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The effect of artichoke leaf extract supplementation on lipid profile of chronic kidney disease patients; a double- blind, randomized clinical trial Implication for health policy/practice/research/medical education


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Introduction : Hyperlipidemia is considered a prominent risk factor for coronary heart disease. Coronary heart disease is the most common cause of mortality and morbidity in chronic kidney disease (CKD) patients. Objectives : The aim of this study was to evaluate the effects of artichoke leaf extract (ALE) supplementation on the lipid profile of CKD patients. Patients and Methods : A randomized, double-blind, placebo-controlled clinical trial was conducted in 38 CKD subjects (GFR<60 and >15 mL/min/1.73 m2 ) with hypercholesterolemia (total cholesterol ≥ 200 mg/dL or low-density lipoprotein cholesterol [LDL-C] ≥ 110 mg/dL). The intervention group received an artichoke capsule (320 mg) and an indistinguishable placebo was given to the control group twice daily for 6 weeks. Lipid profile and appetite were assessed at week 8 and the results were compared with the baseline data. Results : ALE supplementation was correlated with a statistically significant decrease in mean total cholesterol (P=0.028) and LDL-C (P=0.005) compared to the control group. The two groups did not show a significant difference in high-density lipoprotein-cholesterol (P=0.071) and triglyceride levels (P=0.22). There was a statistically significant difference in appetite between the two groups (P=0.016). Conclusion : This randomized controlled trial demonstrated that consumption of ALE supplement may improve appetite and lipid profile in CKD patients.
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Journal of Renal Injury Prevention
J Renal Inj Prev. 2019; 8(3): 225-229.
The effect of artichoke leaf extract supplementation on
lipid profile of chronic kidney disease patients; a double-
blind, randomized clinical trial
Seyed Mansour Gatmiri1†
, Ebrahim Khadem2†
, Toktam Fakhrian3, Mohammad Kamalinejad4, Hamed
Hosseini5, Fereshteh Ghorat6, Azam Alamdari1*
, Neda Naderi1*
1Nephrology Research Center, Center of Excellence in Nephrology, Tehran University of Medical Sciences, Tehran, Iran
2Department of Persian Medicine, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran
3School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
4School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
5Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences
6School of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran
These authors contributed equally
*Corresponding authors: Neda Naderi, Email:; Azam Alamdari, Email: DOI: 10.15171/jrip.2019.42
Implication for health policy/practice/research/medical education:
The aim of this study was to evaluate the effects of ALE supplement on the lipid profile of CKD patients. This randomized
controlled trial demonstrated that consumption of ALE supplement may improve lipid profile and appetite in these patients.
Please cite this paper as: Gatmiri SM, Khadem E, Fakhrian T, Kamalinejad M, Hosseini H, Ghorat F, et al. The effect of
artichoke leaf extract supplementation on lipid profile of chronic kidney disease patients; a double-blind, randomized clinical
trial. J Renal Inj Prev. 2019; 8(3): 225-229. DOI: 10.15171/jrip.2019.42.
Chronic kidney disease (CKD) is a worldwide health issue
with a growing incidence and prevalence particularly
due to population aging and increasing frequency of
comorbidities (1). CKD is associated with a higher
cardiovascular mortality. Cardiovascular disease (CVD) is
the main cause of death and morbidity in these patients
(2) and cardiovascular mortality is much higher in CKD
stages 4-5 compared to the general population (3).
Although high serum concentrations of triglyceride
(TG), total cholesterol and low-density lipoprotein
cholesterol (LDL-C) and low serum levels of high-density
Introduction: Hyperlipidemia is considered a prominent risk factor for coronary heart
disease. Coronary heart disease is the most common cause of mortality and morbidity in
chronic kidney disease (CKD) patients.
Objectives: The aim of this study was to evaluate the effects of artichoke leaf extract (ALE)
supplementation on the lipid profile of CKD patients.
Patients and Methods: A randomized, double-blind, placebo-controlled clinical trial was
conducted in 38 CKD subjects (GFR<60 and >15 mL/min/1.73 m2) with hypercholesterolemia
(total cholesterol ≥ 200 mg/dL or low-density lipoprotein cholesterol [LDL-C] ≥ 110 mg/dL).
The intervention group received an artichoke capsule (320 mg) and an indistinguishable
placebo was given to the control group twice daily for 6 weeks. Lipid profile and appetite were
assessed at week 8 and the results were compared with the baseline data.
Results: ALE supplementation was correlated with a statistically significant decrease in mean
total cholesterol (P = 0.028) and LDL-C (P = 0.005) compared to the control group. The two
groups did not show a sign ificant dif ference in high-densit y lipoprotein-cholesterol (P = 0. 071)
and triglyceride levels (P = 0.22). There was a statistically significant difference in appetite
between the two groups (P = 0.016).
Conclusion: This randomized controlled trial demonstrated that consumption of ALE
supplement may improve appetite and lipid profile in CKD patients.
Trial Registration: This RCT has been approved by Iranian Registry of Clinical Trials
identif ier: IRCT2016021622689N3; htt p://en.irct .i r/t rial/19516, Ethics committee reference
number; Ir.tums.rec.1394.1531).
