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Dealcoholized Red Wine Decreases Systolic and Diastolic Blood Pressure and Increases Plasma Nitric Oxide

Short Communication
Originally publishedhttps://doi.org/10.1161/CIRCRESAHA.112.275636Circulation Research. 2012;111:1065–1068

Abstract

Rationale:

Experimental studies have shown a potential blood pressure (BP) lowering effect of red wine polyphenols, whereas the effects of ethanol and polyphenols on BP in humans are not yet clear.

Objective:

The aim of the present work was to evaluate the effects of red wine fractions (alcoholic and nonalcoholic) on BP and plasma nitric oxide (NO) in subjects at high cardiovascular risk.

Methods and Results:

Sixty-seven men at high cardiovascular risk were studied. After a 2-week run-in period, subjects were randomized into 3 treatment periods in a crossover clinical trial, with a common background diet plus red wine (30g alcohol/day), the equivalent amount of dealcoholized red wine, or gin (30g alcohol/day), lasting 4 weeks each intervention. At baseline and after each intervention, anthropometrical parameters, BP and plasma NO were measured. Systolic and diastolic BP decreased significantly after the dealcoholized red wine intervention and these changes correlated with increases in plasma NO.

Conclusions:

Dealcoholized red wine decreases systolic and diastolic BP. Our results point out through an NO-mediated mechanism. The daily consumption of dealcoholized red wine could be useful for the prevention of low to moderate hypertension. Trial registered at controlled-trials.com: ISRCTN88720134.

Introduction

Epidemiological evidence has associated moderate alcohol consumption with decreased cardiovascular risk.1 However, red wine (RW) seems to confer greater protective effects because of its high polyphenolic content. In vitro and experimental studies have shown a potential blood pressure (BP)-lowering effect and/or enhancement of endothelial nitric oxide (NO) production by RW.2 It is unclear whether these effects can be extrapolated to humans, because the amount of RW polyphenols used in these studies is usually higher than that achieved through moderate RW consumption. Recently, small amounts of RW, but not other alcoholic beverages, were shown to increase plasma NO concentrations.3 Although the negative effects of heavy or binge alcohol drinking on BP are well known, the effects of moderate alcohol consumption are controversial, because some studies have observed a linear trend and others a nonlinear or J-shaped association, independently of the beverage consumed.46 Therefore, the aim of the present study was to evaluate the effects of RW fractions (alcoholic and nonalcoholic) on BP and plasma NO concentration in high cardiovascular risk subjects.

Editorial, see p 959

Methods

The study was an open, randomized, crossover, controlled clinical trial comprising three 4-week periods. Detailed Methods have been published7 and are provided in the Online Data Supplement.

Seventy-three men at high cardiovascular risk, aged between 55 and 75 years were included in the study. All subjects had diabetes mellitus or ≥3 cardiovascular disease risk factors.7 After a 2-week run-in period wherein subjects were asked not to consume any alcoholic beverage, they were randomized using a computer-generated table into 3 treatments in a crossover design, with a common background diet plus gin (100 mL, 30 g ethanol/day), RW (272 mL, 30 g ethanol/day; total polyphenols: 798 Eq Gallic Acid/day, EGA/day), and the same amount of polyphenols as RW in the form of dealcoholized red wine (DRW) (272 mL - total phenols: 733 EGA/day), resulting in 6 possible beverage sequences lasting 4 weeks each intervention. No washout periods were included between the interventions.

After the run-in period (baseline) and the day after each intervention period (RW, DRW, and gin), BP and heart rate were measured 3 times at 5-minute intervals on the nondominant arm with an oscillometer (Omron 705 CP; Omron Matsusaka Co Ltd, Matsusaka City, Japan) after 15 minutes resting in a seated position. The mean of the second and the third measures was considered for statistical analysis.

Fasting blood samples for the NO analyses were collected at baseline and after each intervention, and stored at −80°C until assayed. For measurement of NO, the release of NO2 and NO3, the stable breakdown products of NO in plasma, were determined by a chemiluminescence detector in an NO analyzer (Sievers Instruments, Boulder, CO).

Statistical analyses were performed using the Statistical Analysis Systems (version 9.2, SAS Institute Inc, Cary, NC). To analyze the changes within each treatment, a Student t test for paired samples was performed between the data obtained before and after each intervention. One-factor ANOVA for repeated measures and the Bonferroni post-hoc test were used to compare the differences of the changes in outcome variables between the interventions. See the Online Data Supplement for further details of statistical analyses.

