Iron deficiency in heart failure: diagnosis and clinical implications.

Iron deficiency is a widely prevalent finding in patients with heart failure, observed on average in 50% of outpatients and up to 80% of acute patients, regardless of the ejection fraction and the presence of anaemia, being an independent predictor of worst functional capacity and reduced survival. The definition of iron deficiency in heart failure considers the state of chronic inflammation that characterizes the pathology, recognizing a discriminating role for transferrin saturation. The studies conducted so far, which focused on the patient with heart failure with at least moderately reduced ejection fraction, have shown clinical benefit with intravenous supplementation of ferric carboxymaltose in terms of functional capacity, quality of life, laboratory markers of disease and inflammation, and possible reduction of re-hospitalizations, but not in terms of mortality. Based on this evidence, guidelines recommend intravenous ferric carboxymaltose in decompensated and iron-deficient patients, while research is at work to investigate the clinical impact of supplementation in contexts not yet examined, such as that of decompensation in patients with heart failure and preserved ejection fraction.

Acute and Long Term Effects of a Nutraceutical Combination on Lipid Profile, Glucose Metabolism and Vascular Function in Patients with Dyslipidaemia with and Without Cigarette Smoking.

INTRODUCTION: Lifestyle changes present a fundamental role in cardiovascular prevention. Nutraceuticals also supplementing diet could help in controlling the cardiometabolic risk. AIM: (1) to evaluate acute effects of a combination of nutraceuticals (cNUT) on vascular function, BP, metabolism in dyslipidaemic patients before and after smoking; (2) to evaluate 12 weeks effects of the cNUT on lipid profile, insulin resistance and vascular function in patients with hypercholesterolemia not on statins. METHODS: After 14 d run-in period, 33 patients assumed a cNUT [patented formula containing: berberine (531.25 mg), red yeast rice powder (220 mg, 3.3 mg monacolin K) and leaf extract of Morus alba (200 mg) (LopiGLIK®, Akademy Pharma)]. To evaluate acute effects, cNUT or cNUT + smoking (in smoking subjects) on the morning of the first day of the study and then 26 patients prolonged 12 weeks effects. RESULTS: In non smokers, cNUT improved FMD (p = 0.041 for treatment). In smokers, FMD decreased after smoking, this was counteracted by intake of cNUT. In smokers, DBP increased after smoking a cigarette (p = 0.042 for treatment), counteracted by the cNUT intake. In non smokers, thermogenesis was increased after cNUT administration (p < 0.0001 for treatment). After 12 weeks of cNUT, FMD significantly increased (p < 0.05) and SBP (p = 0.04), total cholesterol and LDL cholesterol (p = 0.03) decreased. CONCLUSIONS: Our study suggests benefits of cNUT on cardiovascular prevention in hypercolesterolemic patients, non statin treated, that goes beyond the cholesterol and insulin resistance reduction protecting the subject from negative effects induced by smoking too.

Improvement of Executive Function after Short-Term Administration of an Antioxidants Mix Containing Bacopa, Lycopene, Astaxanthin and Vitamin B12: The BLAtwelve Study.

During the last few years increasing interest has been focused on antioxidants as potentially useful agents in the prevention of the onset and progression of cognitive dysfunction. In this randomized, double-blind, controlled, parallel arm study, the effects of daily consumption of an antioxidant mix on cognitive function in healthy older adults were evaluated. After a 1 week run-in period, 80 subjects aged 60 years or more, and with no evidence of cognitive dysfunction, were randomly allocated to a mix of four bioactive compounds (bacopa, lycopene, astaxanthin, and vitamin B12) or matched placebo, taken orally once a day for 8 weeks. The primary objective of the study was to evaluate the changes in trial making test (TMT) scores from baseline to 8 weeks of treatment, analyzed in the following hierarchical order: TMT-B, TMT-A, and TMT-B minus TMT-A. TMT-B increased in the control group (+3.46 s) and decreased in the active group (-17.63 s). The treatment difference was -21.01 s in favor of the active group (95% C.I. -26.80 to -15.2, p < 0.0001). The decrease in TMT-A was significantly higher in the active group (-6.86 s) than in the control group (-0.37 s). TMT-B minus TMT-A increased in the control group (+3.84 s) and decreased in the active group (-10.46 s). The increase in letter fluency in the verbal fluency test (VFT) was also significantly higher in the active group and statistically significant (+5.28 vs. +1.07 words; p < 0.001). Our findings provide encouraging evidence that regular dietary supplementation with bacopa, lycopene, astaxanthin, and vitamin B12 may be an effective dietary approach for counteracting cognitive changes associated with brain aging.