Chronic kidney disease
Dietary supplement
Cynara scolymus
Article History:
Received: 3 April 2019
Accepted: 19 June 2019
Published online: 11 July 2019
Article Type:
Journal of Renal Injury Prevention, Volume 8, Issue 3, September 2019
Gatmiri SM et al
lipoprotein cholesterol (HDL-C) are known risk factors
for the CVD development in the general population, an
inverse association between non-HDL-C which mainly
consist of TG rich lipoproteins and mortality in end-stage
renal disease (ESRD) patients transitioning to dialysis has
been described (4).
CKD patients who do not have nephrotic syndrome and
do not need renal replacement therapy, usually have low
HDL-C, high TG and normal LDL-C which is smaller,
denser and more atherogenic (5). Dyslipidemia which
is a common complication of CKD has a special role in
the development of atherosclerosis and is the principal
modifiable risk factor for cardiovascular disease (6). It
also has been a target for pharmacological therapeutic
agents and natural lipid lowering compounds in primary
and secondary prevention (7).
Cynara scolymus (Artichoke) is an herbaceous perennial
plant which its’ leaves is widely used as hepato-protective,
diuretic, anti-oxidative and cholesterol biosynthesis
inhibitor (8). A few mechanisms of action for lipid lowering
effect of artichoke leaf extract (ALE) have been considered.
Interaction with 3-hydroxy-3-methylglutaryl coenzyme A
(HMG-CoA) reductase, liver sterol regulatory element-
binding proteins and acetyl-CoA C-acetyltransferase
(ACAT) by Luteolin are proposed mechanisms (9).
In this randomized, double-blind, placebo-controlled
clinical trial we evaluated the effect of 6 weeks ALE
supplementation on the lipid profile of our CKD patients.
Patients and Methods
Study design
This double-blind, placebo controlled, randomized
clinical trial was conducted in CKD patients who were
referred to the nephrology clinic of Imam-Khomeini
hospital in Tehran, Iran from December 2017 to July 2018.
The participants were randomly assigned into two groups
(n=20 patients per group) through block randomization
using quadruple blocks. Blocks were randomly selected
to make the randomization list. The drug and placebo
were administered to the patients in similar packages and
the same dose. The researcher and patients were blind to
nature of the intervention (Figure 1).
Totally 64 CKD patients were consequently enrolled in
the study (Figure 1). Forty participants met the inclusion
criteria consisting of estimated glomerular filtration rate
(eGFR) between 15–59 mL/min/1.73 m2 (stages 3a, 3b
and 4), LDL-C level ≥110 mg/dL or total cholesterol level
≥200 mg/dL, age between 18 and 70 years, body mass
index (BMI) value between 18.5 kg/m2 and 30 kg/m2,
positive history of low lipid diet and statin use for more
than 4 months. Patients with severe chronic disease, type
2 diabetes, liver function impairment, history of biliary
obstructive disorder or gallstone, history of dialysis or
kidney transplantation, pregnancy or breastfeeding,
known or potential allergy to the product under the study,
participation in any other clinical trial at the same time or
within the last 30 days, history of malignancy and drug
abuse, were excluded.
Patients were allocated to receive a capsule containing
320 mg of ALE or an indistinguishable placebo capsule
two times a day for 6 weeks. All participants were
asked to continue their regular diet and medications.
Anthropometrical parameters, such as body weight and
BMI were collected both at the beginning and two weeks
after the trial. Biochemical parameters have been obtained
at weeks 0 and 8, after a 12-hour overnight fasting.
Adherence to treatment/placebo, tolerability, acceptability
and compliance were also assessed.
Ethical issues
The study was conducted in accordance with the
Declaration of Helsinki. The protocol was approved by the
Ethics Committee of Tehran University of Medical Sciences
(Ir.tums.rec.1394.1531). Informed consent was obtained
from all participants before inclusion in the study and they
were informed of their right to withdraw from the study at
any time. This study was also registered in Iranian Registry
of Clinical Trials (IRCT) (# IRCT2016021622689N3;; registration date: 2016-06-
18). This study was part of Toktam Fakhrian dissertation,
granted by Tehran University of Medical Sciences (Grant#
Statistical analysis
We used SPSS (SPSS Inc., Chicago, IL, USA) version 16.0
software for descriptive statistics. Parametric variables
were described using mean and standard deviation and
non-parametric data by using frequency. Parametric
variables were evaluated by Student’s t test. Means were
compared using analysis of variance (ANOVA). P values
less than 0.05 were accepted as statistically significant.
In this clinical trial 20 patients were randomized to ALE
supplement and 20 to placebo. Nineteen patients completed
the 6-week intervention in each arm. Mean age of the
participants was 50.24 ± 11.63 years (n=38) and there was
no statistically significant difference between comparison
groups (P = 0.92). The subjects were predominantly
women (60.5%). Demographic and baseline laboratory
characteristics of each group are presented in Table 1.
