ArticlePDF Available

Beneficial effects of artichoke leaf extract supplementation on increasing HDL-cholesterol in subjects with primary mild hypercholesterolaemia: A double-blind, randomized, placebo-controlled trial

Taylor & Francis
International Journal of Food Sciences and Nutrition
Authors:
  • University of Pavia, Azienda di Servizi alla Persona

Abstract and Figures

The aim of this study was to evaluate the effects of artichoke leaf extract (ALE) supplementation (250 mg, 2 b.i.d.) on the lipid pattern. A randomized, double-blind, placebo-controlled clinical trial was performed on 92 overweight subjects with primary mild hypercholesterolaemia for 8 weeks. Forty-six subjects were randomized to supplementation (age: 54.2 ± 6.6 years, body mass index (BMI): 25.8 ± 3.9 kg/m(2), male/female: 20/26) and 46 subjects to placebo (age: 53.8 ± 9.0 years, BMI: 24.8 ± 1.6 kg/m(2), male/female: 21/25). Verum supplementation was associated with a significant increase in mean high-density lipoprotein (HDL)-cholesterol (p < 0.001) and in mean change in HDL-cholesterol (HDL-C) (p = 0.004). A significantly decreased difference was also found for the mean change in total cholesterol (p = 0.033), low-density lipoprotein (LDL)-cholesterol (p < 0.001), total cholesterol/HDL ratio (p < 0.001) and LDL/HDL ratio (p < 0.001), when verum and placebo treatment were compared. These results indicate that ALE could play a relevant role in the management of mild hypercholesterolaemia, favouring in particular the increase in HDL-C, besides decreasing total cholesterol and LDL-cholesterol.
Content may be subject to copyright.
Beneficial effects of artichoke leaf extract supplementation on increasing
HDL-cholesterol in subjects with primary mild hypercholesterolaemia:
a double-blind, randomized, placebo-controlled trial
MARIANGELA RONDANELLI
1
, ATTILIO GIACOSA
2
, ANNALISA OPIZZI
1
,
MILENA ANNA FALIVA
1
, PATRIZIO SALA
1
, SIMONE PERNA
1
, ANTONELLA RIVA
3
,
PAOLO MORAZZONI
3
, & EZIO BOMBARDELLI
3
1
Section of Human Nutrition, Health Sciences Department, Azienda di Ser vizi alla Persona, University of Pavia, Pavia, Italy,
2
Department of Gastroenterology, Policlinico di Monza, Milan, Italy, and
3
Indena S.p.A., Milan, Italy
Abstract
The aim of this study was to evaluate the effects of artichoke leaf extract (ALE) supplementation (250mg, 2 b.i.d.) on the
lipid pattern. A randomized, double-blind, placebo-controlled clinical trial was perfor med on 92 overweight subjects with primary
mild hypercholesterolaemia for 8 weeks. Forty-six subjects were randomized to supplementation (age: 54.2 ^6.6 years,
body mass index (BMI): 25.8 ^3.9 kg/m
2
, male/female: 20/26) and 46 subjects to placebo (age: 53.8 ^9.0 years, BMI:
24.8 ^1.6 kg/m
2
, male/female: 21/25). Verum supplementation was associated with a significant increase in mean high-density
lipoprotein (HDL)-cholesterol ( p,0.001) and in mean change in HDL-cholesterol (HDL-C) ( p¼0.004). A signifi-
cantly decreased difference was also found for the mean change in total cholesterol ( p¼0.033), low-density lipoprotein
(LDL)-cholesterol ( p,0.001), total cholesterol/HDL ratio ( p,0.001) and LDL/HDL ratio ( p,0.001), when verum and
placebo treatment were compared. These results indicate that ALE could play a relevant role in the management of mild
hypercholesterolaemia, favouring in particular the increase in HDL-C, besides decreasing total cholesterol and LDL-cholesterol.
Keywords: artichoke leaf extract, chlorogenic acid, cholesterol, dietary supplement, HDL cholesterol, luteolin
Introduction
Cardiovascular diseases (CVDs) continue to be the
leading cause of morbidity and mortality in the
industrialized world (Lloyd-Jones et al. 2010).
Although there are many causes for the high
prevalence of CVD, it appears that nutritional factors,
notably high saturated fat consumption, play an
important role in promoting atherosclerosis (Keys
1997). However, one apparent paradox is that the low
saturated fat consumption recommended by several
organizations, including the American Heart Asso-
ciation, the American Diabetes Association and the
American Dietetics Association, often results in
decreasing high-density lipoprotein (HDL) cholesterol
levels (Mensink et al. 2003). This result is not a
favourable one, because epidemiological studies, as
well as studies in animal models of atherosclerosis,
support the cardioprotective role of HDL-cholesterol
(HDL-C) (Gordon et al. 1977; Berliner et al. 1995;
Andersson 1997; Haffner et al. 1998; Turner et al.
1998; Eriksson et al. 1999; Kawahiri et al. 2000;
Mooradian 2003). In addition, interventional trials,
notably the Veterans Affairs High-Density Lipoprotein
Cholesterol Intervention Trial, showed that the
rate of coronary heart disease (CHD) is reduced
by raising HDL-C levels (Rubins et al. 1999; Boden
2000; Goldenberg et al. 2009).
Low-density lipoprotein (LDL)-cholesterol-lowering
drugs and dietary supplements currently used to
ISSN 0963-7486 print/ISSN 1465-3478 online q2012 Informa UK, Ltd.
DOI: 10.3109/09637486.2012.700920
Correspondence: Mariangela Rondanelli, Endocrinology and Nutrition Unit, Section of Human Nutrition and Dietetics, Department of
Applied Health Sciences, Faculty of Medicine, ASP, University of Pavia, Pavia, Italy. Tel: þ39 0382381749. Fax: þ39 0382381218.
E-mail: mariangela.rondanelli@unipv.it
International Jour nal of Food Sciences and Nutrition,
2012; Early Online: 1–9
Int J Food Sci Nutr Downloaded from informahealthcare.com by Univ Degli Studi di Pavia on 06/29/12
For personal use only.
improve the serum lipid profile are not effective in
raising HDL-C (Sirtori et al. 2009). Therefore, a great
deal of attention is now dedicated to the study of
bioactive molecules that could increase HDL-C, in
addition to decreasing LDL-cholesterol (LDL-C).
This effect could be achieved by some bioactive
molecules present in artichoke leaves. The pharmaco-
logical properties of artichoke leaf extract (ALE) are
well documented in several studies, and the Cochrane
Database reports that ALE has potential in lowering
cholesterol levels in humans (Wider et al. 2009). The
bioactivity displayed by ALE is strictly related to its
polyphenolic content and this justifies its wide
phytopharmaceutical use (Wegener and Fintelmann
1999; Thompson Coon and Ernst 2003). Chlorogenic
acid, 1,5 and 3,4-di-O-caffeoylquinic acid and cynarin
are the predominant polyphenolic compounds among
hydroxycinnamates of ALE, while the main flavonoids
are apigenin and luteolin, and their glycosides
(Pandino et al. 2010). The cholesterol-lowering effect
of ALE has been demonstrated in animal models
(Ku
¨sku
¨-Kiraz et al. 2010; Qiang et al. 2011) as well
as in humans (Englisch et al. 2000; Lupattelli et al.
2004; Bundy et al. 2008).
Given this background, the aim of the present
randomized, placebo-controlled study was to assess
the efficacy of 8 weeks ALE supplementation on the
HDL-C increase, as the primary end-point, in subjects
with mild hypercholesterolaemia. As secondary end-
points, the decrease in total cholesterol (T-C) and
LDL-C is considered.
Methods
Subjects
The experimental protocol was approved by the
Ethics Committee of the University of Pavia and
volunteers gave their written, informed consent.
Subjects were recruited from Pavia county by
advertisement in a local newspaper and were screened
through a procedure involving a clinical assessment,
an interview and total HDL- and LDL-cholesterol
serum evaluation. Ninety-two subjects, aged 1860
years, with body mass index (BMI) ranging between
19 and 30 kg/m
2
, with mild hypercholesterolaemia
(5.4 –7.0 mmol/l) and no history of CVD, volunteered
for the trial. None of the subjects had ever taken any
medication likely to affect lipid metabolism, and all
of them were free of overt liver, kidney and metabolic
diseases, such as diabetes and thyroid disease. The
screening excluded subjects who smoked or drank
more than two standard alcoholic beverages/day
(20 g of alcohol/day) as well as those who were preg-
nant or lactating, or if they had entered menopause.
