
Regarding MUFAs, they have been reported to modulate a number of biological pathways of immune competent cells [155]. In this regard, in a randomized controlled trial with healthy males, there was a significant decrease in the expression of intercellular adhesion molecule 1 by peripheral blood mononuclear cells after MUFA-rich 2 month-diet. Nevertheless, natural killer cell activity and the proliferation of mitogen-stimulated leukocytes were not affected [143].
The consumption of a functional VOO showed an increase in the proportion of IgA-coated bacteria, which indicates a local stimulation of the intestinal mucosal immunity [156]. Based on the effects of OO intake on the immune system, it has been suggested that OO consumption may have benefits on rheumatoid arthritis [155]. In contrast, other authors have published that OO-rich diets do not alter host resistance to infection [157, 158]. Given that data are scarce, more studies are required to establish the possible immunostimulation of OO in vivo.
5.8 Microbiome
Gut microbiota, a complex and dynamic ecosystem, is an emergent factor of a number of diseases including obesity and type-II diabetes [159]. PCs can selectively stimulate growth bacteria, such as Lactobacillus [160], which can play a role in lowering cholesterol levels [161]. Intestinal lactobacilli produce bile-salt hydrolase, which deconjugates bile acids, prevents their reabsorption, and therefore promotes their fecal excretion [162]. This can be one of the mechanisms involved in the decrease of systemic cholesterol after PC consumption [163]. PCs may also be related to the growth of other bacterial populations (such as Bifidobacterium) which might be linked to a lesser development of the atherosclerotic plaque [164].
Since most PCs are not fully absorbed into the upper gastrointestinal tract and reach the large intestine, they can be metabolized by gut microflora [165]. A 3-week intake of a phenol-enriched VOO (with OO and thyme PCs) increased populations of Bifidobacteria and the levels of microbial metabolites of antioxidant PCs, such as protocatechuic acid and hydroxytyrosol, in hypercholesterolemic individuals [166].
6 Conclusion
In summary, current evidence indicates the potential benefits of olive oil, within the framework of a healthy diet such as the Mediterranean one, on the prevention of chronic degenerative diseases including cardiovascular and degenerative ones. To date, the majority of these effects have been demonstrated from the perspectives of atherosclerosis and cardiovascular risk research. Nevertheless, there is increasing evidence that such beneficial properties also display a protection towards other diseases including neurodegenerative ones and cancer.
The daily diet represents the consumption of a mixture of foods in which the type of cooking plays an indisputable role in the availability and properties of nutrients. Furthermore, synergism among nutrients and foods, and their cumulative effects, must also be taken into consideration. With respect to the Mediterranean diet, olive oil as the main source of fat is determinant with respect to the properties attributed to this dietary pattern.
Olive oil intake facilitates more vegetable consumption and thus benefits on health can be maximized. Nutrient-specific biases and type of olive oil should be considered in order to disentangle the benefits of MUFA and/or other minor components. Further well-designed, large-scale cohort studies in Mediterranean and non-Mediterranean areas are needed to reaffirm the therapeutic properties of olive oil and establish in which subjects and under which conditions benefits can be more easily achieved.
Abbreviations
- CRP:
-
C-reactive protein
- EFSA:
-
European Food Safety Agency
- GcMAF:
-
Gc protein-derived macrophage activating factor
- HDL:
-
High-density lipoprotein
- ICAM-1:
-
Intercellular adhesion molecule-1
- IL:
-
Interleukin
- LDL:
-
Low-density lipoprotein
- MD:
-
Mediterranean diet
- MUFA:
-
Monounsaturated fatty acid
- OO:
-
Olive oil
- OOPC:
-
Olive oil phenolic compound
- PUFA:
-
Polyunsaturated fatty acid
- SFA:
-
Saturated fatty acid
- VCAM-1:
-
Vascular cell adhesion molecule-1
- VOO:
-
Virgin olive oil
References
Keys A, Menotti A, Karvonen MJ, Aravanis C, Blackburn H, Buzina R, Djordjevic BS, Dontas AS, Fidanza F, Keys MH (1986) The diet and 15-year death rate in the seven countries study. Am J Epidemiol 124:903–915
Serra-Majem L, Roman B, Estruch R (2006) Scientific evidence of interventions using the Mediterranean diet: a systematic review. Nutr Rev 64:S27–S47
Sofi F, Macchi C, Abbate R, Gensini GF, Casini A (2013) Mediterranean diet and health. Biofactors 39:335–342
Trichopoulou A (2004) Traditional Mediterranean diet and longevity in the elderly: a review. Public Health Nutr 7:943–947
Trichopoulou A, Costacou T, Bamia C, Trichopoulos D (2003) Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med 348:2599–2608
Féart C, Samieri C, Rondeau V, Amieva H, Portet F, Dartigues J-F, Scarmeas N, Barberger-Gateau P (2009) Adherence to a Mediterranean diet, cognitive decline, and risk of dementia. JAMA 302:638–648
Scarmeas N, Stern Y, Tang M-X, Mayeux R, Luchsinger JA (2006) Mediterranean diet and risk for Alzheimer’s disease. Ann Neurol 59:912–921
Urpi-Sarda M, Casas R, Chiva-Blanch G, Romero-Mamani ES, Valderas-Martínez P, Arranz S, Andres-Lacueva C, Llorach R, Medina-Remón A, Lamuela-Raventos RM, Estruch R (2012) Virgin olive oil and nuts as key foods of the Mediterranean diet effects on inflammatory biomakers related to atherosclerosis. Pharmacol Res 65:577–583
