# Supplements and Foods with Potential Reduction of Blood Pressure in Prehypertensive and Hypertensive Subjects: A Systematic Review

Authors: Aline de Freitas Brito; Caio Victor Coutinho de Oliveira; Lydiane Tavares Toscano; Alexandre Sérgio Silva
Journal: ISRN Hypertension
 (2013)

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## Abstract

Although the dietary approaches for stop hypertension (DASH) is well established and effective in reduction of blood pressure, in recent years, new scientific studies have indicated that specific food, nutrients isolated from foods, and even commercial food supplements are not covered by DASH. In this research, these nutrients were evaluated through a review using the databases of PubMed with the terms “dietary supplements and blood pressure” without a limit of date. Vitamins (C, D, and E) and minerals (potassium and copper) promote the greatest reductions in BP, around 7 to 14 mmHg for systolic blood pressure (SBP) and 4 to 5 mmHg for diastolic blood pressure (PAD). Antioxidants reduce SBP and DBP in 3 to 27 mmHg and 3 to 4 mmHg, respectively. Among the amino acids, only L-arginine was effective in promoting reduction of 20 and 15 mmHg for SBP and DBP, respectively. In food, the grape juice promoted the highest reductions in SBP and DBP, around 8 mmHg and 6 mmHg, respectively. Finally, for commercial supplements, the fermented milk product GAIOR, the grain salba, and fish oil promoted reductions of about  4,4; 6; and 5 mmHg and 3,4; 3; and 1 mmHg for SBP and DBP, respectively. Therefore, new nutrients, foods, and supplements can enrich the recommendations of the DASH.


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## Body

## 1. Introduction

The degenerative diseases are the most prevalent in the world today, representing one of the greatest public health problems in the actuality [1]. According to estimates of the World Health Organization [2], these diseases are responsible for about 60% of all deaths worldwide, and 46% of the global burden of diseases affecting the population. Among them predominate obesity (12% of world population) [2], diabetes (10% of world population) [3], and dyslipidemia (7.9% of deaths worldwide) [2]. The main cause of these comorbidities have been the stress, sedentary lifestyle and eating habits.All of these diseases are potentially able to promote increased blood pressure. While the fatty produced substances such as angiotensinogen and proinflammatory contribute to elevate blood pressure [4]; hyperlipidemia results in excessive oxidation of low density lipoproteins with subsequent atherosclerotic process [5]. The state of diabetes promotes strong oxidative stress that contributes unequivocally to endothelial dysfunction, inflammation, and vasoconstriction which increases blood pressure [6]. Therefore, these three states of morbidity are among the risk factors of hypertension that are, among all chronic diseases, the most prevalent, affecting about 30% of the world population [2], and that causes the greatest financial expenditure on health in most countries of the world.A healthy lifestyle with physical exercise, emotional stress management, and correct eating habits are the main factors that could be altered in order to prevent these diseases [7] and minimizing the resulting increase in blood pressure. In nutritional context, the DASH dietary pattern (dietary approaches to stop hypertension), which recommends a diet rich in fruits, vegetables, fiber, minerals, and dairy products low in fat, has an important impact on reducing BP [8, 9], in addition to enhancing weight loss, and reduction of cardiovascular risk biomarkers [10].Despite the worldwide acceptance of the procedure DASH, recent research has provided new information about the hypotension effect of specific nutrients isolated from food (i.e., vitamins, minerals, amino acids, and antioxidants). Consequently, the industry has available supplementation on the market of a variety of nutritional supplements with proposed improvement cardiometabolic performance at the same time, a scientific research has evaluated the efficacy of these products in BP reduction. Additionally, other recent studies also suggest some new food as capable of promoting hypotensive action.Therefore, this study is a systematic review conducted for the purpose of providing an update of the evidence available in the literature until the year 2012 about effectiveness of isolated nutrients extracted from food, nutritional supplements, and novel foods proposed to have the capacity to reduce blood pressure hypercholesterolemic, diabetic, and obese hypertensive patients.


## 2. Methods

The search for articles was performed systematically in PUBMED/MEDLINE (Medical Literature Analysis and Retrieval System Online) unlimited data and previous to the May 17, 2012, with both genders, also with no age limits. The studies were evaluated independently by three reviewers in a blinded way. Possible misunderstandings that arose were resolved by consensus between the reviewers.We adopted the crossing of the descriptors: (1) dietary supplements and (2) blood pressure. We observed the occurrence of 1073 studies. Only randomized-controlled studies, conducted with human subjects, found that the influence of dietary supplementation on blood pressure reduction was considered. Based on this, first were eliminated through the titles and abstracts of studies that have used to compose your sample: animals, pregnant women, and patients with diseases hadn't cardiovascular risk. At this stage yet, studies of literature review and systematic review were also eliminated. In the second selection, through the full text longitudinal studies were excluded, those involving a group of volunteers to physical exercise, the experimental group who had normotensive subjects, studies without baseline or end-systolic and/or diastolic pressures in its results, and those who have not included subjects with cardiometabolic diseases that were not randomized controlled trials.Thus, 31 articles met the criteria for composing the reference of this study. Figure1 presents a detailed organization chart of the activities that were carried out to select articles. The selected studies were categorized according to the nutrient intake in the following categories: vitamins and minerals, antioxidant compounds, aminoacids, fresh food, and commercial supplements.Figure 1
Organogram of activities to select articles.


## 3. Results and Discussion

### 3.1. Quality Control Studies

Quality control was conducted by filling the criteria of scale present in PEDro.20. Only studies with methodological quality score of above three were included in this paper. Of the 31 studies chosen to compose the review, 22 received score of 10, five note 9, four notes 7, and  two studies only, received 8 and 5, respectively.