There were not any significant differences in the baseline
laboratory characteristics between the participants in each
Journal of Renal Injury Prevention, Volume 8, Issue 3, September 2019 227
Artichoke and lipid prole in CKD
At the end of the study, compliance with artichoke
and placebo capsules were 97.6% and 95.8% of expected
doses, respectively (P = 0.38). Mean total cholesterol in
the supplement group was 202 ± 8.18 mg/dL and in the
placebo group was 228 ± 8.18 mg/dL, the mean difference
was –26.57 ± 11.59 mg/dL that was statistically significant
(CI: –50.1- –3.0, P = 0.028). Mean LDL-C in the ALE
supplement group was 119±5.9 mg/dL, in the placebo
group was 144 ± 5.9 mg/dL and the mean difference was
–25.09 ± 8.45 mg/dL that was statistically significant
(95% CI –42.24- –7.93, P = 0.005). Mean HDL-C in ALE
group was 44.53 ± 0.8 mg/dL and in the other group was
42.25±0.8 mg/dL while, the mean difference was not
statistically significant between the two groups (95% CI
–0.2-4.7, P = 0.071). Comparing the LDL-C to HDL-C
ratio, a statistically significant difference (mean difference
= –0.70 ± 0.18) between two groups was detected (95% CI
–1.05- –0.34, P < 0.001).
Mean serum TG level in the placebo group was
202.8 ± 14.81 mg/dL and in the artichoke group was
176.4 ± 14.81 mg/dL since, there was not a statistically
significant difference between the groups (95% CI –69.56-
16.82, P = 0.22).
To compare appetite based on the participants answer
to visual analogue scale (VAS), a statistically significant
improvement in appetite in ALE supplement group was
found (P = 0.016). There was no significant difference in
blood glucose level between the two groups at the end of
the study.
In this randomized, double-blind placebo-controlled
trial of 38 CKD individuals (stages 3a-4), with mild to
moderate hypercholesterolemia, we found that a 6-week
supplementation with ALE (320 mg, twice daily) was
associated with a significant reduction in serum total
cholesterol and LDL-C level, without any significant
changes in serum triglycerides or HDL-C level.
Active components of ALE are flavonoids (luteolin
and glucosides), caffeoylquinic acids (cynarin and
chlorogenic acid), bitters (sesquiterpene lactones,
including cynaropicrin), and caffeic acids (10,11). it seems
that chlorogenic acid and luteolin which are found in
considerable amounts in artichoke, have an important role
in lipid lowering mechanisms (12). Proposed mechanisms
by which ALE may exert lipid-lowering effects are
interaction of luteolin with HMG-CoA reductase, liver
sterol regulatory element-binding proteins and ACAT,
increasing cholesterol elimination through bile acid
secretions and inhibition of LDL oxidation (10, 13).
The clinical impact of ALE has been evaluated in
several studies proposing potential lipid-lowering
effects of ALE in hypercholesteremic adults (10, 13-
16). Bundy et al evaluated the effect of 1280 mg
standardized ALE administered daily for 12 weeks in
healthy hypercholesteremic adults in a randomized,
Figure 1. Flowchart of patient selection for the study.
Journal of Renal Injury Prevention, Volume 8, Issue 3, September 2019
Gatmiri SM et al
double blind placebo controlled trial. Although they
found a statistically significant difference between two
groups in total cholesterol, there was no significant
difference regarding TG, LDL-C and HDL-C (10). In
another study in 2006, Nazni et al examined the effect of
ALE on lipid profile in type 2 diabetic individuals. The
results of this study indicated a significant reduction in
total cholesterol, triglyceride and LDL-C levels and also a
significant increase in HDL-C levels was seen. In addition,
the beneficial effect of ALE on blood glucose level was
observed in this controlled trial (17). In a randomized,
double-blind, placebo-controlled clinical trial in 2013,
Rondanelli et al considered the effects of ALE on lipid
patterns in 92 overweight subjects affected by primary mild
hypercholesterolemia. The results of this study indicated
that not only ALE decreases serum total cholesterol and
LDL-C, but also it is associated with a significant increase
in HDL-C levels (14). Recently, a systematic review and
meta-analysis was carried out on 9 RCTs (included 702
subjects) investigating the impact of ALE on plasma lipid
levels. The authors found a significant decrease in serum
total cholesterol, LDL-C, and triglyceride levels following
ALE administration, however no significant alteration
was observed in HDL-C levels. Moreover, a significant
association between baseline LDL-C level and lipid-
lowering effect of ALE was observed (13).
It should be mentioned that most of the above studies
have been performed in patients with normal renal
function. Dyslipidemia is common in CKD patients and
is associated with high cardiovascular morbidity and
mortality (5). Individuals with non-dialysis-dependent
CKD have specific feature of lipid profile that is distinct
from the general population and is characterized by low
serum HDL-C, high triglycerides and normal or even low
total cholesterol and LDL-C levels. Of note, LDL-C is not
usually elevated, LDL-C particles are smaller, denser and
more atherogenic, while oxidized LDL-C which is highly
atherogenic, is increased in this population (5, 18, 19).
In CKD, dyslipidemia accelerates atherogenic
processes and in turn increases cardiovascular disease.
Additionally, it accelerates decline in kidney function due
to lipid deposition in the kidneys. Therefore, it is logical
to control dyslipidemia in patients with CKD. According
to the KDIGO guidelines, statin or statin/ezetimibe is
recommended in patients with CKD who fulfill treatment
criteria (5). Artichoke is one of the safest herbal medicines
and has not been associated with significant side effects in
most of the subjects (11). To the best of our knowledge,
this is the first study to demonstrate the impacts of
artichoke on lipid profile of CKD patient and our results
are in concordant with studies performing in patients with
normal kidney function. In this study, no adverse events
related to treatment were reported and even patients
compliance was good.
