Red raspberry (Rubus idaeus) preserves intestinal barrier integrity and reduces oxidative stress in Caco-2 cells exposed to a proinflammatory stimulus.

Growing evidence showed the capacity of (poly)phenols to exert a protective role on intestinal health. Nevertheless, the existing findings are still heterogeneous and the underlying mechanisms remain unclear. This study investigated the potential benefits of a red raspberry (Rubus idaeus) powder on the integrity of the intestinal barrier, focusing on its ability to mitigate the effects of tumor necrosis factor-α (TNF-α)-induced intestinal permeability. Human colorectal adenocarcinoma cells (i.e., Caco-2 cells) were used as a model to assess the impact of red raspberry on intestinal permeability, tight junction expression, and oxidative stress. The Caco-2 cells were differentiated into polarized monolayers and treated with interferon-γ (IFN-γ) (10 ng mL-1) for 24 hours, followed by exposure to TNF-α (10 ng mL-1) in the presence or absence of red raspberry extract (1-5 mg mL-1). The integrity of the intestinal monolayer was evaluated using transepithelial electrical resistance (TEER) and fluorescein isothiocyanate-dextran (FITC-D) efflux assay. Markers of intestinal permeability (claudin-1, occludin, and zonula occludens-1 (ZO-1)) and oxidative stress (8-hydroxy-2-deoxyguanosine (8-OHdG) and protein carbonyl) were assessed using ELISA kits. Treatment with red raspberry resulted in a significant counteraction of TEER value loss (41%; p < 0.01) and a notable reduction in the efflux of FITC-D (-2.5 times; p < 0.01). Additionally, red raspberry attenuated the levels of 8-OHdG (-48.8%; p < 0.01), mitigating the detrimental effects induced by TNF-α. Moreover, red raspberry positively influenced the expression of the integral membrane protein claudin-1 (+18%; p < 0.01), an essential component of tight junctions. These findings contribute to the growing understanding of the beneficial effects of red raspberry in the context of the intestinal barrier. The effect of red raspberry against TNF-α-induced intestinal permeability observed in our in vitro model suggests, for the first time, its potential as a dietary strategy to promote gastrointestinal health.

Wild blueberry (V. angustifolium) improves TNFα-induced cell barrier permeability through claudin-1 and oxidative stress modulation in Caco-2 cells.

Increasing evidence links the impairment of intestinal permeability (IP), a feature of the intestinal barrier, to numerous dysmetabolic and dysfunctional conditions. Several host and environmental factors, including dietary factors, can negatively and/or positively affect IP. In this regard, polyphenol-rich foods including berries have been proposed as potential IP modulators. However, the exact mechanisms involved are not yet fully elucidated. The aim of the present study was to evaluate the effect of a wild blueberry (WB; V. angustifolium) powder, naturally rich in polyphenols, to affect Caco-2 cell monolayer permeability and to identify the potential mechanisms in modulating the IP process. Caco-2 cells were incubated with TNF-α (10 ng mL-1), as a pro-inflammatory stimulus, and supplemented for 24 hours with different concentrations (1 and 5 mg mL-1) of WB powder. The integrity of the intestinal cell monolayer was evaluated by measuring the transepithelial electrical resistance (TEER) and the paracellular transport of FITC-dextran. In addition, the production of the tight junction proteins, such as claudin-1 and occludin, as well as protein carbonyl and 8-hydroxy 2 deoxyguanosine, as oxidative stress markers, were quantified in the supernatant by ELISA kits. Overall, the treatment with WB powder (5 mg mL-1) mitigated the loss of Caco-2 cell barrier integrity, as documented by an increase in TEER and a reduction in FITC values. This modulation was accompanied by an upregulation of claudin-1 and a reduction of 8-OHdG. Conversely, no effect was documented for the lower concentration (1 mg mL-1) and the other IP markers, as well as oxidative stress markers analysed. In conclusion, our findings suggest a potential role of WB in the modulation of cell barrier integrity. This modulation process could be attributed to an increase in claudin-1 expression and a reduction in 8-OHdG. Further studies should be performed to corroborate the results obtained. In addition, since the effects were observed at doses of WB achievable with the diet, these findings should be substantiated also through in vivo approaches.