Subjects were also excluded if they were taking
medications for weight loss. Physical activity was
recorded and patients were asked to maintain their
usual habit throughout the study period.
Before the beginning of the study (BoS), energy and
nutrient intakes were assessed using the food record
method over a period of 3 days (Forster-Coull et al.
2004). Once the data were collected, the food intake
was converted into energy and nutrients, using the
Dieta Ragionata version 7.0 (Sintesi Informatica,
Milan, Italy). A senior dietician delivered advice to all
the subjects in order to suggest a personalized
isocaloric diet, according to the Step 1 American
Heart Association diet (American Heart Association
1988). The energy and nutrient intakes of all the
volunteers were also assessed after 8 weeks of
intervention, using the food record method over
3 days. Blood pressure was measured at the beginning
and at the end of the study.
Nutritional status
At the beginning and at the end of the study, body
weight was assessed and BMI was calculated. Skinfold
thicknesses (biceps, triceps, suprailiac and subscapu-
lar) were measured twice using a Harpenden Skinfold
Caliper at 5-min intervals in each site following a
standardized technique (Frisancho 1984). Sagittal
abdominal diameter at the L
4–5
level in the supine
position and waist girth was also measured on day 0
and after 8 weeks of intervention. Anthropometric
parameters were always collected by the same
investigator.
Dietary supplement
As subjects were enrolled, they were assigned a
progressive subject number. Identical products for
each treatment group were assigned to a subject
number according to a coded (AB) block randomiz-
ation table prepared by an independent statistician.
Investigators were blinded to the randomization table,
the code assignments and the procedure. Indepen-
dently of the treatment (ALE supplement or placebo),
the subjects followed a similar personalized isocaloric
energy diet. The dietary treatment was associated with
two daily oral assumptions (before lunch and dinner)
of film-coated tablets of 250 mg of standardized ALE
(.20% caffeoylquinic acids, .5% flavonoids and
.5% cynaropicrin, according to WO 2010083968) or
placebo. The tablets were provided by Indena, Milan
and Italy. The supplementation period was 8 weeks.
Compliance to the supplementation regimen was
defined as the number of tablets actually taken by each
subject, divided by the number of tablets that should
have been taken over the course of the study.
Analyses
Fasting blood samples were collected between 07.45
and 10.00 am on day 0 and after 8 weeks in both study
arms for the evaluation of LDL-C, T-C, HDL-C,
triglycerides (TG) and glucose. Moreover, the fasting
M. Rondanelli et al.2
Int J Food Sci Nutr Downloaded from informahealthcare.com by Univ Degli Studi di Pavia on 06/29/12
For personal use only.
blood HDL-C was evaluated 8 weeks after the end
of the intervention. The study design is shown in
Figure 1.
In order to avoid venipuncture stress, blood samples
were obtained through an indwelling catheter inserted
in an antecubital vein. Blood samples were immedi-
ately centrifuged and stored at 2808C until assayed.
Fasting blood glucose, T-C, LDL-C, HDL-C and TG
levels were measured by an automatic biochemical
analyser (Hitachi 747, Tokyo, Japan). All assays were
carried out on Cobas Mira Plus
w
(Roche Diagnostic
Systems, Welwyn Garden City, UK) equipment using
a standard control serum to ensure accuracy of
measurements. Finally, for the assessment of safety,
routine blood biochemistry parameters (blood cell
count, serum protein electrophoresis, serum creati-
nine, liver and thyroid function) were evaluated with
routine methods at the beginning and at the end of
the intervention.
Statistical methods
All statistical analyses were carried out by the SAS
w
System version 9.2, choosing 5% ( p#0.05) as the
threshold value of statistical significance.
A 0.2 mmol/l standard deviation of changes in
HDL-C after 8 weeks of intervention has been drawn
from our unpublished data, in absence of published
data on the effect of ALE on HDL-C in humans.
A difference of 0.12 mmol/l at least in HDL-C
between the intervention and the placebo group at
the end of the treatment was considered clinically
relevant. Assuming a 5% type I error (two tailed
alpha ¼0.05), the sample size of 45 subjects per
group will have 80% power to detect this difference.
The primary efficacy end-point of this study was the
change in HDL-C levels between the baseline and the
end of treatment (EoT). The primary end-point did
not contemplate multiple comparisons. As far as the
secondary end-points are concerned, no adjustment
of the 5% significance level was made for multiple
comparisons, due to their descriptive nature. Second-
ary efficacy end-points were the changes in glycaemia
and in the other parameters of lipidic metabolism
between the baseline and the EoT.
The HDL-C was also evaluated at the end of the
follow-up (EoF), which is 8 weeks after the end of
treatment (Figure 1). Differences in gender distri-
bution between the two groups were assessed by the
Chi-square test. Parametric tests were adopted to
analyse the discrete or continuous data due to the
relative largeness of the sample size and the not
statistically significant departure from normality of
data distribution of baseline values of glycaemia and
main lipid parameters. At each assessment time, the
comparison of the raw data of the two groups was done
by the unpaired t-test (t). The changes within groups
and percent changes from baseline were analysed
by the paired t-test (pt). Due to the incomplete
baseline homogeneity of the two experimental groups,
the comparisons of the changes between groups and
percent changes from baseline were done by the
analysis of covariance (ANCOVA) with the baseline
value as a covariate. With regard to T-C, HDL-C,
LDL-C and TG, the comparison between groups was
also done after stratifying by gender. A within gender
stratified descriptive and comparative analysis of
HDL-C data was also carried out choosing the median
of baseline values as cut-off point. An additional within
gender stratification of HDL-C data by the quartiles
of baseline values was presented only by descriptive
statistics and graphics, due to the small number of
observations per stratum.
Safety
Safety was assessed by the measurement of blood
pressure and by assessing routine blood biochemistry
parameters at baseline and EoT and by recording
all the adverse events (AEs). AEs were based on
spontaneous reporting by subjects as well as open-
ended enquiries by members of the research staff.
T0:
Assessment of:
Fasting blood glucose (FBG),
total cholesterol (TC),
low-density lipoprotein-cholesterol
(LDL-C), high-density
lipoprotein-cholesterol (HDL-C)
and triglyceride (TG), BMI,
blood pressure,
routine blood biochemistry
parameters
End of treatment (EoT):
Assessment of:
Fasting blood glucose (FBG),
total cholesterol (TC),
low-density lipoprotein-cholesterol
(LDL-C), high-density
lipoprotein-cholesterol (HDL-C)
and triglyceride (TG), BMI,
blood pressure, routine blood
biochemistry parameters
8 weeks 8 weeks
Treatment No treatment
T0 EoT EoF
End of Follow-up (EoF):
Assessment of: HDL-C
Figure 1. Study design.
Beneficial effects of artichoke leaf extract 3
Int J Food Sci Nutr Downloaded from informahealthcare.com by Univ Degli Studi di Pavia on 06/29/12
For personal use only.
Results
All the 92 subjects completed the 8-week intervention
trial (Figure 2) and their demographic characteristics
at the baseline are shown in Table I. Forty-six subjects
were randomized to ALE supplements and 46 to
placebo. The supplemented and placebo groups were
homogeneous for all parameters. Table II shows the
baseline characteristic of lipid parameters in the two
studied groups. Table III shows the least squares
means (LSM) of changes from baseline at EoT, as well
as the difference in the LSM between the two groups
and their comparison by ANCOVA. As regards blood
pressure, all patients had normal values, either at the
beginning or at the end of the study (supplemented
group: BoS 123.75 ^10.93/84.31 ^8.24 mm Hg,
EoT 125.46 ^11.21/85.51 ^9.33 mm Hg; placebo
group: BoS 122.46 ^9.97/82.44 ^9.65 mm Hg,
EoT 126.01 ^9.11/86.04 ^9.21 mmHg). The diet
composition at screening and at the end of the trial is
shown in Table IV. BMI remained stable in both
groups. BMI at screening was 25.36 ^3.03 kg/m
2
and
at EoT was 25.82 ^2.01 kg/m
2
. In the supplemented
group, BMI at screening was 25.86 ^3.96 kg/m
2
and
at EoT was 25.46 ^3.11 kg/m
2
, while that in the
placebo group was 24.87 ^1.16 kg/m
2
at screening
and 26.01 ^2.08 kg/m
2
at EoT.
