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Cocoa, Blood Pressure, and Vascular Function


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The consumption of a high amount of fruits and vegetables was found to be associated with a lower risk of coronary heart disease and stroke. Epidemiologically, a similar relationship has been found with cocoa, a naturally polyphenol-rich food. Obviously, double blind randomized studies are difficult to perform with cocoa and chocolate, respectively. However, intervention studies strongly suggest that cocoa has several beneficial effects on cardiovascular health, including the lowering of blood pressure, the improvement of vascular function and glucose metabolism, and the reduction of platelet aggregation and adhesion. Several potential mechanisms through which cocoa might exert its positive effects have been proposed, among them activation of nitric oxide synthase, increased bioavailability of nitric oxide as well as antioxidant, and anti-inflammatory properties. It is the aim of this review to summarize the findings of cocoa and chocolate on blood pressure and vascular function.
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Cocoa, Blood Pressure and Vascular Function 19.4.2012 V1
Cocoa, Blood Pressure
and Vascular Function
Isabella Sudano1, MD; Andreas J Flammer1,2, MD; Susanne Roas1, MD; Frank Enseleit1, MD;
Frank Ruschitzka1,3, MD; Roberto Corti1,3, MD; Georg Noll1,3, MD
1Cardiovascular Center Cardiology, University Hospital Zurich, Switzerland; 2Division of Cardiovascular
Diseases, Department of Internal Medicine, Mayo Clinic and College of Medicine, Rochester, MN, USA;
3Center for Integrative Human Physiology, University Zurich, Switzerland
Prof. Dr. med. Georg Noll
Cardiovascular Center, Cardiology
University Hospital
Raemistrasse 100
CH-8091 Zurich
Tel: +41-44-255 2266
Fax: +41-44-255 4859
Cocoa, Blood Pressure and Vascular Function 19.4.2012 V1
The consumption of a high amount of fruits and vegetables was found to be associated with a
lower risk of coronary heart disease and stroke. Epidemiologically, a similar relationship has
been found with cocoa, a naturally polyphenol-rich food. Obviously, double blind randomized
studies are difficult to perform with cocoa and chocolate, respectively. However, intervention
studies strongly suggest that cocoa has several beneficial effects on cardiovascular health,
including the lowering of blood pressure, the improvement of vascular function and glucose
metabolism, and the reduction of platelet aggregation and adhesion. Several potential
mechanisms through which cocoa might exert its positive effects have been proposed, among
them activation of nitric oxide synthase, increased bioavailability of nitric oxide as well as
antioxidant, and anti-inflammatory properties. It is the aim of this review to summarize the
findings of cocoa and chocolate on blood pressure and vascular function.
Key words: cocoa, flavanols, polyphenols, antioxidants, endothelial function, blood pressure,
nitric oxide, vascular compliance.
Cocoa, Blood Pressure and Vascular Function 19.4.2012 V1
In epidemiological studies, regular dietary intake of plant-derived foods and beverages
was found to be associated with a reduced risk of coronary heart disease (CAD)[1-4] and
stroke[5], and to be inversely associated with the risk of cardiovascular disease in general.[2, 4]
The Iowa Women's Health Study is a prospective study in 34’489 postmenopausal women
free of cardiovascular disease who were followed for up to 16 years.[6] In this population regular
consumption of food rich in flavonoids was associated with a decreased risk of death due to CAD
and the inverse association between chocolate intake and cardiovascular mortality remained
significant after multivariate adjustment.[6] Moreover, the Zutphen Elderly Study, involving 470
elderly men free of chronic disease, suggest that habitual cocoa intake per se might reduce
cardiovascular risk and is inversely related to cardiovascular and all-cause mortality).[7]
Moreover, a retrospective analysis of the Potsdam arm of the European Prospective
Investigation into Cancer and Nutritionrecently showed that high consumption of cocoa was
associated with a lower prevalence of stroke and myocardial infarction.[8]
It has been proposed that polyphenols may play an important role in cardiovascular
Several food sources are exceptionally rich in polyphenols, among them green and black teas,
wine, grape juices, berries and cocoa, the later with particularly high amounts.[9, 10](Table 1)
Several groups of polyphenols are found in fruits, whereas the most important are the flavanols
which can be further subdivided into the monomers epicatechin and catechin,[11, 12] and their
dimers, oligomers and polymers, the so-called procyanidins,[13, 14] responsible for the bitterness
of cacao, through the formation of the complexes with salivary proteins.[15] Although the
flavanols are likely responsible for the beneficial health effects, conventional chocolate
Cocoa, Blood Pressure and Vascular Function 19.4.2012 V1
manufacturing processes, such as fermentation and roasting markedly decrease the concentration
of these substances. [10, 16]
In humans, flavanol plasma concentration dose-dependently increases after ingestion,
reaching its peak usually after 2-3h[17, 18] after cocoa ingestion and are still measurable in
plasma 8 hours after cocoa ingestion.[19]
Cocoa and its flavanols might increase nitric oxide (NO) bioavailability, activate nitric
oxide synthase (NOS), and exert antioxidative, anti-inflammatory, and anti-platelet effects, which
in turn might improve vascular function, reduced blood pressure and therefore, explain the
positive impact on clinical outcome proposed by epidemiological studies.[10, 16, 20, 21]
This review will focus on the effect of cocoa on blood pressure and vascular function.
