Increased nitrate intake from beetroot juice over 4 weeks affects nitrate metabolism, but not vascular function or blood pressure in older adults with hypertension.

The decline in vascular function and increase in blood pressure with aging contribute to an increased cardiovascular disease risk. In this randomized placebo-controlled crossover study, we evaluated whether previously reported cardiovascular benefits of plant-derived inorganic nitrate via nitric oxide (NO) translate into improved vascular function and blood pressure-lowering in 15 men and women (age range: 56-71 years) with treated hypertension. We investigated the effects of a single ∼400 mg-dose at 3 hours post-ingestion (3H POST) and the daily consumption of 2 × âˆ¼400 mg of nitrate through nitrate-rich compared with nitrate-depleted (placebo) beetroot juice over 4 weeks (4WK POST). Measurements included nitrate and nitrite in plasma and saliva; endothelial-dependent and -independent forearm blood flow (FBF) responses to acetylcholine (FBFACh) and glyceryltrinitrate (FBFGTN); and clinic-, home- and 24-hour ambulatory blood pressure. Compared to placebo, plasma and salivary nitrate and nitrite increased at 3H and 4WK POST following nitrate treatment (P < 0.01), suggesting a functioning nitrate-nitrite-NO pathway in the participants of this study. There were no differences between treatments in FBFACh and FBFGTN-area under the curve (AUC) ratios [AUC ratios after (3H POST, 4WK POST) compared with before (PRE) the intervention], or 24-hour ambulatory blood pressure or home blood pressure measures (P > 0.05). These findings do not support the hypothesis that an increased intake of dietary nitrate exerts sustained beneficial effects on FBF or blood pressure in hypertensive older adults, providing important information on the efficacy of nitrate-based interventions for healthy vascular aging. This study was registered under ClinicialTrials.gov (NCT04584372).

Long-term dietary nitrate supplementation slows the progression of established atherosclerosis in ApoE-/- mice fed a high fat diet.

BACKGROUND AND AIMS: Atherosclerosis is associated with a reduction in the bioavailability and/or bioactivity of endogenous nitric oxide (NO). Dietary nitrate has been proposed as an alternate source when endogenous NO production is reduced. Our previous study demonstrated a protective effect of dietary nitrate on the development of atherosclerosis in the apoE-/- mouse model. However most patients do not present clinically until well after the disease is established. The aims of this study were to determine whether chronic dietary nitrate supplementation can prevent or reverse the progression of atherosclerosis after disease is already established, as well as to explore the underlying mechanism of these cardiovascular protective effects. METHODS: 60 apoE-/- mice were given a high fat diet (HFD) for 12 weeks to allow for the development of atherosclerosis. The mice were then randomized to (i) control group (HFD + 1 mmol/kg/day NaCl), (ii) moderate-dose group (HFD +1 mmol/kg/day NaNO3), or (iii) high-dose group (HFD + 10 mmol/kg/day NaNO3) (20/group) for a further 12 weeks. A group of apoE-/- mice (n = 20) consumed a normal laboratory chow diet for 24 weeks and were included as a reference group. RESULTS: Long-term supplementation with high dose nitrate resulted in ~ 50% reduction in plaque lesion area. Collagen expression and smooth muscle accumulation were increased, and lipid deposition and macrophage accumulation were reduced within atherosclerotic plaques of mice supplemented with high dose nitrate. These changes were associated with an increase in nitrite reductase as well as activation of the endogenous eNOS-NO pathway. CONCLUSION: Long-term high dose nitrate significantly attenuated the progression of established atherosclerosis in the apoE-/- mice fed a HFD. This appears to be mediated in part through a XOR-dependent reduction of nitrate to NO, as well as enhanced eNOS activation via increased Akt and eNOS phosphorylation.