Healthy Eating for Elective Major Orthopedic Surgery: Quality, Quantity, and Timing.

Improvements to enhanced recovery pathways in orthopedic surgery are reducing the time that patients spend in the hospital, giving an increasingly vital role to prehabilitation and/or rehabilitation after surgery. Nutritional support is an important tenant of perioperative medicine, with the aim to integrate the patient's diet with food components that are needed in greater amounts to support surgical fitness. Regardless of the time available between the time of contemplation of surgery and the day of admission, a patient who eats healthy is reasonably more suitable for surgery than a patient who does not meet the daily requirements for energy and nutrients. Moreover, a successful education for healthy food choices is one possible way to sustain the exercise therapy, improve recovery, and thus contribute to the patient's long-term health. The expected benefits presuppose that the patient follows a healthy diet, but it is unclear which advice is needed to improve dietary choices. We present the principles of healthy eating for patients undergoing major orthopedic surgery to lay the foundations of rational and valuable perioperative nutritional support programs. We discuss the concepts of nutritional use of food, requirements, portion size, dietary target, food variety, time variables of feeding, and the practical indications on what the last meal to be consumed six hours before the induction of anesthesia may be together with what is meant by clear fluids to be consumed until two hours before. Surgery may act as a vital "touch point" for some patients with the health service and is therefore a valuable opportunity for members of the perioperative team to promote optimal lifestyle choices, such as the notion and importance of healthy eating not just for surgery but also for long-term health benefit.

Berry Dietary Interventions in Metabolic Syndrome: New Insights.

Metabolic Syndrome (MetS) is characterized by a group of dysmetabolic conditions, including abdominal obesity, dyslipidemia, glucose intolerance and/or insulin resistance, and hypertension. Generally, MetS is accompanied by an exacerbation of oxidative stress, inflammation, and vascular dysfunction. Increasing evidence suggests that berries and berry bioactives could play a potential role in the prevention and mitigation of the risk factors associated with MetS. The present systematic review summarizes the more recently available evidence deriving from human intervention studies investigating the effect of berries in subjects with at least three out of five MetS parameters. The PubMed, Scopus, and Embase databases were systematically searched from January 2010 until December 2022. A total of 17 human intervention trials met the inclusion criteria. Most of them were focused on blueberry (n = 6), cranberry (n = 3), and chokeberry (n = 3), while very few or none were available for the other berries. If considering MetS features, the main positive effects were related to lipid profile (low and high-density lipoproteins, cholesterol, and triglycerides) following blueberries and chokeberries, while conflicting results were documented for anthropometric parameters, blood pressure, and fasting blood glucose levels. Other markers analyzed within the studies included vascular function, oxidative stress, and inflammation. Here, the main positive effects were related to inflammation with a reduction in interleukin 6 and tumor necrosis factor-alpha following the intake of different berries. In conclusion, although limited, the evidence seems to support a potential role for berries in the modulation of lipid profile and inflammation in subjects with MetS. Furthermore, high-quality intervention trials are mandatory to demonstrate the role of berries in reducing risk factors for MetS and related conditions. In the future, such a demonstration could bring the adoption of berries as a potential dietary strategy to prevent/counteract MetS and related risk factors.

Prediction of Long-Term Recovery From Disability Using Hemoglobin-Based Models: Results From a Cohort of 1,392 Patients Undergoing Spine Surgery.

