Flavonoid-rich Foods Research Articles

Flavonoid intake and all-cause mortality

Flavonoids are bioactive compounds found in foods such as tea, chocolate, red wine, fruit, 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 flavonoids in preventing all-cause mortality remains uncertain. The objective was to explore the association between flavonoid intake and risk of 5-y mortality from all causes by using 2 comprehensive food composition databases to assess flavonoid intake. The study population included 1063 randomly selected women aged >75 y. All-cause, cancer, and cardiovascular mortalities were assessed over 5 y of follow-up through the Western Australia Data Linkage System. Two estimates of flavonoid intake (total flavonoidUSDA and total flavonoidPE) were determined by using food composition data from the USDA and the Phenol-Explorer (PE) databases, respectively. During the 5-y follow-up period, 129 (12%) deaths were documented. Participants with high total flavonoid intake were at lower risk [multivariate-adjusted HR (95% CI)] of 5-y all-cause mortality than those with low total flavonoid consumption [total flavonoidUSDA: 0.37 (0.22, 0.58); total flavonoidPE: 0.36 (0.22, 0.60)]. Similar beneficial relations were observed for both cardiovascular disease mortality [total flavonoidUSDA: 0.34 (0.17, 0.69); flavonoidPE: 0.32 (0.16, 0.61)] and cancer mortality [total flavonoidUSDA: 0.25 (0.10, 0.62); flavonoidPE: 0.26 (0.11, 0.62)]. Using the most comprehensive flavonoid databases, we provide evidence that high consumption of flavonoids is associated with reduced risk of mortality in older women. The benefits of flavonoids may extend to the etiology of cancer and cardiovascular disease.

Effects of the pure flavonoids epicatechin and quercetin on vascular function and cardiometabolic health: a randomized, double-blind, placebo-controlled, crossover trial

Prospective cohort studies showed inverse associations between the intake of flavonoid-rich foods (cocoa and tea) and cardiovascular disease (CVD). Intervention studies showed protective effects on intermediate markers of CVD. This may be due to the protective effects of the flavonoids epicatechin (in cocoa and tea) and quercetin (in tea). We investigated the effects of supplementation of pure epicatechin and quercetin on vascular function and cardiometabolic health. Thirty-seven apparently healthy men and women aged 40-80 y with a systolic blood pressure (BP) between 125 and 160 mm Hg at screening were enrolled in a randomized, double-blind, placebo-controlled, crossover trial. CVD risk factors were measured before and after 4 wk of daily flavonoid supplementation. Participants received (-)-epicatechin (100 mg/d), quercetin-3-glucoside (160 mg/d), or placebo capsules for 4 wk in random order. The primary outcome was the change in flow-mediated dilation from pre- to postintervention. Secondary outcomes included other markers of CVD risk and vascular function. Epicatechin supplementation did not change flow-mediated dilation significantly (1.1% absolute; 95% CI: -0.1%, 2.3%; P = 0.07). Epicatechin supplementation improved fasting plasma insulin (Δ insulin: -1.46 mU/L; 95% CI: -2.74, -0.18 mU/L; P = 0.03) and insulin resistance (Δ homeostasis model assessment of insulin resistance: -0.38; 95% CI: -0.74, -0.01; P = 0.04) and had no effect on fasting plasma glucose. Epicatechin did not change BP (office BP and 24-h ambulatory BP), arterial stiffness, nitric oxide, endothelin 1, or blood lipid profile. Quercetin-3-glucoside supplementation had no effect on flow-mediated dilation, insulin resistance, or other CVD risk factors. Our results suggest that epicatechin may in part contribute to the cardioprotective effects of cocoa and tea by improving insulin resistance. It is unlikely that quercetin plays an important role in the cardioprotective effects of tea. This study was registered at clinicaltrials.gov as NCT01691404.

