Relevance of dietary glycerophospholipids and sphingolipids to human health.

Glycerophospholipids and sphingolipids participate in a variety of indispensable metabolic, neurological, and intracellular signaling processes. In this didactic paper we review the biological roles of phospholipids and try to unravel the precise nature of their putative healthful activities. We conclude that the biological actions of phospholipids activities potentially be nutraceutically exploited in the adjunct therapy of widely diffused pathologies such as neurodegeneration or the metabolic syndrome. As phospholipids can be recovered from inexpensive sources such as food processing by-products, ad-hoc investigation is warranted.

Argan oil reduces, in rats, the high fat diet-induced metabolic effects of obesity.

BACKGROUND AND AIM: Obesity is a multi-factorial disorder which is of worldwide concern. In addition to calorie control, some specific dietary components might help resolving some of the complication of obesity, by providing antioxidant and anti-inflammatory activities. We investigated the effect of argan oil supplementation on plasma lipid profile and oxidant-antioxidant status of rats with high-fat diet (HFD)-induced obesity compared with rats fed a normal diet (ND). METHODS AND RESULTS: We used an animal model of high fat diet-induced obesity to study the metabolic effects of argan oil and we measured several markers lipid and redox statuses. Consumption of a high-fat diet led to an increase in serum total cholesterol (TC), LDL-cholesterol (LDL-C), and triacylglycerols (TAG) concentrations; however, argan oil blunted the increases of TC, LDL-C and TG, glucose, and insulin. Plasma total antioxidant capacity, erythrocyte catalase and superoxide dismutase activities were lower, whereas plasma hydroperoxide, thiobarbituric acid-reacting substances, and susceptibility of LDL to copper-induced oxidation were higher in obese rats compared with normal rats. Administration of argan oil ameliorated all these indices of redox status. CONCLUSIONS: Proper diet and lifestyle should be foremost implemented to reduce the lipoprotein metabolism and oxidant/antioxidant status alterations brought about by obesity. In addition, argan oil reduces the metabolic effects of obesity and its use might be promoted within the context of a balanced diet.

Chronic hydroxytyrosol feeding modulates glutathione-mediated oxido-reduction pathways in adipose tissue: a nutrigenomic study.

BACKGROUND AND AIM: Hydroxytyrosol (HT) is the most prominent phenolic component of olives, olive oil, and their by-products, e.g. olive mill waste water. As the link between HT consumption (via extra virgin olive oil intake) and better cardiovascular prognosis is being scientifically validated, HT is entering the market as a potentially useful supplement for cardiovascular disease prevention. One of the target organs in cardiometabolic prevention is the adipose tissue, where inflammation, oxidative stress, and secretion of adipocytokines contribute to cardiovascular risk. METHODS AND RESULTS: We explored the nutrigenomic effects of long-term supplementation with nutritionally-relevant doses of HT, i.e. 0.03 gm% - with specific reference to the adipose tissue and glutathione metabolism - and we explored underlying mechanisms in vitro. We show that HT modulates the antioxidant network in the adipose tissue, as mediated by glutathione (GSH) and associated enzymes. We also confirmed the GSH-modulating activities of HT in cultured adipocytes, where low, physiological HT concentrations were able to blunt the H2O2-induced GSH/GSSG alteration indicative of oxidative stress. In terms of surrogate markers of cardiovascular disease, we recorded significantly decreased circulating leptin concentrations in mice fed with HT as compared with controls. CONCLUSIONS: HT - in nutritionally relevant amounts - is able to positively modulate the glutathione-driven antioxidant enzymatic machinery in the adipose tissue. Because HT is generally recognized as safe (GRAS) and exhibits an excellent safety profile in vitro and in vivo, its future employment as adjunct treatment of metabolic syndrome can be envisioned, pending specific trials.

Infusion of docosahexaenoic acid protects against myocardial infarction.

