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Background Higher flavonoid intakes are hypothesised to confer protection against type 2 diabetes mellitus. Objective We aimed to 1) investigate associations between flavonoid intakes and diabetes, 2) examine the mediating impact of body fat, and 3) identify subpopulations that may receive the greatest benefit from higher flavonoid intakes in participants of the Danish Diet, Cancer, and Health Study followed-up for 23 years. Design Cross-sectional associations between baseline flavonoid intake, estimated using food frequency questionnaires and the Phenol Explorer database, and body fat estimated by bioelectrical impedance, were assessed using multivariable-adjusted linear regression models. Non-linear associations between flavonoid intake and incident diabetes were examined using restricted cubic splines with multivariable-adjusted Cox proportional hazards models. Results Among 54,787 participants (median [IQR] age of 56 [52-60] years; (47.3%) men), 6700 individuals were diagnosed with diabetes. Participants in the highest total flavonoid intake quintile (median, 1,202 mg/d) had a 1.52 kg lower body fat (95%CI: -1.74, -1.30) and a 19% lower risk of diabetes [hazard ratio (95%CI): 0.81 (0.75, 0.87)] after multivariable adjustments and compared to participants in the lowest intake quintile (median, 174 mg/d). Body fat mediated 57% (95% CI: 42%, 83%) of the association between flavonoid intake and incident diabetes. Of the flavonoid subclasses, moderate to high intakes of flavonols, flavanol monomers, flavanol oligo + polymers, and anthocyanins were significantly associated with a lower risk of diabetes. While associations were not modified by sex, smoking status, BMI or physical activity (pinteraction > 0.05 for all), findings on an absolute scale suggest that those at a higher risk (those with obesity) may benefit the most from a higher flavonoid intake. Conclusions These findings suggest that a diet abundant in flavonoid-rich foods may help to ameliorate diabetes risk, in part through a reduction in body fat.

Introduction Higher flavonoid intakes are beneficially associated with pulmonary function parameters;however, their association with chronic obstructive pulmonary disease (COPD) is unknown. This studyaimed to examine associations between intakes of 1) total flavonoids, 2) flavonoid subclasses and 3) majorflavonoid compounds with incident COPD in participants from the Danish Diet, Cancer and Health study.Methods This prospective cohort included 55 413 men and women without COPD, aged 50–65 years atrecruitment. Habitual flavonoid intakes at baseline were estimated from a food frequency questionnaireusing Phenol-Explorer. Danish nationwide registers were used to identify incident cases of COPD.Associations were modelled using restricted cubic splines within Cox proportional hazards models.Results During 23 years of follow-up, 5557 participants were diagnosed with COPD. Of these, 4013 werecurrent smokers, 1062 were former smokers and 482 were never-smokers. After multivariable adjustments,participants with the highest total flavonoid intakes had a 20% lower risk of COPD than those with thelowest intakes (quintile 5 versus quintile 1: HR 0.80, 95% CI 0.74–0.87); a 6–22% lower risk wasobserved for each flavonoid subclass. The inverse association between total flavonoid intake and COPDwas present in both men and women but only in current smokers (HR 0.77, 95% CI 0.70–0.84) andformer smokers (HR 0.82, 95% CI 0.69–0.97), not never-smokers. Furthermore, higher flavonoid intakesappeared to lessen, but not negate, the higher risk of COPD associated with smoking intensity.Conclusion Dietary flavonoids may be important for partially mitigating the risk of smoking-relatedCOPD. However, smoking cessation should remain the highest priority Introduction Higher flavonoid intakes are beneficially associated with pulmonary function parameters; however, their association with chronic obstructive pulmonary disease (COPD) is unknown. This study aimed to examine associations between intakes of 1) total flavonoids, 2) flavonoid subclasses and 3) major flavonoid compounds with incident COPD in participants from the Danish Diet, Cancer and Health study.Methods This prospective cohort included 55 413 men and women without COPD, aged 50-65 years at recruitment. Habitual flavonoid intakes at baseline were estimated from a food frequency questionnaire using Phenol-Explorer. Danish nationwide registers were used to identify incident cases of COPD. Associations were modelled using restricted cubic splines within Cox proportional hazards models.Results During 23 years of follow-up, 5557 participants were diagnosed with COPD. Of these, 4013 were current smokers, 1062 were former smokers and 482 were never-smokers. After multivariable adjustments, participants with the highest total flavonoid intakes had a 20% lower risk of COPD than those with the lowest intakes (quintile 5 versus quintile 1: HR 0.80, 95% CI 0.74-0.87); a 6-22% lower risk was observed for each flavonoid subclass. The inverse association between total flavonoid intake and COPD was present in both men and women but only in current smokers (HR 0.77, 95% CI 0.70-0.84) and former smokers (HR 0.82, 95% CI 0.69-0.97), not never-smokers. Furthermore, higher flavonoid intakes appeared to lessen, but not negate, the higher risk of COPD associated with smoking intensity.Conclusion Dietary flavonoids may be important for partially mitigating the risk of smoking-related COPD. However, smoking cessation should remain the highest priority.

Soybeans are a rich source of isoflavones, which are classified as phytoestrogens. Despite numerous proposed benefits, isoflavones are often classified as endocrine disruptors, based primarily on animal studies. However, there are ample human data regarding the health effects of isoflavones. We conducted a technical review, systematically searching Medline, EMBASE, and the Cochrane Library (from inception through January 2021). We included clinical studies, observational studies, and systematic reviews and meta-analyses (SRMA) that examined the relationship between soy and/or isoflavone intake and endocrine-related endpoints. 417 reports (229 observational studies, 157 clinical studies and 32 SRMAs) met our eligibility criteria. The available evidence indicates that isoflavone intake does not adversely affect thyroid function. Adverse effects are also not seen on breast or endometrial tissue or estrogen levels in women, or testosterone or estrogen levels, or sperm or semen parameters in men. Although menstrual cycle length may be slightly increased, ovulation is not prevented. Limited insight could be gained about possible impacts of in utero isoflavone exposure, but the existing data are reassuring. Adverse effects of isoflavone intake were not identified in children, but limited research has been conducted. After extensive review, the evidence does not support classifying isoflavones as endocrine disruptors.

In an era where preventive medicine is increasingly important due to an ageing population and rising obesity, optimised diets are key to improving health and reducing risk of ill health. The Wellcome Trust‐funded, EDESIA: Plants, Food and Health: a cross‐disciplinary PhD programme from Crop to Clinic (218 467/Z/19/Z) focuses on investigating plant‐based nutrition and health, from crop to clinic, drawing on the world‐class interdisciplinary research expertise of partner institutions based on the Norwich Research Park (University of East Anglia, John Innes Centre, Quadram Institute and Earlham Institute). Through a rotation‐based programme, EDESIA PhD students will train in a wide range of disciplines across the translational pathway of nutrition research, including analyses of epidemiological datasets, assessment of nutritional bioactives, biochemical, genetic, cell biological and functional analyses of plant metabolites, in vitro analyses in tissue and cell cultures, investigation of efficacy in animal models of disease, investigation of effects on composition and functioning of the microbiota and human intervention studies. Research rotations add a breadth of knowledge, outside of the main PhD project, which benefits the students and can be brought into project design. This comprehensive PhD training programme will allow the translation of science into guidelines for healthy eating and the production of nutritionally improved food crops, leading to innovative food products, particularly for prevention and treatment of chronic diseases where age is a major risk factor. In this article, we summarise the programme and showcase the experiences of the first cohort of students as they start their substantive PhD projects after a year of research rotations.