### 3.2. Characteristics of Study Subjects

Of the 31 articles, 11 were conducted with hypertensive individuals, the majority with hypertension mild degree. In most studies, no subjects discontinued the use of antihypertensive medication during the research. Ten studies were conducted with type 2 diabetes, four with obese grade 1 based on BMI, five with hypercholesterolemia, and one with renal disease. These studies, the subjects of a group of diabetics, obese in another group, and another group of hypercholesterolemic, were concomitantly hypertensive. Blood pressure of the subjects of other studies was consistent with values of prehypertension (between 120 to 160 and 77 to 88 mmHg for systolic and diastolic components of blood pressure). With respect to age, 21 trials were conducted with middle-aged subjects (40–58 years) and 10 performed with elderly (60–70 years). Of these studies, 24 were conducted for both genders, six were with males and one with females. The main characteristics of several studies found are shown in Table1.Table 1
Characteristics of the subjects, supplementation protocol, and the effects of interventions on blood pressure.
Studies
Sample
Supplements
Quantity
Administration(intake/day)
Time ofsupplementation
Methods measurement
Results (mmHg)
Vitamins and minerals
Berry et al. [11]
23 M/25 WHypertensives 45 ± 10 years
Potassium citrate
40 mmol
2 dose of 20 mmol/2x
6 weeks
Analysis ofradial pulse wave
SBP—(−1.5 mmHg)DBP—(−0.3 mmHg)
Sugden et al. [12]
10 M/7 WDiabetics 64 ± 10 years
Vitamin D
100 00 IU
1x
8 weeks
Finometer
*SBP—145 ± 9 versus 137 ± 12DBP—82 ± 11 versus  80 ± 9
Major et al. [13]
30 W/Obese41 ± 6 years
Vitamin DCalcium
400 mg1200 mg
2 dose of 200 + 600 mg2x
15 weeks
Sphyg
SBP—112 ± 11 versus  109 ± 10DBP—75 ± 9 versus  72 ± 7
Ward et al. [14]
13 M/5 WDiabetics 64 ± 7 years
Vitamin E
500 mg
2 dose of 250 mg/2x
6 weeks
ABPM
*SBP—130 ± 13 versus  123 ± 7*DBP—76 ± 6 versus  71 ± 5
Plantinga et al.  [15]
30 M/Hypertensives50 ± 12 years
Vitamin CVitamin E
1000 mg 400 UI
1000 mg + 400 UI/1x
8 weeks
ABPM
SBP—134 ± 10 versus  134 ± 10 DBP—87 ± 7 versus  86 ± 7
Farvid et al. [16]
9 M/8 W Diabetics50 ± 9 years
MagnesiumZinc Vitamin C Vitamin E
200 mg30 mg200 mg150 mg
2 dose of Mg/Zn (100 + 15 mg) + Vit C/E (100 + 75 mg)2x
12 weeks
Sphyg
*SBP—130 ± 19 versus  122 ± 16*DBP—83 ± 11 versus  77 ± 9
Farvid et al. [16]
7 M/9 W Diabetics51 ± 7 years
MagnesiumZinc
200 mg30 mg
2 dose of Mg/Zn (100 + 15 mg)2x
12 weeks
Sphyg
SBP—122 ± 15 versus  120 ± 10DBP—78 ± 12 versus  78 ± 10
Farvid et al. [16]
8 M/10 W Diabetics49 ± 9 years
Vitamin CVitamin E
200 mg150 mg
2 dose ofVit C/E (100 + 75 mg)2x
12 weeks
Sphyg
SBP—125 ± 15 versus  122 ± 12DBP—81 ± 9 versus  79 ± 12
Ward et al. [17]
12 M/7 W Hypertensives59 ± 5 years
Vitamin C
500 mg
2 dose of 250 mg/2x
6 weeks
ABPM
*SBP—134 ± 10 versus  130 ± 8  DBP—81 ± 8 versus  86 ± 7
Ward et al. [17]
10 M/6 W Hypertensives62 ± 7 years
Vitamin CPolyphenols (grape seed)
500 mg1000 mg
2 dose of 250 + 500 mg2x
6 weeks
ABPM
*SBP—139 ± 11 versus  134 ± 8*DBP —80 ± 11 versus  76 ± 6
Morán; Romero [18]
NR32 Diabetics59.7 ± 8 years
Magnesiumchloride
2500 mg
1x
16 weeks
NR
SBP—148 ± 32 versus 140 ± 28DBP—86 ± 17  versus 83 ± 16
Alarcón et al. [19]
15 M/60 W Hypertensives49 ± 5, years
Copper
5 mg
1x
8 weeks
Sphyg
*SBP—158 ± 17 versus  119 ±  3*DBP—106 ± 14 versus  80 ± 1
Mullan et al. [20]
12 M/3 W Diabetics 61 ± 6 years
Vitamin C
500 mg
1x
4 weeks
Sphyg
*SBP—130 ± 12 versus 120 ± 12*DBP—85 ± 5 versus 80 ± 6
Palumbo et al. [21]
NR/142Hypertensives Idade ≥ 50 years
Vitamin E
300 mg
1x
12 weeks
Sphyg and ABPM
SBP—147 ± 6 versus 139 ± 17DBP—88 ± 9 versus 85 ± 8
Gazis et al. [22]
36 M/12 WDiabetics  57 ± 11 years
Vitamin E
1600 UI
1x
8 weeks
Sphyg
SBP—150 ± 15 versus 146 ± 16DBP—79 ± 9 versus 79 ± 7
Kawano et al. [23]
35 M/25 WHypertensives 58 ± 1 years
Calcium
1000 mg
2 dose of 500 mg/2x
8 weeks
Sphyg
SBP—(−2.0 ± 1.2 mmHg)DBP—(−1.1 ± 0.7 mmHg)
De Valk et al. [24]
16 M/9 WDiabetics 62 ± 7 years
Magnesium
15 mmol
1x
12 weeks
NR
SBP—159 ± 20 versus  147 ± 22 DBP—83 ± 8 versus 77 ± 8
Siani  et al. [25]
18 M/Hypertensives45 ± 2 years
Potassium
24 mmol
3 dose of 8 mmol/3x
15 weeks
Sphyg
*SBP—144 ± 22 versus  132 ± 3*DBP—92 ± 1 versus 82 ± 2
Antioxidants components
Egert et al. [26]
42 M/51 WObeses 43 ± 10 years
Quercetin
150 mg
3 dose of 50 mg/3x
6 weeks
Sphyg
*SBP—127 ± 14 versus  124  ± 14  DBP—81 ± 9 versus  82 ±  8
Ward et al. [27]
10 M/6 WHypertensives 62.3 ± 7.1 years
Grape seed
500  mg
2 dose of 250 mg/2x
6 weeks
ABPM
*SBP—134 ± 11 versus  132 ± 9*DBP—80 ± 10 versus  73 ± 8
Aviram; Fuhrman [28]
12 MHypercholesterolemic  52 ± 1 years
Licorice Root Extract
100 mg
1x
4 weeks
Sphyg
*SBP—10% DBP—10%
Hodgson et al. [29]
61 M/19 WDiabetics 52.3 ± 1.4 years
Coenzyme Q10
200 mg
4 dose of 50 mg/2x
12 weeks
DINAMAP
*SBP—127 ± 4 versus 123 ± 3*DBP—76 ± 2 versus 71 ± 2
Burke et al. [30]
46 M/37 WDiabetics 69 ± 6 years
Coenzyme Q10
120 mg
2 dose of 60 mg/2x
12 weeks
Sphyg
*SBP—165 ± 5 versus 147 ± 8  DBP—81 ± 1 versus 78 ± 3
Aminoacids and proteins
Lee et al. [31]
8 M/10 WDiabetics 52.1 ± 2.3 years
Spirulina
8 g
40 dose of 0.2 g2x
12 weeks
Sphyg
SBP—131 ± 4 versus  129 ± 3DBP—84 ± 2  versus  80 ± 2
Torres-Duran et al. [32]
16 M/20 WHypercholesterolemic/Hypertensives 44.3 ± 9.6 years
Spirulina
4.5 g
3 dose of 0.5 g3x
6 weeks
Sphyg
SBP—120 ± 9 versus  109 ± 9DBP—85 ± 9 versus  79 ± 8
West et al. [33]
18MHypercholesterolemic 45 ± 1.9 years
L-arginine
12 g
4 doses of 3 g4x
3 weeks
ABPM
*SBP—134 ± 3 versus  114 ± 4*DBP—87 ± 2 versus  71 ± 2
Foods in nature
Duda et al. [34]
38 M/32 WHypertensives52.0 ± 8.3 years
Garlic
1620 mg
6 doses of 270 mg 2x
4 weeks
Sphyg
*SBP—142 ± 2 versus  139 ± 2  DBP—87 ± 11 versus  84 ± 10
Mizushima et al. [35]
45 M/Hypertensives44 ± 10 years
Milk
160 g
1x
4 weeks
Sphyg
*SBP—148 ± 10 versus  143 ± 8  DBP—96 ± 10 versus  94 ± 6
Park et al. [36]
40 MHypertensives46 ± 2 years
Grape juice
5.5 mL porKg corporal
2x
8 weeks
Sphyg
* SBP—146 ± 3 versus  138 ± 4* DBP—94 ± 3 versus  88 ± 3
Burke et al. [37]
36 Hypertensivesde 50 years
Soy and psyllium
25% VET + 12 gfibra 25% VET + 12 g
66 g/Maltodextrin,soy protein/66 g and psyllium/12 1x
8 weeks
ABPM
SBP—135 (120; 150) versus 126.6 (114; 139.2)DBP—74.1 (66.7; 81.4) versus 71.8 (65; 78.5)
Commercial supplements
Vuksan et al. [38]
11 M/9 WDiabetics  64 ± 8 years
Grain Salba
37 g
1x
12 weeks
Sphyg
*SBP—129 ± 17 versus  123 ± 16  DBP—81 ± 9 versus 78 ± 8
Paschos et al. [39]
59 M/Hypercholesterolemic52.0 ± 1.0 years
Alpha-linolenic
8000 mg
1x
12 weeks
Sphyg
SBP—120 versus  110DBP—80 versus  72
Wang et al. [40]
17 M/6 WObeses/Hypertensives41.7 ± 3.4
Fish oil
3000 mg
3 doses of 1000 mg 1x
8 weeks
Sphyg
*SBP—129 ± 7 versus  124 ± 12  DBP—89.6 ± 7 versus  88 ± 7
Iwata et al. [41]
20 M/20 W Obeses43 ± 10
Linoleic Acid
5.4 g
1x
12 weeks
Sphyg automatic
SBP—124 ± 11 versus  120 ± 12DBP—73 ± 2 versus  72 ± 9
Iwata et al. [41]
20 M/20 W Obeses40 ± 8
Linoleic Acid
10.8 g
1x
12 weeks
Sphyg automatic
SBP—127 ± 10 versus  123 ± 12DBP—76 ± 7 versus  72 ± 8
Svensson et al. [42]
39 M/19 WKidney Disease 60 ± 11 years
Fatty acids polyunsaturated n-3
2.4 g
1x
8 weeks
ABPM
SBP—135 ± 14 versus  135 ± 17DBP—75 ± 9 versus  76 ± 8
Jenkins et al. [43]
15 M/12 WHypercholesterolemic, 64 ± 9 years
Almonds
73 g/d
1x
4 weeks
NR
SBP—120 ± 2 versus 120 ± 3DBP—75 ± 2 versus 76 ± 2
Jenkins et al. [43]
15 M/12 HHypercholesterolemic, 64 ± 9 years
Half-almonds
37 g/d
1x
4 weeks
NR
SBP—121 ± 3 versus 121 ± 2DBP—75 ± 2 versus 76 ± 2
Burke et al. [37]
36 M/Hypertensivemiddle-aged
Psyllium
25% VET + 12 gfibra 25% VET + 12 g
66 g/Malto, 66 g/soyprotein + 12 g psyllium 1x
8 weeks
ABPM
SBP—131.6 (122.6; 141.0) versus 134.1 (123.7; 144.5)DBP—78.1 (69.4; 86.9) versus 78.7 (69.9; 87.6)
Agerholm-Larsen et al. [44]
20 M/50 WObeses 18 to55 years
StLa (Streptococcus thermophilus + Lactobacillus acidophilus)
450 mL of milkCAUSIDO
1x
8 weeks
Sphyg
*SBP—−4.4 ± 1.8*DBP—−3.4 ± 1.5
Agerholm-Larsen et al. [44]
20 M/50 WObeses 18 to55 years
StLr (Streptococcus thermophilus + Lactobacillus rhamnosus)
450 mLof milk CAUSIDO
1x
8 weeks
Sphyg automatic
SBP—2.6 ± 3.1DBP—0.8 ± 2.0
Agerholm-Larsen et al. [44]
20 M/50 WObeses 18 to55 years
G (Enterococcus faecium + Streptococcus thermophilus)
450 mLof milk CAUSIDO
1x
8 weeks
Sphyg automatic
SBP—(−8.0 ± 2.3 mmHg)DBP—(−4.0 ± 2.4 mmHg)

*Statistically significant, M: men, W: women, g: grams, mL: milliliter, SBP: systolic blood pressure, DBP: diastolic blood pressure, Sphyg: sphygmomanometer, ABPM: ambulatory blood pressure monitoring, NR: not reported, finometer: finger plethysmograph, DINAMAP: automatic sphygmomanometer.


### 3.3. Nutrients Investigated in Studies

Nutrients investigated in the selected articles were classified by us into vitamins and minerals, antioxidant compounds, proteins, or amino acids. We also found studies with fresh food and commercial supplements. Ten studies were conducted with vitamins and seven with minerals. Among the vitamins, the most used were vitamin C and vitamin E. For studies with minerals, wasn't observed a nutrient relapsing, so that potassium, calcium, magnesium, zinc, and copper minerals were investigated. For the five studies with antioxidants, three used flavonoids and two coenzyme Q10. Only three studies were selected in the category of aminoacids or proteins, two with spirulin, one with L-arginine and five with foodin nature (soy, milk, grape juice, and garlic). With respect to commercial supplements, eight studies were selected to comprise this category, of which, oilseeds received six of these studies. The forms of nutrients are categorized in Table 1.


