Quercetin Mengurangi Tekanan Darah di Subjek hipertensi (SHALLY MARLI MAULANA)
Quercetin Reduces Blood Pressure in Hypertensive Subjects1,2
Randi L. Edwards,3 Tiffany Lyon,3 Sheldon E. Litwin,4 Alexander Rabovsky,6 J. David Symons,3,5 and Thunder Jalili3*
Division of Nutrition, 4Division of Cardiology, and 5Department of Exercise and Sports Science, University of Utah, Salt Lake City, UT 84112 and 6USANA Health Sciences, Salt Lake City, UT 84120
Quercetin Reduces Blood Pressure in Hypertensive Subjects1,2
Randi L. Edwards,3 Tiffany Lyon,3 Sheldon E. Litwin,4 Alexander Rabovsky,6 J. David Symons,3,5 and Thunder Jalili3*
Division of Nutrition, 4Division of Cardiology, and 5Department of Exercise and Sports Science, University of Utah, Salt Lake City, UT 84112 and 6USANA Health Sciences, Salt Lake City, UT 84120
Introduction
Quercetin is a flavonol that belongs to a group of polyphenolic compounds known as flavonoids (1). Widespread epidemiological evidence indicates that quercetin contained in onions, apples,berries, and red wine aids in preventing cardiovascular disease and stroke (2–8). Along with these promising data, recent laboratory studies have demonstrated that quercetin has important vasorelaxant properties on isolated arteries and lowers blood pressure in the spontaneously hypertensive rat (9,10). In addition, we have shown that quercetin administered to rats prevents the development of hypertension and cardiac hypertrophy in response to pressure overload created by abdominal aortic constriction (11). The beneficial effects of quercetin concerning vasorelaxation and blood pressure in rodents have been attributed at least in part to the ability of this flavonoid to decrease indices of oxidative stress (9,11,12). Despite existing epidemiological and animal-based research concerning quercetin and cardiovascular disease, no studies have evaluated whether quercetin supplementation lowers blood pressure in hypertensive humans. Therefore, we performed a randomized, placebo-controlled crossover trial to test the hypothesis that quercetin reduces blood pressure in prehypertensive and stage 1 hypertensive subjects. Systemic markers of oxidant load also were examined as secondary outcomes to determine whether reductions in blood pressure were associated with lower indices of oxidative stress.
Quercetin is a flavonol that belongs to a group of polyphenolic compounds known as flavonoids (1). Widespread epidemiological evidence indicates that quercetin contained in onions, apples,berries, and red wine aids in preventing cardiovascular disease and stroke (2–8). Along with these promising data, recent laboratory studies have demonstrated that quercetin has important vasorelaxant properties on isolated arteries and lowers blood pressure in the spontaneously hypertensive rat (9,10). In addition, we have shown that quercetin administered to rats prevents the development of hypertension and cardiac hypertrophy in response to pressure overload created by abdominal aortic constriction (11). The beneficial effects of quercetin concerning vasorelaxation and blood pressure in rodents have been attributed at least in part to the ability of this flavonoid to decrease indices of oxidative stress (9,11,12). Despite existing epidemiological and animal-based research concerning quercetin and cardiovascular disease, no studies have evaluated whether quercetin supplementation lowers blood pressure in hypertensive humans. Therefore, we performed a randomized, placebo-controlled crossover trial to test the hypothesis that quercetin reduces blood pressure in prehypertensive and stage 1 hypertensive subjects. Systemic markers of oxidant load also were examined as secondary outcomes to determine whether reductions in blood pressure were associated with lower indices of oxidative stress.
Materials and Methods
Participants and recruitment criteria This study was approved by the University of Utah Human Use Review Committee, University of Utah Institutional Review Board, and written informed consent was obtained from each participant. Recruitment efforts in the greater Salt Lake City area targeted males and females with prehypertension (120–139 mm Hg systolic/80–89 mm Hg diastolic) and stage 1 hypertension (140–159 mm Hg systolic/90–99 mm Hg diastolic) as defined by the 7th Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (13). Figure 1 summarizes the number of subjects screened, recruited, and enrolled in this study. Initial screening consisted of asking volunteers if they had a history of high blood pressure, followed by a single blood pressure measurement using an Omron random zero blood pressure analyzer. If blood pressure criteria were met during the initial screening, subjects were referred to the Nutrition Clinic for further evaluation of blood pressure and confirmation of eligibility criteria. Subjects who met blood pressure guidelines and eligibility criteria after the clinical evaluation were enrolled in the study. We recruited participants from October 2004 to June 2005. Forty-four patients who met study criteria consented and were enrolled, 21 prehypertensive and 23 stage 1 hypertensive. Forty-one subjects completed the entire protocol and 3 withdrew (1 male and 1 female from the prehypertensive group and 1 male from the stage 1 hypertensive group).
