Potential of garlic (Allium sativum) in lowering high blood pressure: mechanisms of action and clinical relevance

Abstract

Garlic supplements have shown promise in the treatment of uncontrolled hypertension, lowering blood pressure (BP) by about 10 mmHg systolic and 8 mmHg diastolic, similar to standard BP medication. Aged garlic extract, which contains S-allylcysteine as the bioactive sulfur compound, in particular is standardizable and highly tolerable, with little or no known harmful interaction when taken with other BP-reducing or blood-thinning medication. Here we describe biologically plausible mechanisms of garlic's BP-lowering effect. Garlic-derived polysulfides stimulate the production of the vascular gasotransmitter hydrogen sulfide (H2S) and enhance the regulation of endothelial nitric oxide (NO), which induce smooth muscle cell relaxation, vasodilation, and BP reduction. Several dietary and genetic factors influence the efficiency of the H2S and NO signaling pathways and may contribute to the development of hypertension. Sulfur deficiency might play a part in the etiology of hypertension, and could be alleviated with supplementation of organosulfur compounds derived from garlic.

Keywords: S-allylcysteine; garlic; hydrogen sulfide (H2S); hypertension; nitric oxide (NO); redox signaling.

Figure 1

Effect of garlic on blood pressure via the NO pathway. Notes: Blue rectangles illustrate metabolites, blue circles represent enzymes, orange circles are dietary cofactors, green star shapes are garlic and other organosulfur-containing nutrients, red rectangle represents NO, and purple rectangles denote direct and indirect influence of NO on vasodilation and blood pressure. NO pathway: in the presence of BH₄, eNOS produces NO, which triggers pathways leading to smooth muscle cell relaxation and vasodilation. eNOS uncoupling leads to the formation of O₂⁻. NO and O₂⁻ combine to form OONO⁻, which rapidly reacts with thiols and tyrosine residues of proteins, which in turn, leads to vasodilation and BP reduction independent of cGMP. Garlic and other dietary organosulfides may play a role in the regulation of the NO signaling pathway by creating a more reductive environment and therefore supporting NO production. Abbreviations: BH₂, dihypdrobiopterin; BH₄, tetrahydrobiopterin; Ca²⁺, calcium ion; cGMP, cyclic-guanosyl-monophosphate; GSSG, oxidized glutathione; eNOS, endothelial-nitric-oxide-synthase; GSH, reduced free glutathione; GTP, guanosyl-tri-phosphate; NO, nitric oxide (radical); ONOO, peroxynitrite; O₂, oxygen; O₂⁻, superoxide anion radical; PKB, protein kinase-B.

Figure 2

Effect of garlic on blood pressure via the hydrogen sulfide (H₂S) pathway, and influence of dietary and genetic factors on homocysteine levels. Notes: Blue rectangles illustrate metabolites, blue circles represent enzymes, orange circles are dietary cofactors, green star shapes show garlic and other polysulfide-containing nutrients, red rectangle indicates H₂S, and purple rectangles represent direct and indirect influence of H₂S on vasodilation and blood pressure. Red circles 1–7: Influence of dietary and genetic factors on H₂S pathway 1= genetic polymorphism, homozygous for deleterious allele, leads to impaired folate metabolism. 2= common polymorphisms, some of which lead to increased homocysteine and decreased methylation and SAM levels; these respond well to folate supplementation. 3= genetic defects lead to increased homocysteine levels. 4= low Vit B12 levels lead to increased homocysteine levels. 5= defect in CBS enzyme leads to increased homocysteine levels and reduced H₂S production. 6= low Vit B₆* levels may increase homocysteine levels and reduce H₂S production, and may respond to Vit B₆ supplementation. 7= dietary intake of garlic polysulfides and thiosulfides can increase H₂S nonenzymatically, and may ameliorate genetic defects in the CBS enzyme, or dietary deficiencies in Vit B₆ and/or the sulfur-containing amino acids cysteine and methionine. Abbreviations: CAT, cysteine-amino-transferase; CBS, cystathionine-β-synthase; CSE, cystathionine-γ-lyase; CysSSCys, oxidized cysteine/cystine; eNOS, endothelial nitric oxide synthase; Glu, L-glutamic acid; Gly, glycine; GSSG, oxidized glutathione; GSH, reduced glutathione; H₂O₂, hydrogen peroxide; K⁺, potassium ion; MPST, mercapto pyruvate sulfur transferase; NADPH, nicotinamide adenine dinucleotide phosphate; MTHFR, methylene-tetra-hydro-folate reductase; SAH, S-adenosyl-homocysteine; SAM, S-adenosyl-methionine; Se, selenium; Vit B₆*, activated form of Vit B₆ = pyridoxal-phosphate; Vit B₂, vitamin B₂ (riboflavin); Vit B₁₂, vitamin B₁₂.