Tea flavonoids have been suggested to offer potential benefits to cardiovascular health. This review synthesized the evidence on the relation between tea consumption and risks of cardiovascular disease (CVD) and all-cause mortality among generally healthy adults. PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, Food Science and Technology Abstracts, and Ovid CAB Abstract databases were searched to identify English-language publications through 1 November 2019, including randomized trials, prospective cohort studies, and nested case-control (or case-cohort) studies with data on tea consumption and risk of incident cardiovascular events (cardiac or peripheral vascular events), stroke events (including mortality), CVD-specific mortality, or all-cause mortality. Data from 39 prospective cohort publications were synthesized. Linear meta-regression showed that each cup (236.6 mL) increase in daily tea consumption (estimated 280 mg and 338 mg total flavonoids/d for black and green tea, respectively) was associated with an average 4% lower risk of CVD mortality, a 2% lower risk of CVD events, a 4% lower risk of stroke, and a 1.5% lower risk of all-cause mortality. Subgroup meta-analysis results showed that the magnitude of association was larger in elderly individuals for both CVD mortality (n = 4; pooled adjusted RR: 0.89; 95% CI: 0.83, 0.96; P = 0.001), with large heterogeneity (I(2) = 72.4%), and all-cause mortality (n = 3; pooled adjusted RR: 0.92; 95% CI: 0.90, 0.94; P < 0.0001; I(2) = 0.3%). Generally, studies with higher risk of bias appeared to show larger magnitudes of associations than studies with lower risk of bias. Strength of evidence was rated as low and moderate (depending on study population age group) for CVD-specific mortality outcome and was rated as low for CVD events, stroke, and all-cause mortality outcomes. Daily tea intake as part of a healthy habitual dietary pattern may be associated with lower risks of CVD and all-cause mortality among adults.

Phthalates are widely used as plasticizers. Laboratory-based mechanistic and epidemiological studies suggest that phthalates are detrimental to human health. Here, we present prospective analyses on phthalate exposure and all-cause, as well as cause-specific, mortality from the National Health and Nutrition Examination Survey (NHANES), a population-based cohort. Between 1999 and 2018, urinary concentrations of 12 phthalate metabolites were measured by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry in spot urine samples of 10,881 adults aged 40-85 years, of which 2382 died over a median duration of 8.9 years after sample provision. Multivariable Cox regression analyses adjusted for a wide range of lifestyle factors and comorbidities showed that higher concentrations of mono-benzyl phthalate (MBzP) and Mono-n-butyl phthalate (MnBP) were associated with increased mortality. The hazard ratios for participants in the highest quartiles of MBzP and MnBP concentrations were at 1.27 [95% confidence interval: 1.08, 1.49; p linear trend = 0.002] and 1.35 [1.13, 1.62; p linear trend = 0.005). These findings reinforce the need for monitoring of phthalate exposure in relation to health outcomes.

BACKGROUND & AIMS: Vitamin B6 status and mortality risk are inversely associated in different patient groups, while prospective studies in the general population are lacking. Here, for the first time, we evaluated the association between biomarkers of vitamin B6 status and mortality risk in a large population-based study.METHODS: The vitamin B6 vitamers pyridoxal-5'-phosphat (PLP) and 4-pyridoxic acid (4-PA) were measured by high-performance liquid chromatography in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2010. Participants' vital status and causes of death were recorded until December 2015. Multivariable Cox regression analyses were carried out to estimate Hazard Ratios (HRs) and 95% confidence intervals (CIs) of mortality across quintiles of PLP, 4-PA, and the ratio of 4-PA and PLP.RESULTS: Out of 15,304 study participants aged between 20 and 85 years at baseline, 1666 (7.7%) died during a median follow-up time of 7.8 years. An inverse association between PLP and mortality was found in a multivariable model adjusted for socioeconomic and lifestyle factors but became statistically non-significant upon adjustment for routine biomarkers (C-reactive protein, creatinine, albumin, and alkaline phosphatase). There was a significant linear trend for a positive association between 4-PA levels and mortality risk in the fully adjusted regression model, although a comparison of extreme quintiles (quintile 5 vs. quintile 1) did not show a significant difference (HRQ5vs.Q1 (95% CI): 1.19 (0.93, 1.51), plinear trend = 0.02). A positive association between the 4-PA/PLP ratio and all-cause mortality was observed in the multivariable model, with an HRsQ5vs.Q1 of 1.45 (95% CI: 1.14, 1.85; plinear trendCONCLUSION: Increased vitamin B6 turnover, as indicated by a higher 4-PA/PLP ratio, was associated with all-cause and cancer mortality among the older U.S. general population. Intervention trials are needed to assess whether older individuals with a high 4-PA/PLP ratio would benefit from increased vitamin B6 intake.

Background Flavonoid-rich foods may contribute to a lower risk of ischemic stroke through their anti-inflammatory, anti-atherogenic, and anti-thrombotic properties. We aimed to examine the relationship between flavonoid intake and ischemic stroke incidence in participants from the Danish Diet, Cancer, and Health study. Methods In this prospective cohort study, 55,169 Danish citizens without a prior ischemic stroke (median [IQR] age at enrolment of 56 [52 – 60] years), were followed for 21 [20 – 22] years. Baseline flavonoid intake was estimated from food frequency questionnaires using the Phenol-Explorer database. Incident cases of stroke were identified from Danish nation-wide public health registries. Associations between quintiles of flavonoid intake and incident ischemic stroke were assessed using Cox proportional hazard models adjusting for age, sex, BMI, smoking status, physical activity, alcohol intake, education, and income. Results During follow-up, 4,317 individuals experienced an ischemic stroke. Compared to participants in quintile one and after multivariable adjustments, those in quintile five for intake of total flavonoids, flavonols and oligo+polymers had a 12% [HR (95% CI): 0.88 (0.81, 0.96)], 10% [0.90 (0.82, 0.98)], and 18% [0.82 (0.75, 0.89)], lower risk of ischemic stroke incidence, respectively. Intake of flavan-3-ol monomers, anthocyanins, flavanones and flavones were not associated with incident ischemic stroke. Conclusions A moderate habitual intake of flavonoids, in particular the flavonol and flavan-3-ol oligo+polymer subclasses, is associated with a lower risk of ischemic stroke. Key messages Flavonoid rich foods appear protective against ischemic stroke.

