Recent Research on the Health Benefits of Blueberries and Their Anthocyanins

Awareness of the human health benefits of blueberries is underpinned by a growing body of positive scientific evidence from human observational and clinical research, plus mechanistic research using animal and in vitro models. Blueberries contain a large number of phytochemicals, including abundant anthocyanin pigments. Of their various phytochemicals, anthocyanins probably make the greatest impact on blueberry health functionality. Epidemiological studies associate regular, moderate intake of blueberries and/or anthocyanins with reduced risk of cardiovascular disease, death, and type 2 diabetes, and with improved weight maintenance and neuroprotection. These findings are supported by biomarker-based evidence from human clinical studies. Among the more important healthful aspects of blueberries are their anti-inflammatory and antioxidant actions and their beneficial effects on vascular and glucoregulatory function. Blueberry phytochemicals may affect gastrointestinal microflora and contribute to host health. These aspects have implications in degenerative diseases and conditions as well as the aging process. More evidence, and particularly human clinical evidence, is needed to better understand the potential for anthocyanin-rich blueberries to benefit public health. However, it is widely agreed that the regular consumption of tasty, ripe blueberries can be unconditionally recommended

Dietary inflammatory index and inflammatory gene interactions in relation to colorectal cancer risk in the Bellvitge colorectal cancer case-control study

Chronic inflammation is an important factor in colorectal carcinogenesis. However, evidence on the effect of pro-inflammatory and anti-inflammatory foods and nutrients is scarce. Moreover, there are few studies focusing on diet-gene interactions on inflammation and colorectal cancer (CRC). This study was designed to investigate the association between the novel dietary inflammatory index (DII) and CRC and its potential interaction with polymorphisms in inflammatory genes. Data from the Bellvitge Colorectal Cancer Study, a case-control study (424 cases with incident colorectal cancer and 401 hospital-based controls), were used. The DII score for each participant was obtained by multiplying intakes of dietary components from a validated dietary history questionnaire by literature-based dietary inflammatory weights that reflected the inflammatory potential of components. Data from four important single nucleotide polymorphisms located in genes thought to be important in inflammation-associated CRC: i.e., interleukin (IL)-4, IL-6, IL-8, and peroxisome proliferator-activated receptor-γ (PPARG) were analyzed. A direct association was observed between DII score and CRC risk (ORQ4 vs. Q1 1.65, 95 % CI 1.05-2.60, and P trend 0.011). A stronger association was found with colon cancer risk (ORQ4 vs. Q1 2.24, 95 % CI 1.33-3.77, and P trend 0.002) than rectal cancer risk (ORQ4 vs. Q1 1.12, 95 % CI 0.61-2.06, and P trend 0.37). DII score was inversely correlated with SNP rs2243250 in IL-4 among controls, and an interaction was observed with CRC risk. Neither correlation nor interaction was detected for other inflammatory genes. Overall, high-DII diets are associated with increased risk of CRC, particularly for colon cancer, suggesting that dietary-mediated inflammation plays an important role in colorectal carcinogenesis

Total urinary polyphenols and longitudinal changes of bone properties. The InCHIANTI study

SummaryThe aim of this study was to evaluate the association of levels of urinary total polyphenols considered as a proxymeasure of polyphenol intake, with longitudinal changes of bone properties, in the InCHIANTI study. Dietary intake ofpolyphenols appears to be associated with future accelerated deterioration of bone health.IntroductionPolyphenols, micronutrients ingested through plant-based foods, have antioxidant and anti-inflammatory propertiesand may contribute to osteoporosis prevention. We evaluated associations of high levels of urinary total polyphenols (UTP), aproxy measure of polyphenol intake, with longitudinal changes of bone properties in a representative cohort of free-livingparticipants of the InCHIANTI study.MethodsThe InCHIANTI study enrolled representative samples from the registry list of two towns in Tuscany, Italy. Baselinedata were collected in 1998 and follow-up visits in 2001 and 2004. Of the 1453 participants enrolled, 956 consented to donate a24-h urine sample used to assess UTP, had dietary assessment, a physical examination, and underwent a quantitative comput-erized tomography (pQCT) of the tibia. From pQCT images, we estimated markers of bone mass (BM), diaphyseal design (DD),and material quality (MQ). Mixed models were used to study the relationship between baseline tertiles of UTP with changes ofthe bone characteristics over the follow-up.ResultsAt baseline, higher levels of UTP were positively correlated with markers of BM, DD, and MQ. Compared with lowertertile of UTP, participants in the intermediate and highest tertiles had higher cortical bone area, cortical mineral content, andcortical thickness. However, participants in the intermediate and highest UTP tertiles experienced accelerated deterioration ofthese same parameters over the follow-up compared with those in the lowest UTP tertile.ConclusionsDietary intake of polyphenols estimated by UTP and dietary questionnaire was associated with long-term acceler-ated deterioration of bone health. Our study does not support the recommendation of increasing polyphenol intake for osteopo-rosis prevention