Schwingshackl L, Hoffmann G (2014) Monounsaturated fatty acids, olive oil and health status: a systematic review and meta-analysis of cohort studies. Lipids Health Dis 13:154
Covas M-I, de la Torre K, Farré-Albaladejo M, Kaikkonen J, Fitó M, López-Sabater C, Pujadas-Bastardes MA, Joglar J, Weinbrenner T, Lamuela-Raventós RM, de la Torre R (2006a) Postprandial LDL phenolic content and LDL oxidation are modulated by olive oil phenolic compounds in humans. Free Radic Biol Med 40:608–616
Covas M-I, Nyyssönen K, Poulsen HE, Kaikkonen J, Zunft HF, Kiesewetter H, Gaddi A, de la Torre R, Mursu J, Bäumler H, Nascetti S, Salonen JT, Fitó M, Virtanen J, Marrugat J (2006b) The effect of polyphenols in olive oil on heart disease risk factors: a randomized trial. Ann Intern Med 145:333–341
Weinbrenner T, Fitó M, de la Torre R, Saez GT, Rijken P, Tormos C, Coolen S, Albaladejo MF, Abanades S, Schroder H, Marrugat J, Covas M-I (2004a) Olive oils high in phenolic compounds modulate oxidative/antioxidative status in men. J Nutr 134:2314–2321
Donaldson MS (2004) Nutrition and cancer: a review of the evidence for an anti-cancer diet. Nutr J 3:19
Block G, Patterson B, Subar A (1992) Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence. Nutr Cancer 18:1–29
Bradbury KE, Appleby PN, Key TJ (2014) Fruit, vegetable, and fiber intake in relation to cancer risk: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC). Am J Clin Nutr 100:394S–398S
Sofi F, Cesari F, Abbate R, Gensini GF, Casini A (2008) Adherence to Mediterranean diet and health status: meta-analysis. BMJ 337:a1344
Trichopoulou A, Lagiou P, Kuper H, Trichopoulos D (2000) Cancer and Mediterranean dietary traditions. Cancer Epidemiol Biomarkers Prev 9:869–873
Toledo E, Salas-Salvadó J, Donat-Vargas C, Buil-Cosiales P, Estruch R, Ros E, Corella D, Fitó M, Hu FB, Arós F, Gómez-Gracia E, Romaguera D, Ortega-Calvo M, Serra-Majem L, Pintó X, Schröder H, Basora J, Sorlí JV, Bulló M, Serra-Mir M, Martínez-González MA (2015) Mediterranean diet and invasive breast cancer risk among women at high cardiovascular risk in the PREDIMED trial: a randomized clinical trial. JAMA Intern Med 175:1752–1760
Buckland G, Travier N, Agudo A, Fonseca-Nunes A, Navarro C, Lagiou P, Demetriou C, Amiano P, Dorronsoro M, Chirlaque MD, Huerta JM, Molina E, Pérez MJS, Ardanaz E, Moreno-Iribas C, Quirós JR, Naska A, Trichopoulos D, Giurdanella MC, Tumino R, Agnoli C, Grioni S, Panico S, Mattiello A, Masala G, Sacerdote C, Polidoro S, Palli D, Trichopoulou A, González CA (2012b) Olive oil intake and breast cancer risk in the Mediterranean countries of the European Prospective Investigation into Cancer and Nutrition study. Int J Cancer 131:2465–2469
Buckland G, Agudo A, Luján L, Jakszyn P, Bueno-de-Mesquita HB, Palli D, Boeing H, Carneiro F, Krogh V, Sacerdote C, Tumino R, Panico S, Nesi G, Manjer J, Regnér S, Johansson I, Stenling R, Sanchez M-J, Dorronsoro M, Barricarte A, Navarro C, Quirós JR, Allen NE, Key TJ, Bingham S, Kaaks R, Overvad K, Jensen M, Olsen A, Tjønneland A, Peeters PHM, Numans ME, Ocké MC, Clavel-Chapelon F, Morois S, Boutron-Ruault M-C, Trichopoulou A, Lagiou P, Trichopoulos D, Lund E, Couto E, Boffeta P, Jenab M, Riboli E, Romaguera D, Mouw T, González CA (2010) Adherence to a Mediterranean diet and risk of gastric adenocarcinoma within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study. Am J Clin Nutr 91:381–390
Castro M, Romero C, de Castro A, Vargas J, Medina E, Millán R, Brenes M (2012) Assessment of Helicobacter pylori eradication by virgin olive oil. Helicobacter 17:305–311
Stamatiou K, Delakas D, Sofras F (2007) Mediterranean diet, monounsaturated: saturated fat ratio and low prostate cancer risk. A myth or a reality? Minerva Urol Nefrol 59:59–66
Martin-Moreno JM (2000) The role of olive oil in lowering cancer risk: is this real gold or simply pinchbeck? J Epidemiol Community Health 54:726–727
Psaltopoulou T, Kosti RI, Haidopoulos D, Dimopoulos M, Panagiotakos DB (2011) Olive oil intake is inversely related to cancer prevalence: a systematic review and a meta-analysis of 13,800 patients and 23,340 controls in 19 observational studies. Lipids Health Dis 10:127
Ruggiero M, Ward E, Smith R, Branca JJV, Noakes D, Morucci G, Taubmann M, Thyer L, Pacini S (2014) Oleic Acid, deglycosylated vitamin D-binding protein, nitric oxide: a molecular triad made lethal to cancer. Anticancer Res 34:3569–3578
Roberts RO, Cerhan JR, Geda YE, Knopman DS, Cha RH, Christianson TJH, Pankratz VS, Ivnik RJ, O’Connor HM, Petersen RC (2010) Polyunsaturated fatty acids and reduced odds of MCI: the Mayo Clinic Study of Aging. J Alzheimers Dis 21:853–865
Polidori MC, Praticó D, Mangialasche F, Mariani E, Aust O, Anlasik T, Mang N, Pientka L, Stahl W, Sies H, Mecocci P, Nelles G (2009) High fruit and vegetable intake is positively correlated with antioxidant status and cognitive performance in healthy subjects. J Alzheimers Dis 17:921–927
Valls-Pedret C, Lamuela-Raventós RM, Medina-Remón A, Quintana M, Corella D, Pintó X, Martínez-González MÁ, Estruch R, Ros E (2012) Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk. J Alzheimers Dis 29:773–782
Gandhi S, Abramov AY (2012) Mechanism of oxidative stress in neurodegeneration. Oxid Med Cell Longev 2012:428010
Ramassamy C (2006) Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: a review of their intracellular targets. Eur J Pharmacol 545:51–64
Williams RJ, Spencer JPE (2012) Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for Alzheimer disease. Free Radic Biol Med 52:35–45
Kanoski SE, Davidson TL (2011) Western diet consumption and cognitive impairment: links to hippocampal dysfunction and obesity. Physiol Behav 103:59–68
