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Hypertension - Effects of Garlic Oil on Platelet Aggregations, Serum Lipids and Blood Pressure in Hu
Effects of Garlic Oil on Platelet Aggregation,
Serum Lipids and Blood Pressure in Humans
Stephen A, Barrie, N.D.;
Jonathan V. Wright, M.D.; Joseph E. Pizzorno, N.D.
Journal of Orthomolecular
Medicine Vol 2, Number 1, 1987
Abstract
The effect of oral ingestion of garlic oil was studied
in 20 healthy human volunteers in a double-blind, two period, cross-over trial,
The individuals were randomly divided into two groups. Each group rotated for
four week periods through 2 different sequences of oral supplementation
including: 18 mg of garlic oil (extracted from 9 grams of fresh garlic) and
placebo, The amount of platelet aggregation decreased significantly (p <
.005) during garlic administration. Serum cholesterol levels and mean blood
pressure both decreased significantly (p<.011, p<.009) during garlic
supplementation. Serum high density lipoprotein levels rose significantly p.<
.001) during garlic administration. There was a significant rise in arachidonic
acid in red cell phospholipids following garlic administration. The results of
this study (the first double-blind, crossover study) suggest that garlic has
therapeutic potential as an anti-atherosclerotic, antithrombotic and
anti-hypertensive agent in normal healthy adults. Garlic, known botanically as
Album sativum, is a widely distributed common plant. It is used in all parts of
the world not only as a spice and food, but also as a popular folk remedy for a
variety of ailments. Its importance had been recognized several thousand years
ago in China, India and Egypt. In 1944 the essential oil, believed to be the
active ingredient, was distilled out and named Allicin.1 There recently has been
renewed research in the therapeutic uses of garlic. Hypolipidemic2-13, platelet
aggregation inhibition14-18, antiatherosclerotic 1O-24 fibrinolytic enhancement
25,26, antibacterial and anti-fungal 27 properties have all been
reported.
Atherosclerosis and coronary artery disease remain the
number one killers in civilized countries of the world. It is now recognized
that hyperlipidema is associated with increased incidence of premature ischemic
heart disease.28 Hypercholesterolemia correlates highly with the risk of
myocardial infarction.29 Elevated high density lipoprotein (HDL) levels may
exert a protective effect against coronary artery disease30. Due to the
previously reported positive effect of garlic on these blood components in
unblinded tests on animals and humans, this study was designed to test some of
these parameters in a controlled doubleblinded study with normal human
volunteers.
Methods
Twenty student volunteers, average 26 years
of age, enrolled in the project. All completed informed consent letters and the
project was approved by the Human Subjects Review Committee of the College. All
were in good health and showed no signs of degenerative cardiovascular disease.
Each person was given a list of drugs that affected platelet aggregation and was
asked to avoid these during the trial. Individuals were also asked to limit
dietary garlic. No other dietary restrictions were imposed. The design of the
acuity was a double-blind, two-period crossover trial. The individuals were
randomly divided into 2 groups.
Each group rotated through the following
four-week supplementation periods: 18 mg of cold pressed garlic oil (extracted
from 9 g of fresh garlic) per day; and placebo. The active regime perles also
contained 158 mg coconut oil, 30 mg glycerin and 54 mg gelatin. The placebo
perles contained 160 mg coconut oil, 30 mg glycerin and 54 mg gelatin. The
placebo perle bottles (containing 60 capsules) were laced with 500 mcg of garlic
oil. Both the active and placebo bottles had strong garlic odors. There was a
three week wash-out period between each four week supplementation period during
which no capsules were taken, Capsules were taken with meals, The supplements
were formulated and coded by General Nutrition Research Laboratories, Fargo,
North Dakota.
Platelet aggregation percentages, serum lipid levels and
blood pressure readings were measured before and after each supplementation
period. Fasting (6 h) blood samples were obtained by venipuncture from the
antecubetal fossa using a Wee vacutainer (BD 6430).