In addition, there was a significant difference in appetite,
favoring those participants receiving ALE supplement.
This was consistent with the reports of a review study
by Wegener et al in 1999 showed that ALE improved
gastrointestinal complaints such as nausea, abdominal
pain, and loss of appetite in patients with hepatobiliary
dysfunction. It was probably, flavonoids and caffeoylquinic
that were mainly responsible for these actions(20).
In conclusion, this study demonstrated that consumption
of ALE supplement may improve appetite and lipid profile
in CKD patients.
Limitations of the study
The small number of participants is an important
limitation of this study. In addition, antioxidant effects of
artichoke were not assessed in these CKD patients. Hence,
further prospective and long- term clinical studies are
necessary to clarify whether artichoke has other beneficial
effects in CKD patients similar to the general population.
Authors’ contribution
SMG and EK joined in concept, design and editing.
NN and AA contributed to manuscript preparation and
editing. TF joined in data collection and data analysis.
MK, HH and FG participated in study design and data
Table 1. Distribution of demographic characteristics and laboratory data of
the participants before the intervention
Variable ALE supplement Placebo P value
Age (y) 50.42± 11.77 50.05 ± 11.48 0.92
Sex 0.74
Male 7 8
Female 12 11
BMI (kg/m2) 27.31 ± 2.56 26.57 ± 4.19 0.51
LDL (mg/dL) 159.9±29.5 143.8±40.3 0.16
HDL (mg/dL) 43.5±7.9 42.9±9.0 0.83
Total CHOL (mg/dL) 241.6±35.8 233.5±46.9 0.55
TG (mg/dL) 177.8±64.9 235.9±150.7 0.13
LDL /HDL 3.8±0.8 3.4±0.9 0.22
BUN (mg/dL) 15.6±6.0 20.3±14.7 0.21
Cr (mg/dL) 1.1±0.3 1.4±0.9 0.15
WBC (cells/mcl) 7246.1±2351.4 6254.3±1155.9 0.23
Hb (g/dL) 13.7±2.2 13.9±0.8 0.79
PLT (cells/mcl) 256000±70579 264000 ± 28589 0.75
AST (IU/l) 27.5±14.6 23.0±11.7 0.52
ALT (IU/l) 36.6±22.1 31.7±27.7 0.68
Alkp (IU/l) 226.6±66.7 111.0±45.2 0.05
FBS (mg/dL) 135.8±75.0 144.0±34.8 0.28
Fe (mcg/dL) 68.5±24.7 62.0±9.9 0.42
ESR (mm/h) 15.7±12.0 25.3±14.1 0.42
TIBC (mg/dL) 304.5±30.4 369.5±133.6 0.57
Journal of Renal Injury Prevention, Volume 8, Issue 3, September 2019 229
Artichoke and lipid prole in CKD
Conflicts of interest
All authors declare no conflicts of interest.
Ethical considerations
Ethical issues (including plagiarism, data fabrication,
double publication) have been completely observed by the
This study was supported by Tehran University of Medical
Sciences research council with code of 940314630407.
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Copyright © 2019 The Author(s); Published by Nickan Research Institute. This is an open-access article distributed under the
terms of the Creative Commons Attribution License (, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.
... Indeed, achieving better management of dyslipidemia often needs multi-drug treatment, but many clinical studies indicated that changing lifestyle and dietary patterns are most effective by medications therapy (Englisch, Beckers, Unkauf, Ruepp, & Zinserling, 2000;Huseini et al., 2012). Hence, to the various side effects of the chemical drugs, the alternative herbal remedies can be promising, especially after long-term use of chemical lipid-lowering drugs (Aguiar et al., 2015;Englisch et al., 2000;Ferrari et al., 2016;Gatmiri et al., 2019;Huseini et al., 2012;Roghani-Dehkordi & Kamkhah, 2009). ...
... Artichoke (Cynara scolymus) is an herbaceous plant that is frequently grown in Mediterranean countries. Artichoke is known for its herbal remedy with antioxidant benefits, cholesterol lowering, diuretic and hepato-protective effects (Gatmiri et al., 2019;Rangboo, Noroozi, Zavoshy, Rezadoost, & Mohammadpoorasl, 2016). A randomized controlled trial by Gatmiri et al. demonstrated that artichoke leaf extract supplementation could improve serum levels of lipids in people with chronic renal failure (Gatmiri et al., 2019). ...
... Artichoke is known for its herbal remedy with antioxidant benefits, cholesterol lowering, diuretic and hepato-protective effects (Gatmiri et al., 2019;Rangboo, Noroozi, Zavoshy, Rezadoost, & Mohammadpoorasl, 2016). A randomized controlled trial by Gatmiri et al. demonstrated that artichoke leaf extract supplementation could improve serum levels of lipids in people with chronic renal failure (Gatmiri et al., 2019). Potential mechanisms by which artichoke can exert lipid-lowering effects are cholesterol synthesis inhibition and prevention of LDL oxidation and stimulation of bile secretion (Skarpanska-Stejnborn, Pilaczynska-Szczesniak, Basta, Deskur-Smielcka, & Horoszkiewicz-Hassan, 2008). ...
