Enzymatically modified isoquercitrin improves endothelial function in volunteers at risk of cardiovascular disease

A higher intake of food rich in flavonoids such as quercetin can reduce the risk of CVD. Enzymatically modified isoquercitrin (EMIQ®) has a bioavailability 17-fold higher than quercetin aglycone and has shown potential CVD moderating effects in animal studies. The present study aimed to determine whether acute ingestion of EMIQ® improves endothelial function, blood pressure (BP) and cognitive function in human volunteers at risk of CVD. Twenty-five participants (twelve males and thirteen females) with at least one CVD risk factor completed this randomised, controlled, crossover study. In a random order, participants were given EMIQ® (2 mg aglycone equivalent)/kg body weight or placebo alongside a standard breakfast meal. Endothelial function, assessed by flow-mediated dilatation (FMD) of the brachial artery was measured before and 1·5 h after intervention. BP, arterial stiffness, cognitive function, BP during cognitive stress and measures of quercetin metabolites, oxidative stress and markers of nitric oxide (NO) production were assessed post-intervention. After adjustment for pre-treatment measurements and treatment order, EMIQ® treatment resulted in a significantly higher FMD response compared with the placebo (1·80 (95 % CI 0·23, 3·37) %; P = 0·025). Plasma concentrations of quercetin metabolites were significantly higher (P \u3c 0·001) after EMIQ® treatment compared with the placebo. No changes in BP, arterial stiffness, cognitive function or biochemical parameters were observed. In this human intervention study, the acute administration of EMIQ® significantly increased circulating quercetin metabolites and improved endothelial function. Further clinical trials are required to assess whether health benefits are associated with long-term EMIQ® consumption

Associations between dietary flavonoids and retinal microvasculature in older adults

Purpose In this study, we assessed whether there are independent associations between dietary total flavonoid intake and major flavonoid classes with retinal arteriolar and venular calibre. Methods Blue Mountains Eye Study participants aged 49+ years who had complete data on diet and retinal vessel measures were analysed (n = 2821). Dietary intake was assessed using a semi-quantitative Food-Frequency Questionnaire (FFQ). Flavonoid content of foods in the FFQ was estimated using the US Department of Agriculture Flavonoid, Isoflavone and Proanthocyanidin databases. Fundus photographs were taken and retinal vascular calibre was measured using validated computer-assisted techniques. The associations of intake of dietary flavonoids with retinal vessel calibre were examined in linear regression models and general linear model. Results The highest quartile of intake was compared with the lowest quartile using multivariable-adjustment models. Participants with the highest proanthocyanidin intake had narrower retinal venules (223.9 ± 0.62 versus 226.5 ± 0.63, respectively; Ptrend = 0.01); and the highest isoflavone intake was associated with wider retinal arterioles (188.1 ± 0.55 versus 186.3 ± 0.56, respectively; Ptrend = 0.01). The highest apple/pear consumption (a dietary source of catechin) was associated with narrower retinal venules (223.8 ± 0.57 versus 226.1 ± 0.52; Ptrend = 0.01) and wider retinal arterioles (187.9 ± 0.51 versus 186.2 ± 0.51; Ptrend = 0.02). Further, participants who were in the highest versus lowest quartile of chocolate consumption had ~ 2.1 μm narrower retinal venules (multivariable-adjusted P = 0.03). Conclusions This study shows that higher intakes of specific flavonoid subclasses are associated with a favourable retinal microvascular profile. Greater consumption of flavonoid-rich apples/pears and chocolate was also associated with beneficial variations in retinal vascular calibre

Associations between intake of dietary flavonoids and 10-year incidence of age-related hearing loss

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Dietary flavonoids are vasoactive phytochemicals with promising anti-inflammatory properties. We aimed to assess the associations between baseline intakes of six commonly consumed flavonoid subclasses and 10-year incidence of age-related hearing loss. At baseline, 1691 participants aged 50+ years had information on dietary intakes and hearing status. Hearing loss was defined as the pure-tone average of frequencies 0.5, 1.0, 2.0, and 4.0 kHz \u3e 25 dB hearing level (HL). Dietary data were collected through a semi-quantitative food frequency questionnaire. The flavonoid content of foods was estimated using US databases. During the 10-year follow-up, 260 (31.6%) new cases of hearing loss (incident) were observed. After multivariable adjustment, participants in the fourth versus first quartile (reference group) of intake of dietary isoflavone had 36% lower risk of incident hearing loss after 10 years: odds ratios (OR) 0.64 (95% confidence intervals, CI, 0.42–0.99); p-value for trend = 0.03. Nonsignificant associations were observed between the other five flavonoid subclasses and 10-year incidence of hearing loss. Our findings do not support the hypothesis that the intake of dietary flavonoids protect against long-term risk of hearing loss. The association with isoflavone intake needs to be confirmed by other population-based studies

