Bioavailability and systemic transport of oleanolic acid in humans, formulated as a functional olive oil.

Evidence of the pharmacological activity of oleanolic acid (OA) suggests its potential therapeutic application. However, its use in functional foods, dietary supplements, or nutraceuticals is hindered by limited human bioavailability studies. The BIO-OLTRAD trial is a double-blind, randomized controlled study with 22 participants that received a single dose of 30 mg OA formulated as a functional olive oil. The study revealed that the maximum serum concentration of OA ranged from 500 to 600 ng mL-1, with an AUC0-∞ value of 2862.50 ± 174.50 ng h mL-1. Furthermore, we discovered a physiological association of OA with serum albumin and triglyceride-rich lipoproteins (TRL). UV absorption spectra showed conformational changes in serum albumin due to the formation of an adduct with OA. Additionally, we demonstrated that TRL incorporate OA, reaching a maximum concentration of 140 ng mL-1 after 2-4 hours. We conjecture that both are efficient carriers to reach target tissues and to yield high bioavailability.

Nutritional Analysis of the Spanish Population: A New Approach Using Public Data on Consumption.

Official population consumption data are frequently used to characterize the diet of countries; however, this information may not always be representative of reality. This study analyses the food consumption of the Spanish population by reconstructing the whole food chain. The results have been compared with the data provided by the National Consumption Panel to which the food losses/waste reported in the literature along the distribution chain have been added. The difference between them allowed a new calculation of the estimated food consumption that was subjected to a dietary-nutritional analysis. Most of the foods were consumed more than those officially reported (range of 5-50%). The unhealthy ratios of consumed foods and recommended servings were: meat products (Rcr = 3.6), fruits and legumes (Rcr = 0.5), and nuts (Rcr = 0.14). Caloric intake surpasses needs. The results were consistent with the data on the prevalence of overweight and obesity in Spain, as well as with the prevalence of associated diseases. To make a judgment about the quality of a country's diet, it is necessary to have reliable data on food consumption, as well as energy and nutrient intake. This study encourages other authors to implement this method to verify and quantify the possible difference between official and real consumption data.

Effect of Acute Intake of Fermented Orange Juice on Fasting and Postprandial Glucose Metabolism, Plasma Lipids and Antioxidant Status in Healthy Human.

Higher postprandial plasma glucose and lipemia, and oxidative and inflammatory responses, are considered important cardiovascular risk factors. Fermentation of fruits has generated products with high concentrations of bioactive compounds. The aim of this study was to evaluate the potential acute effects that fermented orange juice (FOJ) can exert in healthy humans by modulating postprandial response, and inflammatory/antioxidant status, compared with orange juice (OJ). Nine volunteers were recruited for a randomized, controlled, and crossover study. Participants ingested 500 mL of FOJ. At 4 h post intake, subjects consumed a standardized mixed meal. Blood samples were collected at 0-8 h hours post intake. The subjects repeated the protocol with OJ following a 2-week washout period. Glucose and lipid metabolism, plasma antioxidant capacity (ORAC, FRAP), endogenous antioxidants (albumin, bilirubin, uric acid), C-reactive protein and fibrinogen were measured in plasma samples. There was a trend of a smaller increase in LDL-C after FOJ intake compared with OJ, a significant decrease in apo-B and significant increase in ORAC. The glycemic and triglyceride response of meal was attenuated with FOJ. No differences were obtained in endogenous antioxidants and inflammation status between the treatments. The acute consumption of FOJ could play a protective role against cardiovascular risk factors.

Sustainable Diets as Tools to Harmonize the Health of Individuals, Communities and the Planet: A Systematic Review.

BACKGROUND: Climate change and global health are inextricably linked. Thus, health systems and their professionals must adapt and evolve without losing quality of care. AIM(S): To identify health and environmental co-benefits derived from a sustainable diet and promotion strategies that favor its implementation. METHODS: A systematic search for articles published on sustainable diets and human/planetary health published between 2013 and 2020 was conducted on the databases PubMed, Cinahl, Scopus and Trip from 4 to 7 May 2020 in accordance with the PRISMA guideline. RESULTS: A total of 201 articles was retrieved, but only 21 were included. A calorie-balanced diet mainly based on food of plant origin that would allow the attainment of 60% of daily caloric requirements and a low protein intake from animal foods (focusing in fish and poultry) could significantly reduce global morbi-mortality and the dietary environmental impact maintaining a framework of sustainability conditioned by the consumption of fresh, seasonal, locally produced and minimally packaged products. DISCUSSION: The implementation of sustainable diets requires working on the triangulation of concepts of food-health-environment from schools and that is permanently reinforced during all stages of the life by healthcare workers, who should establish the appropriate modifications according to the age, gender and health situation.