Neuroprotective activities of bacopa, lycopene, astaxanthin, and vitamin B12 combination on oxidative stress-dependent neuronal death.

Oxidative stress is considered the common effector of the cascade of degenerative events in many neurological conditions. Thus, in this paper we tested different nutraceuticals in H2 O2 in vitro model to understand if could represent an adjuvant treatment for neurological diseases. In this study, nutraceuticals bacopa, lycopene, astaxanthin, and vitamin B12 were used alone or in combination in human neuronal differentiated SH-SY5Y cells upon hydrogen peroxide-induced injury and neuroprotective, neuronal death pathways were analyzed. The nutraceuticals analyzed were able to protect H2 O2 cytotoxic effects, through increasing cell viability and proteins involved in neuroprotection pathways and restoring proteins involved in cell death pathways. On this basis, it is possible to propose the use of these compounds as dietary supplement for the prevention or as adjuvant to the only symptomatic treatments so far available for neurodegenerative diseases.

Nutraceutical support in heart failure: a position paper of the International Lipid Expert Panel (ILEP).

Heart failure (HF) is a complex clinical syndrome that represents a major cause of morbidity and mortality in Western countries. Several nutraceuticals have shown interesting clinical results in HF prevention as well as in the treatment of the early stages of the disease, alone or in combination with pharmacological therapy. The aim of the present expert opinion position paper is to summarise the available clinical evidence on the role of phytochemicals in HF prevention and/or treatment that might be considered in those patients not treated optimally as well as in those with low therapy adherence. The level of evidence and the strength of recommendation of particular HF treatment options were weighed up and graded according to predefined scales. A systematic search strategy was developed to identify trials in PubMed (January 1970 to June 2019). The terms 'nutraceuticals', 'dietary supplements', 'herbal drug' and 'heart failure' or 'left verntricular dysfunction' were used in the literature search. The experts discussed and agreed on the recommendation levels. Available clinical trials reported that the intake of some nutraceuticals (hawthorn, coenzyme Q10, l-carnitine, d-ribose, carnosine, vitamin D, probiotics, n-3 PUFA and beet nitrates) might be associated with improvements in self-perceived quality of life and/or functional parameters such as left ventricular ejection fraction, stroke volume and cardiac output in HF patients, with minimal or no side effects. Those benefits tended to be greater in earlier HF stages. Available clinical evidence supports the usefulness of supplementation with some nutraceuticals to improve HF management in addition to evidence-based pharmacological therapy.

Vitamin D and blood pressure control among hypertensive adults: results from NHANES 2001-2014.

