Flavonoid-rich Foods Research Articles

SU87PCSK9 GENETIC VARIANTS, LIFE-LONG LOWERING OF LOW-DENSITY LIPOPROTEIN CHOLESTEROL, AND COGNITIVE ABILITIES

Limited information exists on the impact of flavonoid intake on nonalcoholic fatty liver disease (NAFLD). We evaluated the link between flavonoid intake, liver tests and risk of NAFLD in a randomly selected sample of US adults (from the National Health and Nutrition Examination Survey, NHANES, 2005–2010). Of the 17,685 participants, 46.9% were men and 45.4% had NAFLD. NAFLD patients had a significantly lower mean flavonoid intake than healthy individuals (111.3±3.6 vs. 201.3±2.3 mg/d, respectively; P<.001). Fatty liver index (FLI) and serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly higher in the first tertile (T1) of flavonoid intake compared with the highest tertile (T3: with the highest flavonoid intake) (FLI: 67.1 vs. 36.2, AST: 31.2 VS 26.8 U/L and, ALT: 34.2 vs. 24.2 U/L, respectively; P<.001 for all comparisons). Adjusted linear regression displayed significant and negative associations between FLI, AST, ALT and flavonoid intake (P<.001 for all comparisons). Multivariable logistic regression showed that the risk for NAFLD significantly decreased as flavonoid intake tertiles increased in a stepwise manner (odds ratio: 0.81, 95% confidence interval: 0.78–0.86). Moderation analysis revealed that C-reactive protein (CRP) strongly modulated the impact of flavonoid intake on FLI; participants with higher CRP levels benefited less from flavonoid intake compared with those with lower CRP concentrations. In conclusions, our results suggest a reverse significant association between flavonoid consumption, liver tests and the risk for NAFLD. Furthermore, CRP was shown to essentially moderate this relationship. These findings support recommendations for consumption of flavonoid-rich foods to prevent cardiometabolic diseases.

P10 - The Role of the Vascular System in Flavonoid-Induced Cognitive Enhancement

Evidence suggests that dietary phytochemicals, in particular flavonoids, may exert beneficial effects on the central nervous system by protecting neurons against stress-induced injury, by suppressing neuroinflammation and by improving cognitive function. Historically, they were believed to do this via an ability to express classical antioxidant activity in the brain. However, their poor brain bioavailability and extensive metabolism means that this is unlikely. Instead, their actions on the brain appear to be mediated by effects on both the peripheral and cerebro-vascular system that lead to improved blood flow to the brain capable of inducing enhanced activity within specific domains of cognitive function. Such vascular effects may also lead to the activation of critical protein and lipid kinase signalling cascades in the brain, leading to a suppression of neuroinflammation and the promotion of synaptic plasticity. This talk will focus on the acute and chronic effects of flavonoid and flavonoid-rich food intake on human executive function (attention, sustained attentiveness and task responsiveness) and episodic memory and how such effects may be mediated by changes in peripheral and cerebrovascular blood flow, measured using flow-mediated dilatation and fMRI. Through such a mechanism, the consumption of flavonoid-rich foods throughout life holds the potential to limit neurodegeneration and to prevent or reverse age-dependent loses in cognitive performance. In addition, flavonoids may represent important precursor molecules in the quest to develop a new generation of brain enhancing drugs.

Structurally Different Flavonoid Subclasses Attenuate High-Fat and High-Fructose Diet Induced Metabolic Syndrome in Rats.

