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Hesperidin Bioavailability Is Increased by the Presence of 2S-Diastereoisomer and Micronization-A Randomized, Crossover and Double-Blind Clinical Trial.
Crescenti, A, Caimari, A, Alcaide-Hidalgo, JM, Mariné-Casadó, R, Valls, RM, Companys, J, Salamanca, P, Calderón-Pérez, L, Pla-Pagà, L, Pedret, A, et al
Nutrients. 2022;(12)
Abstract
Hesperidin is a flavanone abundantly found in citrus fruits for which health beneficial effects have been reported. However, hesperidin shows a low bioavailability among individuals. The aim of this study was to evaluate the effects of the micronization process and 2R- and 2S-hesperidin diastereoisomers ratio on hesperidin bioavailability. In a first phase, thirty healthy individuals consumed 500 mL of orange juice with 345 mg of hesperidin, and the levels of hesperidin metabolites excreted in urine were determined. In the second phase, fifteen individuals with intermediate hesperidin metabolite levels excreted in urine were randomized in a crossover, postprandial and double-blind intervention study. Participants consumed 500 mg of the hesperidin-supplemented Hesperidin epimeric mixture (HEM), the micronized Hesperidin epimeric mixture (MHEM) and micronized 2S-Hesperidin (M2SH) in each study visit with 1 week of washout. Hesperidin metabolites and catabolites were determined in blood and urine obtained at different timepoints over a 24 h period. The bioavailability-relative urinary hesperidin excretion (% of hesperidin ingested)-of M2SH (70 ± 14%) formed mainly by 2S-diastereoisomer was significantly higher than the bioavailability of the MHEM (55 ± 15%) and HEM (43 ± 8.0%), which consisted of a mixture of both hesperidin diastereoisomers. Relative urinary excretion of hesperidin metabolites for MHEM (9.2 ± 1.6%) was significantly higher compared to the HEM (5.2 ± 0.81%) and M2SH (3.6 ± 1.0%). In conclusion, the bioavailability of 2S-hesperidin extract was higher compared to the standard mixture of 2S-/2R-hesperidin extract due to a greater formation of hesperidin catabolites. Furthermore, the micronization process increased hesperidin bioavailability.
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Effects of hesperidin in orange juice on blood and pulse pressures in mildly hypertensive individuals: a randomized controlled trial (Citrus study).
Valls, RM, Pedret, A, Calderón-Pérez, L, Llauradó, E, Pla-Pagà, L, Companys, J, Moragas, A, Martín-Luján, F, Ortega, Y, Giralt, M, et al
European journal of nutrition. 2021;(3):1277-1288
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Abstract
PURPOSE To assess the sustained and acute effects, as well as the influence of sustained consumption on the acute effects, of orange juice (OJ) with a natural hesperidin content and hesperidin-enriched OJ (EOJ) on blood (BP) and pulse (PP) pressures in pre- and stage-1 hypertensive individuals. METHODS In a randomized, parallel, double-blind, placebo-controlled trial, participants (n = 159) received 500 mL/day of control drink, OJ, or EOJ for 12 weeks. Two dose-response studies were performed at baseline and after 12 weeks. RESULTS A single EOJ dose (500 mL) reduced systolic BP (SBP) and PP, with greater changes after sustained treatment where a decrease in diastolic BP (DBP) also occurred (P < 0.05). SBP and PP decreased in a dose-dependent manner relative to the hesperidin content of the beverages throughout the 12 weeks (P < 0.05). OJ and EOJ decreased homocysteine levels at 12 weeks versus the control drink (P < 0.05). After 12 weeks of EOJ consumption, four genes related to hypertension (PTX3, NLRP3, NPSR1 and NAMPT) were differentially expressed in peripheral blood mononuclear cells (P < 0.05). CONCLUSION Hesperidin in OJ reduces SBP and PP after sustained consumption, and after a single dose, the chronic consumption of EOJ enhances its postprandial effect. Decreases in systemic and transcriptomic biomarkers were concomitant with BP and PP changes. EOJ could be a useful co-adjuvant tool for BP and PP management in pre- and stage-1 hypertensive individuals.