BackgroundAlthough the pathophysiology of cognitive decline is multifactorial, and modifiable by lifestyle, the evidence for the role of diet on cognitive function is still accumulating, particularly the potentially preventive role of constituents of plant-based foods.MethodsWe aimed to determine whether higher habitual intake of dietary flavonoids, key components of plant-based diets, were associated with improved cognition and medial temporal lobe volumes using three complementary approaches (longitudinal, cross-sectional and co-twin analyses). In 1126 female twins (n=224 with a 10-year follow-up of diet and cognition data) aged 18–89 years, habitual intakes of total flavonoids and seven subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, polymeric flavonoids (and proanthocyanidins separately)) were calculated using validated food frequency questionnaires. Cognition was assessed using the Cambridge Neuropsychological Test Automated Battery test. Hippocampal volumes were measured in a subset using magnetic resonance imaging (16 monozygotic-twin pairs). Statistical models were adjusted for a range of diet and lifestyle factors.ResultsHigher intakes of flavanones (tertile (T)3-T1=0.45, 95%CI 0.13,0.77;p=0.01) and anthocyanins (T3-T1=0.45, 95%CI 0.08,0.81;p=0.02) were associated with improvements in age-related cognition score over 10 years. In cross-sectional analysis higher intake of flavanones (T3-T1= 0.12, 95% CI 0.02, 0.21;p=0.02) and proanthocyanidins (T3-T1= 0.13, 95% CI 0.02, 0.24;p=0.02) were associated with improved paired-associates learning. Higher intake of anthocyanins was significantly associated with improved executive function (T3-T1= −0.52, 95% CI 0.19, 0.84;p=0.001) and with faster simple reaction times (T3-T1= −18.1, 95% CI −35.4, −0.7; p=0.04). In co-twin analysis, those with higher anthocyanin (2.0%,p=0.01) and proanthocyanidin (2.0%,p=0.02) intakes at baseline had the largest left hippocampal volumes after 12 years.ConclusionSmall increases in habitual intake of flavonoid-rich foods (containing anthocyanins, flavanones and proanthocyanidins; equivalent to approximately two servings of oranges and blueberries per day) over long time periods have the potential to attenuate cognitive ageing.

Background and ObjectivesAlthough flavonoids have the potential to exert neuroprotective benefits, evidence of their role in improving survival rates among individuals with Parkinson disease (PD) remains lacking. We aimed to prospectively study the association between prediagnosis and postdiagnosis flavonoid intakes and risk of mortality among individuals with PD identified from 2 large ongoing cohorts of US men and women.MethodsIncluded in the current analysis were 599 women from the Nurses' Health Study and 652 men from the Health Professionals Follow-Up Study who were newly diagnosed with PD during follow-up. Dietary intakes of total flavonoid and its subclasses, together with major flavonoid-rich foods (tea, apples, berries, orange and orange juice, and red wine), were repeatedly assessed with a validated food frequency questionnaire every 4 years. Mortality was ascertained via the National Death Index and state vital statistics records.ResultsWe documented 944 deaths during 32 to 34 years of follow-up. A higher total flavonoid intake before PD diagnosis was associated with a lower future risk for all-cause mortality in men (hazard ratio [HR] comparing 2 extreme quartiles 0.53, 95% confidence interval [CI] 0.39, 0.71; p for trend < 0.001) but not in women (HR 0.93, 95% CI 0.68, 1.28; p for trend = 0.69) after adjustment for age, smoking status, total energy intake, and other covariates. The pooled HR comparing the extreme quartiles was 0.70 (95% CI 0.40, 1.22; p for trend = 0.25) with significant heterogeneity (p = 0.01). For flavonoid subclasses, the highest quartile of anthocyanins, flavones, and flavan-3-ols intakes before diagnosis had a lower mortality risk compared to the lowest quartile (pooled HR 0.66, 0.78, and 0.69, respectively; p < 0.05 for all); for berries and red wine, participants consuming ≥3 servings per week had a lower risk (pooled HR 0.77, 95% CI 0.58, 1.02; and pooled HR 0.68, 95% CI 0.51, 0.91, respectively) compared to p < 0.05 for all).DiscussionAmong individuals with PD, higher consumption of flavonoids, especially anthocyanins and flavan-3-ols, and flavonoid-rich food such as berries and red wine was likely to be associated with a lower risk of mortality.

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 (>20 g/d) vs. low-moderate (, The studies showing health benefits of flavonoids and their impact on cancer mortality are incomplete. Here, the authors perform a prospective cohort study in Danish participants and demonstrate an inverse association between regular flavonoid intake and both cardiovascular and cancer related mortality.

Background:Flavonoids are a diverse group of plant constituents with demonstrated neuroprotective and anti-tumor effects. Flavonoid intake may decrease the risk of glioma, but the possibility of an association has not yet been investigated in humans.Objectives:We evaluated the association between dietary flavonoid consumption and the risk of glioma.Methods:We followed participants in the female Nurses’ Health Study (1984–2014; n = 81,688) and Nurses’ Health Study II (1991–2017; n = 95,228) and the male Health Professionals Follow-Up Study (1986–2014; n = 49,885). We used multivariable-adjusted Cox proportional hazards regression models to evaluate the associations between average long-term (up to 30 years) or recent (up to 12 years) dietary flavonoid intake (total flavonoids and each of 6 subclasses) and risks of incident glioma. Flavonoid intake was derived from validated quadrennial FFQs. Incident glioma was self-reported and confirmed by a medical record review or was determined by a medical record review after death.Results:We documented 536 incident cases of glioma across 5,936,386 person-years of follow-up. Long-term total flavonoid, flavan-3-ol, and polymeric flavonoid (polymer) intakes were associated with decreased glioma risks in pooled analyses comparing the highest to lowest quintiles of consumption [HR, 0.79 (95% CI, 0.59–1.05; P-trend = 0.04) for total flavonoids; 0.76 (95% CI, 0.57–1.01; P-trend = 0.04) for flavan-3-ols; and 0.82 (95% CI, 0.61–1.09; P-trend = 0.05) for polymers]. Associations with recent intake were weaker. There were no associations with other flavonoid subclasses. After additional adjustment for tea consumption, there were no associations between flavan-3-ol or polymer consumption and glioma.Conclusions:Increased dietary intakes of flavan-3-ol and polymeric flavonoids, especially those predominant in tea, were associated with decreased glioma risks in a prospective cohort of men and women.

Introduction: The promotion of evidence-based diets is an important s trategy to mitigate the global health and economic burden of diabetes. Higher flavonoid intakes are associated with a lower risk of obesity and diabetes. Less clear are associations of the flavonoid subclasses with diabetes, the mediating impact of body fat, and the identification of subpopulations that may receive the greatest benefit. Hypothesis: Higher flavonoid intakes will be associated with lower body fat at baseline and a lower risk of diabetes during follow-up. Methods: Incident diabetes was assessed in 54,787 participants of the Danish Diet, Cancer, and Health Study followed-up for 23 years. Dietary intake and objective measures of body fat were assessed at baseline; habitual flavonoid intake was calculated using the Phenol-Explorer database and body fat was objectively assessed using bioelectrical impedance. Incidence of diabetes was obtained using Danish National Patient and Prescription Registries. Cross-sectional associations between flavonoid intakes and body fat were assessed using multivariable-adjusted linear regression models. Non-linear associations between flavonoid intake and incident diabetes were examined using restricted cubic splines based on multivariable-adjusted Cox proportional hazards models. Results: Among 54,787 participants without diabetes at baseline (median [IQR] age of 56 [52 - 60] years; (47.3%) men), 6,700 individuals were diagnosed with diabetes. Participants in the highest total flavonoid intake quintile (median, 1,202 mg/d) had a 1.52 kg lower body fat (95% CI: -1.74, -1.30) and a 19% lower risk of diabetes [HR (95% CI): 0.81 (0.75, 0.87)] after multivariable adjustments and compared to participants in the lowest intake quintile (median, 174 mg/d). Body fat mediated 51.6% of the association between flavonoid intake and incident diabetes. Neither smoking status, BMI, nor sex appeared to modify the association between total flavonoid intake and incident diabetes. However, the difference (flavonoid intake quintile 5 - quintile 1) in the 20-year estimated absolute risk of diabetes was greatest for current smokers (males: 2.19%, females: 1.65%) and those with a BMI ≥30 kg/m 2 (males: 5.56%, females: 4.59%), likely owing to the higher prevalence of diabetes in these “at risk” subgroups. Moderate to high intakes of flavonols, flavanol monomers, flavanol oligo+polymers, and anthocyanins, and the individual compounds within these subclasses, were associated with a lower risk of diabetes. Conclusion: In this Danish prospective cohort study, we observed that higher flavonoid intakes were cross-sectionally associated with lower body fat, and longitudinally associated with a lower risk of diabetes. Our results suggest that promoting a diet abundant in flavonoid-rich foods may help to ameliorate diabetes risk, in part through a reduction in body fat.