Martínez-Lapiscina EH, Clavero P, Toledo E, San Julián B, Sanchez-Tainta A, Corella D, Lamuela-Raventós RM, Martínez JA, Martínez-Gonzalez MÁ (2013) Virgin olive oil supplementation and long-term cognition: the PREDIMED-NAVARRA randomized, trial. J Nutr Health Aging 17:544–552
Larsson SC (2014) Coffee, tea, and cocoa and risk of stroke. Stroke 45:309–314
Rodríguez-Campello A, Jiménez-Conde J, Ois Á, Cuadrado-Godia E, Giralt-Steinhauer E, Schroeder H, Romeral G, Llop M, Soriano-Tárraga C, Garralda-Anaya M, Roquer J (2014) Dietary habits in patients with ischemic stroke: a case-control study. PLoS One 9:e114716
Wang Z-M, Zhao D, Nie Z-L, Zhao H, Zhou B, Gao W, Wang L-S, Yang Z-J (2014) Flavonol intake and stroke risk: a meta-analysis of cohort studies. Nutrition 30:518–523
Daccache A, Lion C, Sibille N, Gerard M, Slomianny C, Lippens G, Cotelle P (2011) Oleuropein and derivatives from olives as Tau aggregation inhibitors. Neurochem Int 58:700–707
International Diabetes Ferderation (2013) IDF diabetes atlas, 6th edn [Internet]. Available from: https://www.idf.org/e-library/epidemiology-research/diabetes-atlas/19-atlas-6th-edition.html
WHO (2017) Diabetes – fact sheet. http://www.who.int/mediacentre/factsheets/fs312/en
Panagiotakos DB, Tzima N, Pitsavos C, Chrysohoou C, Zampelas A, Toussoulis D et al (2007) The association between adherence to the mediterranean diet and fasting indices of glucose homoeostasis: the ATTICA Study. J Am Coll Nutr 26(1):32–38
Salas-Salvadó J, Bulló M, Estruch R, Ros E, Covas MI, Ibarrola-Jurado N et al (2014) Prevention of diabetes with mediterranean diets: a subgroup analysis of randomized trial. Ann Intern Med 160(1):1–11
Koloverou E, Esposito K, Giugliano D, Panagiotakos D (2014) The effect of Mediterranean diet on the development of type 2 diabetes mellitus: a meta-analysis of 10 prospective studies and 136,846 participants. Metabolism 63(7):903–911. https://doi.org/10.1016/j.metabol.2014.04.010
Schwingshackl L, Missbach B, König J, Hoffmann G (2015) Adherence to a Mediterranean diet and risk of diabetes: a systematic review and meta-analysis. Public Health Nutr 18(7):1292–1299
Esposito K, Maiorino MI, Bellastella G, Chiodini P, Panagiotakos D, Giugliano D (2015) A journey into a Mediterranean diet and type 2 diabetes: a systematic review with meta-analyses. BMJ Open 5(8):e008222
Esposito K, Chiodini P, Maiorino MI, Bellastella G, Panagiotakos D, Giugliano D (2014) Which diet for prevention of type 2 diabetes? A meta-analysis of prospective studies. Endocrine 47(1):107–116
Tierney AC, Roche HM (2007) The potential role of olive oil-derived MUFA in insulin sensitivity. Mol Nutr Food Res 51(10):1235–1248
Trevisan M, Krogh V, Freudenheim J, Blake A, Muti P, Panico S et al (1990) Consumption of olive oil, butter and vegetable oils and coronary heart disease risk factors. The Research Group ATS-RF2 of the Italian National Research Council. J Am Med Assoc 26:688–692
Guasch-Ferre M, Hruby A, Salas-salvado J, Martinez-Gonzalez MA, Sun Q, Willett WC et al (2015) Olive oil consumption and risk of type 2 diabetes in US women. Am J Clin Nutr 102(1):479–486
Ceriello A, Esposito K, La Sala L, Pujadas G, De Nigris V, Testa R et al (2014) The protective effect of the Mediterranean diet on endothelial resistance to GLP-1 in type 2 diabetes: a preliminary report. Cardiovasc Diabetol 13(1):1–9
Ryan M (2000) Diabetes and the Mediterranean diet: a beneficial effect of oleic acid on insulin sensitivity, adipocyte glucose transport and endothelium-dependent vasoreactivity. QJM [Internet] 93(2):85–91 Available from: https://academic.oup.com/qjmed/article-lookup/doi/10.1093/qjmed/93.2.85
Perona JS, Vögler O, Sánchez-Domínguez JM, Montero E, Escribá PV, Ruiz-Gutierrez V (2007) Consumption of virgin olive oil influences membrane lipid composition and regulates intracellular signaling in elderly adults with type 2 diabetes mellitus. Journals Gerontol – Ser A Biol Sci Med Sci 62(3):256–263
Guasch-Ferre M, Merino J, Sun Q, Fito M, Salas-Salvado J (2017) Dietary polyphenols, Mediterranean diet, prediabetes, and type 2 diabetes: a narrative review of the evidence. Oxid Med Cell Longev 2017:6723931
Santangelo C, Filesi C, Varì R, Scazzocchio B, Filardi T, Fogliano V et al (2016) Consumption of extra-virgin olive oil rich in phenolic compounds improves metabolic control in patients with type 2 diabetes mellitus: a possible involvement of reduced levels of circulating visfatin. J Endocrinol Invest 39(11):1295–1301
Lairon D (2008) Macronutrient intake and modulation on chylomicron production and clearance. Atheroscler Suppl 9:45–48
Weinbrenner T, Fitó M, Farré Albaladejo M, Saez GT, Rijken P, Tormos C, Coolen S, De La Torre R, Covas MI (2004b) Bioavailability of phenolic compounds from olive oil and oxidative/antioxidant status at postprandial state in healthy humans. Drugs Exp Clin Res 30:207–212
Farnetti S, Malandrino N, Luciani D, Gasbarrini G, Capristo E (2011) Food fried in extra-virgin olive oil improves postprandial insulin response in obese, insulin-resistant women. J Med Food 14:316–321
Rodríguez-Rejón AI, Castro-Quezada I, Ruano-Rodríguez C, Ruiz-López MD, Sánchez-Villegas A, Toledo E, Artacho R, Estruch R, Salas-Salvadó J, Covas MI, Corella D, Gómez-Gracia E, Lapetra J, Pintó X, Arós F, Fiol M, Lamuela-Raventós RM, Ruiz-Gutierrez V, Schröder H, Ros E, Martínez-González MÁ, Serra-Majem L (2014) Effect of a Mediterranean diet intervention on dietary glycemic load and dietary glycemic index: the PREDIMED Study. J Nutr Metab 2014:985373
Ross R (1999) Atherosclerosis – an inflammatory disease. N Engl J Med 340:115–126