Beneficial effects of inorganic nitrate in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic representation of the metabolic disorders. Inorganic nitrate/nitrite can be converted to nitric oxide, regulate glucose metabolism, lower lipid levels, and reduce inflammation, thus raising the hypothesis that inorganic nitrate/nitrite could be beneficial for improving NAFLD. This study assessed the therapeutic effects of chronic dietary nitrate on NAFLD in a mouse model. 60 ApoE-/- mice were fed a high-fat diet (HFD) for 12 weeks to allow for the development of atherosclerosis with associated NAFLD. The mice were then randomly assigned to different groups (20/group) for a further 12 weeks: (i) HFD + NaCl (1 mmol/kg/day), (ii) HFD + NaNO3 (1 mmol/kg/day), and (iii) HFD + NaNO3 (10 mmol/kg/day). A fourth group of ApoE-/- mice consumed a normal chow diet for the duration of the study. At the end of the treatment, caecum contents, serum, and liver were collected. Consumption of the HFD resulted in significantly greater lipid accumulation in the liver compared to mice on the normal chow diet. Mice whose HFD was supplemented with dietary nitrate for the second half of the study, showed an attenuation in hepatic lipid accumulation. This was also associated with an increase in hepatic AMPK activity compared to mice on the HFD. In addition, a significant difference in bile acid profile was detected between mice on the HFD and those receiving the high dose nitrate supplemented HFD. In conclusion, dietary nitrate attenuates the progression of liver steatosis in ApoE-/- mice fed a HFD.

Phenolic composition of 91 Australian apple varieties: towards understanding their health attributes.

INTRODUCTION: Apples, an important contributor to total dietary phenolic intake, are associated with cardiovascular health benefits. Determining the phenolic composition of apples, their individual variation across varieties, and the phenolic compounds present in plasma after apple consumption is integral to understanding the effects of apple phenolics on cardiovascular health. METHODS: Using liquid chromatography we quantified five important polyphenols and one phenolic acid with potential health benefits: quercetin glycosides, (-)-epicatechin, procyanidin B2, phloridzin, anthocyanins, and chlorogenic acid, in the skin and flesh of 19 apple varieties and 72 breeding selections from the Australian National Apple Breeding program. Furthermore, we measured the phenolic compounds in the plasma of 30 individuals post-consumption of an identified phenolic-rich apple, Cripp's Pink. RESULTS: Considerable variation in concentration of phenolic compounds was found between genotypes: quercetin (mean ± SD: 16.1 ± 5.9, range: 5.8-30.1 mg per 100 g); (-)-epicatechin (mean ± SD: 8.6 ± 5.8, range: 0.2-19.8 mg per 100 g); procyanidin B2 (mean ± SD: 11.5 ± 6.6, range: 0.5-26.5 mg per 100 g); phloridzin (mean ± SD: 1.1 ± 0.6, range: 0.3-4.3 mg per 100 g); anthocyanins (mean ± SD: 1.8 ± 4.4, range: 0-40.8 mg per 100 g); and chlorogenic acid (mean ± SD: 11.3 ± 9.9, range: 0.4-56.0 mg per 100 g). All phenolic compounds except chlorogenic acid were more concentrated in the skin compared with flesh. We observed a significant increase, with wide variation, in 14 phenolic compounds in plasma post-consumption of a phenolic-rich apple. CONCLUSION: This information makes an important contribution to understanding the potential health benefits of apples.

Quantifying dietary vitamin K and its link to cardiovascular health: a narrative review.

Cardiovascular disease is the leading cause of death and disability worldwide. Recent work suggests a link between vitamin K insufficiency and deficiency with vascular calcification, a marker of advanced atherosclerosis. Vitamin K refers to a group of fat-soluble vitamins important for blood coagulation, reducing inflammation, regulating blood calcium metabolism, as well as bone metabolism, all of which may play a role in promoting cardiovascular health. Presently, there is a lack of a comprehensive vitamin K database on individual foods, which are required to accurately calculate vitamin K1 and K2 intake for examination in epidemiological studies. This has likely contributed to ambiguity regarding the recommended daily intake of vitamin K, including whether vitamin K1 and K2 may have separate, partly overlapping functions. This review will discuss the presence of: (i) vitamin K1 and K2 in the diet; (ii) the methods of quantitating vitamin K compounds in foods; and (iii) provide an overview of the evidence for the cardiovascular health benefits of vitamin K in observational and clinical trials.