Metabolic syndrome is a serious health problem worldwide. Increasing evidence indicates that flavonoid-rich foods exert beneficial effects. However, the function of flavonoids in metabolic syndrome is controversial. Here, we focus on the structural effects of flavonoids by comparing the effect of five purified subclasses of flavonoids on high-fat and high-fructose diet (HFFD) induced metabolic syndrome in vivo. Sprague-Dawley (SD) rats were fed with (i) basal diet (3.21 kcal/g) (ii) HFFD (25% lard and 25% fructose, 4.70 kcal/g), and (iii) HFFD with flavonoids representing different subclasses (2.6 mmol/kg diet): apigenin (flavones), quercetin (flavonols), genistein (isoflavones), naringenin (flavanones), and epigallocatechin gallate (flavanols) for 13 weeks. Our results showed that structurally different flavonoid subclasses prevented the HFFD-induced metabolic syndrome. Apigenin significantly decreased adipose fat and leptin levels and increased adiponectin levels. Epigallocatechin gallate and naringenin were both effective on dyslipidemia and hepatic lipid accumulations. The proinflammatory cytokines TNF-α and IL-6 were alleviated by quercetin, genistein, and naringenin. All the flavonoids exerted significant functions on improving insulin resistance and fasting glucose. In conclusion, flavonoid subclasses structurally exert antihyperlipidemic, antidiabetic, and anti-inflammatory functions by attenuating the lipid metabolism, glucose metabolism, and inflammation of metabolic syndrome.

A higher flavonoid intake is associated with less likelihood of nonalcoholic fatty liver disease: results from a multiethnic study

Limited information exists on the impact of flavonoid intake on nonalcoholic fatty liver disease (NAFLD). We evaluated the link between flavonoid intake, liver tests and risk of NAFLD in a randomly selected sample of US adults (from the National Health and Nutrition Examination Survey, NHANES, 2005–2010). Of the 17,685 participants, 46.9% were men and 45.4% had NAFLD. NAFLD patients had a significantly lower mean flavonoid intake than healthy individuals (111.3±3.6 vs. 201.3±2.3 mg/d, respectively; P<.001). Fatty liver index (FLI) and serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly higher in the first tertile (T1) of flavonoid intake compared with the highest tertile (T3: with the highest flavonoid intake) (FLI: 67.1 vs. 36.2, AST: 31.2 VS 26.8 U/L and, ALT: 34.2 vs. 24.2 U/L, respectively; P<.001 for all comparisons). Adjusted linear regression displayed significant and negative associations between FLI, AST, ALT and flavonoid intake (P<.001 for all comparisons). Multivariable logistic regression showed that the risk for NAFLD significantly decreased as flavonoid intake tertiles increased in a stepwise manner (odds ratio: 0.81, 95% confidence interval: 0.78–0.86). Moderation analysis revealed that C-reactive protein (CRP) strongly modulated the impact of flavonoid intake on FLI; participants with higher CRP levels benefited less from flavonoid intake compared with those with lower CRP concentrations. In conclusions, our results suggest a reverse significant association between flavonoid consumption, liver tests and the risk for NAFLD. Furthermore, CRP was shown to essentially moderate this relationship. These findings support recommendations for consumption of flavonoid-rich foods to prevent cardiometabolic diseases.

Nutritional approach to preeclampsia prevention.

Although not fully understood, the physiopathology of preeclampsia is thought to involve an abnormal placentation, diffuse endothelial cell dysfunction and increased systemic inflammation. As micronutrients play a key role in placental endothelial function, oxidative stress and expression of angiogenic factors, periconceptional micronutrient supplementation has been proposed to reduce the risk of preeclampsia. However, recent studies reported conflicting results. Calcium intake (>1 g/day) may reduce the risk of preeclampsia in women with low-calcium diet. Data from recently updated Cochrane reviews did not support routine supplementation of vitamins C, E or D for either the prevention or treatment of preeclampsia. Evidences are also poor to support zinc or folic acid supplementation for preeclampsia prevention. Dark chocolate, flavonoid-rich food, and long-chain polyunsaturated fatty acids might also be candidates for prevention of preeclampsia. Through antioxidant, anti-inflammatory or vasoactive proprieties, micronutrients are good candidates for preeclampsia prevention. Calcium supplementation is recommended to prevent preeclampsia in women with low-calcium intake. Despite positive clinical and in-vitro data, strong evidence to support periconceptional supplementation of other micronutrients for preeclampsia risk-reduction is still lacking. Further studies are also needed to evaluate the benefit of nutritional supplementation such as chocolate and long-chain polyunsaturated fatty acids.