### 3.4. Protocols Studies

The interventions lasted three to twelve weeks, with administration performed one to four times daily, and five or seven days per week. The dosage of each product varies considerably in all categories in which nutrients were categorized. The more frequent form of BP measurement was auscultatory method, using apparatus type sphygmomanometer. Table1 presents each of the selected studies, showing the characteristics of the subjects, supplementation protocol, how to measure blood pressure, and the effects of nutritional interventions on blood pressure. Meanwhile, Table 2 shows a summary of Table 1, which presents the highest and lowest blood pressure reductions, as well as the mode for each of the categories in which the nutrients are categorized.Table 2
Descriptive statistics for variables in supplementation.
Studies
Minimum
Maximum
Mode
Vitamins and minerals
Dosage
15
1
4
1 x ao dia (8 studies)
Supplementation time
15
4
16
8 weeks (5 studies)
Reduction in SBP
15
2.0
12.0
8 mmHg (2 studies)
Reduction in DBP
15
1.0
10.0
6 mmHg (2 studies)
Antioxidants components
Dosage
5
1
3
2 x ao dia (2 studies)
Supplementation time
5
4
12
6 weeks (2 studies)
Reduction in SBP
5
3.0
18.0
4 mmHg (2 studies)
Reduction in DBP
5
5.0
7.0
4 mmHg (2 studies)
Aminoacids and proteins
Dosage
3
1
4
—
Supplementation time
3
3
12
—
Reduction in SBP
3
1.0
10.0
—
Reduction in DBP
3
3.0
6.0
—
Foods in nature
Dosage
4
1
4
1 x/day (2 studies)
Supplementation time
4
4
8
8 weeks (3 studies)
Reduction in SBP
4
3.0
15.0
8 mmHg (2 studies)
Reduction in DBP
4
4.0
6.0
4 mmHg (2 studies)
Commercial supplements
Dosage
13
1
3
1 x/day (7 studies)
Supplementation time
8
4
12
6 weeks (5 studies)
Reduction in SBP
8
6.0
8.0
5 mmHg (2 studies)
Reduction in DBP
13
4.0
8.0
—
SBP: systolic blood pressure. DBP: diastolic blood pressure.


### 3.5. Vitamins and Minerals

Evidence support an inverse relationship between vitamin intake and cardiovascular events [45–47]. In fact, the therapeutic use of some vitamins minimizes the risk of atherosclerotic plaque formation and its main determinants [48]. Meanwhile, the minerals are involved in almost all metabolic pathways in the body and play an important role in the treatment of cardiovascular diseases and their risk factors [16].Among the vitamins, C and E are the most studied from the standpoint antioxidants and enzyme, besides being nutrients with potential biological functions [49]. In this paper [14–17, 20–22], studied collected showed the consumption of vitamins C and E as probable lowering of blood pressure.Mullan et al. [20] observed that a 500 mg dose/day of vitamin C for four weeks was able to reduce SBP (10 mmHg) DBP (4 mmHg) in diabetic subjects. When the same amount was administered daily in hypertensive subjects, supplementation decreased the SBP for only 4 mmHg [17]. Another group studied by these authors was treated with the same amount of vitamin C enriched with 1000 mg/day of polyphenols (1000 mg/d) grape seeds, and the hypotensive effect was potentiated in both SBP (5±11 mmHg) and for DBP (4±11 mmHg). Moreover, the study of Plantinga et al. [15], the amount of dietary intake of vitamin C was the double (1000 mg) and, associated with vitamin E (400 IU), however, BP reduction did not occur in hypertensive subjects. Similarly, a combination of vitamin C (200 mg/d) and E (150 mg/d) also was not effective in reducing blood pressure in diabetic subjects [16].Some studies corroborate findings of this paper pointing to a reduction in blood pressure from the consumption of vitamin C [50, 51] in hypertensive patients. Duffy et al. [51] evaluated 500 mg/day of vitamin C in hypertensive patients for four weeks and observed a reduction in SBP of 13 mmHg, but not in DBP. Fotherby et al. [50] also using the same protocol intake in hypertensive patients, for a period of 12 weeks and an observed reduction of 3 mmHg in SBP, however, DBP remained unchanged. A long period of intake of vitamin C may be needed to obtain vasodilatation and consequently reduce blood pressure [52, 53]. However, evidence from human studies are not sufficient to determine the ideal time-consuming vitamins to lower blood pressure without possible adverse effects [54].Supplementation of vitamin E (500 mg/d) for six weeks was effective in reducing SBP (7 mmHg) and DBP (5 mmHg) in diabetic patients [14]. In contrast, the consumption of vitamin E (1600 IU/d), for eight weeks, did not cause changes in pressure values in diabetic [22] as well as in hypertensive patients who consumed controlled 300 mg/d during 12 weeks, having no significant effect on BP [21]. This result corroborates other studies that evaluated the chronic effects of vitamin E in blood pressure [55, 56] using the same dose (300 mg/d) in people with cardiovascular risks. Gazis et al. [22] found a significant reduction in SBP in hypertensive patients when a doubled (600 mg/d) dose is administered. This fact suggests that a higher dose of vitamin E, however, within the values recommended daily, may possibly be more effective.Vitamins C (hydrophilic antioxidant) and E (lipophilic antioxidant) act through nonenzymatic system in the prevention and capture of reactive oxygen species (ROSs), generated by vascular cells [57]. The redox imbalance of hypertension often leads to functional alterations mediated by angiotensin II, stimulating the enzyme NADPH oxidase to increase the production of superoxide anion radical (O2-•), favoring the buffer nitric oxide (NO•) action to oxidative stress, detriment its vasodilator function [57]. However, it is unclear whether the intake of these vitamins may influence the antioxidant activity and enzyme cofactor, and how you can help prevent the formation of ROS [58, 59].Evidence suggests that vitamin D may also improve cardiometabolic profile, reducing the risk factors associated [60, 61]. In this paper, some studies were pooled studies of vitamin D addressing this perspective [12, 13]. In the study of Sugden et al. [12] oral dose (100 000 IU/day) of vitamin D was used for eight weeks, which has been shown to decrease significantly the systolic blood pressure by 14 mmHg, improving endothelial function in patients with type 2 diabetes and deficiency of vitamin D. This can be explained via the renin-angiotensin system and vascular function, where the  first hydroxylase-1-α enzyme metabolite converting of vitamin D (25[OH]D to 1,25[OH]2D3) acts as a binder for the nuclear transcription factor, regulating cell function in tissues such as endothelial cells and vascular smooth muscle, and thereby reducing blood pressure levels [62]. In contrast, when obese women were supplemented with vitamin D (400 mg/d) combined with calcium (1200 mg/d), they showed no improvement in cardiometabolic profile [13]. The low dose compared with the study of Sugden et al. [12] may explain these results.Anyway, the current data allow to infer that there is no consensus that vitamins are really effective in reducing blood pressure. The lack of a conclusion is given by the fact that prospective studies and intervention in humans that prove the effectiveness of vitamin D in the prevention and treatment of cardiometabolic diseases are scarce. The researches that explain the exact mechanisms, by which the active form (1,25[OH]2D3) improves β-cell function, the renin-angiotensin system, and regulation, are also inconclusive.Zinc, magnesium [16, 24], copper [19], potassium [11, 25], and calcium [13, 23] have been adopted in research, hypothesizing its hypotensive effect. Farvid et al. [16] showed that 12 weeks of consumption of 200 mg of magnesium and 30 mg of zinc supplementation did not reduce blood pressure in diabetic subjects. Magnesium and zinc, when enriched with vitamin C 200 mg and 150 mg vitamin E, promoted a significant reduction in the levels of PAS (8 mmHg) and diastolic (6 mmHg) in the same population [16]. Therefore, we cannot establish from this study, the efficacy of these minerals in reducing BP, because only when associated with the vitamin C and E, they were able to reduce blood pressure levels in diabetics. The solution of magnesium chloride when applied to diabetics for a period of 16 weeks also did not modify the blood pressure values [18]. Corroborating this finding, De Valk et al. [24] observed that magnesium supplementation (15 mmol/d) for 12 weeks, in diabetic patients, did not alter the blood pressure values. Therefore, there is no evidence that zinc and magnesiummay be able to promote BP reduction.Consumption of potassium (24 mmol) in hypertensive men, over a period of 15 weeks, decreased the SBP by 10 mmHg and DBP by 7 mmHg [25]. Several mechanisms have been proposed to explain the antihypertensive effect of a high intake of potassium, including an increased loss of water and sodium, suppression of secretion of renin and angiotensin, and stimulation of the activity of sodium-potassium pump. However, Berry et al. [11] found no change in blood pressure after administration of 40 mmol of potassium in hypertensive subjects for six weeks. Alarcón et al. [19] demonstrated that administration of another mineral, copper (5 mg/day), significantly decreased the SBP levels (r=0.963) and DBP (r=0.981) in treated hypertensive patients. Some studies show that cardiometabolic protective effect of minerals was not observed in blood pressure values during supplementation of calcium (1000 mg/d) for eight weeks in hypertensive subjects [23], even when that (1200 mg/d) was associated with vitamin D (400 mg/d), supplementing obese women for 15 weeks [13].Based on these data, it can be stated that there is strong evidence linking vitamins to hypotensive effect, however, there is still no consensus that the minerals are effective in reducing blood pressure.


