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(Circulation. 1997;96:2649-2655.)
© 1997 American Heart Association, Inc.
Articles |
Protective Effect of Chronic Garlic Intake on Elastic Properties of Aorta in the Elderly
From the Centre for Cardiovascular Pharmacology, ZeKaPha GmbH (K.B.-G., M.L., G.G.B.), Mainz, Germany, and Division of Cardiology (H.B.), Ohio State University, Columbus, Ohio.
Correspondence to Prof Gustav G. Belz, MD, PhD, FAAC, Zentrum für Kardiovaskuläre Pharmakologie, Mathildenstraße 8, 55116 Mainz, Germany.
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Abstract |
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Background Epidemiological studies have suggested that garlic may have protective effects against cardiovascular diseases. We undertook this cross-sectional observational study to test the hypothesis that regular garlic intake would delay the stiffening of the aorta relating to aging.
Methods and Results We studied healthy adults (n=101;
age, 50 to 80 years) who were taking 
300 mg/d of standardized garlic
powder for 2 years and 101 age- and sex-matched control subjects.
Pulse wave velocity (PWV) and pressure-standardized elastic vascular
resistance (EVR) were used to measure the elastic properties of the
aorta. Blood pressures, heart rate, and plasma lipid levels were
similar in the two groups. PWV (8.3±1.46 versus 9.8±2.45 m/s;
P<.0001) and EVR (0.63±0.21 versus 0.9±0.44
m2 · s-2 ·
mm Hg-1; P<.0001) were lower in
the garlic group than in the control group. PWV showed significant
positive correlation with age (garlic group, r=.44; control
group, r=.52) and systolic blood pressure (SBP)
(garlic group, r=.48; control group, r=.54). With
any degree of increase in age or SBP, PWV increased less in the garlic
group than in the control group (P<.0001). ANCOVA and
multiple regression analyses demonstrated that age and SBP were
the most important determinants of PWV and that the effect of garlic on
PWV was independent of confounding factors.
Conclusions Chronic garlic powder intake attenuated age-related increases in aortic stiffness. These data strongly support the hypothesis that garlic intake had a protective effect on the elastic properties of the aorta related to aging in humans.
Key Words: aorta • arteriosclerosis • elasticity • garlic • waves
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Introduction |
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Ecological studies have suggested an inverse relationship between nutritional garlic intake and cardiovascular mortality; this has been attributed to a protective effect of garlic against cardiovascular diseases.1 2 Although it has been reported that garlic intake may have beneficial effects on blood pressure, blood lipids, and blood coagulation factors, the precise mechanism or mechanisms responsible for the effect or effects remain to be defined.1 2 3 4
It is well appreciated that the aorta does not only serve a conduit function but also plays an important role in the modulation of left ventricular performance, myocardial perfusion, and arterial function throughout the entire cardiovascular system.5 6 7 8 9 Several indices have been used to evaluate the elastic properties of the aorta in humans; PWV is a simple, noninvasive, highly reproducible index that can be used to measure elastic properties of the aorta. Increased PWV is associated with increased aortic stiffness, and vice versa.10
Elastic properties of the aorta decrease with age even in the absence of underlying cardiovascular pathology.11 12 It was hypothesized that if garlic had any protective effect against cardiovascular diseases related to aging, regular garlic intake would delay the stiffening of the aorta related to aging. The present study was undertaken to test this hypothesis in an observational, cross-sectional design using a matched-pairs technique in healthy individuals aged 50 to 80 years.
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Methods |
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Study Population
The study was performed according to the revised Declarations of Helsinki, and the protocol was approved by an independent ethics committee. Written informed consent was obtained from all subjects before the study. Healthy, nonsmoking individuals with an age range of 50 to 80 years and a history of regular garlic intake (
300 mg powder
preparation/d for 2 years immediately preceding the study) were
included in the garlic group. Healthy individuals without regular
garlic intake, who were age (±5 years) and sex matched with similar
body weight (±10%), were used as control subjects. Two hundred two
subjects were studied; none were endurance-trained athletes. All
subjects were Caucasians who lived within the same geographic area. The
garlic group included 101 subjects (52 women and 49 men; mean age, 63.1
years), and the control group included 101 subjects (52 women and 49
men; mean age, 62.4 years) (Table
). Garlic users
reported ingesting an average of 4.6 (range, 3 to 9) 100-mg garlic
tablets for an average of 7.1 years (range, 2 to 16 years; median, 5.7
years). Subjects receiving regular treatment with medications that may
alter the elastic properties of the aorta (eg, ACE
inhibitors, direct vasodilators, lipid-lowering agents) as
well as garlic intake were excluded from the study. Specific questions
were asked that were related to casual performance of sports
and composition of diet in general. Physical examination was within
normal limits in all studied subjects.