Intake of branched chain amino acids favors post-exercise muscle recovery and may improve muscle function: optimal dosage regimens and consumption conditions.

INTRODUCTION: Numerous sportspeople consume nutritional ergogenic aids, including branched chain amino acids (BCAA), considered to favor post-exercise muscle recovery. The purpose of this study was to assess the effect of BCAA on recovery from muscle damage produced by high-intensity exercise and muscle function. This allowed to define the optimal dosage regimen and consumption conditions taking into account the combination of BCAA with other products. EVIDENCE ACQUISITION: A systematic review of the scientific literature published over the past 15 years using the PubMed/MEDLINE, Scopus and Web of Science databases was carried out. Nineteen articles were selected. EVIDENCE SYNTHESIS: The most optimal regimen for post-exercise muscle recovery and/or muscle function after high-intensity resistance exercise was 2-10 g BCAA/day (leucine: isoleucine: valine at 2:1:1), consumed as a supplement alone or combined with arginine and carbohydrates, 3 previous days before exercise, immediately before and after exercise, regardless of training level. This treatment can improve perceived muscle damage, fatigue, circumference of arm/leg, counter movement jump, maximum muscle strength and maximum voluntary contraction, and reduce creatine kinase and lactate dehydrogenase levels, mainly in young males. CONCLUSIONS: Intake of BCAA favors post-exercise muscle recovery and may improve muscle function. The present review can serve as a guidance for high intensity endurance athletes who need to reduce post-exercise muscle damage and maintain or improve muscle function, especially in training periods and competition events planned with short rest periods.

Absorption, metabolism, and excretion of orange juice (poly)phenols in humans: The effect of a controlled alcoholic fermentation.

The consumption of orange juice provides high concentrations of health-promoting bioactive compounds, the amount of which may increase upon alcoholic fermentation. Although fermentation may offer new prospects for the industry of orange-related products, there is a lack of studies reporting the influence of controlled alcoholic fermentation on the bioavailability of orange juice (poly)phenols in humans. The aim of this study was to evaluate the absorption profile, pharmacokinetic parameters, and urinary excretion of orange juice (poly)phenols in nine volunteers after acute administration of an orange juice and a beverage prepared after controlled alcoholic fermentation of the juice. Plasma and urine samples were analysed through a UHPLC-ESI-MS/MS targeted approach. A total of 24 (poly)phenol metabolites including both flavanone and phenolic acid derivatives were quantified, most of them being recorded only in urine. Phase II conjugates of hesperetin and naringenin were the main metabolites in plasma, while phenolic acids, in particular hydroxybenzoic acids, were the main compounds in urine. (Poly)phenols in both beverages were highly bioavailable (between 46 and 59%) and a notable inter-individual variability was seen. Significant treatment × time interactions were recorded for the sum of flavanones and phenolic acids in plasma, the (poly)phenols in the fermented juice being absorbed faster than after orange juice intake. Nevertheless, despite the food matrix having an impact on the absorption profile of orange juice (poly)phenols, this did not influence the pharmacokinetic parameters and urinary excretion of the (poly)phenol metabolites.

ß-Cryptoxanthin is more bioavailable in humans from fermented orange juice than from orange juice.

Carotenoids, especially ß-cryptoxanthin, exert multiple biological activities in the organism. Various processing techniques can improve carotenoid bioavailability in relation to the food matrix. The study objective was to compare the bioavailability of carotenoids from orange juice (OJ) with that from a beverage obtained by alcoholic fermentation of orange juice (FOB). Seven volunteers were recruited for a randomized, controlled, and crossover study. Post-intake plasma carotenoid concentrations were measured by HPLC in the subjects at 0-8 h after their consumption of OJ or FOB. ß-Cryptoxanthin and lutein absorption was significantly higher from FOB than from OJ, but no significant difference in zeaxanthin absorption was found. The mean baseline-corrected area under the concentration curve (AUC0-8 h) for ß-cryptoxanthin, lutein and zeaxanthin was 24.6-, 1.3- and 4.65-fold larger, respectively, after FOB versus OJ consumption. This fermented orange beverage could be an abundant source of bioavailable carotenoids, and its regular consumption may exert healthy effects.

