Moderate Consumption of Beer (with and without Ethanol) and Menopausal Symptoms: Results from a Parallel Clinical Trial in Postmenopausal Women.

The menopausal transition can be a challenging period for women's health and a trigger of uncomfortable symptoms. Beer is the main food source of isoxanthohumol, a precursor of 8-prenylnaringenin, the strongest phytoestrogen identified to date. As phytoestrogens are reported to reduce perimenopausal symptoms, we evaluated if a daily moderate consumption of beer with (AB) and without alcohol (NAB) could improve menopausal symptoms and modify cardiovascular risk factors. A total of 37 postmenopausal women were enrolled in a parallel controlled intervention trial and assigned to three study groups: 16 were administered AB (330 mL/day), 7 NAB (660 mL/day), and 14 were in the control group. After a 6-month follow-up of the 34 participants who finished the trial, both interventions (AB and NAB) significantly reduced the severity of the menopause-related symptoms (p-value AB vs. Control: 0.009; p-value NAB vs. Control: 0.033). Moreover, AB had a beneficial net effect on psychological menopausal discomforts compared to the control group. As the sex hormone profile did not differ significantly between the study groups, the effects of both types of beers (AB and NAB) are attributed to the non-alcoholic fraction of beer. Furthermore, moderate NAB consumption improved the lipid profile and decreased blood pressure in postmenopausal women.

Dual Behavior of Long-Chain Fatty Acids and Their Cyclooxygenase/Lipoxygenase Metabolites on Human Intestinal Caco-2 Cell Growth.

Etiology of colorectal cancer (CRC) is related, at least in part, with nutritional profile and epidemiological data indicating a key role of dietary fat on CRC pathogenesis. Moreover, inflammation and eicosanoids produced from arachidonic acid might have a pivotal role in CRC development. However, the effect of specific fatty acids (FAs) on intestinal epithelial cell growth is not completely studied now. By this reason, the aim of this work is to unravel the effect of different saturated and unsaturated long-chain fatty acids (LCFA) and some LCFA metabolites on CRC cell line growth and their possible mechanisms of action. Our results demonstrated that oleic acid is a potent mitogenic factor to Caco-2 cells, at least in part, through 10-hydroxy-8-octadecenoic synthesized by lipoxigenase pathway, whereas polyunsaturated FAs such as eicosapentaenoic (EPA) acid has a dual behavior effect depending on its concentration. A high concentration, EPA induced apoptosis through intrinsic pathway, whereas at low concentration induced cell proliferation that could be related to the synthesis of eicosanoids such as prostaglandin E3 and 12-hydroxyeicosapentaenoic acid and the subsequent induction of mitogenic cell signaling pathways (ERK 1/2, CREB, p38α). Thus, this study contributes to understand the complicated relationship between fat ingest and CRC.

Effects of the Non-Alcoholic Fraction of Beer on Abdominal Fat, Osteoporosis, and Body Hydration in Women.

Several studies have shown that binge drinking of alcoholic beverages leads to non-desirable outcomes, which have become a serious threat to public health. However, the bioactive compounds in some alcohol-containing beverages might mitigate the negative effects of alcohol. In beer, the variety and concentration of bioactive compounds in the non-alcoholic fraction suggests that its consumption at moderate levels may not only be harmless but could also positively contribute to an improvement of certain physiological states and be also useful in the prevention of different chronic diseases. The present review focuses on the effects of non-alcoholic components of beer on abdominal fat, osteoporosis, and body hydration in women, conditions selected for their relevance to health and aging. Although beer drinking is commonly believed to cause abdominal fat deposition, the available literature indicates this outcome is inconsistent in women. Additionally, the non-alcoholic beer fraction might improve bone health in postmenopausal women, and the effects of beer on body hydration, although still unconfirmed seem promising. Most of the health benefits of beer are due to its bioactive compounds, mainly polyphenols, which are the most studied. As alcohol-free beer also contains these compounds, it may well offer a healthy alternative to beer consumers.

Polyphenols in Urine and Cardiovascular Risk Factors: A Cross-Sectional Analysis Reveals Gender Differences in Spanish Adolescents from the SI! Program.

