Current Pharmaceutical Design - Volume 17, Issue 8, 2011

Currently, nutrition therapy, in addition to their dietary support, can exert therapeutic effects without the undesirable effects that accompany the classical pharmacotherapy. In the last years, it has been highlighted that consumption of some foods as well as a nutritive function, has a profound influence on health outcomes. Importantly, recent research has suggested that dietary patterns such as the traditional Mediterranean diet of countries that surround the Mediterranean Sea, may confer protection from certain chronic diseases related to oxidative stress, inflammation and the immune system. Mediterranean diet is characterised by large amounts of foods naturally derived, such as vegetables, fruits, nuts, fish and grains and, in opposition to all other healthy diets, has a high content of total fat as its most distinctive feature. This is because of the usual high intake of olive oil, from olive tree, Olea europaea, the characteristic culinary fat of the Mediterranean area. In this respect, recent epidemiological studies have confirmed that habitual consumption of olive oil is effective in the prevention and treatment of certain pathologies especially, cardiovascular, neurodegeneration and aging, obesity, metabolic syndrome and diabetes, and diverse types of cancer principally breast colorectal cancer, lung, stomach, but also endometrium, ovary, and prostate [1-3]. The monounsaturated oleic acid, the more ubiquitous monounsaturated fat, is the main component of olive oil, accounting up to 80% of the total lipidic composition. The other major fatty acids present are the polyunsaturated linoleic acid (2.5-20%) and the saturated palmitic acid (10-20%). Olive oil also contains multiple minor components, present in a small amount (about 2 % of oil weight) with important biological properties. They are classified into two types: the unsaponifiable fraction, defined as the fraction extracted with solvents after the saponification of the oil and the soluble fraction. Together contain more than 230 chemical compounds such as aliphatic and triterpenic alcohols, sterols, hydrocarbons, vitamins such as α- and γ-tocopherols (around 200 ppm) and β-carotene, phytosterols and pigments, volatile compounds and polyphenols including, simple phenols (hydroxytyrosol, tyrosol), aldehydic secoiridoids, flavonoids and lignans acetoxypinoresinol, pinoresinol) among others. In fact, the phenolic fraction is in part, responsible for olive oil oxidative stability and sensory attributes, and it is considered an important parameter in the evaluation of virgin olive oil quality [4] The content of the minor components of an olive oil varies, depending on the cultivar, climate, ripeness of the olives at harvesting, and the processing system employed to produce the types of olive oil currently present on the market: extra-virgin, virgin, olive oil or pomace. Virgin olive oil (VOO) is that one obtained from the fruit of the olive tree solely by mechanical or other physical means under conditions that do not lead to alteration in the oil. It has not undergone any treatment other than washing, decantation, centrifugation or filtration. Extra-VOOs are VOOs with a free acidity, expressed as g of oleic acid/100 g of olive oil, less than 0.8 g. Certain VOOs in agreement with the International Olive Oil Council Regulation are submitted to a refining process in which some components, mainly phenolic compounds, and to a lesser degree squalene, are lost. By mixing virgin and refined olive oil an ordinary olive oil (olive oil) is produced and marketed. After VOO production, the rest of the olive drupe and seed is processed and submitted to a refining process, resulting in pomace olive oil, to which a certain quantity of VOO is added before marketing [5]. Traditionally the beneficial effects of VOO have been attributed to its high monounsaturated fatty acid (MUFA) content (oleic acid) as it protects lipoproteins and cellular membranes, from oxidative damage. There is likewise good evidence that the high proportion of oleic acid plays a protective role in cardiovascular diseases [6]. Besides, in most case-control and cohort studies have shown that oleic acid is associated with a reduction in the risk of cancer (mainly breast as it prevents the overexpression of HER2 (Her-2/neu, erB-2), a well-characterized oncogene that plays a key role in etiology, progression and response to chemotherapy and endocrine therapy, in approximately 20% of breast carcinomas [7] but also colorectal and prostate cancer [8,9]. In addition to MUFA evidences have accumulated on the favourable properties of minor though highly bioactive components of VOOs, particularly the phenolic compounds, which have shown a broad spectrum of bioactive properties, including anti-inflammatory, antioxidant, antimicrobial, antiproliferative, antiarrhythmic, platelet antiaggregant and vasodilatory effects [10-13]. Nevertheless, dietary intervention trials, observational studies or in vitro and in vivo experiments have shown that the health benefit of VOO is attributable to the combined properties of all its constituents, namely MUFA and minor polar and non-polar compounds. Actually, it has been shown significant effects on the lipid profile with a decrease in LDL-cholesterol, and higher HDL/total cholesterol ratio versus saturated fatty acids and a reduction of LDL oxidizability. In the same way, it has been confirmed olive oil consumption is accompanied by a recovery of endothelial function and blood pressure control in addition to a promotion a reduction in thrombogenesis, both by a decrease of coagulation factors and platelet aggregation [14] In normal subjects and patients with type-2 diabetes it has been observed an improvement of glucose metabolism. Also there is experimental evidence concerning the favourable influence of olive oil on chronic inflammatory diseases such as gastric ulcer and inflammatory bowel disease [15,16]. Besides, studies in human cell lines and experimental models suggest a potential protective effect of VOO on the initiation, promotion and progression of carcinogenesis. Such protective action on cancer may be mediated through several mechanisms, mainly, changes in the composition and structure of tumour cells membranes, changes in eicosanoid biosynthesis or intracellular signaling pathways, modulation of gene expression, reduced cellular oxidative stress and DNA damage, and modulation of the immune system and hormonal balance in hormone-dependent cancers, such as breast and prostate [12]. Furthermore, recent studies have brought new insights of the favourable effects olive oil effects on obesity enhancing fat oxidation and optimizing energy metabolism in obesity conditions. On the other hand, recent reports suggest that VOO diets protects in age-related cognitive decline and Alzheimer's disease [9,12]. The purpose of this issue is intended to provide the reader an up-date of the beneficial activity of olive oil its bioactive constituents and the plausible molecular mechanisms of action.