Most of the cardioprotective effects of long-chain omega 3 fatty acids, namely docosahexaenoic (DHA; 22:6n-3) and eicosapentaenoic (EPA; 20:5n-3), are due to their hypotriglyceridemic and anti-inflammatory effects, which lower the risk for cardiovascular disease and myocardial infarction. Little is known on the direct preventive activities of DHA and EPA on heart function. In isolated hearts, we studied (1) whether infused DHA is able to protect the heart from ischemia/reperfusion damage and (2) the role played by Notch-mediated signal transduction pathways in myocardial infarction. Perfusion with DHA before and before/after induction of ischemia reperfusion significantly diminished cardiac damage and afforded antioxidant protection. Mechanistically, infusion of DHA before and before/after the induction of ischemia differentially modulated the expression of Notch2 and 3 target genes. In particular, DHA increased the expression of Hey1 when infused pre- and pre/post-ischemia; Jagged 1 and the Notch2 receptors increased with DHA pre-ischemia, but not pre/post; Notch2 and 3 receptors as well as Delta increased following DHA administration pre- and (especially) pre/post-ischemia. In conclusion, while the precise nature of the Notch-mediated protection from ischemia/reperfusion afforded by DHA is as yet to be fully elucidated, our data add to the growing body of literature that indicates how systemic administration of DHA provides cardiovascular protection.

Polyphenols and cardiovascular disease: a critical summary of the evidence.

Epidemiological studies are clear: diets in which plant foods provide the major portion of caloric intake, e.g. the Mediterranean and the Japanese diets, are associated with a reduced risk of certain degenerative diseases like cancer and atherosclerosis. Although fats and proteins in plants, as opposed to those of animal origin, are responsible to some extent for these protective effects, the contribution of other plant food components may also be relevant. In the past few years, research on polyphenols has remarkably expanded and is unveiling several biological activities of these compounds. Alas, the marketing departments of several industries are jumping ahead of solid scientific evidence; as a consequence, unsubstantiated claims are being made and whole foods or fortified, enriched, or enhanced foods are being created and sold. Science is beginning to corroborate some of these claims, but much more research is needed and several myths are to be disproven. In this mini-review we critically discuss the current limitations of polyphenol research and we contend that, in addition to their putative antioxidant action, several biochemical and physiological processes might be influenced by polyphenols.

Olive oil and health: summary of the II international conference on olive oil and health consensus report, Jaén and Córdoba (Spain) 2008.

Olive oil (OO) is the most representative food of the traditional Mediterranean Diet (MedDiet). Increasing evidence suggests that monounsaturated fatty acids (MUFA) as a nutrient, OO as a food, and the MedDiet as a food pattern are associated with a decreased risk of cardiovascular disease, obesity, metabolic syndrome, type 2 diabetes and hypertension. A MedDiet rich in OO and OO per se has been shown to improve cardiovascular risk factors, such as lipid profiles, blood pressure, postprandial hyperlipidemia, endothelial dysfunction, oxidative stress, and antithrombotic profiles. Some of these beneficial effects can be attributed to the OO minor components. Therefore, the definition of the MedDiet should include OO. Phenolic compounds in OO have shown antioxidant and anti-inflammatory properties, prevent lipoperoxidation, induce favorable changes of lipid profile, improve endothelial function, and disclose antithrombotic properties. Observational studies from Mediterranean cohorts have suggested that dietary MUFA may be protective against age-related cognitive decline and Alzheimer's disease. Recent studies consistently support the concept that the OO-rich MedDiet is compatible with healthier aging and increased longevity. In countries where the population adheres to the MedDiet, such as Spain, Greece and Italy, and OO is the principal source of fat, rates of cancer incidence are lower than in northern European countries. Experimental and human cellular studies have provided new evidence on the potential protective effect of OO on cancer. Furthermore, results of case-control and cohort studies suggest that MUFA intake including OO is associated with a reduction in cancer risk (mainly breast, colorectal and prostate cancers).

Antioxidant activity of wild plants collected in Valsesia, an alpine region of Northern Italy.