### 3.6. Antioxidants Compounds

Oxidative stress contributes to increase blood pressure by acting on eNOS uncoupling and decrease bioavailability of nitric oxide [63]. The result is a predominant on factors vasoconstrictors and low action of vasodilators in vascular bed [63]. In the cardiovascular system, the reactive oxygen species (ROSs) are produced in vascular cells by a number of oxidases, including NADPH oxidase, xanthine oxidase, lipoxygenase, and cytochrome P450 [63, 64]. Furthermore, clinical data have suggested that there is increased endogenous antioxidant, introducing exogenous antioxidants present in food. In fact, the reduction of oxidative stress has been accompanied by decreasing cardiovascular risk and blood pressure in humans [65–70].Antioxidants commonly used include vitamins A, C, and E, L-arginine, flavonoids, coenzyme Q10, and alpha-lipoic acid [64, 71]. Of these, flavonoids have gained attention for their higher antioxidant power than the others (Ross and Kasum). These phenolic compounds are commonly found in high concentrations in many fruits, vegetables, and beverages, including apples, strawberries, grapes, onions, pomegranate, red wine, tea, cocoa, and dark chocolate [72].In fact, the selected studies that used supplements based on flavonoids, all demonstrated significant reductions in blood pressure in hypertensive [27], obese [26], and hypercholesterolemic individuals [28]. The reductions were more pronounced for systolic blood pressure, with a reduction of around 3 mmHg. For diastolic blood pressure, only the study by Ward et al., [27] identified a significant reduction (3 mmHg). Interestingly, in this study, the doses of flavonoids were much higher (500 mg versus 150 mg in the others). Although these reductions are relatively discreet, these are clinically significant, so that hypotension afforded by the flavonoid is equivalent to the use of a class of antihypertensive medication [73].In addition to flavonoids, another supplement with strong action antioxidant is coenzyme Q10. Molecule lipid soluble, derived mainly from endogenous synthesis, plays an essential role as the carrier of electrostatic mitochondrial oxidative phosphorylation [74]. The studies of this paper involving the use of coenzyme Q10 [29, 30] were performed with diabetic subjects and also identified significant reductions in blood pressure of 4 mmHg [30] and 27 mmHg [29]. Hodgson et al. [29] found a reduction of 4 mmHg diastolic. Interestingly, the study showed that diastolic hypotension, as well as flavonoids, was also performed with larger amount of coenzyme Q10 against the others (200 versus 60 mg), which enables to infer that the reduced pressure in response to supplementation with antioxidants appears to be dependent on the concentration.The mechanism of cell signaling by flavonoids give up buffering of ROS (Ross and Kasum) or limits its formation [69]. The actions of the polyphenols as buffering occurs through their ability to modulate the levels of activity of nitric oxide synthase (eNOS) and, therefore, the bioavailability of endothelial nitric oxide (NO) [75–79]. The flavonoids reduce the formation through interaction with inhibitory kinase signaling pathways, such as via the PI3-kinase/Akt and intracellular Ca2+ [80, 81], and promote inhibition of the enzyme NADPH oxidase, which is the enzyme responsible for the production of ROS. Furthermore, prevents vascular injury by inhibition of MAPK inhibition of transcription factors (NF-kB), and matrix metalloproteinases (MMP), allowing reduction in angiogenesis, migration and proliferation of vascular cells.It is well established that the flavonoids inhibit the oxidation of low density lipoprotein (LDL) [82] to reduce the formation of atherosclerotic lesions [83], inhibit platelet aggregation [83], decrease expression of vascular cell adhesion molecule [84], and reduce blood pressure or prevent its rise [85].


### 3.7. Aminoacids and Proteins

Some isolated nutrients of food have been investigated on possible hypotensive effect in individuals with cardiometabolic risk. Among those selected in this paper, proteins [31, 32] and amino acids were observed [33]. These nutrients are positively associated with the control of metabolic disorders (e.g., hypertension) [86, 87]. Spirulina has a high protein content and is considered one of the richest sources of vitamins and minerals, besides presenting phenolic compounds and essential fatty acids [88]. Furthermore, the research shows its various biological activities, among them is the vasodilator, proposing its antihypertensive action [89] as well as improved glycemic profile [90].Torres-Duran et al. [32] studied the effects of oral supplementation of spirulina 4.5 g/d in hypertensive and dyslipidemic subjects for six weeks and noted a reduction in SBP (120±9 versus 109±9 mmHg) and DBP (85±9 versus 79±8 mmHg), being observed since the fourth week of intervention. Corroborating this study, Lee et al. [31] also observed a significant reduction in DBP (84±2 versus 79±2 mmHg) when diabetic patients consumed 8 g/d of spirulina for 12 weeks, however, the SBP remained unchanged.According to Hsiao et al. [91], hypotension can be explained by vasodilation determined by an increase in nitric oxide synthesis, by inhibition of platelet aggregation, by inhibiting calcium mobilization, and by mediating the release of free radicals. Guan et al. [86] proposed that the high concentration of potassium and the low sodium content of spirulina would be able to generate positive implications PA, supported by a classic effect that food mediate several steps in the process of inflammation reducing atherothrombotic plaque formation. Based on these data, we can say that spirulina acts favorably on serum lipids, antioxidant capacity, and inflammatory response in diabetic, hypertensive, and dyslipidemic subjects. However, the mechanisms by which spirulina lowers blood pressure are not well understood.Among the observed amino acid L-arginine is an amino acid which proposes to improve endothelial function contributing to the hypotensive effect from the synthesis of nitric oxide (NO) [92, 93]. Additionally, other benefits such as improved blood flow and reduction in platelet aggregation have been attributed to L-arginine in human models [87]. West et al. [33], after oral intervention 12 g/d of L-arginine in hypercholesterolemic men for three weeks, observed a reduction in SBP (134±3 versus 114±4) and DBP (87±2 versus 71±2), suggesting that L-arginine is involved in the mechanisms  hemodynamic of hypotension. In fact, one mechanism that may explain these data is related to endothelial function [94]. The increase in plasma nitrite reflects an improvement in endothelial function and may explain the significant reduction of baseline blood pressure.


### 3.8. Foods in Nature

Despite that studies have demonstrated the efficacy of isolated nutrients (i.e., vitamins, minerals, and flavonoids) [16, 20] in reducing blood pressure, studies evaluating the effects of food in nature on blood pressure of hypertensive patients are scarce. Methodological difficulties and the impossibility of determining which particular food component is the active compound are some of the likely factors that may explain this paucity in the literature. Moreover, studies within natural food have the advantage of external validity, approaching more to the reality of population’s eating habits and how these habits result in the proposed benefits in the studies.Among the studies selected in this paper, we have investigated the effects of garlic [34], grape juice [36], and whey [35], all in hypertensive middle-aged people. While the wine had been well investigated, this paper found only studies with normotensive, which was an exclusion criterion at the time of selection of papers.Dhawan and Jain [95] and Durak et al. [96] found that administration of garlic preparations resulted in significant reductions in blood pressure in hypertensive patients. The first garlic supplementation for eight weeks was able to reduce blood pressure in young hypertensive subjects. The latter, supplementing hypercholesterolemic patients for 16 weeks, found a significant decrease of systolic blood pressure around 22 mmHg. In contrast, Duda et al. [34] observed that the use of aged garlic extract, containing 1.62 mg of allicin/day, resulted in modest reduction in blood pressure both systolic and diastolic blood pressure (about 1 mmHg for both systolic and diastolic) without statistical differences. These results corroborate the findings of Brace [97], where they found no effect of preparations containing garlic on blood pressure.Some factors may explain this discrepancy in the results. Among them is the duration of administration and the dosage used. In their study, Duda et al. [34], 1.62 mg of allicin was administered for 4 weeks, while in studies of Dhawan and Jain [95] and Durak et al. [96] doses of 250 mg and 10 g were administered, during 2 and 4 months, respectively.Among compounds present in garlic, allicin is involved in most of the therapeutic benefits promoted by this food [98]. The benefits include reduction of low density lipoprotein cholesterol (LDL) and elimination of reactive oxygen species [98]. Warshafsky et al. [99] found that the consumption of 1–1.5 garlic cloves daily (containing approximately 1.5 mg of allicin) can reduce cholesterol around 9%. Likewise, [34] found a reduction in total cholesterol of around 9%, despite not finding lower blood pressure in his study.Therefore, the data of this paper support the premise that the incorporation of consumption of garlic compounds or derivatives have beneficial effects such as reduction of oxidative stress and lipid peroxidation in hypertensive subjects. For these benefits to be extended, it appears that the consumer must take chronically (at least 2 months) a minimum amount of allicin 250 mg/day (about 2.5 garlic cloves).The contained polyphenols in purple grape, red wine, and other dark red to purple color fruits are compounds with protective properties of the cardiovascular system since they increase the plasma concentration of high density lipoproteins (HDLs), slow the development of atherosclerosis, function as potent antioxidants, improve endothelial function, and are able to reduce blood pressure in hypertensive subjects [100]. The improvement of endothelial function would be due to the stimulation of increased production of nitric oxide by the vascular endothelium. This vessel has relaxants and antiaggregatory properties and in the long term can modulate the expression of protective genes of the cardiovascular system [101]. Studies with polyphenols isolated from foods are conclusive in demonstrating their cardiovascular protective effects, including lowering blood pressure.Considering these effects for isolated polyphenols, Park et al. [36] investigated whether the ingestion of these nutrients contained in foods, grape juice, would be able to decrease blood pressure. They tested the hypothesis that chronic consumption (8 weeks) would reduce blood pressure via increased availability of nitric oxide. They observed a 9% reduction in systolic blood pressure (around −7.2 mmHg) and diastolic (around −6.2 mmHg), confirming Opie and Lecour [100]. However, the author proposes increase in NO production for explaining the hypotensive effect but does not have any data that supporting this idea.Its important to note that the consumption of grape juice in the study of Park et al. [36] gave an average 881.14 mg/day of flavonoids, whereas in these studies from isolated nutrients it was 500 mg [26–28]. This corroborates the ability of grape juice (being consumed daily around 425.6 mL) to promote beneficial effects on blood pressure and great applicability to the general population. Therefore, the inclusion of grape juice in the diet, even in low amounts, is an interesting strategy of eating habits to lower BP.The potassium and calcium supplementation has been suggested as modulators of systemic arterial pressure [35]. The fermented skim-milk, Calpis sour milk, can serve as a nutritional strategy to control hypertension, since, besides possessing these nutrients, it has certain strains of bacteria, such as Lactobacillus helveticus and Saccharomyces cerevisiae, which has been shown to promote antihypertensive effect in SHR rats [102]. Additionally, this milk peptide fractions (valine-proline-proline and isoleucine-proline-proline) would be responsible for ACE inhibition, key enzyme in the pathophysiology of hypertension.Based on this, Mizushima et al. [35] tested the hypothesis that consumption of this beverage (160 g/dia) for 4 weeks would be sufficient to reduce blood pressure, in hypertensive subjects, about −5 mmHg and 2 mmHg, in systolic blood pressure, and diastolic respectively.Although not proven in humans, the peptide fractions of the milk (valine and proline-proline-isoleucine-proline-proline) has the ability to inhibit ACE activity in SHR rats [102]. If this inhibitory effect is extended to humans is unclear [35]. It is proposed that these compounds in Calpis sour-milk (at doses of 0.033 and 0.025 mL/kg, resp.) have pharmacological activity sufficient for inhibition of the ACE activity and contribute to reducing pressure levels.Because it contains a high concentration of Ca, this nutrient could be considered responsible for blood pressure reductions observed in this study. However, the [Ca] was similar between the placebo and treatment groups, making it impossible to draw a cause-effect relationship for this particular nutrient. Furthermore, the [Ca] in the milk would be well below what is needed (about 90 mg) to promote positive effects as observed in other studies when used in isolation (1000 mg) [103].In short, it is interesting to note that the daily intake of 2.5 cloves of garlic, about 385 mL of grape juice, and 160 g of Calpis sour-milk can promote significant reductions in blood pressure. It should be noted that the amount of feed required to ensure hypotensive effect is so small that it can be easily implemented in the diet even by persons who may not display any of these taste in the food. Additionally, although it was not contemplated by the inclusion criteria, recent studies have shown that eating 100 g of dark chocolate [104] and 6 g of watermelon extract [105] were also able to promote BP reduction, may attenuate up to between 11.9±7.7 and −15.1±2.8 mmHg for SBP.