Libby P, Ridker PM, Hansson GK (2009) Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol 54:2129–2138
Benetou V, Trichopoulou A, Orfanos P, Naska A, Lagiou P, Boffetta P, Trichopoulos D, Greek EPIC cohort (2008) Conformity to traditional Mediterranean diet and cancer incidence: the Greek EPIC cohort. Br J Cancer 99:191–195
Parikh P, McDaniel MC, Ashen MD, Miller JI, Sorrentino M, Chan V, Blumenthal RS, Sperling LS (2005) Diets and cardiovascular disease: an evidence-based assessment. J Am Coll Cardiol 45:1379–1387
Dégano IR, Elosua R, Marrugat J (2013) Epidemiology of acute coronary syndromes in Spain: estimation of the number of cases and trends from 2005 to 2049. Rev española Cardiol (English ed) 66:472–481
Tunstall-Pedoe H, Kuulasmaa K, Mähönen M, Tolonen H, Ruokokoski E, Amouyel P (1999) Contribution of trends in survival and coronary-event rates to changes in coronary heart disease mortality: 10-year results from 37 WHO MONICA project populations. Monitoring trends and determinants in cardiovascular disease. Lancet (London, England) 353:1547–1557
Gjonça A, Bobak M (1997) Albanian paradox, another example of protective effect of Mediterranean lifestyle? Lancet (London, England) 350:1815–1817
Masiá R, Pena A, Marrugat J, Sala J, Vila J, Pavesi M, Covas M, Aubó C, Elosua R (1998) High prevalence of cardiovascular risk factors in Gerona, Spain, a province with low myocardial infarction incidence. REGICOR Investigators. J Epidemiol Community Health 52:707–715
Renaud S, de Lorgeril M (1992) Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet (London, England) 339:1523–1526
Aravanis C, Corcondilas A, Dontas AS, Lekos D, Keys A (1970) Coronary heart disease in seven countries. IX. The Greek islands of Crete and Corfu. Circulation 41:88–100
McGovern PG, Pankow JS, Shahar E, Doliszny KM, Folsom AR, Blackburn H, Luepker RV (1996) Recent trends in acute coronary heart disease – mortality, morbidity, medical care, and risk factors. The Minnesota Heart Survey Investigators. N Engl J Med 334:884–890
de Lorgeril M, Salen P, Martin JL, Monjaud I, Delaye J, Mamelle N (1999) Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Circulation 99:779–785
Estruch R, Ros E, Salas-Salvadó J, Covas M-I, Corella D, Arós F, Gómez-Gracia E, Ruiz-Gutiérrez V, Fiol M, Lapetra J, Lamuela-Raventos RM, Serra-Majem L, Pintó X, Basora J, Muñoz MA, Sorlí JV, Martínez JA, Martínez-González MA (2013) Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med 368:1279–1290
Martínez-González MÁ, Toledo E, Arós F, Fiol M, Corella D, Salas-Salvadó J, Ros E, Covas MI, Fernández-Crehuet J, Lapetra J, Muñoz MA, Fitó M, Serra-Majem L, Pintó X, Lamuela-Raventós RM, Sorlí JV, Babio N, Buil-Cosiales P, Ruiz-Gutierrez V, Estruch R, Alonso A, PREDIMED Investigators (2014) Extravirgin olive oil consumption reduces risk of atrial fibrillation: the PREDIMED (Prevención con Dieta Mediterránea) trial. Circulation 130:18–26
Salas-Salvadó J, Bulló M, Babio N, Martínez-González MÁ, Ibarrola-Jurado N, Basora J, Estruch R, Covas MI, Corella D, Arós F, Ruiz-Gutiérrez V, Ros E, Study Investigators PREDIMED (2011) Reduction in the incidence of type 2 diabetes with the Mediterranean diet: results of the PREDIMED-Reus nutrition intervention randomized trial. Diabetes Care 34:14–19
Ruiz-Canela M, Estruch R, Corella D, Salas-Salvadó J, Martínez-González MA (2014) Association of Mediterranean diet with peripheral artery disease. JAMA 311:415
Bendinelli B, Masala G, Saieva C, Salvini S, Calonico C, Sacerdote C, Agnoli C, Grioni S, Frasca G, Mattiello A, Chiodini P, Tumino R, Vineis P, Palli D, Panico S (2011) Fruit, vegetables, and olive oil and risk of coronary heart disease in Italian women: the EPICOR Study. Am J Clin Nutr 93:275–283
Buckland G, Mayén AL, Agudo A, Travier N, Navarro C, Huerta JM, Chirlaque MD, Barricarte A, Ardanaz E, Moreno-Iribas C, Marin P, Quirós JR, Redondo M-L, Amiano P, Dorronsoro M, Arriola L, Molina E, Sanchez M-J, Gonzalez CA (2012a) Olive oil intake and mortality within the Spanish population (EPIC-Spain). Am J Clin Nutr 96:142–149
Buckland G, Travier N, Barricarte A, Ardanaz E, Moreno-Iribas C, Sánchez M-J, Molina-Montes E, Chirlaque MD, Huerta JM, Navarro C, Redondo ML, Amiano P, Dorronsoro M, Larrañaga N, Gonzalez CA (2012c) Olive oil intake and CHD in the European Prospective Investigation into Cancer and Nutrition Spanish cohort. Br J Nutr 108:2075–2082
Samieri C, Féart C, Proust-Lima C, Peuchant E, Tzourio C, Stapf C, Berr C, Barberger-Gateau P (2011) Olive oil consumption, plasma oleic acid, and stroke incidence: the Three-City Study. Neurology 77:418–425
Guasch-Ferré M, Hu FB, Martínez-González MA, Fitó M, Bulló M, Estruch R, Ros E, Corella D, Recondo J, Gómez-Gracia E, Fiol M, Lapetra J, Serra-Majem L, Muñoz MA, Pintó X, Lamuela-Raventós RM, Basora J, Buil-Cosiales P, Sorlí JV, Ruiz-Gutiérrez V, Martínez JA, Salas-Salvadó J (2014) Olive oil intake and risk of cardiovascular disease and mortality in the PREDIMED Study. BMC Med 12:78
Schwingshackl L, Strasser B, Hoffmann G (2011) Effects of monounsaturated fatty acids on glycaemic control in patients with abnormal glucose metabolism: a systematic review and meta-analysis. Ann Nutr Metab 58:290–296
Ferrara LA, Raimondi AS, d’Episcopo L, Guida L, Dello Russo A, Marotta T (2000) Olive oil and reduced need for antihypertensive medications. Arch Intern Med 160:837–842
Estruch R, Martínez-González MA, Corella D, Salas-Salvadó J, Ruiz-Gutiérrez V, Covas MI, Fiol M, Gómez-Gracia E, López-Sabater MC, Vinyoles E, Arós F, Conde M, Lahoz C, Lapetra J, Sáez G, Ros E (2006) Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann Intern Med 145:1–11