A selection of wild plants collected in Valsesia (Northwest Italy) was screened for their in vitro antioxidant activity. Aerial parts of selected plants were dried at room temperature and powdered. Then, four sequential extractions were performed with increasing polarity solvents, i.e. n-hexane, chloroform, chloroform-methanol (9:1, v/v) and methanol. By employing different assays, it was shown that all the methanol extracts of the samples collected were endowed with antioxidant activity, though, as expected, their potency varied according to the different tests. In particular, plants of the Thymus and Achillea genus displayed the highest activity. Given that a diet rich in wild plants is associated with a reduced incidence of degenerative diseases, such as atherosclerosis and cancer, this study suggests that some Valsesia plants could be pharmaceutically exploited.

Lepidium meyenii (Maca) does not exert direct androgenic activities.

Maca is the edible root of the Peruvian plant Lepidum meyenii, traditionally employed for its purported aphrodisiac and fertility-enhancing properties. This study aimed at testing the hypothesis that Maca contains testosterone-like compounds, able to bind the human androgen receptor and promote transcription pathways regulated by steroid hormone signaling. Maca extracts (obtained with different solvents: methanol, ethanol, hexane and chloroform) are not able to regulate GRE (glucocorticoid response element) activation. Further experiments are needed to assess which compound, of the several Maca's components, is responsible of the observed in vivo effects.

International conference on the healthy effect of virgin olive oil.

1. Ageing represents a great concern in developed countries because the number of people involved and the pathologies related with it, like atherosclerosis, morbus Parkinson, Alzheimer's disease, vascular dementia, cognitive decline, diabetes and cancer. 2. Epidemiological studies suggest that a Mediterranean diet (which is rich in virgin olive oil) decreases the risk of cardiovascular disease. 3. The Mediterranean diet, rich in virgin olive oil, improves the major risk factors for cardiovascular disease, such as the lipoprotein profile, blood pressure, glucose metabolism and antithrombotic profile. Endothelial function, inflammation and oxidative stress are also positively modulated. Some of these effects are attributed to minor components of virgin olive oil. Therefore, the definition of the Mediterranean diet should include virgin olive oil. 4. Different observational studies conducted in humans have shown that the intake of monounsaturated fat may be protective against age-related cognitive decline and Alzheimer's disease. 5. Microconstituents from virgin olive oil are bioavailable in humans and have shown antioxidant properties and capacity to improve endothelial function. Furthermore they are also able to modify the haemostasis, showing antithrombotic properties. 6. In countries where the populations fulfilled a typical Mediterranean diet, such as Spain, Greece and Italy, where virgin olive oil is the principal source of fat, cancer incidence rates are lower than in northern European countries. 7. The protective effect of virgin olive oil can be most important in the first decades of life, which suggests that the dietetic benefit of virgin olive oil intake should be initiated before puberty, and maintained through life. 8. The more recent studies consistently support that the Mediterranean diet, based in virgin olive oil, is compatible with a healthier ageing and increased longevity. However, despite the significant advances of the recent years, the final proof about the specific mechanisms and contributing role of the different components of virgin olive oil to its beneficial effects requires further investigations.

Mediterranean food and health: building human evidence.

Adherence to a Mediterranean style diet affords protection from degenerative diseases such as cardiovascular disorders and cancer. Identification of the active constituents of the Mediterranean diet is crucial to the formulation of appropriate dietary guidelines. Also, research on the pharmacological properties of the "minor components" of this diet, eg vitamins and polyphenols, is very active and might lead to the formulation of functional foods and nutraceuticals. Even though in vitro data are plentiful, human studies are difficult to perform due to ethical and practical reasons. Yet, intervention trials represent the best approach to validate claims of healthful activities. This article reviews human evidence of the biological properties of olive oil and tomato constituents and illustrates a research approach by which the bioactive elements of a wild plant (Cynara cardunculus) are first studied in vitro to build biochemical evidence, then in vivo to obtain proof of their vasomodularoty activity.

The protective ability of the Mediterranean plant extracts against the oxidative DNA damage. The role of the radical oxygen species and the polyphenol content.