Participants and recruitment criteria This study was approved by the University of Utah Human Use Review Committee, University of Utah Institutional Review Board, and written informed consent was obtained from each participant. Recruitment efforts in the greater Salt Lake City area targeted males and females with prehypertension (120–139 mm Hg systolic/80–89 mm Hg diastolic) and stage 1 hypertension (140–159 mm Hg systolic/90–99 mm Hg diastolic) as defined by the 7th Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (13). Figure 1 summarizes the number of subjects screened, recruited, and enrolled in this study. Initial screening consisted of asking volunteers if they had a history of high blood pressure, followed by a single blood pressure measurement using an Omron random zero blood pressure analyzer. If blood pressure criteria were met during the initial screening, subjects were referred to the Nutrition Clinic for further evaluation of blood pressure and confirmation of eligibility criteria. Subjects who met blood pressure guidelines and eligibility criteria after the clinical evaluation were enrolled in the study. We recruited participants from October 2004 to June 2005. Forty-four patients who met study criteria consented and were enrolled, 21 prehypertensive and 23 stage 1 hypertensive. Forty-one subjects completed the entire protocol and 3 withdrew (1 male and 1 female from the prehypertensive group and 1 male from the stage 1 hypertensive group).
Results
Patient characteristics. Nearly 1000 patients were interviewed and screened for eligibility. The majority (i.e. ;800) were not considered further for participation because they met 1 or more of the exclusion criteria or did not have blood pressure within study limits. From this initial screening, 204 individuals were evaluated in more detail at a subsequent clinic visit to determine whether all inclusion/exclusion criteria were met and if blood pressure was within the study limits (Fig. 1). Forty-four subjects were initially enrolled and 41 completed the entire 12-wk study. The age of prehypertensive (n ¼ 19, n ¼ 13 males) and stage 1 hypertensive (n ¼ 22, n ¼ 13 males) subjects was 47.8 6 3.5 and 49.2 6 2.9 y old, respectively. No adverse effects of quercetin or placebo treatment were reported during the course of the study.Weight and BMI did not change between treatments in either group (Table 2). Heart rate was unchanged throughout
the study (data not shown).
Plasma quercetin was 695 6 103 nmol/L after placebo treatment and increased to 1419 6 189 nmol/L after quercetin treatment. Our preliminary experiments indicated that a 1-wk washout period was sufficient to bring plasma quercetin concentrations to 562 6 27 nmol/L. These values are similar to those obtained from subjects who consumed placebo but had not yet been exposed to quercetin. There was also no effect of treatment order on the observed changes in blood pressure (r ¼ 0.194; P ¼ 0.388), indicating that the antihypertensive effect of quercetin did not persist in those who received quercetin supplements before
placebo.
Patient characteristics. Nearly 1000 patients were interviewed and screened for eligibility. The majority (i.e. ;800) were not considered further for participation because they met 1 or more of the exclusion criteria or did not have blood pressure within study limits. From this initial screening, 204 individuals were evaluated in more detail at a subsequent clinic visit to determine whether all inclusion/exclusion criteria were met and if blood pressure was within the study limits (Fig. 1). Forty-four subjects were initially enrolled and 41 completed the entire 12-wk study. The age of prehypertensive (n ¼ 19, n ¼ 13 males) and stage 1 hypertensive (n ¼ 22, n ¼ 13 males) subjects was 47.8 6 3.5 and 49.2 6 2.9 y old, respectively. No adverse effects of quercetin or placebo treatment were reported during the course of the study.Weight and BMI did not change between treatments in either group (Table 2). Heart rate was unchanged throughout
the study (data not shown).
Plasma quercetin was 695 6 103 nmol/L after placebo treatment and increased to 1419 6 189 nmol/L after quercetin treatment. Our preliminary experiments indicated that a 1-wk washout period was sufficient to bring plasma quercetin concentrations to 562 6 27 nmol/L. These values are similar to those obtained from subjects who consumed placebo but had not yet been exposed to quercetin. There was also no effect of treatment order on the observed changes in blood pressure (r ¼ 0.194; P ¼ 0.388), indicating that the antihypertensive effect of quercetin did not persist in those who received quercetin supplements before
placebo.
Our study is, to our knowledge, the first to show that quercetin reduces blood pressure in stage I hypertensive individuals. Though we used a powerful experimental design (double blinded, placebo-controlled, crossover) and found quercetin supplementation to be efficacious in reducing blood pressure, extrapolation of our results to the general population should be done with caution given the homogeneous cohort (middle-aged, Caucasian men and women) and modest sample size. Nevertheless, our data indicate that potential exists for this polyphenolic compound to be used as adjunct therapy in diet/ lifestyle interventions to help control blood pressure in hypertensive individuals.
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