Polyphenols, Antioxidants and the Sympathetic Nervous System.

A high dietary intake of polyphenols has been associated with a reduced cardiovascular mortality, due to their antioxidant properties. However, growing evidence suggests that counteracting oxidative stress in cardiovascular disease might also reduce sympathetic nervous system overactivity. This article reviews the most commonly used techniques to measure sympathetic activity in humans; the role of sympathetic activation in the pathophysiology of cardiovascular diseases; current evidence demonstrating that oxidative stress is involved in the regulation of sympathetic activity and how antioxidants and polyphenols might counteract sympathetic overactivity, particularly focusing on preliminary data from human studies. The main mechanisms by which polyphenols are cardioprotective are related to the improvement of vascular function and their anti-atherogenic effect. Furthermore, a blood pressure-lowering effect was consistently demonstrated in randomized controlled trials in humans, when the effect of flavonoid-rich foods, such as tea and chocolate, was tested. More recent studies suggest that inhibition of sympathetic overactivity might be one of the mechanisms by which these substances exert their cardioprotective effects. Indeed, an increased adrenergic traffic to the vasculature is a major mechanism of disease in a number of cardiovascular and extra-cardiac diseases, including hypertension, obesity, metabolic syndrome and heart failure. A considerable body of evidence, mostly from experimental studies, support the hypothesis that reactive oxygen species might exert sympathoexcitatory effects both at the central and at the peripheral level. Accordingly, supplementation with antioxidants might reduce adrenergic overdrive to the vasculature and blunt cardiovascular reactivity to stress. While supplementation with "classical" antioxidants such as ROS-scavengers has many limitations, increasing the intake of polyphenol-rich foods seems to be a promising novel therapeutic strategy to reduce the deleterious effects of increased adrenergic tone, particularly in essential hypertension.

Sexual Dysfunction Among Young Men: Overview of Dietary Components Associated With Erectile Dysfunction

BackgroundSexual dysfunction is relatively common in young men, presenting in diverse manifestations, including erectile dysfunction (ED), for which dietary modifications, including increased intake of dietary antioxidants, have been suggested as promising and cost-efficient approaches. AimTo assess the consumption of selected dietary antioxidants, in particular flavonoids, in relation to ED symptoms in young men. MethodsMen 18 to 40 years old were invited to complete an anonymous web-based questionnaire for this case-control study. ED was diagnosed with the International Index of Erectile Function (IIEF) and flavonoid intake was recorded using food-frequency questionnaires, with an emphasis on flavonoid-rich foods such as coffee, fruits, etc. Participants without ED (IIEF score ≥ 26; n = 264) formed the control group and those with ED (IIEF score < 26; n = 86) formed the case group. OutcomesDietary flavonoid intake. ResultsMen with ED reported a lower median monthly intake of total flavonoids (−2.18 g, 95% CI = −3.15 to −1.21, P < .001) and all flavonoid subclasses (P < .001) compared with controls. Adjustment of intake for age and body mass index showed that consumption of flavonoids 50 mg/day lowered the risk for ED by 32% (odds ratio = 0.68, 95% CI = 0.55–0.85, P < .001). Of all recorded flavonoids, flavones appeared to contribute the most to healthy erectile function. Controls reported a greater consumption of vegetables and fruits, a lower intake of dairy and alcoholic beverages, and a less intense smoking habit compared with cases (P < .001). Clinical ImplicationsIncreased intake of fruits, vegetables, and flavonoids decreases the risk of ED in young men. Strength and LimitationsThe strength of this study stems from the innovative hypothesis, the young age of participants, and the suggested therapeutic effects of cheap dietary components against ED. Limitations include the relatively small sample and cross-sectional design. ConclusionLow flavonoid—in particular flavone—intake is associated with ED in young adult men.Mykoniatis I, Grammatikopoulou MG, Bouras E, et al. Sexual Dysfunction Among Young Men: Overview of Dietary Components Associated With Erectile Dysfunction. J Sex Med 2018;15:176–182.