Five cc of blood were
transferred to a plastic tube containing 3.8% sodium citrate, incubated at 370C
for 30 no and then spun at slow speed, with 500 ul extracted as platelet rich
sample; the remainder was spun at high speed for platelet poor sample. Using a
Chronolog Aggregometer (#430) and an experimental Chronolog Whole Blood
Aggregometer for comparison, agglutination times were measured after exposure to
ADP.31
The remaining 5 cc of blood was allowed to clot and then spun at
high speed with the serum being removed and subject to direct quantitative
colorimetric determination of total and HDL cholesterol levels using the
modified Lieberman-Burchard reaction procedures32 and a Baush & Lomb
Spectomic 21 spectrophotometer. Individual mean bilateral sitting brachial blood
pressures were measured by an experienced technician after each blood sample was
drawn. Participants were asked to refrain from any strenuous exercise for 4 It
prior to sampling. Paired t tests for pairs and class were used to identify
statistically significant differences between mean values of changes and
differences in change, Students t test was calculated using the computer program
'Statistical Package for the Social
Sciences'.
Results
Cholesterol, HDL, mean blood pressure levels
and platelet aggregation percent after supplementation with placebo and with
garlic are presented in Table 1. During garlic administration, platelet
aggregation was reduced significantly, by 16.4% (p <.005) as compared to no
significant change during placebo administration (between classes with no
cross-over).
Figure 1 illustrates the change in mean cholesterol levels
during the two different supplementation periods. Mean serum cholesterol levels
dropped significantly (from 195 to 180 mg/ 100 ml, p <.001) during garlic
administration. There was a slight insignificant drop during placebo trial. The
difference in change during the garlic versus placebo administration was also
significant (12.5 mg/ 100 ml, p <.01).
Results from HDL measurements
are presented in Figure 2. Mean HDL levels rose significantly during garlic
supplementation (from 56 to 69 mill 100ml, p < .001). The difference in
change between the two periods was also significant (8.3 mg/ 100m], p < .01).
There was an insignificant rise in the HDL levels during placebo trial. Figure 3
shows the mean blood pressure measurements during each period. Levels dropped
significantly during garlic administration (94 to 88 mm FIG, p < .009). The
difference in change between the two supplementation periods was also
significant (3 mm FIG, p <.07). There was a small insignificant drop during
placebo trial.
Discussion
Garlic contains an essential oil,
allicin (C6H1OS20), which contains allylpropyl-disulphide diallyldisulphide and
several other sulphur compounds. The active principal of garlic appears to be
the essential oil. The concentration of essential oil in garlic is 0.3 to 0.
0.4%.In our study garlic administration has led to significant decreases in
platelet aggregation, serum cholesterol, mean blood pressure as well as a
significant rise in serum HDL's in normal healthy humans when compared to
placebo supplementation. Due to the odoriferous nature of garlic oil, no double
blind studies have been previously reported. We feel a measure of the success of
our novel 'blinding' is the small, but insignificant placebo changes in the same
direction as the active trial.
Previous work by Makheja et al.33 has shown
garlic extract to inhibit platelet aggregation in vitro. The results of their
work indicate that garlic almost completely suppresses thromboxane B2 synthesis.
Further results indicate that garlic inhibits platelet aggregation by
alterations in both the platelet cyclooxygenase and lipooxygenase pathway.
Studies by Ariga et al. 34 have isolated this component as methyl allyl
trisulphide (MATS) which is a minor component in garlic oil. Bordia17 has shown
that in vitro platelet aggregation was markedly inhibited in a dose-related
manner when human blood was exposed to garlic oil. Bordia has also shown that
oral administration of 25 mgs of garlic for 5 days significantly inhibited
platelet aggregation in humans and may inhibit some aspects of thrombus
formation. Boullin35 has reported that eating 10 grams of garlic cloves
significantly inhibited platelet aggregation in 3 human volunteers. Work by
Apitz-Castro et al.36 suggests that garlic's inhibitory effect might be mediated
through modification of the physiochemical properties of the plasma membrane,
rather than by affecting the arachichidonic or calcium metabolism of
platelets.