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Effect of Hesperidin on Cardiovascular Disease Risk Factors: The Role of Intestinal Microbiota on Hesperidin Bioavailability.
Mas-Capdevila, A, Teichenne, J, Domenech-Coca, C, Caimari, A, Del Bas, JM, Escoté, X, Crescenti, A
Nutrients. 2020;12(5)
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Cardiovascular diseases (CVDs) cause around 31% of all deaths worldwide. Certain dietary patterns have been associated with a reduction in CVDs and so the use of natural-based products has gained importance as a preventive strategy. Hesperidin is a bioactive compound found in high levels in citrus fruits. The reported beneficial properties include antitumor, antioxidant, anti-inflammatory; cholesterol and glucose lowering effects. Many animal studies show multiple beneficial effects but are inconclusive in human studies. The aim of this review is to describe the effects of hesperidin on CVD factors and to highlight the individual differences in its bioavailability and effectiveness. The gut bacteria play an important role in this. Hesperidin is not broken down by the normal digestive process and reaches the colon largely intact. It is the job of the gut bacteria to break it down into bioavailable substances that can be absorbed and utilised. The discrepancies observed in some of the results from human clinical trials may be partly due to individual differences, including that of the gut bacteria. Further clinical trials should be considered as well as classifying individuals according to individual differences in metabotypes.
Abstract
Recently, hesperidin, a flavonone mainly present in citrus fruits, has emerged as a new potential therapeutic agent able to modulate several cardiovascular diseases (CVDs) risk factors. Animal and in vitro studies demonstrate beneficial effects of hesperidin and its derived compounds on CVD risk factors. Thus, hesperidin has shown glucose-lowering and anti-inflammatory properties in diabetic models, dyslipidemia-, atherosclerosis-, and obesity-preventing effects in CVDs and obese models, and antihypertensive and antioxidant effects in hypertensive models. However, there is still controversy about whether hesperidin could contribute to ameliorate glucose homeostasis, lipid profile, adiposity, and blood pressure in humans, as evidenced by several clinical trials reporting no effects of treatments with this flavanone or with orange juice on these cardiovascular parameters. In this review, we focus on hesperidin's beneficial effects on CVD risk factors, paying special attention to the high interindividual variability in response to hesperidin-based acute and chronic interventions, which can be partly attributed to differences in gut microbiota. Based on the current evidence, we suggest that some of hesperidin's contradictory effects in human trials are partly due to the interindividual hesperidin variability in its bioavailability, which in turn is highly dependent on the α-rhamnosidase activity and gut microbiota composition.
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Detection of Early Disease Risk Factors Associated with Metabolic Syndrome: A New Era with the NMR Metabolomics Assessment.
Hernandez-Baixauli, J, Quesada-Vázquez, S, Mariné-Casadó, R, Gil Cardoso, K, Caimari, A, Del Bas, JM, Escoté, X, Baselga-Escudero, L
Nutrients. 2020;(3)
Abstract
The metabolic syndrome is a multifactorial disease developed due to accumulation and chronification of several risk factors associated with disrupted metabolism. The early detection of the biomarkers by NMR spectroscopy could be helpful to prevent multifactorial diseases. The exposure of each risk factor can be detected by traditional molecular markers but the current biomarkers have not been enough precise to detect the primary stages of disease. Thus, there is a need to obtain novel molecular markers of pre-disease stages. A promising source of new molecular markers are metabolomics standing out the research of biomarkers in NMR approaches. An increasing number of nutritionists integrate metabolomics into their study design, making nutrimetabolomics one of the most promising avenues for improving personalized nutrition. This review highlight the major five risk factors associated with metabolic syndrome and related diseases including carbohydrate dysfunction, dyslipidemia, oxidative stress, inflammation, and gut microbiota dysbiosis. Together, it is proposed a profile of metabolites of each risk factor obtained from NMR approaches to target them using personalized nutrition, which will improve the quality of life for these patients.
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Potential Use of Mobile Phone Applications for Self-Monitoring and Increasing Daily Fruit and Vegetable Consumption: A Systematized Review.