Cocoa, Blood Pressure and Vascular Function 19.4.2012 V1
Effect of cocoa on blood pressure
Initial findings, which suggested possible antihypertensive effects of cocoa, came from
observations of the Kuna Indians, a native population living on islands off the Panama coast,
which have a very low incidence of hypertension and, remarkably, do not show an age-dependent
increase in blood pressure. These effects are likely environmental because they are lost upon
migration to urban Panama City and are likely linked to the reduction in intake of natural cocoa
drinks rich in flavanols.[22]
A relationship between cocoa consumption and reduced blood pressure was first observed
in a cross sectional analysis of the Zutphen Elderly Study[7] .The association of chocolate
consumption with blood pressure and the incidence of cardiovascular disease was further
evaluated in the population included in a Potsdam arm of the European Prospective
Investigation into Cancer”.[8] The later study showed over a follow up p to 8 years that a high
consumption of chocolate was associated with a lower cardiovascular risk with a strong inverse
association for stroke (more than for myocardial infarction). The authors emphasized that this
positive effect could be explained at least in part by a reduction in blood pressure, observed in the
group with high as compared to low chocolate-consumption.[8]
Randomized controlled trials have confirmed this epidemiological association mostly in
patients with concurrent arterial hypertension or other cardiovascular risk factors.[23-26]
A meta-analysis of ten such trials[27] found that cocoa consumption was associated with
significant reductions in systolic (-4.5±1.35 mmHg) and diastolic (-2.5±1.36 mmHg) blood
pressures confirming the results of a previous meta-analysis published 2007.[28]
A number of mechanisms have been proposed to explain the cocoa‘s effects on blood pressure.
Because of their importance in blood pressure maintenance, the improvements in nitric oxide
availability and endothelial function associated with cocoa consumption may explain much, of its
Cocoa, Blood Pressure and Vascular Function 19.4.2012 V1
antihypertensive effects. However, there is some evidence that flavanols and flavanol-rich foods
including cocoa can inhibit angiotensin-converting enzyme (ACE) activity in vitro.[29, 30] ACE
regulates the reninangiotensin system; it cleaves angiotensin-I into angiotensin-II, which
stimulates the release of vasopressin or aldosterone and antidiuretic hormone, increasing sodium
and water retention. It also inactivates vasodilators bradykinin and kallidin. Whether ACE
inhibition mediates the antihypertensive activity of cocoa flavanols in humans is not yet
completely clear.[31]
One study also looked at the blood pressure responsiveness after exercise showing as an high
flavonols drink reduced the BP response to exercise.[32]
Cocoa, Blood Pressure and Vascular Function 19.4.2012 V1
Cocoa and vascular function
The vascular endothelium plays a fundamental role in modulating vascular tone and
structure. Physiological production of vascular relaxing factors, including “nitric oxide”,
“prostacyclin” and “hyperpolarizing relaxing factor” protect the vessel wall by antagonizing the
initial pathological steps of atherosclerosis and thrombosis[33].(Figure 1) Cardiovascular risk
factors and disease are associated with endothelial dysfunction or damage.[34, 35] Endothelial
dysfunction in the forearm circulation correlates with the presence of coronary vascular
dysfunction and is predictive of future coronary events.[36-38]
A meta-analysis published in 2008 showed that consumption of polyphenol-rich foods
mostly was associated with an improvement in endothelial function in the short- and long-
term[39] as exemplified with the effect of tea[40] and other flavanoid-rich food such as red wine,
grape juice, dealcoholized red wine extract from grape seeds [41, 42] and orange juice.[43],
As cocoa is particularly rich in polyphenols it is not surprising that cocoa induces NO-
dependent vasodilatation in rat[44] and improve endothelial function in healthy humans and in
patients with cardiovascular risk factors or disease.[10, 16]
Studies evaluating the effect of cocoa/chocolate an endothelial function are summarized in Table
A cocoa drink high in flavanols content enhances the circulating pool of bioactive NO by a third
and in turn improves flow-mediated vasodilation in patients with cardiovascular risk factors.[45,
46] The increase in NO and the improvement of endothelial function induced by cocoa intake
was inhibited by the infusion of L-NMMA, an inhibitor of NO-synthesis.[46] Commercially
available dark chocolate (74% cocoa), but not white chocolate, improves flow-mediated
vasodilatation (FMD) by 80% in young healthy smokers. This effect was seen two hours after
chocolate ingestion and lasted for up to 8 hours. Because plasma antioxidant status, was
Cocoa, Blood Pressure and Vascular Function 19.4.2012 V1
significantly improved 2 hours after ingestion, it is likely that not only an induction of endothelial
nitric oxide synthase (NOS) and in turn elevated NO levels, but also a reduction in oxidative
stress and in turn a reduced breakdown of NO by reactive oxidant species, contributes to the
enhanced endothelial function, especially under conditions with a high oxidative stress burden,
such as in smokers.[47] Indeed, antioxidants may prevent NO transformation into peroxynitrite
and in turn protect against vasoconstriction and vascular damage.[48] Oxidative stress and
reduced antioxidant defenses play also a crucial role in the pathogenesis of atherosclerosis and in
in transplant vasculopathy. Indeed, we were able to demonstrate that flavonoid-rich dark
chocolate improved epicardial coronary vasomotion in cardiac transplant recipients. [49]
Interestingly 40g dark chocolate induced coronary vasodilatation, improved coronary vascular
function, and decreased platelet adhesion two hours after consumption.