The association between an energy-adjusted dietary inflammatory index and inflammation in rural and urban Black South Africans

Objective: To quantify the inflammatory potential of the diet of rural and urban Black South Africans using an adapted energy-adjusted dietary inflammatory index (AE-DII) and to investigate its relationship with inflammatory and cardio-metabolic disease risk markers. Dietary inflammatory potential has not been investigated in African populations. Design: Cross-sectional investigation. Setting: Rural and urban sites in the North West province of South Africa. Participants: 1,885 randomly selected, apparently healthy Black South Africans older than 30 years. Results: AE-DII scores ranged from -3.71 to +5.08 with a mean of +0.37. AE-DII scores were significantly higher in men (0.47±1.19) than in women (0.32±1.29), and in rural (0.55±1.29) than urban participants (0.21±1.19). Apart from its dietary constituents, AE-DII scores primarily associated with age, rural-urban status and education. Contrary to the literature, alcohol consumption was positively associated with AE-DII scores. Of the four tested inflammatory and 13 cardio-metabolic biomarkers, the AE-DII was only significantly negatively associated with albumin and high-density lipoprotein cholesterol, and positively with waist circumference and fasting glucose, upon full adjustment. Conclusion: Rural men consumed the most pro-inflammatory diet, and urban women the least pro-inflammatory diet. The diet of the participants was not overtly pro- or anti-inflammatory and was not associated with measured inflammatory markers. The inflammatory potential of alcohol at different levels of intake requires further research. Understanding dietary inflammatory potential in the context of food insecurity, unhealthy lifestyle practices and lack of dietary variety remains limited

Development of a food composition database for assessing nitrate and nitrite intake from animal-based foods

Scope: Nitrate and nitrite are approved food additives in some animal-based food products. However, nitrate and nitrite in foods are strictly regulated due to health concerns over methaemoglobinaemia and the potential formation of carcinogenic nitrosamines. In contrast, plants (like leafy vegetables) naturally accumulate nitrate ions; a growing body of research reveals beneficial metabolic effects of nitrate via its endogenous conversion to nitric oxide. To refine the association of dietary nitrate and nitrite intake with health outcomes, reliable measures of nitrate and nitrite intake from dietary food records are required. While a vegetable nitrate content database has been developed, there is a need for a comprehensive up-to-date nitrate and nitrite content database of animal-based foods. Methods and Results: A systematic literature search (1980–September 2020) on the nitrate and nitrite content of animal-based foods is carried out. Nitrate and nitrite concentration data and other relevant information are extracted and compiled into a database. The database contains 1921 entries for nitrate and 2077 for nitrite, extracted from 193 publications. The highest median nitrate content is observed in chorizo (median [IQR]; 101.61 [60.05–105.93] mg kg-1). Canned fish products have the highest median nitrite level (median [IQR]; 20.32 [6.16–30.16] mg kg-1). By subgroup, the median nitrate value in industrial processed meat products (e.g., uncured burger, patties and sausages), whole milk powder and in particular red meat are higher than cured meat products. Processed meat products from high-income regions have lower median nitrate and nitrite content than those of middle-income regions. Conclusion: This database can now be used to investigate the associations between nitrate and nitrite dietary intake and health outcomes in clinical trials and observational studies

Flavonoid-Rich Apple Improves Endothelial Function in Individuals at Risk for Cardiovascular Disease: A Randomized Controlled Clinical Trial