Storniolo CE, Casillas R, Bulló M, Castañer O, Ros E, Sáez GT, Toledo E, Estruch R, Ruiz-Gutiérrez V, Fitó M, Martínez-González MA, Salas-Salvadó J, Mitjavila MT, Moreno JJ (2017) A Mediterranean diet supplemented with extra virgin olive oil or nuts improves endothelial markers involved in blood pressure control in hypertensive women. Eur J Nutr 56(1):89–97
Hohmann CDD, Cramer H, Michalsen A, Kessler C, Steckhan N, Choi K, Dobos G (2015) Effects of high phenolic olive oil on cardiovascular risk factors: a systematic review and meta-analysis. Phytomedicine 22:631–640
Ruano J, Lopez-Miranda J, Fuentes F, Moreno JA, Bellido C, Perez-Martinez P, Lozano A, Gómez P, Jiménez Y, Pérez Jiménez F (2005) Phenolic content of virgin olive oil improves ischemic reactive hyperemia in hypercholesterolemic patients. J Am Coll Cardiol 46:1864–1868
Valls R-M, Farràs M, Suárez M, Fernández-Castillejo S, Fitó M, Konstantinidou V, Fuentes F, López-Miranda J, Giralt M, Covas M-I, Motilva M-J, Solà R (2015) Effects of functional olive oil enriched with its own phenolic compounds on endothelial function in hypertensive patients. A randomised controlled trial. Food Chem 167:30–35
Widmer RJ, Freund MA, Flammer AJ, Sexton J, Lennon R, Romani A, Mulinacci N, Vinceri FF, Lerman LO, Lerman A (2013) Beneficial effects of polyphenol-rich olive oil in patients with early atherosclerosis. Eur J Nutr 52:1223–1231
Moreno-Luna R, Muñoz-Hernandez R, Miranda ML, Costa AF, Jimenez-Jimenez L, Vallejo-Vaz AJ, Muriana FJGG, Villar J, Stiefel P (2012) Olive oil polyphenols decrease blood pressure and improve endothelial function in young women with mild hypertension. Am J Hypertens 25:1299–1304
Fitó M, Cladellas M, de la Torre R, Martí J, Alcántara M, Pujadas-Bastardes M, Marrugat J, Bruguera J, López-Sabater MC, Vila J, Covas MI, Members of the SOLOS Investigators (2005) Antioxidant effect of virgin olive oil in patients with stable coronary heart disease: a randomized, crossover, controlled, clinical trial. Atherosclerosis 181:149–158
Visioli F, Caruso D, Grande S, Bosisio R, Villa M, Galli G, Sirtori C, Galli C (2005) Virgin Olive Oil Study (VOLOS): vasoprotective potential of extra virgin olive oil in mildly dyslipidemic patients. Eur J Nutr 44:121–127
Ruano J, López-Miranda J, de la Torre R, Delgado-Lista J, Fernández J, Caballero J, Covas MI, Jiménez Y, Pérez-Martínez P, Marín C, Fuentes F, Pérez-Jiménez F (2007) Intake of phenol-rich virgin olive oil improves the postprandial prothrombotic profile in hypercholesterolemic patients. Am J Clin Nutr 86:341–346
Capurso C, Massaro M, Scoditti E, Vendemiale G, Capurso A (2014) Vascular effects of the Mediterranean diet part I: anti-hypertensive and anti-thrombotic effects. Vascul Pharmacol 63:118–126
Delgado-Lista J, Garcia-Rios A, Perez-Martinez P, Lopez-Miranda J, Perez-Jimenez F (2011) Olive oil and haemostasis: platelet function, thrombogenesis and fibrinolysis. Curr Pharm Des 17:778–785
Fernández de la Puebla RA, Pérez-Martínez P, Carmona J, López-Miranda Carmen Marín J, Paniagua JA, Fuentes F, Pérez-Jiménez F (2007) Factor VII polymorphisms influence the plasma response to diets with different fat content, in a healthy Caucasian population. Mol Nutr Food Res 51:618–624
Pacheco YM, López S, Bermúdez B, Abia R, Muriana FJG (2006) Extra-virgin vs. refined olive oil on postprandial hemostatic markers in healthy subjects. J Thromb Haemost 4:1421–1422
Oosthuizen W, Vorster HH, Jerling JC, Barnard HC, Smuts CM, Silvis N, Kruger A, Venter CS (1994) Both fish oil and olive oil lowered plasma fibrinogen in women with high baseline fibrinogen levels. Thromb Haemost 72:557–562
Harland JI (2012) Food combinations for cholesterol lowering. Nutr Res Rev 25:249–266
Trichopoulou A, Lagiou P (1997) Worldwide patterns of dietary lipids intake and health implications. Am J Clin Nutr 66:961S–964S
Hooper L, Martin N, Abdelhamid A, and Davey Smith G (2015) Reduction in saturated fat intake for cardiovascular disease. Cochrane database Syst Rev CD011737
Schwingshackl L, Hoffmann G (2013) Comparison of effects of long-term low-fat vs high-fat diets on blood lipid levels in overweight or obese patients: a systematic review and meta-analysis. J Acad Nutr Diet 113(12):1640–1661
EFSA Panel on Dietetic Products N and A (NDA) (2012) Scientific opinion on the substantiation of a health claim related to polyphenols in olive and maintenance of normal blood HDL cholesterol concentrations (ID 1639, further assessment) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA J 10:2848
Marrugat J, Covas M-I, Fitó M, Schröder H, Miró-Casas E, Gimeno E, López-Sabater MC, de la Torre R, Farré M, SOLOS Investigators (2004) Effects of differing phenolic content in dietary olive oils on lipids and LDL oxidation – a randomized controlled trial. Eur J Nutr 43:140–147
US Food and Drug Administration (2004) Press release P04-100, 1 Nov 2004
EFSA Panel on Dietetic Products N and A (NDA) (2011) Scientific opinion on the substantiation of health claims related to polyphenols in olive oil and protection of LDL particles from oxidative damage. EFSA J 2011:9
Holvoet P, Mertens A, Verhamme P, Bogaerts K, Beyens G, Verhaeghe R, Collen D, Muls E, Van de Werf F (2001) Circulating oxidized LDL is a useful marker for identifying patients with coronary artery disease. Arterioscler Thromb Vasc Biol 21:844–848
Meisinger C, Baumert J, Khuseyinova N, Loewel H, Koenig W (2005) Plasma oxidized low-density lipoprotein, a strong predictor for acute coronary heart disease events in apparently healthy, middle-aged men from the general population. Circulation 112:651–657
