Flavonoids and nitrates in fruits and vegetables may protect against cardiovascular disease. Dietary flavonoids and nitrates can augment nitric oxide status via distinct pathways, which may improve ...endothelial function and lower blood pressure. Recent studies suggest that the combination of flavonoids and nitrates can enhance nitric oxide production in the stomach. Their combined effect in the circulation is unclear. Here, our objective was to investigate the independent and additive effects of flavonoid-rich apples and nitrate-rich spinach on nitric oxide status, endothelial function, and blood pressure. A randomized, controlled, crossover trial with healthy men and women (n=30) was conducted. The acute effects of four energy-matched treatments (control, apple, spinach, and apple+spinach), administered in random order, were compared. Measurements included plasma nitric oxide status, assessed by measuring S-nitrosothiols+other nitrosylated species (RXNO) and nitrite, blood pressure, and endothelial function, measured as flow-mediated dilatation of the brachial artery. Results are means and 95% CI. Relative to control, all treatments resulted in higher RXNO (control, 33nmol/L, 26, 42; apple, 51nmol/L, 40, 65; spinach, 86nmol/L, 68, 110; apple+spinach, 69nmol/L, 54, 88; P<0.01) and higher nitrite (control, 35nmol/L, 27, 46; apple, 69nmol/L, 53, 90; spinach, 99nmol/L, 76, 129; apple+spinach, 80nmol/L, 61, 104; P<0.01). Compared to control, all treatments resulted in higher flow-mediated dilatation (P<0.05) and lower pulse pressure (P<0.05), and apple and spinach resulted in lower systolic blood pressure (P<0.05). No significant effect was observed on diastolic blood pressure. The combination of apple and spinach did not result in additive effects on nitric oxide status, endothelial function, or blood pressure. In conclusion, flavonoid-rich apples and nitrate-rich spinach can independently augment nitric oxide status, enhance endothelial function, and lower blood pressure acutely, outcomes that may benefit cardiovascular health.
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► Flavonoids and nitrates can augment nitric oxide status via distinct pathways ► We investigate acute effects of flavonoid-rich apples and nitrate-rich spinach ► We employ a randomised controlled, crossover trial including healthy men and women ► Apples and spinach enhance nitric oxide status and improve endothelial function
Apples are an important contributor to the intake of dietary components linked with cardiovascular disease (CVD) prevention. Apples have been shown to have beneficial effects on vascular function, ...blood pressure, lipids, inflammation and hyperglycaemia. The cardioprotective effects of apples, and other fruits, have been primarily ascribed to their high polyphenol content. There is emerging evidence that the bioavailability and bioefficacy of polyphenols is affected by the food matrix in which they are consumed.
This review will discuss the differences in the consumption of apple as a whole food in comparison to the consumption of isolated key components, predominantly polyphenols and fibre. The bioavailability and absorption of major apple polyphenols, such as procyanidins, catechin, epicatechin, phloridzin, chlorogenic acid, and the quercetin glycosides, will be described. The methods by which apples may ameliorate risk factors for CVD will be discussed and results from key human intervention studies conferred. The list of studies described in this paper is exemplary and not exhaustive.
There are a number of factors influencing the bioavailability of polyphenols in an individual including colonic microbial composition, the dose consumed and the presence of other polyphenols and macronutrients within the food matrix. There is evidence of a synergistic relationship between the fibre and flavonoids found in a whole apple, which is likely mediated in part by the gut microbiota. Further human intervention studies investigating the effects of apples of cardiovascular risk factors, and the critical role of the gut microbiota, are warranted.
•The effect of the apple food matrix on absorption of polyphenols is described.•Role of the gut microbiota in polyphenol metabolism is highlighted.•Potential cardioprotective effects of apples and main apple components discussed.•Results from key human intervention studies with apples or apple products conferred.
Scope
Nitrate from vegetables improves vascular health with short‐term intake. Whether this translates into improved long‐term health outcomes has yet to be investigated. To enable reliable analysis ...of nitrate intake from food records, there is a strong need for a comprehensive nitrate content of vegetables database.
Methods and results
A systematic literature search (1980–2016) was performed using Medline, Agricola and Commonwealth Agricultural Bureaux s databases. The nitrate content of vegetables database contains 4237 records from 255 publications with data on 178 vegetables and 22 herbs and spices. The nitrate content of individual vegetables ranged from Chinese flat cabbage (median; range: 4240; 3004–6310 mg/kg FW) to corn (median; range: 12; 5–1091 mg/kg FW). The database was applied to estimate vegetable nitrate intake using 24‐h dietary recalls (24‐HDRs) and food frequency questionnaires (FFQs). Significant correlations were observed between urinary nitrate excretion and 24‐HDR (r = 0.4, P = 0.013), between 24‐HDR and 12 month FFQs (r = 0.5, P < 0.001) as well as two 4 week FFQs administered 8 weeks apart (r = 0.86, P < 0.001).
Conclusion
This comprehensive nitrate database allows quantification of dietary nitrate from a large variety of vegetables. It can be applied to dietary records to explore the associations between nitrate intake and health outcomes in human studies.
Dietary nitrate found in vegetables increases NO through the NO3‐NO2‐NO pathway improves vascular health. It has yet to be investigated if this translates into improved long‐term health outcomes. To enable reliable analysis of nitrate intake from dietary records,a nitrate content of vegetables database is constructed containing 4237 records from 255 publications with data on 178 vegetables and 22 herbs and spices. This will allow quantification of nitrate from a large variety of vegetables to explore associations between nitrate intake and health outcomes in human studies.