Changes in Intake and Major Food Sources of Flavonoids among U.S. Adults between 1999‐2002 and 2007‐2010

Epidemiologic evidence has implicated that dietary flavonoids or flavonoid rich foods are associated with a reduced risk of certain chronic diseases. However, incomplete food composition data and changes in diet over time likely affect the accuracy of flavonoid intake estimates. The current study was conducted to: 1) demonstrate an updated method of combining food consumption data and USDA flavonoid database; 2) estimate the current intake and major food sources of dietary flavonoids of US adults; and 3) determine if dietary intake and sources of flavonoids changed during the past decade. Differences over time in the average daily intake and food sources of flavonoids were estimated using 24‐hour dietary recall data from NHANES 1999‐2002 (n = 8,833) and 2007‐2010 (n = 9,801). The total flavonoid intake of US adults aged 蠅19 years was similar between 1999‐2002 (201.8 mg/d) and 2007‐2010 (199.9 mg/d) with tea being the major food source of flavonoids. However, intake of anthocyanidins increased during this period, which was mostly attributable to greater consumption of berries and wine in 2007‐2010 (p < 0.001) and coincided with per capita food consumption from USDA food availability data. This study demonstrates temporal trends in the dietary sources and intake of flavonoids in the US over the past decade and provides a basis for further research on the health effects of flavonoid consumption.

Dietary flavonoid intake at midlife and healthy aging in women

Dietary flavonoids have been related to lower risks of various chronic diseases, but it is unclear whether flavonoid intake in midlife helps to maintain good health and wellbeing in aging. We examined the relation of flavonoid intake in midlife with the prevalence of healthy aging. We included 13,818 women from the Nurses' Health Study with dietary data and no major chronic diseases in 1984-1986 when they were aged in their late 50s (median age: 59 y); all women provided information on multiple aspects of aging an average of 15 y later. Intakes of 6 major flavonoid subclasses in midlife were ascertained on the basis of averaged intakes of flavonoid-rich foods from 2 food-frequency questionnaires (1984-1986). We defined healthy compared with usual aging as of age 70 y; healthy aging was based on survival to ≥70 y with maintenance of 4 health domains (no major chronic diseases or major impairments in cognitive or physical function or mental health). Of women who survived until ≥70 y of age, 1517 women (11.0%) met our criteria for healthy aging. Compared with women in the lowest quintile of intake, women in the highest quintile of intake of several flavonoid subclasses at midlife had greater odds of healthy aging. After multivariable adjustment, ORs were as follows: flavones, 1.32 (95% CI: 1.10, 1.58); flavanone, 1.28 (95% CI: 1.08, 1.53); anthocyanin, 1.25 (95% CI: 1.04, 1.50); and flavonol, 1.18 (95% CI: 0.98, 1.42) (all P-trend ≤ 0.02). Consistently, greater intakes of major sources of these flavonoids (i.e., oranges, berries, onions, and apples) were associated with increased odds of healthy aging. We showed no association with flavan-3-ol monomers (P-trend = 0.80) or polymers (P-trend = 0.63). Higher intake of flavonoids at midlife, specifically flavones, flavanones, anthocyanins, and flavonols, is associated with greater likelihood of health and wellbeing in individuals surviving to older ages.

Flavonoids and Immune Function in Human: A Systematic Review

Flavonoids, through a modulation of immune function, have been suggested to be involved in the role played by plant foods in disease prevention. We performed a systematic search in the MEDLINE database to review the effect of flavonoid-rich foods and flavonoids supplements on immune function. A total of 58 studies, were identified as suitable: 41 addressed in vivo proinflammatory cytokines and 15 measured ex vivo markers of immune function. According to our findings and on the basis of single food items, the number of studies in humans is limited and, for galenic supplements, only quercetin has been investigated. More evidences are needed to clarify the role of flavonoids as modulator of immune function in humans.

Association between flavonoid-rich fruit and vegetable consumption and total serum bilirubin.

Emerging work demonstrates that serum bilirubin is a novel biomarker implicated in cardiovascular and metabolic diseases. However, we have a limited understanding of the influence of flavonoid-rich fruit and vegetable consumption on bilirubin levels, which was the purpose of this study. Data from the 2003 to 2006 National Health and Nutrition Examination survey were used (n = 1783; 18-85 years of age), with analyses performed in 2014. Total serum bilirubin was measured from a blood sample. Using a food frequency questionnaire (FFQ), a flavonoid index variable was created summing the frequency of consumption of flavonoid-rich foods. After adjustments, greater consumption of flavonoid-rich fruits and vegetables was positively associated with bilirubin levels. Our findings suggest an association between flavonoid-rich fruit and vegetable consumption and bilirubin levels. If confirmed by prospective and experimental studies, then regular consumption of flavonoid-rich fruits and vegetables should be promoted to increase levels of bilirubin.