### 3.9. Commercial Supplements

Dietary supplements are products added to the diet, which contain at least one of the following ingredients: vitamins, minerals, amino acids, proteins, metabolites, antioxidants, carbohydrates, lipids, fatty acids, or a combination of any of these [106]. Historically, dietary supplements have a wide acceptance and use by exercise practitioners, believing these products improve their sports performance and health [107].Concomitant to the advancement and dissemination of information in the area of nutrition, the market potential of these products to other niche market products has grown rapidly. In this context, products intended for the general population, and specifically for hypertensive and cardiac subjects, began to have its production increased. However, these products are not always grounded in reliable scientific findings, often occurring in misinterpretation of results.Among the selected studies by this paper, it was observed that the responsible components for the modulation of blood pressure were dietary fiber products, probiotics, and antioxidant compounds [30, 38, 40, 41, 43, 44].Vuksan et al. [38] verified the effectiveness of chia supplement on cardiovascular diseases markers. Despite finding satisfactory results (chia consumption of 37 g/d for 12 weeks resulted in about −6 mmHg and −3 mmHg for systolic and diastolic blood pressure, resp.) it is not yet possible to draw firm conclusions because of the study’s limitations. Among them, it is not known which of the various components of the product would be responsible for the positive effects, and it is unknown whether the effects of positive pressure of this food consumption were associated with direct consumption of chia or by changes in diet composition between treatments (intervention versus placebo).As in the case of chia, there is no body of evidence linking the essential fatty acid supplementation or consumption of fermented milk CAUSIDO with lower blood pressure in hypertensive subject. Despite the remarkable relationship between fish consumption (source of essential fatty acids) and improvement in cardiovascular health, there is insufficient evidence to assert that supplementation of this type of product shows the same physiological effects.In short, despite the growing interest and use of dietary supplements for blood pressure control, it is necessary to observe if there is a body of evidence in the specific literature to justify the use of these compounds for hypertension.


## 3.1. Quality Control Studies

Quality control was conducted by filling the criteria of scale present in PEDro.20. Only studies with methodological quality score of above three were included in this paper. Of the 31 studies chosen to compose the review, 22 received score of 10, five note 9, four notes 7, and  two studies only, received 8 and 5, respectively.


## 3.2. Characteristics of Study Subjects

Of the 31 articles, 11 were conducted with hypertensive individuals, the majority with hypertension mild degree. In most studies, no subjects discontinued the use of antihypertensive medication during the research. Ten studies were conducted with type 2 diabetes, four with obese grade 1 based on BMI, five with hypercholesterolemia, and one with renal disease. These studies, the subjects of a group of diabetics, obese in another group, and another group of hypercholesterolemic, were concomitantly hypertensive. Blood pressure of the subjects of other studies was consistent with values of prehypertension (between 120 to 160 and 77 to 88 mmHg for systolic and diastolic components of blood pressure). With respect to age, 21 trials were conducted with middle-aged subjects (40–58 years) and 10 performed with elderly (60–70 years). Of these studies, 24 were conducted for both genders, six were with males and one with females. The main characteristics of several studies found are shown in Table1.Table 1
Characteristics of the subjects, supplementation protocol, and the effects of interventions on blood pressure.
Studies
Sample
Supplements
Quantity
Administration(intake/day)
Time ofsupplementation
Methods measurement
Results (mmHg)
Vitamins and minerals
Berry et al. [11]
23 M/25 WHypertensives 45 ± 10 years
Potassium citrate
40 mmol
2 dose of 20 mmol/2x
6 weeks
Analysis ofradial pulse wave
SBP—(−1.5 mmHg)DBP—(−0.3 mmHg)
Sugden et al. [12]
10 M/7 WDiabetics 64 ± 10 years
Vitamin D
100 00 IU
1x
8 weeks
Finometer
*SBP—145 ± 9 versus 137 ± 12DBP—82 ± 11 versus  80 ± 9
Major et al. [13]
30 W/Obese41 ± 6 years
Vitamin DCalcium
400 mg1200 mg
2 dose of 200 + 600 mg2x
15 weeks
Sphyg
SBP—112 ± 11 versus  109 ± 10DBP—75 ± 9 versus  72 ± 7
Ward et al. [14]
13 M/5 WDiabetics 64 ± 7 years
Vitamin E
500 mg
2 dose of 250 mg/2x
6 weeks
ABPM
*SBP—130 ± 13 versus  123 ± 7*DBP—76 ± 6 versus  71 ± 5
Plantinga et al.  [15]
30 M/Hypertensives50 ± 12 years
Vitamin CVitamin E
1000 mg 400 UI
1000 mg + 400 UI/1x
8 weeks
ABPM
SBP—134 ± 10 versus  134 ± 10 DBP—87 ± 7 versus  86 ± 7
Farvid et al. [16]
9 M/8 W Diabetics50 ± 9 years
MagnesiumZinc Vitamin C Vitamin E
200 mg30 mg200 mg150 mg
2 dose of Mg/Zn (100 + 15 mg) + Vit C/E (100 + 75 mg)2x
12 weeks
Sphyg
*SBP—130 ± 19 versus  122 ± 16*DBP—83 ± 11 versus  77 ± 9
Farvid et al. [16]
7 M/9 W Diabetics51 ± 7 years
MagnesiumZinc
200 mg30 mg
2 dose of Mg/Zn (100 + 15 mg)2x
12 weeks
Sphyg
SBP—122 ± 15 versus  120 ± 10DBP—78 ± 12 versus  78 ± 10
Farvid et al. [16]
8 M/10 W Diabetics49 ± 9 years
Vitamin CVitamin E
200 mg150 mg
2 dose ofVit C/E (100 + 75 mg)2x
12 weeks
Sphyg
SBP—125 ± 15 versus  122 ± 12DBP—81 ± 9 versus  79 ± 12
Ward et al. [17]
12 M/7 W Hypertensives59 ± 5 years
Vitamin C
500 mg
2 dose of 250 mg/2x
6 weeks
ABPM
*SBP—134 ± 10 versus  130 ± 8  DBP—81 ± 8 versus  86 ± 7
Ward et al. [17]
10 M/6 W Hypertensives62 ± 7 years
Vitamin CPolyphenols (grape seed)
500 mg1000 mg
2 dose of 250 + 500 mg2x
6 weeks
ABPM
*SBP—139 ± 11 versus  134 ± 8*DBP —80 ± 11 versus  76 ± 6
Morán; Romero [18]
NR32 Diabetics59.7 ± 8 years
Magnesiumchloride
2500 mg
1x
16 weeks
NR
SBP—148 ± 32 versus 140 ± 28DBP—86 ± 17  versus 83 ± 16
Alarcón et al. [19]
15 M/60 W Hypertensives49 ± 5, years
Copper
5 mg
1x
8 weeks
Sphyg
*SBP—158 ± 17 versus  119 ±  3*DBP—106 ± 14 versus  80 ± 1
Mullan et al. [20]
12 M/3 W Diabetics 61 ± 6 years
Vitamin C
500 mg
1x
4 weeks
Sphyg
*SBP—130 ± 12 versus 120 ± 12*DBP—85 ± 5 versus 80 ± 6
Palumbo et al. [21]
NR/142Hypertensives Idade ≥ 50 years
Vitamin E
300 mg
1x
12 weeks
Sphyg and ABPM
SBP—147 ± 6 versus 139 ± 17DBP—88 ± 9 versus 85 ± 8
Gazis et al. [22]
36 M/12 WDiabetics  57 ± 11 years
Vitamin E
1600 UI
1x
8 weeks
Sphyg
SBP—150 ± 15 versus 146 ± 16DBP—79 ± 9 versus 79 ± 7
Kawano et al. [23]
35 M/25 WHypertensives 58 ± 1 years
Calcium
1000 mg
2 dose of 500 mg/2x
8 weeks
Sphyg
SBP—(−2.0 ± 1.2 mmHg)DBP—(−1.1 ± 0.7 mmHg)
De Valk et al. [24]
16 M/9 WDiabetics 62 ± 7 years
Magnesium
15 mmol
1x
12 weeks
NR
SBP—159 ± 20 versus  147 ± 22 DBP—83 ± 8 versus 77 ± 8
Siani  et al. [25]
18 M/Hypertensives45 ± 2 years
Potassium
24 mmol
3 dose of 8 mmol/3x
15 weeks
Sphyg
*SBP—144 ± 22 versus  132 ± 3*DBP—92 ± 1 versus 82 ± 2
Antioxidants components
Egert et al. [26]
42 M/51 WObeses 43 ± 10 years
Quercetin
150 mg
3 dose of 50 mg/3x
6 weeks
Sphyg
*SBP—127 ± 14 versus  124  ± 14  DBP—81 ± 9 versus  82 ±  8
Ward et al. [27]
10 M/6 WHypertensives 62.3 ± 7.1 years
Grape seed
500  mg
2 dose of 250 mg/2x
6 weeks
ABPM
*SBP—134 ± 11 versus  132 ± 9*DBP—80 ± 10 versus  73 ± 8
Aviram; Fuhrman [28]
12 MHypercholesterolemic  52 ± 1 years
Licorice Root Extract
100 mg
1x
4 weeks
Sphyg
*SBP—10% DBP—10%
Hodgson et al. [29]
61 M/19 WDiabetics 52.3 ± 1.4 years
Coenzyme Q10
200 mg
4 dose of 50 mg/2x
12 weeks
DINAMAP
*SBP—127 ± 4 versus 123 ± 3*DBP—76 ± 2 versus 71 ± 2
Burke et al. [30]
46 M/37 WDiabetics 69 ± 6 years
Coenzyme Q10
120 mg
2 dose of 60 mg/2x
12 weeks
Sphyg
*SBP—165 ± 5 versus 147 ± 8  DBP—81 ± 1 versus 78 ± 3
Aminoacids and proteins
Lee et al. [31]
8 M/10 WDiabetics 52.1 ± 2.3 years
Spirulina
8 g
40 dose of 0.2 g2x
12 weeks
Sphyg
SBP—131 ± 4 versus  129 ± 3DBP—84 ± 2  versus  80 ± 2
Torres-Duran et al. [32]
16 M/20 WHypercholesterolemic/Hypertensives 44.3 ± 9.6 years
Spirulina
4.5 g
3 dose of 0.5 g3x
6 weeks
Sphyg
SBP—120 ± 9 versus  109 ± 9DBP—85 ± 9 versus  79 ± 8
West et al. [33]
18MHypercholesterolemic 45 ± 1.9 years
L-arginine
12 g
4 doses of 3 g4x
3 weeks
ABPM
*SBP—134 ± 3 versus  114 ± 4*DBP—87 ± 2 versus  71 ± 2
Foods in nature
Duda et al. [34]
38 M/32 WHypertensives52.0 ± 8.3 years
Garlic
1620 mg
6 doses of 270 mg 2x
4 weeks
Sphyg
*SBP—142 ± 2 versus  139 ± 2  DBP—87 ± 11 versus  84 ± 10
Mizushima et al. [35]
45 M/Hypertensives44 ± 10 years
Milk
160 g
1x
4 weeks
Sphyg
*SBP—148 ± 10 versus  143 ± 8  DBP—96 ± 10 versus  94 ± 6
Park et al. [36]
40 MHypertensives46 ± 2 years
Grape juice
5.5 mL porKg corporal
2x
8 weeks
Sphyg
* SBP—146 ± 3 versus  138 ± 4* DBP—94 ± 3 versus  88 ± 3
Burke et al. [37]
36 Hypertensivesde 50 years
Soy and psyllium
25% VET + 12 gfibra 25% VET + 12 g
66 g/Maltodextrin,soy protein/66 g and psyllium/12 1x
8 weeks
ABPM
SBP—135 (120; 150) versus 126.6 (114; 139.2)DBP—74.1 (66.7; 81.4) versus 71.8 (65; 78.5)
Commercial supplements
Vuksan et al. [38]
11 M/9 WDiabetics  64 ± 8 years
Grain Salba
37 g
1x
12 weeks
Sphyg
*SBP—129 ± 17 versus  123 ± 16  DBP—81 ± 9 versus 78 ± 8
Paschos et al. [39]
59 M/Hypercholesterolemic52.0 ± 1.0 years
Alpha-linolenic
8000 mg
1x
12 weeks
Sphyg
SBP—120 versus  110DBP—80 versus  72
Wang et al. [40]
17 M/6 WObeses/Hypertensives41.7 ± 3.4
Fish oil
3000 mg
3 doses of 1000 mg 1x
8 weeks
Sphyg
*SBP—129 ± 7 versus  124 ± 12  DBP—89.6 ± 7 versus  88 ± 7
Iwata et al. [41]
20 M/20 W Obeses43 ± 10
Linoleic Acid
5.4 g
1x
12 weeks
Sphyg automatic
SBP—124 ± 11 versus  120 ± 12DBP—73 ± 2 versus  72 ± 9
Iwata et al. [41]
20 M/20 W Obeses40 ± 8
Linoleic Acid
10.8 g
1x
12 weeks
Sphyg automatic
SBP—127 ± 10 versus  123 ± 12DBP—76 ± 7 versus  72 ± 8
Svensson et al. [42]
39 M/19 WKidney Disease 60 ± 11 years
Fatty acids polyunsaturated n-3
2.4 g
1x
8 weeks
ABPM
SBP—135 ± 14 versus  135 ± 17DBP—75 ± 9 versus  76 ± 8
Jenkins et al. [43]
15 M/12 WHypercholesterolemic, 64 ± 9 years
Almonds
73 g/d
1x
4 weeks
NR
SBP—120 ± 2 versus 120 ± 3DBP—75 ± 2 versus 76 ± 2
Jenkins et al. [43]
15 M/12 HHypercholesterolemic, 64 ± 9 years
Half-almonds
37 g/d
1x
4 weeks
NR
SBP—121 ± 3 versus 121 ± 2DBP—75 ± 2 versus 76 ± 2
Burke et al. [37]
36 M/Hypertensivemiddle-aged
Psyllium
25% VET + 12 gfibra 25% VET + 12 g
66 g/Malto, 66 g/soyprotein + 12 g psyllium 1x
8 weeks
ABPM
SBP—131.6 (122.6; 141.0) versus 134.1 (123.7; 144.5)DBP—78.1 (69.4; 86.9) versus 78.7 (69.9; 87.6)
Agerholm-Larsen et al. [44]
20 M/50 WObeses 18 to55 years
StLa (Streptococcus thermophilus + Lactobacillus acidophilus)
450 mL of milkCAUSIDO
1x
8 weeks
Sphyg
*SBP—−4.4 ± 1.8*DBP—−3.4 ± 1.5
Agerholm-Larsen et al. [44]
20 M/50 WObeses 18 to55 years
StLr (Streptococcus thermophilus + Lactobacillus rhamnosus)
450 mLof milk CAUSIDO
1x
8 weeks
Sphyg automatic
SBP—2.6 ± 3.1DBP—0.8 ± 2.0
Agerholm-Larsen et al. [44]
20 M/50 WObeses 18 to55 years
G (Enterococcus faecium + Streptococcus thermophilus)
450 mLof milk CAUSIDO
1x
8 weeks
Sphyg automatic
SBP—(−8.0 ± 2.3 mmHg)DBP—(−4.0 ± 2.4 mmHg)