Accumulating evidence regarding the effect of artichoke on lipid profile is equivocal. We updated a previous meta‐analysis on the effect of artichoke extract supplementation on lipid profile and performed dose–response analysis. We searched PubMed, Scopus, Web of Science, and Cochrane Library from inception to June 2021 using relevant keywords. Papers from identified articles were collected. Two researchers rated the certainty in the estimates using the GRADE approach. Combining 15 effect sizes from 14 studies based on the random‐effects analysis, we found that artichoke significantly reduced TG (weighed mean difference [WMD]: −17.01 mg/dl, 95% CI: −23.88, −10.13, p = .011), TC (WMD: −17.01 mg/dl, 95% CI: −23.88, −10.13, p < .001), and LDL‐C (WMD: −17.48 mg/dl, 95%CI: −25.44, −9.53, p < .001). No significant effect of artichoke on HDL‐C level was detected (WMD: 0.78 mg/dl, 95%CI: −0.93, 2.49, p = .371). Combining the two effect sizes revealed that artichoke juice supplementation significantly reduced TG (WMD: −3.34 mg/dl, 95%CI: −5.51, −1.17, p = .003), TC (WMD: −18.04 mg/dl, 95%CI: −20.30, −15.78, p < .001), LDL‐C (WMD: −1.75 mg/dl, 95%CI: −3.02, −0.48, p = .007), and HDL‐C levels (WMD: −4.21 mg/dl, 95%CI: −5.49, −2.93, p < .001). In conclusion, we found that artichoke supplementation may favor CVD prevention by acting in improving the lipid profile.
... In a double-blind, randomized clinical trial on 38 CKD patients, it was observed that artichoke leaf extract supplementation was wellcorrelated with a decrease in cholesterol and low-density lipoprotein. A significant difference was also found in the appetite of CKD patients (Gatmiri et al., 2019). It has been reported that the effects of the atherogenic diet were found to be suppressed by the supplementation with artichoke leaf extract vis reduction in monocyte chemoattractant protein-1 expression and controlling oxidative damage in rats (Bogavac-Stanojevic et al., 2018). ...
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Background Due to the toxicity issues of synthetic compounds, herbal medicines are preferred in treating or curing many diseases in recent times. Because of limited treatment options for chronic kidney disease (CKD), the use of traditional herbal medication to alleviate urogenital problems is the alternate therapeutic selection. Purpose Here, we summarized the research outcomes for the use of herbal medicine in the treatment of CKD and hurdles in the way for further research. Methods A relevant literature based on combinations of keywords such as herbal medicines, Chinese herbal medicine, CKD, chronic renal failure, nephroprotection, renoprotection, vegetable-based diet, and plant-based diets was searched using Pub med, Google Scholar, and Science Direct databases. The original articles published from 2006 to 2021 were taken into consideration. The literature was evaluated by studying the abstract or full text, all irrelevant studies were ignored. Results About 54 studies were found to describe the utilization of herbal drugs in the treatment of CKD in both human and laboratory animals, 17 studies described the clinical application of about 13 medicinal plants used against CKD in humans and 37 studies demonstrated the beneficial use of 24 medicinal plants in animal models and in vitro studies for CKD treatment explaining possible mechanisms of their action. The herbal treatment displayed anti-inflammatory, antioxidant, chemopreventive, and immune-mediated properties. The anti-inflammatory action is well implicated via regulation of cyclooxygenase-2, signal transducer, and activation of transcription 3 and IκB kinase β pathways. These pathways are being hypothesized to produce convincing results in CKD. The CKD and gut microbiota is known to be closely related through inflammatory, renal, cardiovascular, and endocrine processes. The various concerns encountered during the use of herbal therapy in CKD are unpredictable pharmacokinetics, herbal and physiological interactions, electrolytic imbalance, and interaction with co-morbid conditions. The combined use of Chinese herbal medicine and Western medicine for the treatment of advanced-stage CKD was found to be effective in delaying dialysis initiation and reducing dialysis incidence. Conclusions A large number of medicinal plants have shown promising beneficial effects against several diseases including cancer, but only a handful of studies are available on CKD. Several studies explained the possible mechanisms of herbal medications in CKD for therapeutic use; however, the focussed molecular studies for identification of active components of medicinal herbs with their mechanism of action and safety standard are still awaited. The demand for well-designed clinical trials and rigorous pharmacological studies as well as a surge for combined use of herbal medicine and Western medicine for the treatment of CKD has been noticed. The nephrotoxicity issues of medicinal plants should not be ignored.
... Dyslipidemia in T2DM patients is associated with an elevated risk for atherosclerosis and coronary heart disease in people with diabetes [43,44]. Thus, therapeutic strategies, including a range of dietary supplements such as administration of Mg, have been developed to improve lipid profile [45][46][47]. ...