As outlined in Table 2, cocoa consistently improved endothelial function in patients with
atherosclerosis and/or cardiovascular risk factors such as in patients with arterial
hypertension,[24] diabetes mellitus,[50] overweight and obesity,[51] coronary artery disease,[52]
and hart failure.[53] Not only endothelial function improved after consumption of cocoa or
chocolate. Vlachopoulos and colleagues showed that chocolate acutely decrease augmentation
index of the central (aortic) pressure waveform suggesting dilation of small and medium-sized
peripheral arteries and arterioles.[54] Moreover, an observational study in 198 healthy subjects
showed that habitual cocoa consumption is associated with decreased aortic stiffness and wave
reflections and with improved central hemodynamics in healthy subjects.[55]
A possible mechanism explaining the effects of cocoa on the vasculature is the
antioxidative effect of the flavanols and procyanidins contained in cocoa which may reduce the
production of oxygen free-radicals and therefore improve nitric oxide bioavailability and a eNOS
activation.[10, 16](Figure 1) However, the antioxidative effect of cocoa is discussed
Cocoa, Blood Pressure and Vascular Function 19.4.2012 V1
controversial because in addition to flavanols,[56] macro- and micronutrients, as well as the
increased uric-acid levels resulting from fructose metabolism[57] could affect antioxidative
capacity of plasma.
Ramirez and coauthors showed that epicatechins increase the synthesis of NO via eNOS
activation in human coronary artery endothelial cells.[58] Furthermore, this epicatechin-induced
NO production in human endothelial cells can be obtained through both Ca2+-dependent and
Ca2+-independent eNOS phosphorylation,[59] suggesting that epicatechin may act to retain
vascular function in diseases where NO production is limited.
However, further studies are still needed to clarify the exact mechanisms underlying the
beneficial vascular effects due to cocoa consumption.
For many centuries, cocoa has been loved for its good taste and praised for its beneficial effects
on health. In the last ten years many research studies confirmed that cocoa does indeed exert
beneficial effects on vascular and platelet function, probably mainly mediated by its high
polyphenol content, a heterogeneous group of molecules mainly found in fruits and vegetables.
The beneficial effects of cacao are most likely due to a decrease in oxidative stress, induction of
NOS and in turn an increased bioavailability of NO.
Work of the authors was partly supported by the Swiss National Science Foundation (grant Nr.
32000BO-109905/1 to R.C.) The authors received a unrestricted research grant by Nestlé.
Cocoa, Blood Pressure and Vascular Function 19.4.2012 V1
Table and Figure legend
Table 1 Catechin/Epicatechin Concentrations found in foods. Modified from Manach et al[15]
Table 2 Studies Investigating Cocoa and Endothelial Function. LDL, low density lipoprotein;
NO, nitric oxide; FMD, flow mediated dilatation; CAD, coronary artery disease. Modified
from[10, 16]
Figure 1 Endothelium-dependent effect of cocoa polyphenols. AII indicates angiotensin II; AI,
angiotensin I; PKC, protein kinase C; SOD, superoxide dismutase; PGI2, prostacyclin; ACE,
angiotensin-converting enzyme; ECE, endothelin-converting enzyme; AT1, angiotensin receptor;
ET-1, endothelin 1; bET-1, big endothelin 1; ETa/b, endothelin receptor a and b; cGMP, cyclic
guanosine monophosphate; and ROS, reactive oxygen species. Modified from Corti R et al.[10]
Cocoa, Blood Pressure and Vascular Function 19.4.2012 V1
Table 1:
Flavanol content
per mg/kg or mg/L
Green tea
Black tea
Red wine
Cocoa, Blood Pressure and Vascular Function 19.4.2012 V1
Table 2
Patients with
at least 1 CV
risk factor
2 hours
Flavanol rich cocoa drink
Improvement of FMD and
levels of nitrosated and
nitrosylated species.