OBJECTIVE: Observational evidence supports an inverse association between hypovitaminosis D and blood pressure (BP), but intervention data have failed to demonstrate beneficial effects of vitamin D supplementation on BP. Following the downwards redefinition of hypertension treatment targets and the need to better identify individuals at greater risk for uncontrolled BP, our aim was to test the association of serum vitamin D levels with the definition of uncontrolled BP according to European guidelines in treated hypertensive adults. METHODS: We retrospectively analyzed cross-sectional, nationally representative data from treated hypertensive adults aged at least 18 years with available serum 25 (OH)D measurements. BP was examined as continuous (mmHg) and categorical (at or above treatment goal, as recommended by guidelines) variable; BP means and odds ratios for uncontrolled BP according to vitamin D levels were calculated using progressively adjusted models. RESULTS: Treated hypertensive adults with vitamin D deficiency had higher mean BP (+2.4/3.5 mmHg; P < 0.01) and 25-29% higher risk of uncontrolled BP compared to those with vitamin levels at least 75 nmol/l. These results were confirmed across age, sex, and racial/ethnic strata. Vitamin D insufficiency was associated with higher BP by 0.5/2.4 mmHg, but not with an increased risk of uncontrolled hypertension. CONCLUSIONS: 25 (OH)D levels might indicate host-specific features related to poor BP control. The attempt to use a biomarker of exposure as an indicator of need for treatment risks to be misleading.

Nutrients and Nutraceuticals for the Management of High Normal Blood Pressure: An Evidence-Based Consensus Document.

Essential hypertension still represents the most common cardiovascular risk factor, which is responsible for the vast majority of global burden of disease, worldwide. Antihypertensive treatment aimed at lowering blood pressure (BP) levels to the recommended therapeutic targets has demonstrated to reduce risk of developing major cardiovascular, cerebrovascular and renal complications. Despite these evidence, overall rates of BP control are dramatically low in most European and Western countries, as well as in the so called developing countries, thus contributing to the increasingly amount of hypertension-related costs and disabilities. For these reasons, preventive strategies aimed at improving BP control rates in treated hypertensive patients and reducing high-normal BP levels in asymptomatic otherwise healthy individuals may contribute to reduce the burden of disease related to hypertension. In this view, an extensive use of nutrients and nutraceuticals has demonstrated to provide favorable effects in hypertension management and control, beyond the adoption of pharmacological and non-pharmacological interventions. These interventions can effectively and safely reduce BP levels to targets and prevent disease progression form high-normal BP levels towards stage 1 hypertension. The present consensus document will systematically describe and critically analyze the currently available evidence in favor of the use of nutrients and nutraceuticals in those individuals with high-normal BP levels at different cardiovascular risk profile.

Vitamin D Axis in Inflammatory Bowel Diseases: Role, Current Uses and Future Perspectives.

Increasing evidence supports the concept that the vitamin D axis possesses immunoregulatory functions, with vitamin D receptor (VDR) status representing the major determinant of vitamin D's pleiotropic effects. Vitamin D promotes the production of anti-microbial peptides, including ß-defensins and cathelicidins, the shift towards Th2 immune responses, and regulates autophagy and epithelial barrier integrity. Impairment of vitamin D-mediated pathways are associated with chronic inflammatory conditions, including inflammatory bowel diseases (IBD). Interestingly, inhibition of vitamin D pathways results in dysbiosis of the gut microbiome, which has mechanistically been implicated in the development of IBD. Herein, we explore the role of the vitamin D axis in immune-mediated diseases, with particular emphasis on its interplay with the gut microbiome in the pathogenesis of IBD. The potential clinical implications and therapeutic relevance of this interaction will also be discussed, including optimizing VDR function, both with vitamin D analogues and probiotics, which may represent a complementary approach to current IBD treatments.

Black Tea Increases Circulating Endothelial Progenitor Cells and Improves Flow Mediated Dilatation Counteracting Deleterious Effects from a Fat Load in Hypertensive Patients: A Randomized Controlled Study.