(1) Background: Epidemiological studies have shown an inverse association between polyphenol intake and cardiovascular risk factors (CVRFs) in adults, but few have provided information about adolescents. The aim of this study was to evaluate the relationship between urinary total polyphenol excretion (TPE) and CVRFs in adolescents. (2) Methods: A cross-sectional study was performed in 1194 Spanish adolescents from the SI! (Salud Integral) program. TPE in urine samples was determined by the Folin-Ciocalteu method, after solid-phase extraction, and categorized into quartiles. The association between TPE and CVRFs was estimated using mixed-effect linear regression and a structural equation model (SEM). (3) Results: Linear regression showed negative associations among the highest quartile of TPE and body fat percentage (B = -1.75, p-value = <0.001), triglycerides (TG) (B = -17.68, p-value = <0.001), total cholesterol (TC) (B = -8.66, p-value = 0.002), and low-density lipoprotein (LDL)-cholesterol (LDL-C) (B = -4.09, p-value = 0.008) in boys, after adjusting for all confounder variables. Negative associations between TPE quartiles and systolic blood pressure (SBP), diastolic blood pressure (DBP), and TC were also found in girls. Moreover, a structural equation model revealed that TPE was directly associated with body composition and blood glucose and indirectly associated with blood pressure, TG, LDL-C, and high-density lipoprotein-cholesterol (HDL-C) in boys. (4) Conclusions: Higher concentrations of TPE were associated with a better profile of cardiovascular health, especially in boys, while in girls, the association was not as strong.

Bioactive Compounds of Mediterranean Cooked Tomato Sauce (Sofrito) Modulate Intestinal Epithelial Cancer Cell Growth Through Oxidative Stress/Arachidonic Acid Cascade Regulation.

Mediterranean diet (MD) is associated with a low incidence of colorectal cancer, but the specific dietary constituents involved and mechanisms related to these beneficial effects are still sparse. Sofrito, a traditional MD preparation, is a mix of foods characteristics of MD such as tomato, onion, garlic, and extra virgin olive oil, which contains many bioactive phenolic compounds and carotenoids. The aim of the present study was to determine the action of these components of sofrito on reactive oxygen species and eicosanoid production as well as the cell growth/cell cycle in adenocarcinoma cell cultures. We observed that hydroxytyrosol, naringenin, naringenin glucuronide, and to a lesser extent lycopene and ß-carotene modulate these events in Caco-2 cell cultures. Interestingly, we also found an additive action of these bioactive compounds that could explain these biological actions on concentrations reached after the consumption of a traditional MD.

Erratum: Dietary Patterns and Cardiovascular Risk Factors in Spanish Adolescents: A Cross-Sectional Analysis of the SI! Program for Health Promotion in Secondary Schools; Nutrients 2019, 11, 2297.

The authors have requested that the following changes be made to their paper [...].

Dietary Patterns and Cardiovascular Risk Factors in Spanish Adolescents: A Cross-Sectional Analysis of the SI! Program for Health Promotion in Secondary Schools.

Previous studies on the association between dietary habits and cardiovascular risk factors (CVRF) in adolescents have generated conflicting results. The aim of this study was to describe dietary patterns (DP) in a large sample of Spanish adolescents and to assess their cross-sectional relationship with CVRF. In total, 1324 adolescents aged 12.5 ± 0.4 years (51.6% boys) from 24 secondary schools completed a self-reported food frequency questionnaire. DPs were derived by cluster analysis and principal component analysis (PCA). Anthropometric measurements, blood pressure, lipid profile, and glucose levels were assessed. Linear mixed models were applied to estimate the association between DPs and CVRF. Three DP-related clusters were obtained: Processed (29.2%); Traditional (39.1%); and Healthy (31.7%). Analogous patterns were obtained in the PCA. No overall differences in CVRF were observed between clusters except for z-BMI and z-FMI values, total cholesterol, and non-HDL cholesterol, with the Processed cluster showing the lowest mean values. However, differences were small. In conclusion, the overall association between DPs, as assessed by two different methods, and most analyzed CVRF was weak and not clinically relevant in a large sample of adolescents. Prospective analysis may help to disentangle the direction of these associations.

Extra Virgin Olive Oil Minor Compounds Modulate Mitogenic Action of Oleic Acid on Colon Cancer Cell Line.

