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Metabolic benefits of curcumin supplementation in patients with metabolic syndrome: A systematic review and meta‐analysis of randomized controlled trials

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The finding of studies on the effect of curcumin extract on metabolic factor in patients with metabolic syndrome has had arguable results. This systematic review with meta‐analysis of randomized controlled trials (RCT) aimed to analyze the effect of curcumin/turmeric on metabolic factors in patients with metabolic syndrome. The PICO strategy was used to establish the guiding question of this review. Several databases for RCT were searched until September 2018. Of the 144 articles initially identified, seven trials met the eligibility criteria. A random‐effects model with a mean weight difference (WMD) and a 95% confidence interval was performed for quantitative data synthesis. Pooled estimates of WMD were calculated between intervention and control groups using random‐effects model in the presence of high level of heterogeneity between the studies. The results showed significant improvement of fasting blood glucose (p = 0.01), triglycerides (p < 0.001), high‐density lipoprotein cholesterol (p = 0.003), and diastolic blood pressure (p = 0.007) levels. Curcumin was not associated with a significant change in waist circumference measurement (p = 0.6) and systolic blood pressure level (p = 0.269). Curcumin supplementation improves some components of metabolic syndrome.
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REVIEW
Metabolic benefits of curcumin supplementation in patients
with metabolic syndrome: A systematic review and meta
analysis of randomized controlled trials
Maryam Azhdari
1,2
|Majid Karandish
3
|Anahita Mansoori
1
1
Nutrition and metabolic Diseases Research
Center, Ahvaz Jundishapur University of
Medical Sciences, Ahvaz, Iran
2
Department of clinical biochemistry, Faculty
of Medicine, Shahid Sadoughi University of
Medical Sciences and Health Services, Yazd,
Iran
3
Health Research Institute, Diabetes Research
Center, Ahvaz Jundishapur University of
Medical Sciences, Ahvaz, Iran
Correspondence
Anahita Mansoori, PhD (Nutrition Sciences),
Assistant Professor, Nutrition Department,
Faculty of Paramedicine, Ahvaz Jundishapur
University of Medical Sciences, P.O. Box
6135715794, Ahvaz, Iran.
Email: mansoori_anahita@yahoo.com;
mansooria@ajums.ac.ir
Funding information
Ahvaz Jundishapur University of Medical Sci-
ences, Grant/Award Number: NRC9721
The finding of studies on the effect of curcumin extract on metabolic factor in
patients with metabolic syndrome has had arguable results. This systematic review
with metaanalysis of randomized controlled trials (RCT) aimed to analyze the effect
of curcumin/turmeric on metabolic factors in patients with metabolic syndrome.
The PICO strategy was used to establish the guiding question of this review. Several
databases for RCT were searched until September 2018. Of the 144 articles initially
identified, seven trials met the eligibility criteria. A randomeffects model with a mean
weight difference (WMD) and a 95% confidence interval was performed for quantita-
tive data synthesis. Pooled estimates of WMD were calculated between intervention
and control groups using randomeffects model in the presence of high level of
heterogeneity between the studies. The results showed significant improvement of
fasting blood glucose (p= 0.01), triglycerides (p< 0.001), highdensity lipoprotein cho-
lesterol (p= 0.003), and diastolic blood pressure (p= 0.007) levels. Curcumin was not
associated with a significant change in waist circumference measurement (p= 0.6)
and systolic blood pressure level (p= 0.269). Curcumin supplementation improves
some components of metabolic syndrome.
KEYWORDS
curcumin, metabolic syndrome, turmeric
1|INTRODUCTION
Metabolic syndrome (MetS) is a multifactorial disease, and aging,
genetics, and lifestyle (physical inactivity, inappropriate nutrition,
obesity) have important roles in its prevalence (Wilborn et al.,
2005). The National Cholesterol Education Program Adult Treatment
Panel III (NCEPATP III) and the International Diabetes Federation
(IDF) are two of the most appropriate diagnostic criteria for
MetS (Deepa et al., 2007; Kelliny et al., 2008). Both of the criteria
include fasting plasma glucose, blood pressure (BP), triglycerides
(TG), highdensity lipoprotein cholesterol (HDLC), and central obe-
sity (waist circumference [WC]) Rezaianzadehet al., 2012). About
20% to 25% of the adult population worldwide have MetS according
to IDF definition, and it is increasing in all over the world (Alberti
et al., 2006).
Turmeric (Curcuma longa L) from Zingiberaceae family (Hosseini &
Hosseinzadeh, 2018) is a golden spice. Turmeric is a traditional
medicinal plant that is used extensively in domestic use and its appli-
cation to improve the taste and color and therapeutic properties
(Nelson et al., 2017) without any toxicity in oral administration
Abbreviation: ACVD, atherosclerotic cardiovascular diseases; BMI, body mass index; BP,
blood pressure; C/EBPα, CCAAT/enhancer binding protein α; CI, confidence intervals; CVD,
cardiovascular diseases; DBP, diastolic blood pressure; FFA, free fatty acids; HDLC, high
density lipoprotein cholesterol; IDF, International Diabetes Federation; LPL, lipoprotein
lipase; MetS, metabolic syndrome; NCEPATP III, National Cholesterol Education Program
Adult Treatment Panel III; NFκB, nuclear factorkappa B; Nrf2, nuclear factor erythroid2
related factor2; PPARγ, peroxisome proliferatoractivated receptorgamma; PRISMA,
Preferred Reporting Items for Systematic Reviews and Metaanalyses; RCTs, randomized
controlled trials; SBP, systolic blood pressure; T2D, type 2 diabetes; TG, triglycerides; WC,
waist circumference; WMD, weighted mean differences
Received: 29 November 2018 Revised: 19 January 2019 Accepted: 31 January 2019
DOI: 10.1002/ptr.6323
Phytotherapy Research. 2019;113. © 2019 John Wiley & Sons, Ltd.wileyonlinelibrary.com/journal/ptr 1
(Soleimani et al., 2018). Curcumin or diferuloylmethane (chemical
name of curcumin) (Ghosh et al., 2011) is bioactive yellow molecules
(Prasad et al., 2014) with phenolic, antidiabetic, antioxidant, anti
inflammatory (Selvi et al., 2015), antibacterial, antiviral, antifungal
(Zorofchian Moghadamtousi et al., 2014), and anticancer properties
(Prasad et al., 2014). Several components can enhance bioavailability
of curcumin like piperine.
The result of a metaanalysis study showed turmeric and curcumin
decrease serum LDLC, total cholesterol and TG levels in cardiovascu-
lar diseases (CVD) patients. However, serum HDLC levels did not
change, significantly (Qin et al., 2017). Curcumin can reduce lipid per-
oxidation (Panahi et al., 2018) and the risk of cardiovascular factors in
patients with type 2 diabetes and dyslipidemia (Panahi et al., 2017b).