Quercetin-3-O-glucoside Improves Glucose Tolerance in Rats and Decreases Intestinal Sugar Uptake in Caco-2 Cells

Flavonoid-rich foods intake has been associated with lower risk of non-communicable chronic diseases. Quercetin is the most abundant flavonoid in nature (fruits, vegetables, leaves and grains) as well as the most consumed flavonol. This study aims to investigate the potential effects of its conjugated form quercetin-3- O-glucoside (or isoquercetin) on glucose metabolism in rats and Caco-2 cells. To analyse the effect of quercetin-3- O-glucoside on postprandial hyperglycemia, an oral glucose tolerance test (OGTT) was conducted in Wistar rats. Additionally, Caco-2 cells were used to determine the effect of quercetin-3- O-glucoside (30 to 60 μM) on mRNA expression of genes involved in glucose uptake by RT-PCR. Thereby, in vivo studies demonstrated that quercetin-3- O-glucoside decreased blood glucose levels evaluated by OGTT in rats. Furthermore, in the presence of Na+, quercetin-3- O-glucoside inhibited methylglucoside (MG) uptake in enterocytes and both sodium dependent glucose transporter-1 (SGLT1)- and glucose transporter-2 (GLUT2)-mediated glucose uptake were downregulated in Caco-2 cells incubated with quercetin-3- O-glucoside. In summary, our results show that quercetin-3- O-glucoside improves postprandial glycemic control in rats and reduces sugar uptake in Caco-2 cells, possible by decreasing the expression of glucose transporters (SGLT1 and GLUT2) according to the results obtained through RT-PCR.

Decrease of the affinity of theophylline bind to serum proteins induced by flavonoids and their synergies on protein conformation

In this study, the single and simultaneous interactions of theophylline and flavonoids with human serum albumin (HSA) were studied by multi-spectroscopic and molecular docking approaches. The influences of flavonoids on the binding constant (Kb) and the binding distance (r) of theophylline bind to HSA were determined and the changes of HSA conformation caused by the synergies of theophylline and flavonoids were investigated. Because theophylline, rutin and baicalin are all bond to the same binding site, the competitive bind of theophylline and flavonoids to HSA leads to the reduction of the Ka value of theophylline binding to HSA. The addition of rutin and baicalin can increase the value of r of theophylline binding to HSA, which further confirm the existence of the competitive bind of theophylline and flavonoids to HSA. Additionally, the results of synchronous fluorescence, three-dimensional fluorescence and circular dichroism spectra indicate that the presence of rutin and baicalin can give rise to the further changes of HSA conformation. These results suggest that the intake of flavonoid-rich food and beverages can increase the serum concentrations of theophylline and induce a high incidence of toxic symptom in clinic.

Studies on the competitive binding of cleviprex and flavonoids to plasma protein by multi-spectroscopic methods: A prediction of food-drug interaction

Cleviprex is a short-acting dihydropyridine calcium channel antagonist used as an antihypertensive drug. In this work, the binding characterization of cleviprex to human serum albumin (HSA) and the competitive binding to HSA between cleviprex and two flavonoids, baicalin and rutin, were studied using multi-spectroscopic techniques and molecular docking method. The fluorescence quenching of HSA by cleviprex was initiated by the formation of HSA-cleviprex complex, which was confirmed by UV–vis spectra measurements. The results of thermodynamic analysis and molecular docking revealed that the hydrophobic interactions and hydrogen bonding were the major acting forces in stabilizing HSA-cleviprex complex. The results of substitution experiments and molecular docking demonstrated that cleviprex was mainly situated within the site I of HSA. Baicalin and rutin could reduce the values of binding constant and enhance the values of binding distance of cleviprex binding to HSA because they bind to the same binding site. The results of synchronous fluorescence and CD spectra suggested that the binding reaction of cleviprex to HSA could give rise to the changes of protein conformation and the combined actions of cleviprex and flavonoids could cause further changes of HSA conformation. Consequently, the intakes of flavonoid-rich foods and beverages should be lessened under the treatment of cleviprex to avoid food-drug interactions.