Chronic inflammation is a critical factor in the pathogenesis of many inflammatory disease states including cardiovascular disease, cancer, diabetes, degenerative joint diseases and neurodegenerative diseases. Chronic inflammatory states are poorly understood, however it is known that dietary habits can evoke or attenuate inflammatory responses. Popular methods to deal with inflammation and its associated symptoms involve the use of non steroidal anti-inflammatory drugs, however the use of these drugs are associated with severe side effects. Therefore, investigations concerned with natural methods of inflammatory control are warranted. A traditional Mediterranean diet has been shown to confer some protection against the pathology of chronic diseases through the attenuation of proinflammatory mediators and this has been partially attributed to the high intake of virgin olive oil accompanying this dietary regime. Virgin olive oil contains numerous phenolic compounds that exert potent anti-inflammatory actions. Of interest to this paper is the recently discovered phenolic compound oleocanthal. Oleocanthal is contained in virgin olive oil and possesses similar anti-inflammatory properties to ibuprofen. This pharmacological similarity has provoked interest in oleocanthal and the few studies conducted thus far have verified its anti-inflammatory and potential therapeutic actions. A review of the health benefits of the Mediterranean diet and antiinflammatory properties of virgin olive oil is presented with the additional emphasis on the pharmacological and anti-inflammatory properties of the phenolic compound oleocanthal.

After decades of epidemiological, clinical and experimental research, it has become clear that consumption of Mediterranean dietary patterns rich in olive oil has a profound influence on health outcomes, including obesity, metabolic syndrome (MetS) and diabetes mellitus. Traditionally, many beneficial properties associated with this oil have been ascribed to its high oleic acid content. Olive oil, however, is a functional food that, besides having high-monounsaturated (MUFA) content, contains other minor components with biological properties. In this line, phenolic compounds have shown antioxidant and antiinflammatory properties, prevent lipoperoxidation, induce favorable changes of lipid profile, improve endothelial function, and disclose antithrombotic properties. Research into the pharmacological properties of the minor components of olive oil is very active and could lead to the formulation of functional food and nutraceuticals. Although more data are mandatory the Mediterranean diet rich in olive oil does not contribute to obesity and appears to be a useful tool in the lifestyle management of the MetS. Moreover there is good scientific support for MUFA diets, especially those based on olive oil, as an alternative approach to low-fat diets for the medical nutritional therapy in diabetes. The objective of this review is to present evidence illustrating the relationship between Mediterranean diet, olive oil and metabolic diseases, including obesity, MetS and diabetes mellitus and to discuss potential mechanisms by which this food can help in disease prevention and treatment

Mediterranean diet is one of the healthiest nutritional models used in developed countries. The actual interest in this dietary model is based in two main premises. First, the high palatability for the consumer, which aids to the adherence to the model on a life-long basis, and second, the mounting evidence on the beneficial properties that its consumption provokes in cardiovascular risk factors, cancer and cognitive age associated decline. Olive oil is the principal component of Mediterranean diet, both by its predominant position as the main energy source, and its presence in almost all cooked and/or seasoned food. The influence of the olive oil on the beneficial effects of the Mediterranean diet is well known. Albeit an initial stage in which monounsaturated fatty acids (mainly oleic acid) were studied as the sole player of these effects, the knowledge about the micronutrients has evolved to a much more complex model in which the processing of the oil and the content in some minor contents of the virgin olive oil play a fundamental role. In this article we will review the current evidences that relate olive oil with the haemostatic system.