Navab M, Ananthramaiah GM, Reddy ST, Van Lenten BJ, Ansell BJ, Fonarow GC, Vahabzadeh K, Hama S, Hough G, Kamranpour N, JA B, Lusis AJ, Fogelman AM (2004) The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL. J Lipid Res 45:993–1007
Gimeno E, de la Torre-Carbot K, Lamuela-Raventós RM, Castellote AI, Fitó M, de la Torre R, Covas M-I, MC L-S (2007) Changes in the phenolic content of low density lipoprotein after olive oil consumption in men. A randomized crossover controlled trial. Br J Nutr 98:1243–1250
Gimeno E, Fitó M, Lamuela-Raventós RM, Castellote AI, Covas M, Farré M, de La Torre-Boronat MC, López-Sabater MC (2002) Effect of ingestion of virgin olive oil on human low-density lipoprotein composition. Eur J Clin Nutr 56:114–120
Castañer O, Fitó M, López-Sabater MC, Poulsen HE, Nyyssönen K, Schröder H, Salonen JT, De la Torre-Carbot K, Zunft H-F, De la Torre R, Bäumler H, Gaddi AV, Saez GT, Tomás M, Covas M-I, EUROLIVE Study Group (2011) The effect of olive oil polyphenols on antibodies against oxidized LDL. A randomized clinical trial. Clin Nutr 30:490–493
Vázquez-Velasco M, Esperanza Díaz L, Lucas R, Gómez-Martínez S, Bastida S, Marcos A, Sánchez-Muniz FJ (2011) Effects of hydroxytyrosol-enriched sunflower oil consumption on CVD risk factors. Br J Nutr 105:1448–1452
Ashton EL, Best JD, Ball MJ (2001) Effects of monounsaturated enriched sunflower oil on CHD risk factors including LDL size and copper-induced LDL oxidation. J Am Coll Nutr 20:320–326
Nicolaïew N, Lemort N, Adorni L, Berra B, Montorfano G, Rapelli S, Cortesi N, Jacotot B (1998) Comparison between extra virgin olive oil and oleic acid rich sunflower oil: effects on postprandial lipemia and LDL susceptibility to oxidation. Ann Nutr Metab 42:251–260
Hernáez Á, Remaley AT, Farràs M, Fernández-Castillejo S, Subirana I, Schröder H, Fernández-Mampel M, Muñoz-Aguayo D, Sampson M, Solà R, Farré M, de la Torre R, López-Sabater M-C, Nyyssönen K, Zunft H-JF, Covas M-I, Fitó M (2015) Olive oil polyphenols decrease LDL concentrations and LDL atherogenicity in men in a randomized controlled trial. J Nutr 145:1692–1697
Svegliati Baroni S, Amelio M, Fiorito A, Gaddi A, Littarru G, Battino M (1999) Monounsaturated diet lowers LDL oxidisability in type IIb and type IV dyslipidemia without affecting coenzyme Q10 and vitamin E contents. Biofactors 9:325–330
Fitó M, Guxens M, Corella D, Sáez G, Estruch R, de la Torre R, Francés F, Cabezas C, López-Sabater Mdel C, Marrugat J, García-Arellano A, Arós F, Ruiz-Gutierrez V, Ros E, Salas-Salvadó J, Fiol M, Solá R, Covas MI (2007) Effect of a traditional Mediterranean diet on lipoprotein oxidation: a randomized controlled trial. Arch Intern Med 167(11):1195–1203
Castelli WP, Garrison RJ, Wilson PW, Abbott RD, Kalousdian S, Kannel WB (1986) Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. JAMA 256:2835–2838
Barter PJ, Caulfield M, Eriksson M, Grundy SM, Kastelein JJP, Komajda M, Lopez-Sendon J, Mosca L, Tardif J-C, Waters DD, Shear CL, Revkin JH, Buhr KA, Fisher MR, Tall AR, Brewer B (2007) Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 357:2109–2122
Keene D, Price C, Shun-Shin MJ, Francis DP (2014) Effect on cardiovascular risk of high density lipoprotein targeted drug treatments niacin, fibrates, and CETP inhibitors: meta-analysis of randomised controlled trials including 117,411 patients. BMJ 349:g4379
Voight BF, Peloso GM, Orho-Melander M, Frikke-Schmidt R, Barbalic M, Jensen MK, Hindy G, Hólm H, Ding EL, Johnson T, Schunkert H, Samani NJ, Clarke R, Hopewell JC, Thompson JF, Li M, Thorleifsson G, Newton-Cheh C, Musunuru K, Pirruccello JP, Saleheen D, Chen L, Stewart AFR, Schillert A, Thorsteinsdottir U, Thorgeirsson G, Anand S, Engert JC, Morgan T, Spertus J, Stoll M, Berger K, Martinelli N, Girelli D, McKeown PP, Patterson CC, Epstein SE, Devaney J, Burnett M-S, Mooser V, Ripatti S, Surakka I, Nieminen MS, Sinisalo J, Lokki M-L, Perola M, Havulinna A, de Faire U, Gigante B, Ingelsson E, Zeller T, Wild P, de Bakker PIW, Klungel OH, Maitland-van der Zee A-H, Peters BJM, de Boer A, Grobbee DE, Kamphuisen PW, Deneer VHM, Elbers CC, Onland-Moret NC, Hofker MH, Wijmenga C, Verschuren WMM, Boer JMA, van der Schouw YT, Rasheed A, Frossard P, Demissie S, Willer C, Do R, Ordovas JM, Abecasis GR, Boehnke M, Mohlke KL, Daly MJ, Guiducci C, Burtt NP, Surti A, Gonzalez E, Purcell S, Gabriel S, Marrugat J, Peden J, Erdmann J, Diemert P, Willenborg C, König IR, Fischer M, Hengstenberg C, Ziegler A, Buysschaert I, Lambrechts D, Van de Werf F, Fox KA, El Mokhtari NE, Rubin D et al (2012) Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet 380:572–580
Rosenson RS, Brewer HB, Ansell BJ, Barter P, Chapman MJ, Heinecke JW, Kontush A, Tall AR, Webb NR (2016) Dysfunctional HDL and atherosclerotic cardiovascular disease. Nat Rev Cardiol 13:48–60
Khera AV, Cuchel M, de la Llera-Moya M, Rodrigues A, Burke MF, Jafri K, French BC, Phillips JA, Mucksavage ML, Wilensky RL, Mohler ER, Rothblat GH, Rader DJ (2011) Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. N Engl J Med 364:127–135
Rohatgi A, Khera A, Berry JD, Givens EG, Ayers CR, Wedin KE, Neeland IJ, Yuhanna IS, Rader DR, de Lemos JA, Shaul PW (2014) HDL cholesterol efflux capacity and incident cardiovascular events. N Engl J Med 371:2383–2393
Rosenson RS, Brewer HB, Davidson WS, Fayad ZA, Fuster V, Goldstein J, Hellerstein M, Jiang X-C, Phillips MC, Rader DJ, Remaley AT, Rothblat GH, Tall AR, Yvan-Charvet L (2012) Cholesterol efflux and atheroprotection: advancing the concept of reverse cholesterol transport. Circulation 125:1905–1919