Experimental and clinical findings suggest that olive oil has a protective effect, whereas oleic acid consumption induces colorectal cancer (CRC). Considering this apparent contradiction and that olive oil is a complex mix of fatty acids, mainly oleic acid and minor compounds such as phenolic compounds, lignans, hydrocarbons, and triterpenes, we study its effects on intestinal epithelial cell growth. Our results show that oleic acid (1-100 µM) but not elaidic acid induced DNA synthesis and Caco-2 cell growth (2-fold higher than cells without growth factors, p < 0.05). These effects were inhibited by 5-lipoxygenase inhibitors as well as the leukotriene antagonist (p < 0.05), suggesting the implication of this pathway in this mitogenic action. Hydroxytyrosol, oleuropein, pinoresinol, squalene, and maslinic acid (0.1-10 µM) reverted DNA synthesis and Caco-2 cell growth induced by oleic acid. These effects were not the consequence of the cell cycle arrest or the impairment of cell viability with the exception of hydroxytyrosol and maslinic acid that induced cell detachment and apoptosis (35.6 ± 2.3 and 43.2 ± 2.4%, respectively) at the higher concentration assayed. Oleuropein effects can be related with hydroxytyrosol release as a consequence of oleuropein hydrolysis by Caco-2 cells (up to 25%). Furthermore, hydroxytyrosol modulates the arachidonic acid cascade, and this event can be associated with its antimitogenic action. In conclusion, oleic acid and oleic acid in the presence of olive oil representative minor components have opposite effects, suggesting that the consumption of seed oils, high oleic acid seed oils, or olive oil will probably have different effects on CRC.

Bioactive Compounds of Cooked Tomato Sauce Modulate Oxidative Stress and Arachidonic Acid Cascade Induced by Oxidized LDL in Macrophage Cultures.

Sofrito is a mix of tomato, onion, garlic, and olive oil, which contains phenolic compounds and carotenoids. Consumption of tomato-based sofrito has been related to a lower risk of cardiovascular events, but the mechanisms behind such beneficial effects remain unclear. This study aimed to analyze the effects of representative sofrito compounds such as naringenin, hydroxytyrosol, lycopene, and ß-carotene on mechanisms involved in the pathogenesis of atherosclerosis. We demonstrated that both phenolic compounds and both carotenoids studied were able to inhibit low density lipoproteins (LDL) oxidation, as well as oxidative stress and eicosanoid production induced by oxidized LDL (oxLDL) in macrophage cultures. These effects were not the consequences of disturbing oxLDL uptake by macrophages. Finally, we observed an additive effect of these sofrito compounds, as well as the activity of a main naringenin metabolite, naringenin 7-O-ß-d-glucuronide on LDL oxidation and oxidative stress.

Rationale and design of the school-based SI! Program to face obesity and promote health among Spanish adolescents: A cluster-randomized controlled trial.

Unhealthy habits in adolescents are increasing at an alarming rate. The school offers a promising environment in which to implement effective preventive strategies to improve adolescents' lifestyle behaviors. The SI! Program is a multilevel multicomponent school-based health-promotion intervention aimed at all stages of compulsory education in Spain. We present the study design of the SI! Program for Secondary Schools, targeting adolescents aged 12 to 16 years. AIM: The main goal of this study is to evaluate the impact of the SI! Program educational intervention on adolescent lifestyle behaviors and health parameters. METHODS: The study was designed as a cluster-randomized controlled intervention trial and enrolled 1326 adolescents from 24 public secondary schools in Spain, together with their parents/caregivers. Schools and their students were randomly assigned to the intervention group (the SI! curriculum-based educational program over 2 or 4 academic years) or to the control group (usual curriculum). The primary endpoint will be the change from baseline at 2-year and 4-year follow-up in the composite Ideal Cardiovascular Health (ICH) score, consisting of four health behaviors (body mass index, dietary habits, physical activity, and smoking) and three health factors (blood pressure, total cholesterol, and glucose). Secondary endpoints will include 2-year and 4-year changes from baseline in ICH score subcomponents, the Fuster-BEWAT health scale, adiposity markers (waist circumference and body composition), polyphenol and carotenoid intake, and emotion management. DISCUSSION: The overarching goal of the SI! Program is to instill healthy behaviors in children and adolescents that can be sustained into adulthood. The SI! Program for Secondary School is a comprehensive health-promotion intervention targeting 12-16-year-old adolescents and their immediate environment. The present study addresses the optimal timing and impact of the educational intervention on health in adolescence.