*Statistically significant, M: men, W: women, g: grams, mL: milliliter, SBP: systolic blood pressure, DBP: diastolic blood pressure, Sphyg: sphygmomanometer, ABPM: ambulatory blood pressure monitoring, NR: not reported, finometer: finger plethysmograph, DINAMAP: automatic sphygmomanometer.


## 3.3. Nutrients Investigated in Studies

Nutrients investigated in the selected articles were classified by us into vitamins and minerals, antioxidant compounds, proteins, or amino acids. We also found studies with fresh food and commercial supplements. Ten studies were conducted with vitamins and seven with minerals. Among the vitamins, the most used were vitamin C and vitamin E. For studies with minerals, wasn't observed a nutrient relapsing, so that potassium, calcium, magnesium, zinc, and copper minerals were investigated. For the five studies with antioxidants, three used flavonoids and two coenzyme Q10. Only three studies were selected in the category of aminoacids or proteins, two with spirulin, one with L-arginine and five with foodin nature (soy, milk, grape juice, and garlic). With respect to commercial supplements, eight studies were selected to comprise this category, of which, oilseeds received six of these studies. The forms of nutrients are categorized in Table 1.


## 3.4. Protocols Studies

The interventions lasted three to twelve weeks, with administration performed one to four times daily, and five or seven days per week. The dosage of each product varies considerably in all categories in which nutrients were categorized. The more frequent form of BP measurement was auscultatory method, using apparatus type sphygmomanometer. Table1 presents each of the selected studies, showing the characteristics of the subjects, supplementation protocol, how to measure blood pressure, and the effects of nutritional interventions on blood pressure. Meanwhile, Table 2 shows a summary of Table 1, which presents the highest and lowest blood pressure reductions, as well as the mode for each of the categories in which the nutrients are categorized.Table 2
Descriptive statistics for variables in supplementation.
Studies
Minimum
Maximum
Mode
Vitamins and minerals
Dosage
15
1
4
1 x ao dia (8 studies)
Supplementation time
15
4
16
8 weeks (5 studies)
Reduction in SBP
15
2.0
12.0
8 mmHg (2 studies)
Reduction in DBP
15
1.0
10.0
6 mmHg (2 studies)
Antioxidants components
Dosage
5
1
3
2 x ao dia (2 studies)
Supplementation time
5
4
12
6 weeks (2 studies)
Reduction in SBP
5
3.0
18.0
4 mmHg (2 studies)
Reduction in DBP
5
5.0
7.0
4 mmHg (2 studies)
Aminoacids and proteins
Dosage
3
1
4
—
Supplementation time
3
3
12
—
Reduction in SBP
3
1.0
10.0
—
Reduction in DBP
3
3.0
6.0
—
Foods in nature
Dosage
4
1
4
1 x/day (2 studies)
Supplementation time
4
4
8
8 weeks (3 studies)
Reduction in SBP
4
3.0
15.0
8 mmHg (2 studies)
Reduction in DBP
4
4.0
6.0
4 mmHg (2 studies)
Commercial supplements
Dosage
13
1
3
1 x/day (7 studies)
Supplementation time
8
4
12
6 weeks (5 studies)
Reduction in SBP
8
6.0
8.0
5 mmHg (2 studies)
Reduction in DBP
13
4.0
8.0
—
SBP: systolic blood pressure. DBP: diastolic blood pressure.