Besler C, Lüscher TF, Landmesser U (2012) Molecular mechanisms of vascular effects of high-density lipoprotein: alterations in cardiovascular disease. EMBO Mol Med 4:251–268
Norata GD, Pirillo A, Catapano AL (2006) Modified HDL: biological and physiopathological consequences. Nutr Metab Cardiovasc Dis 16:371–386
Shao B (2012) Site-specific oxidation of apolipoprotein A-I impairs cholesterol export by ABCA1, a key cardioprotective function of HDL. Biochim Biophys Acta 1821:490–501
Bonnefont-Rousselot D, Motta C, Khalil AO, Sola R, La Ville AE, Delattre J, Gardès-Albert M (1995) Physicochemical changes in human high-density lipoproteins (HDL) oxidized by gamma radiolysis-generated oxyradicals. Effect on their cholesterol effluxing capacity. Biochim Biophys Acta 1255:23–30
Kontush A, Chapman MJ (2006) Functionally defective high-density lipoprotein: a new therapeutic target at the crossroads of dyslipidemia, inflammation, and atherosclerosis. Pharmacol Rev 58:342–374
Pirillo A, Norata GD, Catapano AL (2013) High-density lipoprotein subfractions – what the clinicians need to know. Cardiology 124:116–125
Sola R, Motta C, Maille M, Bargallo MT, Boisnier C, Richard JL, Jacotot B (1993) Dietary monounsaturated fatty acids enhance cholesterol efflux from human fibroblasts. Relation to fluidity, phospholipid fatty acid composition, overall composition, and size of HDL3. Arterioscler Thromb 13:958–966
Solà R, La Ville AE, Richard JL, Motta C, Bargalló MT, Girona J, Masana L, Jacotot B (1997) Oleic acid rich diet protects against the oxidative modification of high density lipoprotein. Free Radic Biol Med 22:1037–1045
Hernáez Á, Fernández-Castillejo S, Farràs M, Catalán Ú, Subirana I, Montes R, Solà R, Muñoz-Aguayo D, Gelabert-Gorgues A, Díaz-Gil Ó, Nyyssönen K, Zunft H-JF, de la Torre R, Martín-Peláez S, Pedret A, Remaley AT, Covas M-I, Fitó M (2014) Olive oil polyphenols enhance high-density lipoprotein function in humans: a randomized controlled trial. Arterioscler Thromb Vasc Biol 34:2115–2119
Farràs M, Castañer O, Martín-Peláez S, Hernáez Á, Schröder H, Subirana I, Muñoz-Aguayo D, Gaixas S, de la TR, Farré M, Rubió L, Díaz Ó, Fernández-Castillejo S, Solà R, Motilva MJ, Fitó M (2015) Complementary phenol-enriched olive oil improves HDL characteristics in hypercholesterolemic subjects. A randomized, double-blind, crossover, controlled trial. The VOHF study. Mol Nutr Food Res 59:1758–1770
Loued S, Berrougui H, Componova P, Ikhlef S, Helal O, Khalil A (2013) Extra-virgin olive oil consumption reduces the age-related decrease in HDL and paraoxonase 1 anti-inflammatory activities. Br J Nutr 110:1272–1284
Farràs M, Valls RM, Fernández-Castillejo S, Giralt M, Solà R, Subirana I, Motilva M-J, Konstantinidou V, Covas M-I, Fitó M (2013) Olive oil polyphenols enhance the expression of cholesterol efflux related genes in vivo in humans. A randomized controlled trial. J Nutr Biochem 24:1334–1339
Hernáez Á, Castañer O, Elosua R, Pintó X, Estruch R, Salas-Salvadó J, Corella D, Arós F, Serra-Majem L, Fiol M, Ortega-Calvo M, Ros E, Martínez-González MÁ, de la Torre R, López-Sabater MC, Fitó M (2017) Mediterranean diet improves high-density lipoprotein function in high-cardiovascular-risk individuals: A randomized controlled trial. Circulation 135(7):633–643
Servili M, Montedoro G (2002) Contribution of phenolic compounds to virgin olive oil quality. Eur J Lipid Sci Technol 104:602–613
Li L, Ishdorj G, Gibson SB (2012) Reactive oxygen species regulation of autophagy in cancer: implications for cancer treatment. Free Radic Biol Med 53:1399–1410
Lönn ME, Dennis JM, Stocker R (2012) Actions of “antioxidants” in the protection against atherosclerosis. Free Radic Biol Med 53:863–884
Wang JC, Bennett M (2012) Aging and atherosclerosis: mechanisms, functional consequences, and potential therapeutics for cellular senescence. Circ Res 111:245–259
Konstantinidou V, Covas M-I, Sola R, Fitó M (2013) Up-to date knowledge on the in vivo transcriptomic effect of the Mediterranean diet in humans. Mol Nutr Food Res 57:772–783
Pacheco YM, López S, Bermúdez B, Abia R, Villar J, Muriana FJG (2008) A meal rich in oleic acid beneficially modulates postprandial sICAM-1 and sVCAM-1 in normotensive and hypertensive hypertriglyceridemic subjects. J Nutr Biochem 19:200–205
Yaqoob P, Knapper JA, Webb DH, Williams CM, Newsholme E a, Calder PC (1998) Effect of olive oil on immune function in middle-aged men. Am J Clin Nutr 67:129–135
Voon PT, Ng TKW, Lee VKM, Nesaretnam K (2011) Diets high in palmitic acid (16:0), lauric and myristic acids (12:0 + 14:0), or oleic acid (18:1) do not alter postprandial or fasting plasma homocysteine and inflammatory markers in healthy Malaysian adults. Am J Clin Nutr 94:1451–1457
Dennis EA, Norris PC (2015) Eicosanoid storm in infection and inflammation. Nat Rev Immunol 15:511–523
Wardhana, Surachmanto ES, EA D (2011) The role of omega-3 fatty acids contained in olive oil on chronic inflammation. Acta Med Indones 43:138–143
Capron L (1993) Marine oils and prevention of cardiovascular diseases. Rev Prat 43:164–170
Beauchamp GK, Keast RSJ, Morel D, Lin J, Pika J, Han Q, Lee C-H, Smith AB, Breslin PAS (2005) Phytochemistry: ibuprofen-like activity in extra-virgin olive oil. Nature 437:45–46
Lucas L, Russell A, Keast R (2011) Molecular mechanisms of inflammation. Anti-inflammatory benefits of virgin olive oil and the phenolic compound oleocanthal. Curr Pharm Des 17:754–768
Migliori M, Panichi V, de la Torre R, Fitó M, Covas M, Bertelli A, Muñoz-Aguayo D, Scatena A, Paoletti S, Ronco C (2015) Anti-inflammatory effect of white wine in CKD patients and healthy volunteers. Blood Purif 39:218–223