Red wine flavonoids and vascular health

Relative to non-drinkers, a low to moderate alcohol intake is associated with lower risk of cardiovascular and total mortality. Epidemiological studies also suggest that a low to moderate red wine consumption may protect against cardiovascular disease. Because epidemiological studies show a similar relationship for different types of alcoholic beverages, the alcohol (ethanol), at low to moderate intakes, is proposed to provide protection. However, it remains uncertain whether there is a causal link between alcohol generally or red wine specifically and cardiovascular disease. This is very difficult to explore in epidemiological studies because of the many confounding social and dietary factors, and because risk of cardiovascular disease increases substantially from moderate to very high intakes of alcohol. The other major components of red wine that have received attention as potentially cardioprotective are the flavonoids. There is mounting evidence that flavonoids and foods and beverages rich in flavonoids can make an important contribution to cardiovascular health. Fruit and vegetables, tea and cocoa are important sources of flavonoids in the human diet. The intake of these foods hasl been associated with reduced risk of cardiovascular disease in population studies. Flavonoids are potent antioxidants in vitro, but it is their ability to cause vasorelaxation that is likely to be important for any vascular health benefits. Red grapes, their skin, their seeds and the wine derived from them are rich in flavonoids. Population studies have found that higher intakes of flavonoids are associated with lower risk for cardiovascular disease. In vitro studies, studies using animal models and human intervention studies have investigated how flavonoids might contribute to reduced risk of cardiovascular disease. A variety of mechanisms and outcomes have been explored and there is now strong evidence that flavonoids can improve endothelial function. A number of human studies have been performed to investigate the in vivo effects of red wine derived flavonoids on endothelial function. The results of these studies are mixed, with several studies indicating acute improvements, while other studies suggest little benefit of regular short-term consumption of red wine flavonoids. The effects of other rich dietary sources of flavonoids, such as tea and cocoa, to improve endothelial function may also provide a guide to the potential benefits of red wine flavonoids. Results of human trials and meta-analyses of these trials suggest that tea, cocoa and flavonoid-rich fruits can improve endothelial function. Therefore there is good evidence that flavonoid-rich foods and beverages can have vascular health benefits. However, because bioactivity of different flavonoids varies, health effects cannot be generalized to all flavonoids and flavonoid-rich foods. Further studies are needed to establish any vascular health benefits of the red wine flavonoids.

Phenolic Acid Intake, DeliveredViaModerate Champagne Wine Consumption, Improves Spatial Working MemoryViathe Modulation of Hippocampal and Cortical Protein Expression/Activation

While much data exist for the effects of flavonoid-rich foods on spatial memory in rodents, there are no such data for foods/beverages predominantly containing hydroxycinnamates and phenolic acids. To address this, we investigated the effects of moderate Champagne wine intake, which is rich in these components, on spatial memory and related mechanisms relative to the alcohol- and energy-matched controls. In contrast to the isocaloric and alcohol-matched controls, supplementation with Champagne wine (1.78 ml/kg BW, alcohol 12.5% vol.) for 6 weeks led to an improvement in spatial working memory in aged rodents. Targeted protein arrays indicated that these behavioral effects were paralleled by the differential expression of a number of hippocampal and cortical proteins (relative to the isocaloric control group), including those involved in signal transduction, neuroplasticity, apoptosis, and cell cycle regulation. Western immunoblotting confirmed the differential modulation of brain-derived neurotrophic factor, cAMP response-element-binding protein (CREB), p38, dystrophin, 2',3'-cyclic-nucleotide 3'-phosphodiesterase, mammalian target of rapamycin (mTOR), and Bcl-xL in response to Champagne supplementation compared to the control drink, and the modulation of mTOR, Bcl-xL, and CREB in response to alcohol supplementation. Our data suggest that smaller phenolics such as gallic acid, protocatechuic acid, tyrosol, caftaric acid, and caffeic acid, in addition to flavonoids, are capable of exerting improvements in spatial memory via the modulation in hippocampal signaling and protein expression. Changes in spatial working memory induced by the Champagne supplementation are linked to the effects of absorbed phenolics on cytoskeletal proteins, neurotrophin expression, and the effects of alcohol on the regulation of apoptotic events in the hippocampus and cortex.