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We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effects of magnesium (Mg) supplementation on the lipid profile in type 2 diabetes (T2DM) patients. Web of Science, Scopus, PubMed, and Embase databases were searched to infinity until 30 January 2020. Weighted mean differences (WMD) were pooled using a random-effects model. Heterogeneity, sensitivity analysis, and publication bias were reported using standard methods. The pooled analysis of 12 randomized controlled trials indicated that Mg administration led to significant reduction of serum low-density lipoprotein (LDL) levels (p = 0.006). However, our results revealed that Mg supplementation did not have any effect on triglycerides (TG), total cholesterol (TC), and high-density lipoprotein (HDL) serum concentrations among T2DM patients in comparison with the control group. Subgroup analysis based on duration of study suggested that more than 12 weeks of Mg supplementation significantly decreased the serum TC levels (p = 0.002). Subgroup analysis comparing the dose of intervention indicated that Mg supplementation less than 300 mg significantly decreased the serum LDL concentrations (p < 0.001), while more than 300 mg of Mg supplementation significantly increased the serum HDL levels (p = 0.026). In a subgroup analysis comparing the type of intervention, it displayed that inorganic Mg supplementation decreased the LDL (p < 0.001) and TC (p = 0.003) levels, while organic Mg supplementation showed no difference. Mg supplementation has a beneficial effect on lowering LDL level in T2DM patients. However, we have to note that any research performed so far is not sufficient for making robust guidelines to use Mg supplementation in clinical practice.
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Background There is accumulating evidence that serum levels of non–high‐density lipoprotein cholesterol (non– HDL ‐C) are a more accurate predictor of cardiovascular outcomes when compared with low‐density lipoprotein cholesterol. However, we recently found that higher serum concentrations of triglycerides are associated with better outcomes in patients undergoing hemodialysis. Therefore, we hypothesized that the association of serum levels of non– HDL ‐C (which includes triglyceride‐rich lipoproteins) with outcomes may also be different in patients undergoing hemodialysis when compared with other patient populations. Methods and Results We studied the association of baseline and time‐dependent serum levels of non– HDL ‐C with all‐cause and cardiovascular mortality using Cox proportional hazard regression models in a nationally representative cohort of 50 118 patients undergoing incident hemodialysis from January 1, 2007, to December 31, 2011. In time‐dependent models adjusted for case mix and surrogates of malnutrition and inflammation, a graded inverse association between non– HDL ‐C level and mortality was demonstrated with hazard ratios (95% confidence intervals) of the lowest (<60 mg/dL) and highest (≥160 mg/dL) categories: 1.88 (1.72–2.06) and 0.73 (0.64–0.83) for all‐cause mortality and 2.07 (1.78–2.41) and 0.75 (0.60–0.93) for cardiovascular mortality, respectively (reference, 100–115 mg/dL). In analyses using baseline values, non– HDL ‐C levels <100 mg/dL were also associated with significantly higher mortality risk across all levels of adjustment. Similar associations were found when evaluating non‐ HDL / HDL cholesterol ratio and mortality, with the highest all‐cause and cardiovascular mortality being observed in patients with decreased non‐ HDL / HDL‐C ratio (<2.5). Conclusions Contrary to the general population, decrements in non– HDL ‐C and non‐ HDL / HDL cholesterol ratio were paradoxically associated with increased all‐cause and cardiovascular mortality in patients undergoing incident hemodialysis. The underlying mechanisms responsible for these associations await further investigation.
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Introduction: chronic kidney disease (CKD) is a world-wide health concern associated with a significantly higher cardiovascular morbidity and mortality. One of the principal cardiovascular risk factors is the lipid profile. CKD patients have a more frequent and progressive atheromatous disease that cannot be explained by the classical lipid parameters used in the daily clinical practice. Areas covered: the current review summarizes prevailing knowledge on the role of lipids in atheromathosis in CKD patients, including an overview of lipoprotein metabolism highlighting the CKD-induced alterations. Moreover, to obtain information beyond traditional lipid parameters, new state-of-the-art technologies such as lipoprotein subfraction profiling and lipidomics are also reviewed. Finally, we analyse the potential of new lipoprotein subclasses as therapeutic targets in CKD. Expert opinion: the CKD-induced lipid profile has specific features distinct from the general population. Besides quantitative alterations, renal patients have a plethora of qualitative lipid alterations that cannot be detected by routine determinations and are responsible for the excess of cardiovascular risk. New parameters, such as lipoprotein particle number and size, together with new biomarkers obtained by lipidomics will personalize the management of these patients. Therefore, nephrologists need to be aware of new insights into lipoprotein metabolism to improve cardiovascular risk assessment.
