Effects of total dietary polyphenols on plasma nitric oxide and blood pressure in a high cardiovascular risk cohort. The PREDIMED randomized trial

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Highlights

  • Effects of one-year intervention with a traditional Med-diet supplemented with either extra virgin olive oil or nuts.

  • Decrease in blood pressure (BP) was mediated by plasma nitric oxide (NO) production.

  • Total polyphenol excretion in spot urine was positively correlated with plasma NO.

  • Mediterranean diets may help to decrease BP due to a high polyphenol consumption.

Abstract

Background and aim

Hypertension is one of the main cardiovascular risk factors in the elderly. The aims of this work were to evaluate if a one-year intervention with two Mediterranean diets (Med-diet) could decrease blood pressure (BP) due to a high polyphenol consumption, and if the decrease in BP was mediated by plasma nitric oxide (NO) production.

Methods and results

An intervention substudy of 200 participants at high cardiovascular risk was carried out within the PREDIMED trial. They were randomly assigned to a low-fat control diet or to two Med-diets, one supplemented with extra virgin olive oil (Med-EVOO) and the other with nuts (Med-nuts). Anthropometrics and clinical parameters were measured at baseline and after one year of intervention, as well as BP, plasma NO and total polyphenol excretion (TPE) in urine samples. Systolic and diastolic BP decreased significantly after a one-year dietary intervention with Med-EVOO and Med-nuts. These changes were associated with a significant increase in TPE and plasma NO. Additionally, a significant positive correlation was observed between changes in urinary TPE, a biomarker of TP intake, and in plasma NO (Beta = 4.84; 95% CI: 0.57–9.10).

Conclusions

TPE in spot urine sample was positively correlated with plasma NO in Med-diets supplemented with either EVOO or nuts. The statistically significant increases in plasma NO were associated with a reduction in systolic and diastolic BP levels, adding to the growing evidence that polyphenols might protect the cardiovascular system by improving the endothelial function and enhancing endothelial synthesis of NO.

Introduction

Hypertension is one of the main cardiovascular risk factors in the elderly. Hypertension can be managed by following a healthy diet rich in fruits and vegetables, such as the Mediterranean [1] or DASH (Dietary-Approaches-to-Stop-Hypertension) diets, and improving other lifestyle factors [2].

Several epidemiological studies have demonstrated an inverse association between adherence to traditional Mediterranean diet (Med-diet) and death from coronary heart diseases (CHD) [3], [4]. This protective effect has been partially attributed to a high content of bioactive compounds such as phytosterols, and phenolic compounds [4], which seems to be inversely associated with BP [5], [6]. In a previous study, polyphenol intake, assessed via total polyphenols excreted (TPE) in urine, was negatively associated with BP levels in an elderly Mediterranean population at high cardiovascular risk. In addition, epidemiological studies have concluded that polyphenol-rich food intake may decrease systolic and diastolic BP in humans [7], [8], [9]. A plausible mechanism for this effect afforded by polyphenol-rich foods is an induction of vasodilation via activation of the NO system [5], [10].

The aims of this study were to evaluate within the PREDIMED trial if a high polyphenol consumption, measured via TPE in spot urine samples, in a one-year intervention with a traditional Med-diet supplemented with either extra virgin olive oil (Med-EVOO) or nuts (Med-nuts), would decrease systolic and diastolic BP compared with a control diet, and if the decrease in BP was mediated by plasma nitric oxide (NO) production.

Section snippets

Subjects

The PREDIMED study is a large, parallel-group, multicenter, randomized, controlled clinical trial of 4.8-year duration aimed at evaluating the preventative effects of the traditional Med-diet on cardiovascular events (www.predimed.org). The detailed recruitment method and study protocol have been described previously [3], [11]. For this substudy, between October-2003 and July-2004 we selected 200 randomly participants recruited from five primary health centers. Eligible participants were

Results

Baseline characteristics of the total group according to intervention are shown in Table 1. No differences were observed between intervention groups at baseline. By study design, participants were over 54 years old [mean age (SD): 67.6 (6.0)], 56.5% women, mostly overweight [mean BMI(SD): 29.0 (3.4) kg/m2], and with a sizeable burden of cardiovascular risk factors (62.5% diabetics, 77.0% hypertensive, 72.0% with dyslipidemia, 16.5% active smokers and 46.3% with a family history of early-onset

Discussion

In the elderly participants at high cardiovascular risk included in the PREDIMED trial, we observed that the changes in plasma NO were associated with significantly lower systolic and diastolic BP after one-year interventions with Med-diets supplemented with EVOO or nuts, compared with the control diet. We also observed a significant positive correlation between changes in urinary TPE, as a biomarker of TP intake, and changes in plasma NO.

Olive oil is the main natural fat in the Med-diet [3],

Acknowledgments

We would like to thank all the volunteers involved in the PREDIMED study for their valuable cooperation. This study was supported in part by CICYT (AGL2010-22319-C03 and AGL2013-49083-C3-1-R), RD06/0045 and CIBEROBN from the ISCIII (Spanish Ministry of Science and Innovation, MICINN), Quality Group from Generalitat de Catalunya 2009-SGR-724 and 2014-SGR-773, and Grant of support to research groups no.35/2011 (Balearic Islands Gov. and EU FEDER funds). A.M.-R. thanks the “Juan de la Cierva”

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