Association of flavonoid-rich foods and flavonoids with risk of all-cause mortality.

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 (P<0·05), with the strongest associations observed for red wine and tea; multivariable-adjusted hazard ratios 0·60 (95 % CI 0·49, 0·74) and 0·73 (95 % CI 0·65, 0·83), respectively. Conversely, frequent grapefruit consumers were at increased risk of all-cause mortality, compared with their non-grapefruit consuming counterparts (P<0·05). When compared with those in the lowest consumption quintile, participants in the highest quintile of total-flavonoid intake were at reduced risk of all-cause mortality in the age-adjusted model; 0·81 (95 % CI 0·71, 0·93). However, this association was attenuated following multivariable adjustment; 0·92 (95 % CI 0·80, 1·06). Similar results were observed for consumption of flavan-3-ols, proanthocyanidins and anthocyanins. Flavonols, flavanones and flavones were not associated with all-cause mortality in any model. Despite null associations at the compound level and select foods, higher consumption of red wine, tea, peppers, blueberries and strawberries, was associated with reduced risk of total and cause-specific mortality. These findings support the rationale for making food-based dietary recommendations.

Nutraceutical Value of Citrus Flavanones and Their Implications in Cardiovascular Disease.

Background- Cardiovascular diseases, including myocardial infarction, dyslipidaemia and coronary artery pathology, are a major cause of illness and death in Western countries. Therefore, identifying effective therapeutic approaches and their cellular signalling pathways is a challenging goal for medicine. In this regard, several epidemiological studies demonstrate a relationship between the intake of flavonoid-rich foods and the reduction of cardiovascular risk factors and mortality. In particular, flavonoids present in citrus fruits, such as oranges, bergamots, lemons and grapefruit (95% from flavanones), are emerging for their considerable nutraceutical value. Methods- In this review an examination of literature was performed while considering both epidemiological, clinical and pre-clinical evidence supporting the beneficial role of the flavanone class. We evaluated studies in which citrus fruit juices or single flavanone administration and cardiovascular risk factors were analysed; to identify these studies, an electronic search was conducted in PUBMED for papers fulfilling these criteria and written in English. Results- In addition to epidemiological evidence and clinical studies demonstrating that fruits in the Citrus genus significantly reduce the incidence of cardiovascular disease risk, pre-clinical investigations highlight cellular and subcellular targets that are responsible for these beneficial effects. There has been special attention on evaluating intracellular pathways involved in direct cardiovascular and cardiometabolic effects mediated by naringenin, hesperetin and eriodictyol or their glycosylated derivatives. Conclusions- Although some mechanisms of action remain unclear and bioavailability problems remain to be solved, the current evidence supports the use of a nutraceutical approach with citrus fruits to prevent and cure several aspects of cardiovascular disease.

Higher dietary flavonoid intakes are associated with lower objectively measured body composition in women: evidence from discordant monozygotic twins ,

