A Systematic Review of the Cardiometabolic Benefits of Plant Products Containing Mixed Phenolics and Polyphenols in Postmenopausal Women: Insufficient Evidence for Recommendations to This Specific Population.

Menopause is characterized by endocrine and physiological changes and is often accompanied by increased body weight and cholesterol, glucose intolerance, and/or hypertension. These alterations are associated with increased risk for cardiovascular diseases (CVDs) and Type II diabetes mellitus (T2DM) that may be moderate by dietary plant phenolic compounds. In this review, we examine the current evidence of the impact of a variety of plant products (foods, extracts, beverages) rich in a mixture of phenolics and polyphenols on: (i) glucose and insulin levels; (ii) lipid profile; (iii) blood pressure; and (iv) biomarkers of inflammation and oxidative stress in postmenopausal women. We critically evaluate both the results of a range of intervention studies conducted in this specific subpopulation and the level of evidence supporting the benefits of consuming those products after the menopause. Overall, the current available evidence does not allow for specific dietary recommendations of these plant products rich in phenolics and polyphenols in this high-risk subpopulation. Our data show rather variable and small effects of the different products examined on the cardiometabolic biomarkers and further support the need to: (1) improve the quality of the study designs and data reporting; and (2) understand the variability in the response of the different biomarkers and establish clear differences between healthy and cardiometabolic disease levels.

[Influence of dietary carotenoids on biomarkers of cardiometabolic risk in peri- and post-menopausal women]. / Influencia de los carotenoides sobre los marcadores de riesgo cardiometabólico en mujeres peri y posmenopáusicas.

INTRODUCTION: Background: peri- and post-menopausal women exhibit a high tendency towards obesity and visceral fat deposition, which increases cardiometabolic risk. Objective: to evaluate through a prospective nutritional study the effect of carotenoid consumption on cardiometabolic risk biomarkers in peri- and post-menopausal women. Material and methods: twelve peri- and post-menopausal women without previous symptoms of cardiovascular disease, but with some cardiometabolic risk factor, were recruited. Their diet was supplemented during 4 weeks with orange-carrot juice, tomato juice, and boiled spinach, providing 415 mg of total carotenoids/week (carotenes, cryptoxanthin, lycopene, and lutein + zeaxanthin). At the beginning (TI) and at the end (TF) of the intervention period blood samples were drawn to measure biochemical parameters, oxidative stress, inflammation and endothelial function biomarkers, and plasma carotenoid levels. Results: at TF a significant decrease (p < 0.05) in LDL-cholesterol and atherogenic index, and an increase in HDL-cholesterol were observed. Plasma carotenoids increased significantly (p < 0.05) from 0.56 µg/mL at TI to 1.22 µg/mL at TF. Concurrently, a shift in oxidative stress and inflammation biomarkers was detected, with a decrease in plasma C-reactive protein and malonaldehyde levels, and an increase in adiponectin. However, endothelial dysfunction biomarkers (sVCAM and sICAM) and total antioxidant capacity remained unchanged. Conclusions: dietary supplementation with carotenoids leads to an increase in plasma carotenoids, a decrease in atherogenic dyslipidemia, and an improvement in oxidative stress and inflammation biomarkers, which indicates a reduction in cardiometabolic risk.