In another study, curcumin supplementation did not improve anthro-
pometric indices, serum lipid profiles (except TC), systolic blood pres-
sure (SBP), and diastolic blood pressure (DBP) in the patients with
MetS (SaberiKarimian et al., 2018).
The results of previous studies about the effects of curcumin
supplement on metabolic factors in patients with MetS are conflict-
ing (Cicero & Colletti, 2016; Patti et al., 2018; Selmanovic et al.,
2017), possibly due to variations in several factors such as the trials'
sample size, intervention duration, dosage, and race. A comprehen-
sive systematic review and metaanalysis of accessible clinical trials
can prove medical plant efficacy (Colalto, 2018; Izzo et al., 2016).
Therefore, the present systematic review was undertaken to deter-
mine the effects of curcumin supplement on metabolic factors in
patients with MetS.
2|METHODS
This literature was performed in accordance with the Preferred
Reporting Items for Systematic Reviews and Metaanalyses statement
to ensure its quality (Moher, et al., 2009). The PICO strategy was used
to establish the guiding question of this review (Santos et al., 2007).
Population: The patients (males and females) for whom a diagno-
sis of MetS was made according to the criteria
defined by NCEPATP III guidelines or IDF criteria,
age: 1865 year.
Intervention: curcumin or curcuminoid supplement, curcumin
extract, turmeric powder.
Comparison: compared with a placebo or control group.
Outcome: WC, HDLC, TG, FBG, SBP, DBP.
In brief, the search strategy was as follows:
2.1 |Search strategy
Electronic databases including ISI Web of Science (www.
webofknowledge.com/), MEDLINE (source: PubMed; https://www.
ncbi.nlm.nih.gov/pubmed/), Google Scholar databases, Scopus,
Cochrane, and CINAHL were searched until September 2018 to find
relevant articles. A comprehensive search strategy was employed in
relevant MeSH terms and/or text word for randomized controlled tri-
als (RCTs; randomized, placebocontrolled/controlled/clinical trials).
Relevant studies were identified through a search in databases follow-
ing the search words:
Turmeric, curcumin, curcuminoid, curcuma.
Metabolic syndrome, metabolic syndrome x, insulin resistance syn-
drome x, metabolic x syndrome, dysmetabolic syndrome x, reaven
syndrome x, metabolic cardiovascular syndrome, insulin resistance,
national cholesterol education program adult treatment panel iii,
nutritional and metabolic diseases, metabolic diseases, syndrome
of affluence, plurimetabolic syndrome, atherothrombogenic syn-
drome, syndrome x plus, deadly quartet, cardiovascular and
metabolic syndrome, metsyn, wohlstands syndrome, android
obesity syndrome, dysmetabolic syndrome, hypertriglyceridemic
syndrome, obesity syndrome, obesity dyslipidemia syndrome,
hypertriglyceridemic waist.
Reference lists of all selected articles were retrieved manually to
identify more relevant studies. The search was not restricted
based on the publication year and language. The registration number
of present systematic review and metaanalysis in PROSPERO is
CRD42018105167.
2.2 |Study selection
The studies were RCTs using the following criteria: (1) male/female
over 18 years, (2) for whom a diagnosis of MetS was made according
to the criteria defined by NCEPATP III guidelines or IDF guidelines
(Alberti et al., 2005), (3) the studies assessed the effects of
turmeric/curcumin supplement on at least one metabolic factor, and
(4) data of the studies were collected at the baseline and at the end
of the trial in both intervention and control groups or changes by
group. In the case of multiple reports for the same studied population,
the most complete dataset was analyzed. There were no restrictions
based on sex or race of the individuals included.
Exclusion criteria were the following: (a) uncontrolled trial, (b) the
studies do not report sufficient data, (c) consumption for the antihy-
pertensive antidyslipidemic or antidiabetic drugs, (d) study period
<4 weeks, and (e) presence of malignancies and systematic or chronic
diseases, except diabetes.
2.3 |Data extraction
At first, two researchers (A. M. and M. A.) scanned the title and
abstract, then they read full texts of the included records for selecting
the eligible studies for metaanalysis (Figure 1). The studies that did
not meet the inclusion criteria were excluded. The disagreement was
resolved by the consensus with a third researcher (M. K.). Finally,
seven studies met the eligibility criteria (Amin et al., 2015; Y Panahi
et al., 2015; Panahi et al., 2014; Pierro et al., 2015; SaberiKarimian
2AZHDARI ET AL.
et al., 2018; Salimi Avansar, 2017; Yang et al., 2014). The data of these
eligible studies were reviewed and abstracted by two researchers
independently as follows:
First author's name, year of publication, location, the number of
the participants (intervention and placebo), MetS diagnostic criteria,
age and gender of participants, the dose of intervention, duration of
the study, reported side effects, and outcomes.
2.4 |Quality assessment
The quality of the selected studies was independently checked by
two researchers (M. A. and A. M.). The Cochrane Collaboration's tool
was used to evaluate methodological quality of the eligible studies
(Higgins & Green, 2015). It includes seven items in six domains of
bias: selection bias(two items): (a) random sequence generation
and (b) allocation concealment, performance bias(one item):
blinding of participants and personnel, detection bias(one item):
blinding of outcome assessment, attrition bias(one item): incom-
plete outcome data, reporting bias(one item): selective reporting,
and other sources of bias(one item): the assessment of supple-
ment compliance. In regard to each item, risk of bias was considered
as low, high, and unclear. The overall quality of individual trials was
classified into three categories: good (low risk for more than two
items), fair (low risk for two items), or weak (low risk for less than
two items) (Higgins et al., 2011). If RCTs explained the method for
the assessment of supplement compliance, the risk of bias was con-
sidered as low.
2.5 |Statistical analysis
Changes in variable valves were reported as absolute differences
between mean values in the baseline and end of study. Correlation
coefficient was calculated to impute standard deviation (SD) of the
change from the baseline for five criteria of MetS (FBS, WC, TG,
HDLC, SBP, and DBP) in the intervention/control groups.
We calculated pooled estimates of weighted mean differences
(WMD) between the intervention and control groups using a
randomeffects model in the presence of high level of heterogeneity
between studies. Fixed effects model was used for metaanalyses of
homogeneous data. Betweenstudy heterogeneity was tested by
chisquare test (Cochran Qtest) and I
2
. Heterogeneity was considered
low if I
2
< 30%, moderate if I
2
=3075%, and high if I
2
> 75%.
FIGURE 1 Flow diagram for selection of trials [Colour figure can be viewed at wileyonlinelibrary.com]
AZHDARI ET AL.3
Chisquare p< 0.1 was set as a level of significant heterogeneity
(Higgins & Thompson, 2002).
Subgroup analysis did not perform to detect sources of heteroge-
neity due to insufficient available trials and data. Moreover,
sensitivity analysis using influence analysis was carried out to test
assess the impact of each study on the overall effect size by the
leaveoneout method (when one study had been excluded in each
turn and repeated the analysis). Funnel plots were not performed
to indicate the presence of publication bias. They would be
unreliable because this review included less than 10 studies (Higgins
& Green, 2015).