Background: Although dietary flavonoid intake has been associated with less weight gain, there are limited data on its impact on fat mass, and to our knowledge, the contribution of genetic factors to this relation has not previously been assessed.Objective: We examined the associations between flavonoid intakes and fat mass.Design: In a study of 2734 healthy, female twins aged 18–83 y from the TwinsUK registry, intakes of total flavonoids and 7 subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, polymers, and proanthocyanidins) were calculated with the use of food-frequency questionnaires. Measures of dual-energy X-ray absorptiometry–derived fat mass included the limb-to-trunk fat mass ratio (FMR), fat mass index, and central fat mass index.Results: In cross-sectional multivariable analyses, higher intake of anthocyanins, flavonols, and proanthocyanidins were associated with a lower FMR with mean ± SE differences between extreme quintiles of −0.03 ± 0.02 (P-trend = 0.02), −0.03 ± 0.02 (P-trend = 0.03), and −0.05 ± 0.02 (P-trend < 0.01), respectively. These associations were not markedly changed after further adjustment for fiber and total fruit and vegetable intakes. In monozygotic, intake-discordant twin pairs, twins with higher intakes of flavan-3-ols (n = 154, P = 0.03), flavonols (n = 173, P = 0.03), and proanthocyanidins (n = 172, P < 0.01) had a significantly lower FMR than that of their co-twins with within-pair differences of 3–4%. Furthermore, in confirmatory food-based analyses, twins with higher intakes of flavonol-rich foods (onions, tea, and pears; P = 0.01) and proanthocyanidin-rich foods (apples and cocoa drinks; P = 0.04) and, in younger participants (aged <50 y) only, of anthocyanin-rich foods (berries, pears, grapes, and wine; P = 0.01) had a 3–9% lower FMR than that of their co-twins.Conclusions: These data suggest that higher habitual intake of a number of flavonoids, including anthocyanins, flavan-3-ols, flavonols, and proanthocyanidins, are associated with lower fat mass independent of shared genetic and common environmental factors. Intervention trials are needed to further examine the effect of flavonoid-rich foods on body composition.

Soybean Milk Inhibits Absorption and Intestinal Transmembrane Transport of Gegen in Rats.

Puerariae Lobatae Radix, known as Gegen in Chinese, is widely used to treat cardiovascular diseases, diabetes, and many other chronic illnesses. Flavonoids are the main active components in Gegen and are found in high concentrations in soybeans. Few studies, however, have focused on the effects of flavonoid-rich food on the absorption of Gegen. Here, we report an in vivo pharmacokinetic study on rats to explore the effects of soybean milk on the absorption of Gegen and an in vitro Ussing chamber study of puerarin intestinal transmembrane absorption. Area under the plasma concentration-time curve (AUC0–t) and maximum plasma concentration (Cmax) values of puerarin in rats were significantly decreased after drinking soybean milk, when taking Gegen decoction or a Gegen patent medicine (P < 0.01). In the Ussing chamber experiment, cumulative transmission (Qtn) after 2 h and apparent permeability coefficient (Papp) were lower in the puerarin-daidzin and puerarin-soybean milk solution groups than in the puerarin group. Daidzin in soybean milk inhibited the transmembrane transport of puerarin, resulting in decreased bioavailability of puerarin in Gegen. The results of this study strongly suggest that Gegen should not be taken with flavonoid-rich food, particularly soybean products.

Genetic studies regarding the control of seed pigmentation of an ancient European pointed maize (Zea mays L.) rich in phlobaphenes: the “Nero Spinoso” from the Camonica valley

Several preclinical studies have suggested that the regular consumption of flavonoid-rich foods is associated to a reduced risk of chronic diseases. For this reason, in the last years a renewed interest for the ancient landraces rich in flavonoids or other bioactive molecules is growing. Preservation and valorisation of these ancient landraces is very important, not only for economic considerations regarding the farmers within the small rural communities, where the particular maize germplasm has been developed, but also from a scientific point of view. In this work we characterized the ancient cultivar named “Nero Spinoso” from the Camonica valley, the biggest valley in the north-west region of Lombardy (Italy). The peculiarity of this landrace is the colour and the pointed shape of the kernels. We showed after spectrophotometric and TLC analysis that this variety accumulates high amounts of phlobaphenes (320 A510/100 g flour). Genetic data demonstrate that phlobaphene pigmentation is under the control of a monogenic dominant gene. Further mapping and sequencing data showed that the pigmentation is driven by the presence of a strong allele of Pericarp 1 (P1) gene, a transcription factor belonging to the myb transcription factor gene family. The “Nero Spinoso” variety represents an ancient landrace that could be considered a real functional food and a useful tool in future breeding programmes.