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Study Procedure
Carotid and femoral artery pressure pulse waves were
recorded simultaneously using a noninvasive
sphygmographical technique; PWV (m/s) was calculated from the time
delay in pulse pressure waves from the carotid to the femoral artery
divided by the length of arterial segment (distance between
transducers), as we previously described.13 14 15 SBP and DBP
were obtained using a standard mercury sphygmomanometer. Measurements
were performed with subjects in the supine position at rest and during
isometric handgrip exercise at 30% of individual maximal capacity. The
average values of three recordings of PWV and blood pressure at
rest and the measurement at 3 minutes of handgrip exercise were used
for further analysis. EVR, a pressure-standardized index of
aortic stiffness, was calculated using the formula
EVR=(PWV)2/MAP (m2 ·
s-2 ·
mm Hg-1).15 MAP was calculated
using the formula MAP=DBP+0.43(SBP-DBP).16
In subsets of 24 subjects from each group the effects of wave reflection on pulse height were studied. Analyses of carotid wave contours were performed as described by O'Rourke et al17 and augmentation of the late systolic peak was determined as percentage of the total pulse height.
Body mass index was calculated as the ratio of weight to the height in the second power (weight/height2). Total cholesterol, HDL cholesterol, and serum triglyceride levels were determined with automatic analyzers; LDL cholesterol was calculated according to the Friedewald formula as follows: LDL=total cholesterol-HDL cholesterol-(triglycerides/5).
Statistical Analysis
Statistical analyses included standard descriptive
measures, linear regressions, and correlations (least-squares fitting
procedure according to Marquardt18 modified by Siegel and
Klüßendorf [unpublished data; Department of Physiology, FU
University of Berlin, Germany, 1996]), multiple regression
analysis with backward and forward elimination procedures, and
ANCOVA. Wilcoxon test and 
2 distribution
were used to determine statistical differences between groups. The
Student's t test with Cochran and Cox approximation was
done to analyze subsets of data. Statistical significance was
accepted at the 
=5% level except for multiple regression
elimination procedures, when an =10% boundary was set to minimize
type II errors.
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Results |
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SBP and heart rate at rest and during handgrip exercise were not statistically different between the two groups (Table
); likewise, HDL
and LDL were not statistically different (Table). Both groups were
receiving a similar regional German diet. Casual participation in
sports was reported by 43% of garlic users and 38% of control
subjects.
PWV was significantly lower in the garlic group than in the control
group at rest and during handgrip isometric exercise
(P<.0001; Table, Fig 1).
Likewise, the standardized EVR values at rest and during isometric
handgrip exercise were significantly different between the groups
(P<.0001; Table, Fig 1).
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The difference in PWV between the two group means was 1.49 m/s. This
difference, however, was smaller in the younger and greater in the
older age groups. Thus, the mean difference between garlic users and
controls was 0.53 m/s in the age group of 50 to 59 years
(P=.06), 1.93 m/s in the age group of 60 to 69 years
(P=.0001), and 2.21 m/s in the age group of 70 to 80 years
(P=.0016, Fig 2).
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The difference in EVR at rest between the two group means was 0.27 m2 · s-2 · mm Hg-1. This difference, like PWV, was smaller in the younger and greater in the older age groups. Thus, the difference between garlic users and controls was 0.08 m2 · s-2 · mm Hg-1 in the age group of 50 to 59 years (P=.06), 0.36 m2 · s-2 · mm Hg-1 in the age group of 60 to 69 years (P=.0001), and 0.41 m2 · s-2 · mm Hg-1 in the age group of 70 to 80 years (P=.0004).
A good correlation was found between PWV and age in both groups (garlic
group, r=.44; control group, r=.52). The slope of
the lines relating PWV and age was different between the two groups;
with any degree of increase in age, the PWV increased less in the
garlic group than in the control group (P<.0001, Fig 3). A similar correlation was found
between age and the blood pressure–standardized index of EVR (garlic
group, r=.44; control group, r=.48). Again, the
regression line was flatter in the garlic group than in the control
group (P<.0001, Fig 3).