Vitamin B6 from plant foods may have lower bioavailability than vitamin B6 from animal foods, but studies on objectively measured vitamin B6 status among vegetarians compared to non-vegetarians are lacking. Thus, the vitamin B6 status among vegetarians, but also pescatarians, and flexitarians, compared to meat-eaters was assessed in the population-based NHANES study (cycles 2007–2008 and 2009–2010). Data on serum pyridoxal-5′-phosphate (PLP) and 4-pyridoxic acid (4-PA) measured by high-performance liquid chromatography (HPLC) as well as dietary intakes from 24-h recalls were available for 8968 adults aged 20–80 years. Geometric mean (±standard error) PLP concentrations were 58.2 ± 6.0, 52.1 ± 3.7, 49.2 ± 4.6 and 51.0 ± 1.1 nmol/L among vegetarians, pescatarians, flexitarians, and meat-eaters. The 4-PA concentrations were 32.7 ± 4.0, 29.0 ± 2.5, 34.8 ± 5.6 and 33.0 ± 0.7, respectively. There were no statistically significant differences in PLP, 4-PA, and their ratio across the groups in multivariable linear regression models. Overall, the use of vitamin B6 supplements was the strongest predictor of the vitamin B6 status, followed by the dietary vitamin B6 intake. Interestingly, several other covariates were significantly associated with vitamin B6 biomarker levels, particularly serum albumin, creatinine and alkaline phosphatase, and should be considered when assessing the vitamin B6 status. In summary, our findings suggest that a vegetarian diet does not pose a risk for vitamin B6 deficiency.

Summary Background & aims Whilst the cardioprotective effects of blueberry intake have been shown in prospective studies and short-term randomized controlled trials (RCTs), it is unknown whether anthocyanin-rich blueberries can attenuate the postprandial, cardiometabolic dysfunction which follows energy-dense food intakes; especially in at-risk populations. We therefore examined whether adding blueberries to a high-fat/high-sugar meal affected the postprandial cardiometabolic response over 24 h. Methods A parallel, double-blind RCT (n = 45; age 63.4 ± 7.4 years; 64% male; BMI 31.4 ± 3.1 kg/m2) was conducted in participants with metabolic syndrome. After baseline assessments, an energy-dense drink (969 Kcals, 64.5 g fat, 84.5 g carbohydrate, 17.9 g protein) was consumed with either 26 g (freeze-dried) blueberries (equivalent to 1 cup/150 g fresh blueberries) or 26 g isocaloric matched placebo. Repeat blood samples (30, 60, 90, 120, 180, 360 min and 24 h), a 24 h urine collection and vascular measures (at 3, 6, and 24 h) were performed. Insulin and glucose, lipoprotein levels, endothelial function (flow mediated dilatation (FMD)), aortic and systemic arterial stiffness (pulse wave velocity (PWV), Augmentation Index (AIx) respectively), blood pressure (BP), and anthocyanin metabolism (serum and 24 h urine) were assessed. Results Blueberries favorably affected postprandial (0–24 h) concentrations of glucose (p

OBJECTIVE: To evaluate the validity and reproducibility of a 152-item SFFQ for estimating flavonoid intakes. DESIGN: Over a one-year period, participants completed two SFFQs and two weighed 7-day dietary records (7DDR). Flavonoid intakes from the SFFQ were estimated separately using Harvard (SFFQ(Harvard)) and Phenol-Explorer (SFFQ(PE)) food composition databases. 7DDRs flavonoid intakes were derived using the Phenol-Explorer database (7DDR(PE)). Validity was assessed using Spearman rank correlation coefficients deattenuated for random measurement error(r(s)) and reproducibility was assessed using rank intraclass correlation coefficients. SETTING: This validation study included primarily participants from two large observational cohort studies. PARTICIPANTS: 641 men and 724 women RESULTS: When compared to two 7DDR(PE), the validity of total flavonoid intake assessed by SFFQ(PE) was high for both men and women (r(s)=0.77 and r(s)=0.74, respectively). The r(s) for flavonoid subclasses ranged from 0.47 for flavones to 0.78 for anthocyanins in men, and from 0.46 for flavonols to 0.77 for anthocyanins in women. We observed similarly moderate (0.4 - 0.7) to high (⩾ 0.7) validity when using SFFQ(Harvard) estimates, except for flavones(Harvard) (r(s)=0.25 for men and r(s)=0.19 for women). The SFFQ demonstrated high reproducibility for total flavonoid and flavonoid subclass intake estimates when using either food composition database. The intraclass correlation coefficients ranged from 0.69 (flavonols(PE)) to 0.80 (proanthocyanidins(PE)) in men and from 0.67 (flavonols(PE)) to 0.77 (flavan-3-ol monomers(Harvard)) in women. CONCLUSIONS: SFFQ-derived intakes of total flavonoids and flavonoid subclasses (except for flavones) are valid and reproducible for both men and women.

Background: The role of nutrition in the primary prevention of peripheral artery disease (PAD), the third leading cause of atherosclerotic cardiovascular disease, is undetermined. Flavonoids may attenuate atherosclerosis and therefore persons who consume flavonoid-rich foods may have a lower risk of developing PAD.Objectives: We aimed to examine the association between flavonoid intake and PAD hospitalizations and investigate if the association differs according to established risk factors for PAD.Methods: Baseline data from 55,647 participants of the Danish Diet, Cancer, and Health Study without PAD, recruited from 1993 to 1997, were cross-linked with Danish nationwide registries. Flavonoid intake was calculated from FFQs using the PhenolExplorer database. Associations were examined using multivariableadjusted restricted cubic splines based on Cox proportional hazards models.Results: After a median [IQR] follow-up time of 21 [20-22] y, 2131 participants had been hospitalized for any PAD. The association between total flavonoid intake and total PAD hospitalizations was nonlinear, reaching a plateau at similar to 750-1000 mg/d. Compared with the median flavonoid intake in quintile 1 (174 mg/d), an intake of 1000 mg/d was associated with a 32% lower risk of any PAD hospitalization (HR: 0.68; 95% CI: 0.60, 0.77), a 26% lower risk of atherosclerosis (HR: 0.74; 95% CI: 0.62, 0.88), a 28% lower risk of an aneurysm (HR: 0.72; 95% CI: 0.59, 0.88), and a 47% lower risk of a hospitalization for other peripheral vascular disease (HR: 0.53; 95% CI: 0.42, 0.67). A higher total flavonoid intake was also significantly associated with a lower incidence of revascularization or endovascular surgery and lower extremity amputation. The association between total flavonoid intake and PAD hospitalizations differed according to baseline smoking status, alcohol intake, BMI, and diabetes status.Conclusions: Ensuring the adequate consumption of flavonoid-rich foods, particularly in subpopulations prone to the development of atherosclerosis, may be a key strategy to lower the risk of PAD.