Hemoglobin and its associated blood values are important laboratory biomarkers that mirror the strength of constitution of patients undergoing spine surgery. Along with the clinical determinants available during the preadmission visit, it is important to explore their potential for predicting clinical success from the patient's perspective in order to make the pre-admission visit more patient-centered. We analyzed data from 1,392 patients with spine deformity, disc disease, or spondylolisthesis enrolled between 2016 and 2019 in our institutional Spine Registry. Patient-reported outcome measure at 17 months after surgery was referred to the Oswestry disability index. High preoperative hemoglobin was found to be the strongest biochemical determinant of clinical success along with high red blood cells count, while low baseline disability, prolonged hospitalization, and long surgical times were associated with poor recovery. The neural network model of these predictors showed a fair diagnostic performance, having an area under the curve of 0.726 and a sensitivity of 86.79%. However, the specificity of the model was 15.15%, thus providing to be unreliable in forecasting poor patient-reported outcomes. In conclusion, preoperative hemoglobin may be one of the key biomarkers on which to build appropriate predictive models of long-term recovery after spine surgery, but it is necessary to include multidimensional variables in the models to increase the reliability at the patient's level.

Perioperative Anesthesia and Acute Smell Alterations in Spine Surgery: A "Sniffing Impairment" Influencing Refeeding?

Medications for general anesthesia can cause smell alterations after surgery, with inhalation anesthetics being the most acknowledged drugs. However, spine patients have been poorly studied in past investigations and whether these alterations could influence the refeeding remains unclear. This research aims to observe detectable dysosmias after spine surgery, to explore any amplified affection of halogenates (DESflurane and SEVoflurane) against total intravenous anesthesia (TIVA), and to spot potential repercussions on the refeeding. Fifty patients between 50 and 85 years old were recruited before elective spine procedure and tested for odor acuity and discrimination using the Sniffin' Sticks test. The odor abilities were re-assessed within the first 15 h after surgery together with the monitoring of food intakes. The threshold reduced from 4.92 ± 1.61 to 4.81 ± 1.64 (p = 0.237) and the discrimination ability reduced from 10.50 ± 1.83 to 9.52 ± 1.98 (p = 0.0005). Anesthetic-specific analysis showed a significant reduction of both threshold (p = 0.004) and discrimination (p = 0.004) in the SEV group, and a significant reduction of discrimination abilities (p = 0.016) in the DES group. No dysosmias were observed in TIVA patients after surgery. Food intakes were lower in the TIVA group compared to both DES (p = 0.026) and SEV (p = 0.017). The food consumed was not associated with the sniffing impairment but appeared to be inversely associated with the surgical time. These results confirmed the evidence on inhalation anesthetics to cause smell alterations in spine patients. Furthermore, the poor early oral intake after complex procedures suggests that spinal deformity surgery could be a practical challenge to early oral nutrition.

A mix of chlorogenic and caffeic acid reduces C/EBPß and PPAR-γ1 levels and counteracts lipid accumulation in macrophages.

PURPOSE: Chlorogenic acid (CGA) and caffeic acid (CA) are bioactive compounds in whole grains, berries, apples, some citrus fruits and coffee, which are hypothesized to promote health-beneficial effects on the cardiovascular system. This study aimed to evaluate the capacity of CGA and CA to reduce lipid accumulation in macrophages, recognized as a critical stage in the progression of atherosclerosis. Furtherly, the modulation of CCAAT/enhancer-binding protein ß (C/EBPß) and peroxisome proliferator-activated receptor- γ1 (PPAR-γ1), as transcription factors involved in lipid metabolism, was evaluated. METHODS: THP-1-derived macrophages were treated for 24 h with 0.03, 0.3, 3 and 30 µM of CGA and CA, tested alone or in combination, and a solution of oleic/palmitic acid (500 µM, 2:1 ratio). Lipid storage was assessed spectrophotometrically through fluorescent staining of cells with Nile red. C/EBPß and PPAR-γ1 mRNA and protein levels were evaluated by RT-PCR and enzyme-linked immunosorbent assay, respectively. RESULTS: The mix of CGA + CA (1:1 ratio) reduced lipid accumulation at all concentrations tested, except for the highest one. The greatest effect ( - 65%; p < 0.01) was observed at the concentration of 0.3 µM for each compound. The same concentration significantly (p < 0.01) downregulated C/EBPß and PPAR-γ1 gene expression and reduced their protein levels at 2 h and 24 h, respectively. CONCLUSION: The results indicate that the capacity of CGA + CA mix to reduce lipid storage in macrophages is mediated by a reduction in the expression of transcription factors C/EBPß and PPAR-γ1.