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) and control subjects (
). The slope of the lines
relating age and PWV was different between the two groups
(P<.0001). The linear regression line was less steep in the
garlic group than in the control group; garlic group: PWV=0.08 (SD,
0.017) age+3.03 (SD, 1.081); control group: PWV=0.18 (SD, 0.029)
age-1.25 (SD, 1.822). Bottom, Relationships between age and EVR in the
garlic users (
A good correlation was also present between PWV and SBP in both
groups (garlic group, r=.48; control group,
r=.54; Fig 4). The slope of
the lines, however, relating SBP and PWV differed between the two
groups. Thus, for any degree of increase in blood pressure, the
increase in PWV was smaller in the garlic group than in the control
group (P<.0001, Fig 4). Correlations were also found
between EVR (MAP-standardized index) and SBP in both groups (garlic
group, r=.26; control group, r=.42), with the
correlation coefficients somewhat smaller than for PWV. The slope of
the lines, however, relating EVR and SBP differed between the two
groups. Thus, for any degree of increase in blood pressure, the
increase in EVR was smaller in the garlic group than in the control
group (P<.0001, Fig 4).
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The difference in PWV between the two group means was smaller in the
lower-pressure and greater in the higher-pressure groups. Thus, the
difference between the two groups was 0.51 m/s in individuals with SBPs
of 
134 mm Hg (P=.22), 1.38 m/s in individuals with
SBPs of 135 to 149 mm Hg (P=.0005), and 2.63 m/s in
individuals with SBPs of 150 mm Hg (P=.0001, Fig 2).
Likewise, the difference in EVR between the two group mean values was
smaller in the lower-pressure and greater in the higher-pressure
groups. Thus, the difference between the two groups was 0.09
m2 · s-2 ·
mm Hg-1 in individuals with SBP of 134
mm Hg (P=.17), 0.24 m2 ·
s-2 ·
mm Hg-1 in individuals with SBP of 135 to
149 mm Hg (P=.0014), and 0.49 m2 ·
s-2 ·
mm Hg-1 in individuals with SBP of 150
mm Hg (P=.0001).
Similar correlations were found during handgrip exercise test between age and PWV (garlic group, r=.37; control group, r=.53), age and EVR (garlic group, r=.38; control group, r=.45), and SBP and PWV (garlic group, r=.40; control group, r=.34). Again, with any degree of increase in age or SBP, the increase in PWV or EVR was less in the garlic group than in the control group (P<.0001).
The augmentation of the late systolic peak of the carotid pulse was diminished in garlic users (10.3%; 95% confidence interval, 4.0 to 16.5) compared with the control group (20.0%; 95% confidence interval, 16.8 to 23.2; P<.01).
Garlic users were subdivided in those with reported doses of 300 mg/d (n=36), 400 mg/d (n=21), and 600 mg/d (n=39) garlic powder. The remaining 5 patients were taking 500 or 900 mg/d. Analysis of the relations between PWV and age, PWV and pressure, EVR and age, and EVR and pressure for these three subgroups did not reveal a dose effect between garlic use and alterations in aortic stiffness associated with aging and blood pressure.
Multiple regression analyses for both collectives revealed age and SBP as the most important confounders of PWV among all variables tested (ie, age, blood pressure, heart rate, body mass index, and serum lipids and subfractions); with these influences taken into account as well as that of casual participation in sports, ANCOVA results revealed that garlic had exerted its influence completely independent of confounding factors.
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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In the present study, it was demonstrated for the first time that in apparently healthy nonsmoking adults with an age range of 50 to 80 years, chronic garlic intake of a standardized powder preparation was associated with a decrease in PWV and blood pressure–standardized index of EVR compared with age- and sex-matched control subjects. The data suggested that the elastic properties of the aorta were maintained better in the garlic group than in the control group. Thus, the detrimental effects of age on the elastic properties of the aorta were blunted in the garlic users compared with the control subjects.
The present results confirmed previous observations in which the PWV correlated positively with age.11 12 16 19 20 21 This correlation was seen in both groups. The slope of regression lines, however, relating age and PWV were different in the two groups. For any degree of increase in age, the PWV was less in the garlic group than in the control group. The difference in PWV between garlic users and controls was greater in the older than in the younger age subgroups. This might well reflect the relatively normal elastic properties of the aortic wall in younger individuals with PWVs of 7 to 8 m/s. For this reason, the effect of garlic on the elastic properties of the aorta was more obvious in the advanced age group.