## 3.5. Vitamins and Minerals

Evidence support an inverse relationship between vitamin intake and cardiovascular events [45–47]. In fact, the therapeutic use of some vitamins minimizes the risk of atherosclerotic plaque formation and its main determinants [48]. Meanwhile, the minerals are involved in almost all metabolic pathways in the body and play an important role in the treatment of cardiovascular diseases and their risk factors [16].Among the vitamins, C and E are the most studied from the standpoint antioxidants and enzyme, besides being nutrients with potential biological functions [49]. In this paper [14–17, 20–22], studied collected showed the consumption of vitamins C and E as probable lowering of blood pressure.Mullan et al. [20] observed that a 500 mg dose/day of vitamin C for four weeks was able to reduce SBP (10 mmHg) DBP (4 mmHg) in diabetic subjects. When the same amount was administered daily in hypertensive subjects, supplementation decreased the SBP for only 4 mmHg [17]. Another group studied by these authors was treated with the same amount of vitamin C enriched with 1000 mg/day of polyphenols (1000 mg/d) grape seeds, and the hypotensive effect was potentiated in both SBP (5±11 mmHg) and for DBP (4±11 mmHg). Moreover, the study of Plantinga et al. [15], the amount of dietary intake of vitamin C was the double (1000 mg) and, associated with vitamin E (400 IU), however, BP reduction did not occur in hypertensive subjects. Similarly, a combination of vitamin C (200 mg/d) and E (150 mg/d) also was not effective in reducing blood pressure in diabetic subjects [16].Some studies corroborate findings of this paper pointing to a reduction in blood pressure from the consumption of vitamin C [50, 51] in hypertensive patients. Duffy et al. [51] evaluated 500 mg/day of vitamin C in hypertensive patients for four weeks and observed a reduction in SBP of 13 mmHg, but not in DBP. Fotherby et al. [50] also using the same protocol intake in hypertensive patients, for a period of 12 weeks and an observed reduction of 3 mmHg in SBP, however, DBP remained unchanged. A long period of intake of vitamin C may be needed to obtain vasodilatation and consequently reduce blood pressure [52, 53]. However, evidence from human studies are not sufficient to determine the ideal time-consuming vitamins to lower blood pressure without possible adverse effects [54].Supplementation of vitamin E (500 mg/d) for six weeks was effective in reducing SBP (7 mmHg) and DBP (5 mmHg) in diabetic patients [14]. In contrast, the consumption of vitamin E (1600 IU/d), for eight weeks, did not cause changes in pressure values in diabetic [22] as well as in hypertensive patients who consumed controlled 300 mg/d during 12 weeks, having no significant effect on BP [21]. This result corroborates other studies that evaluated the chronic effects of vitamin E in blood pressure [55, 56] using the same dose (300 mg/d) in people with cardiovascular risks. Gazis et al. [22] found a significant reduction in SBP in hypertensive patients when a doubled (600 mg/d) dose is administered. This fact suggests that a higher dose of vitamin E, however, within the values recommended daily, may possibly be more effective.Vitamins C (hydrophilic antioxidant) and E (lipophilic antioxidant) act through nonenzymatic system in the prevention and capture of reactive oxygen species (ROSs), generated by vascular cells [57]. The redox imbalance of hypertension often leads to functional alterations mediated by angiotensin II, stimulating the enzyme NADPH oxidase to increase the production of superoxide anion radical (O2-•), favoring the buffer nitric oxide (NO•) action to oxidative stress, detriment its vasodilator function [57]. However, it is unclear whether the intake of these vitamins may influence the antioxidant activity and enzyme cofactor, and how you can help prevent the formation of ROS [58, 59].Evidence suggests that vitamin D may also improve cardiometabolic profile, reducing the risk factors associated [60, 61]. In this paper, some studies were pooled studies of vitamin D addressing this perspective [12, 13]. In the study of Sugden et al. [12] oral dose (100 000 IU/day) of vitamin D was used for eight weeks, which has been shown to decrease significantly the systolic blood pressure by 14 mmHg, improving endothelial function in patients with type 2 diabetes and deficiency of vitamin D. This can be explained via the renin-angiotensin system and vascular function, where the  first hydroxylase-1-α enzyme metabolite converting of vitamin D (25[OH]D to 1,25[OH]2D3) acts as a binder for the nuclear transcription factor, regulating cell function in tissues such as endothelial cells and vascular smooth muscle, and thereby reducing blood pressure levels [62]. In contrast, when obese women were supplemented with vitamin D (400 mg/d) combined with calcium (1200 mg/d), they showed no improvement in cardiometabolic profile [13]. The low dose compared with the study of Sugden et al. [12] may explain these results.Anyway, the current data allow to infer that there is no consensus that vitamins are really effective in reducing blood pressure. The lack of a conclusion is given by the fact that prospective studies and intervention in humans that prove the effectiveness of vitamin D in the prevention and treatment of cardiometabolic diseases are scarce. The researches that explain the exact mechanisms, by which the active form (1,25[OH]2D3) improves β-cell function, the renin-angiotensin system, and regulation, are also inconclusive.Zinc, magnesium [16, 24], copper [19], potassium [11, 25], and calcium [13, 23] have been adopted in research, hypothesizing its hypotensive effect. Farvid et al. [16] showed that 12 weeks of consumption of 200 mg of magnesium and 30 mg of zinc supplementation did not reduce blood pressure in diabetic subjects. Magnesium and zinc, when enriched with vitamin C 200 mg and 150 mg vitamin E, promoted a significant reduction in the levels of PAS (8 mmHg) and diastolic (6 mmHg) in the same population [16]. Therefore, we cannot establish from this study, the efficacy of these minerals in reducing BP, because only when associated with the vitamin C and E, they were able to reduce blood pressure levels in diabetics. The solution of magnesium chloride when applied to diabetics for a period of 16 weeks also did not modify the blood pressure values [18]. Corroborating this finding, De Valk et al. [24] observed that magnesium supplementation (15 mmol/d) for 12 weeks, in diabetic patients, did not alter the blood pressure values. Therefore, there is no evidence that zinc and magnesiummay be able to promote BP reduction.Consumption of potassium (24 mmol) in hypertensive men, over a period of 15 weeks, decreased the SBP by 10 mmHg and DBP by 7 mmHg [25]. Several mechanisms have been proposed to explain the antihypertensive effect of a high intake of potassium, including an increased loss of water and sodium, suppression of secretion of renin and angiotensin, and stimulation of the activity of sodium-potassium pump. However, Berry et al. [11] found no change in blood pressure after administration of 40 mmol of potassium in hypertensive subjects for six weeks. Alarcón et al. [19] demonstrated that administration of another mineral, copper (5 mg/day), significantly decreased the SBP levels (r=0.963) and DBP (r=0.981) in treated hypertensive patients. Some studies show that cardiometabolic protective effect of minerals was not observed in blood pressure values during supplementation of calcium (1000 mg/d) for eight weeks in hypertensive subjects [23], even when that (1200 mg/d) was associated with vitamin D (400 mg/d), supplementing obese women for 15 weeks [13].Based on these data, it can be stated that there is strong evidence linking vitamins to hypotensive effect, however, there is still no consensus that the minerals are effective in reducing blood pressure.


## 3.6. Antioxidants Compounds

Oxidative stress contributes to increase blood pressure by acting on eNOS uncoupling and decrease bioavailability of nitric oxide [63]. The result is a predominant on factors vasoconstrictors and low action of vasodilators in vascular bed [63]. In the cardiovascular system, the reactive oxygen species (ROSs) are produced in vascular cells by a number of oxidases, including NADPH oxidase, xanthine oxidase, lipoxygenase, and cytochrome P450 [63, 64]. Furthermore, clinical data have suggested that there is increased endogenous antioxidant, introducing exogenous antioxidants present in food. In fact, the reduction of oxidative stress has been accompanied by decreasing cardiovascular risk and blood pressure in humans [65–70].Antioxidants commonly used include vitamins A, C, and E, L-arginine, flavonoids, coenzyme Q10, and alpha-lipoic acid [64, 71]. Of these, flavonoids have gained attention for their higher antioxidant power than the others (Ross and Kasum). These phenolic compounds are commonly found in high concentrations in many fruits, vegetables, and beverages, including apples, strawberries, grapes, onions, pomegranate, red wine, tea, cocoa, and dark chocolate [72].In fact, the selected studies that used supplements based on flavonoids, all demonstrated significant reductions in blood pressure in hypertensive [27], obese [26], and hypercholesterolemic individuals [28]. The reductions were more pronounced for systolic blood pressure, with a reduction of around 3 mmHg. For diastolic blood pressure, only the study by Ward et al., [27] identified a significant reduction (3 mmHg). Interestingly, in this study, the doses of flavonoids were much higher (500 mg versus 150 mg in the others). Although these reductions are relatively discreet, these are clinically significant, so that hypotension afforded by the flavonoid is equivalent to the use of a class of antihypertensive medication [73].In addition to flavonoids, another supplement with strong action antioxidant is coenzyme Q10. Molecule lipid soluble, derived mainly from endogenous synthesis, plays an essential role as the carrier of electrostatic mitochondrial oxidative phosphorylation [74]. The studies of this paper involving the use of coenzyme Q10 [29, 30] were performed with diabetic subjects and also identified significant reductions in blood pressure of 4 mmHg [30] and 27 mmHg [29]. Hodgson et al. [29] found a reduction of 4 mmHg diastolic. Interestingly, the study showed that diastolic hypotension, as well as flavonoids, was also performed with larger amount of coenzyme Q10 against the others (200 versus 60 mg), which enables to infer that the reduced pressure in response to supplementation with antioxidants appears to be dependent on the concentration.The mechanism of cell signaling by flavonoids give up buffering of ROS (Ross and Kasum) or limits its formation [69]. The actions of the polyphenols as buffering occurs through their ability to modulate the levels of activity of nitric oxide synthase (eNOS) and, therefore, the bioavailability of endothelial nitric oxide (NO) [75–79]. The flavonoids reduce the formation through interaction with inhibitory kinase signaling pathways, such as via the PI3-kinase/Akt and intracellular Ca2+ [80, 81], and promote inhibition of the enzyme NADPH oxidase, which is the enzyme responsible for the production of ROS. Furthermore, prevents vascular injury by inhibition of MAPK inhibition of transcription factors (NF-kB), and matrix metalloproteinases (MMP), allowing reduction in angiogenesis, migration and proliferation of vascular cells.It is well established that the flavonoids inhibit the oxidation of low density lipoprotein (LDL) [82] to reduce the formation of atherosclerotic lesions [83], inhibit platelet aggregation [83], decrease expression of vascular cell adhesion molecule [84], and reduce blood pressure or prevent its rise [85].