Resveratrol Analogs with Antioxidant Activity Inhibit Intestinal Epithelial Cancer Caco-2 Cell Growth by Modulating Arachidonic Acid Cascade.

trans-Resveratrol has beneficial effects on colorectal cancer, through its antioxidant capacity, and its roles in regulating eicosanoid synthesis. This study determines how changes in resveratrol structure affected its biological activities. Our results showed that trans- and cis-resveratrol and hydroxylated analogs (piceatannol) (10-25 µM) displayed similar antioxidant activities (2-3 fold higher than trolox) and inhibit eicosanoid synthesis and Caco-2 growth (76.5 ± 2.7%, 48.2 ± 3.1% and 41.1 ± 2.3%, p ≤ 0.05). These effects can be related with an increase of the percentage of cells in the S phase (156.3 ± 5.6, 91.2 ± 3.3 and 64.1 ± 2.8, p ≤ 0.05) as a consequence of the impairment of the cells in G0/G1. Furthermore, we observed that these molecules induce apoptosis at 100 µM (48.2 ± 6.6%, p ≤ 0.05; 4.3 ± 2.5% and 21.2 ± 3.3%, p ≤ 0.05). These actions were related with changes of the mitochondrial membrane potential involved in the intrinsic pathway of apoptosis. However, methoxylated (pterostilbene, pinostilbene, trans-trimethoxy-resveratrol, and CAY10616) (0.1-10 µM) and halogenated (PDM11, CAY10464, PDM2, and CAY465) (1-10 µM) stilbenes inhibited Caco-2 cell growth, with a higher potency than resveratrol (50% inhibition at 0.1-1 µM) but without effects on oxidative stress and arachidonic acid cascade. Thus, our results show that the antioxidant effect of hydroxyl stilbenes is related to eicosanoid synthesis regulation and the basic stilbene structure of two benzene rings bonded through a central ethylene, is responsible for its effects on Caco-2 cell growth/DNA synthesis/cell cycle independently of redox state/eicosanoid synthesis modulation.

Health Effects of Resveratrol: Results from Human Intervention Trials.

The effect of resveratrol (RV) intake has been reviewed in several studies performed in humans with different health status. The purpose of this review is to summarize the results of clinical trials of the last decade, in which RV was determined in biological samples such as human plasma, urine, and feces. The topics covered include RV bioavailability, pharmacokinetics, effects on cardiovascular diseases, cognitive diseases, cancer, type 2 diabetes (T2D), oxidative stress, and inflammation states. The overview of the recent research reveals a clear tendency to identify RV in plasma, showing that its supplementation is safe. Furthermore, RV bioavailability depends on several factors such as dose, associated food matrix, or time of ingestion. Notably, enterohepatic recirculation of RV has been observed, and RV is largely excreted in the urine within the first four hours after consumption. Much of the research on RV in the last 10 years has focused on its effects on pathologies related to oxidative stress, inflammatory biomarkers, T2D, cardiovascular diseases, and neurological diseases.

Polyphenol fraction of extra virgin olive oil protects against endothelial dysfunction induced by high glucose and free fatty acids through modulation of nitric oxide and endothelin-1.

Epidemiological and clinical studies have reported that olive oil reduces the incidence of cardiovascular disease. However, the mechanisms involved in this beneficial effect have not been delineated. The endothelium plays an important role in blood pressure regulation through the release of potent vasodilator and vasoconstrictor agents such as nitric oxide (NO) and endothelin-1 (ET-1), respectively, events that are disrupted in type 2 diabetes. Extra virgin olive oil contains polyphenols, compounds that exert a biological action on endothelial function. This study analyzes the effects of olive oil polyphenols on endothelial dysfunction using an in vitro model that simulates the conditions of type 2 diabetes. Our findings show that high glucose and linoleic and oleic acids decrease endothelial NO synthase phosphorylation, and consequently intracellular NO levels, and increase ET-1 synthesis by ECV304 cells. These effects may be related to the stimulation of reactive oxygen species production in these experimental conditions. Hydroxytyrosol and the polyphenol extract from extra virgin olive oil partially reversed the above events. Moreover, we observed that high glucose and free fatty acids reduced NO and increased ET-1 levels induced by acetylcholine through the modulation of intracellular calcium concentrations and endothelial NO synthase phosphorylation, events also reverted by hydroxytyrosol and polyphenol extract. Thus, our results suggest a protective effect of olive oil polyphenols on endothelial dysfunction induced by hyperglycemia and free fatty acids.

