Watermelon extract reduces blood pressure but does not change sympathovagal balance in prehypertensive and hypertensive subjects

Abstract

Previous studies have shown that watermelon extract reduces blood pressure through vasodilation. However, those studies have not verified whether sympathetic nervous activity is influenced by watermelon extract. This study aimed to evaluate the effect of supplementation with watermelon extract for 6 weeks on blood pressure and sympathovagal balance of prehypertensive and hypertensive individuals. Forty volunteers participated in a randomized, double-blind, experimental and placebo-controlled study. They consumed 6 g of watermelon extract daily (n = 20; age 48.7 ± 1.9 years, 10 men) or a placebo (n = 20; age 47.4 ± 1.2 years, 11 men) for 6 weeks. Blood pressure and cardiac autonomic modulation were measured. Watermelon extract promoted a significant reduction in systolic (137.8 ± 3.9 to 126.0 ± 4.0 mmHg, p < 0.0001) and diastolic (79.2 ± 2.2 to 72.3 ± 2.0 mmHg, p < 0.001) blood pressure, but showed no differences compared to the placebo group. This significant reduction in blood pressure occurred without a significant change in sympathovagal balance from the beginning (1.7 ± 0.1) to the end of the study (1.7 ± 0.4). In conclusion, supplementation with watermelon extract reduces systolic and diastolic blood pressure in prehypertensive and hypertensive individuals, but does not alter the cardiac autonomic modulation of these individuals.

Keywords:

• Arginine
• autonomic nervous system
• blood pressure
• hypertension
• watermelon

Introduction

L-arginine is able to decrease blood pressure in hypertensive individuals by increasing the bioavailability of this amino acid, which serves as a substrate for endothelial production of the vasodilator nitric oxide.[1,2] Studies have shown that consumption of watermelon in extract form was effective at reducing blood pressure.[3–6] The authors attribute this hypotensive effect to the L-citrulline present in watermelon, which efficiently converts to L-arginine, resulting in increased production of endothelial nitric oxide.[7]

Beyond the increase in nitric oxide production, reduced blood pressure through supplementation with L-arginine or watermelon has also been accompanied by a decrease in the carotid reflection wave,[3,6] a reduction in arterial stiffness and wave amplitude reflection,[4] a decrease in myocardial oxygen demand during the cold pressor test and an increase in the magnitude of reflection waves induced by cold.[5]

Despite the findings that watermelon extract reduces blood pressure and the investigations into proposed mechanisms, one has to consider that the most evident mechanisms controlling blood pressure are the baroreflex and autonomic nervous activity.[8,9] The exacerbation of sympathetic nervous activity is one of the key mechanisms involved in the maintenance of high blood pressure in hypertensive individuals.[10]

Although the hypotensive effect of watermelon is well documented, these data are from a single group. Moreover, it is unclear whether some of the nutrients from watermelon could reduce sympathetic nervous activity in hypertensive individuals. In fact, Bruno et al. [11] showed that isolated vitamin C was able to restore the sympathovagal balance and baroreflex sensitivity in hypertensive individuals. Therefore, the aim of the present study was to evaluate the effect of 6 weeks of watermelon extract supplementation on blood pressure and sympathovagal balance in prehypertensive and hypertensive individuals.

Methods

Participants

Participants were employees of a public university. Forty prehypertensive and hypertensive individuals were recruited and randomized into two groups, watermelon (n = 20; age 48.7 ± 1 years, 10 men) and placebo (n = 20; age 47.4 ± 1 years, 11 men), to participate in a randomized, double-blind, experimental and placebo-controlled study. The following inclusion criteria were utilized: age between 40 and 60 years, body mass index between 25 and 35 kg/m², hypertensive stage I in drug treatment or prehypertensive (without diagnosed hypertension, but with initial systolic values between 130 and 139 mmHg and diastolic values between 85 and 89 mmHg) according to the VI Brazilian guidelines on arterial hypertension,[12] no other known pathology, and no habitual watermelon or fruit supplement consumption. Participants who changed their antihypertensive drug therapy or dietary and physical activity habits over the course of the study were excluded from the study.

The study was approved by the Ethics Committee of Research involving Humans of the Lauro Wanderley University Hospital, Federal University of Paraiba, under protocol no. 472/11.

