Dietary Nitrate from Beetroot Juice for Hypertension: A Systematic Review

Abstract

According to current therapeutic approaches, a nitrate-dietary supplementation with beetroot juice (BRJ) is postulated as a nutritional strategy that might help to control arterial blood pressure in healthy subjects, pre-hypertensive population, and even patients diagnosed and treated with drugs. In this sense, a systematic review of random clinical trials (RCTs) published from 2008 to 2018 from PubMed/MEDLINE, ScienceDirect, and manual searches was conducted to identify studies examining the relationship between BRJ and blood pressure. The specific inclusion criteria were: (1) RCTs; (2) trials that assessed only the BRJ intake with control group; and (3) trials that reported the effects of this intervention on blood pressure. The search identified 11 studies that met the inclusion criteria. This review was able to demonstrate that BRJ supplementation is a cost-effective strategy that might reduce blood pressure in different populations, probably through the nitrate/nitrite/nitric oxide (NO₃^-/NO₂^-/NO) pathway and secondary metabolites found in Beta vulgaris. This easily found and cheap dietary intervention could significantly decrease the risk of suffering cardiovascular events and, in doing so, would help to diminish the mortality rate associated to this pathology. Hence, BRJ supplementation should be promoted as a key component of a healthy lifestyle to control blood pressure in healthy and hypertensive individuals. However, several factors related to BRJ intake (e.g., gender, secondary metabolites present in B. vulgaris, etc.) should be studied more deeply.

Keywords: Beta vulgaris; blood pressure; dietary supplements; hypertension; nitric oxide.

Figure 1

The nitrate/nitrite/nitric oxide (NO₃⁻/NO₂⁻/NO) pathway after beetroot juice (BRJ) ingestion. Next to BRJ ingestion, oral microbiota on the posterior surface of the tongue is able to reduce NO₃⁻ to NO₂⁻ by means of their enzymatic machinery. The strict anaerobes Veillonella atypical and Veillonella dispar are the most important NO₃⁻ reducers; however, Actinomyces, Rothia, Prevotella, Neisseria, and Haermophilus are also present on the oral cavity. Even though this non-enzymatic reduction process continues in stomach, where more NO₂⁻ and NO are produced due to the acid environment, a considerable amount of NO₃⁻ from blood (≈25%) is taken up by an electrogenic 2NO₃⁻/H⁺ symporter called SLC17A5 (also known as sialin, UniProt ID: Q9NRA2) in the salivary gland acinar cells [14]. Both dietary and saliva NO₃⁻, and its reduced forms NO₂⁻ and NO, enter directly to systemic circulation after the absorption process in the stomach and intestine. Thus, the increase of NO₃⁻ and NO₂⁻ concentrations in blood allow the generation of NO by either enzymatic or non-enzymatic mechanisms (such as xanthine oxidoreductase, respiratory chain enzymes, aldehyde oxidase, methemoglobin formation, protons, etc.), especially under physiologic hypoxia and low pH [12]. Because of its short half-life (1–2 ms), once NO is produced in blood it is broken down by hemoglobin or it can diffuse into the vascular smooth muscle cells and binds to guanylyl cyclase, which allows the allosteric activation of this last and subsequent cGMP production. Here, cGMP acts as a second messenger and activates PKG, which in turn can modulate smooth muscle relaxation by several interlinked mechanisms: (i) activation of K⁺ channels leading to hyperpolarization; (ii) reduction of intracellular Ca²⁺ concentration; and (iii) activation of the myosin-light-chain phosphatase [15]. Finally, NO₃⁻ is normally excreted in the urine by the kidneys. BP: blood pressure. Original material.

Figure 2

Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow chart.

Figure 3

Risk of bias summary.

Figure 4

Individual factors influencing the effects of BRJ supplementation on blood pressure. Dietary administration of BRJ has been associated with beneficial effects on SBP and DBP; however, these effects appear to depend on age, gender, baseline blood pressure, body weight, and body composition.