The antioxidant capacity of milk--the application of different methods in vitro and in vivo.

Milk contains a wide array of compounds with established or putative pro- or anti-oxidant function. The functions of these compounds have been intensively studied. This review focusses on some important aspects in this wide field namely the methodology for measurement of the total antioxidant capacity (TAC), the content of TAC and some related compounds in human and animal milks and infant formulas, and the effect of milk intake on antioxidant status in the body and on the activity of dietary flavonoids as studied in vitro and in vivo. Regarding methodology TAC in milk can be measured by spectrophotometric and electrochemical methods and some of their characteristics are reviewed. Milk, whey, high-molecular-weight and low-molecular-weight (LMW) fractions of whey have all been found to have antioxidant capacity using these techniques. The major antioxidant in the LMW fraction has been identified as urate. An extensive literature survey was made regarding data on the antioxidant capacity and related variables of milk obtained from different sources (human milk, infant formulas and animal milk) and subjected to different treatments. Differences in TAC between milks from different sources have been observed but due to the variety of techniques used no clear pattern is evident at present. Another important aspect is the putative effects of the intake of milk products on the antioxidant status of the consumer. A few studies performed in adults and premature infants are reviewed and it is stated that too little information is available to make any firm conclusions in this regard. Finally, a high interest has been devoted to the possible interference of milk with the antioxidant properties of flavonoid-rich food like tea. Most in vitro studies show an inhibition by milk on tea flavonoid activity whereas the results from the corresponding in vivo studies are equivocal. Our general conclusion is that several compounds in various milk fractions contribute to the antioxidant capacity of milk and that much further work is needed to unravel the complex interactions among the pro- and antioxidants, and their putative health effects on the consumer.

Rutin activates the MAPK pathway and BDNF gene expression on beta-amyloid induced neurotoxicity in rats

Flavonoids are present in foods such as fruits and vegetables. A relationship between the consumption of flavonoid-rich foods and prevention of human disease including neurodegenerative disorders has been demonstrated. We assessed the effect of rutin (3,3′,4′,5,7-pentahydroxyflavone-3-rhamnoglucoside) on the mitogen-activated protein kinase (MAPK) pathway, memory retrieval and oxidative stress in rats injected with β-amyloid (Aβ), which is implicated to have an important role in Alzheimer's disease (AD). Aβ was injected bilaterally in the deep frontal cortex of rat brain. Next, rutin and saline were injected (i.p.) for 3 weeks. In comparison to the control group, rutin significantly increased extracellular signal-regulated protein kinase 1 (ERK1), cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) gene expression in the hippocampus of rats. Rutin (100mg/kg) significantly increased memory retrieval compared to the control group. Malondialdehyde (MDA) level in the hippocampus of the rutin group was significantly lower than those in the control group. The content of sulfhydryl groups in the rutin group was higher than that in the control group. The findings show a possibility that rutin may have beneficial effects against neurotoxicity of Aβ on memory in rats.

Antigenotoxic Effect of Tartary (Fagopyrum tataricum) and Common (Fagopyrum esculentum) Buckwheat Flour

The aim of our work was to determine and to compare the possible antigenotoxic effect of methanolic extracts of common buckwheat (CB) and Tartary buckwheat (TB) flour, containing naturally present rutin (R), and quercetin (Q), and of R and Q in chemical form, against tert-butyl hydroperoxide (t-BOOH) induced DNA damage in human hepatoma cell line (HepG2). R and Q content of CB and TB flour extracts was determined by reversed phase-high performance liquid chromatography and antigenotoxic effect of flour extracts, R and Q was evaluated using the comet assay. R (100 μM) and Q (50 μM) decreased the extent of t-BOOH induced DNA damage for 51% and 67%, respectively. CB and TB flour extracts showed high antioxidant capacity and prominent genoprotective ability. CB extract containing up to 0.1 μM R decreased t-BOOH induced DNA damage for 34%, and TB extract containing up to 12.64 μM R, and 2.86 μM Q for 40%. The obtained results show high antigenotoxic activity of buckwheat and furthermore, they suggest that complex nutrient and flavonoid rich food products are more efficient in their health promoting effects compared to a single active substance.