Consumption of orange fermented beverage improves antioxidant status and reduces peroxidation lipid and inflammatory markers in healthy humans.

BACKGROUND: Alcoholic fermentation of fruits has generated novel products with high concentrations of bioactive compounds and moderate alcohol content. The aim of this study was to evaluate the potential effect on cardiovascular risk factors of the regular consumption by healthy humans of a beverage obtained by alcoholic fermentation and pasteurization of orange juice. RESULTS: Thirty healthy volunteers were enrolled in a randomized controlled study. The experimental group (n = 15) drank 500 mL orange beverage (OB) per day for 2 weeks (intervention phase), followed by a 3-week washout phase. Blood samples were collected at baseline (E-T0) and at the end of the intervention (E-T1) and washout (E-T2) phases. Controls (n = 15) did not consume OB during a 2-week period. OB intake significantly increased oxygen radical absorbance capacity (43.9%) and reduced uric acid (-8.9%), catalase (CAT) (-23.2%), thiobarbituric acid reactive substances (TBARS) (-30.2%) and C-reactive protein (-2.1%) (E-T1 vs. E-T0). These effects may represent longer-term benefits, given the decreased uric acid (-8.9%), CAT (-34.6%), TBARS (-48.4%) and oxidized low-density lipoprotein (-23.9%) values recorded after the washout phase (E-T2 vs. E-T0). CONCLUSION: The regular consumption of OB improved antioxidant status and decreased inflammation state, lipid peroxidation and uric acid levels. Thus OB may protect the cardiovascular system in healthy humans and be considered a novel functional beverage. © 2017 Society of Chemical Industry.

Effect of thermal processing on the profile of bioactive compounds and antioxidant capacity of fermented orange juice.

Previously, we reported that alcoholic fermentation enhanced flavanones and carotenoids content of orange juice. The aim of this work was to evaluate the influence of pasteurization on the qualitative and quantitative profile of bioactive compounds and the antioxidant capacity of fermented orange juice. Ascorbic acid (203 mg/L), total flavanones (647 mg/L), total carotenoids (7.07 mg/L) and provitamin A (90.06 RAEs/L) values of pasteurized orange beverage were lower than those of fermented juice. Total phenolic remained unchanged (585 mg/L) and was similar to that of original juice. The flavanones naringenin-7-O-glucoside, naringenin-7-O-rutinoside, hesperetin-7-O-rutinoside, hesperetin-7-O-glucoside and isosakuranetin-7-O-rutinoside, and the carotenoids karpoxanthin and isomer, neochrome, lutein, ζ-carotene, zeaxanthin, mutatoxanthin epimers, ß-cryptoxanthin and auroxanthin epimers were the major compounds. Pasteurization produced a decrease in antioxidant capacity of fermented juice. However, TEAC (5.45 mM) and ORAC (6353 µM) values of orange beverage were similar to those of original orange juice. The novel orange beverage could be a valuable source of bioactive compounds with antioxidant capacity and exert potential beneficial effects.

Consumption of orange fermented beverage reduces cardiovascular risk factors in healthy mice.

The consumption of fruits prevents the risk of cardiovascular diseases. Alcoholic fermentation has been carried out in fruits resulting in products which provide high concentration of bioactive compounds and variable alcohol content. The aim of this study was to assess the potential beneficial effect of an orange beverage obtained by alcoholic fermentation and pasteurization of orange juice on cardiovascular risk biomarkers. For this purpose, four mice groups (n = 8) ingested orange beverage (equivalent volume to 250 mL/day in human), orange juice, alcoholic solution (at the proportional amount of orange beverage) or water during 12 weeks. The equivalent amount to double serving of orange beverage (500 mL/day) was administered to mice in a subsequent intervention, and a control group was also evaluated. Orange beverage consumption increased levels of glutathione and uric acid, improved lipid profile, decreased oxidized LDL and maintained levels of IL-6 and C-reactive protein. Synergistic effects between the bioactive compounds and the alcohol content of orange beverage may occur. The intake of double serving also increased antioxidant enzyme activities, bilirubin content and plasma antioxidant capacity. These results suggest that orange beverage may produce greater protection against cardiovascular risk factors than orange juice in healthy mice.

