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The Mechanism for Garlic's (Allium sativum) Ability to Lower Blood Pressure

Summary:

  • Garlic (Allium sativum) is frequently used for the treatment of many cardiovascular diseases that include high cholesterol, heart disease, and hypertension.        
  • The active ingredient in garlic is known to be allicin (diallyl thiosulfinate).
  • Garlic's ability to lower the blood pressure is multifactorial and includes: increasing the availability and activities of nitric oxide, inhibiting ACE thereby reducing a number of pathways that are known to decrease plasma volume and vasoconstriction, and lastly, increasing the production of H2S that results in hyperpolarization of vascular smooth muscle cells.

Editor-in-Chief: Anthony J. Busti, MD, PharmD, FNLA, FAHA
Last Reviewed: October 2015

Explanation

  • The public's use of natural medicines for the treatment of cardiovascular disease is increasing.1,2  In particular, garlic (Allium sativum) is frequently used for the treatment of many cardiovascular diseases including high cholesterol, heart disease, and hypertension.3-5  Garlic's effect on blood pressure is the focus of this question. 

    The active ingredient in garlic is known to be allicin (diallyl thiosulfinate), which is the main organosulfur compound.  It is formed when garlic is chopped or crushed, thereby causing the allinase enzyme present in the garlic to convert alliin to allicin.6  Upon ingestion with an aqueous solution, the allicin decomposes to diallyl sulfide, diallyl disulfide, and diallyl trisulfide that make up the organic polysulfides noted in figure 1.7  Garlic's blood pressure lowering effects appear to be a contribution of a number of mechanisms/factors.    

    The first proposed mechanism is garlic's ability to indirectly and directly increase the activity and vasodilatory properties of nitric oxide (NO).8  One way garlic accomplishes this is through its contribution of arginine, which is a known precursor for the production of NO when acted upon by nitric oxide synthase.9,10 

    Garlic has also been shown to inhibit the renin angiotensin aldosterone system (RAAS) and prostaglandin synthesis.  The change in this balance favors vasodilation.  This, in part, is thought to be from garlic's inhibition of angiotensin converting enzyme (ACE) activity.11 The reductions in ACE activity results in a number of favorable effects that cause reductions in blood pressure.  The first effect is the reduction in angiotensin II (ATII), which is known to be a direct vasoconstrictor. Secondly, a reduction in ATII will decrease adrenal production of aldosterone.12 This reduction in aldosterone production will ultimately decrease the reabsorption of sodium and water from the distal convoluted renal tubule, thereby decreasing plasma volume.13,14  Third, while reductions in ATII can reduce the availability of the vasodilatory prostaglandin (PGE2), the increased bradykinin levels (due to ACE inhibition) can increase PGE2.  This is important since garlic is thought to inhibit cyclooxygenase activity that would allow for the production of thromboxane B2, which is a known vasoconstrictor.15 As such, this change in balance towards PGE2 favors vasodilation.15 The decrease in the metabolism of bradykinin through ACE inhibition by garlic is also known to increase the production of NO, thereby further contributing to an environment in favor of vasodilation.16

    The final mechanism of garlic associated vasodilation is its ability to increase the production of hydrogen sulfide (H2S).17  It is known that red blood cells will produce H2S when provided with sulfur containing products.  As mentioned earlier, allicin is degraded when taken with water to produce organic polysulfides.  These garlic derived polysulfides contribute the sulfur needed by the RBC to increase the production of H2S.  Upon its production, H2S will bind to and activate vascular KATPchannels, thereby resulting in hyperpolarization of the vascular smooth muscle cells.18  Hyperpolarization of these cells causes vasodilation or vascular relaxation that facilitates a reduction in blood pressure.18

    As previously mentioned, the blood pressure lowering effects of garlic are multifactorial.

    References:

    1. Yeh GY, Davis RB, Phillips RS.  Use of complementary therapies in patients with cardiovascular disease.  Am J Cardiol  2006;98:673-80.
    2. National Center for Complementary and Alternative Medicine: National Institutes of Health.  The Use of complementary and alternative medicine in the United States: 2007 National Health Interview Survey Report.  Last accessed on 2/14/2009.
    3. National Center for Complementary and Alternative Medicine: National Institutes of Health.  Herbs at a glance: Garlic.  Last accessed on 3-16-2009.
    4. Garlic: Effects on Cardiovascular Risks and Disease, Protective Effects Against Cancer, and Clinical Adverse Effects. Summary, Evidence Report/Technology Assessment: Number 20. AHRQ Publication No. 01-E022, October 2000. Agency for Healthcare Research and Quality, Rockville, MD.
    5. Ackerman RT, Mulrow CD, Ramirez G et al.  Garlic shows promise for improving some cardiovascular risk factors.  Arch Intern Med  2001;161:813-24.
    6. Banerjee SK, Mukherjee PK, Maulik SK.  Garlic as an antioxidant: the good, the bad and the ugly.  Phytother Res  2003;17:97-106.
    7. Amagase H.  Clarifying the real bioactive constituents of garlic.  J Nutr  2006;136:716S-725S.
    8. Kim-Park S, Ku DD.  Garlic elicits a nitric oxide-dependent relaxation and inhibits hypoxic pulmonary vasoconstriction in rats.  Clin Exp Pharmacol Physiol 2000;27:780-6.
    9. Morihara N, Sumioka I, Morguchi T et al. Aged garlic extract enhances production of nitric oxide.  Life Sci  2002;71:509-17.
    10. Kim KM, Chun SB, Koo MS et al.  Differential regulation of NO availability from macrophages and endothelial cells by the garlic component S-allyl cysteine.  Free Radic Biol Med  2001;30:747-56.
    11. Sharifi AM, Darabi R, Akbarloo N.  Investigation of antihypertensive mechanism of garlic in 2K1C hypertensive rat.  J Ethnopharmacol  2003;86:219-24.
    12. Palmer BF.  Managing hyperkalemia caused by inhibitors of the renin-angiotensin-aldosterone system.  N Engl J Med  2004;351:585-92.
    13. Garty H.  Mechanisms of aldosterone action in tight epithelia.  J Membr Biol  1986;90:193-205.
    14. Verrey F, Schaerer E, Zoerkler P et al.  Regulation by aldosterone of Na+,K+-ATPase mRNAs, protein synthesis, and sodium transport in cultured kidney cells.  J Cell Biol  1987;104:1231-7.
    15. Al-Qattan KK, Khan I, Alnaqeeb MA et al.  Thromboxane-B2, prostaglandin-E2 and hypertension in the rat 2-kidney 1-clip model: a possible mechanism of the garlic induced hypotension.  Prostaglandins Leukot Essent Fatty Acids  2001;64:5-10.
    16. Liu YH, Tang XP, Sharov VG et al.  Effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists in rats with heart failure.  Role of kinins and angiotensin II type 2 receptors.  J Clin Invest  1997;99:1926-35.
    17. Benavides GA, Squadrito GL, Mills RW et al.  Hydrogen sulfide mediates the vasoactivity of garlic.  Proc Natl Acad Sci USA  2007;104:17977-82.
    18. Zhao W, Zhang J, Lu Y et al.  The vasorelaxant effect of H(2)S as a novel endogenous gaseous K(ATP)channel opener.  EMBO J  2001;20:6008-16.

MESH Terms & Keywords

  • Garlic, Allium Sativum, Blood Pressure, Herbal Supplements for Hypertension