Scope The cardioprotective effects of apples are primarily attributed to flavonoids, found predominantly in the skin. This study aimed to determine if acute and/or chronic (4 weeks) ingestion of flavonoid-rich apples improves endothelial function, blood pressure (BP), and arterial stiffness in individuals at risk for cardiovascular diseases (CVD). Methods and results In this randomized, controlled cross-over trial, acute and 4 week intake of apple with skin (high flavonoid apple, HFA) is compared to intake of apple flesh only (low flavonoid apple, LFA) in 30 participants. The primary outcome is endothelial function assessed using flow-mediated dilation (FMD) of the brachial artery, while main secondary outcomes are 24 h ambulatory BP and arterial stiffness. Other outcomes include fasting serum glucose and lipoprotein profile, plasma heme oxygenase-1 (Hmox-1), F2-isoprostanes, flavonoid metabolites, and plasma and salivary nitrate (NO3−) and nitrite (NO2−) concentrations. Compared to LFA control, the HFA results in a significant increase in FMD acutely (0.8%, p \u3c 0.001) and after 4 weeks chronic intake (0.5%, p \u3c 0.001), and in plasma flavonoid metabolites (p \u3c 0.0001). Other outcomes are not altered significantly. Conclusion A lower risk of CVD with higher apple consumption could be mediated by the beneficial effect of apple skin on endothelial function, both acutely and chronically

Nitrate: The Dr. Jekyll and Mr. Hyde of human health?

Background: Dietary nitrate has a controversial role in human health. For over half a century, the nitrate content of the three major dietary sources – vegetables, meat, and water – has been legislated, regulated, and monitored due to public health concerns over cancer risk. In contrast, a growing and compelling body of evidence indicates that dietary nitrate, particularly from vegetables, protects against cardiovascular disease and other chronic diseases. This evidence for the protective effect of nitrate is overshadowed by the potential for nitrate to form carcinogenic N-nitrosamines. Scope and approach: The nitrate content, regulations and estimated intake from vegetables, meat and water are described. The evidence that nitrate, through its effects on nitric oxide, improves cardiovascular disease outcomes, cognitive health, musculoskeletal health, and exercise performance as well as the potential to protect against other debilitating health outcomes (nitrate as Dr Jekyll) is discussed. The underlying assumption that all nitrate, irrespective of source, leads to the formation of carcinogenic N-nitrosamines and the evidence of an association between the different sources of nitrate and cancer (nitrate as Mr Hyde) is examined. Key findings and conclusions: The current theory that nitrate, is a carcinogenic contaminant in meat, water, and vegetables is not fully supported by available evidence. Definitive studies examining the beneficial or harmful effects of source-dependent nitrate have yet to be performed. Studies with improved exposure assessment and accurate characterization of factors that affect endogenous nitrosation are also needed to draw conclusions about risk of cancer from dietary nitrate intake

Associations between habitual flavonoid intake and hospital admissions for atherosclerotic cardiovascular disease: A prospective cohort study

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 (\u3e20 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

Higher habitual flavonoid intakes are associated with a lower risk of peripheral artery disease hospitalizations

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 Phenol-Explorer database. Associations were examined using multivariable-adjusted 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 ∼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

Habitual flavonoid intake and ischemic stroke incidence in the Danish diet, cancer, and health cohort

Background Flavonoid-rich foods have antiinflammatory, antiatherogenic, and antithrombotic properties that may contribute to a lower risk of ischemic stroke. Objectives We aimed to investigate the relationship between habitual flavonoid consumption and incidence of ischemic stroke in participants from the Danish Diet, Cancer and Health Study. Design In this prospective cohort study, 55,169 Danish residents without a prior ischemic stroke [median (IQR) age at enrolment of 56 y (52–60)], were followed for 21 y (20–22). We used Phenol-Explorer to estimate flavonoid intake from food frequency questionnaires obtained at study entry. Incident cases of ischemic stroke were identified from Danish nationwide registries and restricted cubic splines in Cox proportional hazards models were used to investigate relationships with flavonoid intake. Results During follow-up, 4237 individuals experienced an ischemic stroke. Compared with participants in Q1 and after multivariable adjustment for demographics and lifestyle factors, those in Q5—for intake of total flavonoids, flavonols, and flavanol 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. Multivariable (demographic and lifestyle) adjusted associations for anthocyanins and flavones with risk of ischemic stroke were not linear, with moderate but not higher intakes associated with lower risk [anthocyanins Q3 vs. Q1 HR (95% CI): 0.85 (0.79, 0.93); flavones: 0.90 (0.84, 0.97)]. Following additional adjustment for dietary confounders, similar point estimates were observed; however, significance was only retained for anthocyanins and flavanol oligo + polymers [anthocyanins Q3 vs. Q1 HR (95% CI): 0.86 (0.79, 0.94); flavanol oligo + polymers Q5 vs. Q1 0.86 (0.78, 0.94)]. Conclusions These findings suggest that moderate habitual consumption of healthy flavonoid-rich foods is associated with a lower risk of ischemic stroke and further investigation is therefore warranted