In addition to its high proportion of oleic acid (which is considered as “neutral” in terms of cardioprotection), extra virgin olive oil is rich in phenolic compounds, which other vegetable oils do not contain. This review critically appraises the current scientific evidence of a healthful role of olive phenols, with particular emphasis on hydroxytyrosol and related molecules.

Consumption of olive oil has been related to reduced risk of several diseases, including various neoplasms. In this paper, we reviewed epidemiological studies on olive oil and cancer published up to 2010. We performed a systematic literature search in the Medline database and, after assessment of relevant papers, we included 25 studies providing original data on olive oil consumption and cancer risk. We also performed a meta-analysis of studies of breast cancer, calculating the pooled relative risk (RR), and the corresponding 95% confidence intervals (CI), for high vs. low olive oil consumption. Several studies conducted in Southern Europe reported olive oil consumption as a favourable indicator of breast, digestive tract, and particularly upper aero-digestive tract cancers. For the latter, after adjustment for alcohol and tobacco use, the RRs between extreme levels of olive oil consumption were 0.3-0.4, and there was an over 5- fold difference in risk between subjects consuming mainly olive oil and those consuming mainly butter. The summary RR of breast cancer was 0.62 (95% CI, 0.44-0.88) for the highest vs. lowest level of olive oil consumption. Thus, preferring olive oil to other added lipids, particularly those rich in saturated fats, can decrease the risk of upper digestive and respiratory tract neoplasms, breast and, possibly, colorectal and other cancer sites.

Breast cancer is the most common cancer among women worldwide. In addition to genetic and endocrine factors, the environment, and specifically dietary habits, plays a key role in the aetiology of this malignancy. Epidemiological and, especially, experimental studies have shown a relationship between dietary lipids and breast cancer although there are conflicting results concerning their potential to modify cancer risk in humans. Abundant data have attributed a potential chemopreventive effect to extra-virgin olive oil (EVOO), the main source of fat in the Mediterranean diet, which is associated with low incidence and mortality rates from cardiovascular disease and some cancers, including that of the breast. It is well-established that the healthy effects of EVOO can be attributed both to its particular fatty acid composition (a high content in oleic acid (OA), a suitable quantity of essential polyunsaturated fatty acids (PUFA) and a relatively low n-6 PUFA/n-3 PUFA ratio) and its richness in minor bioactive compounds such as squalene and phenolic antioxidants. The specific mechanisms by which EVOO and other dietary lipids may exert their modulatory effects on cancer are not fully understood although abundant research has proposed the following: They influence in the stages of the carcinogenesis process, oxidative stress, alteration of the hormonal status, modification of the structure and function of cell membranes, modulation of cell signalling transduction pathways, regulation of gene expression and influence in the immune system. This article will explore the current knowledge of these mechanisms, including our own results in the context of the international literature.

Traditionally, nutrients such as fatty acids have been viewed as substrates for the generation of high-energy molecules and as precursors for the biosynthesis of macromolecules. However, accumulating data from multiple lines of evidence suggest that dietary fatty acids are linked not only to health promotion but also to disease pathogenesis. Metabolism in humans is regulated by complex hormonal signals and substrate interactions. For many years, the clinical focus has centered on a wide metabolic picture after an overnight fast. Nonetheless, the postprandial state (i.e., “the period that comprises and follows a meal”) is an important one, and silent disturbances in this period are involved in the genesis of numerous pathological conditions, including atherosclerosis. In this review article, we present an overview of the evidence demonstrating the relevance of oleic acid in olive oil on different nutritionrelated issues. We also discuss the impact of oleic acid in olive oil and its clinical relevance to major risk factors for cardiovascular disease in the context of the postprandial state and with regard to other dietary fatty acids.

NGAL (Neutrophil Gelatinase-Associated Lipocalin) is a small 25-kD peptide belonging to the lipocalin superfamily. Several studies highlight its role as an organ injury and disease activity biomarker. In the present review, instead, we wanted to study NGAL as a precocious marker of therapeutic response in renal and non-renal diseases (glomerulonephritis, vasculitis, LES, Crohn's disease and other chronic inflammatory pathologies). The obtained outcomes support the hypothesis that NGAL could be employed as a biomarker of response to different therapeutic schemes, because its levels sensibly and precociously change compared to other haematologic and biochemical parameters.