STATA 14.0 (Stata Corp., College Station, TX, USA) was used for
analysis of data. Statistically, pvalue was a doubletailed test, and a
significant difference was considered as p< 0.05 (Egger et al., 1997;
Terrin et al., 2003).
3|RESULTS
3.1 |Literature search and study characteristics
A summary of the selection of studies is shown in Figure 1 and Table
S1; 144 studies were identified by the initial search strategy and the
reference list of studies. After duplicate removal, 60 records were
excluded, and 84 studies were screened on the basis of titles and
abstracts. From 21 studies selected for fulltext screening, 14 studies
were excluded because of different types of supplement (Cicero
et al., 2017; Rahimi et al., 2016; Kocher et al., 2016; Tariq et al.,
2016), patients without a diagnosis of MetS (CamposCervantes
et al., 2011; Chuengsamarn et al., 2012; Esmaily et al., 2015; Ismail
et al., 2016; Panahi, et al., 2017a; Panahi, et al., 2017b), lack of
desired variables (CamposCervantes et al., 2011), and reporting
duplicate data (A. Mohammadi et al., 2017). Seven studies fulfilled
inclusion criteria for quantitative data synthesis. Four studies
reported sufficient data on WC (Amin et al., 2015; Pierro et al.,
2015; SaberiKarimian et al., 2018; Salimi Avansar, 2017), five
reported HDLC, TG (Amin et al., 2015; Panahi et al., 2014; Saberi
Karimian et al., 2018; Salimi Avansar, 2017; Yang et al., 2014), and
FBS data (Amin et al., 2015; Panahi et al., 2015; SaberiKarimian
et al., 2018; Salimi Avansar, 2017; Yang et al., 2014), and three
reported SBP and DBP (Amin et al., 2015; Y Panahi et al., 2015;
Salimi Avansar, 2017; Table S2).
The characters of the seven included studies for metaanalysis are
summarized in Table 1. Overall, six studies evaluated the effects of
curcumin supplement (Panahi et al., 2015; Panahi et al., 2014; Pierro
et al., 2015; SaberiKarimian et al., 2018; Salimi Avansar, 2017; Yang
et al., 2014), and one study considered the effect of administration
of turmeric (Amin et al., 2015) on our desired outcomes.
The total sample size included 503 MetS participants (224
female/279 male). All studies were parallel RCTs (Amin et al.,
2015; Y Panahi et al., 2015; Panahi et al., 2014; Pierro et al.,
2015; SaberiKarimian et al., 2018; Salimi Avansar, 2017;
Yang et al., 2014). The range of the study's duration was 4 to
12 weeks; four studies lasted 8 weeks (Panahi et al., 2015; Panahi
et al., 2014; SaberiKarimian et al., 2018) and three studies lasted
4 (Pierro et al., 2015), 6 (SaberiKarimian et al., 2018), and 12 weeks
(Yang et al., 2014).
Ranges of daily dosages were as follows: 800 mg/day (twice;
Pierro et al., 2015), 1,000 mg/day (twice) (Panahi et al., 2015; Panahi
et al., 2014; SaberiKarimian et al., 2018), 1,890 mg/day (thrice) (Yang
et al., 2014), 2,400 mg/day (thrice) (Amin et al., 2015), and one trial
based on 20 mg/Kg/day (Salimi Avansar, 2017).
3.2 |Quality assessment
Table S3 shows the summary of the quality assessment of trials; all of
them (Amin et al., 2015; Y Panahi et al., 2015; Panahi et al., 2014;
Pierro et al., 2015; SaberiKarimian et al., 2018; Yang et al., 2014)
had a good score based on the Cochrane Collaboration tool except
in the trial by Salimi Avansar. The trial by Salimi Avansar has received
a fair score (score = 2) because of achieving only two scores in two
items (incomplete outcome data and selective outcome reporting).
3.3 |Qualitative synthesis
The trial by Amin et al., which evaluated the effect of turmeric,
showed a significant improvement in the HDLC, TG, SBP, and DBP
levels and no significant difference in FBS level and WC measurement
(Amin et al., 2015). The results of other studies, which examined the
effect of curcumin, are as follows:
No significant decrease was observed in WC (Pierro et al., 2015;
SaberiKarimian et al., 2018; Salimi Avansar, 2017), DBP, and SBP levels
(Panahi et al., 2015; SaberiKarimian et al., 2018) between the study
groups. However, a significant improvement was observed in the
curcumin group compared with the placebo group in HDL and TG
levels (Panahi et al., 2014; SaberiKarimian et al., 2018; Salimi Avansar,
2017; Yang et al., 2014).
3.4 |Quantitative synthesis
Forest plot diagrams, influence analysis, and metaanalysis and
leaveoneout sensitivity analysis on our outcomes are depicted in
Figures 27 and S1S3 and Table 2, respectively.
3.5 |Metaanalysis for WC
No significant reduction of WC measurement is revealed in the treat-
ment group in comparison with the placebo group (p= 0.6); (WMD):
0.40 cm (95% confidence intervals [95% CI]: 1.95, 1.13). No hetero-
geneity was detected in the analysis (n=4,I
2
= 0.0%; p= 0.59;
Figure 2, Table 2).
4AZHDARI ET AL.
TABLE 1 Characteristics of trials included in the metaanalysis
Reference
MetS
diagnostic
criteria Location
Mean
age
No. of
participant
(intervention/control)
Sex
(female/male)
Type of
intervention/placebo
Dose of
intervention
(mg/day)
Duration
of study
(weeks) Side effects Outcome
Panahi et al.
(2014)
NCEP
ATP III
Iran 44.13 50/50 50/50 Curcuminoid
supplement/lactose
1000 8 Gastrointestinal LDLC, HDLC, Lp(a), sdLDL, TG, T.chol
Yang et al.
(2014)
NCEP
ATP III
Taiwan 59.32 30/29 36/23 Supplement of curcumin
extract/placebo
1890 12 Stomach pain,
mild diarrhea,
nausea
Weight, BMI, FBG, HbA1c, LDLC, HDLC,
nonHDLC, TG, T.chol, T.chol/HDL, VLDL
Panahi et al.
(2015)
NCEP
ATP III
Iran 44.13 50/50 50/50 Curcuminoid
supplement/lactose
1000 8 Gastrointestinal FBG, HbA1c, SBP, DBP, SOD, MDA
Pierro et al.
(2015)
NCEP
ATP III
Italy 40.47 22/22 27/17 Curcumin supplement/
phosphatidylserine
800 4 None Weight, BMI, WC, HC, FAT%
Amin et al.