Factors Determining Aortic Function
Any change in structure of the arterial wall may
result in abnormal aortic function.5 10 22 23 24 25 26 In
experimental animals, changes of the arterial wall
structure during the progression and regression of
atherosclerosis paralleled indices of aortic
elastic properties. Regression of atherosclerosis
resulted in a decrease in PWV, and vice versa.27 Similar
findings have been reported during the development and treatment of
arterial hypertension.15 28 29 Abnormal aortic
function, however, may be present in cases in which structural
abnormalities of the aortic wall cannot be precisely defined with
contemporary technology. For example, acute changes of blood supply to
the aortic wall due to a decrease in vasa vasorum flow may result in
aortic dysfunction.5 30
Endothelium-derived relaxant factor (nitric oxide), endothelin, atrial natriuretic peptides, catecholamines, and prostaglandins may alter the elastic properties of the aorta directly through their effects on the smooth muscle of the aortic wall and indirectly by their effects on vasa vasorum flow. In addition, the autonomic nervous system may play a significant role in the determination of the aortic wall function through a direct effect on the smooth muscle, vasa vasorum flow, or neurohumoral activation.31 32 33 34
Factors That May Account for Differences in Elastic Properties
Between the Two Groups
PWV and its derivative EVR were used as indices of the elastic
properties of the aorta in the present study. It is known, however,
that arterial pressure may have some effect on these
indices,11 12 15 35 36 yet in the present study, blood
pressures were similar in the two groups. Furthermore, for any degree
of increase in blood pressure, the elastic properties of the aorta were
better maintained in the garlic group than in the control group. Thus,
the observed differences in PWV cannot be attributed to differences in
blood pressure. In addition, determination of the pressure-standardized
stiffness index EVR has demonstrated similar results.
Pharmacological agents, cigarette smoking, and composition of general diet may change the elastic properties of the aorta.10 15 29 37 38 39 To avoid the effects of these factors, only healthy individuals, not those receiving therapy with cardiovascular drugs and nonsmokers who lived within the same geographic area, with similar nutritional habits were included in the study.
It is known that increased cholesterol has detrimental effects on the arterial elastic properties; cholesterol and aortic stiffness have been shown to be positively correlated.5 19 20 40 41 Some studies have suggested that garlic intake may decrease plasma cholesterol.2 3 42 Differences in cholesterol, however, cannot account for differences in the elastic properties of the aorta because serum lipid levels were similar in the two groups. Furthermore, in a recent double-blind, placebo-controlled, cross-over study of 28 patients with hypercholesterolemia, the administration of 900 mg/d garlic powder for 3 months had no effect on plasma cholesterol.43
Possible Mechanisms Involved in the Vasoprotective Effects of
Garlic
Recent data suggested that endothelium-derived
relaxant factor (nitric oxide) regulates vascular homeostasis by
controlling vascular resistance, blood pressure, cell-cell contact, and
proliferation.44 45 Fröhlich et al46
demonstrated that stimulation of endogenous nitric oxide
formation increased nutritive muscular capillary blood flow in patients
with peripheral occlusive disease. In addition, the same
group presented data showing that activation of nitric oxide
synthetase in cholesterol-fed rabbits had a stronger
inhibitory effect on the progression of
atherosclerosis than cholesterol-lowering
therapy with lovastatin.47
Incubation of human tissues with garlic extracts has been shown to increase nitric oxide synthase activity.48 Increased nitric oxide synthase activity may facilitate endothelium-dependent smooth muscle relaxation through the intracellular second messenger cAMP, which in turn may increase vasa vasorum flow. Vasa vasorum flow contributes to the nutrition of the outer layers of the thoracic aorta, and its impairment induced structural changes of the aortic wall with deterioration of the elastic aortic properties.5 30 It is also known that vasa vasorum flow is decreased in advancing age.34 Thus, garlic intake may possibly restore impaired endothelium function by nitric oxide synthase activation and so maintain the elastic properties of the aorta.
Other studies also have suggested that regular garlic intake may have an inhibitory effect on platelet aggregation, increase fibrinolytic activity, and inhibit atherosclerotic plaque formation.1 2 49 50 51 Nevertheless, the present study demonstrated that garlic delays the stiffening of the aorta relating to aging. The precise mechanism or mechanisms of this effect of garlic on the elastic properties of the aorta remain to be defined.