We also measured the full range of fatty acids in plasma, and
red blood cell total phospholipids were measured in order to, monitor the
possibility that garlic might affect levels of polyunsaturated fatty acids known
to influence platelet aggregation. There were no significant changes in plasma
or red cell fatty acids in the placebo group or in plasma fatty acids in the
garlic group. There was however, a significant rise in arachidonic acid in red
cell phospholipids following garlic administration. This might be consistent
with reduced conversion of arachidonic acid to thromboxane A2, a mechanism of
garlic action which has been proposed elsewhere.
This study provides the first support for these previous findings in healthy
adults using a controlled double-blind two-period crossover trial. Previous
research examining the effect of garlic on blood lipids in rats, rabbits and
humans has been extensive. In cholesterol fed rats, Chi et al.2 found that
garlic feeding increased the excretion of neutral and acidic steroids and
exerted a hypocholesterolemic effect, Kamanna et al.9 showed that garlic perles
produced a significant decrease in serum and liver cholesterol levels in rats
fed an atherogenic diet. Interestingly, Kamanna compared and calculated the
efficacy of garlic perles (containing the volatile oil) as being 6 times greater
than that of garlic powder. Jain and Konar8 demonstrated similar results when
they fed rabbits an atherogenic diet and observed that garlic oil decreased
tissue cholesterol and minimized atheromatous changes in the rabbit aorta. They
hypothesize that the low ester cholesterol (EC) value found in the garlic- fed
rabbits contributed to the low EC that was found in the vessel intima. Bordia
and his coworkers7 suggest that the protective action of garlic against induced
atherosclerosis in rabbits is due to several factors; the restriction of the
rise in blood cholesterol and lipids; the minimization of the fall in alpha
lipoproteins; and the increased fibrinolytic activity of plasma. In humans, the
effect of garlic has been studied in induced alimentary hyperlipidemia, in
hypercholesterolemic persons, and in normals. In two separate studies, Bordia
and co-workers4, 10 showed that the essential oil of garlic can prevent the
harmful effects of fatty meals on humans by preventing the fall in fibrinolytic
activity, the rise in serum triglycerides and the rise in the platelet adhesive
index normally associated with this type of diet. Bordia13 also found that in
healthy humans fed garlic for six months, serum cholesterol and trigyclerides
were reduced and HDL levels raised. Augusti5 hypothesizes that these effects of
garlic may be due to allicin lowering the amount of reduced NAD and NADP in the
body, Allicin can combine with SH groups, the functional part of CoA, a
necessary part of the biosynthesis of cholesterol. The effect of raw garlic on
normal blood cholesterol in humans was studied by Bhusan et al.37 They found
that blood levels decreased significantly in all the participants after two
months of garlic ingestion.
Our results parallel those studies reported
above. Serum cholesterol levels (initial range from 130 to 270 mg / 100 ml) were
lowered. and HDL levels (initial range 41 to 94 mg/100 ml) were raised
significantly in humans during our blinded trail.
Using spontaneously
hypertensive rats, Foushee and Ruffin38 have reported that 0.5 ml/kg of garlic
oil lowered the systolic blood pressure to a normal level and sustained the
decrease for up to 24 It, We have found that administration of garlic oil to
normotensive humans (mean blood pressure range from 88 to 108 man HG) for four
weeks significantly reduced the mean blood pressure.
Acknowledgements
The authors thank Ray Suen, Director,
Meridian Valley Laboratories for his invaluable technical assistance. We would
also like to thank Dr. M.S. Manku and Nancy Morsa of EFAMOL Research
Laboratories for the EFA analysis.