Effect of alcoholic fermentation on the carotenoid composition and provitamin A content of orange juice.

Orange juice is considered a rich source of carotenoids, which are thought to have diverse biological functions. In recent years, a fermentation process has been carried out in fruits resulting in products that provide higher concentrations of bioactive compounds than their original substrates. The aim of this study was to evaluate the effect of a controlled alcoholic fermentation process (15 days) on the carotenoid composition of orange juice. Twenty-two carotenoids were identified in samples. The carotenoid profile was not modified as result of the fermentation. Total carotenoid content and provitamin A value significantly increased from day 0 (5.37 mg/L and 75.32 RAEs/L, respectively) until day 15 (6.65 mg/L and 90.57 RAEs/L, respectively), probably due to a better extractability of the carotenoids from the food matrix as a result of processing. Therefore, the novel beverage produced could provide a rich source of carotenoids and exert healthy effects similar to those of orange juice.

Fermented orange juice: source of higher carotenoid and flavanone contents.

The intake of bioactive compounds and moderate alcohol decreases the risk of cardiovascular diseases. These effects could be joined in a beverage created by a controlled alcoholic fermentation of orange juice. The influence of controlled alcoholic fermentation on the bioactive compound profile of orange juice has not been previously evaluated, and this is the purpose of the present study. Total and individual flavanones and carotenoids significantly increased throughout the fermentation. The reason for this was an enhanced extraction of these compounds from the pulp. Besides, the potential bioavailability of flavanones increased due to a higher content of hesperetin-7-O-glucoside (2-fold higher at the end of the fermentation process). Ascorbic acid did not undergo a significant change, and only total phenolics decreased. Antioxidant capacity was also evaluated. TEAC and FRAP values remained constant throughout the process. However, ORAC and DPPH values significantly increased. Correlation analysis concluded that the increase in ORAC and DPPH values could be due to enhancement of flavanones.

Blocking of melatonin synthesis and MT(1) receptor impairs the activation of Jurkat T cells.

Melatonin has been proposed as regulating the immune system by affecting cytokine production in immunocompetent cells, enhancing the production of several T helper (Th)1 cytokines. To further investigate the melatonin's role in IL-2/IL-2R system, we established an inducible T-REx expression system in Jurkat cells in which the protein levels of HIOMT enzyme or MT(1) receptor were significantly down-regulated upon tetracycline incubation. We found that T-REx Jurkat cells with lower levels of HIOMT activity, and consequently lower content of endogenous melatonin, showed IL-2 production decrease after activation with lectin. Likewise, tetracycline-inducible stable cell line expressing MT(1) antisense produced decreased amounts of IL-2 (mRNA and protein levels) after stimulation. Moreover, in T-Rex-MT(1) cells incubated with tetracycline, a sub-optimal PHA dose failed to induce the early activation marker CD25 on the cell surface. The results shown here support the relevance of endogenous melatonin and its signaling in T cell activation.

Evidence of immune system melatonin production by two pineal melatonin deficient mice, C57BL/6 and Swiss strains.

We evaluated two pineal melatonin deficient mice described in the literature, i.e., C57BL/6 and Swiss mice, as animal models for studying the immunomodulatory action of melatonin. Plasma melatonin levels in C57BL/6 and Swiss strains were detectable, but lower than levels in control C3H/HENHSD mice. Since these strains are suppose to be pineal melatonin deficient an extrapineal melatonin synthesis may contribute to plasma levels. Regarding cells and tissues from the immune system, all of them were found to synthesize melatonin although at low levels. N-acetyltransferase (AANAT) mRNA was also amplified in order to analyze the alternative splicing between exons 3-4 described for pineal C57BL/6 mice which generates an inclusion of a pseudoexon of 102 bp. For the pineal gland, both the wild type and the mutant isoforms were present in all mice strains although in different proportions. We observed a predominant wild type AANAT mature RNA in thymus, spleen and bone marrow cells. Peripheral blood mononuclear cells (PBMC) culture shown an evident AANAT amplification in all strains studied. Although the bands detected were less intense in melatonin deficient mice, the amplification almost reached the control cell intensity after stimulation with phytohemaglutinin (PHA). In summary, melatonin detection and AANAT mRNA expression in inbred and outbred mice clearly indicate that different cells and tissues from the immune system are able to synthesize melatonin. Thus, the pineal defect seems not to be generalized to all tissues, suggesting that other cells may compensate the low pineal melatonin production contributing to the measurable plasma melatonin level.