## 3.7. Aminoacids and Proteins

Some isolated nutrients of food have been investigated on possible hypotensive effect in individuals with cardiometabolic risk. Among those selected in this paper, proteins [31, 32] and amino acids were observed [33]. These nutrients are positively associated with the control of metabolic disorders (e.g., hypertension) [86, 87]. Spirulina has a high protein content and is considered one of the richest sources of vitamins and minerals, besides presenting phenolic compounds and essential fatty acids [88]. Furthermore, the research shows its various biological activities, among them is the vasodilator, proposing its antihypertensive action [89] as well as improved glycemic profile [90].Torres-Duran et al. [32] studied the effects of oral supplementation of spirulina 4.5 g/d in hypertensive and dyslipidemic subjects for six weeks and noted a reduction in SBP (120±9 versus 109±9 mmHg) and DBP (85±9 versus 79±8 mmHg), being observed since the fourth week of intervention. Corroborating this study, Lee et al. [31] also observed a significant reduction in DBP (84±2 versus 79±2 mmHg) when diabetic patients consumed 8 g/d of spirulina for 12 weeks, however, the SBP remained unchanged.According to Hsiao et al. [91], hypotension can be explained by vasodilation determined by an increase in nitric oxide synthesis, by inhibition of platelet aggregation, by inhibiting calcium mobilization, and by mediating the release of free radicals. Guan et al. [86] proposed that the high concentration of potassium and the low sodium content of spirulina would be able to generate positive implications PA, supported by a classic effect that food mediate several steps in the process of inflammation reducing atherothrombotic plaque formation. Based on these data, we can say that spirulina acts favorably on serum lipids, antioxidant capacity, and inflammatory response in diabetic, hypertensive, and dyslipidemic subjects. However, the mechanisms by which spirulina lowers blood pressure are not well understood.Among the observed amino acid L-arginine is an amino acid which proposes to improve endothelial function contributing to the hypotensive effect from the synthesis of nitric oxide (NO) [92, 93]. Additionally, other benefits such as improved blood flow and reduction in platelet aggregation have been attributed to L-arginine in human models [87]. West et al. [33], after oral intervention 12 g/d of L-arginine in hypercholesterolemic men for three weeks, observed a reduction in SBP (134±3 versus 114±4) and DBP (87±2 versus 71±2), suggesting that L-arginine is involved in the mechanisms  hemodynamic of hypotension. In fact, one mechanism that may explain these data is related to endothelial function [94]. The increase in plasma nitrite reflects an improvement in endothelial function and may explain the significant reduction of baseline blood pressure.


## 3.8. Foods in Nature

Despite that studies have demonstrated the efficacy of isolated nutrients (i.e., vitamins, minerals, and flavonoids) [16, 20] in reducing blood pressure, studies evaluating the effects of food in nature on blood pressure of hypertensive patients are scarce. Methodological difficulties and the impossibility of determining which particular food component is the active compound are some of the likely factors that may explain this paucity in the literature. Moreover, studies within natural food have the advantage of external validity, approaching more to the reality of population’s eating habits and how these habits result in the proposed benefits in the studies.Among the studies selected in this paper, we have investigated the effects of garlic [34], grape juice [36], and whey [35], all in hypertensive middle-aged people. While the wine had been well investigated, this paper found only studies with normotensive, which was an exclusion criterion at the time of selection of papers.Dhawan and Jain [95] and Durak et al. [96] found that administration of garlic preparations resulted in significant reductions in blood pressure in hypertensive patients. The first garlic supplementation for eight weeks was able to reduce blood pressure in young hypertensive subjects. The latter, supplementing hypercholesterolemic patients for 16 weeks, found a significant decrease of systolic blood pressure around 22 mmHg. In contrast, Duda et al. [34] observed that the use of aged garlic extract, containing 1.62 mg of allicin/day, resulted in modest reduction in blood pressure both systolic and diastolic blood pressure (about 1 mmHg for both systolic and diastolic) without statistical differences. These results corroborate the findings of Brace [97], where they found no effect of preparations containing garlic on blood pressure.Some factors may explain this discrepancy in the results. Among them is the duration of administration and the dosage used. In their study, Duda et al. [34], 1.62 mg of allicin was administered for 4 weeks, while in studies of Dhawan and Jain [95] and Durak et al. [96] doses of 250 mg and 10 g were administered, during 2 and 4 months, respectively.Among compounds present in garlic, allicin is involved in most of the therapeutic benefits promoted by this food [98]. The benefits include reduction of low density lipoprotein cholesterol (LDL) and elimination of reactive oxygen species [98]. Warshafsky et al. [99] found that the consumption of 1–1.5 garlic cloves daily (containing approximately 1.5 mg of allicin) can reduce cholesterol around 9%. Likewise, [34] found a reduction in total cholesterol of around 9%, despite not finding lower blood pressure in his study.Therefore, the data of this paper support the premise that the incorporation of consumption of garlic compounds or derivatives have beneficial effects such as reduction of oxidative stress and lipid peroxidation in hypertensive subjects. For these benefits to be extended, it appears that the consumer must take chronically (at least 2 months) a minimum amount of allicin 250 mg/day (about 2.5 garlic cloves).The contained polyphenols in purple grape, red wine, and other dark red to purple color fruits are compounds with protective properties of the cardiovascular system since they increase the plasma concentration of high density lipoproteins (HDLs), slow the development of atherosclerosis, function as potent antioxidants, improve endothelial function, and are able to reduce blood pressure in hypertensive subjects [100]. The improvement of endothelial function would be due to the stimulation of increased production of nitric oxide by the vascular endothelium. This vessel has relaxants and antiaggregatory properties and in the long term can modulate the expression of protective genes of the cardiovascular system [101]. Studies with polyphenols isolated from foods are conclusive in demonstrating their cardiovascular protective effects, including lowering blood pressure.Considering these effects for isolated polyphenols, Park et al. [36] investigated whether the ingestion of these nutrients contained in foods, grape juice, would be able to decrease blood pressure. They tested the hypothesis that chronic consumption (8 weeks) would reduce blood pressure via increased availability of nitric oxide. They observed a 9% reduction in systolic blood pressure (around −7.2 mmHg) and diastolic (around −6.2 mmHg), confirming Opie and Lecour [100]. However, the author proposes increase in NO production for explaining the hypotensive effect but does not have any data that supporting this idea.Its important to note that the consumption of grape juice in the study of Park et al. [36] gave an average 881.14 mg/day of flavonoids, whereas in these studies from isolated nutrients it was 500 mg [26–28]. This corroborates the ability of grape juice (being consumed daily around 425.6 mL) to promote beneficial effects on blood pressure and great applicability to the general population. Therefore, the inclusion of grape juice in the diet, even in low amounts, is an interesting strategy of eating habits to lower BP.The potassium and calcium supplementation has been suggested as modulators of systemic arterial pressure [35]. The fermented skim-milk, Calpis sour milk, can serve as a nutritional strategy to control hypertension, since, besides possessing these nutrients, it has certain strains of bacteria, such as Lactobacillus helveticus and Saccharomyces cerevisiae, which has been shown to promote antihypertensive effect in SHR rats [102]. Additionally, this milk peptide fractions (valine-proline-proline and isoleucine-proline-proline) would be responsible for ACE inhibition, key enzyme in the pathophysiology of hypertension.Based on this, Mizushima et al. [35] tested the hypothesis that consumption of this beverage (160 g/dia) for 4 weeks would be sufficient to reduce blood pressure, in hypertensive subjects, about −5 mmHg and 2 mmHg, in systolic blood pressure, and diastolic respectively.Although not proven in humans, the peptide fractions of the milk (valine and proline-proline-isoleucine-proline-proline) has the ability to inhibit ACE activity in SHR rats [102]. If this inhibitory effect is extended to humans is unclear [35]. It is proposed that these compounds in Calpis sour-milk (at doses of 0.033 and 0.025 mL/kg, resp.) have pharmacological activity sufficient for inhibition of the ACE activity and contribute to reducing pressure levels.Because it contains a high concentration of Ca, this nutrient could be considered responsible for blood pressure reductions observed in this study. However, the [Ca] was similar between the placebo and treatment groups, making it impossible to draw a cause-effect relationship for this particular nutrient. Furthermore, the [Ca] in the milk would be well below what is needed (about 90 mg) to promote positive effects as observed in other studies when used in isolation (1000 mg) [103].In short, it is interesting to note that the daily intake of 2.5 cloves of garlic, about 385 mL of grape juice, and 160 g of Calpis sour-milk can promote significant reductions in blood pressure. It should be noted that the amount of feed required to ensure hypotensive effect is so small that it can be easily implemented in the diet even by persons who may not display any of these taste in the food. Additionally, although it was not contemplated by the inclusion criteria, recent studies have shown that eating 100 g of dark chocolate [104] and 6 g of watermelon extract [105] were also able to promote BP reduction, may attenuate up to between 11.9±7.7 and −15.1±2.8 mmHg for SBP.


## 3.9. Commercial Supplements

Dietary supplements are products added to the diet, which contain at least one of the following ingredients: vitamins, minerals, amino acids, proteins, metabolites, antioxidants, carbohydrates, lipids, fatty acids, or a combination of any of these [106]. Historically, dietary supplements have a wide acceptance and use by exercise practitioners, believing these products improve their sports performance and health [107].Concomitant to the advancement and dissemination of information in the area of nutrition, the market potential of these products to other niche market products has grown rapidly. In this context, products intended for the general population, and specifically for hypertensive and cardiac subjects, began to have its production increased. However, these products are not always grounded in reliable scientific findings, often occurring in misinterpretation of results.Among the selected studies by this paper, it was observed that the responsible components for the modulation of blood pressure were dietary fiber products, probiotics, and antioxidant compounds [30, 38, 40, 41, 43, 44].Vuksan et al. [38] verified the effectiveness of chia supplement on cardiovascular diseases markers. Despite finding satisfactory results (chia consumption of 37 g/d for 12 weeks resulted in about −6 mmHg and −3 mmHg for systolic and diastolic blood pressure, resp.) it is not yet possible to draw firm conclusions because of the study’s limitations. Among them, it is not known which of the various components of the product would be responsible for the positive effects, and it is unknown whether the effects of positive pressure of this food consumption were associated with direct consumption of chia or by changes in diet composition between treatments (intervention versus placebo).As in the case of chia, there is no body of evidence linking the essential fatty acid supplementation or consumption of fermented milk CAUSIDO with lower blood pressure in hypertensive subject. Despite the remarkable relationship between fish consumption (source of essential fatty acids) and improvement in cardiovascular health, there is insufficient evidence to assert that supplementation of this type of product shows the same physiological effects.In short, despite the growing interest and use of dietary supplements for blood pressure control, it is necessary to observe if there is a body of evidence in the specific literature to justify the use of these compounds for hypertension.


## 4. Conclusion and Perspectives

There is scientific evidence to support the idea that there is a reasonable variety of foods or isolated foods nutrients capable of promoting reduction of blood pressure in hypertensive, obese, diabetic, and hypercholesterolemic subjects. Interestingly, the magnitude of the blood pressure reduction is equivalent, in some cases, it is obtained by pharmacological agents. Some food and nutrients studied are already included in the DASH protocol, but others had their antihypertensive properties revealed only recently. Therefore, this paper provides subsidies to propose range of foods and nutrients that can be incorporated into the diet of people that need care for blood pressure and may provide a basis for future updates in DASH protocol.



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*Source: 581651-2013-03-26.xml*