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:
- Yeh GY, Davis RB, Phillips RS. Use of complementary therapies in
patients with cardiovascular disease. Am J Cardiol 2006;98:673-80.
- 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.
- National
Center for Complementary and Alternative Medicine: National Institutes
of Health. Herbs at a glance: Garlic. Last accessed on 3-16-2009.
- 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.
- Ackerman
RT, Mulrow CD, Ramirez G et al. Garlic shows promise for improving
some cardiovascular risk factors. Arch Intern Med 2001;161:813-24.
- Banerjee
SK, Mukherjee PK, Maulik SK. Garlic as an antioxidant: the good, the
bad and the ugly. Phytother Res 2003;17:97-106.
- Amagase H. Clarifying the real bioactive constituents of garlic. J Nutr 2006;136:716S-725S.
- 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.
- Morihara N, Sumioka I, Morguchi T et al. Aged garlic extract enhances production of nitric oxide. Life Sci 2002;71:509-17.
- 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.
- Sharifi
AM, Darabi R, Akbarloo N. Investigation of antihypertensive mechanism
of garlic in 2K1C hypertensive rat. J Ethnopharmacol 2003;86:219-24.
- Palmer
BF. Managing hyperkalemia caused by inhibitors of the
renin-angiotensin-aldosterone system. N Engl J Med 2004;351:585-92.
- Garty H. Mechanisms of aldosterone action in tight epithelia. J Membr Biol 1986;90:193-205.
- 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.
- 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.
- 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.
- Benavides
GA, Squadrito GL, Mills RW et al. Hydrogen sulfide mediates the
vasoactivity of garlic. Proc Natl Acad Sci USA 2007;104:17977-82.
- 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.