An Overview of Registered Clinical Trials on Glucosinolates and Human Health: The Current Situation.

Epidemiological studies suggest a potential role of glucosinolates (GSLs) and isothiocyanates on human health. However, evidence from intervention studies, due to heterogeneity in features of study design, duration, participants, food or food components administered, and outcomes analyzed, is still insufficient. The current review aims to provide an overview of the trials on GSLs and GSL-rich foods registered over the last 20 years with the intention to summarize the main topics and results, but also the existing gaps that still need to be covered. Studies were collected by using ClinicalTrials.gov and the International Standard Randomized Controlled Trial Number (ISRCTN) registry. A total of 87 registered trials were identified with which most of them were performed by using extracts or pure compounds (n = 60) while few were conducted with GSL-rich foods (n = 27). In detail, sulforaphane was the most investigated compound, while broccoli was the most frequent food tested in the trials. The majority of the studies assessed the health effects of GSLs focusing on outcomes related to cancer and cognitive function, even if the current findings are not univocal. Emerging topics also included the study of GSLs and gut microbiota interaction and impact on skin health. Further attention was also drawn to the bioavailability of GSLs and/or derivatives from foods, extracts, and single compounds by also considering the contribution of the different genetic polymorphisms. In conclusion, although considerable efforts have been made to study GSLs and GSL-rich foods, further studies are necessary to provide evidence-based research and to corroborate the findings obtained. The interindividual response due to genetic polymorphisms should be further investigated in order to explore the contribution to the overall beneficial effect.

Association between Food Intake, Clinical and Metabolic Markers and DNA Damage in Older Subjects.

The use of DNA damage as marker of oxidative stress, metabolic dysfunction and age-related diseases is debated. The present study aimed at assessing the level of DNA damage (evaluated as DNA strand-breaks, endogenous and oxidatively-induced DNA damage) in a group of older subjects with intestinal permeability enrolled within the MaPLE (Gut and Blood Microbiomics for Studying the Effect of a Polyphenol-Rich Dietary Pattern on Intestinal Permeability in the Elderly) intervention trial, to evaluate its association with clinical, metabolic and dietary markers. DNA damage in peripheral blood mononuclear cells was assessed by the comet assay in 49 older subjects participating in the study. Clinical and metabolic markers, markers of inflammation, vascular function and intestinal permeability were determined in serum. Food intake was estimated by weighted food diaries. On the whole, a trend towards higher levels of DNA damage was observed in men compared to women (p = 0.071). A positive association between DNA damage and clinical/metabolic markers (e.g., uric acid, lipid profile) and an inverse association with dietary markers (e.g., vitamin C, E, B6, folates) were found and differed based on sex. By considering the importance of DNA stability during aging, the results obtained on sex differences and the potential role of dietary and metabolic factors on DNA damage underline the need for further investigations in a larger group of older adults to confirm the associations found and to promote preventive strategies.

Mechanistic aspects of carotenoid health benefits - where are we now?