(1) Background: Endothelial dysfunction predicts cardiovascular events. Circulating angiogenic cells (CACs) maintain and repair the endothelium regulating its function. Tea flavonoids reduce cardiovascular risk. We investigated the effects of black tea on the number of CACs and on flow-mediated dilation (FMD) before and after an oral fat in hypertensives; (2) Methods: In a randomized, double-blind, controlled, cross-over study, 19 patients were assigned to black tea (150 mg polyphenols) or a placebo twice a day for eight days. Measurements were obtained in a fasted state and after consuming whipping cream, and FMD was measured at baseline and after consumption of the products; (3) Results: Compared with the placebo, black tea ingestion increased functionally active CACs (36 ± 22 vs. 56 ± 21 cells per high-power field; p = 0.006) and FMD (5.0% ± 0.3% vs. 6.6% ± 0.3%, p < 0.0001). Tea further increased FMD 1, 2, 3, and 4 h after consumption, with maximal response 2 h after intake (p < 0.0001). Fat challenge decreased FMD, while tea consumption counteracted FMD impairment (p < 0.0001); (4) Conclusions: We demonstrated the vascular protective properties of black tea by increasing the number of CACs and preventing endothelial dysfunction induced by acute oral fat load in hypertensive patients. Considering that tea is the most consumed beverage after water, our findings are of clinical relevance and interest.

Effects of a Novel Fixed Combination of Nutraceuticals on Serum Uric Acid Concentrations and the Lipid Profile in Asymptomatic Hyperuricemic Patients : Results from the PICONZ-UA Study.

INTRODUCTION: Asymptomatic hyperuricemia is not a current indication for therapy as the definite role of serum uric acid elevation as a cardiovascular risk factor is extremely likely but still controversial. AIM: We designed a double blind, placebo-controlled, randomized study to assess the effects of a combination of nutraceuticals (ZinutriK®, containing a fixed combination of kampferol, baicalin, caffeine, and rutin) on serum uric acid levels, lipid variables and the global cardiovascular risk profile. METHODS: Sixteen individuals (mean age 59.0 ± 11.9 years, 4 women) with asymptomatic hyperuricemia completed the study. RESULTS: ZinutriK® treatment (4 weeks) reduced serum uric acid concentrations (from 7.9 + 0.9 to 7.0 + 0.7 mg/dL) when compared to both baseline and placebo (p < 0.006 and p < 0.001, respectively). Compared to both placebo and baseline, the same fixed combination of nutraceuticals also reduced circulating LDL cholesterol and increased HDL cholesterol concentrations within 4 weeks (p < 0.001 or less), thereby improving the Framingham risk score (p < 0.001 or less). Neither minor nor major side effects were observed. CONCLUSIONS: This study represents the first demonstration that a short-term therapy with a fixed combination of different natural substances can significantly reduce serum uric acid concentrations in asymptomatic hyperuricemic patients, with no side effects and a significant improvement in the lipid pattern and then in the global cardiovascular risk profile.

Lipid profile changes after pomegranate consumption: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Transport of oxidized low-density lipoprotein across the endothelium into the artery wall is considered a fundamental priming step for the atherosclerotic process. Recent studies reported potential therapeutic effects of micronutrients found in natural products, indicating positive applications for controlling the pathogenesis of chronic cardiovascular disease driven by cardiovascular risk factors and oxidative stress. A particular attention has been recently addressed to pomegranate; however findings of clinical studies have been contrasting. PURPOSE: To evaluate the effects of pomegranate consumption on plasma lipid concentrations through a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: The study was designed according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement. Scopus and Medline databases were searched to identify randomized placebo-controlled trials investigating the impact of pomegranate on plasma lipid concentrations. A fixed-effects model and the generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the one-study remove approach. Random-effects meta-regression was performed to assess the impact of potential confounders on the estimated effect sizes. RESULTS: A total of 545 individuals were recruited from the 12 RCTs. Fixed-effect meta-analysis of data from 12 RCTs (13 treatment arms) did not show any significant effect of pomegranate consumption on plasma lipid concentrations. The results of meta-regression did not suggest any significant association between duration of supplementation and impact of pomegranate on total cholesterol and HDL-C, while an inverse association was found with changes in triglycerides levels (slope: -1.07; 95% CI: -2.03 to -0.11; p = 0.029). There was no association between the amount of pomegranate juice consumed per day and respective changes in plasma total cholesterol, LDL-C, HDL-C and triglycerides. CONCLUSION: The present meta-analysis of RCTs did not suggest any effect of pomegranate consumption on lipid profile in human.