5 days
Flavanol rich cocoa
Peripheral vasodilatation,
improved vasodilator response to
ischemia assessed by pulse wave
amplitude on the finger
2 weeks
High flavonoid chocolate
(213mg procyanidins,
46mg epicatechin) vs. low
flavonoid chocolate
Improvement of FMD of the
brachial artery, increased
epicatechin concentrations
15 days
100 g dark chocolate
(21.91mg catechin, 65,97
mg epicatechins) vs.
flavanol free white
Increased FMD of the brachial
artery. Decrease in blood-pressure
and LDL cholesterol, increase of
insulin sensitivity
2 hours
100ml cocoa drink with
high (176-
18mg) or low
(<11mg) flavanol content
Increase of FMD and circulating
NO pool. Increase of flavanol
2 hours
40g commercially
available dark chocolate
vs. white chocolate
Increase in FMD of the brachial
artery. Improvement of antioxidant
status and improvement of platelet
rabbit rings
2 hours
Drink with high flavonoid
Improvement of FMD, paralleled
the appearance of flavanoles in
plasma. Concentrations in plasma
enough to mediate ex vivo
vasodilatation. Pure epicatechins
mimics vascular effects of cocoa.
High flavanol diet is associated
with high urinary excretion of NO
2 hours
40g commercially
available dark chocolate
vs. flavonoid free placebo
Inducing coronary vasodilation,
improvement in coronary
endothelial function and
improvement of platelet function.
30 days
flavanol-rich cocoa (321
mg flavanolsx3) or a
matched control
(25 mg flavanolsx3)
Improvement in brachial FMD
2 weeks
45g commercially
available dark chocolate
vs. white chocolate
Improvement in coronary
circulation as measured by
coronary velocity flow reserve
Cocoa, Blood Pressure and Vascular Function 19.4.2012 V1
Obese and
12 weeks
Dietary high (902 mg) vs.
low (36 mg) flavanol
Improvement in brachial FMD
30 days
Dietary high (375 mgx2)
low (9 mgx2) flavanol
Improvement in FMD and
mobilization of endothelial
progenitor cells
Healthy BMI
6 weeks
sugar-free cocoa beverage
or placebo, sugar-
sweetened cocoa beverage
or placebo
Improvement in FMD, n
o change
in weight
Heart Failure
2 hours and
30 days
40g commercially
available dark chocolate
vs. flavonoid free placebo
Inducing brachial vasodilation,
improvement in endothelial
function and acute improvement of
platelet function.
Cocoa, Blood Pressure and Vascular Function 19.4.2012 V1
Figure 1
Cocoa, Blood Pressure and Vascular Function 19.4.2012 V1
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... Epidemiological and clinical studies show and confirm that regular intake of cocoa powder and/or dark chocolate (50%-70% cacao) is related to a decrease in systolic blood pressure (SBP) (−3.2 to −5.88 mmHg) and diastolic blood pressure (DBP) (−2.0 to −3.30 mmHg), as well as to an improvement of the vascular endothelial function (measured as a function of endothelium vasodilatation and an increase in the production of nitric oxide) in groups with some type of cardiovascular disease or with multiple risk factors [5][6][7]. Cocoa flavanols reduce the blood pressure by increasing the availability of nitric oxide (increasing the nitric oxide synthase activity and reducing the oxidative stress), consequently vasodilatation increases and finally blood pressure is reduced; or, by inhibition of angiotensin-converting enzyme, interrupting the chain of reactions of angiotensinogen that by the action of renin produces angiotensin I which in turn by action of angiotensin converting enzyme (ACE) is transformed into angiotensin II and finally increases blood pressure [8]. ...
... In accordance with these results, the consumption of a high-flavanol cocoa drink (985 mg/serving) showed a decreased arginase activity in human erythrocytes. Further in vivo evidence showed that high-flavanol containing cocoa-based diet (4% cocoa) lowers renal arginase-2 activity in rats [6,60]. ...
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The interest in cacao flavanols is still growing, as bioactive compounds with potential benefits in the prevention of chronic diseases associated with inflammation, oxidative stress and metabolic disorders. Several analytical methodologies support that the flavanols in cacao-derived products can be absorbed, have bioactive properties, and thus can be responsible for their beneficial effects on human health. However, it must be considered that their biological actions and underlying molecular mechanisms will depend on the concentrations achieved in their target tissues. Based on the antioxidant properties of cacao flavanols, this review focuses on recent advances in research regarding their potential to improve metabolic syndrome risk factors. Additionally, it has included other secondary plant metabolites that have been investigated for their protective effects against metabolic syndrome. Studies using laboratory animals or human subjects represent strong available evidence for biological effects of cacao flavanols. Nevertheless, in vitro studies are also included to provide an overview of these phytochemical mechanisms of action. Further studies are needed to determine if the main cacao flavanols or their metabolites are responsible for the observed health benefits and which are their precise molecular mechanisms.