All of the participants were informed of the specifics of the study and provided their written informed consent.

Design

The participants initially underwent nutritional assessment, blood pressure measurement and cardiac autonomic modulation measurement. Twenty-four hours after the initial assessment, the supplementation protocol began with either watermelon extract or placebo for 6 weeks. Forty-eight hours after the intervention period, the participants were tested in the same manner as the baseline assessment.

Nutritional assessment

Dietary intake was assessed by a 24 h dietary recall administered three times for each individual, with two dietary recalls representing the weekday diet and one dietary recall representing the weekend diet. The mean of the three values was adopted to investigate the consumption of nutrients using Avanutri Revolution software version 4.0 (Avanutri®, Rio de Janeiro, Brazil).

Supplementation protocols

The volunteers were supplemented daily with 6 g of watermelon extract (L-citrulline/L-arginine 2/1) or placebo for 6 weeks using the same procedure described in Figueroa et al..[3–6] The watermelon extract used in this study was provided by Milne Fruit Products (Prosser, WA, USA) and made from freshly picked watermelons with the dry solids consisting of 100% natural watermelon. According to the manufacturer, the extract contained the following composition per 100 g of product: 205 kcal, 12 mg of vitamin C, 3600 IU of beta-carotene, 24 mg of lycopene, 27 mg of calcium, 18.2 mg of sodium, 0.2% dietary fibre, 4.1% protein, 0.1% fat and 46.9% carbohydrate, of which 24.7% was fructose, 12.3% was dextrose, 13% was sucrose, <0.3% was maltose and <0.3% was lactose. The daily intake of 6 g of fruit extract is equivalent to approximately 1.04 kg of watermelon pulp.[3] The placebo consisted of glucose, sucrose and fructose in a ratio of 2:2:1, which was similar to the composition of watermelon extract carbohydrates. The appearance, colour, texture and flavour were identical between the watermelon extract and placebo. The volunteers received a table with instructions for taking the supplement/placebo and recording daily consumption. Each week, the volunteers were asked about the use of the supplements by the study nutritionist, and electronic messages via mobile phone were sent frequently to remind them to consume the supplements.

Blood pressure measurements

Twenty-four hours before the beginning of the intervention and 48 h after the 6 weeks of supplementation, each volunteer’s blood pressure was assessed in the afternoon. Three measurements were performed with a 5 min interval, using a validated oscillometric device (Omron HEM-7113, Shanghai, China), and the mean of the last two blood pressure measurements was recorded. The blood pressure measurements were performed as recommended by the VI Brazilian guidelines on hypertension [12] and by observing all recommendations about food intake, urine voiding and prior physical activity. The measurements were obtained with the subjects in a seated position with their legs uncrossed after sitting for at least 10 min.

Cardiac autonomic modulation

Autonomic nervous activity was obtained by recording the heart rate R-R interval variability through a Polar® heart rate monitor model RS800CX (Polar, Kempele, Finland). Volunteers were at rest for 10 min before starting the recording of R-R intervals for a minimum of 5 min, so that at least 300 beats were obtained. This measure was taken before the blood pressure measurement. Data were analysed in the time and frequency domain using Kubios HRV software version 2.0 (University of Kuopio, Finland).

Statistical analyses

The data are presented as means ± SE. Normality and homogeneity were evaluated by the Shapiro–Wilk and Levene tests. Unpaired t tests were used to compare baseline and postintervention measurements between the groups. A paired t test was used to evaluate possible differences between preintervention and postintervention. Statistical significance was defined as p < 0.05. Statistical analyses were performed using GraphPad InStat® version 3.0 (GraphPad Software, San Diego, CA, USA).

Results

As shown in Table 1, the groups were similar in age and were normoglycaemic, overweight and dyslipidaemic. The watermelon group had a significantly worse lipid profile and minor sympathovagal balance differences compared to the placebo group. Despite this difference, they had very similar initial blood pressure values. The watermelon group had higher dietary intake of calories and lipids compared to the placebo group. The groups did not change their eating habits during the study. Supplementation with watermelon extract was well tolerated by all of the volunteers and no adverse effects were reported.

Table 1. Baseline characteristics of the study subjects.