Primary end-point
The mean HDL-C significantly increased in the
supplemented group ( p,0.001), while it did not
show any significant change in the placebo
group. These differences in the patterns of two groups
were statistically significant in the whole sample
(p¼0.004), as well as in m ales ( p¼0.001).
The results of the analyses carried out on HDL-C
data stratified by gender and the median of baseline
values reported the following statistically significant
changes from baseline observed in the supplemented
group:
.the HDL-C values were higher than baseline at
EoT ( p¼0.010 and p¼0.009, respectively, for
changes and per cent changes from baseline) and
EoF ( p¼0.005 and p¼0.006, respectively, for
changes and per cent changes from baseline) in
the females belonging to the stratum ‘#median’;
.the HDL-C values were higher than baseline at EoT
in the males belonging to both strata ( p¼0.003
for changes from baseline p¼0.006 for per cent
changes from baseline in the stratum ‘#median’ and
p¼0.002 for both changes and per cent changes
from baseline in the stratum ‘.median’);
.the HDL-C values were higher than baseline at EoF
in the males belonging to the stratum ‘#median’
(p¼0.027 and p¼0.019, respectively, for changes
and per cent changes from baseline).
The following statistically significant differences
between the groups were found:
.females belonging to the stratum #median’ at
EoT ( p¼0.007 and p¼0.004, respectively, for
changes and per cent changes from baseline) as well
as at EoF ( p¼0.006 and p¼0.003, respectively,
for changes and per cent changes from baseline);
46 allocated
to the supplementation
with Cynara scolimus (Cs)
Followed up at
week 8: n = 46
92 eligible: fulfilled inclusion criteria
46 allocated
to placebo
46 analysed 46 analysed
101 subjects assessed for eligibility
92 randomized
9 excluded:
3 refused to participate
6 with laboratory abnormalities
Followed up at
week 8: n = 46
Figure 2. Flow diagram of a trial of supplementation versus placebo in the treatment of healthy overweight subjects.
M. Rondanelli et al.4
Int J Food Sci Nutr Downloaded from informahealthcare.com by Univ Degli Studi di Pavia on 06/29/12
For personal use only.
.males belonging to the stratum ‘ .median’ at EoT
(p¼0.002 for both changes and per cent changes
from baseline);
.males belonging to the stratum ‘ #median’ at EoF
(p¼0.021 for per cent changes from baseline).
Figure 3 shows the mean values and 95% CI by
treatment and gender.
Secondary end-point
Glycaemia showed no statistically significant changes
within groups from baseline nor differences between
groups.
With regard to the whole sample, T-C significantly
decreased in both supplemented group ( p,0.001)
and pla cebo group ( p,0.010), but the effect of the
supplemented group was significantly higher than
that of the placebo group ( p¼0.012). The lowering
of baseline values was found statistically significant
in both females ( p,0.050) and males ( p,0.050) of
the supplemented group, whereas it was not statis-
tically significant in the placebo group. However, the
differences between groups in the changes from
baseline within each gender were not statistically
significant.
Table II. Baseline values of lipid metabolism.
Supplemented (N¼46) Placebo (N¼46) Total (N¼92)
F M Total F M Total F M Total
Total cholesterol (mmol/l)
N 262046252146514192
Mean 6.730 6.282 6.535 6.612 6.575 6.595 6.672 6.432 6.565
SD 0.669 0.628 0.683 0.407 0.403 0.401 0.554 0.539 0.558
P(t) whole sample, p¼0.610
P(t) females, p¼0.452
P(t) males, p¼0.082
HDL-cholesterol (mmol/l)
Mean 2.321 1.795 2.092 1.999 1.886 1.948 2.163 1.841 2.020
SD 0.455 0.516 0.545 0.690 0.586 0.640 0.599 0.548 0.596
P(t) whole sample, p¼0.246
P(t) females, p¼0.054
P(t) males, p¼0.602
Total cholesterol/HDL ratio
Mean 3.005 3.785 3.344 3.683 3.763 3.719 3.337 3.773 3.532
SD 0.650 1.085 0.941 1.240 0.982 1.118 1.032 1.021 1.045
P(t) whole sample, p¼0.085
P(t) females, p¼0.017
P(t) males, p¼0.946
LDL-cholesterol (mmol/l)
Mean 3.866 3.811 3.843 4.021 4.086 4.050 3.942 3.952 3.946
SD 0.746 0.613 0.684 0.506 0.416 0.463 0.638 0.533 0.590
P(t) whole sample, p¼0.091
P(t) females, p¼0.393
P(t) males, p¼0.100
LDL/HDL ratio
Mean 1.761 2.336 2.011 2.334 2.394 2.361 2.042 2.366 2.186
SD 0.594 0.879 0.778 1.080 0.824 0.961 0.905 0.841 0.887
P(t) whole sample, p¼0.058
P(t) females, p¼0.022
P(t) males, p¼0.826
Triglycerides (mmol/l)
Mean 1.179 1.469 1.305 1.298 1.314 1.306 1.238 1.390 1.305
SD 0.455 0.810 0.643 0.637 0.511 0.577 0.549 0.670 0.607
P(t) whole sample, p¼0.960
P(t) females, p¼0.444
P(t) males, p¼0.495
Note: t, unpaired t-test.
Table I. Demographic characteristics at the baseline of the subjects
studied.
Variable
Supplemented
(N¼46)
Placebo
(N¼46)
Total
(N¼92)
p
(test)
Gender
F 26 (56.5%) 25 (54.3%) 51 (55.4%) p¼0.834
M 20 (43.5%) 21 (45.7%) 41 (44.6%) (
x
2
)
Age (years)
Mean 54.2 53.8 54.0 p¼0.823
SD 6.6 9.0 7.8 (t)
BMI (kg/m
2
)
Mean 25.86 24.87 25.36 p¼0.120
SD 3.96 1.61 3.03 (t)
Note:
x
2
, Chi-square; t, unpaired t-test.
Beneficial effects of artichoke leaf extract 5
Int J Food Sci Nutr Downloaded from informahealthcare.com by Univ Degli Studi di Pavia on 06/29/12
For personal use only.
The ratio between T-C and HDL-C significantly
decreased from baseline in the supplemented
group (whole sample, females and males: p,0.001).
The values of the placebo group did not show any
significant changes from baseline. The between-
group differences in the changes from baseline were
statistically significant in the whole sample
(p,0.001) as well as in females ( p¼0.002) and
males ( p¼0.001).
LDL-C levels significantly decreased in both the
supplemented group (whole sample: p,0.001;
females: p,0.001; males: p,0.010) and in the
whole sample ( p,0.050) an d females ( p,0.050) of
placebo group. The between-group differences in the
changes from baseline were statistically significant for
the whole sample ( p,0.001) as well as for females
(p¼0.001).
The LDL/HDL ratio significantly decreased in the
supplemented group (whole sample: p,0.001;
females: p,0.001; males: p,0.001) but not in the
placebo group. The between-group differences in the
changes from baseline were statistically significant for
the whole sample ( p,0.001) as well as for females
(p¼0.002) and males ( p¼0.005).
TG showed a not statistically significant decrease in
the supplemented group and a not statistically
significant increase in the placebo group. These
opposite patterns of the two groups were statistically
significant in females ( p¼0.013).
Safety
Treatment was well tolerated by all subjects, with
excellent compliance. The fact that there were no study
dropouts further indicates the tolerability of the study
treatments. No AEs were reported. The routine blood
biochemistry parameters (blood count, serum protein
electrophoresis, creatinine, liver and thyroid function)
were within the normal range at the beginning and
at the end of treatment (data not shown).
Discussion
In this double-blind, randomized, placebo-controlled
trial, carried out on subjects with primary mild
Table IV. Dietary intake (by food record method for 3 days) at
screening and at the end of treatment (mean ^SD).