INTRODUCCIÓN: Introducción: durante la menopausia hay una mayor tendencia a la obesidad y el depósito de grasa visceral, aumentando el riesgo cardiometabólico. Objetivos: evaluar mediante un estudio de intervención el efecto del consumo de carotenoides sobre los biomarcadores relacionados con el riesgo cardiometabólico en mujeres peri y posmenopáusicas. Métodos: se seleccionaron 12 mujeres peri y posmenopáusicas, sin antecedentes de enfermedad cardiovascular pero con algún factor de riesgo cardiometabólico. Durante 4 semanas se suplementó su dieta con zumo de naranja-zanahoria, zumo de tomate y espinacas cocidas, proporcionando una ingesta de 415 mg de carotenoides totales a la semana (carotenos, criptoxantina, licopeno y luteína + zeaxantina). En el momento inicial (TI) y en el final (TF) se midieron los parámetros antropométricos y se analizaron los parámetros bioquímicos, los carotenoides plasmáticos y los biomarcadores de estrés oxidativo, de inflamación y de función endotelial. Resultados: en el TF se observaron cambios significativos, disminuyendo el colesterol unido a LDL y el índice aterogénico, y aumentando el colesterol-HDL. Los carotenoides plasmáticos se incrementaron significativamente (p < 0,05) de 0,56 µg/ml en el TI hasta 1,22 µg/ml en el TF. Paralelamente se observaron cambios significativos (p < 0,05) en los biomarcadores de estrés oxidativo e inflamación, disminuyendo la proteína C-reactiva y el malonaldehído, y aumentando la adiponectina. Por el contrario, los biomarcadores de daño endotelial (sVCAM y sICAM) y la capacidad antioxidante (ORAC) no mostraron cambios tras la intervención. Conclusiones: el consumo de carotenoides aumenta los niveles plasmáticos de carotenoides y disminuye la dislipemia aterogénica, y mejora los biomarcadores de inflamación y el estrés oxidativo, lo que está relacionado con una disminución del riesgo cardiometabólico.

Consumption of Spinach and Tomato Modifies Lipid Metabolism, Reducing Hepatic Steatosis in Rats.

Non-alcoholic fatty liver disease (NAFLD) is currently a serious and growing clinical problem in developed and developing countries and is considered one of the most frequent chronic liver diseases in the world. The aim of this study was to evaluate the functionality of dietary carotenoids provided by tomato and spinach in the dietary treatment of steatosis. Twenty-two Sprague-Dawley rats with induced steatosis were grouped into three groups and fed standard diet (CD group) and two experimental diets supplemented with 12.75% (LC12.75 group) and 25.5% (HC25.5 group) of a mixture of spinach and tomato powder. Rats fed carotenoid-rich feeds showed an improvement in the plasma biomarkers of steatosis, with lower levels of glucose, total cholesterol, VLDL, TG, proteins, ALT and AST. Likewise, a decrease in oxidative stress was observed, with a significant reduction of malondialdehyde (MDA) in plasma (up to 54%), liver (up to 51.42%) and urine (up to 78.89%) (p < 0.05) and an increase in plasma antioxidant capacity (ORAC) (up to 73.41%) (p < 0.05). Furthermore, carotenoid-rich diets led to an accumulation of carotenoids in the liver and were inversely correlated with the content of total cholesterol and hepatic triglycerides, increasing the concentrations of MUFA and PUFA (up to 32.6% and 48%, respectively) (p < 0.05). The accumulation of carotenoids in the liver caused the modulation of genes involved in lipid metabolism, and we particularly observed an overexpression of ACOX1, APOA1 and NRIH2 (LXR) and the synthesis of the proteins. This study suggests that dietary carotenoids from spinach and tomato aid in the dietary management of steatosis by reversing steatosis biomarkers.

Ameliorative Effect of Spinach on Non-Alcoholic Fatty Liver Disease Induced in Rats by a High-Fat Diet.

The purpose of this work was to evaluate the effect of dietary carotenoids from spinach on the inflammation and oxidative stress biomarkers, liver lipid profile, and liver transcriptomic and metabolomics profiles in Sprague-Dawley rats with steatosis induced by a high-fat diet. Two concentrations of spinach powder (2.5 and 5%) were used in two types of diet: high-fat (H) and standard (N). Although rats fed diet H showed an accumulation of fat in hepatocytes, they did not show differences in the values of adiponectin, tumor necrosis factor alpha (TNF-α), and oxygen radical absorption (ORAC) in plasma or of isoprostanes in urine compared with animals fed diet N. The consumption of spinach and the accumulation of α and ß carotenes and lutein in the liver was inversely correlated with serum total cholesterol and glucose and the content of hepatic cholesterol, increasing monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA) and reducing cholesterol in the livers of rats fed diet H and spinach. In addition, changes in the expression of genes related to the fatty liver condition occurred, and the expression of genes involved in the metabolism of fatty acids and cholesterol increased, mainly through the overexpression of peroxisome proliferator activated receptors (PPARs). Related to liver metabolites, animals fed with diet H showed hypoaminoacidemia, mainly for the glucogenic aminoacids. Although no changes were observed in inflammation and oxidative stress biomarkers, the consumption of spinach modulated the lipid metabolism in liver, which must be taken into consideration during the dietary treatment of steatosis.