(2015)
NCEP
ATP III
Pakistan 44 56/52 0/108 Supplement of turmeric
powder/ispaghula
husk capsule
2400 8 Dyspepsia Weight, BMI, WC, HC, FBG, FAT%, SBP, DBP, CBC,
LDLC, HDLC, Lp(a), sdLDL, TG, T.chol, Apo A,
Apo B, Lp(a)
Salimi
Avansar
(2017)
NCEP
ATP III
Iran 48 10/10 0/20 Curcumin supplement/
placebo
20 mg/kg 8 None Weight, BMI, WC, FBG, FAT%, BP, HDLC, TG
Saberi
Karimian
et al.
(2018)
IDF Iran 38.05 36/36 61/11 Curcumin supplement/
(lactose and starch)
1,000 6 None Weight, BMI, WC, FBG, HsCRP, FAT%, SBP, DBP,
CBC, LDLC, HDLC, Lp(a), sdLDL, TG, T.chol,
Apo A, Apo B, Lp(a)
Note. MetS: metabolic syndrome; LDLC: lowdensity lipoprotein cholesterol; HDLC: highdensity lipoprotein cholesterol; Lp(a): lipoprotein(a); sdLDL: small dense LDL cholesterol; TG: triglyceride; T.chol: total
cholesterol; BMI: body mass index; FBG: fasting blood glucose; HbA1c: hemoglobin A1c, LDLC; non HDLC: nonhighdensity lipoprotein cholesterol; VLDL: verylowdensity lipoprotein; BP: blood pressure;
SBP: systolic blood pressure; DBP: diastolic blood pressure; SOD: superoxide dismutase; MDA: malondialdehyde; WC: waist circumference; HC: hip circumference; Apo A: apolipoprotein A; Apo B: apolipopro-
tein B; CBC: complete blood count; HsCRP: highsensitivity Creactive protein.
AZHDARI ET AL.5
Overall (I-squared = 0.0%, p = 0.595)
ID
DI Pierro F et al (2015)
Salimi Avansar M et al (2017)
Saberi-Karimian M et al (2018)
Amin F et al (2015)
Study
-0.41 (-1.95, 1.13)
WMD (95% CI)
-3.40 (-8.65, 1.85)
-1.53 (-6.11, 3.05)
0.27 (-1.79, 2.33)
-0.39 (-3.53, 2.75)
0105-5-10
Intervention Placebo
FIGURE 2 Forest plot detailing weighted mean differences (WMD) and 95% confidence intervals for the impact of curcumin supplementation on
waist circumference [Colour figure can be viewed at wileyonlinelibrary.com]
NOTE: Weights are from random effects analysis
Overall (I-squared = 90.1%, p = 0.000)
ID
Yi-Sun Yang (2014)
Amin F et al (2015)
Salimi Avansar M et al (2017)
Saberi-Karimian M et al (2018)
Panahi Y et al (2015)
Study
-9.18 (-16.70, -1.66)
WMD (95% CI)
-4.72 (-6.99 , -2.45)
2.10 (-0.80, 5.00)
-33.60 (-51.11 , -16.09)
-2.06 (-10.34, 6.22)
-31.36 (-45.94 , -16.78)
050-50 25-25
Intervention Placebo
FIGURE 3 Forest plot detailing weighted mean differences (WMD) and 95% confidence intervals for the impact of curcumin supplementation on
fasting blood glucose [Colour figure can be viewed at wileyonlinelibrary.com]
Overall (I- squared = 48.2%, p = 0.145)
Study
Panahi Y et al (2015)
Amin F et al ( 2015)
ID
Saberi-Karim ian M et al (2018)
-1.69 (-4.68, 1.30 )
-2.06 (-8.84, 4.72 )
-4.40 (-8.75, -0.0 5)
WMD (95% CI)
2.38 (-2.81, 7.57)
010-10 5-5
Intervention Placebo
FIGURE 4 Forest plot detailing weighted mean differences (WMD) and 95% confidence intervals for the impact of curcumin supplementation on
systolic blood pressure [Colour figure can be viewed at wileyonlinelibrary.com]
6AZHDARI ET AL.
Overall (I-squared = 48.7%, p = 0.142)
ID
Study
Saberi-Karim ian M et al (2018)
Panahi Y et al (2015)
Amin F et al (2015)
-2.96 (-5.09, -0.83 )
WMD (95% CI)
1.30 (-3.44, 6.04)
-3.94 (-7.94, 0.06 )
-4.10 (-7.08, -1.12 )
00 10
5
-10 -5
Intervention Placebo
FIGURE 5 Forest plot detailing weighted mean differences (WMD) and 95% confidence intervals for the impact of curcumin supplementation on
diastolic blood pressure [Colour figure can be viewed at wileyonlinelibrary.com]
NOTE: Weights are f rom random effects analysis
Overall (I-squared = 94.4%, p = 0.000)
Yi-Sun Yang (2014)
Panahi Y et al (2014)
Saberi-Karimian M et al (2018)
Amin F et al (2015)
Study
ID
Salimi Avansar M et al (2017)
-33.66 (-51.28 , -16.04)
-50.51 (-61.32 , -39.70)
-18.14 (-23.46 , -12.82)
-69.50 (-87.82 , -51.18)
-8.40 (-14.83, -1.97)
WMD (95% CI)
-27.95 (-45.06 , -10.84)
010050-50-100
Intervention Placebo
FIGURE 6 Forest plot detailing weighted mean differences (WMD) and 95% confidence intervals for the impact of curcumin supplementation on
triglyceride [Colour figure can be viewed at wileyonlinelibrary.com]
Overall (I-squared = 98.6%, p = 0.000)
Salimi Avansar M et al (2017)
ID
Amin F et al (2015 )
Panahi Y et al (2014)
Yi-Sun Yang (2014)
Study
Saberi-Karimian M et al (2018)
4.89 (4.59, 5.18)
8.20 (7.71, 8.69)
WMD (95% CI)
2.60 (2.13, 3.07)
4.26 (3.12, 5.40)
3.36 (2.64, 4.08)
2.65 (-1.20, 6.50)
100.00
36.65
Weight
39.59
6.64
16.53
%
0.58
0 105-5-10
Intervention
Placebo
FIGURE 7 Forest plot detailing weighted mean differences (WMD) and 95% confidence intervals for the impact of curcumin supplementation on
highdensity lipoprotein [Colour figure can be viewed at wileyonlinelibrary.com]
AZHDARI ET AL.7
3.6 |Metaanalysis for FBS
The effect of curcumin on FBS levels has shown a significant reduc-
tion in comparison with placebo (p= 0.01); WMD: 9.17 (95% CI
[16.69, 1.65]; Figure 3). The randomeffect metaanalysis was used
to estimate of intervention effect. Influence analysis showed that
three studies affected the overall result (Panahi et al., 2015; Salimi
Avansar, 2017; Yang et al., 2014; Figure S2). So sensitivity analysis
was tested through the leaveoneout analyses to explore the source
of heterogeneity observed in the FBS analysis (n=5,I
2
= 90.1%;
p< 0.001). The heterogeneity did not change by sensitivity analysis.