Energy (kJ) 11,019.69 (^688.47) 10,972.3 (^391.63)
Protein (g) 88.95 (^6.55) 85.81 (^6.89)
% Energy 13.38 (^0.71) 12.95 (^0.79)
Fat (g) 80.60 (^3.53) 78.29 (^3.39)
% Energy 27.32 (^1.35) 26.65 (^1.73)
Carbohydrate (g) 397.96 (^34.04) 406.24 (^31.38)
% Energy 56.03 (^1.59) 57.44 (^1.53)
Complex (g) 305.73 (^41.93) 302.44 (^33.20)
% Energy 42.16 (^2.59) 42.72 (^2.76)
Simple (g) 98.16 (^8.60) 103.79 (^8.48)
% Energy 13.87 (^1.35) 14.72 (^1.35)
Dietary fibre (g) 25.70 (^3.38) 27.33 (^3.29)
Cholesterol (mg) 286 (^92) 280 (^95)
Table III. LSM of changes from baseline at EoT, difference in the LSM of the two groups and their comparisons by ANCOVA.
LSM (95% CI)
Parameter Supplemented Placebo Difference in LSM (95% CI) pbetween groups (ANCOVA)
Glycaemia (mmol/l)
All 0.016 (20.085 to 0.117) 20.086 (20.187 to 0.016) 0.102 (20.041 to 0.245) p¼0.160
Total cholesterol (mmol/l)
All 20.397 (20.544 to 20.249) 20.127 (20.274 to 0.020) 20.270 (20.478 to 20.061) p¼0.012
Females 20.440 (20.661 to 20.220) 20.176 (20.401 to 0.049) 20.265 (20.581 to 0.052) p¼0.099
Males 20.292 (20.482 to 20.103) 20.114 (20.299 to 0.071) 20.178 (20.448 to 0.091) p¼0.189
HDL-cholesterol (mmol/l)
All 0.207 (0.113 to 0.302) 0.005 (20.089 to 0.100) 0.202 (0.067 to 0.337) p¼0.004
Females 0.199 (0.047 to 0.350) 0.012 (20.143 to 0.167) 0.187 (20.034 to 0.408) p¼0.095
Males 0.237 (0.129 to 0.345) (0.192) 20.020 (20.125 to 0.086) 0.257 (0.105 to 0.408) p¼0.001
Total cholesterol/HDL ratio
All 20.548 (20.696 to 20.400) 20.022 (20.171 to 0.126) 20.526 (20.737 to 20.314) p,0.001
Females 20.499 (20.693 to 20.305) 20.039 (20.237 to 0.159) 20.460 (20.744 to 20.175) p¼0.002
Males 20.608 (20.855 to 20.362) 20.006 (20.247 to 0.235) 20.602 (20.947 to 20.258) p¼0.001
LDL-cholesterol (mmol/l)
All 20.561 (20.709 to 20.413) 20.149 (20.297 to 20.001) 2412 (20.623 to 20.201) p,0.001
Females 20.637 (20.829 to 20.446) 20.166 (20.362 to 0.030) 20.472 (20.747 to 20.196) p¼0.001
Males 20.454 (20.697 to 20.210) 20.136 (20.374 to 0.101) 20.317 (20.663 to 0.029) p¼0.071
LDL/HDL ratio
All 20.478 (20.613 to 20.342) 20.044 (20.179 to 0.091) 20.434 (20.627 to 20.240) p,0.001
Females 20.456 (20.622 to 20.289) 20.058 (20.228 to 0.112) 20.398 (20.642 to 20.153) p¼0.002
Males 20.511 (20.747 to 20.276) 20.023 (20.253 to 0.207) 20.488 (20.818 to 20.159) p¼0.005
Triglycerides (mmol/l)
All 20.098 (20.224 to 0.029) 0.067 (20.058 to 0.193) 20.165 (20.343 to 0.013) p¼0.070
Females 20.133 (20.246 to 20.019) 0.077 (20.039 to 0.192) 20.209 (20.372 to 20.047) p¼0.013
Males 20.084 (20.332 to 0.163) 0.088 (20.147 to 0.324) 20.173 (20.516 to 0.170) p¼0.314
Note: ANCOVA, analysis of covariance; 95% CI, 95% confidence interval.
M. Rondanelli et al.6
Int J Food Sci Nutr Downloaded from informahealthcare.com by Univ Degli Studi di Pavia on 06/29/12
For personal use only.
hypercholesterolaemia, we observed that the 8-week
supplementation with artichoke leaves extract is
associated with a significant HDL-C increase, thus
fulfilling the primary end-point of the study. This
result appears of relevant clinical interest due to the
potential preventive role of HDL-C in CVD. As a
matter of fact, long-term, follow-up studies have
demonstrated that incremental HDL-C elevation in
either absolute or percentage values can predict
cardiovascular risk. Goldenberg et al. have shown a
29% CVD risk reduction per 5 mg/dl increment in
HDL-C among patients with LDL-C levels below
130 mg/dl (Goldenberg et al. 2009). In other
cholesterol-reducing drug trials, for every 1% increase
in HDL-C, there was a 3% reduction in death or
myocardial infarction (Boden 2000). Statins represent
gold standard treatment of dyslipidaemia: anyhow
their use is associated with frequent unwanted
side effects (Kostapanos et al. 2010). Therefore,
different therapeutical strategies should be identified
at least to treat subjects with mild hypercholester-
olaemia. Although the mechanisms explaining the
HDL-cholesterol-increasing effect of ALE are not
well known, the most likely explanation could be
related to their polyphenolic content and in particular
to chlorogenic acid (Brown and Rice-Evans 1998;
Gebhardt 2002; Wider et al. 2009). This compound
could favour the increase in HDL-C through the
enhancement of the activities of paraoxonase-1
(PON-1). PON-1 is an enzyme associated with HDL
which prevents the oxidation of HDL-C, thus
favouring its anti-oxidative and anti-inflammatory
effects (Goue
´dard et al. 2004). Gugliucci et al.
demonstrated that chlorogenic acid protects PON-1
activity in HDL-C by means of an in vitro study. In this
experiment, chlorogenic acid protects PON-1 activity
in human HDLs from inactivation caused by hypo-
chlorite (HOCl), at concentrations of HOCl (50 mM)
and chlorogenic acid (2 – 10 mM) compatible with
those found in humans (Gugliucci and Bastos 2009).
Previous human studies proved that the increase in
PON-1 activity correlates strongly with the increase in
HDL-C (van der Gaag et al. 1999; Sierksma et al.
2002). Based on these data, it can be hypnotized that
chlorogenic acid, present in ALE extract, may induce
an increase in PON-1 activity and as a consequence,
may favour the increase in HDL-C in humans.
Previous intervention studies with ALE failed to
show an increase in HDL-C (Englisch et al. 2000;
Lupattelli et al. 2004; Bundy et al. 2008). This
different result could be due to the smaller sample size
and lower homogeneity of the studied population,
as compared to this study. Moreover, the different
purification and standardization, as well as the
stability, of the supplements could play a key role in
elucidating the clinical and biological effects of
artichoke extracts.
As far as the secondary end-points of the study are
concerned, a significant decrease in T-C, LDL-C,
LDL/HDL and total/HDL ratio is found in the
supplemented group, while no difference is observed
in the placebo group. The quantitative decrease in T-C
and LDL-C observed in this study is similar to those
observed in other studies carried out with ALEs in
animal models (Ku
¨sku
¨-Kiraz et al. 2010; Qiang et al.
2011) and in humans (Englisch et al. 2000; Lupattelli
et al. 2004; Bundy et al. 2008). The biological
mechanism which is involved in this effect is mainly
played by luteolin, a polyphenol contained in ALEs.
Luteolin inhibits the 3-hydroxy-3-methylglutaryl
coenzyme A (HMG-CoA) reductase activity, which
is a key enzyme in the liver cholesterol biosynthesis
pathway (Gebhardt 2002). Moreover, in vitro studies
showed that chlorogenic acid and luteolin may inhibit
LDL oxidation (Brown and Rice-Evans 1998), thus
reducing the critical effects of oxidized LDL-C and
reducing their atherogenic effect.
A meta-analysis published by Gould et al. on more
than 125,000 subjects confirmed that cholesterol
reduction yields clinical benefits (Gould et al. 2007).
Among all patients, for every 1 mmol/l decrease in
T-C, there was a 17.5% reduction in relative risk (RR)
for all-cause mortality; 24.5%, for CHD-related
mortality and 29.5% for any CHD event. Correspond-
ing reductions for every 1 mmol/l decrease in LDL-C
were 15.6%, 28.0% and 26.6%, respectively. Similar
relationships were observed in patients without CHD.
No significant relationship was found between lipid
reduction and non-CHD-related mortality risk.
Based on the results obtained in this study, it can
be stated that an ALE supplementation may favour
CVD prevention by acting on two different factors,
which is increasing HDL-C and decreasing LDL-C.