Weight change trajectory from diet and lifestyle interventions typically involves rapid weight loss followed by a weight plateau after approximately 6 months. Changing from one weight-loss diet to ...another at the time of the plateau could instigate renewed weight loss. Therefore, our secondary analysis aimed to assess trajectory of weight loss in a 12-month, randomized, cross-over study. Forty-two adults were randomized to eat a healthy low-fat or healthy low-carbohydrate diet for 6 months then switched to the opposite diet for an additional 6 months. Regardless of diet assignment, participants experienced rapid initial weight loss, which slowed between 3 to 6 months. After switching diets at 6 months, weight modestly decreased until 9 months, but at a rate slower than the initial 3 months and slower than the rate from 3 to 6 months. This suggests that the weight loss plateau typically seen at 6 months is physiological and cannot be overcome by simply switching to a different weight-loss diet.
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 < 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.
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.
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 < 0.001) and after 4 weeks chronic intake (0.5%, p < 0.001), and in plasma flavonoid metabolites (p < 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.
In this randomized, controlled cross‐over study, changes in vascular function were assessed after acute (2 hours) and chronic (4 weeks) ingestion of a high‐flavonoid apple treatment (apple + skin) compared to a low‐flavonoid apple control (apple flesh only). An improvement in vascular function was only seen after the high‐flavonoid apple treatment, providing evidence for the theory that the cardiovascular health benefits of apples are, at least in part, attributable to the high concentration of flavonoids found in apple skin.
Dietary nitrate is an important source of nitric oxide (NO), a molecule critical for cardiovascular health. Nitrate is sequentially reduced to NO through an enterosalivary nitrate-nitrite-NO pathway ...that involves the oral microbiome. This pathway is considered an important adjunct pathway to the classical l-arginine–NO synthase pathway.
The objective of this study was to systematically assess the evidence for dietary nitrate intake and improved cardiovascular health from both human and animal studies.
A systematic literature search was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines by using key search terms in Medline and EMBASE databases and defined inclusion and exclusion criteria.
Thirty-seven articles on humans and 14 articles on animals were included from 12,541 screened references. Data on the effects of dietary nitrate on blood pressure, endothelial function, ischemic reperfusion injury, arterial stiffness, platelet function, and cerebral blood flow in both human and animal models were identified. Beneficial effects of nitrate on vascular health have predominantly been observed in healthy human populations, whereas effects in populations at risk of cardiovascular disease are less clear. Few studies have investigated the long-term effects of dietary nitrate on cardiovascular disease clinical endpoints. In animal studies, there is evidence that nitrate improves blood pressure and endothelial function, particularly in animal models with reduced NO bioavailability. Nitrate dose seems to be a critical factor because there is evidence of cross-talk between the 2 pathways of NO production.
Evidence for a beneficial effect in humans at risk of cardiovascular disease is limited. Furthermore, there is a need to investigate the long-term effects of dietary nitrate on cardiovascular disease clinical endpoints. Further animal studies are required to elucidate the mechanisms behind the observed effects.
The unfolded protein response in the endoplasmic reticulum (UPR
) is involved in a number of metabolic diseases. Here, we characterize UPR
-induced metabolic changes in mouse livers in vivo through ...metabolic labeling and mass spectrometric analysis of lipid and proteome-wide fluxes. We induced UPR
by tunicamycin administration and measured synthesis rates of proteins, fatty acids and cholesterol, as well as RNA-seq. Contrary to reports in isolated cells, hepatic de novo lipogenesis and cholesterogenesis were markedly reduced, as were mRNA levels and synthesis rates of lipogenic proteins. H&E staining showed enrichment with lipid droplets while electron microscopy revealed ER morphological changes. Interestingly, the pre-labeling of adipose tissue prior to UPR
induction resulted in the redistribution of labeled fatty acids from adipose tissue to the liver, with replacement by unlabeled glycerol in the liver acylglycerides, indicating that the liver uptake was of free fatty acids, not whole glycerolipids. The redistribution of adipose fatty acids to the liver was not explicable by altered plasma insulin, increased fatty acid levels (lipolysis) or by reduced food intake. Synthesis of most liver proteins was suppressed under UPR
conditions, with the exception of BiP, other chaperones, protein disulfide isomerases, and proteins of ribosomal biogenesis. Protein synthesis rates generally, but not always, paralleled changes in mRNA. In summary, this combined approach, linking static changes with fluxes, revealed an integrated reduction of lipid and cholesterol synthesis pathways, from gene expression to translation and metabolic flux rates, under UPR
conditions. The reduced lipogenesis does not parallel human fatty liver disease. This approach provides powerful tools to characterize metabolic processes underlying hepatic UPR
in vivo.
Adequate vegetable consumption is one of the cornerstones of a healthy diet. The recommendation to increase vegetable intake is part of most dietary guidelines. Despite widespread and long-running ...public health messages to increase vegetable intake, similar to other countries worldwide, less than 1 in 10 adult Australians manage to meet target advice. Dietary guidelines are predominantly based on studies linking diets high in vegetables with lower risk of chronic diseases. Identifying vegetables with the strongest health benefits and incorporating these into dietary recommendations may enhance public health initiatives around vegetable intake. These enhanced public health initiatives would be targeted at reducing the risk of chronic diseases, such as cardiovascular diseases (CVD). Specific vegetable types contain high levels of particular nutrients and phytochemicals linked with cardiovascular health benefits. However, it is not clear if increasing intake of these specific vegetable types will result in larger benefits on risk of chronic diseases. This review presents an overview of the evidence for the relationships of specific types of vegetables, including leafy green, cruciferous, allium, yellow-orange-red and legumes, with subclinical and clinical CVD outcomes in observational epidemiological studies.
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