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

Flavonoids, plant-derived polyphenolic compounds, have been linked with health benefits. However, evidence from observational studies is incomplete; studies on cancer mortality are scarce and moderating effects of lifestyle risk factors for early mortality are unknown. In this prospective cohort study including 56,048 participants of the Danish Diet, Cancer, and Health cohort crosslinked with Danish nationwide registries and followed for 23 years, there are 14,083 deaths. A moderate habitual intake of flavonoids is inversely associated with all-cause, cardiovascular- and cancer-related mortality. This strong association plateaus at intakes of approximately 500 mg/day. Furthermore, the inverse associations between total flavonoid intake and mortality outcomes are stronger and more linear in smokers than in non-smokers, as well as in heavy (>20 g/d) vs. low-moderate (<20 g/d) alcohol consumers. These findings highlight the potential to reduce mortality through recommendations to increase intakes of flavonoid-rich foods, particularly in smokers and high alcohol consumers.

Effect of adding milk to black tea on vascular function in healthy men and women: a randomised controlled crossover trial.

BACKGROUND: Tea consumption may improve endothelial function and blood pressure via increased bioavailability and bioactivity of nitric oxide. However, questions remain as to the impact of the common practice of adding milk. OBJECTIVE: To investigate the effect of regular consumption of black tea, with and without milk, on vascular function and blood pressure in healthy volunteers. DESIGN: A randomised, controlled, crossover study was performed in 17 healthy volunteers; 7 men and 10 women, mean age 22.4 ± 3.0 years. Participants received each of the following treatments in random order for 4 weeks, with no washout period in between, (i) hot water, (ii) black tea and (iii) black tea with milk. Vascular function was assessed using flow-mediated dilatation (FMD) of the brachial artery at the end of each treatment period. In addition, participants monitored their home blood pressure for the last 7 days of each treatment period. A blood and urine sample was also collected at the end of each treatment period. RESULTS: Black tea increased FMD compared to the hot water control group (1.00 ± 0.18%, P < 0.0001). Black tea with milk decreased FMD compared to both the hot water control (-0.64 ± 0.19%, P = 0.001) and black tea (-1.64 ± 0.19%, P < 0.0001). Compared with hot water, black tea did not alter blood pressure, while black tea with milk increased systolic (1.1 ± 0.5 mmHg, P = 0.03) and diastolic blood pressure (2.0 ± 0.5 mmHg, P < 0.0001). Black tea (-1.8 ± 0.5 bpm, P < 0.001) and black tea with milk (-1.8 ± 0.6 bpm, P < 0.001) lowered heart rate compared to hot water. No significant difference for plasma nitrate or nitrite was observed between treatment groups. CONCLUSIONS: The addition of milk to black tea alters the acute/short-term impact of regular tea consumption on vascular function and blood pressure in young healthy men and women. The exact mechanism for this affect remains unknown and longer-term trials to establish this effect in a range of populations are warranted.

Effect of dietary nitrate supplementation on thermoregulatory and cardiovascular responses to submaximal cycling in the heat.

PURPOSE: This study investigated whether reported improvements in blood flow distribution, and the possible related effects on thermoregulation during exercise following supplementation with beetroot juice (BR), a rich source of dietary nitrate (NO3-), are mitigated in the heat. METHODS: 12 male endurance-trained cyclists (age 27 ± 6 years, VO2peak 68.6 ± 8.1 ml kg-1 min-1) completed two 60 min submaximal cycling trials at 60% of VO2peak power output. Trials were performed in hot environmental conditions (33.3 ± 0.4 °C, 48.8 ± 3.0% RH) following 3 days of supplementation with either NO3--rich BR (6.5 mmol NO3- for 2 days and 13 mmol NO3- on the final day) or NO3--depleted placebo (PLA). Salivary NO3- and nitrite (NO2-) were measured before and after the supplementation period. During exercise, cutaneous blood flow, blood pressure (MAP), core temperature (Tc), mean skin temperature (Tsk), indices of muscle oxygenation and oxygen (O2) consumption were measured. RESULTS: Salivary NO3- and NO2- increased significantly following BR by 680 and 890%, respectively. There were no significant differences observed for cutaneous blood flow, MAP, Tc, Tsk, muscle oxygenation, or O2 consumption between BR and PLA. CONCLUSION: This investigation shows that the ergogenic effects and health benefits of BR supplementation, such as augmented cutaneous blood flow, reduced MAP, increased muscle oxygenation, and improved aerobic efficiency may be attenuated when exercise is performed in hot conditions.

