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GARLIC AND BIOMARKERS FOR CARDIOVASCULAR DISEASE 1327
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Lipids and lipoproteins
Garlic treatment did not influence the total cholesterol, HDL-
cholesterol, LDL-cholesterol, and triacylglycerol concentrations
when compared with placebo treatment. In contrast, atorvastatin
treatment resulted in lower concentrations of total cholesterol
(37.2%; 97.5% CI: 33.1%, 41.1%), LDL cholesterol (52.7%;
97.5% CI: 47.9%, 57.1%), and triacylglycerols (31.9%; 97.5%
CI: 20.8%, 41.5%) when compared with placebo treatment.
HDL-cholesterol concentrations were not significantly affected
by atorvastatin (P 0.34; Table 3).
DISCUSSION
The present placebo-controlled study investigated the effects
of a 12-wk treatment intervention with a chemically well-
characterized and production-controlled garlic powder in sub-
jects with known risk factors for CVD. A group receiving ator-
vastatin was used as positive control. The study aimed to identify
the effects of garlic powder on inflammatory markers (in partic-
ular CRP), endothelial function, and measures of lipid metabo-
lism. The main finding of the study is that garlic powder has no
detectable effects on CRP, TNF-, in the basal and stimulated
state or lipid concentrations, whereas these concentrations were
positively affected by atorvastatin. This makes it unlikely that
garlic exerts a beneficial effect on CVD by antiinflammatory or
lipid-lowering mechanisms.
The emphasis on the potential antiinflammatory effects of
garlic was chosen because of the observations of in vitro studies
which showed that high concentrations of garlic decreased cy-
tokine production in endothelial cells which in turn suggested
distinct antiinflammatory properties (20, 21, 28). In addition, a
growing body of evidence suggests that inflammatory processes
play an important role in the pathophysiology of atherosclerosis.
Because it has been shown that CRP is one of the strongest
predictors for the risk of atherosclerosis and cardiovascular
events in subjects with and without CVD (1618), this marker
was chosen as primary endpoint in the current study. Note that
our study had an a priori power of 7080% to detect a 2530%
decrease in plasma CRPconcentration. This percentage decrease
was considered relevant because other studies have shown sim-
ilar effects of atorvastatin on CRP (26). Because our study pop-
ulation had a relatively high mean plasma concentration of CRP
(2 mg/L) when compared with healthy volunteers (2 mg/L),
this allowedus todetect possible effects of garlic andatorvastatin
treatment on the inflammatory status of these subjects.
It can be argued that the results obtained in our population
might not be representative for patients with a higher risk of
CVD. Indeed, our population had only 2 known risk factors
(overweight and smoking) for CVD, and the participants were
normotensive and normocholestrolemic. We feel, however, that
the choice for this population is justified. First, it may be con-
sidered unethical to performa similar study in patients with overt
hypercholesterolemia because indicated medical treatments for
these conditions are available. Second, it has been shown that
elevatedCRPconcentrations as observedinour populationare an
independent risk factor for CVD. Finally, it has been shown that
effective treatments have a CRP- and lipid-lowering effect in
overweight subjects (22) and even in healthy volunteers (23).
Thus, by choosing this population with not readily amendable
risk factors for CVD a relevant population was studied.
The relatively high garlic dose administered in the present
study was chosen because there are some indications that higher
garlic doses are associated with greater effects. Indeed, previous
studies that showed no beneficial effects of garlic on lipid me-
tabolismand blood pressure in humans used garlic powder doses
that variedfrom0.3g/dto1g/d(913) for whichit maybe argued
that the garlic dose was too low. Therefore, in the present study,
we choose a relatively high dose of the garlic powder (2.1 g/d,
approximately equivalent to 9.4 mg allicin/d or 5.2 g fresh gar-
lic/d) to be able to detect potentially beneficial effects of garlic
powder. Furthermore, a pharmaceutical formulation was used that
complies withall requirements for optimal release andbioavailabil-
ity of the supposedly active compounds of garlic (25, 29).
The compliance data suggested that the adherence to the dos-
ing regimens was good. Obviously, measurement of garlic com-
ponents and atorvastatin plasma concentrations could have cor-
roborated this observation, but, unfortunately, these data were
not available. The effects of atorvastatin were as expected, sup-
porting the notion that compliance was good, at least in the
positive control group.
Apart from the primary endpoint, other markers of inflamma-
tion (fibrinogen and leukocyte TNF- production in response to
lipopolysaccharide), our data show that garlic powder had no
significant effects on any of these markers, whereas atorvastatin
showed antiinflammatory effects also on TNF-concentrations.
This suggests that garlic has no significant effect on the inflam-
matory processes associated with atherosclerosis.
For a long time the lipid- and lipoprotein-lowering properties
of garlic have been raised as a mechanism by which garlic could
exert a beneficial effect on atherogenesis, although this is not
unambiguously supported. Our data appear to be in keeping with
the latter findings because we did not observe any effect of garlic
on plasma lipids and lipoproteins. In contrast, atorvastatin treat-
ment significantly decreased total cholesterol, LDL-cholesterol,
and triacylglycerol concentrations. A posteriori power analysis
withthe data obtainedinthe present studyindicatedthat the study
had a power of 80% at a 2-sided level, P 0.05, to detect a
decrease of 0.95 mmol/L in total cholesterol concentration (a
17% decrease).
In conclusion, our data showed that 12 wk of treatment with a
high-dose, chemically well-characterized, production-controlled
garlic powder had no antiinflammatory or lipid-lowering effect
in a normolipidemic population with known risk factors for
CVD. As such, we conclude that evidence does not showthat the
garlic powder Printanor that was speciallyselectedandoptimally
pharmaceutically formulated has beneficial effects on athero-
genesis and, consequently, cardiovascular events in a relevant
population through antiinflammatory processes or lipid-
lowering effects. The findings of the present study lead us to
speculate that garlic powder (and probably garlic in general) has
no relevant place in the prevention or treatment of the inflam-
matory and dyslipidemic features of atherosclerosis.
We thank all the people involved in the European Union project Garlic and
Health for their collaboration.
SMES analyzed the data and wrote the manuscript; MBAvDexecuted the
study, analyzed the data, and wrote the manuscript; PM, VD, and AV per-
formedthe laboratoryassays; IMKwrote the protocol andexecutedthe study;
RCS developed the protocol, analyzed the statistics, and wrote the manu-
script; TH developed the garlic and garlic-placebo formulations; RG per-
formed the study setup; AFCdeveloped the protocol, executed the study, and
1328 VAN DOORN ET AL
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reviewed the manuscript; HMP developed the protocol, supervised the lab-
oratory assays, and reviewed the manuscript; JB developed the protocol,
executedthe study, analyzedthe data, wrote andreviewedthe manuscript and
review, and was the principal investigator. SMES and MBAvD contributed
equallytothe study. THis anemployee of Lichtwehr Pharma AG; none of the
other authors had a conflict of interest.
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GARLIC AND BIOMARKERS FOR CARDIOVASCULAR DISEASE 1329
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