Effects of rutin on oxidative stress in mice with kainic acid-induced seizure

Flavonoids are present in foods such as fruits and vegetables. Several studies have demonstrated a relationship between the consumption of flavonoid-rich foods and prevention of human disease, including neurodegenerative disorders. We assessed the effect of rutin (quercetin-3-O-rutinoside) on oxidative stress in kainic acid (KA)-induced seizure. Thirty-six BALB/c mice were randomly divided into three groups. In the control group, saline (intra-peritoneal, i.p.) was administered for 7 d, and on the last day, KA (10 mg/kg, i.p.) was injected 30 min after administration of saline. In rutin groups, mice were pretreated with rutin (100 and 200 mg/kg, i.p.) for 7 d, and on the last day, KA (10 mg/kg, i.p.) was injected 30 min after administration of rutin. Subsequently, behavioural changes were observed in mice. Lipid peroxidation and oxidative stress were measured respectively in the early and late phases after KA-induced seizures. Seizure scores in the rutin groups were significantly lower than those in the control group (P < 0.01). Furthermore, rutin dose-dependently inhibited the number of wet-dog shakes (WDS) (P < 0.05). Malondialdehyde level in the hippocampus of the rutin groups was significantly lower than that in the hippocampus of the control group on days 1 and 21 after KA administration. In the rutin groups, the thiol levels observed on day 1 after KA administration were higher than that in the control group (P < 0.01). These results indicate that rutin has potential anticonvulsant and antioxidative activities against oxidative stress in KA-induced seizure in mice.

Chemopreventive potential of flavonoids in oral squamous cell carcinoma in human studies.

Evidence available from nutritional epidemiology has indicated an inverse association between regular consumption of fruits and vegetables and the risk of developing certain types of cancer. In turn, preclinical studies have attributed the health-promoting effects of plant foods to some groups of phytochemicals, by virtue of their many biological activities. In this survey, we briefly examine the chemopreventive potential of flavonoids and flavonoid-rich foods in human oral carcinogenesis. Despite the paucity of data from clinical trials and epidemiological studies, in comparison to in vitro/in vivo investigations, a high level of evidence has been reported for epigallocatechin gallate (EGCG) and anthocyanins. These flavonoids, abundant in green tea and black raspberries, respectively, represent promising chemopreventive agents in human oral cancer.

Dietary Levels of Pure Flavonoids Improve Spatial Memory Performance and Increase Hippocampal Brain-Derived Neurotrophic Factor

Evidence suggests that flavonoid-rich foods are capable of inducing improvements in memory and cognition in animals and humans. However, there is a lack of clarity concerning whether flavonoids are the causal agents in inducing such behavioral responses. Here we show that supplementation with pure anthocyanins or pure flavanols for 6 weeks, at levels similar to that found in blueberry (2% w/w), results in an enhancement of spatial memory in 18 month old rats. Pure flavanols and pure anthocyanins were observed to induce significant improvements in spatial working memory (p = 0.002 and p = 0.006 respectively), to a similar extent to that following blueberry supplementation (p = 0.002). These behavioral changes were paralleled by increases in hippocampal brain-derived neurotrophic factor (R = 0.46, p<0.01), suggesting a common mechanism for the enhancement of memory. However, unlike protein levels of BDNF, the regional enhancement of BDNF mRNA expression in the hippocampus appeared to be predominantly enhanced by anthocyanins. Our data support the claim that flavonoids are likely causal agents in mediating the cognitive effects of flavonoid-rich foods.

Dietary flavonoids and the development of type 2 diabetes and cardiovascular diseases

This review summarizes the results on flavonoid intakes and the development of type 2 diabetes and cardiovascular diseases. Recent advances in food composition databases have allowed the evaluation of a more comprehensive range of flavonoids in epidemiological studies. In addition, the number of randomized trials of flavonoid-rich foods has increased rapidly. Results from both cohort studies and randomized trials suggest that anthocyanidins from berries and flavan-3-ols from green tea and cocoa may lower the risk of type 2 diabetes and cardiovascular diseases. Meta-analyses of randomized trials indicate that the strongest evidence exists for a beneficial effect of green tea on LDL-cholesterol and a beneficial effect of flavan-3-ol-rich cocoa on endothelial function and insulin sensitivity. Few randomized trials had a long duration or evaluated pure flavonoid compounds. Evidence from cohort studies and randomized trials suggest beneficial effects of food sources of anthocyanidins (berries) and flavan-3-ols (green tea and cocoa) on cardiovascular health. These findings need to be confirmed in long-term randomized trials, and evaluation of pure compounds will be important to establish what specific flavonoids and doses are effective.