Dietary nitrate supplementation does not improve cycling time-trial performance in the heat.

This investigation examined the effect of beetroot juice (BR) supplementation, a source of dietary nitrate (NO3-), on cycling time-trial (TT) performance and thermoregulation in the heat. In a double-blind, repeated-measures design, 12 male cyclists (age 26.6 ± 4.4 years, VO2peak 65.8 ± 5.5 mL.kg-1.min-1) completed four cycling TTs (14 kJ.kg-1) in hot (35°C, 48% relative humidity) and euthermic (21°C, 52%) conditions, following 3 days supplementation with BR (6.5 mmol NO3- for 2 days and 13 mmol NO3- on the final day), or NO3-depleted placebo (PLA). Salivary NO3- and nitrite, core (Tc) and mean skin temperature (Tsk) were measured. Salivary NO3- and nitrite increased significantly post-BR supplementation (p < 0.001). Average TT completion time (mm:ss) in hot conditions was 56:50 ± 05:08 with BR, compared with 58:30 ± 04:48 with PLA (p = 0.178). In euthermic conditions, average completion time was 53:09 ± 04:35 with BR, compared with 54:01 ± 04:05 with PLA (p = 0.380). The TT performance decreased (p < 0.001), and Tc (p < 0.001) and Tsk (p < 0.001) were higher in hot compared with euthermic conditions. In summary, BR supplementation has no significant effect on cycling TT performance in the heat.

Screening plant derived dietary phenolic compounds for bioactivity related to cardiovascular disease.

The potential health benefits of phenolic acids found in food and beverages has been suggested from a number of large population studies. However, the mechanism of how these compounds may exert biological effects is less well established. It is also now recognised that many complex polyphenols in the diet are metabolised to simple phenolic acids which can be taken up in the circulation. In this paper a number of selected phenolic compounds have been tested for their bioactivity in two cell culture models. The expression and activity of endothelial nitric oxide synthase (eNOS) in human aortic endothelial cells and the uptake of glucose in muscle cells. Our data indicate that while none of the compounds tested had a significant effect on eNOS expression or activation in endothelial cells, several of the compounds increased glucose uptake in muscle cells. These compounds also enhanced the translocation of the glucose transporter GLUT4 to the plasma membrane, which may explain the observed increase in cellular glucose uptake. These results indicate that simple cell culture models may be useful to help understand the bioactivity of phenolic compounds in relation to cardiovascular protection.

The acute effect of coffee on endothelial function and glucose metabolism following a glucose load in healthy human volunteers.

A diet rich in plant polyphenols has been suggested to reduce the incidence of cardiovascular disease and type 2 diabetes mellitus, in part, via improvements in endothelial function. Coffee is a rich source of phenolic compounds including the phenolic acid, chlorogenic acid (CGA). The aim of the study was to investigate the effect of coffee as a whole beverage on endothelial function, blood pressure and blood glucose concentration. Twelve healthy men and women were recruited to a randomised, placebo-controlled, cross-over study, with three treatments tested: (i) 18 g of ground caffeinated coffee containing 300 mg CGA in 200 mL of hot water, (ii) 18 g of decaffeinated coffee containing 287 mg CGA in 200 mL of hot water, and (iii) 200 mL of hot water (control). Treatment beverages were consumed twice, two hours apart, with the second beverage consumed simultaneously with a 75 g glucose load. Blood pressure was recorded and the finger prick glucose test was performed at time = 0 and then every 30 minutes up to 2 hours. Endothelial function, assessed using flow-mediated dilatation (FMD) of the brachial artery, was measured at 1 hour and a blood sample taken at 2 hours to measure plasma nitrate/nitrite and 5-CGA concentrations. The FMD response was significantly higher in the caffeinated coffee group compared to both decaffeinated coffee and water groups (P < 0.001). There was no significant difference in the FMD response between decaffeinated coffee and water. Blood glucose concentrations and blood pressure were not different between the three treatment groups. In conclusion, the consumption of caffeinated coffee resulted in a significant improvement in endothelial function, but there was no evidence for benefit regarding glucose metabolism or blood pressure. Although the mechanism has yet to be elucidated the results suggest that coffee as a whole beverage may improve endothelial function, or that caffeine is the component of coffee responsible for improving FMD.