Tomato Juice Supplementation Influences the Gene Expression Related to Steatosis in Rats.

The objective of this work was to identify the effect of tomato juice on the expression of genes and levels of metabolites related to steatosis in rats. Male Sprague Dawley rats (8 weeks-old) were grouped (6 rats/group) in four experimental groups: NA (normal diet and water), NL (normal diet and tomato juice), HA (high-fat diet and water), and HL (high-fat diet and tomato juice). After an intervention period of 5 weeks, rats were sacrificed and biochemical parameters, biomarkers of oxidative stress, liver metabolites, and gene expression were determined. Although the H diet provoked dislipemia related to steatosis, no changes in isoprostanes or liver malondialdehyde (MDA) were observed. Changes in the gene expression of the HA group were produced by the high consumption of fat, whereas the consumption of tomato juice had different effects, depending on the diet. In the NL group, the genes involved in ß-oxidation were upregulated, and in groups NL and HL upregulation of CD36 and downregulation of APOB and LPL were observed. In addition, in the HL group the accumulation of lycopene upregulated the genes FXR and HNF4A, which have been suggested as preventive factors in relation to steatosis. Regarding the metabolomics study, intake of tomato juice stimulated the biosynthesis of glutathione and amino acids of the transulfurization pathway, increasing the levels of metabolites related to the antioxidant response.

The effect of tomato juice supplementation on biomarkers and gene expression related to lipid metabolism in rats with induced hepatic steatosis.

PURPOSE: Tomato products are a dietary source of natural antioxidants, especially lycopene, which accumulates in the liver, where it exerts biological effects. Taking into consideration this fact, the aim of the present study was to ascertain the effect of tomato consumption on biomarkers and gene expression related to lipid metabolism in rats with induced steatosis. METHODS: Adult male Sprague-Dawley rats (8 weeks old) were randomly grouped (n = 6 rats/group) in four experimental groups: NA (normal diet and water), NL (normal diet and tomato juice), HA (high fat diet and water) and HL (high fat diet and tomato juice). After 7 weeks, rats were euthanized, and plasma, urine, feces and liver were sampled to analyze the biomarkers related to lipid metabolism, inflammation and oxidative stress. RESULTS: The H diet induced steatosis (grade II) in the HA and HL groups, which was confirmed by the levels of alanine aminotransferase and aspartate aminotransferase, histological examination and the presence of dyslipidemia. The intake of tomato juice led to an accumulation of all-E and Z-lycopene and its metabolites in the livers of these animals; levels were higher in HL than in NL, apparently due to higher absorption (63.07 vs. 44.45%). A significant improvement in the plasma level of high-density lipoprotein was observed in the HL group compared with HA animals, as was an alleviation of oxidative stress through reduction of isoprostanes in the urine. In relation to fatty acid gene expression, an overexpression of several genes related to fatty acid transport, lipid hydrolysis and mitochondrial and peroxisomal ß-fatty acid oxidation was observed in the HL group. CONCLUSIONS: The consumption of tomato juice and tomato products reduced hallmarks of steatosis, plasmatic triglycerides and very low-density lipoproteins, and increased lipid metabolism by inducing an overexpression of genes involved in more efficient fatty acid oxidation.

The inhibitory effects of bioactive compounds of tomato juice binding to hepatic HMGCR: in vivo study and molecular modelling.

The hypocholesterolemic effect of tomato juice has been investigated in an intervention study with rats, along with the possible inhibition effect of bioactive tomato compounds binding to the HMGCR enzyme. Two experimental groups (n = 8 Sprague-Dawley rats) were fed ad libitum for five weeks, with water or tomato juice provided to the control and intervention groups, respectively. Total, LDL and HDL cholesterol, and total triglycerides were analysed in plasma, and the lycopene content and the expression and activity of the enzyme HMGCR were determined in liver samples. A computational molecular modelling was carried out to determine the interactions between HMGCR and lycopene, chlorogenic acid and naringenin. Total, LDL and HDL cholesterol were significantly lower in the intervention group after the intake of tomato juice. In addition, a significant reduction in HMGCR activity was observed, although this was not accompanied by changes in gene expression. The molecular modelling showed that components of tomato can bind to the active site of the enzyme and compete with the ligand HMGCoA. Lycopene, from tomato juice, accumulates in the liver and can inhibit the activity of the rate-limiting enzyme of cholesterol biosynthesis, HMGCR.