Association between habitual dietary flavonoid and lignan intake and colorectal cancer in a Spanish case–control study (the Bellvitge Colorectal Cancer Study)

Flavonoid-rich foods, such as fruits, vegetables, and tea, may have a protective effect upon colorectal cancer. However, current epidemiological evidence for a protective effect of flavonoid intake upon colorectal cancer is promising but not conclusive. To examine the relation between dietary flavonoid and lignan intakes and the risk of colorectal cancer within a Spanish population. Data from the Bellvitge Colorectal Cancer Study, a case-control study (424 cases with incident colorectal cancer and 401 hospital-based controls), were used. A reproducible and validated food frequency questionnaire was administered in personal interviews. An ad hoc food composition database on flavonoids and lignans was compiled, mainly using data from the US Department of Agriculture and Phenol-Explorer databases. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. An inverse association was found between intake of total flavonoids (OR, 0.59; 95% CI, 0.35-0.99 for the highest vs. the lowest quartile; p for trend=0.04), lignans (OR, 0.59; 95% CI, 0.34-0.99; p for trend=0.03), and some individual flavonoid subgroups (flavones, proanthocyanidins) and the risk of colorectal cancer. Separate analyses by cancer site showed similar results. Intake of total dietary flavonoids (particularly certain flavonoid subgroups) and lignans was inversely associated with colorectal cancer risk in a Spanish population.

Blueberry supplementation induces spatial memory improvements and region-specific regulation of hippocampal BDNF mRNA expression in young rats

Flavonoid-rich foods have been shown to be able to reverse age-related cognitive deficits in memory and learning in both animals and humans. However, to date, there have been only a limited number of studies investigating the effects of flavonoid-rich foods on cognition in young/healthy animals. The aim of this study was to investigate the effects of a blueberry-rich diet in young animals using a spatial working memory paradigm, the delayed non-match task, using an eight-arm radial maze. Furthermore, the mechanisms underlying such behavioural effects were investigated. We show that a 7-week supplementation with a blueberry diet (2 % w/w) improves the spatial memory performance of young rats (2 months old). Blueberry-fed animals also exhibited a faster rate of learning compared to those on the control diet. These behavioural outputs were accompanied by the activation of extracellular signal-related kinase (ERK1/2), increases in total cAMP-response element-binding protein (CREB) and elevated levels of pro- and mature brain-derived neurotrophic factor (BDNF) in the hippocampus. Changes in hippocampal CREB correlated well with memory performance. Further regional analysis of BDNF gene expression in the hippocampus revealed a specific increase in BDNF mRNA in the dentate gyrus and CA1 areas of hippocampi of blueberry-fed animals. The present study suggests that consumption of flavonoid-rich blueberries has a positive impact on spatial learning performance in young healthy animals, and these improvements are linked to the activation of ERK-CREB-BDNF pathway in the hippocampus.

Abstract 625: Flavonoid intake and risk of pancreatic cancer in the National Institutes of Health-AARP Diet and Health Study Cohort