The polyphenol plant extracts content seems to be responsible for the scavenging activity of the reactive oxygen species (ROS), resulting in protection against DNA damage induced by the oxidative stress. This assumption was verified analyzing the effect of six Mediterranean plant extracts (Crepis vesicaria L, Origanum heracleoticum, Scandix australis L, Amaranthus sp., Scolymus hispanicus L, Thymus piperella L) on the oxidative DNA damage induced in lymphocytes by H(2)O(2) in relation to the polyphenolic content and the lymphocyte scavenging ability of ROS. The comet assay was used to evaluate oxidative DNA damage and the polyphenol content was analyzed by the Folin-Ciocalteu method. The fluorescence resulting from oxidation of ROS-sensitive dye, dihydrorofluorescein (DHF), was utilized as indicator of the ROS level. Pretreatment with all plant extracts produced the dose-dependent increase in the DNA protection up to the 0.2 microg/ml polyphenol content and the decrease above that dose. Only the Thymus piperella, similarly to quercetin, showed a strong positive correlation between the DNA protection and the polyphenol content, but negative correlation with ROS formation. In conclusion, the DNA protective ability of plant extracts seems to be related to the low polyphenol concentration and only to certain extent depends on the polyphenol ROS scavenging activity.

The role of antioxidants in the mediterranean diets: focus on cancer.

The incidence of certain cancers in the Mediterranean area is lower than in other areas of the world (e.g. in northern Europe and the USA). As nutrition and dietary factors comprise one of the three major factors for human carcinogenesis, the hypothesis was formulated that the dietary profile of the Mediterranean diet, rich in antioxidants, might exert preventive actions. Alas, the vast majority of experiments to prove this hypothesis have been obtained in vitro, and most of the necessary information on the absorption, distribution and metabolism of oligonutrients is currently lacking. Yet, even though the exact role of antioxidants in the Mediterranean diet is yet to be fully established, data from observational studies are strong enough to reinforce the notion that a diet low in saturated fat and alcohol and rich in plant food and whole grain, such as the traditional Mediterranean diet, is associated with lower risk of cancer and should be actively promoted.

Synthesis of long-chain polyunsaturated fatty acids is inhibited in vivo in hypercholesterolemic rabbits and in vitro by oxysterols.

Plasma total lipids, total cholesterol (cholesterol esters and free cholesterol) and oxysterol (mainly 7 beta-hydroxycholesterol (7 beta OH)) concentrations were significantly elevated in New Zealand rabbits fed a 2% cholesterol-containing diet with respect to controls fed the same diet without cholesterol. In addition, linoleic (18:2 n-6) and alpha-linolenic acid (18:3 n-3) plasma concentrations were significantly elevated in hypercholesterolemic rabbits, while concentrations of long-chain n-6 and n-3 derivatives were reduced. Studies in monocytic cell line THP-1 revealed that 7 beta OH markedly inhibited the conversion of 18:2 to 20:4 n-6 and of 18:3 to 22:6 n-3, indicating depression of the desaturation steps; in particular the inhibition was greater for the Delta 5 desaturation step. Furthermore, experiments of Real-Time PCR showed that 5-10 microM 7 beta OH decreased the Delta 5 gene expression. In conclusion, atherogenic oxysterols interfere with the production of long-chain polyunsaturated fatty acids from their precursors both in hypercholesterolemic rabbits and in cultured cells.

In vitro cytotoxicity to human cells in culture of some phenolics from olive oil.

The neutral red in vitro cytotoxicity assay was used to evaluate the comparative responses of human cells isolated from tissues of the oral cavity to olive oil phenolics. The cell lines used included normal gingival fibroblasts, immortalized, nontumorigenic gingival epithelial cells, and carcinoma cells from the salivary gland. No differences in the relative sensitivities to the phenolics amongst the three cell types were noted. In general, for all cell types, the sequence of increasing cytotoxicity was: oleuropein aglycone>oleuropein glycoside, caffeic acid>o-coumaric acid>cinnamic acid>>tyrosol, syringic acid, protocatechuic acid, vanillic acid. Cytotoxicity was noted only at phenolic concentrations far exceeding those attainable after habitual consumption, thus indicating that consumption of phenol-rich olive oil is safe.

Urinary excretion of olive oil phenols and their metabolites in humans.