Bioactive compounds, folates and antioxidant properties of tomatoes (Lycopersicum esculentum) during vine ripening.

Bioactive compounds and their relationship with antioxidant activity were determined in three tomato cultivars (Ronaldo, Siena and Copo) during vine ripening. The lycopene, chlorophyll (total, a and b), total phenolic, flavonoid, vitamin C and folate contents, and the antioxidant activity, by the ferric reducing/antioxidant power assay and the beta-carotene lineolate system, were determined in the samples. Tomato ripening involved the breakdown of chlorophylls, accompanied by a continuous increase in the lycopene content. Total phenolics, flavonoids and vitamin C increased significantly during ripening, whereas the folate content fell markedly as tomatoes turned from green to red. The lycopene and flavonoid content was highest in the Copo cultivar, vitamin C and folate highest in Ronaldo, and total phenolics highest in Siena. The antioxidant activity, as measured with the ferric reducing/antioxidant power assay, increased significantly during ripening in all extracts, and showed a positive correlation with the total phenolic and flavonoid contents. However, when measured with the beta-carotene lineolate system, the antioxidant activity decreased significantly during ripening; perhaps due to the antioxidant activity of chlorophylls and the peroxidation activity of vitamin C.

Oxidative stress status in an institutionalised elderly group after the intake of a phenolic-rich dessert.

The elderly population undergoes a series of physiological and sociological changes common to old age with a high probability of suffering degenerative illness and malnutrition. A dessert rich in phenolic compounds has been designed by using concentrated juices of grape, cherry, blackberry, blackcurrant and raspberry with the aim of it being used as a complementary food in adulthood. In the present study, we investigated the effect of the intake of this dessert (a jar of 200 g daily for a period of 2 weeks), with an antioxidant activity equivalent to ten servings of fruits and vegetables, on several markers of oxidative and antioxidant status in DNA and plasma in a group of elderly individuals. Non-smoking institutionalised elderly subjects were recruited from a pool of volunteers in an old-age home in Murcia (Spain). Twenty-two subjects (six men and sixteen women) participated in the study. The study was designed as a randomised intervention trial with a period of 2 weeks. At days 1 and 15, blood samples were collected to analyse total antioxidant capacity, biochemical parameters, antioxidant vitamins, LDL peroxidation, and DNA damage in peripheral blood lymphocytes. The conclusion of the present study is that a 2-week intervention with our dessert enriched with natural polyphenol compounds in elderly individuals does not give enough time to find changes in the antioxidant and oxidative status. Also, the view that the marked antioxidant ability of polyphenols in vitro does not translate to analogous effects in vivo was confirmed. Moreover, a highly oxidative stress status during ageing was confirmed, together with the need to perform follow-up nutritional studies to improve this situation.

Assessment of contamination by heavy metals and petroleum hydrocarbons in sediments of Montevideo Harbour (Uruguay).

As part of the first environmental assessment within Montevideo Harbour, in summer and winter of 1998, sediments samples were collected at eight locations to determine the spatial distribution of anthropogenic pollutants. Muddy sediments with high organic matter content dominate the study area. Heavy metal levels indicated that sediments were highly polluted with Zn (overall mean: 312+/-102 microg g(-1) dry sediment), Pb (85+/-31), Cu (89+/-25), Cr (162+/-62), and Hg (0.63+/-0.3) and moderately with Ni (30+/-2) and Ag (1.2+/-0.4). Depending on location and season, aliphatic hydrocarbons reached from 21 to 120 microg g(-1), while the unresolved complex mixture represented up to 76% of the total aliphatic fraction. Total PAH concentrations ranged from 1.56 to 90.44 microg g(-1); except at one location, petroleum derivatives were identified as main local source. The results pointed out that almost all the harbour area presented some substances that can cause adverse biological effects, especially in the inner region where all metals are above PEL levels. Principal components analysis confirmed that the inner harbour region is most severely affected by the pollutants and it was possible to differentiate three regions according to their environmental quality.