Dietary intake and tissue levels of carotenoids have been associated with a reduced risk of several chronic diseases, including cardiovascular diseases, type 2 diabetes, obesity, brain-related diseases and some types of cancer. However, intervention trials with isolated carotenoid supplements have mostly failed to confirm the postulated health benefits. It has thereby been speculated that dosing, matrix and synergistic effects, as well as underlying health and the individual nutritional status plus genetic background do play a role. It appears that our knowledge on carotenoid-mediated health benefits may still be incomplete, as the underlying mechanisms of action are poorly understood in relation to human relevance. Antioxidant mechanisms - direct or via transcription factors such as NRF2 and NF-κB - and activation of nuclear hormone receptor pathways such as of RAR, RXR or also PPARs, via carotenoid metabolites, are the basic principles which we try to connect with carotenoid-transmitted health benefits as exemplified with described common diseases including obesity/diabetes and cancer. Depending on the targeted diseases, single or multiple mechanisms of actions may play a role. In this review and position paper, we try to highlight our present knowledge on carotenoid metabolism and mechanisms translatable into health benefits related to several chronic diseases.

A polyphenol-rich dietary pattern improves intestinal permeability, evaluated as serum zonulin levels, in older subjects: The MaPLE randomised controlled trial.

BACKGROUND & AIM: Increased intestinal permeability (IP) can occur in older people and contribute to the activation of the immune system and inflammation. Dietary interventions may represent a potential strategy to reduce IP. In this regard, specific food bioactives such as polyphenols have been proposed as potential IP modulator due to their ability to affect several critical targets and pathways that control IP. The trial aimed to test the hypothesis that a polyphenol-rich dietary pattern can decrease serum zonulin levels, an IP surrogate marker involved in tight junction modulation, and can beneficially alter the intestinal microbiota, and IP-associated biochemical and clinical markers in older subjects. METHODS: A randomised, controlled, cross-over intervention trial was performed. Sixty-six subjects (aged ≥ 60 y) with increased IP based on serum zonulin levels, were randomly allocated to one of the two arms of the intervention consisting of a control diet (C-diet) vs. a polyphenol-rich diet (PR-diet). Each intervention was 8-week long and separated by an 8-week wash out period. At the beginning and at the end of each intervention period, serum samples were collected for the quantification of zonulin and other biological markers. Faecal samples were also collected to investigate the intestinal microbial ecosystem. In addition, anthropometrical/physical/biochemical parameters and food intake were evaluated. RESULTS: Fifty-one subjects successfully completed the intervention and a high compliance to the dietary protocols was demonstrated. Overall, polyphenol intake significantly increased from a mean of 812 mg/day in the C diet to 1391 mg/day in the PR-diet. Two-way analysis of variance showed a significant effect of treatment (p = 0.008) and treatment × time interaction (p = 0.025) on serum zonulin levels, which decreased after the 8-week PR-diet. In addition, a treatment × time interaction was observed showing a reduction of diastolic blood pressure (p = 0.028) following the PR-diet, which was strongest in those not using antihypertensive drugs. A decrease in both diastolic (p = 0.043) and systolic blood pressure (p = 0.042) was observed in women. Interestingly, a significant increase in fibre-fermenting and butyrate-producing bacteria such as the family Ruminococcaceae and members of the genus Faecalibacterium was observed following the PR intervention. The efficacy of this dietary intervention was greater in subjects with higher serum zonulin at baseline, who showed more pronounced alterations in the markers under study. Furthermore, zonulin reduction was also stronger among subjects with higher body mass index and with insulin resistance at baseline, thus demonstrating the close interplay between IP and metabolic features. CONCLUSIONS: These data show, for the first time, that a PR-diet can reduce serum zonulin levels, an indirect marker of IP. In addition, PR-diet reduced blood pressure and increased fibre-fermenting and butyrate-producing bacteria. These findings may represent an initial breakthrough for further intervention studies evaluating possible dietary treatments for the management of IP, inflammation and gut function in different target populations. THIS STUDY WAS REGISTERED AT WWW.ISRCTN. ORG AS: ISRCTN10214981.

A Review of Registered Clinical Trials on Dietary (Poly)Phenols: Past Efforts and Possible Future Directions.