Results

The baseline characteristics of the 67 subjects who completed the study are detailed in Table 1. Reasons for exclusion of 6 participants are described in the Online Data Supplement. No significant differences in body mass index, waist-to-hip ratio, and heart rate were observed (Table 2). Systolic BP (SBP) and diastolic BP (DBP) decreased significantly after the DRW intervention (P=0.0001 and 0.017, respectively) (Figure). These changes were significantly different from those observed after the gin intervention (P=0.026 and 0.045 for SBP and DPB, respectively) (Table 2). Plasma NO concentration increased after the DRW intervention (P=0.041) and the change was also significantly different from that observed after the gin intervention (P=0.026). The changes in BP and NO after the DRW period were correlated (r=0.598; P<0.001 and r=0.362; P=0.002 for SBP and DBP, respectively; Online Figure I). The intervention with RW did not differ from the DRW and gin interventions, although SBP and DBP tended to decrease and NO tended to increase after the RW intervention compared to the gin period (P=0.069, 0.075, and 0.079 for SBP, DBP, and NO, respectively). In addition, changes in SBP correlated with changes in NO after the RW intervention (r=0.251, P=0.035). Exclusion of participants with hypertension or antihypertensive treatment did not materially change the results (Online Table I). Intervention compliance and dietary data during the three interventions are also shown in the Online Data Supplement. No carryover effect was observed for any outcome.

Figure.

Figure. SBlood pressure and plasma nitric oxide in the 67 subjects studied. *Comparisons between before and after the interventions (Student t test for paired samples). Before each intervention is the value of the previous intervention or the baseline in the first intervention.

Table 1 Baseline Characteristics of the Study Subjects

CharacteristicMean±SD*
Age, y60±8
Current smokers [n (%)]16 (23.9)
Sedentarism [n (%)]40 (59.7)
Family history of premature CHD n (%)52 (77.6)
Type-2 diabetes [n (%)]15 (22.4)
Hypertension [n (%)]38 (56.7)
Dyslipemia [n (%)]16 (23.9)
Medications [n (%)]
  ACE inhibitors28 (41.8)
  Diuretics5 (7.5)
  Statins22 (32.8)
  Oral hypoglycemic drugs14 (20.9)
  Aspirin or antiplatelet drugs15 (22.4)
Triglycerides (mg/dL)128±60
Total cholesterol (mg/dL)204 ± 33
LDL-cholesterol (mg/dL)133 ± 32
HDL-cholesterol (mg/dL)43 ± 7
LDL/HDL ratio3.08±0.10

**Mean+SD or n (%), when indicated (n=67).

CHD indicates coronary heart disease; ACE, angiotensin-converting enzyme.

Table 2 Changes in Anthropometric Parameters, Blood Pressure, and Plasma Concentrations of Nitric Oxide in the 67 Subjects Studied After the 3 Interventions

Red Wine InterventionDealcoholized Red Wine InterventionGin InterventionP *
Body mass index (kg/m2)0.6 (–0.7, 0.2)–0.1 (–0.4, 0.1)–0.1 (–0.3, 0.1)0.200
Waist-to-hip ratio–0.006 (–0.013, 0.001)–0.001 (–0.006, 0.005)0.007 (–0.002, 0.015)0.118
Systolic blood pressure (mm Hg)–2.3 (–5.1, 0.5),–5.8 (–8.9, 2.7)–0.8 (–4.1, 2.5)0.028
Diastolic blood pressure (mm Hg)–1.0 (–2.5, 0.5),–2.3 (–4.1, 0.4)0.1 (–1.8, 1.9)0.027
Heart rate (beats/min)–0.2 (–1.9, 1.5)–1.7 (–3.4, 0.1)1.1 (–0.8, 3.0)0.187
Nitric oxide (µmol/L)–0.6 (–3.3, 4.3),4.1 (0.5, 7.6)–1.4 (–4.1, 1.3)0.022

Results expressed as mean differences (95% confidence interval) between after and before each intervention. Before each intervention is the value of the previous intervention or the baseline (run-in period) in the first intervention.

*P value of the repeated-measures ANOVA from the differences between interventions.

†,‡Values in a row with different symbols are significantly different.

Discussion

After the 4-week interventions with RW, DRW, and gin in a crossover study in high cardiovascular risk subjects, we observed that DRW decreased SBP and DBP while increasing plasma NO concentration. RW tended to have similar effects to those of DRW but BP changes were nonsignificant and gin had no effect. Therefore, the BP-lowering and NO-raising effects should be attributed to the RW polyphenols and not to alcohol, which seems to counteract the effects of the nonalcoholic fraction of RW.