Moreover, sensitivity analysis by excluding trials by Amin et al.
(2015; turmeric used as a supplement) and SaberiKarimian et al.
(2018; duration of RCT was 6 weeks; Table 2) did not change results
significantly.
3.7 |Metaanalysis for BP
SBP was not significantly changed by the intervention effect
of curcumin (p= 0.269); WMD: 1.68 (95% CI [4.68, 1.3]). DBP
showed a significant reduction (p= 0.007); WMD: 2.96 (95%
CI [5.09, 0.82]). No significant heterogeneity was found in the
metaanalysis of SBP and DBP (n=3,I
2
= 48%; p= 0.14; Figures 4
and 5, Table 2).
3.8 |Metaanalysis for TG
The randomeffect model of the metaanalysis showed a significant
decrease in TG levels (p< 0.001); WMD: 33.65 (95% CI [51.27,
16.03]) with significant heterogeneity (n=4,I
2
= 94.4%; p< 0.001;
Figure 6). In influence analysis, no one study changed the overall
effect of curcumin on pooled serum TG (Figure S2). The leaveone
out analyses were performed for two studies, one of them due to tur-
meric used as a supplement (Amin et al., 2015) and another one
because of the duration of the RCT was less than 8 weeks (6 weeks)
(SaberiKarimian et al., 2018). Any study did not contribute to
betweenstudy heterogeneity (Table 2).
3.9 |Metaanalysis for HDL
For HDL measurements, the randomeffect model of metaanalysis
revealed a significant increase in the intervention group in comparison
with placebo (p= 0.003); WMD: 4.31 (95% CI [1.50, 7.11]). Heteroge-
neity was significant in the HDL analysis (n=5,I
2
= 98.6%; p< 0.001;
Figure 7). By influence analysis, no one study changed the overall
results (Figure S3), but sensitivity analysis was performed through
the leaveoneout analyses of two studies by removing the study by
turmeric used as a supplement (Amin et al., 2015) and duration of
RCT was 6 weeks (Saberi_Karimian et al., 2018) . Any study did not
contribute to betweenstudy heterogeneity (Table 2).
4|DISCUSSION
In this systematic review with metaanalyses, the effect of curcumin
supplement on FBS, TG, HDL, WC, and BP levels in patients with
MetS were evaluated through an analysis of seven RCTs. The least
duration of these studies was 6 weeks. The results showed significant
improvement of FBS, TG, HDL, and DBP levels. Curcumin supplemen-
tation was not associated with a significant change in WC measure-
ments and SBP levels. The observed heterogeneity across studies
may be related to studying population (different races, age, sex, sever-
ity of disease, and body mass index [BMI]) and type of intervention
(different doses and duration) that were not detected by performing
a sensitivity analysis for FBS, TG, and HDL.
In an RCT that was published in 2013, the results of curcumin sup-
plement for 3 months in 100 patients with overweight/obese type 2
diabetes showed a significant decrease in FBS, HbA1c, HOMAIR,
serum total free fatty acids, and TG and an increase in lipoprotein
lipase activity. Antidiabetic effect of curcumin supplement, at least in
part, is due to decreasing in serum free fatty acids (Na et al., 2013).
The possible mechanisms of the effect of curcumin on glycemia in
human/animal diabetes models and in vitro may be understood as fol-
lows: (a) decrease tumor necrosis factorα(TNFα) levels (ElAzab
et al., 2011; ElMoselhy et al., 2011), (b) decrease plasma free fatty
acids (ElMoselhy et al., 2011); through increasing peroxisomal fatty
acid βoxidation) (Asai & Miyazawa, 2001); (c) attenuate oxidative
stress (Murugan & Pari, 2007); (d) decrease circulating concentrations
of resistin and fetuinA (Sahebkar, 2014b); (e) inhibit nuclear factor
kappa B (NFκB) activation (Soetikno et al., 2011), (f) inhibit protein
carbonyl (Suryanarayana et al., 2007); (g) inhibits lipid peroxidation
(ElAzab, Attia, & ElMowafy, 2011), (h) inhibits lysosomal enzyme
activities (Chougala et al., 2012); (i) induce the mRNA and protein
expression of PPARγ(Nishiyama et al., 2005; Pan et al., 2017); (j)
active nuclear factor erythroid2related factor2 (Nrf2) function
(He et al., 2012); (k) increase plasma insulin level lipoprotein lipase
activity (Seo et al., 2008); (l) downregulation of JNK phosphorylation
and activity (ShaoLing et al., 2009).
In other RCT, the effects of curcumin supplement (1 g/day for
30 days) on dyslipidemia in the patients with obesity led to a signif-
icant reduction in serum TG concentrations but did not show a sig-
nificant change on serum total cholesterol, LDLC, HDLC, and hs
CRP concentrations, nor on BMI and body fat (Akram Mohammadi
et al., 2013). Moreover, the findings of a study confirmed the effi-
cacy of curcumin supplementation in significantly reducing liver fat
content, BMI, and serum levels of total cholesterol, LDLC, TG, glu-
cose, and HbA1c of patients with nonalcoholic fatty liver disease
and MetS (Rahmani et al., 2016). The multiple mechanisms of
curcumin on lipids may be explained as follows: (a) decrease oxida-
tive stress (Lin et al., 2009); (b) inhibit membrane translocation and
GLUT2mediated gene expression; (c) increase expression of the
advanced glycation end products receptor (Lin et al., 2012); (d)
increase expression LDLreceptor (enhance plasma removal and bili-
ary excretion of cholesterol) (Sahebkar, 2014b); (e) increase expres-
sion of genes involved in lipid accumulation (Hegarty et al., 2003);
8AZHDARI ET AL.
(f) stimulate the activity of PPARγ(Hegarty et al., 2003); (g) activate
the process of lipolysis of TGs (Pan et al., 2017; VázquezVela et al.,
2008); (h) regulate adipocyte differentiation and macrophage activa-
tion (Gonzales & Orlando, 2008; Gustafson & Smith, 2006); (i) inhibit
the foam cell formation (Li et al., 2004); (j) decrease intestinal
absorption of cholesterol (Sahebkar, 2014b); (k) downregulate sev-
eral enzymes and receptors involved in lipogenesis (Sahebkar,
2014a); (l) stimulate fatty acid oxidation, 13reduce glycerol lipid
synthesis (Ejaz et al., 2009). However, it is unclear which mechanism
will have the most important impact.
The expression of PPARγand C/EBPαin mice and in adipocytes
(3T3L1 cells) by curcumin improved insulin resistance, glucose uptake
(Pan et al., 2017), lipolysis of circulating TGs, and their storage in adi-
pose tissue (Kim et al., 2013; B. Lee et al., 2014). But a dose of
curcumin is important for upregulating the protein expression of
PPARγand C/EBPαin adipocytes, and a high dose of curcumin was
ineffective in the adipocyte (Pan et al., 2017).