Antihypertensive and antioxidant effects of supplementation with red wine pomace in spontaneously hypertensive rats.

Hypertension is associated with enhanced vascular oxidative stress and impaired endothelial function, which is related to an imbalance between reactive oxygen species and nitric oxide bioavailability. Short-term supplementation with a polyphenol-rich powdered red wine pomace seasoning (RWPS) was investigated for its effects on blood pressure and biomarkers of endothelial dysfunction and oxidative status in a model of essential hypertension. Male spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (12-week-old, 5 rats per group) were administered RWPS (300 mg kg-1 day-1; equivalent to 7.32 mg gallic acid per kg per day) or vehicle by gavage. In SHRs, 4-week RWPS supplementation progressively decreased blood pressure, reaching 11.5% reduction at the end of the study (p < 0.001). RWPS consumption also increased the ferric reducing ability of plasma and attenuated the oxidation of plasma lipids and proteins, as evidenced by F2-isoprostanes, malondialdehyde and protein carbonyl groups as oxidative stress biomarkers. Moreover, nitric oxide production (indirectly measured) was 1.5-fold higher in SHRs + RWPS than that in SHRs (p < 0.05). These beneficial effects were partly attributed to the ability of RWPS-derived bioactive compounds to modulate aortic gene expression, with eNOS, SOD2 and HO-1 over-expression, ACE down-regulation, and no changes in NOX4. In conclusion, this study suggests the potential of red wine pomace-derived seasonings to help in the management of hypertension.

Association of dietary nitrate with atherosclerotic vascular disease mortality: a prospective cohort study of older adult women.

Background: Nitrate-rich vegetables lower blood pressure and improve endothelial function in humans. It is not known, however, whether increased consumption of nitrate-rich vegetables translates to a lower risk of atherosclerotic vascular disease (ASVD) mortality.Objective: The objective was to investigate the association of nitrate intake from vegetables with ASVD mortality.Design: A total of 1226 Australian women aged 70-85 y without prevalent ASVD and/or diabetes were recruited in 1998 and were studied for 15 y. We assessed demographic and ASVD risk factors at baseline (1998), and we used a validated food-frequency questionnaire to evaluate dietary intake. Nitrate intake from vegetables was calculated by use of a newly developed comprehensive database. The primary outcome was any death attributed to ASVD ascertained by using linked data that were provided via the Western Australian Data Linkage system. We used Cox proportional hazards modeling to examine the association between nitrate intake and ASVD mortality before and after adjustment for lifestyle and cardiovascular disease risk factors.Results: During a follow-up period of 15,947 person-years, 238 of 1226 (19.4%) women died of ASVD-related causes. The mean ± SD vegetable nitrate intake was 67.0 ± 29.2 mg/d. Each SD higher vegetable nitrate intake was associated with a lower risk of ASVD mortality in both unadjusted [HR: 0.80 (95% CI: 0.70, 0.92), P = 0.002] and multivariable-adjusted [HR: 0.79 (95% CI: 0.68, 0.93), P = 0.004] analyses. This relation was attenuated after further adjustment for diet quality [HR: 0.85 (95% CI: 0.72, 1.01), P = 0.072]. Higher vegetable nitrate intake (per SD) also was associated with a lower risk of all-cause mortality [multivariable-adjusted HR: 0.87 (95% CI: 0.78, 0.97), P = 0.011].Conclusions: Nitrate intake from vegetables was inversely associated with ASVD mortality independent of lifestyle and cardiovascular disease risk factors in this population of older adult women without prevalent ASVD or diabetes. These results support the concept that nitrate-rich vegetables may reduce the risk of age-related ASVD mortality. This trial was registered at www.anzctr.org.au as ACTRN12617000640303.