Introduction: Prospective studies investigating flavonoid intake and dementia risk are scarce. The aims of this study were to examine associations between flavonoid intake and the risk of incident dementia and to investigate whether this association differs in the presence of lifestyle risk factors for dementia.Methods: We examined associations in 55,985 participants of the Danish Diet, Cancer, and Health Study followed for 23 years. The Phenol-Explorer database was used to estimate flavonoid intakes. Information on incident dementia and dementia subtypes was obtained using Danish patient and prescription registries. Hazard ratios (HRs) were calculated using restricted cubic splines in multivariable-adjusted Cox proportional hazards models.Results: For incident dementia, moderate compared to low intakes of flavonols (HR: 0.90 [0.82, 0.99]), flavanol oligo+polymers (HR: 0.87 [0.79, 0.96]), anthocyanins (HR: 0.84 [0.76, 0.93]), flavanones (HR: 0.89 [0.80, 0.99]), and flavones (HR: 0.85 [0.77, 0.95]) were associated with a lower risk. For vascular dementia, moderate intakes of flavonols (HR: 0.69 [0.53, 0.89]) and flavanol oligo + polymers (HR: 0.65 [0.51, 0.83]) were associated with lower risk. Flavonoid intakes were not significantly associated with Alzheimer's disease or unspecified dementia. The inverse association between total flavonoid intake and incident dementia was stronger in "ever" smokers than in "never" smokers and in those without hypercholesterolemia versus those with hypercholesteremia. Furthermore, the inverse association of vascular dementia with a moderate total flavonoid intake was stronger in "ever" smokers and those who were "normal" to "overweight" versus "never" smokers or those who were "obese," respectively.Conclusion: A moderate intake of flavonoid-rich foods may help to reduce dementia risk.

Made available in DSpace on 2021-06-25T11:45:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-12-01 National Institutes of Health National Health and Medical Research Council fellowship National Heart, Lung and Blood Institute Objective: To evaluate the validity and reproducibility of a 152-item semi-quantitative FFQ (SFFQ) for estimating flavonoid intakes. Design: Over a 1-year period, participants completed two SFFQ and two weighed 7-d dietary records (7DDR). Flavonoid intakes from the SFFQ were estimated separately using Harvard (SFFQ(Harvard)) and Phenol-Explorer (SFFQ(PE)) food composition databases. 7DDR flavonoid intakes were derived using the Phenol-Explorer database (7DDR(PE)). Validity was assessed using Spearman's rank correlation coefficients deattenuated for random measurement error (r ( s )), and reproducibility was assessed using rank intraclass correlation coefficients. Setting: This validation study included primarily participants from two large observational cohort studies. Participants: Six hundred forty-one men and 724 women. Results: When compared with two 7DDR(PE), the validity of total flavonoid intake assessed by SFFQ(PE) was high for both men and women (r ( s ) = 0 center dot 77 and r ( s ) = 0 center dot 74, respectively). The r ( s ) for flavonoid subclasses ranged from 0 center dot 47 for flavones to 0 center dot 78 for anthocyanins in men and from 0 center dot 46 for flavonols to 0 center dot 77 for anthocyanins in women. We observed similarly moderate (0 center dot 4-0 center dot 7) to high (>= 0 center dot 7) validity when using SFFQ(Harvard) estimates, except for flavones(Harvard) (r ( s ) = 0 center dot 25 for men and r ( s ) = 0 center dot 19 for women). The SFFQ demonstrated high reproducibility for total flavonoid and flavonoid subclass intake estimates when using either food composition database. The intraclass correlation coefficients ranged from 0 center dot 69 (flavonols(PE)) to 0 center dot 80 (proanthocyanidins(PE)) in men and from 0 center dot 67 (flavonols(PE)) to 0 center dot 77 (flavan-3-ol monomers(Harvard)) in women. Conclusions: SFFQ-derived intakes of total flavonoids and flavonoid subclasses (except for flavones) are valid and reproducible for both men and women. Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA Harvard Med Sch, Dept Populat Med, Boston, MA 02115 USA Harvard Pilgrim Hlth Care Inst, Boston, MA USA Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA Harvard Med Sch, Boston, MA 02115 USA Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA Univ Estado Sao Paulo Julio Mesquita Filho, Botucatu, SP, Brazil Queens Univ Belfast, Inst Global Food Secur, Belfast, Antrim, North Ireland South Australian Hlth & Med Res Inst, Infect & Immun Theme, Adelaide, SA, Australia Flinders Univ S Australia, Coll Nursing & Hlth Sci, Dept Nutr & Dietet, Adelaide, SA, Australia Univ Estado Sao Paulo Julio Mesquita Filho, Botucatu, SP, Brazil National Institutes of Health: UM1 CA186107 National Institutes of Health: UM1 CA176726 National Institutes of Health: P01 CA055075-18S1 National Institutes of Health: U01CA152904 National Institutes of Health: U01CA167552 National Heart, Lung and Blood Institute: T32HL098048

Background & Aims: Primary prevention of atrial fibrillation (AF) through behavioural and dietary modification is a critically important and unmet need. Flavonoids are bioactive dietary compounds with promising cardiovascular health benefits. Our aim was to investigate the association between flavonoid intake and clinically apparent AF. Methods: Baseline data from 55 613 participants of the Danish Diet, Cancer and Health Study, without AF, recruited between 1993 and 1997, were cross-linked with Danish nationwide registries. Total flavonoid and flavonoid subclass intakes were calculated from validated food frequency questionnaires using the Phenol-Explorer database. Associations between flavonoid intake and incident AF (first-time hospitalization or outpatient visit) were examined using restricted cubic splines based on Cox proportional hazards models. Results: During a median [IQR] follow-up of 21 [18 – 22] years, 7291 participants were diagnosed with AF. Total flavonoid intake was not statistically significantly associated with risk of incident AF in the whole cohort. However, compared to the lowest quintile, a total flavonoid intake of 1000 mg/day was associated with a lower risk of AF in smokers [0.86 (0.77, 0.96)] but not in non-smokers [0.96 (0.88, 1.06)], and a lower risk of AF in high alcohol consumers [>20 g/d: 0.84 (0.75, 0.95)] but not in low-to-moderate alcohol consumers [

There is an accumulating body of literature reporting on dietary flavonoid intake and the risk of cardiovascular disease (CVD) in prospective cohort studies. This makes apparent the need for an overview and update on the current state of the science. To date, at least 27 prospective cohorts (in 44 publications) have evaluated the association between estimated habitual flavonoid intake and CVD risk. At this time, the totality of evidence suggests long-term consumption of flavonoid-rich foods may be associated with a lower risk of fatal and non-fatal ischemic heart disease (IHD), cerebrovascular disease, and total CVD; disease outcomes which are principally, though not exclusively, composed of cases of atherosclerotic CVD (ASCVD). To date, few studies have investigated outcome specific ASCVD, such as peripheral artery disease (PAD) or ischemic stroke. Of the flavonoid subclasses investigated, evidence more often implicates diets rich in anthocyanins, flavan-3-ols, and flavonols in lowering the risk of CVD. Although inferences are restricted by confounding and other inherent limitations of observational studies, causality appears possible based on biological plausibility, temporality, and the relative consistency of the reported associations. However, whether the associations observed represent a benefit of the isolated bioactives per se, or are a signal of the bioactives acting in concert with the co-occurring nutrient matrix within flavonoid-bearing foods, are issues of consideration. Thus, the simple interpretation, and the one most relevant for dietary advice, is that consumption of flavonoid-rich foods or diets higher in flavonoids, appear nutritionally beneficial in the prevention of CVD.