Fitó M, Cladellas M, de la Torre R, Martí J, Muñoz D, Schröder H, Alcántara M, Pujadas-Bastardes M, Marrugat J, López-Sabater MC, Bruguera J, Covas MI, SOLOS Investigators (2008) Anti-inflammatory effect of virgin olive oil in stable coronary disease patients: a randomized, crossover, controlled trial. Eur J Clin Nutr 62:570–574
Mena M-P, Sacanella E, Vazquez-Agell M, Morales M, Fitó M, Escoda R, Serrano-Martínez M, Salas-Salvadó J, Benages N, Casas R, Lamuela-Raventós RM, Masanes F, Ros E, Estruch R (2009) Inhibition of circulating immune cell activation: a molecular antiinflammatory effect of the Mediterranean diet. Am J Clin Nutr 89:248–256
Casas R, Urpi-Sardà M, Sacanella E, Arranz S, Corella D, Castañer O, Lamuela-Raventós RM, Salas-Salvadó J, Lapetra J, Portillo MP, Estruch R (2017) Anti-inflammatory effects of the Mediterranean diet in the early and late stages of atheroma plaque development. Mediators Inflamm 2017:3674390
Casas R, Sacanella E, Urpí-Sardà M, Corella D, Castañer O, Lamuela-Raventos RM, Salas-Salvadó J, Martínez-González MA, Ros E, Estruch R (2016) Long-term immunomodulatory effects of a Mediterranean diet in adults at high risk of cardiovascular disease in the PREvención con DIeta MEDiterránea (PREDIMED) randomized controlled trial. J Nutr 146(9):1684–1693
Carrillo C, Cavia Mdel M, Alonso-Torre S (2012) Role of oleic acid in immune system; mechanism of action; a review. Nutr Hosp 27:978–990
Martín-Peláez S, Castañer O, Solà R, Motilva MJ, Castell M, Pérez-Cano FJ, Fitó M (2016) Influence of phenol-enriched olive oils on human intestinal immune function. Nutrients 8:213
Puertollano MA, Puertollano E, Alvarez de Cienfuegos G, de Pablo Martínez MA (2010) Olive oil, immune system and infection. Nutr Hosp 25:1–8
Puertollano MA, Puertollano E, Alvarez de Cienfuegos G, de Pablo MA (2007) Significance of olive oil in the host immune resistance to infection. Br J Nutr 98(Suppl 1):S54–S58
Baothman OA, Zamzami MA, Taher I, Abubaker J, Abu-Farha M (2016) The role of gut microbiota in the development of obesity and Diabetes. Lipids Health Dis 15:108
Landete JM, Curiel JA, Rodríguez H, de las Rivas B, Muñoz R (2008) Study of the inhibitory activity of phenolic compounds found in olive products and their degradation by Lactobacillus plantarum strains. Food Chem 107:320–326
Martínez I, Wallace G, Zhang C, Legge R, Benson AK, Carr TP, Moriyama EN, Walter J (2009) Diet-induced metabolic improvements in a hamster model of hypercholesterolemia are strongly linked to alterations of the gut microbiota. Appl Environ Microbiol 75:4175–4184
De Smet I, Van Hoorde L, De Saeyer N, Woestyne MV, Verstraete W (1994) In vitro study of bile salt hydrolase (BSH) activity of BSH isogenic Lactobacillus plantarum 80 strains and estimation of cholesterol lowering through enhanced BSH activity. Microb Ecol Health Dis 7:315–329
Brown MS, Goldstein JL (1983) Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis. Annu Rev Biochem 52:223–261
Leahy SC, Higgins DG, Fitzgerald GF, van Sinderen D (2005) Getting better with bifidobacteria. J Appl Microbiol 98:1303–1315
Corona G, Tzounis X, Assunta Dessì M, Deiana M, Debnam ES, Visioli F, Spencer JPE (2006) The fate of olive oil polyphenols in the gastrointestinal tract: implications of gastric and colonic microflora-dependent biotransformation. Free Radic Res 40:647–658
Martín-Peláez S, Mosele JI, Pizarro N, Farràs M, de la Torre R, Subirana I, Pérez-Cano FJ, Castañer O, Solà R, Fernandez-Castillejo S, Heredia S, Farré M, Motilva MJ, and Fitó M (2015) Effect of virgin olive oil and thyme phenolic compounds on blood lipid profile: implications of human gut microbiota. Eur J Nutr. https://doi.org/10.1007/s00394-015-1063-2
Soriguer F, Esteva I, Rojo-Martinez G, Ruiz de Adana MS, Dobarganes MC, García-Almeida JM, Tinahones F, Beltrán M, González-Romero S, Olveira G, Gómez-Zumaquero JM (2004) Oleic acid from cooking oils is associated with lower insulin resistance in the general population (Pizarra study). Eur J Endocrinol 150(1):33–39
Estruch R, Martínez-González MA, Corella D, Salas-Salvadó J, Ruiz-Gutiérrez V, Covas MI, Fiol M, Gómez-Gracia E, López-Sabater MC, Vinyoles E, Arós F, Conde M, Lahoz C, Lapetra J, Sáez G, Ros E (2006) PREDIMED Study Investigators. Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann Intern Med 145(1):1–11
Bogani P, Galli C, Villa M, Visioli F (2007) Postprandial anti-inflammatory and antioxidant effects of extra virgin olive oil. Atherosclerosis 190(1):181–6
Konstantinidou V, Covas MI, Muñoz-Aguayo D, Khymenets O, de la Torre R, Saez G, Tormos Mdel C, Toledo E, Marti A, Ruiz-Gutiérrez V, Ruiz Mendez MV, Fito M (2010) In vivo nutrigenomic effects of virgin olive oil polyphenols within the frame of the Mediterranean diet: a randomized controlled trial. FASEB J 24(7):2546–57
Acknowledgments
This work was supported by: Agència de Gestió d’Ajuts Universitaris i de Recerca (2014-SGR-240), Instituto de Salud Carlos III (CB06/03/0028, JR14/00008, JR17/00022, CD17/00122, and CES12/025), and the Spanish Ministry of Education, Culture and Sport (FPU12/01318). The CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN) is an initiative of the Instituto de Salud Carlos III.
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Hernáez, Á., Valussi, J., Pérez-Vega, A., Castañer, O., Fitó, M. (2019). Olive Oil and Health Effects. In: Mérillon, JM., Ramawat, K.G. (eds) Bioactive Molecules in Food. Reference Series in Phytochemistry. Springer, Cham. https://doi.org/10.1007/978-3-319-78030-6_33
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