Mandracchia, F, Llauradó, E, Tarro, L, Del Bas, JM, Valls, RM, Pedret, A, Radeva, P, Arola, L, Solà, R, Boqué, N
Nutrients. 2019;11(3)
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A wide range of chronic diseases could be prevented through healthier lifestyle choices, such as consuming five portions of fruits and vegetables daily, but most adults don’t meet this recommendation. Health-related mobile phone applications (Apps) are growing in popularity and can guide users through various lifestyle changes. This systematised review aimed to assess the potential of Apps to increase fruit and vegetable intake. The authors looked at eight previous randomised controlled trials evaluating Apps for their ability to increase fruit and/or vegetable intake over a period of between two and nine months. Apps used in the trials included MyFitnessPal, LoseIt! CalorieMama and FatSecret, amongst others. In six of the studies, the Apps were effective in increasing fruit and/or vegetable intake by at least 2.4 portions per day. These studies focused on overweight adults and adults or young adults with unhealthy lifestyles, and age did not seem to affect the outcome. Apps seemed to be more effective in people with health problems, compared to people who were otherwise healthy. Apps that targeted children via their parents were not effective. The authors concluded that using health-related Apps can be a useful way to increase fruit and vegetable consumption in adults. Further research is needed into which features of Apps are most effective and to determine their success over the long term.
Abstract
A wide range of chronic diseases could be prevented through healthy lifestyle choices, such as consuming five portions of fruits and vegetables daily, although the majority of the adult population does not meet this recommendation. The use of mobile phone applications for health purposes has greatly increased; these applications guide users in real time through various phases of behavioural change. This review aimed to assess the potential of self-monitoring mobile phone health (mHealth) applications to increase fruit and vegetable intake. PubMed and Web of Science were used to conduct this systematized review, and the inclusion criteria were: randomized controlled trials evaluating mobile phone applications focused on increasing fruit and/or vegetable intake as a primary or secondary outcome performed from 2008 to 2018. Eight studies were included in the final assessment. The interventions described in six of these studies were effective in increasing fruit and/or vegetable intake. Targeting stratified populations and using long-lasting interventions were identified as key aspects that could influence the effectiveness of these interventions. In conclusion, evidence shows the effectiveness of mHealth application interventions to increase fruit and vegetable consumption. Further research is needed to design effective interventions and to determine their efficacy over the long term.
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Mediterranean Diet and Multi-Ingredient-Based Interventions for the Management of Non-Alcoholic Fatty Liver Disease.
Suárez, M, Boqué, N, Del Bas, JM, Mayneris-Perxachs, J, Arola, L, Caimari, A
Nutrients. 2017;(10)
Abstract
Non-alcoholic fatty liver disease (NAFLD) comprises a wide spectrum of hepatic disorders, from simple steatosis to hepatic necro-inflammation leading to non-alcoholic steatohepatitis (NASH). Although the prevalence of these multifactorial pathologies is continuously increasing in the population, there is still not an established methodology for their treatment other than weight loss and a change in lifestyle habits, such as a hypocaloric diet and physical exercise. In this framework, there is increasing evidence that several food bioactives and dietary patterns are effective for reversing and preventing the onset of these pathologies. Some studies have claimed that better responses are obtained when treatments are performed under a multifaceted approach, using different bioactive compounds that act against complementary targets. Thus, in this work, current strategies for treating NAFLD and NASH based on multi-ingredient-based supplements or the Mediterranean diet, a dietary pattern rich in bioactive compounds, are reviewed. Furthermore, the usefulness of omics techniques to design effective multi-ingredient nutritional interventions and to predict and monitor their response against these disorders is also discussed.
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White adipose tissue reference network: a knowledge resource for exploring health-relevant relations.