Proposal of a Mediterranean diet index for pregnant women.

Numerous studies have addressed the nutritional needs of pregnant women. The nutritional status of the woman before and during gestation affects the growth of the fetus and the course of the pregnancy and influences the risk of obesity for mother and infant. The aim of this study was to propose a diet quality index for pregnancy based on a Mediterranean-type diet (MDS-P), evaluating the diet of a group of pregnant women by applying the Mediterranean Diet Score (MDS) and evaluating their intake of micronutrients required in optimal amounts during pregnancy, such as Fe, folic acid and Ca. The data used to construct this index (MDS-P) were gathered by means of a FFQ specifically designed for pregnant women. The mean MDS of this group, was 4.31 (sd 1.32), considered to represent satisfactory compliance with the Mediterranean diet (range 0-8). The mean MDS-P (range 0-11), which also takes account of dietary intake or supplements of folic acid, Fe and Ca was 7.53 (sd 1.44), indicating a compliance of around 70 %. The present study findings suggest that the MDS-P, which evaluates the adequacy of folic acid, Fe and Ca as well as compliance with the Mediterranean diet, may represent a valid tool for the specific assessment of the diet of pregnant women living in countries in the Mediterranean area. Further studies are required to complete the validation process.

Pesticide exposure of two age groups of women and its relationship with their diet.

The widespread presence of organochlorine (OC) pesticides in human samples may be explained by the environmental exposure of the population. Foods are considered a constant source of exposure, despite compliance with maximum permitted residue levels. This study aimed to examine the relationship between nutritional habits of women in Southeast Spain and their serum concentrations of OCs. A semi-quantitative questionnaire was used to estimate the frequency of consumption of foods by two age groups of women, pre-menopausal (Pre-M) and post-menopausal (Post-M), and their serum pesticide levels were measured by gas chromatography (GC) with electron capture detector and confirmed by GC and mass spectrometry. The Pre-M group showed significantly higher serum concentrations of all OCs studied with the exception of DDE. The groups significantly differed in consumption of all food groups with the exception of fruit. In the Pre-M group, the mean serum p,p-DDT concentration was significantly associated with milk/yoghurt (p<0.045) and red meat (p<0.023), serum o,p-DDT with red meat (p<0.049), serum aldrin with eggs (p<0.038) and poultry (p<0.024), and serum DDE with eggs (p<0.025). In the Post-M group, serum lindane was associated with fresh and cured cheese (p<0.001), red meat (p<0.001) and white and oily fish (p<0.001), and both serum DDE and dieldrin were associated with fresh cheese, cured cheese, red meat, and white and oily fish (p<0.001). These results confirm foods as a source of human exposure to persistent organic molecules. Consideration should be given to the reduction of permitted residue levels to minimize this threat to human and animal health.

Endosulfan and its metabolites in fertile women, placenta, cord blood, and human milk.

Although industrialized nations have restricted or banned many organochlorine pesticides, some of these chemicals (e.g., endosulfans) are still used, on the assumption that they pose little threat to the environment, wildlife, or human health. According to available information, Spain is the main consumer of endosulfans within the European Union, accounting for almost half of the total consumption. Reports on human exposure in Southern Spain to persistent bioacumulable organochlorine pesticides have indicated considerable exposure to endosulfans. The present study investigated the presence of endosulfan I, endosulfan II, and endosulfan metabolites in fatty and non-fatty tissues and fluids from women of reproductive age and children in Southern Spain. The highest concentration of commercial endosulfan I and endosulfan II was found in adipose tissue, with a mean value (I+II) of 17.72 ng/g lipid, followed by human milk, with a mean value (I+II) of 11.38 ng/mL milk. These findings support the lipophilicity of these chemicals and their elimination by milk secretion. The concentration in the placenta homogenate was similar to that in the blood from the umbilical cord (7.74 and 6.11 ng/mL, respectively) and reflected their lower fat content. Endosulfan diol and endosulfan sulfate were more frequently found in placenta homogenate, with a mean concentration of 12.56 and 3.57 ng/mL, respectively, and in blood from umbilical cord, at 13.23 and 2.82 ng/mL, respectively. Therefore, women of reproductive age in Southern Spain appear to be currently exposed to endosulfans. Because these chemicals can be mobilized during pregnancy and lactation, further research is warranted to investigate the health consequence in children resulting from exposure to chemicals suspected of immunotoxic, neurotoxic, or endocrine-disrupting effects.