Therefore, ALE represents a potential treatment
option for subjects with primary mild hypercholester-
olaemia. ALE also proved to be safe and well tolerated.
Future studies are needed to confirm the present
clinical results over a longer duration with the inter-
vention with ALE, as well as to assess the PON-1
Figure 3. HDL-cholesterol (mmol/l). Mean values and 95% CI by
treatment and gender.
Beneficial effects of artichoke leaf extract 7
Int J Food Sci Nutr Downloaded from informahealthcare.com by Univ Degli Studi di Pavia on 06/29/12
For personal use only.
behaviour in order to confirm the biological mechan-
ism that we hypothesized.
Conclusion
In conclusion, an 8-week intervention with ALE is well
tolerated and efficacious in increasing HDL-C and in
decreasing T-C and LDL-C, in subjects affected with
primary mild hypercholesterolaemia.
Declaration of interest: The authors report no
conflict of interest. The authors alone are responsible
for the content and writing of the paper.
References
American Heart Association 1988. Dietary guidelines for healthy
American adults. A statement for physicians and health
professional by the Nutrition Committee. Circulation 77:
721A–724A.
Andersson LO. 1997. Pharmacology of apolipoprotein A-I. Curr
Opin Lipidol 8:225– 228.
Berliner JA, Navab M, Fogelman AM, Frank JS, Demer LL,
Edwards PA, et al. 1995. Atherosclerosis: basic mechanisms:
oxidation, inflammation, and genetics. Circulation 91:
2488– 2496.
Boden WE. 2000. High-density lipoprotein cholesterol as
an independent risk factor in cardiovascular disease: assessing
the data from Framingham to the Veterans Affairs High-Density
Lipoprotein Intervention Trial. Am J Cardiol 86:19L– 22L.
Brown JE, Rice-Evans CA. 1998. Luteolin-rich artichoke extract
protects low density lipoprotein from oxidation in vitro. Free
Radic Res 29:247–255.
Bundy R, Walker AF, Middleton RW, Wallis C, Simpson HC. 2008.
Artichoke leaf extract (Cynara scolymus)reducesplasma
cholesterol in otherwise healthyhypercholesterolemic adults: a
randomized, double blind placebo controlled trial. Phytomedi-
cine 15:668– 675.
Englisch W, Beckers C, Unkauf M, Ruepp M, Zinserling V. 2000.
Efficacy of Artichoke dry extract in patients with hyperlipopro-
teinemia. Arzneimittelforschung 50:260– 265.
Eriksson M, Carlson LA, Miettinen TA, Angelin B. 1999.
Stimulation of fecal steroid excretion after infusion of
recombinant proapolipoprotein A-I: potential reverse cholesterol
transport in humans. Circulation 100:594 –598.
Forster-Coull L, Barr SI, Levy-Milne R. 2004. British Columbia
nutrition survey: report on food group use. Victoria: British
Columbia Ministry of Health Services.
Frisancho AR. 1984. New standards of weight and body
composition by frame size and height for assessment of
nutritional status of adults and the elderly. Am J Clin Nutr 40:
808– 819.
Gebhardt R. 2002. Inhibition of cholesterol biosynthesis in HepG2
cells by artichoke extracts is reinforced by glucosidase pretreat-
ment. Phytother Res 16:368– 372.
Goldenberg I, Benderly M, Sidi R, Boyko V, Tenenbaum A,
Tanne D, Behar S. 2009. Relation of clinical benefit of raising
high-density lipoprotein cholesterol to serum levels of low-
density lipoprotein cholesterol in patients with coronary heart
disease (from the Bezafibrate Infarction Prevention Trial). Am J
Cardiol 130:41– 45.
Gordon T, Castelli WP, Hjotland MC, Kannel WB, Dawber TR.
1977. High density lipoprotein as a protective factor against
coronary heart disease. The Framingham study. Am J Med 62:
707– 714.
Goue
´dard C, Barouki R, Morel Y. 2004. Dietary poly-
phenols increase paraoxonase 1 gene expression by an aryl
hydrocarbon receptor-dependent mechanism. Mol Cell Biol 24:
5209–5222.
Gould AL, Davies GM, Alemao E, Yin DD, Cook JR. 2007.
Cholesterol reduction yields clinical benefits: meta-analysis
including recent trials. Clin Ther 29:778–794.
Gugliucci A, Bastos DH. 2009. Chlorogenic acid protects
paraoxonase 1 activity in high density lipoprotein from
inactivation caused by physiological concentrations of hypo-
chlorite. Fitoterapia 80:138–142.
Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. 1998.
Mortality from coronary heart disease in subjects with type 2
diabetes and in non-diabetic subjects with and without prior
myocardial infarction. N Engl J Med 339:229 –234.
Kawahiri M, Maugeais C, Rader D. 2000. High-density lipoprotein
metabolism: molecular targets for new therapies for athero-
sclerosis. Curr Atheroscler Rep 2:363– 372.
Keys A. 1997. Coronary heart disease in seven countries. Nutrition
13:250– 252.
Kostapanos MS, Milionis HJ, Elisaf MS. 2010. Rosuvastatin-
associated adverse effects and drug-drug interactions in the
clinical setting of dyslipidemia. Am J Cardiovasc Drugs 10:
11–28.
Ku
¨sku
¨-Kiraz Z, Mehmetc¸ik G, Dogru-Abbasoglu S, Uysal M. 2010.
Artichoke leaf extract reduces oxidative stress and lipoprotein
dyshomeostasis in rats fed on high cholesterol diet. Phytother Res
24:565– 570.
Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S,
De Simone G, American Heart Association Statistics Committee
and Stroke Statistics Subcommittee et al. 2010. Executive
summary: heart disease and stroke statistics 2010 update: a
report from the American Heart Association. Circulation 121:
948–954, Erratum in: Circulation (2010) 121:e259.
Lupattelli G, Marchesi S, Lombardini R, Roscini AR, Trinca F,
Gemelli F, et al. 2004. Artichoke juice improves endothelial
function in hyperlipemia. Life Sci 76:775–782.
Mensink RP, Zock PL, Kester AD, Katan MB. 2003. Effects of
dietary fatty acids and carbohydrates on the ratio of serum total
to HDL cholesterol and on serum lipids and apolipoproteins:
a meta-analysis of 60 controlled trials. Am J Clin Nutr 77:
1146–1155.
Mooradian AD. 2003. Cardiovascular disease in type 2 diabetes
mellitus: current management guidelines. Arch Intern Med 163:
33–40.
Pandino G, Courts FL, Lombardo S, Mauromicale G, Williamson G.
2010. Caffeoylquinic acids and flavonoids in the immature
inflorescence of globe artichoke, wild cardoon, and cultivated
cardoon. J Agric Food Chem 58:1026–1031.
Qiang Z, Lee SO, Ye Z, Wu X, Hendrich S. 2011. Artichoke
extract lowered plasma cholesterol and increased fecal bile
acids in golden Syrian hamsters. Phytother Res [Epub ahead
of print]. doi:10.1002/ptr.3698.
Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB,
Faas FS, Linares E, Schaefer EJ, Schectman G, Wilt TJ, Wittes J.
1999. Gemfibrozil for the secondary prevention of coronary
heart disease in men with low levels of high-density lipo-
protein cholesterol. Veterans Affairs High-Density Lipoprotein
Cholesterol Intervention Trial Study Group. N Engl J Med 341:
410–418.
Sierksma A, van der Gaag MS, van Tol A, James RW, Hendriks HF.
2002. Kinetics of HDL cholesterol and paraoxonase activity
in moderate alcohol consumers. Alcohol Clin Exp Res 26:
1430–1435.
Sirtori CR, Galli C, Anderson JW, Arnoldi A. 2009. Nutritional
and nutraceutical approaches to dyslipidemia and athero-
sclerosis prevention: focus on dietary proteins. Atherosclerosis
203:8–17.
Thompson Coon JS, Ernst E. 2003. Herbs for serum
cholesterol reduction: a systematic view. J Fam Pract 52:
468–478.
M. Rondanelli et al.8
Int J Food Sci Nutr Downloaded from informahealthcare.com by Univ Degli Studi di Pavia on 06/29/12
For personal use only.