Curcumin can effect on blood pressure through different mecha-
nisms such as (a) decrease oxidative stress (Panahi et al., 2015) (the
oxidative stress can effect on the sympathetic activity and cause neu-
rogenic hypertension). (Wu et al., 2012); (b) reduce inflammatory
markers (Jurenka, 2009; Lee et al., 2016; Panahi et al., 2015); (c)
increasing nitric oxide bioavailability (improves resistance artery endo-
thelial function) (SantosParker et al., 2017); (d) inhibit angiotensin
TABLE 2 Metaanalysis and leaveoneout sensitivity analysis for the impact of curcumin on metabolic factors
No. of
participants
(curcumin/control)
No.
of
trials
Quantitative data synthesis Heterogeneity analysis
WMD 95% CI Zvalue pvalue df (Q)I
2
(%) pvalue
WC
Overall effect 124/120 4 0.409 1.951, 1.132 0.52 0.60 3 0.0 0.59
FBS
Overall effect 182/177 5 9.17 16.69, 1.65 2.39 0.01 4 90.1 <0.001
Leaveoneout sensitivity analysis
Yang et al. (2014) 152/148 4 14.244 29.389, 0.902 1.84 0.06 3 91.2 <0.001
Panahi et al. (2015) 132/127 4 4.870 11.606, 1.867 1.42 0.15 3 88.2 <0.001
Amin et al. (2015) 126/125 4 5.554 7.703, 0.406 5.07 <0.001 3 87 <0.001
Salimi Avansar (2017) 172/167 4 5.568 12.518, 1.382 1.57 0.11 3 89.4 <0.001
SaberiKarimian et al. (2018) 146/141 4 2.874 4.639, 1.110 3.19 <0.001 3 92.6 <0.001
SBP
Overall effect 142/138 3 1.68 4.68, 1.30 1.11 0.269 2 48.2 0.14
DBP
Overall effect 142/138 3 2.96 5.09, 0.82 2.72 0.007 2 48.7 0.142
TG
Overall effect 182/177 5 33.65 51.27, 16.03 3.74 <0.001 4 94.4 <0.001
Leaveoneout sensitivity analysis
Amin et al. (2015) 126/125 4 27.345 31.802, 22.888 12.03 <0.001 3 93.9 <0.001
SaberiKarimian et al. (2018) 146/141 4 19.186 22.924, 15.447 10.06 <0.001 3 93.2 <0.001
HDLC
Overall effect 182/177 5 4.31 1.50, 7.11 3.01 0.00 4 98.6 <0.001
Leaveoneout sensitivity analysis
Amin et al. (2015) 126/125 4 6.389 6.010, 6.767 33.04 <0.001 3 97.8 <0.001
SaberiKarimian et al. (2018) 146/141 4 4.902 4.607, 5.197 32.52 <0.001 3 99.0 <0.001
Note. WC: waist circumference; FBS: fasting blood sugar; SBP: systolic blood pressure;, DBP: Diastolic Blood Pressure; TG: Triglycerides; HDLC; highden-
sity lipoprotein cholesterol.
AZHDARI ET AL.9
converting enzyme (Rachmawati et al., 2016). But in this review,
curcumin did not show significant improvement in SBP between inter-
vention and placebo groups. This inconsistent results can be due to
different baseline BP levels, different doses of curcumin
(Jariyapongskul et al., 2018), small sample size, and few studies. The
baseline blood pressure was in prehypertension level in the Saberi
Karimian et al.,2018 study, but it was normal in two trials (Amin
et al., 2015; Panahi et al., 2015). Therefore, more trials on hyperten-
sive participants should address this concern.
This systematic review had several limitations: first of all, two
included studies did not adjust baseline BMI of patients between
intervention and placebo groups (Panahi et al., 2015; Panahi et al.,
2014). The baseline BMI may be a possible cofounder, and therefore,
there is an increased risk of bias in two studies. This is the main limi-
tation of our study. Second, the participants had a wide range of
BMI from normal to obesity grade 1. Third, one trial with small sample
size was included in the metaanalysis (N= 20); (Salimi Avansar, 2017).
Fourth, heterogeneity among studies was relatively high, regardless of
the study design and sensitivity analyses. Possible reasons for hetero-
geneity include heterogeneous geographical populations, sample size,
the composition of curcumin, duration of intervention, and the status
of participants. Fifth, we could not perform subgroup analysis by a
dose of curcumin and duration of intervention, due to lack of the num-
ber of studies. Sixth, the bioavailability of curcumin has not been eval-
uated in any of the included studies.
5|CONCLUSION
This metaanalysis provided evidence that curcumin supplement has
beneficial effects in patients with MetS. Future RCTs should focus
on the limitations of the present review. More studies should be
carried out with large sample size, among different ethnic groups, dif-
ferent doses and types of the supplement (for access to high solubility
and bioavailability curcumin), adjusting BMI for the target population,
and different age groups. In addition, more detailed studies are
required to assess the amount of turmeric/curcumin during the course
of the trial in order to normalize its dietary intake between treatment
and control groups. This limitation may be solved by carrying out
crossover RCTs. It also seems necessary to design studies to evaluate
the cellular and molecular mechanisms of the effect of curcumin on
metabolic factors in patients with MetS.
AUTHORS' CONTRIBUTION
A. M. and M. A. synthesized the literature. A. M. analyzed the data.
M. A. and A. M. were involved in drafting the paper and conceptual
input. M. K. participated in the coordination. All authors read and
approved the final paper.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
ORCID
Maryam Azhdari https://orcid.org/0000-0003-2110-9817
REFERENCES
Alberti, K. G., Zimmet, P., Shaw, J., & Grundy, S. M. (2006). The IDF consen-
sus worldwide definition of the metabolic syndrome. Brussels:
International Diabetes Federation,23(5), 469480.
Alberti, K. G., Zimmet, P., & Shaw, J. (2005). The metabolic syndromeA
new worldwide definition. Lancet,366(9491), 10591062. https://doi.
org/10.1016/S01406736(05)674028
Amin, F., Islam, N., Anila, N., & Gilani, A. (2015). Clinical efficacy of the
coadministration of Turmeric and Black seeds (Kalongi) in metabolic
syndromeA double blind randomized controlled trialTAKMetS trial.