Dietary flavonoid intake and incidence of erectile dysfunction

Background: The predominant etiology for erectile dysfunction (ED) is vascular, but limited data are available on the role of diet. A higher intake of several flavonoids reduces diabetes and cardiovascular disease risk, but no studies have examined associations between flavonoids and erectile function.Objective: This study examined the relation between habitual flavonoid subclass intakes and incidence of ED.Design: We conducted a prospective study among 25,096 men from the Health Professionals Follow-Up Study. Total flavonoid and subclass intakes were calculated from food-frequency questionnaires collected every 4 y. Participants rated their erectile function in 2000 (with historical reporting from 1986) and again in 2004 and 2008.Results: During 10 y of follow-up, 35.6% reported incident ED. After multivariate adjustment, including classic cardiovascular disease risk factors, several subclasses were associated with reduced ED incidence, specifically flavones (RR = 0.91; 95% CI: 0.85, 0.97; P-trend = 0.006), flavanones (RR = 0.89; 95% CI: 0.83, 0.95; P-trend = 0.0009), and anthocyanins (RR = 0.91; 95% CI: 0.85, 0.98; P-trend = 0.002) comparing extreme intakes. The results remained statistically significant after additional adjustment for a composite dietary intake score. In analyses stratified by age, a higher intake of flavanones, anthocyanins, and flavones was significantly associated with a reduction in risk of ED only in men <70 y old and not older men (11–16% reduction in risk; P-interaction = 0.002, 0.03, and 0.007 for flavones, flavanones, and anthocyanins, respectively). In food-based analysis, higher total intake of fruit, a major source of anthocyanins and flavanones, was associated with a 14% reduction in risk of ED (RR = 0.86; 95% CI: 0.79, 0.92; P = 0.002).Conclusions: These data suggest that a higher habitual intake of specific flavonoid-rich foods is associated with reduced ED incidence. Intervention trials are needed to further examine the impact of increasing intakes of commonly consumed flavonoid-rich foods on men’s health.

Acute reduction in blood pressure following consumption of anthocyanin-rich cherry juice may be dose-interval dependant: a pilot cross-over study

A pilot cross-over study assessed the acute effects on blood pressure and plasma biomarkers associated with consumption of a 300 ml anthocyanin-rich fruit juice, provided in differing dose-intervals. Young adults (n = 6) and older adults (n = 7) received in random order, either a single 300 ml dose or 3 × 100 ml doses of high-flavonoid cherry juice provided at 0, 1 and 2 h. Blood pressure and plasma levels of phenolic metabolites were measured at 0, 2 and 6 h.The single 300 ml dose of cherry juice resulted in a significant reduction in systolic (p = 0.002), and diastolic blood pressure (p = 0.008) and heart-rate (p = 0.033) 2 h after consumption, before returning to baseline levels at 6 h post-consumption. The 3 × 100 ml dose provided over 2 h did not result in significant blood pressure reductions. Plasma phenolic metabolites increased at 2 and 6 h; however, fluctuations were higher after the single 300 ml dose in older adults. These findings have implications for design of intervention studies that investigate vascular effects associated with flavonoid-rich foods.

Association of flavonoid-rich foods and statins in the management of hypercholesterolemia: a dangerous or helpful combination?

Statins and dietary modifications are the cornerstone of hypercholesterolemia management. Although it is well known that possible adverse effect of statins can occur due to drug-drug interactions, food-drug interactions are a commonly overlooked aspect. In particular, flavonoids could interfere with statins' bioavailability through different mechanisms, such as competition with cytochrome P450 (CYP) enzymes, esterases, uridine diphosphate glucuronosyltransferases and transporters (P-glycoprotein, multi-drug resistance-associated proteins, organic anion transporting polypeptides, breast cancer-resistance protein and monocarboxylate transporters). Transporters are characterized by low substrate specificity and flavonoid- rich foods could interfere with the bioavailability of all statins at this level. On the other hand, in addition to being substrates of drug metabolism/ transport systems, flavonoids are also able to modulate gene expression of enzymes and transporters. Therefore, long-term transcriptional induction may increase the clearance of statins, despite flavonoids act as competitive inhibitors after bolus consumption. In humans, major interactions were observed between grapefruit juice and statins that are substrates of P-glycoprotein/CYP3A, but other fruit juices also affect the bioavailability of statins that are not metabolised by CYP. Even if flavonoids could play a role in the prevention of hypercholesterolemia, the question whether there's a helpful or dangerous association between flavonoid-rich foods and statins, due to the interactions between flavonoid-rich foods and statins and the potential associated adverse effects of statins, remain unanswered. Therefore, the anamnesis of patients must include detailed information about their eating habits and the present review suggests monitoring and reporting any possible case of interaction between a prescribed statin and food.