Exposure of women to organochlorine pesticides in Southern Spain.

Organochlorine pesticides are lipophilic compounds that persist in the environment. Because of their lipid solubility and resistance to metabolism, some of these chemicals accumulate in human tissues. The largest area of intensive greenhouse agriculture in Europe is near the Mediterranean coast of Southern Spain, where this type of farming has greatly expanded since the 1960s. We determined and compared the levels of 15 organochlorine pesticides in the adipose tissue and blood of 200 women living in Southern Spain. Aldrin, dieldrin, endrin, lindane, methoxychlor, endosulfans, and DDT and its metabolites were identified. Detectable concentrations of p,p'-DDE were found in 100% of adipose tissue and serum samples. Among the remaining DDTs, p,p'-DDT was the most common, being detected in 39% of adipose tissue and 76.5% of serum samples, followed by endosulfans I and II, which also were found in both adipose tissue and serum samples but at lower concentrations. Endosulfans were followed in frequency by lindane, aldrin, and dieldrin. Endrin and methoxychlor were present at a much lower frequency compared to those of the other organochlorines. Serum concentrations of p,p'-DDE o,p'-DDD, and endosulfan -I, -sulfate, -lactone, and -diol were significantly correlated with their adipose tissue concentrations. No significant relationships were found between the serum and adipose tissue concentrations of the remaining nine compounds determined, raising doubts about the equivalent use of fat/serum samples for the exposure assessment of some pesticides in epidemiological studies. The results suggested that women of reproductive age in Southern Spain have been and are currently exposed to organochlorine pesticides. Because many of these chemicals can mobilize during pregnancy and lactation, further research is warranted to interpret the health consequences for the children of such exposure.

Assessment of total effective xenoestrogen burden in adipose tissue and identification of chemicals responsible for the combined estrogenic effect.

Test systems to screen for estrogenicity and appropriate biomarkers of human exposure are required for epidemiological studies of endocrine disruption. We addressed these issues by developing and standardising a method to assess the total estrogenic xenobiotic burden in human adipose tissue. In this study, which is the continuation of a previous work, we have improved the protocol for extensive fractionation of a higher number of tissue samples in order to investigate bioaccumulated xenoestrogens that are candidates for estrogenicity and to assess their combined estrogenic effect. This was achieved by extensive HPLC separation of xenoestrogens from endogenous hormones followed by testing of individual fractions in the E-Screen test for estrogenicity. Organochlorine pesticides, PCBs and halogenated bisphenols and alkylphenols were collected in the most lipophilic fractions, followed by progestins, androgens and estradiol esters, and then by steroidal estrogens; phyto- and myco-estrogens were collected around the end of the run. These results were confirmed by exhaustive chemical analysis. In 458 human adipose tissue samples, the total effective xenoestrogen burden was positive in 75% of samples in the pooled fraction that contained organohalogenated xenoestrogens (mean 515.3 pM Eeq/g lipid; range 0-14.5 nM) and in 82% of samples in the pooled fraction where natural estrogens eluted (mean 696.6 pM Eeq/g lipid; range 0-12.9 nM). Organochlorine pesticides emerged as candidate chemicals for the estrogenicity of the first pooled fraction, because DDT and derivatives were present in 98.3% of the samples. However, no correlation was found between the concentration of any single chemical and the estrogenicity determined in the bioassay. There may be several reasons for this lack of concordance: (i) the estrogenic effects depicted in the E-Screen bioassay are a consequence of the combined effect of several organohalogens or (ii) the proliferative effect is due to other chemicals not measured. Because additive, synergistic or antagonistic mechanisms may account for the final effect observed in the pooled fractions, the approach proposed in this work is more appropriate for exposure assessment in epidemiological studies than the determination of individual chemicals in human samples.