Brain Protection and Cognitive Function: Cocoa Flavonoids as Nutraceuticals.

Cognitive decline and dementia are major public health social problems, suggesting the specific need to provide research into risk factors for cognitive decline as priority topic. Increasing evidence supports the hypothesis that oxidative stress and neuroinflammation might play a crucial role in the pathophysiology of cognitive decline. Further, cognitive dysfunction and dementia in Alzheimer's disease as well as in vascular dementia seem to be also the consequence of cerebral blood flow decrease and deregulation, also suggesting a putative pathophysiological convergence of mechanisms between atherosclerosis and Alzheimer's disease. In keeping with this, a growing interest has been addressed to flavonoids as potential nutraceuticals with neuroprotective effects. Of interest, cocoa beans have been described as a fundamental source of anti-oxidant flavonoids with the flavan-3-ols and their derivatives being present in high concentrations. Therefore, recent studies specifically focused on the favorable effects of flavonoid-rich cocoa and chocolate on cerebrovascular risk factors and cognitive function. Aim of this review is to summarize new findings concerning the cocoa effects on cognitive function, particularly focusing on some putative mechanisms of vascular and antioxidant action involved in preventing dementia.

Cocoa, blood pressure, and cardiovascular health.

High blood pressure is an important risk factor for cardiovascular disease and cardiovascular events worldwide. Clinical and epidemiological studies suggest that cocoa-rich products reduce the risk of cardiovascular disease. According to this, cocoa has a high content in polyphenols, especially flavanols. Flavanols have been described to exert favorable effects on endothelium-derived vasodilation via the stimulation of nitric oxide-synthase, the increased availability of l-arginine, and the decreased degradation of NO. Cocoa may also have a beneficial effect by protecting against oxidative stress alterations and via decreased platelet aggregation, decreased lipid oxidation, and insulin resistance. These effects are associated with a decrease of blood pressure and a favorable trend toward a reduction in cardiovascular events and strokes. Previous meta-analyses have shown that cocoa-rich foods may reduce blood pressure. Long-term trials investigating the effect of cocoa products are needed to determine whether or not blood pressure is reduced on a chronic basis by daily ingestion of cocoa. Furthermore, long-term trials investigating the effect of cocoa on clinical outcomes are also needed to assess whether cocoa has an effect on cardiovascular events. A 3 mmHg systolic blood pressure reduction has been estimated to decrease the risk of cardiovascular and all-cause mortality. This paper summarizes new findings concerning cocoa effects on blood pressure and cardiovascular health, focusing on putative mechanisms of action and "nutraceutical " viewpoints.

Black tea lowers blood pressure and wave reflections in fasted and postprandial conditions in hypertensive patients: a randomised study.

Hypertension and arterial stiffening are independent predictors of cardiovascular mortality. Flavonoids may exert some vascular protection. We investigated the effects of black tea on blood pressure (BP) and wave reflections before and after fat load in hypertensives. According to a randomized, double-blind, controlled, cross-over design, 19 patients were assigned to consume black tea (129 mg flavonoids) or placebo twice a day for eight days (13 day wash-out period). Digital volume pulse and BP were measured before and 1, 2, 3 and 4 h after tea consumption. Measurements were performed in a fasted state and after a fat load. Compared to placebo, reflection index and stiffness index decreased after tea consumption (p<0.0001). Fat challenge increased wave reflection, which was counteracted by tea consumption (p<0.0001). Black tea decreased systolic and diastolic BP (-3.2 mmHg, p<0.005 and -2.6 mmHg, p<0.0001; respectively) and prevented BP increase after a fat load (p<0.0001). Black tea consumption lowers wave reflections and BP in the fasting state, and during the challenging haemodynamic conditions after a fat load in hypertensives. Considering lipemia-induced impairment of arterial function may occur frequently during the day, our findings suggest regular consumption of black tea may be relevant for cardiovascular protection.