Botden et al observed that RW polyphenol consumption for 4 weeks did not affect the BP in subjects with high-normal BP or grade 1 hypertension8 or in healthy young women9 and postulated that RW polyphenols could only favorably affect BP in subjects with endothelial dysfunction.8 Our study included subjects with high-normal BP or grade 1 hypertension, but we did not measure endothelial function. However, considering the load of cardiovascular risk factors of the study subjects, their probability of having endothelial dysfunction was very high. On the other hand, Huang et al3 reported increased plasma NO in healthy volunteers consuming 100 mL/day of RW during 3 weeks, but not when they consumed equivalent amounts of alcohol as beer or vodka, although no BP changes were reported after any intervention.

The results of our study point out that moderate alcohol consumption does not affect BP. Okubo et al6 observed a J-shaped association between alcohol consumption and BP changes in a normotensive population, with a threshold effect at 18 mL of daily ethanol consumption. Besides, the meta-analysis of Xin et al.10 described a dose-response relationship between the reduction of alcohol consumption in heavy alcohol drinkers (≥3 drinks/day) and the reduction of BP. We studied moderate alcohol consumers who followed a run-in period with abstention from alcohol, and 4 weeks of moderate consumption of RW or gin had little effect on BP, suggesting that moderate alcohol consumption does not affect BP, at least in high cardiovascular risk subjects. These results concur with those of Frisoli et al4 and Stranges et al,11 who observed no consistent association of beer, wine, or liquor consumption with the risk of hypertension. Stranges et al11 also observed that drinking outside meals increased the risk of hypertension independently of the amount of alcohol consumed. Our study subjects were advised to consume the beverages during meals and this may explain, in part, why moderate alcohol consumption did not affect BP.

Finally, although the BP reduction after DRW consumption was modest (5.8 and 2.3 mm Hg of SBP and DBP, respectively), decreases of 4 or 2 mm Hg in SBP or DBP respectively, have been associated with a 14% and 20% reduction in coronary heart disease and stroke risk, respectively,12 conferring clinical significance to our results, especially in the case of DRW.

Our study has limitations. A 4-week intervention may not represent the potential effects of long-term consumption. In addition, the specific substances responsible for the observed effects could not be identified and endothelial function was not measured. In conclusion, DRW decreases SBP and DBP, possibly through an NO-mediated mechanism. Therefore, the daily consumption of DRW may be useful for the prevention of low to moderate hypertension.

Acknowledgments

We thank the participants of the study. We are indebted to Torres S.A. for providing the wines and to Gin Xoriguer for providing the gin. CIBERobn is an initiative of ISCIII, Spain.

Non-standard Abbreviations and Acronyms

BP

blood pressure

DBP

diastolic blood pressure

DRW

dealcoholized red wine

NO

nitric oxide

RW

red wine

SBP

systolic blood pressure

Footnotes

In July 2012, the average time from submission to first decision for all original research papers submitted to Circulation Research was 11.2 days

The online-only Data Supplement is available with this article at http://circres.ahajournals.org/lookup/suppl/doi:10.1161/CIRCRESAHA.112.275636/-/DC1.

Correspondence to Ramon Estruch, Department of Internal Medicine, Hospital Clinic, Villarroel 170, 08036, Barcelona, Spain. E-mail

References

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Novelty and Significance

What Is Known?

  • Hypertension is a major cardiovascular risk factor and is associated with decreased life expectancy.

  • Endothelial secretion of nitric oxide (NO), a potent vasodilator, contributes to lower blood pressure.

  • In experimental studies, dietary compounds such as polyphenols (contained in fruits, vegetables, and fermented alcoholic beverages such as red wine) have been shown to stimulate the secretion of endothelial NO, potentially decreasing blood pressure.

  • The relationship between moderate alcohol consumption and blood pressure has not been clearly established.

What New Information Does This Article Contribute?

  • Moderate red wine consumption (alcohol plus polyphenols) does not significantly affect blood pressure or NO production.

  • Moderate gin consumption (alcohol without polyphenols) does not significantly affect blood pressure or NO production.

  • Dealcoholized red wine consumption (red wine polyphenols without alcohol) significantly decreases systolic and diastolic blood pressure and increases plasma NO concentration.

Although an inverse relationship between moderate alcohol consumption and the incidence of hypertension has been described, the effects of the different alcoholic beverage fractions (alcoholic and nonalcoholic) on blood pressure are unclear. We observed that moderate alcohol consumption, independently of beverage type (red wine or gin) did not significantly affect blood pressure, but dealcoholized red wine decreased blood pressure and these changes were correlated with plasma NO increases. The findings provide new insights into the role of dietary components such as red wine polyphenols in cardiovascular health, particularly in blood pressure regulation. Consumption of dealcoholized red wine might be useful in preventing low- to moderate-degree hypertension.