... 55 Dietary polyphenol antioxidants bind to lipoproteins to inhibit oxidative stress processes that lead to the development of atherosclerosis. 56 In addition, walnuts are rich in omega-3 α-linolenic fatty acids. Dietary omega-3 fatty acid intake has been inversely associated with the incidence of CVD. ...
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Diabetes and its complications are main causes of morbidity and mortality among adults in the USA. An increase in the number of individuals with diabetes is primarily attributed to changes in dietary patterns including increased consumption of obesogenic foods and beverages. Many individuals who are overweight and obese show signs of insulin resistance and are at increased risk of Type 2 diabetes mellitus (T2DM) and cardiovascular disease. Lifestyle interventions (i.e., physical activity and nutrition) are the cornerstone of T2DM management and prevention. Prior research attests to the health benefits of consuming nuts, which have a substantial amount of mono- and polyunsaturated fatty acids, for individuals at risk for or with T2DM, and walnuts appear to be particularly promising. Walnuts are rich in nutrients, minerals, antioxidants, and vitamins that can contribute to improved cardio-metabolic risk factors in individuals at risk for or with T2DM. This review assesses the cardio-metabolic benefits of walnuts in T2DM. The authors’ review indicates that the reported effects of walnuts on glycaemic control have been inconclusive, with several studies showing association with improved glycaemic control while others show no effect. Despite their high energy density and potential to contribute to weight gain, the authors’ review suggests that walnuts can contribute to satiety without association with weight gain. This review also suggests that walnut consumption has been associated with improved low-density lipoprotein cholesterol levels and endothelial function but has not been associated with blood pressure improvement. Meta-analyses are warranted to quantitatively assess impact of walnut consumption on these cardio-metabolic risk factors in T2DM.
... In fact, in these populations, the variations in DBP were between −7 and 6.6 mmHg after daily consumption of cocoa over 2-18 weeks. When consuming cocoa, the flavanols would lead to an increase in NO production and vasodilation by acting on the vascular endothelium (Sudano et al., 2012), with a drop in blood pressure as a drawback. They might also be responsible for a decrease in arterial stiffness and a decrease in the peripheral resistance (Ana et al., 2016), leading to a drop in blood pressure. ...
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Background In Caucasians, regular consumption of cocoa induces a drop in arterial blood pressure via an increase in nitric oxide (NO) production. However, black individuals have a different NO biodisponibility compared to Caucasians. The aim of this study was to determine, in black Africans, the physiological variations in arterial blood pressure among cocoa consumers. Method In total, 49 male black African volunteers, aged between 18 and 30 years old, were randomized into two groups; those consuming 10 g of cocoa powder per day (1,680 mg of flavonoids per day) for 3 weeks (consumer group), and those not consuming cocoa (control group). Systolic (SBP) and diastolic blood pressures (DBP), and heart rate (HR) were measured in the morning on an empty stomach (fasting), on day (D) 1 (without cocoa), D8, D15, and D22. Data were collected by groups and by subgroups established according to the level of SBP, DBP, or HR on D1. The means and variations of the means (between D1 and the subsequent days) of the recorded parameters were calculated and compared between groups and between subgroups. Results On D8, the variations in SBP in the consumer group were significantly different from the control group (−3.72 ± 6.01 versus 0.57 ± 6.66 mmHg; p = 0.02). Between the control and consumer subgroups according to SBP, no statistical difference in the means or variations in SBP was noted. On D8 and D22, the variations in the SBP of consumers with SBP ≥ 110 mmHg on D1 were significantly different from those of other consumers (D8: −6.55 ± 5.96 versus −1.1 ± 4.93 mmHg; p = 0.01; D22: −6.63 ± 7.77 versus 0.35 ± 5.58 mmHg; p = 0.01). In the subgroups with a DBP < 75 mmHg on D1, the mean DBP of the consumers was significantly lower than that of the controls on D8 (65 ± 5 versus 69 ± 6 mmHg; p = 0.03). Conclusion In young black African men living in Côte d’Ivoire, regular consumption of cocoa resulted in a decrease in SBP and DBP. The decrease in SBP appeared to be greater the higher the baseline SBP was.
... The scientific infrastructure of these supplements as ergogenic nutritional supplements has been revealed by recent researches showing that NO intake as a supplement has an enhancing effect on performance and accelerating effect on recovery (46). The literature review showed that there are different tools and methods related to supplements containing arginine, citrulline, and ornithine (7,8), known as NO precursors, and nutrients containing cocoa and caffeine, known to increase NO production in metabolism (19,31,47,48) and many different studies have been carried out on the effect of NO-containing food consumption on ex-ercise performance and recovery (19,20,46,49,50). ...