In recent years, the increasing number of studies on polyphenol demonstrates the efforts in elucidating the potential role of these bioactives on human health. This study reviews the main topics and characteristics of clinical trials on polyphenols registered over the last 20 years, in order to track past and current efforts as well as to highlight the main research gaps in this field. The review was conducted by collecting trials registered in ClinicalTrials.gov and International Standard Randomised Controlled Trial Number (ISRCTN) registry. Overall, 750 clinical trials were selected and included in the final evaluation. Most of the trials were performed on extracts or pure compounds followed by studies conducted on polyphenol-rich foods, in particular berries. A total of 520 clinical trials focused on health effects, 55 on bioavailability, and 175 on both. Regarding outcomes, 139 registered intervention studies had the lipid profile and blood pressure as primary outcomes. The overview provided by this analysis also emphasizes the emerging interest in new outcomes related to polyphenols intervention such as microbiota composition and the evaluation of inter-individual variability in response to the intake of polyphenols. Our review underlines the need of further trials covering unexplored or debated research aspects and provides insights for the design and development of future intervention studies and related research areas.

A Call to Action: Now Is the Time to Screen Elderly and Treat Osteosarcopenia, a Position Paper of the Italian College of Academic Nutritionists MED/49 (ICAN-49).

Aging is a risk factor for the development of multiple chronic diseases, including cardiovascular disease, cancer and dementia. Life expectancy has increased in certain countries but this phenomenon is associated with a reduction of years of healthy life. Aging is associated with a number of physical and functional changes, especially sarcopenia. Sarcopenia is a clinical condition associated with a decrease in skeletal muscle and muscle strength, however, sarcopenia is a reversible condition. On the basis of the current scientific literature, sarcopenia could more appropriately capture an individual's vulnerability to negative health-related outcomes since it represents an early form of the chronic diseases. Recognition of this clinical condition can improve the management of older individuals in many different clinical settings. Despite the limitations of the indirect methods used to study body composition, the Italian College of the Academic Nutritionists ME/49 recommends that health authorities and health professionals around the world should make a greater effort to diagnose sarcopenia earlier and to manage it more effectively. In line with the development of cancer screening, the use of two diagnostic tools for sarcopenia (BIA and DXA) should be implemented.

Estimated Intakes of Nutrients and Polyphenols in Participants Completing the MaPLE Randomised Controlled Trial and Its Relevance for the Future Development of Dietary Guidelines for the Older Subjects.

The evaluation of food intake in older subjects is crucial in order to be able to verify adherence to nutritional recommendations. In this context, estimation of the intake of specific dietary bioactives, such as polyphenols, although particularly challenging, is necessary to plan possible intervention strategies to increase their intake. The aims of the present study were to: (i) evaluate the nutritional composition of dietary menus provided in a residential care setting; (ii) estimate the actual intake of nutrients and polyphenols in a group of older subjects participating in the MaPLE study; and (iii) investigate the impact of an eight-week polyphenol-rich dietary pattern, compared to an eight-week control diet, on overall nutrient and polyphenol intake in older participants. The menus served to the participants provided ~770 mg per day of total polyphenols on average with small variations between seasons. The analysis of real consumption, measured using weighed food diaries, demonstrated a lower nutrient (~20%) and polyphenol intake (~15%) compared to that provided by the menus. The feasibility of dietary patterns that enable an increase in polyphenol intake with putative health benefits for age-related conditions is discussed, with a perspective to developing dietary guidelines for this target population.

The Central Role of Iron in Human Nutrition: From Folk to Contemporary Medicine.