Cocoa consumption dose-dependently improves flow-mediated dilation and arterial stiffness decreasing blood pressure in healthy individuals.

BACKGROUND: Cocoa flavonoids exert beneficial vascular effects and reduce the risk of cardiovascular morbidity and mortality. Nevertheless, the involved mechanisms have not been clarified and no study has yet focused on the dose-response effects. OBJECTIVES: We aimed to investigate the effects of different doses of cocoa flavonoids on flow-mediated dilation (FMD), endothelin-1 (ET-1), pulse wave velocity (PWV), and SBP and DBP. DESIGN: According to a randomized, double-blind, controlled, cross-over design, 20 healthy volunteers (1.5% improvement in FMD in 20 individuals: 0.99 at alpha = 0.05) were assigned to receive either five treatments with daily intake of 10 g cocoa (0, 80, 200, 500 and 800 mg cocoa flavonoids/day) in five periods lasting 1 week each. RESULTS: Cocoa dose-dependently increased FMD from 6.2% (control) to 7.3, 7.6, 8.1 and 8.2% after the different flavonoid doses, respectively (P < 0.0001). Compared with the control, even 80  mg cocoa flavonoids per day increased FMD (P < 0.0001). Cocoa dose-dependently decreased PWV (P < 0.0001). Cocoa intake decreased office blood pressure (BP) (SBP: -4.8 ±â€Š1.03  mmHg, P < 0.0001; DBP: -3.03 ±â€Š1.07 mmHg, P = 0.0011). With respect to control, cocoa ingestion decreased 24-h (P = 0.05) and daytime (P = 0.038) SBP, and 24-h (P = 0.0064), daytime (P = 0.0088) and night-time (P = 0.0352) pulse pressure. Compared with the control, cocoa dose-dependently decreased ET-1 levels [from 17.1 (control) to 15.2, 14.5, 14.2 and 14.1 pg/ml, after the different flavonoid doses, respectively (P for treatment <0.05)]. Compared with the control, significant changes were observed for all doses of flavonoids (ET-1; P < 0.05). CONCLUSION: Our study showed for the first time that cocoa dose-dependently improved FMD and decreased PWV and ET-1 also by ameliorating office and monitored BP. Our findings are clinically relevant, suggesting cocoa, with very low calorie intake, might be reasonably incorporated into a dietary approach, representing a consistent tool in cardiovascular prevention.

Tea, flavonoids, and cardiovascular health: endothelial protection.

Several studies have suggested that tea consumption might protect against the development and progression of cardiovascular disease, one of the leading causes of morbidity and mortality worldwide. The endothelium plays a pivotal role in arterial homeostasis. Reduced nitric oxide (NO) bioavailability with endothelial dysfunction is considered the earliest step in the pathogenesis of atherosclerosis. Endothelial dysfunction has been considered an important and independent predictor of future development of cardiovascular risk and events. The association between brachial NO-dependent flow-mediated dilation (FMD) and cardiovascular disease risk has been investigated in several prospective studies, suggesting that FMD is inversely associated with future cardiovascular events. Dietary flavonoids and tea consumption have been described to improve endothelial function and FMD. A proposed mechanism by which dietary flavonoids could affect FMD is that they improve the bioactivity of the endothelium-derived vasodilator NO by enhancing NO synthesis or by decreasing superoxide-mediated NO breakdown. This could be of clinical relevance and may suggest a mechanistic explanation for the reduced risk of cardiovascular events and stroke observed among tea drinkers in the different studies. The purpose of this article is to provide an overview of the relation between tea consumption and cardiovascular disease, with a focus on clinical implications resulting from the beneficial effects of tea consumption on endothelial function.

Cocoa powder triggers neuroprotective and preventive effects in a human Alzheimer's disease model by modulating BDNF signaling pathway.