Attenuation of oxidative stress in Type 1 diabetic rats supplemented with a seasoning obtained from winemaking by-products and its effect on endothelial function.

Type 1 diabetes mellitus (DM) is characterized by hyperglycemia resulting from insulin deficiency. This is usually accompanied by a pro-oxidative environment, dyslipidemia and endothelial dysfunction, thus leading to several micro- and macro-vascular complications. This study investigated the potential benefits of a seasoning obtained from seedless red wine pomace (RWPS) in protecting against oxidative damage and preserving endothelial function in Type 1 DM, and the underlying mechanisms involved at the level of gene expression. The diet of streptozotocin (45 mg kg-1)-induced diabetic (DB) and control (CN) male Wistar rats (n = 5 rats per group) was supplemented with RWPS (300 mg per kg per day) or vehicle for 4 weeks. Characteristic indicators of DM such as increased food and water intakes and weight loss were significantly ameliorated in DB + RWPS rats, with a notable normalization in their fasting glycemic control and cholesterol profile. Plasma total antioxidant capacity (TAC) was substantially increased, and biomarkers of oxidative damage to lipids (F2-isoprostanes, 24.9%; malondialdehyde, 28.4%) and proteins (carbonyl groups, 5.91%) were significantly decreased. Nitric oxide availability tended to improve in plasma of DB + RWPS compared with DB rats. Insulin levels were increased (1.51-fold) and aortic tissue antioxidant enzymes such as mitochondrial superoxide dismutase (SOD2, 1.93-fold) were up-regulated. Other important genes for endothelial function, including endothelial ß-nicotinamide adenine dinucleotide phosphate oxidase (NOX4), endothelial and inducible nitric oxide synthases (eNOS, iNOS), and angiotensin-converting enzyme-I (ACE), were non-significantly modulated, although certain potentially positive trends were observed. These results indicate that RWPS supplementation might be a useful nutritional approach to manage Type 1 DM and ameliorate its vascular complications.

Hypolipidemic and cardioprotective benefits of a novel fireberry hawthorn fruit extract in the JCR:LA-cp rodent model of dyslipidemia and cardiac dysfunction.

Hawthorn is a widely used herbal alternative medicine for the treatment of various cardiovascular diseases. However, the attributed health benefits, purported to be due to the presence of phenolic compounds, may depend on both the specific species and plant part. Studies to date investigating effects of hawthorn on heart disease(s) have used well-described European and/or Asian species, while little is known regarding the bioactivity of species native to North America. Six weeks of supplementation of both fireberry hawthorn berry (native Crataegus chrysocarpa) and English hawthorn leaf (C. monogyna, naturalized in North America) in the JCR:LA-cp rat, resulted in a significant reduction in heart weight, fasting LDL-C and improved heart function (p < 0.05). Fasting triglyceride and myocardial fibrosis were also reduced, but only by the berry extract. We demonstrate that both of the Canadian-sourced hawthorn extracts (introduced leaf and native berry) have cardioprotective benefits, likely via increased availability of nitric oxide.

Acute effects of quercetin-3-O-glucoside on endothelial function and blood pressure: a randomized dose-response study.