Iron is a fundamental element in human history, from the dawn of civilization to contemporary days. The ancients used the metal to shape tools, to forge weapons, and even as a dietary supplement. This last indication has been handed down until today, when martial therapy is considered fundamental to correct deficiency states of anemia. The improvement of the martial status is mainly targeted with dietary supplements that often couple diverse co-factors, but other methods are available, such as parenteral preparations, dietary interventions, or real-world approaches. The oral absorption of this metal occurs in the duodenum and is highly dependent upon its oxidation state, with many absorption influencers possibly interfering with the intestinal uptake. Bone marrow and spleen represent the initial and ultimate step of iron metabolism, respectively, and the most part of body iron circulates bound to specific proteins and mainly serves to synthesize hemoglobin for new red blood cells. Whatever the martial status is, today's knowledge about iron biochemistry allows us to embrace exceedingly personalized interventions, which however owe their success to the mythical and historical events that always accompanied this metal.

Modulation of Adhesion Process, E-Selectin and VEGF Production by Anthocyanins and Their Metabolites in an in vitro Model of Atherosclerosis.

The present study aims to evaluate the ability of peonidin and petunidin-3-glucoside (Peo-3-glc and Pet-3-glc) and their metabolites (vanillic acid; VA and methyl-gallic acid; MetGA), to prevent monocyte (THP-1) adhesion to endothelial cells (HUVECs), and to reduce the production of vascular cell adhesion molecule (VCAM)-1, E-selectin and vascular endothelial growth factor (VEGF) in a stimulated pro-inflammatory environment, a pivotal step of atherogenesis. Tumor necrosis factor-α (TNF-α; 100 ng mL-1) was used to stimulate the adhesion of labelled monocytes (THP-1) to endothelial cells (HUVECs). Successively, different concentrations of Peo-3-glc and Pet-3-glc (0.02 µM, 0.2 µM, 2 µM and 20 µM), VA and MetGA (0.05 µM, 0.5 µM, 5 µM and 50 µM) were tested. After 24 h, VCAM-1, E-selectin and VEGF were quantified by ELISA, while the adhesion process was measured spectrophotometrically. Peo-3-glc and Pet-3-glc (from 0.02 µM to 20 µM) significantly (p < 0.0001) decreased THP-1 adhesion to HUVECs at all concentrations (-37%, -24%, -30% and -47% for Peo-3-glc; -37%, -33%, -33% and -45% for Pet-3-glc). VA, but not MetGA, reduced the adhesion process at 50 µM (-21%; p < 0.001). At the same concentrations, a significant (p < 0.0001) reduction of E-selectin, but not VCAM-1, was documented. In addition, anthocyanins and their metabolites significantly decreased (p < 0.001) VEGF production. The present findings suggest that while Peo-3-glc and Pet-3-glc (but not their metabolites) reduced monocyte adhesion to endothelial cells through suppression of E-selectin production, VEGF production was reduced by both anthocyanins and their metabolites, suggesting a role in the regulation of angiogenesis.

Effect of a polyphenol-rich dietary pattern on intestinal permeability and gut and blood microbiomics in older subjects: study protocol of the MaPLE randomised controlled trial.

BACKGROUND: During aging, alterations of the intestinal microbial ecosystem can occur contributing to immunosenescence, inflamm-aging and impairment of intestinal barrier function (increased intestinal permeability; IP). In the context of a diet-microbiota-IP axis in older subjects, food bioactives such as polyphenols may play a beneficial modulatory role. METHODS: MaPLE is a project centered on a randomized, controlled cross-over dietary intervention trial [polyphenol-rich diet (PR-diet) versus control diet (C-diet)] targeted to older people (≥ 60 y) living in a well-controlled setting (i.e. nursing home). The 8-week interventions are separated by an 8-week wash-out period. Three small portions per day of selected polyphenol-rich foods are consumed during intervention in substitution of other comparable products within the C-diet. Biological samples are collected before and after each treatment period to evaluate markers related to IP, inflammation, vascular function, oxidative stress, gut and blood microbiomics, metabolomics. A sample size of 50 subjects was defined based on IP as primary outcome. DISCUSSION: Evidence that increasing the consumption of polyphenol-rich food products can positively affect intestinal microbial ecosystem resulting in reduced IP and decreased translocation of inflammogenic bacterial factors into the bloodstream will be provided. The integration of data from gut and blood microbiomics, metabolomics and other IP-related markers will improve the understanding of the beneficial effect of the intervention in the context of polyphenols-microbiota-IP interactions. Finally, findings obtained will provide a proof of concept of the reliability of the dietary intervention, also contributing to future implementations of dietary guidelines directed to IP management in the older and other at risk subjects. TRIAL REGISTRATION: The trial is registered at (ISRCTN10214981); April 28, 2017.