The molecular mechanisms linking Aß to the onset of neurotoxicity are still largely unknown, but several lines of evidence point to reactive oxygen species, which are produced even under the effect of nanomolar concentrations of soluble Aß-oligomers. The consequent oxidative stress is considered as the mediator of a cascade of degenerative events in many neurological disorders. Epidemiological studies indicate that dietary habits and antioxidants from diet can influence the incidence of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. In the recent years, a number of reviews have reported on neuroprotective effects of polyphenols in cell and animal models. However, the majority of these studies have focused only on the anti-oxidant properties of these compounds and less on the mechanism/s of action at cellular level. In this work we investigated the effect of cocoa polyphenolic extract on a human AD in vitro model. The results obtained, other than confirming the anti-oxidant properties of cocoa, demonstrate that cocoa polyphenols triggers neuroprotection by activating BDNF survival pathway, both on Aß plaque treated cells and on Aß oligomers treated cells, resulting in the counteraction of neurite dystrophy. On the light of the results obtained the use of cocoa powder as preventive agent for neurodegeneration is further supported.

Black tea consumption dose-dependently improves flow-mediated dilation in healthy males.

OBJECTIVES: Flavonoids may protect against cardiovascular disease. Tea is a major source of dietary flavonoids. Studies indicate black tea improves endothelial function but data on arterial haemodynamics, blood pressure (BP) and insulin resistance are equivocal. Inconsistency may be due to flaws in study design or flavonoid doses tested. Further, no study has evaluated the dose-response curve. Our study aimed to test the effects of various doses of black tea on vascular function, BP and insulin resistance. METHODS: According to a randomized, double-blind, controlled, cross-over design, 19 healthy men were assigned to receive either five treatments with a twice daily intake of black tea (0, 100, 200, 400 and 800 mg tea flavonoids/day) in five periods lasting 1 week each. RESULTS: Black tea dose dependently increased flow-mediated dilation (FMD) from 7.8% (control) to 9.0, 9.1, 9.6 and 10.3% after the different flavonoid doses, respectively (P = 0.0001). Already 100 mg/day (less than 1 cup of tea) increased FMD compared with control (P = 0.0113). FMD improvement after 800 mg/day was significant compared with control (P < 0.0001) but also to 100 mg/day (P = 0.0121) and 200 mg/day (P = 0.0275). Black tea intake decreased office systolic (-2.6 mmHg, P = 0.0007) and diastolic (-2.2 mmHg, P = 0.006) BP as well as stiffness index (P = 0.0159) without changes in other parameters studied. CONCLUSION: Our study is the first showing black tea ingestion dose dependently improved FMD and decreased peripheral arterial stiffness in healthy volunteers. Our data suggest that worldwide all tea drinkers could benefit from protective cardiovascular effects exerted by tea.

Tea, flavonoids, and nitric oxide-mediated vascular reactivity.

Epidemiological evidence supports the concept that diets rich in fruits and vegetables promote health and attenuate or delay the onset of cardiovascular disease (CVD). Although a variety of factors contribute to the beneficial effects of plant foods, much attention has been addressed to plant polyphenols. In this regard, in the daily Western diet, both black and green teas contribute to a relevant proportion of total phenol intake. The more abundant class of flavonoids that is present in teas is represented by flavanols, i.e., catechin, epicatechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate. Studies using animal models of atherosclerosis indicate that dietary flavonoid consumption delays atherosclerotic plaque development. Accordingly, an inverse association between tea intake and CVD has been demonstrated. Further, flavonoids can reduce endothelial dysfunction, i.e., the key step in the development of atherosclerosis. Concordantly, human data suggest that tea may reduce blood pressure levels. Despite this, although they often show that tea may have cardiovascular protective effects, results from epidemiological studies exploring the association between tea and health are controversial. Conflicting results may be caused by disparate study designs and flavonoid contents in different kinds of tea. Thus, because tea is a popular beverage worldwide, and several studies have shown that it is protective against CVD, further studies are needed to determine the role of tea in primary and secondary cardiovascular prevention.