	Watermelon (n = 20)	Placebo (n = 20)	p
Age (years)	48.7 ± 1.9	47.4 ± 1.2	0.76
BMI (kg/m^2)	29.6 ± 1.1	28.2 ± 0.7	0.30
WC (cm)	98.1 ± 2.4	94.6 ± 2.5	0.63
Total energy intake (kcal/d)	2744.4 ± 211.7*	2262.64 ± 86.2	0.04
Carbohydrates (g/d)	382.2 ± 24.7	330.7 ± 16.5	0.09
Protein (g/d)	98.2 ± 5.0	91.5 ± 4.8	0.33
Lipids (g/d)	91.4 ± 11.5*	63.7 ± 3.7	0.02
Cholesterol (mg/dl)	251.8 ± 9.6*	208.4 ± 8.3	0.01
HDL-C (mg/dl)	42.8 ± 2.9	40.8 ± 1.8	0.54
LDL-C (mg/dl)	171.4 ± 7.8*	141.9 ± 8.7	0.01
VLDL-C (mg/dl)	38 ± 2.9	30.5 ± 1.8	0.05
TG (mg/dl)	276.2 ± 39.8*	167.4 ± 19.7	0.01
Glycaemia (mg/dl)	101 ± 4.7	98.3 ± 5.7	0.21
SBP (mmHg)	137.8 ± 3.9	136.4 ± 2	0.78
DBP (mmHg)	79.2 ± 2.2	78.0 ± 2.4	0.71
LF/HF	1.7 ± 0.1*	3.2 ± 0.4	0.01

Data are shown as mean ± SE.

BMI: body mass index; WC: waist circumference; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; VLDL-C: very low-density lipoprotein cholesterol; TG: triglycerides; SBP: systolic blood pressure; DBP: diastolic blood pressure; LF/HF: low frequency/high frequency.

* p < 0.05, significantly different from placebo (unpaired t test).

Systolic blood pressure decreased by 11.8 mmHg in the watermelon group, producing final mean values of 126.0 ± 4.0 mmHg. Diastolic blood pressure decreased by 6.9 mmHg for this group, producing a final mean of 72.3 ± 2.0 mmHg. The placebo group showed no changes in blood pressure, ending the study with mean values of 132.6 ± 2 mmHg and 78.5 ± 2 mmHg for systolic and diastolic components, respectively. The changes in pressure between the groups are shown in Figure 1. An analysis stratifying the sample was conducted in prehypertensive and hypertensive patients, but the results of the two groups were very similar to the 11.8 mmHg and 6.9 mmHg previously checked for the overall sample, so the differences were not considered according to hypertensive status (stratified data not shown).

Figure 1. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the watermelon and placebo groups at baseline and after 6 weeks of supplementation. Data are mean ± standard error. *p < 0.0001, **p < 0.001 different from baseline (paired t test).

Watermelon supplementation did not cause any change in the time or frequency domains of heart rate R-R interval variability, as shown in Table 2. The placebo group also showed no significant changes in any of the sympathovagal balance variables, despite having started the study with significantly higher values for autonomic balance compared to the watermelon group.

Table 2. Cardiac autonomic modulation before and after supplementation.

	Watermelon (n = 20)		Placebo (n = 20)
	Baseline	6 weeks	Baseline	6 weeks
SDNN (ms)	38.2 ± 3.1	35.0 ± 4.3	44.3 ± 8.9	29.2 ± 2.1
RMSSD (ms)	27.1 ± 3.9	26.1 ± 4.6	22.1 ± 4.6	14.9 ± 2.6
LF (ms)	411.1 ± 115.9	208.7 ± 37.4	304.5 ± 57.6	196.3 ± 39.2
HF (ms)	293.6 ± 91.7	306.7 ± 102.2	175.1 ± 58.8	113.4 ± 38.0
LF/HF	1.7 ± 0.1†	1.7 ± 0.4†	3.2 ± 0.4	4.3 ± 0.9

Data are shown as mean ± SE.

SDNN: standard deviation of NN intervals; RMSSD: root mean square of successive differences; LF: low frequency; HF: high frequency; LF/HF: low frequency/high frequency.

† p = 0.03, significantly different from placebo (unpaired t test).

Discussion

The present study demonstrated that supplementation with 6 g/day of watermelon extract promoted a significant reduction in systolic and diastolic blood pressure in prehypertensive and hypertensive individuals, although the final values in the treated group were not different from those in the placebo group. Our data corroborate results from four previous studies.[3–6] However, all of those studies were from the same research group, in which the authors reproduced the methodological procedures in prehypertensive populations, hypertensive populations and postmenopausal women.