BACKGROUND: Epidemiologic studies have suggested that a flavonoid-rich diet can reduce the risk of developing cardiovascular disease. Certain flavonoids, in particular quercetin, have been shown to ameliorate endothelial dysfunction and reduce blood pressure (BP), possibly by increasing the bioavailability of the potent vasodilator nitric oxide (NO). Several studies have indicated that improvements in measures of cardiovascular health do not occur linearly, but rather, plateau or decrease with an increasing dose of flavonoids. OBJECTIVES: We determined whether the acute administration of increasing doses of a common quercetin glycoside (quercetin-3-O-glucoside) improves endothelial function and reduces BP in a dose-dependent manner. We also explored whether any effects were correlated with changes in plasma NO production. DESIGN: A randomized, controlled, crossover study was performed in 15 healthy volunteers who each completed 5 visits with a minimum washout period of 1 wk between testing days. Participants received each of the following 5 interventions in a random order: 1) 0, 2) 50, 3) 100, 4) 200, or 5) 400 mg quercetin-3-O-glucoside. Endothelial function and BP were assessed before and 60 min after intervention. A blood sample was taken before and 90 min after intervention for the analysis of plasma nitrate and nitrite as markers of NO production as well as of plasma quercetin metabolites. RESULTS: Although we observed a significant correlation between the dose of quercetin-3-O-glucoside and plasma concentrations of total quercetin (R(2) = 0.52, P < 0.001) and isorhamnetin (R(2) = 0.12, P = 0.005), we showed no improvements in endothelial function or BP and no changes in NO production after any dose. CONCLUSION: From these results, we conclude that there are no acute changes in BP or the NO-mediated endothelium-dependent relaxation of the brachial artery with doses of quercetin ranging from 50 to 400 mg in healthy men and women. This trial was registered at www.anzctr.org.au as ACTRN12615001338550.

Acute effects of chlorogenic acids on endothelial function and blood pressure in healthy men and women.

Coffee is a rich source of polyphenols, primarily chlorogenic acids (CGA). Certain polyphenols and polyphenol-rich foods and beverages have been shown to improve endothelial function and lower blood pressure (BP). The aim of the present study was to investigate the acute effect of two doses of CGA (5-CGA) on endothelial function and BP. In a cross-over study, 16 healthy men and women received: (i) 0 mg purified 5-CGA (control group); (ii) 450 mg purified 5-CGA; (iii) 900 mg purified 5-CGA; and (iv) 200 mg purified (-)-epicatechin (positive control) in random order one week apart. Peak and continuous mean (60 to 240 s post ischaemia) flow-mediated dilation (FMD) was measured at baseline, 1 h and 4 h. BP was measured at baseline and every 30 min to 4 h. Plasma CGA and epicatechin levels were significantly increased at both 1 h and 4 h post their respective treatments. Peak FMD was not significantly altered by either dose of 5-CGA or the epicatechin, relative to control (p > 0.05). Relative to control, effects on continuous mean FMD response following 450 mg 5-CGA and 900 mg of 5-CGA (0.47 ± 0.16%, p = 0.016 and 0.65 ± 0.16%, p < 0.001, respectively) at 1 h and (0.18 ± 0.17%, p = 0.99 and 0.44 ± 0.16%, p < 0.05, respectively) at 4 h. There was no significant effect of any of the treatments on BP. In conclusion, the present study has found no significant effect of 5-CGA, at 450 and 900 mg, on peak FMD response. However, there were significant improvements in mean post-ischaemic FMD response, particularly at the 1 h time point in this group of healthy individuals.

Specialized proresolving lipid mediators in humans with the metabolic syndrome after n-3 fatty acids and aspirin.