We have recently demonstrated, in humans, the bioavailability of hydroxytyrosol (3,4-dihydroxyphenylethanol; HT), one of the major antioxidant components of virgin olive oil. In particular, we reported that this compound is present in lipoproteins involved in atherosclerotic processes and is excreted in the urine mainly as glucuronide-conjugate. The aim of the present study was to elucidate, in humans, the metabolic fate of HT after ingestion of virgin olive oil. After administration of virgin olive oil, 24-hour urine collections of healthy volunteers were prepared for gas chromatography-mass spectrometry analyses in order to identify and quantify HT and its metabolites homovanillic alcohol (HVA1c) and homovanillic acid (HVA). The results indicate that this compound undergoes the action of catechol-O-methyl transferase (COMT), enzymes involved in the catecholamine catabolism, resulting in an enhanced excretion of HVA1c. We also found a significant increase of HVA, indicating an oxidation of the ethanolic residue of HT and/or of HVA1c in humans. The excretion of both metabolites significantly correlated with the dose of administered HT.

Direct analysis of total antioxidant activity of olive oil and studies on the influence of heating.

Aim of this study was to evaluate the total antioxidant activity (TAA) of extra virgin olive oil (EVOO) and the effect of heating on the alpha-tocopherol content and TAA in relation to the presence of polyphenols, heating time, and temperature. Experiments included the measurement by ABTS decolorization assay of antioxidant capacity of alpha-tocopherol and 14 simple phenolic compounds present in EVOO, either dissolved in ethanol or added to refined olive oil, and the evaluation of TAA, total phenols, and alpha-tocopherol of six commercial EVOO and three olive oils. Finally, four experimental oils were prepared from refined olive oil containing a fixed amount (300 ppm) of alpha-tocopherol and increasing amounts of polyphenols (25, 125, 225, and 326 ppm) extracted from EVOO. The thermal stability of experimental oils under domestic heating conditions (heating time from 30 to 120 min, heating temperature from 160 to 190 degrees C) was studied by evaluating the loss of alpha-tocopherol and TAA according to a Latin square design. Results indicate that TAA of commercial oils is mainly due to their phenol and alpha-tocopherol content. Heating experiments suggest that polyphenols from EVOO are effective stabilizers of alpha-tocopherol during olive oil heating, thus contributing to the nutritional value of cooked foods.

Hydroxytyrosol, as a component of olive mill waste water, is dose- dependently absorbed and increases the antioxidant capacity of rat plasma.

Hydroxytyrosol is the most potent phenolic antioxidant of olive oil and olive mill waste water (OMWW) and its biological activities have stimulated research on its potential role in cardiovascular protection. However, evidence of the absorption of OMWW phenolics and on their possible in vivo activity has, until now, never been provided. Three groups male Sprague-Dawley rats were administered 1, 5, or 10 mg/Kg of the OMWW extract, respectively, providing 41.4, 207, and 414 microg/Kg of hydroxytyrosol, respectively. Urine was collected for 24 h and the urinary levels of hydroxytyrosol were quantified by mass spectrometry. Hydroxytyrosol was dose-dependently (R(2) = 0.95) absorbed and excreted in the urines mostly as a glucuronide conjugate. Further, the administration of an hydroxytyrosol-rich OMWW extract (10 mg/kg) to the rats was also associated with an increase of their plasma antioxidant capacity. Future experiments will eventually further clarify its metabolic fate and its in vivo actions.

Antiatherogenic components of olive oil.

Olive oil is the principal source of fat in the Mediterranean diet, which has been associated with a lower incidence of coronary heart disease and certain cancers. Olive oil is characterized by a high proportion of monounsaturated oleic acid, but the main peculiarity of extra-virgin oil is the presence of remarkable quantities of phenolic compounds, notably hydroxytyrosol and oleuropein, that provide high stability and strong taste. Recently, several studies have demonstrated that olive oil phenolics are powerful antioxidants, both in vitro and in vivo, and exert additional potent biologic activities that could partially account for the observed cardioprotective effects of the Mediterranean diet.