Study Limitations
This study does not have a randomized, prospective design but
rather an epidemiological and cross-sectional scope. However, we used
matched pairs, and as with case-control studies, these designs are
appropriate for interventions with long-latency studies on dietary
effects. These designs may have potential for bias in selection of
participants and relevant confounding by unknown
factors.52 We tried to keep confounding factors as low as
possible and to eliminate their influence through the use of ANCOVA.
PWV and EVR differed significantly between the garlic and control
groups regardless of whether the influence of confounding variables
was taken into account.
The fact that the effect of garlic on the elastic properties of the aorta was not dose related may simply reflect that the maximal effect (ceiling) had already been reached with the lowest garlic dose reported (300 mg/d). In addition, it should be taken into account that the reported dosage range is narrow and thus not well suited for judgment of dose-effect relations. Finally, these data rely on subjects' reports and may not be quite precise.
There also are limitations related to the method used to assess elastic properties of the aorta. Blood pressure may affect PWV, but in this study, blood pressure was almost the same in the two groups. Furthermore, the same differences in the elastic properties of the aorta were found when an index that was less dependent on blood pressure index (EVR) was used.
Clinical Implications
Under normal conditions, a large proportion of the left
ventricular stroke volume is stored in the aorta during
left ventricular systole, whereas during
diastole, the stored blood flows into
periphery.10 16 This function of the aorta is important
for the maintenance of blood flow and pressure throughout the
cardiac cycle. Aortic storage capacity is diminished or lost in
different disease states and in the elderly.5 11 22 23 24 25 26
When the pulse wave reaches the periphery, it returns back to the ascending aorta. Normally the reflecting waves reach the ascending aorta early in diastole; this results in the formation of the diastolic wave. Reflecting waves that reach the aortic valve early in diastole facilitate coronary blood flow. When the elastic properties of the aorta are diminished and the PWV increases, the reflecting waves from the periphery return earlier into the ascending aorta, fuse with the systolic part of the pulse, and result in an increase in pulse pressure, a late systolic peak in the pulse, and the disappearance of the diastolic wave.17 53 Matching the slower PWV in garlic users, analyses of the carotid wave contours demonstrated that augmentation of the late systolic peak was also decreased compared with control subjects. Late systolic augmentation increases left ventricular work. Left ventricular–vascular coupling is an important determinant of left ventricular performance. In patients with left ventricular dysfunction without appropriate adaptation of the vasculature, overall circulatory performance may not improve and in fact may be diminished despite positive inotropic interventions.5 6 54
Aortic function is an important determinant of myocardial perfusion. Indeed, experimental studies have indicated that decreased aortic distensibility has a detrimental effect on the dynamics of coronary flow and has an aggravating effect on myocardial ischemia in the presence of coronary artery stenosis.7 8 55
Augmentation of the pulse pressure in the stiff aorta will result in an increase in diastolic–systolic expansion of the peripheral arteries and an increase in maximal blood velocity in the arteries during systole; this increased pulsatile stress will promote the development of vascular damage. Thus, a protective effect of garlic on the elastic properties of the aorta may provide an explanation of the protective effects of garlic against cardiovascular diseases.
Conclusions
The results of this cross-sectional observational study suggested
for the first time that regular long-term garlic powder intake
attenuated age- and pressure-related increases in aortic stiffness.
These garlic-related effects might be mediated by nitric oxide synthase
activation and subsequent restoration of impaired
endothelium function. It is well appreciated that the
aorta plays an important role modulating left ventricular
function, myocardial perfusion, and arterial function
throughout the cardiovascular system. Thus, the effect
of garlic in maintaining the elastic properties of the aorta in
advanced age provides insight into the mechanism or mechanisms of
possible cardioprotective effect of garlic.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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This work was supported by a research grant from Lichtwer Pharma GmbH, Berlin, Germany. The authors thank Privatdozent G.K. Wolf, MD, Clinical Research Institute Heidelberg, and Prof G. Siegel, MD, Physiological Institute FU Berlin, for their contributions to the statistical and biometrical analyses of the data, and Prof V. Schulz, MD, Lichtwer Pharma GmbH, Berlin, for his critical and constructive contributions to the study protocol.
Received March 7, 1997; revision received May 6, 1997; accepted May 13, 1997.
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