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Background Diabetes mellitus (DM) is associated with hyperglycemia, inflammatory disorders and abnormal lipid profiles, currently the extracts from leaves of cynara scolymus has been discovered to treat metabolic disorders and has been stated by multitudinous scientists according to a good source of polyphenols compounds. The present study aimed to evaluate the protective effect of the ethanol leaves extract of C. scolymus in alloxan induced stress oxidant, hepatic-kidney dysfunction and histological changes in liver, kidney and pancreas of different experimental groups of rats. Methods We determinate the antioxidant activity by ABTS.+ and antioxidant total capacity (TAC) of all extracts of C. scolymus leaves, the inhibition of α-amylase activity in vitro was also investigated. Forty male Wistar rats were induced to diabetes with a single dose intraperitoneal injection (i.p.) of alloxan (150 mg/kg body weight (b.w.)). Diabetic rats were orally and daily administrated of ethanol extract from C. scolymus at two doses (200-400 mg/kg, b.w) or (12 mg/kg, b.w) with anti-diabetic reference drug, Acarbose for one month. Ethanol extract of C. scolymus effect was confirmed by biochemical analysis, antioxidant activity and histological study. Results The results indicated that the ethanol extract from leaves of C. scolymus showed the highest antioxidant activity by ABTS.+ (499.43g± 39.72 Trolox/g dry extract) and (128.75 ± 8.45 mg VC /g dry extract) for TAC and endowed the powerful inhibition in vitro of α-amylase activity with IC50=72,22 ug/uL. In vivo, the results showed that ethanol extract from the leaves of C. scolymus (200-400 mg/kg) decreased significantly (p < 0.001) the α-amylase levels in serum of diabetic rats, respectively associated with significant reduction (p < 0.001) in blood glucose rate of 42,84% and 37,91% compared to diabetic groups after 28 days of treatment, a significant lowered of plasma total cholesterol (T-Ch) by 18,11% and triglyceride (TG) by 60,47%, significantly and low-density lipoproteins (LDL-C) by 37,77%, compared to diabetic rats, moreover, the administration of ethanol extract appears to exert anti-oxidative activity demonstrated by the increase of CAT, SOD and GSH activities in liver, kidney and pancreas of diabetic rats. This positive effect of the ethanol extract from C. scolymus was confirmed by histological study. Conclusion These observed strongly suggest that ethanol extract from the leaves of C. scolymus has anti-hyperglycemic properties, at least partly mediated by antioxidant and hypolipidemic effects.
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Artichoke is a component of the Mediterranean diet. Therefore, the aim of this meta-analysis was to determine if artichoke extract supplementation affected human lipid parameters. The search included PubMed-Medline, Scopus, Web of Science and Google Scholar databases up to March 28, 2017, to identify RCTs investigating the impact of artichoke extracts on plasma lipid levels. Quantitative data synthesis was performed using a random-effects model, with weighed mean difference (WMD) and 95% confidence interval (CI) as summary statistics. Meta-analysis of data from 9 trials including 702 subjects suggested a significant decrease in plasma concentrations of total cholesterol (WMD: −17.6 mg/dL, 95%CI: −22.0, −13.3, p<0.001), Low Density Lipoprotein-Cholesterol (LDL-C; WMD: −14.9 mg/dL, 95%CI: −20.4, −9.5, p = 0.011) and triglycerides (WMD: −9.2 mg/dL, 95%CI: −16.2, −2.1, p = 0.011). No significant alteration in plasma High Density Lipoprotein-Cholesterol (HDL-C) concentrations was observed (WMD: 1.0 mg/dL, 95%CI: −1.1, 3.1, p = 0.333). A significant association between the LDL-lowering effect of artichoke and baseline LDL-C concentrations (slope: −0.170; 95%CI: −0.288, 0.051; p = 0.005) was observed. Thus, supplementation with artichoke extract was associated with a significant reduction in both total and LDL-C, and triglycerides, suggesting that supplementation may be synergistic with lipid-lowering therapy in patients with hyperlipidemia.
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Ivana Mikolasevic,1,2 Marta Žutelija,3 Vojko Mavrinac,1 Lidija Orlic 2 1Department of Gastroenterology, 2Department of Nephrology, Dialysis and Kidney Transplantation, UHC Rijeka, 3School of Medicine, Rijeka, Croatia Abstract: Patients with chronic kidney disease (CKD), including those with end-stage renal disease, treated with dialysis, or renal transplant recipients have an increased risk for cardiovascular disease (CVD) morbidity and mortality. Dyslipidemia, often present in this patient population, is an important risk factor for CVD development. Specific quantitative and qualitative changes are seen at different stages of renal impairment and are associated with the degree of glomerular filtration rate declining. Patients with non-dialysis-dependent CKD have low high-density lipoproteins (HDL), normal or low total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol, increased triglycerides as well as increased apolipoprotein B (apoB), lipoprotein(a) (Lp (a)), intermediate- and very-low-density lipoprotein (IDL, VLDL; “remnant particles”), and small dense LDL particles. In patients with nephrotic syndrome lipid profile is more atherogenic with increased TC, LDL, and triglycerides. Lipid profile in hemodialysis (HD) patients is usually similar to that in non-dialysis-dependent CKD patients. Patients on peritoneal dialysis (PD) have more altered dyslipidemia compared to HD patients, which is more atherogenic in nature. These differences may be attributed to PD per se but may also be associated with the selection of dialytic modality. In renal transplant recipients, TC, LDL, VLDL, and triglycerides are elevated, whereas HDL is significantly reduced. Many factors can influence post-transplant dyslipidemia including immunosuppressive agents. This patient population is obviously at high risk; hence, prompt diagnosis and management are required to improve their clinical outcomes. Various studies have shown statins to be effective in the cardiovascular risk reduction in patients with mild-to-moderate CKD as well as in renal transplant recipients. However, according to recent clinical randomized controlled trials (4D, A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Dialysis: an Assessment of Survival and Cardiovascular Events, and Study of Heart and Renal protection), these beneficial effects are uncertain in dialyzed patients. Therefore, further research for the most suitable treatment options is needed. Keywords: chronic kidney disease, cardiovascular disease, dyslipidemia