Turner RC, Millns H, Neil HA, Stratton IM, Manley SE, Matthews
DR, Holman RR. 1998. Risk factors for coronary artery disease
in non-insulin dependent diabetes mellitus: United Kingdom
Prospective Diabetes Study (UKPDS:23). Br Med J 316:
823– 828.
van der Gaag MS, van Tol A, Scheek LM, James RW, Urgert R,
SchaafsmaG,HendriksHFJ.1999.Dailymoderate
alcohol consumption increases serum paraoxonase activity:
a diet-controlled, randomized intervention study in middle-
aged men. Atherosclerosis 147:405– 410.
Wegener T, Fintelmann V. 1999. Pharmacological properties and
therapeutic profile of artichoke (Cynara scolymus L.). Wien Med
Wochenschr 149:241– 247.
Wider B, Pitter MH, Thompson-Coon J, Ernst E. 2009. Artichoke
leaf extract for treating hypercholesterolaemia. Cochrane
Database Syst Rev, CD003335.
Beneficial effects of artichoke leaf extract 9
Int J Food Sci Nutr Downloaded from informahealthcare.com by Univ Degli Studi di Pavia on 06/29/12
For personal use only.
... Fourteen investigations with a total of 952 patients reported FBS results (Cicero et al., 2019a;Cicero et al., 2019b;Ebrahimi-Mameghani et al., 2018;Fallah Huseini et al., 2012;Ferro et al., 2020;Fogacci et al., 2022;Panahi et al., 2018;Rangboo et al., 2016;Rezazadeh et al., 2018;Riva et al., 2021;Rolnik & Olas, 2021;Rondanelli et al., 2011Rondanelli et al., , 2013Rondanelli et al., , 2014. The effects of artichoke on FBS were significantly different from those of the control group (WMD = −3.76, ...
... Twenty trials (Bundy et al., 2008;Castellino et al., 2019;Cicero et al., 2019a;Cicero et al., 2019b;Ebrahimi-Mameghani et al., 2018;Englisch et al., 2000;Fallah Huseini et al., 2012;Ferro et al., 2020;Fogacci et al., 2022;Lupattelli et al., 2004;Panahi et al., 2018;Rangboo et al., 2016;Rezazadeh et al., 2018;Riva et al., 2021;Roghani-Dehkordi & Kamkhah, 2009;Rondanelli et al., 2011Rondanelli et al., , 2013Rondanelli et al., , 2014Rondanelli et al., , 2020Skarpañska-Stejnborn et al., 2008) documented artichoke's clinical therapeutic effect on lipid profile. LDL levels in the artichoke-treated group were considerably lower than those in the placebo group (WMD −12.94 mg/dL; 95%CI −18.02, −7.87; p < 0.0001), with signs of heterogeneity across trials (I 2 = 90%, p < 0.00001) ( Figure 5). ...
... The analysis of subgroups based on treatment duration, dosage, and health condition revealed that the therapeutic effectiveness of artichoke doses more than 1,000 mg per day and treatment durations longer than 8 weeks improved LDL, TC, TG, HbA 1c , serum insulin, HOMA-IR, SBP, DBP, and BW. While artichoke resulted in considerably improved outcomes for participants with type 2 diabetes and impaired fasting glycemia, as well as overweight and obese individuals and hypertensive patients, the results were not statistically significant (Table 4) (Cicero et al., 2019a;Cicero et al., 2019b;Ebrahimi-Mameghani et al., 2018;Fallah Huseini et al., 2012;Ferro et al., 2020;Fogacci et al., 2022;Panahi et al., 2018;Rangboo et al., 2016;Rezazadeh et al., 2018;Riva et al., 2021;Rolnik & Olas, 2021;Rondanelli et al., 2011Rondanelli et al., , 2013Rondanelli et al., , 2014 HbA 1c 416; −0.22% (−0.57, 0.13); I 2 = 84.90% 416; −0.07% ...
Article
Background Artichoke ( Cynara scolymus L.) has the potential to treat diabetes, dyslipidemia, hypertension, and obesity. However, the evidence from previous studies is not consistent. Objectives This meta-analysis evaluated the efficacy of products derived from artichokes on blood glucose, lipid level, blood pressure, and anthropometric parameters. Methodology The literature was reviewed via international databases (PubMed, ScienceDirect, and Scopus). A total of 21 RCTs with high quality, assessed by the Cochrane risk-of-bias tool, were included. Results Artichoke was linked to a significant reduction in fasting blood sugar (FBS) (WMD: −3.76 mg/dL: 95%CI −7.31, −0.22), insulin level (WMD: −1.35 mIU/L: 95%CI −2.29, −0.41), and HOMA-IR (WMD: −1.00: 95%CI −1.95, −0.06). Similar results were observed for LDL-c (WMD: −12.94 mg/dL: 95%CI −18.02, −7.87), total cholesterol (TC) (WMD: −19.64 mg/dL: 95%CI −23.94, −15.35), and triglyceride (TG) (WMD: −13.36 mg/dL: 95%CI −19.06, −7.66). Moreover, participants who administered artichoke experienced a significant reduction in SBP (WMD: −1.59 mmHg: 95%CI −3.02, −0.16), body weight (BW) (WMD: −1.17 kg: 95%CI −1.75, −0.60), and BMI (WMD: −0.30 kg/m ² : 95%CI −3.02, −0.16). Conclusion Artichoke may improve blood glucose, lipid profile, blood pressure, and anthropometric parameters. A large, well-designed RCT and head-to-head comparison using a standardized preparation of artichoke will provide definitive data on specific participants.
... Lepszy efekt uzyskano w innym badaniu, do którego zakwali kowano 92 otyłych pacjentów z umiarkowaną hipercholesterolemią. Otrzymane po 8 tygodniach codziennego suplementowania 500 mg wyciągu z karczocha wyniki wskazywały, że ELK obniża poziom LDL, a także cholesterolu całkowitego, zwiększając jednocześnie poziom HDL. W grupie przyjmującej placebo efekty te nie wystąpiły [12]. ...
Article
Full-text available
Karczoch zwyczajny (Cynara scolymus) jest znany za sprawą dużej zawartości aktywnych biologicznie metabolitów: polifenoli oraz terpenoidów. Przypisuje im się działanie hipolipidemiczne, antydyspeptyczne, hepatoprotekcyjne oraz antyoksydacyjne. Mimo to liczba dobrej jakości badań klinicznych dokumentujących działanie lecznicze karczocha i ekstraktu z jego liści (ELK) jest stosunkowo niewielka. Zgromadzone w nich dowody zdają się potwierdzać pozytywny wpływ ELK w hipercholesterolemii i dyspepsji czynnościowej. Sugerują też możliwy efekt terapeutyczny u chorych na niealkoholowe stłuszczeniowe zapalenie wątroby i zespół jelita drażliwego. We wszystkich tych przypadkach potrzebne są dalsze rygorystyczne badania kliniczne, które pozwolą skwanty”kować obserwowane efekty i dawki ELK konieczne do ich wywołania. Dowody zdają się wykluczać jakiekolwiek działanie ELK w leczeniu wirusowego zapalenia wątroby typu C oraz kaca alkoholowego.
... In another study, individuals with primary mild hypercholesterolemia were treated for 8 weeks with artichoke leaf extracts (administered as two daily doses of 250 mg). This treatment significantly reduced total cholesterol (TC), LDL cholesterol (LDL-c), and the TC/HDL cholesterol (HDL-c) ratio, while significantly increasing HDL cholesterol (HDL-c), which plays a crucial role in preventing CVDs [82]. Additionally, to investigate the modulation of the lipidic profile by luteolin, Kwon et al. compared the effects of luteolin-enriched artichoke versus artichoke leaf on the lipidic profile. ...