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Background: The beneficial effect of popular supplements and use of nitric oxide (NO) precursor nutrients in athletes which aim at increase of sports performance. Objective: The aim of this study is to investigate the effect of nitric oxide precursor nutrients and some nutrients with the ability to increase NO levels in the body on increased NO production in metabolism and on the recovery after acute exercise. Materials and Methods: 8 volunteers, male athletes, in shape and trained participated into this study. Athletes were subject to research protocol every other day, a total of three times. Heart rate and lactate levels were determined at resting and recovery. Results: Statistically significant difference was detected between control and cocoa/caffeine (CC) groups in the 1 minute lactate levels. Lactate levels significantly decreased in the CC group compared to the control group in the 1 minute lactate levels (p<0.05). Statistical significance difference was found between the nitric oxide supplement (NOX) and CC groups in the 1 and 10 minutes heart rate levels. Heart rate levels significantly decreased in the CC group compared to the NOX group (p<0.05). Heart rate levels were significantly decreased in the CC group compared to the control and NOX groups in the 15 minute measurement (p<0.05). Conclusions: Nitric oxide consumed as a supplement in line with nutrition and recovery strategies in athletes improved the recovery by accelerating lactate excretion from the body after the exercise. All of these metabolic responses in the present study suggest that NO will have a positive effect on exercise performance and recovery.
... Beneficial effects for human health have been consistently identified in association with cocoa-derived polyphenols intake [19,20]. These benefits include modulation of peripheral and cerebral blood flow [21,22], insulin sensitivity and carbohydrate metabolism [23,24], immune response [25,26], cancer risk [27], inflammation [28,29], modulation of gut microbiota [30], neuroprotection and improvement of cognitive functions [31,32]. ...
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The effects of cocoa-derived polyphenols on cognitive functions have been analyzed through numerous studies using different interventions (doses, vehicles, time frame, cognition tests, and characteristics of participants) which may hamper the interpretation and comparison of findings across investigations. Thus, a systematic review was conducted to analyze the effects of cocoa-derived polyphenols intake on human cognition and discuss the methodological aspects that may contribute to the heterogeneity of findings. Randomized clinical trials evaluating the effect of cocoa polyphenols on cognitive function in healthy subjects were selected according to selection criteria. Twelve studies were selected. Quality was assessed according to the Cochrane risk for bias tool. The most common risk for bias was the lack of information about the sequence generation process. Effects on cognitive function were observed after consumption of 50 mg/day of (-)-epicatechin and in studies using a component-matched placebo and cocoa as the polyphenol vehicle given to healthy adults (18-50 years). Memory (n = 5) and executive function (n = 4) showed the most significant effects with medium and large effect sizes after intake of intermediate doses of cocoa flavanols (500-750 mg/day). Overall, this set of studies suggest a positive effect of cocoa polyphenols on memory and executive function. However, the available evidence is very diverse and future studies may address the identified sources of variation to strengthen current evidence on this promising field.
... Even though the most commonly reported activity of flavonoids is their ability to alter cardiovascular function, in vitro studies often report mechanisms which have a shared role in anti-inflammatory homeostasis, including: scavenging of free radicals, metal chelation, impact on ion channel regulation, inhibition of xanthine oxidase, NOX and lipoxygenase, regulation of inducible nitric oxide synthase (iNOS), COX-2 expression, leukocyte activation, and platelet aggregation (Gilbert & Liu, 2010;Hidalgo et al., 2012;Lazze et al., 2006;Mladenka, Zatloukalova, Filipsky, & Hrdina, 2010;Scholz, Zitron, Katus, & Karle, 2010;Williamson, Barron, Shimoi, & Terao, 2005). Based on this evidence researchers postulated flavonoids may prevent the development of atherosclerosis by either restoring endothelial homeostasis or attenuating the initiation or progression of inflammation (Chen et al., 2011;Quintieri et al., 2013;Romero et al., 2009;Sudano et al., 2012). ...
... Flavonoids scavenge the free radicals, so it can reduce superoxide (O 2 -) concentration and prevent the formation of peroxynitrite (ONOO -). In addition, flavonoids also modulate the bioavailability of NO at the cellular level by increasing the expression of the enzyme NO synthase (NOS) [36,37]. Flavonoids could be a compound that plays a role in their antihypertensive effect. ...
Objective: The aims of this study were to prove the antihypertensive effect of Anredera cordifolia (Madeira vine) in dexamethasone-induced hypertensive rat and to determine the release of nitric oxide (NO).Methods: The rat’s blood pressure was measured by CODA® tail-cuff blood pressure system. A hypertensive rat model was developed on day 7 after administration of dexamethasone injection 0.5 mg/kg body weight (bw). NO levels were measured by spectrophotometry at a wavelength of 546 nm after reacting the serum sample with Griess reagent.Results: Ethanol extract of Madeira vine (EEMV), ethyl acetate fraction (EF), and water fraction (WF) could reduce systolic blood pressure at day 14 with a diastolic blood pressure (DBP) reduction of 26.8, 34.1, and 40.5 mmHg, respectively. DBP began to decrease from day 8 in the EEMV group with a DBP reduction of 24.1 mmHg. In the HF, EF, and WF groups, decreasing in DBP occurred on day 14 which were 22.0, 24.5, and 35.4 mmHg, respectively. NO level in rat serum was increased significantly at 90 min after administration of EEMV 100 mg/kg bw and WF 40.73 mg/kg bw. Increasing in NO levels due to EF with a dose of 1.66 mg/kg bw was not significantly different to control group.Conclusion: Ethanol extract of A. cordifolia had the antihypertensive effect in dexamethasone-induced hypertensive rats, so does its WF and EF. The mechanism of ethanol extract of Madeira vine leaves and its WF most likely due to vasodilation effect through NO-pathway, whereas EF could have other mechanism(s) of action.
