Beetroot, a Remarkable Vegetable: Its Nitrate and Phytochemical Contents Can be Adjusted in Novel Formulations to Benefit Health and Support Cardiovascular Disease Therapies

Abstract

The cardioprotective effects of dietary nitrate from beetroot in healthy and hypertensive individuals are undeniable and irrefutable. Nitrate and nitrate-derived nitrite are precursors for nitric oxide synthesis exhibiting an effect on cardiomyocytes and myocardial ischemia/reperfusion, improving endothelial function, reducing arterial stiffness and stimulating smooth muscle relaxation, decreasing systolic and diastolic blood pressures. Beetroot phytochemicals like betanin, saponins, polyphenols, and organic acids can resist simulated gastrointestinal digestion, raising the hypothesis that the cardioprotective effects of beetroots result from the combination of nitrate/nitrite and bioactive compounds that limit the generation of reactive oxygen species and modulate gene expression. Nitrate and phytochemical concentrations can be adjusted in beet formulations to fulfill requirements for acute or long-term supplementations, enhancing patient adherence to beet intervention. Based on in vitro, in vivo, and clinical trials, beet nitrate and its bioactive phytochemicals are promising as a novel supportive therapy to ameliorate cardiovascular diseases.

Keywords: antioxidant activity; beetroot-food interventions; betanin; clinical trials; nitric oxide; polyphenols.

Figure 1

Biosynthesis pathway and general structures of betalains (reproduced from [161]).

Figure 2

Health effects of betanin: A summary of molecular and metabolic targets of betanin reported in cell cultures and animal models. AGEs, advanced glycation end products; C, carbon; COX, cyclooxygenase; DNA, deoxyribonucleic acid; FBP1, fructose-bisphosphatase 1; G6-P, glucose 6-phosphate; G6PDH, glucose-6-phosphate dehydrogenase; GCK, glucokinase; GPx, glutathione peroxidase; GSTA, glutathione S-transferases A; GSTM, glutathione S-transferases M; GSTP, glutathione S-transferases P; GSTT, glutathione S-transferases T; H, hydrogen; H₂O₂, hydrogen peroxide; IL-1β, interleukin 1 beta; HO-1, heme oxygenase-1; iNOS, inducible nitric oxide synthase; LDL, low-density lipoprotein; LOX; lipoxygenase; mRNA, messenger ribonucleic acid; N, nitrogen; NF-_Κβ, nuclear factor kappa beta; NQO1, quinone dehydrogenase 1; NO, nitric oxide; Nrf2-ARE, nuclear factor erythroid 2-antioxidant responsive element; O, oxygen; O2^•−, superoxide anion; OH, hydroxyl radical; Ox-LDL, oxidized low-density lipoprotein; PK, pyruvate kinase; ROS, reactive oxygen species; SOD, superoxide dismutase; TGF-β, transforming growth factor beta; TNF-α, tumor necrosis factor alpha.

Figure 3

The physiological role of nitric oxide in smooth muscle tissue, maintenance of vascular tone, synaptic transmission, cellular defense, hemostatic-thrombotic balance, and mitochondrial function. ATP, adenosine triphosphate; ATPase, adenosine triphosphatase; Ca²⁺, calcium; Cu²⁺, copper; Fe²⁺, ferrous iron; GMPc, guanosine monophosphate cyclic; GPIIb, glycoprotein IIb; GPIIIa, glycoprotein IIIa; GTP, guanosine-5′-triphosphate; iNOS, inducible nitric oxide synthase; LDL, low-density lipoprotein; N2O3, dinitrogen trioxide; NMDA, N-methyl-D-aspartate; NO, nitric oxide; NO₂⁻, nitrite; NO₃⁻, nitrate; O₂, oxygen; ONOO⁻, peroxynitrite; Ox-LDL, oxidized low-density lipoprotein; PKG, protein kinase G; P_O2, pressure of oxygen; ROS, reactive oxygen species; sGC, soluble guanylate cyclase; TXA2, thromboxane A2; VASP, vasodilator-stimulated phosphoprotein.