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Background: There is an increasing interest for combined nutraceuticals that can act on several points of lipid and glucose metabolism with preventive purposes. However, the simple assemblage of nutraceuticals with potentially additive mechanism of action need to be clinically tested. Methods: To assess the effects of a combination of nutraceuticals based on artichoke, red yeast rice, banaba, and coenzyme Q10, we performed a double bind, cross-over designed trial versus placebo in 30 adults with LDL cholesterol suboptimal in primary prevention of cardiovascular disease. After a period of 3 weeks of dietary habits correction, patients began a period of 6 weeks of treatment with nutraceutical or placebo, followed by 2 weeks of washout and finally 6 weeks in cross-over. Data related to lipid pattern, insulin resistance, renal function, liver and CPK have been obtained at each visit. Results: In particular, the after the nutraceutical treatment the enrolled patients experienced a significant improvement in total cholesterol (-13.6 %), LDL-C (-18.2 %), non-HDL-C (-15 %), glutamic oxaloacetic transaminase (-10 %), glutamate-pyruvate transaminase (-30.9 %), and hs-CRP (-18.2 %) versus placebo. No changes have been observed in the other investigated parameters in both groups. Conclusions: The tested combination of nutraceuticals has shown clinical efficacy in the reduction of total cholesterol, non-HDL, LDL and triglycerides, while improving the level of liver transaminases and high sensitivity C-reactive protein. Further confirmation are needed to verify these observations on the middle and long term with a larger number of subjects.
Incorporating pharmacists into multidisciplinary teams in the outpatient ambulatory care and inpatient acute care settings can circumvent major drug-related problems through the process of medication therapy management (MTM), in which the pharmacist’s care plan includes optimal evidence-based medication, goals of therapy, and, most important, ensuring that appropriate follow-up is carried out. Chronic kidney disease (CKD) patients present with comorbid disease states with often-complex pharmacotherapeutic regimens that can be difficult not only for the patient, but for the prescribers as well. This review evaluates medication-related problems associated with CKD, nonadherence issues, medication reconciliation, and the contributions pharmacists provide through MTM. Care for the chronic kidney disease (CKD) patient poses unique challenges to prescribers and practitioners in terms of overall medication therapy management (MTM). Traditionally, the role of clinical pharmacists in both the ambulatory care and inpatient acute care practice has been to prospectively screen for major drug-related problems through careful laboratory monitoring, evaluate for possible drug interactions, and dose-adjust medications based on patients’ renal function. In 2013, the American College of Clinical Pharmacy (ACCP) clarified its position statement in its description of clinical pharmacy services. In its definition, ACCP recognized the need for pharmacists in the provision of direct patient care, which involves a regular continuing collaboration or practice with other members of the healthcare team in the care of the patient.¹ MTM includes a thorough review of the patient’s full medication list and an evaluation of therapies by screening for the safest and most effective use of medications. The development of a pharmaceutical care plan with evidence- and goal-based therapies and the ensuring of appropriate follow-up are the definition of MTM.² Patients with CKD present with comorbid conditions such as diabetes, hypertension, anemia, osteodystrophy, and electrolyte disturbances. In fact, multiple physicians often prescribe a CKD patient’s medications. This can result in problematic situations due to gaps in communication between healthcare providers as well as unfamiliarity of disease-state management by the patient.³ The purpose of this review is to evaluate the role of the pharmacist in the management of CKD through the use of MTM services and to highlight areas of focus, such as identifying medication-related problems (MRPs) associated with CKD, medication nonadherence in CKD patients, importance of medication reconciliation, and enhancement of pharmacist roles on multidisciplinary teams.
Chronic kidney disease (CKD) is a global public health problem that is associated with excess morbidity, mortality, and health resource utilization. The progression of CKD is defined by a decrease in glomerular filtration rate and leads to a variety of metabolic abnormalities including acidosis, hypertension, anemia, and mineral bone disorder. Lower glomerular filtration rate also bears a strong relationship with an increased risk of cardiovascular events, end-stage renal disease, and death. Patterns of CKD progression include linear and nonlinear trajectories, but kidney function can remain stable for years in some individuals. Addressing modifiable risk factors for the progression of CKD is needed to attenuate its associated morbidity and mortality. Developing effective risk prediction models for CKD progression is critical to identify patients who are more likely to benefit from interventions and more intensive monitoring. Accurate risk-prediction algorithms permit systems to best align health care resources with risk to maximize their effects and efficiency while guiding overall decision making.
Multiple studies demonstrate a strong independent association between CKD and cardiovascular events including death, heart failure, and myocardial infarction. This review focuses on recent clinical studies that expand this spectrum of adverse cardiovascular events to include ventricular arrhythmias and sudden cardiac death. In addition, experimental models suggest structural remodeling of the heart and electrophysiologic changes in this population. These processes may explain the increased arrhythmic risk in kidney disease and aid in identifying patients who are at higher risk for sudden cardiac death. Finally, we review here the data to support the use of pharmacologic and device-based therapies for both the primary and secondary prevention of sudden cardiac death.