ObjectiveAgeing is accompanied by deterioration of multiple bodily functions and inflammation, which collectively contribute to frailty. We and others have shown that frailty co-varies with alterations in the gut microbiota in a manner accelerated by consumption of a restricted diversity diet. The Mediterranean diet (MedDiet) is associated with health. In the NU-AGE project, we investigated if a 1-year MedDiet intervention could alter the gut microbiota and reduce frailty.DesignWe profiled the gut microbiota in 612 non-frail or pre-frail subjects across five European countries (UK, France, Netherlands, Italy and Poland) before and after the administration of a 12-month long MedDiet intervention tailored to elderly subjects (NU-AGE diet).ResultsAdherence to the diet was associated with specific microbiome alterations. Taxa enriched by adherence to the diet were positively associated with several markers of lower frailty and improved cognitive function, and negatively associated with inflammatory markers including C-reactive protein and interleukin-17. Analysis of the inferred microbial metabolite profiles indicated that the diet-modulated microbiome change was associated with an increase in short/branch chained fatty acid production and lower production of secondary bile acids, p-cresols, ethanol and carbon dioxide. Microbiome ecosystem network analysis showed that the bacterial taxa that responded positively to the MedDiet intervention occupy keystone interaction positions, whereas frailty-associated taxa are peripheral in the networks.ConclusionCollectively, our findings support the feasibility of improving the habitual diet to modulate the gut microbiota which in turn has the potential to promote healthier ageing.

International audience; There is a lack of focus on the protective health effects of phytochemicals in dietary guidelines. Although a number of chemical libraries and databases contain dietary phytochemicals belonging to the plant metabolome, they are not entirely relevant to human health because many constituents are extensively metabolized within the body following ingestion. This is especially apparent for the highly abundant dietary (poly)phenols, for which the situation is compounded by confusion regarding their bioavailability and metabolism, partially because of the variety of nomenclatures and trivial names used to describe compounds arising from microbial catabolism in the gastrointestinal tract. This confusion, which is perpetuated in online chemical/metabolite databases, will hinder future discovery of bioactivities and affect the establishment of future dietary guidelines if steps are not taken to overcome these issues. In order to resolve this situation, a nomenclature system for phenolic catabolites and their human phase II metabolites is proposed in this article and the basis of its format outlined. Previous names used in the literature are cited along with the recommended nomenclature, International Union of Pure and Applied Chemistry terminology, and, where appropriate, Chemical Abstracts Service numbers, InChIKey, and accurate mass

BackgroundA recent systematic review of epidemiological evidence suggests that higher amounts of tea intake are associated with lower risks of cardiovascular disease (CVD) incidence and mortality.ObjectivesOur study objective was to assess mechanisms by which tea consumption may influence CVD risks.MethodsA systematic review and meta-analysis was conducted to investigate the effects of green and/or black tea consumption (≥4 wk) on systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride (TG) in healthy populations and among at-risk adults (analyzed separately) with metabolic syndrome, prediabetes, and hypercholesterolemia. The Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the strength of evidence (SoE).ResultsA total of 14 unique RCTs which randomly assigned 798 participants to either green tea, black tea, or placebo controls were included in our analyses. Intervention durations ranged from 4 to 24 wk (mean: 7.4 wk). Individual studies were judged as moderate to high quality based on risk of bias assessments. SoE was low to moderate owing to low sample sizes and insufficient power for most included studies to observe changes in the measured CVD biomarkers. Meta-analyses showed no significant effects of tea consumption on SBP, DBP, total cholesterol, LDL cholesterol, HDL cholesterol, and TG in healthy and at-risk adults (i.e., adults with obesity, prediabetes, borderline hypercholesterolemia, and metabolic syndrome).ConclusionsShort-term (4–24 wk) tea consumption does not appear to significantly affect blood pressure or lipids in healthy or at-risk adults, although the evidence is limited by insufficient power to detect changes in these CVD biomarkers. High-quality RCTs with longer durations and sufficient sample sizes are needed to fully elucidate the effects of tea. This systematic review was registered at www.crd.york.ac.uk/prospero/ as CRD42020134513.

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.

There is increasing evidence that both black and green tea are beneficial for prevention of cardiovascular disease (CVD). We conducted a systematic review and meta-analysis evaluating the effects of tea flavonoids on cardiovascular (CVD) and all-cause mortality outcomes.Searches across five databases including PubMed and Embase were conducted through November 2018 to identify randomized controlled trials (RCTs) and prospective cohort studies reporting cardiovascular and all-cause mortality outcomes. Two investigators independently conducted abstract and full-text screenings, data extractions, and risk of bias (ROB) assessments using the Nutrition Evidence Library Bias Assessment Tool (NEL BAT). Mixed-effects dose-response meta-regression and standard random-effects meta-analyses for outcomes with ≥ 4 studies were performed. 0 RCTs and 38 prospective cohort studies were included in the systematic review. NEL BAT scores ranged from 0–15 (0 being the lowest risk). Our linear meta-regression model showed that each cup increase in daily tea consumption (about 280 mg and 338 mg of total flavonoids for black and green tea, respectively) was associated with 3–4% lower risk of CVD mortality (predicted adjusted RR = 0.96; CI 0.93–0.99 for green tea and RR = 0.97; CI 0.94–0.99 for black tea). Furthermore, eachcup increase in daily tea consumption was associated a 2% lower risk of all-cause mortality (predicted adjusted relative risk (RR) = 0.98; 95% CI 0.97–0.99 for black tea and RR = 0.98; CI 0.96–0.99 for green tea, respectively). Two studies reported multivariable Cox regression analysis results for the relationship between black tea intake and risks of all-cause mortality outcomes. The results from these two studies were combined with our linear meta-regression result in a random-effects model meta-analysis and showed that each cup increase in daily black tea consumption was associated with an average of 3% lower risk of all-cause mortality (pooled adjusted RR = 0.97; 95% CI 0.87- 1.00) with large heterogeneity (I2 = 81.4%; p = 0.005). Current evidence indicates that increased tea consumption may reduce cardiovascular and all-cause mortality in a dose-response manner. This systematic review was registered on PROSPERO.