Flavonoid and lignan intake in relation to bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Item does not contain fulltextBACKGROUND: There is growing evidence of the protective role of dietary intake of flavonoids and lignans on cancer, but the association with bladder cancer has not been thoroughly investigated in epidemiological studies. We evaluated the association between dietary intakes of total and subclasses of flavonoids and lignans and risk of bladder cancer and its main morphological type, urothelial cell carcinoma (UCC), within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: A cohort of 477 312 men and women mostly aged 35-70 years, were recruited in 10 European countries. At baseline, dietary flavonoid and lignan intakes were estimated using centre-specific validated questionnaires and a food composition database based on the Phenol-Explorer, the UK Food Standards Agency and the US Department of Agriculture databases. RESULTS: During an average of 11 years of follow-up, 1575 new cases of primary bladder cancer were identified, of which 1425 were UCC (classified into aggressive (n=430) and non-aggressive (n=413) UCC). No association was found between total flavonoid intake and bladder cancer risk. Among flavonoid subclasses, significant inverse associations with bladder cancer risk were found for intakes of flavonol (hazard ratio comparing fifth with first quintile (HRQ5-Q1) 0.74, 95% confidence interval (CI): 0.61-0.91; P-trend=0.009) and lignans (HRQ5-Q1 0.78, 95% CI: 0.62-0.96; P-trend=0.046). Similar results were observed for overall UCC and aggressive UCC, but not for non-aggressive UCC. CONCLUSIONS: Our study suggests an inverse association between the dietary intakes of flavonols and lignans and risk of bladder cancer, particularly aggressive UCC

Flavonoid intake is associated with lower mortality in the Danish Diet Cancer and Health Cohort

Flavonoids, plant-derived polyphenolic compounds, have been linked with health benefits. However, evidence from observational studies is incomplete; studies on cancer mortality are scarce and moderating effects of lifestyle risk factors for early mortality are unknown. In this prospective cohort study including 56,048 participants of the Danish Diet, Cancer, and Health cohort crosslinked with Danish nationwide registries and followed for 23 years, there are 14,083 deaths. A moderate habitual intake of flavonoids is inversely associated with all-cause, cardiovascular- and cancer-related mortality. This strong association plateaus at intakes of approximately 500 mg/day. Furthermore, the inverse associations between total flavonoid intake and mortality outcomes are stronger and more linear in smokers than in non-smokers, as well as in heavy (\u3e20 g/d) vs. low-moderate (/d) alcohol consumers. These findings highlight the potential to reduce mortality through recommendations to increase intakes of flavonoid-rich foods, particularly in smokers and high alcohol consumers

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 ( 65 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

Lipopolysaccharide-binding protein and future Parkinson's disease risk: a European prospective cohort

INTRODUCTION: Lipopolysaccharide (LPS) is the outer membrane component of Gram-negative bacteria. LPS-binding protein (LBP) is an acute-phase reactant that mediates immune responses triggered by LPS and has been used as a blood marker for LPS. LBP has recently been indicated to be associated with Parkinson's disease (PD) in small-scale retrospective case-control studies. We aimed to investigate the association between LBP blood levels with PD risk in a nested case-control study within a large European prospective cohort. METHODS: A total of 352 incident PD cases (55% males) were identified and one control per case was selected, matched by age at recruitment, sex and study center. LBP levels in plasma collected at recruitment, which was on average 7.8 years before diagnosis of the cases, were analyzed by enzyme linked immunosorbent assay. Odds ratios (ORs) were estimated for one unit increase of the natural log of LBP levels and PD incidence by conditional logistic regression. RESULTS: Plasma LBP levels were higher in prospective PD cases compared to controls (median (interquartile range) 26.9 (18.1-41.0) vs. 24.7 (16.6-38.4) µg/ml). The OR for PD incidence per one unit increase of log LBP was elevated (1.46, 95% CI 0.98-2.19). This association was more pronounced among women (OR 2.68, 95% CI 1.40-5.13) and overweight/obese subjects (OR 1.54, 95% CI 1.09-2.18). CONCLUSION: The findings suggest that higher plasma LBP levels may be associated with an increased risk of PD and may thus pinpoint to a potential role of endotoxemia in the pathogenesis of PD, particularly in women and overweight/obese individuals