Abstract Flavonoids are the most common of the plant polyphenolics and are obtained from foods such as tea, citrus and other fruits. Laboratory and animal studies suggest that through anti-oxidant properties dietary flavonoids may reduce the risk of pancreatic cancer, and the few previous epidemiologic studies on flavonoid intake and pancreatic cancer risk have shown protective associations for specific types of flavonoids. We examined the association between total flavonoid intake, six flavonoid subgroups, flavonoid-rich foods and development of exocrine pancreatic cancer among 537,104 participants in the NIH-AARP Diet and Health Study with complete dietary data. Men and women aged 50 to 71 years completed a self-administered food frequency questionnaire at baseline (1995-1996) that ascertained diet and other lifestyle information. During follow-up through 2006 (median 10.6 years, max 11.2 years), 2379 incident pancreatic cancer cases were identified. Flavonoid intake was estimated from two databases developed from the USDA Nutrient Data laboratory. The distribution of flavonoid intake differed by sex (mean female intake 216 mg/day, range 0.41-9456; mean male intake 153 mg/day, range 0.95-6561); therefore, quintiles were based on sex specific cut-points. We used Cox proportional hazard models with age as the underlying time metric to calculate hazard ratios (HR) for pancreatic cancer. Models were adjusted for sex, smoking, diabetes, body mass index, alcohol use, and saturated fat and red meat intake. We found no association between total flavonoid intake (hazard ratio (HR)=1.09; 95% confidence interval (CI) 0.96-1.24) or the six flavonoid subgroups and risk of pancreatic cancer. Although there was no significant interaction by sex or smoking (p-interaction &amp;gt; 0.10), in stratified analyses we observed significant increased risks for total flavonoid intake among current smokers (Q5 versus Q1 HR=1.45, 95% CI 1.12-1.88, p-trend=0.002), while no such associations were evident among never (HR=1.01, 95% CI 1.00-1.03) or former smokers (HR=0.99, 95% CI 0.98-1.01). Among smokers flavonol and isoflavone intakes were positively associated with pancreatic cancer comparing extreme quintiles, with HRs =1.38 (95% CI 1.05-1.82, p trend=0.019) and 1.39 (95% CI 1.03-1.86, p trend=0.022) respectively. It is possible that exposures correlated to smoking but not accounted for in our analysis explain the observed associations. Our results do not support the hypothesis that flavonoid intake plays a protective role in pancreatic cancer carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 625. doi:1538-7445.AM2012-625

Habitual intake of dietary flavonoids and risk of Parkinson disease

To prospectively examine whether higher intakes of total flavonoids and their subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, and polymers) were associated with a lower risk of developing Parkinson disease (PD). In the current analysis, we included 49,281 men in the Health Professional Follow-up Study and 80,336 women from the Nurses' Health Study. Five major sources of flavonoid-rich foods (tea, berry fruits, apples, red wine, and orange/orange juice) were also examined. Flavonoid intake was assessed using an updated food composition database and a validated food frequency questionnaire. We identified 805 participants (438 men and 367 women) who developed PD during 20-22 years of follow-up. In men, after adjusting for multiple confounders, participants in the highest quintile of total flavonoids had a 40%lower PD risk than those in the lowest quintile (hazard ratio [HR] = 0.60; 95% confidence interval 0.43, 0.83; p trend = 0.001). No significant relationship was observed in women (p trend = 0.62) or in pooled analyses (p trend = 0.23). In the pooled analyses for the subclasses, intakes of anthocyanins and a rich dietary source, berries, were significantly associated with a lower PD risk (HR comparing 2 extreme intake quintiles were 0.76 for anthocyanins and 0.77 for berries, respectively; p trend < 0.02 for both). Our findings suggest that intake of some flavonoids may reduce PD risk, particularly in men, but a protective effect of other constituents of plant foods cannot be excluded.

Flavonoids as modulators of memory and learning: molecular interactions resulting in behavioural effects

There is considerable interest in the potential of a group of dietary-derived phytochemicals known as flavonoids in modulating neuronal function and thereby influencing memory, learning and cognitive function. The present review begins by detailing the molecular events that underlie the acquisition and consolidation of new memories in the brain in order to provide a critical background to understanding the impact of flavonoid-rich diets or pure flavonoids on memory. Data suggests that despite limited brain bioavailability, dietary supplementation with flavonoid-rich foods, such as blueberry, green tea and Ginkgo biloba lead to significant reversals of age-related deficits on spatial memory and learning. Furthermore, animal and cellular studies suggest that the mechanisms underpinning their ability to induce improvements in memory are linked to the potential of absorbed flavonoids and their metabolites to interact with and modulate critical signalling pathways, transcription factors and gene and/or protein expression which control memory and learning processes in the hippocampus; the brain structure where spatial learning occurs. Overall, current evidence suggests that human translation of these animal investigations are warranted, as are further studies, to better understand the precise cause-and-effect relationship between flavonoid intake and cognitive outputs.