Article
Full-text available
Dietary supplements enriched with bioactive compounds represent a promising approach to influence physiological processes and enhance longevity and overall health. Cynara cardunculus var. scolymus serves as a functional food supplement with a high concentration of bioactive compounds, which offers various health-promoting benefits. Several chronic diseases have metabolic, genetic, or inflammatory origins, which are frequently interconnected. Pharmacological treatments, although effective, often result in undesirable side effects. In this context, preventive approaches are gaining increased attention. Recent literature indicates that the consumption of bioactive compounds in the diet can positively influence the organism’s biological functions. Polyphenols, well-known for their health benefits, are widely recognized as valuable compounds in preventing/combating various pathologies related to lifestyle, metabolism, and aging. The C. scolymus belonging to the Asteraceae family, is widely used in the food and herbal medicine fields for its beneficial properties. Although the inflorescences (capitula) of the artichoke are used for food and culinary purposes, preparations based on artichoke leaves can be used as an active ingredient in herbal medicines. Cynara scolymus shows potential benefits in different domains. Its nutritional value and health benefits make it a promising candidate for improving overall well-being. C. scolymus exhibits anti-inflammatory, antioxidant, liver-protective, bile-expelling, antimicrobial, and lipid-lowering neuroprotective properties. Different studies demonstrate that oxidative stress is the leading cause of the onset and progression of major human health disorders such as cardiovascular, neurological, metabolic, and cancer diseases. The large amount of polyphenol found in C. scolymus has an antioxidant activity, enabling it to neutralize free radicals, preventing cellular damage. This reduces the subsequent risk of developing conditions such as cancer, diabetes, and cardiovascular diseases. Additionally, these polyphenols demonstrate anti-inflammatory activity, which is closely associated with their antioxidant properties. As a result, C. scolymus has the potential to contribute to the treatment of chronic diseases, including intestinal disorders, cardiovascular diseases, and neurodegenerative pathologies. The current review discussed the nutritional profiles, potential benefits, and pharmacological effects of C. scolymus.
... A systematic review and meta-analysis by Sahebkar et al. [102] found artichoke extract supplementation to reduce total cholesterol, LDL and triglyceride levels, while another systematic review and meta-analysis by Majnooni et al. [91] confirmed that artichoke supplementation improves the lipid profile in patients with non-alcoholic fatty liver disease. Other studies have also demonstrated that artichoke supplementation appears to have a beneficial effect on lipid profiles in other models, including patients with hypercholesterolemia [78,79,81]. ...
Article
Full-text available
Cynara scolymus, also known as the globe artichoke or artichoke, is grown as a food, mainly in the Mediterranean, Canary Islands, and Egypt, as well as in Asia and South America. It has also been associated with various health benefits and is used in plant-based dietary supplements and herbal infusions. Its edible parts, consisting of the head or capitula, flower, and leaves, have shown various biological activities, including anti-cancer, hepatoprotective and antimicrobial potential. The leaves are mainly used in infusions and extracts for their health-promoting properties, although all their edible parts may also be consumed as fresh, frozen, or canned foods. However, its primary health-promoting activity is associated with its antioxidant potential, which has been linked to its chemical composition, particularly its phenolic compounds (representing 96 mg of gallic acid equivalent per 100 g of raw plant material) and dietary fiber. The main phenolic compounds in the heads and leaves are caffeic acid derivatives, while the flavonoids luteolin and apigenin (both present as glucosides and rutinosides) have also been identified. In addition, heat-treated artichokes (i.e., boiled, steamed or fried), their extracts, and waste from artichoke processing also have antioxidant activity. The present paper reviews the current literature concerning the biological properties of different parts of C. scolymus, its by-products and dietary supplements, as well as their chemical content and toxicity. The literature was obtained by a search of PubMed/Medline, Google Scholar, Web of Knowledge, ScienceDirect, and Scopus, with extra papers being identified by manually reviewing the references.
... Recent studies reveal that naringenin boosts brown adipogenesis via PPARγ activation [34]. Similarly, the use of Cynara cardunculus L. extract (CyC), containing antioxidants like caffeic acid derivatives, flavonoids like luteolin, and sesquiterpenes like cynaropicrin, has demonstrated lipid-lowering and liver-protective effects in patients with high cholesterol levels [35]. Likewise, CyC counteracted hyperglycemia and hyperlipemia in HFD-fed rats. ...
Article
Full-text available
Obesity is one of the world’s most serious public health issues, with a high risk of developing a wide range of diseases. As a result, focusing on adipose tissue dysfunction may help to prevent the metabolic disturbances commonly associated with obesity. Nutraceutical supplementation may be a crucial strategy for improving WAT inflammation and obesity and accelerating the browning process. The aim of this study was to perform a preclinical “proof of concept” study on Bergacyn®, an innovative formulation originating from a combination of bergamot polyphenolic fraction (BPF) and Cynara cardunculus (CyC), for the treatment of adipose tissue dysfunction. In particular, Bergacyn® supplementation in WD/SW-fed mice at doses of 50 mg/kg given orally for 12 weeks, was able to reduce body weight and total fat mass in the WD/SW mice, in association with an improvement in plasma biochemical parameters, including glycemia, total cholesterol, and LDL levels. In addition, a significant reduction in serum ALT levels was highlighted. The decreased WAT levels corresponded to an increased weight of BAT tissue, which was associated with a downregulation of PPARγ as compared to the vehicle group. Bergacyn® was able to restore PPARγ levels and prevent NF-kB overexpression in the WAT of mice fed a WD/SW diet, suggesting an improved oxidative metabolism and inflammatory status. These results were associated with a significant potentiation of the total antioxidant status in WD/SW mice. Finally, our data show, for the first time, that Bergacyn® supplementation may be a valuable approach to counteract adipose tissue dysfunction and obesity-associated effects on cardiometabolic risk.
Chapter
The rising incidences and prevalence of metabolic diseases, creating enormous health and economic burden worldwide, are a global healthcare challenge. Such conditions, which can be inherited or acquired, are exemplified by type II diabetes, high blood pressure, dyslipidemia, non-alcoholic fatty liver disease, obesity, etc. and are caused by dysregulated metabolism, i.e. defects in the body’s energy processing system. Increase in mortality and years of healthy life lost due to metabolic diseases calls for urgent attention to manage these diseases. Current treatment options largely involve prolonged allopathic medication which is disadvantageous because of associated adverse health effects. Moreover, these diseases often occur as a constellation of maladies requiring complex treatment regimens with multiple drugs culminating in adverse drug-drug interactions. Therefore, considering the limitations of existing therapeutic options, there is a renewed and growing interest in the use of ethnomedicines for the management of metabolic diseases. Ethnomedicine offers advantage over allopathy or chemical drugs, because these are part of indigenous traditional knowledge system and hence are time-tested, safer, economically affordable, accessible and hence sustainable in the long run. In this chapter, we discuss about ethnomedicines which are used in the treatment and management of diabetes, obesity, dyslipidemia, hypertension, fatty liver diseases, etc. in various parts of the world. We also discuss about the scientific investigations that have been performed to validate the therapeutic potential of widely used ethnomedicines against metabolic diseases. Finally, clinical trials conducted on ethnomedicinal resources for the cure of metabolic disorders and associated drawbacks will be reported.
Article
Full-text available
Background: Dyslipidaemia is defined as elevated total or low-density lipoprotein (LDL) levels or low levels of high-density lipoprotein (HDL). Patients may often make use of natural cholesterol lowering supplements (NCLSs) available at the pharmacy; however, limited information on these supplements is readily available. Pharmacists should be knowledgeable about NCLSs to ensure that the use of these supplements is supported by evidence and to provide appropriate advice to patients for desirable therapeutic outcomes.Aim: This study aimed to identify the NCLSs being sold in South African pharmacies and review the scientific evidence for each of the ingredients in these NCLSs.Methods: Seventeen NCLS products were identified, and the Joanna Briggs Institute (JBI) scoping review methodology was used to conduct a literature review of NCLSs.Results: From the ingredients reviewed it is evident that co-enzyme Q10, probiotics and sterols have sufficient evidence supporting their use. However, there is still limited scientific evidence available to validate the remaining ingredients.Conclusion: Further research on NCLSs will provide practising pharmacists and practitioners with a guide of the evidence available on the various ingredients in NCLSs.Contribution: This study provides a review of the available literature on the NCLSs being sold in the pharmacies across South Africa to provide pharmacists with a collated document of the evidence behind these popular supplements to assist them in making evidence based informed decision regarding natural products for cholesterol.
Article
Full-text available
Cynara scolymus L., called artichoke or globe artichoke, is a perennial herbaceous plant cultivated worldwide. This plant is a common component of the Mediterranean diet and has been used as a remedy for health conditions since antiquity. The aim of this review is to find the health-promoting properties of artichoke, conducting a literature search in PubMed. The results show that 119 studies describe these effects and 17 health benefits of artichoke are reported in the scientific literature. Antioxidant activity and effects on the liver and lipid profile are the main health-promoting properties of this plant. We found that artichoke also improves cardiovascular and gastrointestinal health and exerts anticancer, antimetabolic and antiobesity, prebiotic and probiotic, renoprotective and antidiabetic activities. Only one or two research articles reported the positive effects of this plant on the immune system, arthritis, photoaging, the reproductive system, the nervous system, fungal infections and periodontal diseases. The health benefits are mainly exerted by phenolics. In conclusion, this review shows the health-promoting properties of artichoke. The main beneficial effects are antioxidant activity and effects on lipid profile and the liver, which are mainly mediated by phenolics. The results of the scientific articles described in this review and the molecular mechanisms related to the health benefits of artichoke should be confirmed by future experimental studies. Impact statement: Artichoke (Cynara scolymus L.) has many health benefits and the main properties are antioxidant activity and effects on the liver and lipid profile.