Supplementation of the Pure Flavonoids Epicatechin and Quercetin Affects Some Biomarkers of Endothelial Dysfunction and Inflammation in (Pre)Hypertensive Adults: A Randomized Double-Blind, Placebo-Controlled, Crossover Trial ,

Background: Consumption of flavonoid-rich foods such as cocoa and tea may reduce cardiovascular disease risk. The flavonoids epicatechin (in cocoa and tea) and quercetin (in tea) probably play a role by reducing endothelial dysfunction and inflammation, 2 main determinants of atherosclerosis.Objective: We studied the effects of supplementation of pure epicatechin and quercetin on biomarkers of endothelial dysfunction and inflammation.Methods: Thirty-seven apparently healthy (pre)hypertensive men and women (40–80 y) participated in a randomized, double-blind, placebo-controlled crossover trial. Participants ingested (-)-epicatechin (100 mg/d), quercetin-3-glucoside (160 mg/d), or placebo capsules for a period of 4 wk, in random order. Plasma biomarkers of endothelial dysfunction and inflammation were measured at the start and end of each 4-wk intervention period. The differences in changes over time between the intervention and placebo periods (Δintervention − Δplacebo) were calculated and tested with a linear mixed model for repeated measures.Results: Epicatechin changed Δepicatechin − Δplacebo for soluble endothelial selectin (sE-selectin) by −7.7 ng/mL (95% CI: −14.5, −0.83; P = 0.03) but did not significantly change this difference (−0.30; 95% CI: −0.61, 0.01; P = 0.06) for the z score for endothelial dysfunction. Quercetin changed Δquercetin − Δplacebo for sE-selectin by −7.4 ng/mL (95% CI: −14.3, −0.56; P = 0.03), that for IL-1β by −0.23 pg/mL (95% CI: −0.40, −0.06; P = 0.009), and that for the z score for inflammation by −0.33 (95% CI: −0.60, −0.05; P = 0.02).Conclusions: In (pre)hypertensive men and women, epicatechin may contribute to the cardioprotective effects of cocoa and tea through improvements in endothelial function. Quercetin may contribute to the cardioprotective effects of tea possibly by improving endothelial function and reducing inflammation. This trial was registered at clinicaltrials.gov as NCT01691404.

Flavonoids and mitochondrial pharmacology: A new paradigm for cardioprotection.

Acute myocardial ischemia is one of the major causes of illness and of deaths in Western society; therefore the definition of the signaling pathways involved in the cardioprotection represents a challenging goal in order to discover novel pharmacological approaches. In this regard, a number of epidemiologic studies demonstrate a relationship between intake of flavonoid-rich foods and reduction of cardiovascular risk factors and mortality. Moreover, numerous experimental studies have examined flavonoid-induced cardioprotective effects on several animal models of myocardial ischemia/reperfusion. As concerns the mechanisms of action, although the antioxidant effect of flavonoids has been long thought to be a crucial factor accounting for cardioprotection, mitochondrial pathways (ion channels, protein kinases, etc.) are presently emerging as specific pharmacological targets more relevantly involved in the anti-ischemic effects of some flavonoids. Since these pharmacodynamic features seem to be poorly considered, this review examines the mitochondrial role in the cardioprotective mechanisms of some members of this phytochemical class, by describing the biological pathways and reporting an overview of the most important experimental evidence in this field.