Piceid presents antiproliferative effects in intestinal epithelial Caco-2 cells, effects unrelated to resveratrol release.

Trans-piceid (T-Pc) is abundant in Polygonum cuspidatum and in grapes and grape products such as wine. Piceid reaches high levels in the stomach and intestine with rapid oral absorption. Tissues, such as liver tissue, can deglycosylate piceid to release resveratrol, so piceid can be considered a source of resveratrol, which has numerous biological activities such as antiproliferative effects. Therefore, the aim of this work was to analyze the action of T-Pc on intestinal epithelial cell growth. Our results show that T-Pc has antioxidant activity similar to that of trans-resveratrol (T-Rv) and higher than that of Trolox. Moreover, T-Pc (1-50 µM) inhibited Caco-2 cell growth and DNA synthesis in a concentration-dependent manner. We observed an increase in the percentage of cells in G0/G1 phase induced by T-Pc and the induction of apoptosis. Furthermore, we observed that Caco-2 cells did not have ß-glucosidase activity and that Caco-2 cell cultures did not significantly deglycosylate T-Pc in our experimental conditions. On the basis of our results we propose, for the first time, that T-Pc must not be considered exclusively as a T-Rv source, and presents antiproliferative effects on intestinal epithelial cells through the modulation of the cell cycle and apoptosis by itself. Moreover, a synergistic action of T-Pc and T-Rv can be considered.

In vitro study of the cytotoxicity and antiproliferative effects of surfactants produced by Sphingobacterium detergens.

The application of biosurfactants in the biomedical field is growing due to their antimicrobial activity, low cytotoxicity and ability to induce apoptosis in cancer cells. In the light of this therapeutic potential, as well as possible applications in cosmetics or as drug vehicles in pharmaceutical products, a new biosurfactant produced by Sphingobacterium detergens was investigated for its haemolytic activity and cytotoxic and antiproliferative effects in different cell lines. Fraction A showed 100% haemolysis in rabbit erythrocytes, but in Fraction B the rate was only 83%. When comparing cytotoxicity values (IC50) of the two fractions in model fibroblast and keratinocyte cell cultures, Fraction B was less cytotoxic, showing lower values than the reference compound SDS, indicating low skin irritability. Finally, in non-differentiated intestinal Caco-2 cultures, Fractions A and B reduced cell proliferation and induced apoptosis by 44% and 75%, respectively. According to these results, biosurfactants produced by S. detergens have potential application in cosmetic and pharmaceutical formulations.

Resveratrol metabolites have an antiproliferative effect on intestinal epithelial cancer cells.

Trans-resveratrol (RV) is an active polyphenol with numerous physiological properties including antitumour activity, especially in colon cancer. RV is metabolized in the intestine and then in the liver to sulphated and glucuronidated forms that are exported to target organs. After exerting their effects, they are eliminated in the urine and stools. There are few and contradictory findings on the biological effects of RV metabolites. On the basis of RV metabolism, we selected three metabolites RV 3-O-sulphate, RV 3-O-glucuronide and RV 4'-O-glucuronide, and studied their effects on cell growth inhibition, the cell cycle and apoptosis using human adenocarcinoma cell line (Caco-2 cell) cultures. Our results show that RV metabolites have an antioxidant activity similar to that RV. Moreover, all metabolites inhibited cell growth in a concentration-dependent manner as well as [(3)H] thymidine incorporation. Furthermore, we observed an increase in the percentage of cell in G0/G1 phase induced by RV metabolite treatments, as well as the induction of apoptosis. On the basis of our results we propose, for the first time, that RV metabolites remain active after their biosynthesis, contributing to the health benefits attributed previously only to RV. These metabolites are a potential target for more research into the prevention and treatment of colon cancer.