Oral Supplementation with Sucrosomial Ferric Pyrophosphate Plus L-Ascorbic Acid to Ameliorate the Martial Status: A Randomized Controlled Trial.

Altered martial indices before orthopedic surgery are associated with higher rates of complications and greatly affect the patient's functional ability. Oral supplements can optimize the preoperative martial status, with clinical efficacy and the patient's tolerability being highly dependent on the pharmaceutical formula. Patients undergoing elective hip/knee arthroplasty were randomized to be supplemented with a 30-day oral therapy of sucrosomial ferric pyrophosphate plus L-ascorbic acid. The tolerability was 2.7% among treated patients. Adjustments for confounding factors, such as iron absorption influencers, showed a relevant response limited to older patients (≥ 65 years old), whose uncharacterized Hb loss was averted upon treatment with iron formula. Older patients with no support lost -2.8 ± 5.1%, while the intervention group gained +0.7 ± 4.6% of circulating hemoglobin from baseline (p = 0.019). Gastrointestinal diseases, medications, and possible dietary factors could affect the efficacy of iron supplements. Future opportunities may consider to couple ferric pyrophosphate with other nutrients, to pay attention in avoiding absorption disruptors, or to implement interventions to obtain an earlier martial status optimization at the population level.

Role of berries in vascular function: a systematic review of human intervention studies.

CONTEXT: Berries are a source of polyphenols with recognized health-promoting activities. Several studies suggest that consumption of berries may improve vascular function. OBJECTIVE: The aim of this systematic review is to provide evidence of short- and long-term benefits of berries on outcomes of vascular function. DATA SOURCES: Human intervention studies were collected from PubMed and Scopus databases. STUDY SELECTION: Studies were eligible if they investigated the effects of acute or chronic berry consumption on one or more markers of vascular function in humans and provided a characterization of the berry polyphenolic content. Only randomized controlled trials were included, and studies were excluded if berries were combined with other foods. DATA EXTRACTION: After selection, 22 randomized controlled trials were included and analyzed, most of which were performed in healthy individuals or patients with cardiovascular risk factors. RESULTS: The overall results seem to suggest a protective role of berries in vascular function, likely dependent on the time of exposure, the type and dose of berry, and the biomarkers analyzed. Flow-mediated dilation and reactive hyperemia index (markers of vascular reactivity) improved following short-term interventions, while pulse wave velocity and augmentation index (markers of arterial stiffness) improved only after medium- to long-term intervention. CONCLUSIONS: Current evidence suggests that berries, at physiological relevant doses, may have a role in the modulation of vascular function and stiffness. High-quality human intervention trials are encouraged in order to strengthen these findings and to better elucidate the mechanisms involved in such modulation.

Polyphenols and Intestinal Permeability: Rationale and Future Perspectives.

Increasing evidence links intestinal permeability (IP), a feature of the intestinal barrier, to several pathological or dysfunctional conditions. Several host and environmental factors, including dietary factors, can affect the maintenance of normal IP. In this regard, food bioactives, such as polyphenols, have been proposed as potential IP modulators, even if the mechanisms involved are not yet fully elucidated. The aim of the present paper is to provide a short overview of the main evidence from in vitro and in vivo studies supporting the role of polyphenols in modulating IP and briefly discuss future perspectives in this research area.