While growing evidence exists on the independent associations between anthocyanins and physical activity on cardiovascular disease (CVD) risk determinants, the possible interaction between these exposures has not yet been studied. We aimed to study the potential synergism between anthocyanin intake and physical activity on lipid profile measures. This cross-sectional study was conducted among 249 US career firefighters participating in the Feeding America&rsquo, s Bravest trial. Anthocyanin intake was calculated using a validated food frequency questionnaire (FFQ) and physical activity level by a validated questionnaire. Multivariable linear regression models determined the extent to which anthocyanin intake and physical activity predicted lipid parameters. Generalized linear models were used for joint effect and interaction analyses on the multiplicative and additive scales. Both anthocyanins and physical activity were independently inversely associated with total cholesterol:high density lipoprotein (HDL) cholesterol. Only physical activity was inversely associated with triglycerides, low density lipoprotein (LDL) cholesterol:HDL, and triglycerides (TG):HDL. Although the combined exposure of low anthocyanin intake and low physical activity was associated with lower (RR = 2.83, 95% CI: 1.42 to 5.67) HDL cholesterol &lt, 40 mg/dL, neither multiplicative (p = 0.72) nor additive interactions were detected (relative excess risk due to interaction (RERI): 0.02, 95% CI: &minus, 1.63 to 1.66, p = 0.98). Our findings provide insight on the potential synergism between anthocyanin intake and physical activity on the lipid profile.

Flavonoids are bioactive compounds found in foods such as tea, red wine, fruits and vegetables. Higher intakes of specific flavonoids, and flavonoid-rich foods, have been linked to reduced mortality from specific vascular diseases and cancers. However, the importance of flavonoid-rich foods, and flavonoids, in preventing all-cause mortality remains uncertain. As such, we examined the association of intake of flavonoid-rich foods and flavonoids with subsequent mortality among 93 145 young and middle-aged women in the Nurses’ Health Study II. During 1 838 946 person-years of follow-up, 1808 participants died. When compared with non-consumers, frequent consumers of red wine, tea, peppers, blueberries and strawberries were at reduced risk of all-cause mortality (PP

At a population level, there is growing evidence of the beneficial effects of dietary flavonoids on health. However, there is extensive heterogeneity in the response to increased intake, which is likely mediated via wide interindividual variability in flavonoid absorption and metabolism. Flavonoids are extensively metabolized by phase I and phase II metabolism (which occur predominantly in the gastrointestinal tract and liver) and colonic microbial metabolism. A number of factors, including age, sex, and genotype, may affect these metabolic processes. In addition, food composition and flavonoid source are likely to affect bioavailability, and emerging data suggest a critical role for the microbiome. This review will focus on the current knowledge for the main subclasses of flavonoids, including anthocyanins, flavonols, flavan-3-ols, and flavanones, for which there is growing evidence from prospective studies of beneficial effects on health. The identification of key factors that govern metabolism and an understanding of how the differential capacity to metabolize these bioactive compounds affect health outcomes will help establish how to optimize intakes of flavonoids for health benefits and in specific subgroups. We identify research areas that need to be addressed to further understand important determinants of flavonoid bioavailability and metabolism and to advance the knowledge base that is required to move toward the development of dietary guidelines and recommendations for flavonoids and flavonoid-rich foods.

Background Findings from existing prospective observational studies on the protective associations of flavonoid intake and the risk of Alzheimer disease and related dementias (ADRD) are inconsistent largely due to limitations of these studies. Objectives To examine the prospective relation between total and 6 classes of dietary flavonoid intake and risk of ADRD and Alzheimer disease (AD) while addressing limitations of earlier observational studies. Methods We used data from the Framingham Heart Study Offspring Cohort exams 5 through 9. Participants were ADRD-free with a valid FFQ at baseline. Flavonoid intakes were updated at each exam to represent the cumulative average intake across the 5 exams, and were expressed as percentile categories of intake (≤15th, >15th to 30th, >30th to 60th, >60th) to handle their nonlinear relation with ADRD and AD. Cox proportional hazards regression was used to estimate the HRs for the association between the flavonoid intakes and incidence of ADRD and AD. Results Over an average follow-up of 19.7 y in 2801 participants (mean baseline age = 59.1 y; 52% females), there were 193 ADRD events of which 158 were AD. After multivariate and dietary adjustments, individuals with the highest (>60th percentile) intakes of flavonols, anthocyanins, and flavonoid polymers had a lower risk of ADRD relative to individuals with the lowest intakes (≤15th percentile), with HRs (95% CI; P-trend) of 0.54 (0.32, 0.90; P = 0.003) for flavonols, 0.24 (0.15, 0.39; P, As the older population continues to grow in the US so does the burden imposed on the health care system due to the rise in the prevalence of Alzheimer's disease and related dementias (ADRD), representing one of the greatest challenges facing the public health. To date, there are no effective treatments for ADRD and thus identifying dietary strategies that would help prevent or mitigate ADRD is of great priority. Evidence on the role of flavonoids, natural pigments found in a wide range of plant-based foods, in ADRD risk is inconsistent due to the many limitations associated with the current studies. Accordingly, this study aimed to more accurately explore the relationship between total and the six classes of flavonoids and risk of ADRD while taking into account the limitations of previous studies. We found that individuals with higher intakes of the three flavonoid classes: flavonols, anthocyanins, and flavonoid polymers had a lower risk of ADRD compared to those with lower intakes. Our results add to the limited evidence that flavonoids could have the potential to reduce the risk of ADRD.

Background Flavonoid intake modifies the composition of the gut microbiome, which contributes to the metabolism of flavonoids. Few studies have examined the contribution of the gut microbiome to the health benefits associated with flavonoid intake. Objectives We aimed to examine associations between habitual intakes of flavonoid subclasses and MRI-determined visceral (VAT) and subcutaneous (SAT) adipose tissue. Uniquely, we also identified associations between the aforementioned measurements and gut microbiome composition sequenced from 16S ribosomal RNA genes. Methods We undertook cross-sectional analyses of 618 men and women (n = 368 male), aged 25–83 y, from the PopGen cohort. Results Higher intake of anthocyanins was associated with lower amounts of VAT [tertile (T)3-T1: −0.49 dm3; β: −8.9%; 95% CI: −16.2%, −1.1%; P = 0.03] and VAT:SAT ratio (T3-T1: −0.04; β: −7.1%; 95% CI: −13.5%, −0.3%; P = 0.03). Higher intakes of anthocyanin-rich foods were also inversely associated with VAT [quantile (Q)4-Q1: −0.39 dm3; β: −9.9%; 95% CI: −17.4%, −1.6%; P = 0.02] and VAT:SAT ratio (Q4-Q1: −0.04; β: −6.5%; 95% CI: −13.3%, −0.9%; P = 0.03). Participants with the highest intakes of anthocyanin-rich foods also had higher microbial diversity (Q4-Q1: β: 0.18; 95% CI: 0.06, 0.31; P