Comparisons between our data and those found by Figueroa et al. [3–6] are possible because we have utilized the same dose of watermelon extract and intervention period. Therefore, the findings are relevant in that they confirm a phenomenon that had already been well demonstrated, but only by one specific research group.

Although only two research groups in the world have demonstrated the hypotensive effect of watermelon, there is other related evidence supporting this effect. The reduction in blood pressure is attributed to watermelon’s high content of L-citrulline, which is converted to L-arginine.[7] Our group has published work showing that a significant reduction in blood pressure after supplementation with 6 g/day of L-arginine in hypertensive middle-aged women was accompanied by an increase in serum nitrite/nitrate from 26.6 ± 2 to 44.6 ± 4.[1] The vasodilatory effect of L-arginine has already been demonstrated in vascular reactivity studies with rats [13,14] and humans.[2,7,15,16] This possibility was confirmed by Figueroa et al.,[3–6] who demonstrated that supplementation produced increased blood flow, which indicates better vasodilator capacity.

Although existing evidence shows the relationship between L-citrulline/L-arginine as involved in the hypotensive effect attributed to watermelon, it should also be considered that watermelon is rich in lycopene,[17] a carotenoid that has been reported to exert cardioprotective [18] and hypotensive effects.[19] Furthermore, watermelon is a source of magnesium, which has also been shown to reduce blood pressure levels.[20]

Despite the evidence of the effects on endothelial function, this mechanism is associated with the autonomic nervous system.[21] Sympathetic activity influences vascular function through several mechanisms, including peripheral vasoconstriction, vascular remodelling, baroreflex dysfunction, increased blood pressure and metabolic alterations that compromise structure and endothelial function.[22] Therefore, we hypothesized that the improved endothelial function observed after watermelon supplementation is influenced by autonomic nervous activity. A previous study demonstrated that intravenous administration of other nutrients (vitamin C) resulted in a reduction of the sympathovagal balance in hypertensive subjects.[11] However, this hypothesis has not been confirmed, and at least for now, the proposed mechanism for pressure reduction promoted by watermelon continues to be only endothelium-dependent vasodilation.

Altogether, based on these data, it seems reasonable to infer that L-arginine supplementation is able to decrease blood pressure, and a food source of this amino acid can produce the same effect. Therefore, the practical implication of this study is the formation of a body of evidence indicating other foods or a new food with these functional properties can reduce blood pressure.

The effectiveness of nutritional intervention for high blood pressure treatment is well established and can be symbolized by the Dietary Approaches to Stop Hypertension (DASH) dietary pattern, which suggests consuming fruits, vegetables, low-fat dairy products and products with reduced amounts of saturated fat.[23] This diet recommends daily consumption of fruits, but does not specify which fruits would possibly have the best hypotensive effect. The present study, in conjunction with the studies by Figueroa et al.,[3–6] consistently demonstrates the therapeutic potential of watermelon. These studies show a reduction of 11.8–15.0 mmHg for systolic and 6.0–7.0 mmHg for diastolic blood pressure. Meanwhile, the adoption of pharmacological monotherapy results in a mean reduction of 6.8–9.3 mmHg in systolic blood pressure.[24] Therefore, we propose investigating the specific potential of each type of fruit to reduce hypertension.

The main limitations of this study are that the data must be weighed for the fact that the experimental group had higher total energy and lipid consumption and elevated serum cholesterol, low-density lipoprotein cholesterol and triglycerides compared to the placebo group at baseline. However, these variables were not investigated in this study and did not lead to differences in initial blood pressure values, which were similar at baseline. The initial sympathovagal balance was lower in the experimental than in the placebo group, but supplementation did not change this variable.

In this sense, the data from this study allow us to conclude that an intervention with ingestion of 6 g/day of watermelon extract for 6 weeks can promote a significant reduction in blood pressure in middle-aged prehypertensive and hypertensive subjects.

Acknowledgement

The authors thank Milne Fruit Products Inc. (Prosser, WA, USA) for donation of the watermelon extract.

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding information

The authors thank the National Council for Scientific and Technological Development (CNPq) for financial support.