BACKGROUND: The metabolic syndrome (MetS) is associated with a chronic low-grade inflammatory state and may be affected by the ability to resolve inflammation, which is an active process that involves specialized proresolving lipid mediators (SPMs) derived from n-3 (ω-3) fatty acids. OBJECTIVE: We compared plasma concentrations of SPMs in men and women with features of the MetS and in healthy matched control subjects in response to intakes of n-3 fatty acids and aspirin. DESIGN: MetS volunteers (n = 22) and healthy, matched controls (n = 21) were studied in parallel for 4 wk. Both groups took n-3 fatty acids (2.4 g/d) for 4 wk with the addition of aspirin (300 mg/d) during the last 7 d. Blood was collected at baseline and at 3 and 4 wk. Plasma SPMs were measured with the use of liquid chromatography-tandem mass spectrometry and included 18-hydroxyeicosapentaenoic acid (18-HEPE), E-series resolvins, 17-hydroxydocosahexaenoic acid (17-HDHA), D-series resolvins, 14-hydroxydocosahexaenoic acid (14-HDHA), and maresin-1. RESULTS: Baseline SPMs did not differ between groups. There was an increase in the SPM precursors 18-HEPE, 17-HDHA, and 14-HDHA after n-3 fatty acid supplementation that was significantly attenuated in the MetS (P < 0.05). However, the E-series resolvins increased to a similar extent in the groups after n-3 fatty acid supplementation, and the D-series resolvins were not different from those at baseline. The addition of aspirin to n-3 fatty acids did not alter any SPMs in either group. CONCLUSIONS: Volunteers with MetS had reduced plasma concentrations of the precursors of the E- and D- series resolvins as well as of 14-HDHA in response to n-3 fatty acid supplementation. However, plasma E-series resolvins were increased to a similar extent after n-3 fatty acid supplementation in both groups, and the addition of aspirin to n-3 fatty acid supplementation did not alter any of the plasma SPMs in MetS and control subjects. Additional studies in the MetS are required to determine whether SPMs affect the ability to mount an appropriate response to infection. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12610000708055.

Absence of an effect of high nitrate intake from beetroot juice on blood pressure in treated hypertensive individuals: a randomized controlled trial.

BACKGROUND: Dietary nitrate, which is in green leafy vegetables and beetroot, decreases blood pressure through the enterosalivary nitrate-nitrite-nitric oxide pathway in healthy individuals. Whether similar effects would occur in individuals with treated hypertension and, therefore, at increased risk of cardiovascular disease is unclear. OBJECTIVE: We assessed whether increased dietary nitrate intake by using beetroot juice for 1 wk lowers blood pressure in treated hypertensive men and women. DESIGN: Participants (n = 27) were recruited to a randomized, placebo-controlled, double-blind crossover trial. The effect of 1-wk intake of nitrate-rich beetroot juice was compared with 1-wk intake of nitrate-depleted beetroot juice (placebo). The primary outcome was blood pressure assessed by measuring home blood pressure during the intervention and 24-h ambulatory blood pressure on day 7 of the intervention. Other outcomes included nitrate metabolism assessed by measuring nitrate and nitrite in plasma, saliva, and urine. RESULTS: Relative to the placebo, 1-wk intake of nitrate-rich beetroot juice resulted in a 3-fold increase in plasma nitrite and nitrate, a 7-fold increase in salivary nitrite, an 8-fold higher salivary nitrate, and a 4-fold increase in both urinary nitrite and nitrate (P < 0.001). However, no differences in home blood pressure and 24-h ambulatory blood pressure were observed with 1-wk intake of nitrate-rich beetroot juice in comparison with the placebo. CONCLUSION: An increase in dietary nitrate intake may not be an effective short-term approach to further lower blood pressure in treated hypertensive subjects.

Dietary flavonoids and nitrate: effects on nitric oxide and vascular function.

Emerging evidence highlights dietary flavonoids and nitrate as candidates that may explain at least part of the cardioprotective effect of a fruit and vegetable diet. Nitric oxide plays a pivotal role in cardiovascular health. Components of a fruit and vegetable diet that are cardioprotective, in part through effects on nitric oxide status, could substantially reduce the cardiovascular risk profile of the general population with increased intake of such a diet. Epidemiological evidence suggests that dietary flavonoids and nitrate have a cardioprotective effect. Clinical trials with flavonoid- and nitrate-rich foods have shown benefits on measures of vascular health. While the molecular mechanisms by which flavonoids and nitrate are cardioprotective are not completely understood, recent evidence suggests both nonspecific and specific effects through nitric oxide pathways. This review presents an overview of nitric oxide and its key role in cardiovascular health and discusses the possible vascular benefits of flavonoids and nitrate, individually and in combination, through effects on nitric oxide status.