Biomarkers of the transsulfuration pathway and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Previous studies have suggested that components of one-carbon metabolism, particularly circulating vitamin B6, have an etiological role in renal cell carcinoma (RCC). Vitamin B6 is a cofactor in the transsulfuration pathway. We sought to holistically investigate the role of the transsulfuration pathway in RCC risk. We conducted a nested case-control study (455 RCC cases and 455 matched controls) within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Plasma samples from the baseline visit were analyzed for metabolites of the transsulfuration pathway, including pyridoxal 5'-phosphate (PLP, the biologically active form of vitamin B6), homocysteine, serine, cystathionine, and cysteine, in addition to folate. Bayesian conditional logistic regression was used to estimate associations of metabolites with RCC risk as well as interactions with established RCC risk factors. Circulating PLP and cysteine were inversely associated with RCC risk, and these association were not attenuated after adjustment for other transsulfuration metabolites (odds ratio (OR) and 90% credible interval (CrI) per 1 SD increase in log concentration: 0.76 [0.66, 0.87]; 0.81 [0.66, 0.96], respectively). A comparison of joint metabolite profiles suggested substantially greater RCC risk for the profile representative of low overall transsulfuration function compared with high function (OR 2.70 [90% CrI 1.26, 5.70]). We found some statistical evidence of interactions of cysteine with body mass index, and PLP and homocysteine with smoking status, on their associations with RCC risk. In conclusion, we found evidence suggesting that the transsulfuration pathway may play a role in metabolic dysregulation leading to RCC development. This article is protected by copyright. All rights reserved

Dietary intakes of flavan-3-ols and cardiovascular health: a field synopsis using evidence mapping of randomized trials and prospective cohort studies

Background: There is considerable interest in the impact of increased flavan-3-ol intake on cardiovascular disease (CVD) and diabetes outcomes. Through evidence mapping, we determined the extent of the evidence base to initiate a future systematic review investigating the impact of flavan-3-ol intake on CVD and diabetes outcomes. Methods: We developed a research protocol, convened a technical expert panel (TEP) to refine the specific research questions, conducted a systematic search in multiple databases, double-screened abstracts and full-text articles, performed data extractions, and synthesized the data. We focused on randomized controlled trials (RCTs) and prospective cohort studies which assessed intakes of flavan-3-ol from foods, beverages, and supplement/extract sources on biomarkers and clinical outcomes of CVD and diabetes. Results: Of 257 eligible articles, 223 and 34 publications contributed to 226 RCTs and 39 prospective cohort studies, respectively. In RCTs, the most frequently studied interventions were cocoa-based products (23.2%); berries (16.1%); tea in the form of green tea (13.9%), black tea (7.2%), or unspecified tea (3.6%); and red wine (11.2%). Mean total flavan-3-ol intake was highest in the cocoa-based trials (618.7 mg/day) and lowest in the interventions feeding red wine (123.7 mg/day). The most frequently reported outcomes were intermediate biomarkers including serum lipid levels (63.4%), blood glucose (50.9%), blood pressure (50.8%), flow-mediated dilation (21.9%), and high-sensitivity C-reactive protein (21.9%). The included 34 prospective cohort studies predominantly examined exposures to flavan-3-ols (26%), cocoa-based products (23.2%), berries (16.1%), and green tea (13.9%) and CVD incidence and mortality. Conclusion: Through a systematic, evidence-based approach, evidence mapping on flavan-3-ol intake and CVD outcomes demonstrated sufficient data relating to flavan-3ol intake and biomarkers and clinical outcomes of CVD and diabetes. The current evidence base highlights the distribution of available data which both support the development of a future systematic review and identified the research need for future long-term RCTs

Systematic Review on Polyphenol Intake and Health Outcomes: Is there Sufficient Evidence to Define a Health-Promoting Polyphenol-Rich Dietary Pattern?

Growing evidence support association between polyphenol intake and reduced risk for chronic diseases, even if there is a broad debate about the effective amount of polyphenols able to exert such protective effect. The present systematic review provides an overview of the last 10-year literature on the evaluation of polyphenol intake and its association with specific disease markers and/or endpoints. An estimation of the mean total polyphenol intake has been performed despite the large heterogeneity of data reviewed. In addition, the contribution of dietary sources was considered, suggesting tea, coffee, red wine, fruit and vegetables as the main products providing polyphenols. Total flavonoids and specific subclasses, but not total polyphenols, have been apparently associated with a low risk of diabetes, cardiovascular events and all-cause mortality. However, large variability in terms of methods for the evaluation and quantification of polyphenol intake, markers and endpoints considered, makes it still difficult to establish an evidence-based reference intake for the whole class and subclass of compounds. Nevertheless, the critical mass of data available seem to strongly suggest the protective effect of a polyphenol-rich dietary pattern even if further well targeted and methodologically sound research should be encouraged in order to define specific recommendations