Complementary Therapies in Medicine,23(2), 165174. https://doi.org/
10.1016/j.ctim.2015.01.008
Asai, A., & Miyazawa, T. (2001). Dietary curcuminoids prevent highfat
dietinduced lipid accumulation in rat liver and epididymal adipose tis-
sue. The Journal of Nutrition,131(11), 29322935. https://doi.org/
10.1093/jn/131.11.2932
CamposCervantes, A., MurilloOrtiz, B. O., AlvaradoCaudillo, Y., Perez
Vazquez, V., & RamirezEmiliano, J. (2011). Curcumin decreases the
oxidative damage indexes and increases the adiponectin levels in
serum of obese subjects. Free Radical Biology and Medicine,51, S95.
https://doi.org/10.1016/j.freeradbiomed.2011.10.463
Chougala, M. B., Bhaskar, J. J., Rajan, M., & Salimath, P. V. (2012). Effect of
curcumin and quercetin on lysosomal enzyme activities in
streptozotocininduced diabetic rats. Clinical Nutrition,31(5),
749755. https://doi.org/10.1016/j.clnu.2012.02.003
Chuengsamarn, S., Rattanamongkolgul, S., Luechapudiporn, R.,
Phisalaphong, C., & Jirawatnotai, S. (2012). Curcumin extract for pre-
vention of type 2 diabetes. Diabetes Care,35(11), 21212127.
https://doi.org/10.2337/dc120116
Cicero, A. F., & Colletti, A. (2016). Role of phytochemicals in the manage-
ment of metabolic syndrome. Phytomedicine,23(11), 11341144.
https://doi.org/10.1016/j.phymed.2015.11.009
Cicero, A. F. G., Fogacci, F., Morbini, M., Colletti, A., Bove, M., Veronesi, M.,
Borghi, C. (2017). Nutraceutical effects on glucose and lipid metabo-
lism in patients with impaired fasting glucose: A pilot, doubleblind,
placebocontrolled, randomized clinical trial on a combined product.
High Blood Pressure & Cardiovascular Prevention,24(3), 283288.
https://doi.org/10.1007/s4029201702063
Colalto, C. (2018). What phytotherapy needs: Evidencebased guidelines
for better clinical practice. Phytotherapy Research,32(3), 413425.
https://doi.org/10.1002/ptr.5977
Deepa, M., Farooq, S., Datta, M., Deepa, R., & Mohan, V. (2007). Preva-
lence of metabolic syndrome using WHO, ATPIII and IDF definitions
in Asian Indians: The Chennai Urban Rural Epidemiology Study
(CURES34). Diabetes/Metabolism Research and Reviews,23(2),
127134. https://doi.org/10.1002/dmrr.658
Egger, M., Smith, G. D., Schneider, M., & Minder, C. (1997). Bias in meta
analysis detected by a simple, graphical test. Biritish Medical Journal,
315(7109), 629634. https://doi.org/10.1136/bmj.315.7109.629
Ejaz, A., Wu, D., Kwan, P., & Meydani, M. (2009). Curcumin inhibits adipo-
genesis in 3T3L1 adipocytes and angiogenesis and obesity in C57/BL
mice. The Journal of Nutrition,139(5), 919925. https://doi.org/
10.3945/jn.108.100966
ElAzab, M. F., Attia, F. M., & ElMowafy, A. M. (2011). Novel role of
curcumin combined with bone marrow transplantation in reversing
experimental diabetes: Effects on pancreatic islet regeneration, oxida-
tive stress, and inflammatory cytokines. European Journal of
10 AZHDARI ET AL.
Pharmacology,658(1), 4148. https://doi.org/10.1016/j.ejphar.2011.
02.010
ElMoselhy, M. A., Taye, A., Sharkawi, S. S., ElSisi, S. F., & Ahmed, A. F.
(2011). The antihyperglycemic effect of curcumin in high fat diet fed
rats. Role of TNFαand free fatty acids. Food and Chemical Toxicology,
49(5), 11291140. https://doi.org/10.1016/j.fct.2011.02.004
Esmaily, H., Sahebkar, A., Iranshahi, M., Ganjali, S., Mohammadi, A., Ferns,
G., & GhayourMobarhan, M. (2015). An investigation of the effects
of curcumin on anxiety and depression in obese individuals: A random-
ized controlled trial. Chinese Journal of Integrative Medicine,21(5),
332338. https://doi.org/10.1007/s116550152160z
Ghosh, M., Singh, A. T., Xu, W., Sulchek, T., Gordon, L. I., & Ryan, R. O.
(2011). Curcumin nanodisks: Formulation and characterization.
Nanomedicine: Nanotechnology, Biology and Medicine,7(2), 162167.
https://doi.org/10.1016/j.nano.2010.08.002
Gonzales, A. M., & Orlando, R. A. (2008). Curcumin and resveratrol inhibit
nuclear factorκBmediated cytokine expression in adipocytes. Nutri-
tion & Metabolism,5(1), 17. https://doi.org/10.1186/17437075517
Gustafson, B., & Smith, U. (2006). Cytokines promote Wnt signaling and
inflammation and impair the normal differentiation and lipid accumula-
tion in 3T3L1 preadipocytes. Journal of Biological Chemistry,281,
95079516. https://doi.org/10.1074/jbc.M512077200
He, H.J., Wang, G.Y., Gao, Y., Ling, W.H., Yu, Z.W., & Jin, T.R. (2012).
Curcumin attenuates Nrf2 signaling defect, oxidative stress in muscle
and glucose intolerance in high fat dietfed mice. World Journal of
Diabetes,3(5), 94104. https://doi.org/10.4239/wjd.v3.i5.94
Hegarty, B., Furler, S., Ye, J., Cooney, G., & Kraegen, E. (2003). The role of
intramuscular lipid in insulin resistance. Acta Physiologica Scandinavica,
178(4), 373383. https://doi.org/10.1046/j.1365201X.2003.01162.x
Higgins, J. P., & Green S. (2015). Cochrane handbook for systematic
reviews of interventions version 5.1.0. The Cochrane Collaboration.
Higgins, J. P., & Thompson, S. (2002). Quantifying heterogeneity in a meta
analysis. Statistics in Medicine,21(11), 15391558. https://doi.org/
10.1002/sim.1186
Higgins, J. P., Altman, D. G., Gøtzsche, P. C., Jüni, P., Moher, D., Oxman, A.
D., Sterne, J. A. (2011). The Cochrane Collaboration's tool for
assessing risk of bias in randomised trials. Biritish Medical Journal,
343, d5928. https://doi.org/10.1136/bmj.d5928
Hosseini, A., & Hosseinzadeh, H. (2018). Antidotal or protective effects of
Curcuma longa (turmeric) and its active ingredient, curcumin, against
natural and chemical toxicities: A review. Biomedicine & Pharmacother-
apy,99, 411421. https://doi.org/10.1016/j.biopha.2018.01.072
Ismail, N. A., Abd El Dayem, S. M., Salama, E., Ragab, S., El Baky, A. N., &
Ezzat, W. M. (2016). Impact of curcumin intake on glucoinsulin
homeostasis, leptin and adiponectin in obese subjects. Research Journal
of Pharmaceutical, Biological and Chemical Sciences,7(1), 18911897.