Article
Full-text available
To evaluate baseline risk factors for coronary artery disease in patients with type 2 diabetes mellitus. A stepwise selection procedure, adjusting for age and sex, was used in 2693 subjects with complete data to determine which risk factors for coronary artery disease should be included in a Cox proportional hazards model. 3055 white patients (mean age 52) with recently diagnosed type 2 diabetes mellitus and without evidence of disease related to atheroma. Median duration of follow up was 7.9 years. 335 patients developed coronary artery disease within 10 years. Angina with confirmatory abnormal electrocardiogram; non-fatal and fatal myocardial infarction. Coronary artery disease was significantly associated with increased concentrations of low density lipoprotein cholesterol, decreased concentrations of high density lipoprotein cholesterol, and increased triglyceride concentration, haemoglobin A1c, systolic blood pressure, fasting plasma glucose concentration, and a history of smoking. The estimated hazard ratios for the upper third relative to the lower third were 2.26 (95% confidence interval 1.70 to 3.00) for low density lipoprotein cholesterol, 0.55 (0.41 to 0.73) for high density lipoprotein cholesterol, 1.52 (1.15 to 2.01) for haemoglobin A1c, and 1.82 (1.34 to 2.47) for systolic blood pressure. The estimated hazard ratio for smokers was 1.41 (1.06 to 1.88). A quintet of potentially modifiable risk factors for coronary artery disease exists in patients with type 2 diabetes mellitus. These risk factors are increased concentrations of low density lipoprotein cholesterol, decreased concentrations of high density lipoprotein cholesterol, raised blood pressure, hyperglycaemia, and smoking.
Article
New therapeutic approaches to the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD) are needed. Plasma levels of high-density lipoprotein (HDL) cholesterol are inversely associated with risk of ASCVD. Genes involved in the metabolism of HDL represent potential targets for the development of such therapies. Because HDL metabolism is a dynamic process, the effect of a specific HDL-oriented intervention on atherosclerosis cannot necessarily be predicted by its effect on the plasma HDL cholesterol level. Based on available data in animal models, some gene products are candidates for pharmacologic upregulation, infusion, or overexpression, including apolipoprotein (apo)A-I, apoE, apoA-IV, lipoprotein lipase (LPL), ATP-binding cassette protein 1 (ABC1), lecithin cholesterol acyltransferase (LCAT), and scavenger receptor B-I (SR-BI). In contrast, some gene products are potential candidates for inhibition, including apoA-II, cholesteryl ester transfer protein (CETP), and hepatic lipase. The next decade will witness the transition from preclinical studies to clinical trials of a variety of new therapies targeted toward HDL metabolism and atherosclerosis.
Article
A study was conducted in hamsters to determine if artichoke leaf extract (ALE) could lower plasma total and non-HDL cholesterol by increasing fecal excretion of neutral bile acids and sterols. Sixty-four Golden Syrian hamsters (8 week old) were fed control diet or a similar diet containing ALE (4.5 g/kg diet) for 6 weeks. No significant changes for total cholesterol, HDL, non-HDL cholesterol triglycerides or fecal neutral sterols and bile acids were found after 21 days for ALE-fed animals compared with controls. But after 42 days, ALE-fed male hamsters had significantly lower total cholesterol (15%), non-HDL cholesterol (30%) and triglycerides (22%) and female hamsters fed ALE showed reductions of 15% for total cholesterol, 29% for non-HDL cholesterol and 29% for triglycerides compared with controls. Total neutral sterol and bile acids concentrations increased significantly by 50% and 53% in fecal samples of ALE fed males, and 82.4% and 25% in ALE fed females compared with controls. The ALE lowered hamster plasma cholesterol levels by a mechanism involving the greater excretion of fecal bile acids and neutral sterols after feeding for 42 days.
Article
Each year, the American Heart Association, in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update is a valuable resource for researchers, clinicians, healthcare policy makers, media professionals, the lay public, and many others who seek the best national data available on disease morbidity and mortality and the risks, quality of care, medical procedures and operations, and costs associated with the management of these diseases in a single document. Indeed, since 2000, the Statistical Update has been cited more than 6500 times in the literature (including citations of all annual versions). In 2008 alone, the various Statistical Updates were cited approximately 1300 times (data from ISI Web of Science). In recent years, the Statistical Update has undergone some major changes with the addition of new chapters and major updates across multiple areas. For this year's edition, the Statistics Committee, which produces the document for the American Heart Association, updated all of the current chapters with the most recent nationally representative data and inclusion of relevant papers from the literature over the past year. In future years, the Committee plans for the Statistical Update to be a major source for monitoring both cardiovascular health and disease in the population, with a focus on progress toward achievement of the American Heart Association's 2020 Impact Goals. In addition, future Statistical Updates will begin to incorporate the vast amounts of data becoming available from large population-based efforts to study the genetics of cardiovascular disease (CVD). Below are a few highlights from this year's Update.
Article
HMG-CoA reductase inhibitors (statins) are the mainstay in the pharmacologic management of dyslipidemia. Since they are widely prescribed, their safety remains an issue of concern. Rosuvastatin has been proven to be efficacious in improving serum lipid profiles. Recently published data from the JUPITER study confirmed the efficacy of this statin in primary prevention for older patients with multiple risk factors and evidence of inflammation. Rosuvastatin exhibits high hydrophilicity and hepatoselectivity, as well as low systemic bioavailability, while undergoing minimal metabolism via the cytochrome P450 system. Therefore, rosuvastatin has an interesting pharmacokinetic profile that is different from that of other statins. However, it remains to be established whether this may translate into a better safety profile and fewer drug-drug interactions for this statin compared with others. Herein, we review evidence with regard to the safety of this statin as well as its interactions with agents commonly prescribed in the clinical setting. As with other statins, rosuvastatin treatment is associated with relatively low rates of severe myopathy, rhabdomyolysis, and renal failure. Asymptomatic liver enzyme elevations occur with rosuvastatin at a similarly low incidence as with other statins. Rosuvastatin treatment has also been associated with adverse effects related to the gastrointestinal tract and central nervous system, which are also commonly observed with many other drugs. Proteinuria induced by rosuvastatin is likely to be associated with a statin-provoked inhibition of low-molecular-weight protein reabsorption by the renal tubules. Higher doses of rosuvastatin have been associated with cases of renal failure. Also, the co-administration of rosuvastatin with drugs that increase rosuvastatin blood levels may be deleterious for the kidney. Furthermore, rhabdomyolysis, considered a class effect of statins, is known to involve renal damage. Concerns have been raised by findings from the JUPITER study suggesting that rosuvastatin may slightly increase the incidence of physician-reported diabetes mellitus, as well as the levels of glycated hemoglobin in older patients with multiple risk factors and low-grade inflammation. Clinical trials proposed no increase in the incidence of neoplasias with rosuvastatin treatment compared with placebo. Drugs that antagonize organic anion transporter protein 1B1-mediated hepatic uptake of rosuvastatin are more likely to interact with this statin. Clinicians should be cautious when rosuvastatin is co-administered with vitamin K antagonists, cyclosporine (ciclosporin), gemfibrozil, and antiretroviral agents since a potential pharmacokinetic interaction with those drugs may increase the risk of toxicity. On the other hand, rosuvastatin combination treatment with fenofibrate, ezetimibe, omega-3-fatty acids, antifungal azoles, rifampin (rifampicin), or clopidogrel seems to be safe, as there is no evidence to support any pharmacokinetic or pharmacodynamic interaction of rosuvastatin with any of these drugs. Rosuvastatin therefore appears to be relatively safe and well tolerated, sharing the adverse effects that are considered class effects of statins. Practitioners of all medical practices should be alert when rosuvastatin is prescribed concomitantly with agents that may increase the risk of rosuvastatin-associated toxicity.