BACKGROUND: Flavonoids, compounds found in plant-based foods and beverages, might ameliorate vascular damage and atherosclerosis. Therefore, our aim was to assess the association between flavonoid intake and hospital admissions due to atherosclerotic cardiovascular disease.METHODS: In this prospective cohort study, participants from the Danish Diet, Cancer, and Health Study were cross-linked with Danish nationwide registries. Eligible participants were aged 50-65 years, had no previous history of atherosclerotic cardiovascular disease, and had completed a food-frequency questionnaire at baseline. We examined associations between flavonoid intake (calculated from food-frequency questionnaires with use of the Phenol-Explorer database) and hospital admissions for atherosclerotic cardiovascular disease, ischaemic heart disease, ischaemic stroke, or peripheral arterial disease. We obtained hazard ratios (HRs) using restricted cubic splines based on Cox proportional hazards models.FINDINGS: Of the participants recruited to the Danish Diet, Cancer, and Health study between 1993 and 1997, our study population was comprised of 53 552 participants, with a median follow-up of 21 years (IQR 15-22). During follow-up, 8773 participants were admitted to hospital for atherosclerotic cardiovascular disease. We observed non-linear associations between flavonoid intake and hospital admissions, plateauing at total flavonoid intakes of approximately 1000 mg per day. Compared with an intake of 175 mg per day, an intake of 1000 mg per day was associated with a 14% lower risk of atherosclerotic cardiovascular disease (HR 0·86, 95% CI 0·81-0·91). For disease subtypes, we observed a 9% lower risk of ischaemic heart disease (0·91, 0·85-0·98), a non-significant 9% lower risk of ischaemic stroke (0·91, 0·82-1·01), and a 32% lower risk of peripheral artery disease (0·68, 0·60-0·78). The overall associations were stronger in smokers than in non-smokers, as well as stronger in consumers of high (>20 g per day) quantities of alcohol than in those consuming low-to-moderate (≤20 g per day) quantities.INTERPRETATION: Our results suggest that ensuring an adequate consumption of flavonoid-rich foods, particularly in subpopulations at risk of atherosclerosis such as smokers and consumers of high quantities of alcohol might mitigate some of the risk of atherosclerotic cardiovascular disease. More studies are needed to support and validate these data.FUNDING: Danish Cancer Society.

Diets rich in berries provide health benefits, however, the contribution of berry phytochemicals to the human metabolome is largely unknown. The present study aimed to establish the impact of berry phytochemicals on the human metabolome. A &ldquo, systematic review strategy&rdquo, was utilized to characterize the phytochemical composition of the berries most commonly consumed in the USA, (poly)phenols, primarily anthocyanins, comprised the majority of reported plant secondary metabolites. A reference standard library and tandem mass spectrometry (MS/MS) quantitative metabolomics methodology were developed and applied to serum/plasma samples from a blueberry and a strawberry intervention, revealing a diversity of benzoic, cinnamic, phenylacetic, 3-(phenyl)propanoic and hippuric acids, and benzyldehydes. 3-Phenylpropanoic, 2-hydroxybenzoic, and hippuric acid were highly abundant (mean &gt, 1 &micro, M). Few metabolites at concentrations above 100 nM changed significantly in either intervention. Significant intervention effects (P &lt, 0.05) were observed for plasma/serum 2-hydroxybenzoic acid and hippuric acid in the blueberry intervention, and for 3-methoxyphenylacetic acid and 4-hydroxyphenylacetic acid in the strawberry intervention. However, significant within-group effects for change from baseline were prevalent, suggesting that high inter-individual variability precluded significant treatment effects. Berry consumption in general appears to cause a fluctuation in the pools of small molecule metabolites already present at baseline, rather than the appearance of unique berry-derived metabolites, which likely reflects the ubiquitous nature of (poly)phenols in the background diet.

Background Our understanding of how diet affects future risk of atrial fibrillation (AF) is limited. Evidence suggests that higher habitual intakes of flavonoids, bio-active compounds found in plant-based foods and beverages, lower cardiovascular disease risk, attenuate inflammation, and may have anti-arrhythmic properties. Purpose To investigate the association between flavonoid intake and clinically apparent AF in a large cohort of Danish men and women. Methods Baseline data from 55 634 participants without AF of the Danish Diet, Cancer and Health Study, recruited from 1993 to 1997, were cross-linked with Danish nationwide registries. Flavonoid intake was calculated from validated food frequency questionnaires using the Phenol-Explorer database. Associations between flavonoid intake and AF hospitalisation were examined using restricted cubic splines based on Cox proportional hazards models with adjustments for age, sex, BMI, smoking status, physical activity, alcohol intake, income, and hyperthyroidism. Results After a median [IQR] follow-up of 21 [18–22] years, 6 301 participants were hospitalised with AF. Non-linear associations were observed for total flavonoid intake and for all flavonoid sub-classes. For total flavonoid intake, after adjusting for potential lifestyle confounders and compared to participants in quintile 1 (median intake: 173 mg/day), those in quintile 3 (median intake: 320 mg/day) and quintile 4 (median intake: 494 mg/day) had a significantly lower risk of AF, with hazard ratios (95% CI) of 0.93 (0.87, 0.99) and 0.92 (0.86, 0.98), respectively. Compared to median intake in the lowest quintile, a total flavonoid intake of 1000 mg/day was associated with a lower risk of AF in smokers [0.86 (0.77, 0.96)] but not in non-smokers [0.96 (0.88, 1.05)], a lower risk of AF in high alcohol consumers [>20 g/d: 0.84 (0.75, 0.94)] but not in low-to-moderate alcohol consumers [ Figure 1 Conclusion We observed an inverse association between total flavonoid intake and AF, most notably in sub-populations with known lifestyle and disease risk factors for AF. This finding warrants investigation in randomised controlled trials. If confirmed, ensuring the adequate consumption of flavonoid-rich foods, particularly in individuals “at risk”, may be an important strategy to mitigate AF risk. Acknowledgement/Funding The Danish Diet, Cancer, and Health Study was funded by the Danish Cancer Society.

Dietary flavonoids, which have been implicated in lowering chronic disease risk and improving blood pressure, represent a diverse group of polyphenolic compounds found in many commonly consumed foods such as tea, red wine, apples, and berries. The bioactivity and bioavailability of more dietary flavonoids can be influenced by gastrointestinal microbiome metabolism. With demonstrated prebiotic and antimicrobial effects in in vitro and in animal models, it is surprising that there are not many human studies investigating the role dietary flavonoids play in shaping the gastrointestinal microbiome. Our analysis revealed patterns of community assembly that uniquely and independently characterize an individual’s exposure to various flavonoid compounds. Furthermore, this study confirmed, independent from effects of other dietary and lifestyle factors included in the multivariate-adjusted model, that flavonoid intake is associated with microbial community assembly., Flavonoids are a group of polyphenolic dietary compounds found in many different plant-based foods. There is increasing evidence that higher flavonoid intake may be causally linked to a reduced risk of cardiovascular disease and other chronic diseases. The bioactivity and bioavailability of many dietary flavonoids can be influenced by gastrointestinal microbiome metabolism. However, the role that habitual flavonoid intake plays in shaping the human gut microbiome is poorly understood. We describe an application of an ecosystem-based analytic approach to nutritional, microbiome, and questionnaire data from a cohort of more than 240 generally healthy adult males to assess the role of dietary flavonoid compounds in driving patterns of microbial community assembly. We identified six subclass-specific microbial communities (SMCs) uniquely and independently associated with intakes of the six flavonoid subclasses. Eggerthela lenta was positively associated with intakes of flavonol and flavanone, and Adlercreutzia equolifaciens was positively associated with intakes of flavonols and flavanol monomers. In contrast, for nearly all flavonoid subclasses, Flavonifractor plautii was inversely associated with subclass consumption. Consuming tea at least once per week explained 10.4% of the total variance in assembly of the 20 species comprising the flavanol monomer SMC. The novel methodology employed, necessitated by multidimensional microbiome data that consist of nonindependent features that exhibit a wide range of distributions and mean values, addresses a major challenge in our ability to understand associations of the microbiome in a wide range of clinical and epidemiologic settings.