Kelder, T, Summer, G, Caspers, M, van Schothorst, EM, Keijer, J, Duivenvoorde, L, Klaus, S, Voigt, A, Bohnert, L, Pico, C, et al
Genes & nutrition. 2015;(1):439
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Abstract
Optimal health is maintained by interaction of multiple intrinsic and environmental factors at different levels of complexity-from molecular, to physiological, to social. Understanding and quantification of these interactions will aid design of successful health interventions. We introduce the reference network concept as a platform for multi-level exploration of biological relations relevant for metabolic health, by integration and mining of biological interactions derived from public resources and context-specific experimental data. A White Adipose Tissue Health Reference Network (WATRefNet) was constructed as a resource for discovery and prioritization of mechanism-based biomarkers for white adipose tissue (WAT) health status and the effect of food and drug compounds on WAT health status. The WATRefNet (6,797 nodes and 32,171 edges) is based on (1) experimental data obtained from 10 studies addressing different adiposity states, (2) seven public knowledge bases of molecular interactions, (3) expert's definitions of five physiologically relevant processes key to WAT health, namely WAT expandability, Oxidative capacity, Metabolic state, Oxidative stress and Tissue inflammation, and (4) a collection of relevant biomarkers of these processes identified by BIOCLAIMS ( http://bioclaims.uib.es ). The WATRefNet comprehends multiple layers of biological complexity as it contains various types of nodes and edges that represent different biological levels and interactions. We have validated the reference network by showing overrepresentation with anti-obesity drug targets, pathology-associated genes and differentially expressed genes from an external disease model dataset. The resulting network has been used to extract subnetworks specific to the above-mentioned expert-defined physiological processes. Each of these process-specific signatures represents a mechanistically supported composite biomarker for assessing and quantifying the effect of interventions on a physiological aspect that determines WAT health status. Following this principle, five anti-diabetic drug interventions and one diet intervention were scored for the match of their expression signature to the five biomarker signatures derived from the WATRefNet. This confirmed previous observations of successful intervention by dietary lifestyle and revealed WAT-specific effects of drug interventions. The WATRefNet represents a sustainable knowledge resource for extraction of relevant relationships such as mechanisms of action, nutrient intervention targets and biomarkers and for assessment of health effects for support of health claims made on food products.
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Cocoa Consumption Alters the Global DNA Methylation of Peripheral Leukocytes in Humans with Cardiovascular Disease Risk Factors: A Randomized Controlled Trial.
Crescenti, A, Solà, R, Valls, RM, Caimari, A, Del Bas, JM, Anguera, A, Anglés, N, Arola, L
PloS one. 2013;(6):e65744
Abstract
UNLABELLED DNA methylation regulates gene expression and can be modified by different bioactive compounds in foods, such as polyphenols. Cocoa is a rich source of polyphenols, but its role in DNA methylation is still unknown. The objective was to assess the effect of cocoa consumption on DNA methylation and to determine whether the enzymes involved in the DNA methylation process participate in the mechanisms by which cocoa exerts these effects in humans. The global DNA methylation levels in the peripheral blood were evaluated in 214 volunteers who were pre-hypertensive, stage-1 hypertensive or hypercholesterolemic. The volunteers were divided into two groups: 110 subjects who consumed cocoa (6 g/d) for two weeks and 104 control subjects. In addition, the peripheral blood mononuclear cells (PBMCs) from six subjects were treated with a cocoa extract to analyze the mRNA levels of the DNA methyltransferases (DNMTs), methylenetetrahydrofolate reductase (MTHFR), and methionine synthase reductase (MTRR) genes. Cocoa consumption significantly reduced the DNA methylation levels (2.991±0.366 vs. 3.909±0.380, p<0.001). Additionally, we found an association between the cocoa effects on DNA methylation and three polymorphisms located in the MTHFR, MTRR, and DNMT3B genes. Furthermore, in PBMCs, the cocoa extract significantly lowered the mRNA levels of the DNMTs, MTHFR, and MTRR. Our study demonstrates for the first time that the consumption of cocoa decreases the global DNA methylation of peripheral leukocytes in humans with cardiovascular risk factors. In vitro experiments with PBMCs suggest that cocoa may exert this effect partially via the down-regulation of DNMTs, MTHFR and MTRR, which are key genes involved in this epigenetic process. TRIAL REGISTRATION Clinicaltrials.govNCT00511420 and NCT00502047.