... Many studies have investigated the possible relationship between dietary intake of phytochemicals with blood pressure reduction. Several authors have demonstrated a certain inverse correlation with diastolic pressure (Biesinger et al., 2016), or both systolic and diastolic (Brull et al., 2015;Medina-Remon et al., 2015Moreno-Luna et al., 2012), thus reducing one of the most harmful risk factor for CVDs (Barona et al., 2012;Ferri et al., 2015;Grassi et al., 2010;Hassellund et al., 2013;Huang et al., 2013;Hugel et al., 2016;Medina-Remon et al., 2013a;Porteri et al., 2010;Sudano et al., 2012). Conversely, others have not found significant effects (Botden et al., 2012;Hodgson et al., 2014;Ras et al., 2013). ...
Polyphenols are secondary metabolites of plants. They comprise several antioxidant compounds and they are generally considered to be involved in the defense against human chronic diseases. During the last years, there has been growing scientific interest in their potential health benefits. In this comprehensive review, we focus on the current evidence defining the position of their dietary intake in the prevention/treatment of human chronic diseases, including prostate cancer and other types of cancer, cardiovascular diseases, diabetes mellitus and neurodegenerative diseases such as Alzheimer's and Parkinson's disease; we also discuss their ability to modulate multiple signalling transduction pathways involved in the pathophysiology of these diseases. Despite the fact that data regarding the biological functions of polyphenols can be considered exhaustive, evidence is still inadequate to support clear beneficial effects on human chronic diseases. Currently, most data suggest that a combination of phytochemicals rather than any single polyphenol is responsible for health benefit. More studies investigating the role of polyphenols in the prevention of chronic human diseases are needed, especially for evaluating factors such as gender, age, genotype, metabolism and bioavailability.
... In this context, several epidemiological studies suggest a strong correlation between daily cocoa intake and better cardiovascular outcome in different population settings (19)(20)(21). Clinical interventional studies demonstrated a positive effect of flavanol-rich cocoa or chocolate intake on BP reduction and improvement in microvascular and macrovascular function (116,117). In vitro and in vivo studies identified increased NO availability, increased NO synthase activity, and inhibition of ACE as putative mechanisms of this beneficial effect (118). ...
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Cardiovascular disease (CVD) represents the most common cause of death worldwide. The consumption of natural polyphenol-rich foods, and cocoa in particular, has been related to a reduced risk of CVD, including coronary heart disease and stroke. Intervention studies strongly suggest that cocoa exerts a beneficial impact on cardiovascular health, through the reduction of blood pressure (BP), improvement of vascular function, modulation of lipid and glucose metabolism, and reduction of platelet aggregation. These potentially beneficial effects have been shown in healthy subjects as well as in patients with risk factors (arterial hypertension, diabetes, and smoking) or established CVD (coronary heart disease or heart failure). Several potential mechanisms are supposed to be responsible for the positive effect of cocoa; among them activation of nitric oxide (NO) synthase, increased bioavailability of NO as well as antioxidant, and anti-inflammatory properties. It is the aim of this review to summarize the findings of cocoa and chocolate on BP and vascular function.
Cerebrovascular diseases (CBD) are one of the most dangerous complications of atherosclerosis. The clinical consequences of CBD deeply impact quality of life and the prognosis of patients. Atherosclerosis is the main cause of CBD development. Hypertension, dyslipidemia, diabetes, smoking, obesity, and other risk factors explain the higher CBD incidence in the general population, as they are able to anticipate the clinical expression of atherosclerosis. These risk factors are effectively able to promote endothelial dysfunction which is the premise for the early, clinical expression of atherosclerosis. The mechanisms by which risk factors can influence the occurrence of CBD are different and not fully understood. The inflammatory background of atherosclerosis can explain a great part of it. In particular, the oxidative stress may promote the development of vascular lesions by negatively influencing biochemical cellular processes of the endothelium, thus predisposing the vascular tree to morphological and functional damages. The aim of this narrative review is to evaluate the role of endothelial dysfunction and oxidative stress in CBD development.
Background Endothelial vasodilator dysfunction is a characteristic feature of patients at risk for coronary atherosclerosis. Therefore, we prospectively investigated whether coronary endothelial dysfunction predicts disease progression and cardiovascular event rates. Methods and Results: Coronary vasoreactivity was assessed in 147 patients using the endothelium-dependent dilator acetylcholine, sympathetic activation by cold presser testing, dilator responses to increased blood flow, and dilation in response to nitroglycerin. Cardiovascular events (cardiovascular death, unstable angina, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary bypass grafting, ischemic stroke, or peripheral artery revascularization) served as outcome variables over a median follow-up period of 7.7 Sears, Patients suffering from cardiovascular events during follow-up (n=16) had significantly increased vasoconstrictor responses to acetylcholine infusion (P=0.009) and cold presser testing (P=0.002), as well as significantly blunted vasodilator responses to increased blood flow (P<0.001) and the intracoronary injection of nitroglycerin (P=0.001). Impaired endothelial and endothelium-independent coronary vasoreactivity were associated with a significantly higher incidence of cardiovascular events 62 Kaplan-Meier analysis, By multivariate analysis, all tests of coronary vasoreactivity were significant, independent predictors of a poor prognosis, even after adjustment for traditional cardiovascular risk factors or the presence of atherosclerosis itself, Conclusions: Coronary endothelial vasodilator dysfunction predicts long-term atherosclerotic disease progression and cardiovascular event rates, Thus, the assessment of coronary endothelial vasoreactivity can pro tide pivotal information as both a diagnostic and prognostic tool in patients at risk for coronary heart disease.
The aim of this study was to examine the effects of procyanidins derived from cocoa on vascular smooth muscle. Two hypotheses were tested: 1) extracts of cocoa, which are rich in procyanidins, cause endothelium-dependent relaxation (EDR), and 2) extracts of cocoa activate endothelial nitric oxide synthase (NOS), The experiments were carried out on aortic rings obtained from New Zealand White rabbits. The polymeric procyanidins (tetramer through decamer of catechin) caused an EDR. In addition, the Ca2+-dependent NOS activity, measured by the L-arginine to L-citrulline conversion assay, was significantly increased in aortic endothelial cells exposed to polymeric procyanidins, whereas monomeric compounds had no such effect. These findings demonstrate that polymeric procyanidins cause an EDR that is mediated by activation of NOS.
Epidemiological studies demonstrate that regular dietary intake of plant-derived foods and beverages reduces the risk of coronary heart disease [1-4] and stroke [5], and is inversely associated with the risk of cardiovascular disease in general [2], [4].
Background: Epidemiological studies suggested that consumption of fruit and vegetables may protect against stroke. The hypothesis that dietary antioxidant vitamins and flavonoids account for this observation is investigated in a prospective study. Methods: A cohort of 552 men aged 50 to 69 years was examined in 1970 and followed up for 15 years. Mean nutrient and food intake was calculated from crosscheck dietary histories taken in 1960, 1965, and 1970. The association between antioxidants, selected foods, and stroke incidence was assessed by Cox proportional hazards regression analysis. Adjustment was made for confounding by age, systolic blood pressure, serum cholesterol, cigarette smoking, energy intake, and consumption of fish and alcohol. Results: Forty-two cases of first fatal or nonfatal stroke were documented Dietary flavonoids (mainly quercetin) were inversely associated with stroke incidence after adjustment for potential confounders, including antioxidant vitamins. The relative risk (RR) of the highest vs the lowest quartile of flavonoid intake (greater than or equal to 28.6 mg/d vs <18.3 mg/d) was 0.27 (95% confidence interval [CI], 0.11 to 0.70). A lower stroke risk was also observed for the highest quartile of beta-carotene intake (RR, 0.54; 95% CI, 0.22 to 1.33). The intake of vitamin C and vitamin E was not associated with stroke risk. Black tea contributed about 70% to flavonoid intake. The RR for a daily consumption of 4.7 cups or more of tea vs less than 2.6 cups of tea was 0.31 (95% CI, 0.12 to 0.84). Conclusions: The habitual intake of flavonoids and their major source (tea) may protect against stroke.
Objective: To determine whether flavonoid intake explains differences in mortality rates from chronic diseases between populations.Design: Cross-cultural correlation study.Setting/Participants: Sixteen cohorts of the Seven Countries Study in whom flavonoid intake at baseline around 1960 was estimated by flavonoid analysis of equivalent food composites that represented the average diet in the cohorts.Main Outcome Measures: Mortality from coronary heart disease, cancer (various sites), and all causes in the 16 cohorts after 25 years of follow-up.Results: Average intake of antioxidant flavonoids was inversely associated with mortality from coronary heart disease and explained about 25% of the variance in coronary heart disease rates in the 16 cohorts. In multivariate analysis, intake of saturated fat (73%; P=.0001), flavonoid intake (8%; P=.01), and percentage of smokers per cohort (9%; P=.03) explained together, independent of intake of alcohol and antioxidant vitamins, 90% of the variance in coronary heart disease rates. Flavonoid intake was not independently associated with mortality from other causes.Conclusions: Average flavonoid intake may partly contribute to differences in coronary heart disease mortality across populations, but it does not seem to be an important determinant of cancer mortality.(Arch Intern Med. 1995;155:381-386)