Izzo, A. A., HoonKim, S., Radhakrishnan, R., & Williamson, E. M. (2016). A
critical approach to evaluating clinical efficacy, adverse events and drug
interactions of herbal remedies. Phytotherapy Research,30(5),
691700. https://doi.org/10.1002/ptr.5591
Jariyapongskul, A., Areebambud, C., & Hideyuki, N. (2018).
Microhemodynamic indices to evaluate the effectiveness of herbal
medicine in diabetes: A comparison between alphamangostin and
curcumin in the retina of type 2 diabetic rats. Clinical Hemorheology
and Microcirculation,69(4), 471480. https://doi.org/10.3233/CH
170345
Jurenka, J. S. (2009). Antiinflammatory properties of curcumin, a major
constituent of Curcuma longa: A review of preclinical and clinical
research. Alternative Medicine Review,14(2), 141153.
Kelliny, C., William, J., Riesen, W., Paccaud, F., & Bovet, P. (2008). Meta-
bolic syndrome according to different definitions in a rapidly
developing country of the African region. Cardiovascular Diabetology,
7, 27. https://doi.org/10.1186/14752840727
Kim, H.S., Hwang, Y.C., Koo, S.H., Park, K. S., Lee, M.S., Kim, K.W., &
Lee, M.K. (2013). PPARγactivation increases insulin secretion
through the upregulation of the free fatty acid receptor GPR40 in pan-
creatic βcells. PLoS ONE,8(1), e50128. https://doi.org/10.1371/
journal.pone.0050128
Kocher, A., Bohnert, L., Schiborr, C., & Frank, J. (2016). Highly bioavailable
micellar curcuminoids accumulate in blood, are safe and do not reduce
blood lipids and inflammation markers in moderately hyperlipidemic
individuals. Molecular Nutrition & Food Research,60(7), 15551563.
https://doi.org/10.1002/mnfr.201501034
Lee, B., Qiao, L., Lu, M., Yoo, H. S., Cheung, W., Mak, R., Shao, J. (2014).
C/EBPαregulates macrophage activation and systemic metabolism.
American Journal of PhysiologyEndocrinology and Metabolism,306(10),
E1144E1154. https://doi.org/10.1152/ajpendo.00002.2014
Lee, H. Y., Kim, S. W., Lee, G. H., Choi, M. K., Jung, H. W., Kim, Y. J.,
Chae, H. J. (2016). Turmeric extract and its active compound, curcumin,
protect against chronic CCl 4induced liver damage by enhancing anti-
oxidation. BMC Complementary and Alternative Medicine,16(1), 316.
https://doi.org/10.1186/s1290601613076
Li, L., Sawamura, T., & Renier, G. (2004). Glucose enhances human macro-
phage LOX1 expression: role for LOX1 in glucoseinduced
macrophage foam cell formation. Circulation Research,94(7),
892901. https://doi.org/10.1161/01.RES.0000124920.09738.26
Lin, J., Tang, Y., Kang, Q., Feng, Y., & Chen, A. (2012). Curcumin inhibits
gene expression of receptor for advanced glycation endproducts
(RAGE) in hepatic stellate cells in vitro by elevating PPARγactivity
and attenuating oxidative stress. British Journal of Pharmacology,
166(8), 22122227. https://doi.org/10.1111/j.14765381.2012.
01910.x
Lin, J., Zheng, S., & Chen, A. (2009). Curcumin attenuates the effects of
insulin on stimulating hepatic stellate cell activation by interrupting
insulin signaling and attenuating oxidative stress. Laboratory Investiga-
tion,89(12), 13971409. https://doi.org/10.1038/labinvest.2009.115
Maithili Karpaga Selvi, N., Sridhar, M. G., Swaminathan, R. P., & Sripradha,
R. (2015). Efficacy of turmeric as adjuvant therapy in type 2 diabetic
patients. Indian Journal of Clinical Biochemistry,30(2), 180186.
https://doi.org/10.1007/s1229101404362
Mohammadi, A., Sadeghnia, H. R., SaberiKarimian, M., Safarian, H., Ferns,
G. A., GhayourMobarhan, M., & Sahebkar, A. (2017). Effects of
curcumin on serum vitamin E concentrations in individuals with meta-
bolic syndrome. Phytotherapy Research,31(4), 657662. https://doi.
org/10.1002/ptr.5779
Mohammadi, A., Sahebkar, A., Iranshahi, M., Amini, M., Khojasteh, R.,
GhayourMobarhan, M., & Ferns, G. A. (2013). Effects of supplementa-
tion with curcuminoids on dyslipidemia in obese patients: A
randomized crossover trial. Phytotherapy Research,27(3), 374379.
https://doi.org/10.1002/ptr.4715
Moher, D., Liberati, A., Tetzlaff, J., & Altman, D. G. (2009). Group P (2009)
Preferred reporting items for systematic reviews and metaanalyses:
The PRISMA statement. British Medical Journal, 339: b2535. https://
doi.org/10.1136/bmj.b2535.
Murugan, P., & Pari, L. (2007). Influence of tetrahydrocurcumin on erythro-
cyte membrane bound enzymes and antioxidant status in experimental
type 2 diabetic rats. Journal of Ethnopharmacology,113(3), 479486.
https://doi.org/10.1016/j.jep.2007.07.004
Na, L. X., Li, Y., Pan, H. Z., Zhou, X. L., Sun, D. J., Meng, M., Sun, C. H.
(2013). Curcuminoids exert glucoselowering effect in type 2 diabetes
AZHDARI ET AL.11
by decreasing serum free fatty acids: A doubleblind, placebo
controlled trial. Molecular Nutrition & Food Research,57(9),
15691577. https://doi.org/10.1002/mnfr.201200131
Nelson, K. M., Dahlin, J. L., Bisson, J., Graham, J., Pauli, G. F., & Walters, M.
A. (2017). The essential medicinal chemistry of curcumin. Journal of
Medicinal Chemistry,60(5), 16201637. https://doi.org/10.1021/acs.
jmedchem.6b00975
Nishiyama, T., Mae, T., Kishida, H., Tsukagawa, M., Mimaki, Y., Kuroda, M.,
Kitahara, M. (2005). Curcuminoids and sesquiterpenoids in turmeric
(Curcuma longa L.) suppress an increase in blood glucose level in type
2 diabetic KKA
y
mice. Journal of Agricultural and Food Chemistry,
53(4), 959963. https://doi.org/10.1021/jf0483873
Pan, Y., Zhao, D., Yu, N., An, T., Miao, J., Mo, F., Jiang, G. (2017).
Curcumin improves glycolipid metabolism through regulating peroxi-
some proliferator activated receptor γsignalling pathway in highfat
dietinduced obese mice and 3T3L1 adipocytes. Royal Society Open
Science,4(11), 170917. https://doi.org/10.1098/rsos.170917
Panahi, Y., Ahmadi, Y., Teymouri, M., Johnston, T. P., & Sahebkar, A. (2018).
Curcumin as a potential candidate for treating hyperlipidemia: A review
of cellular and metabolic mechanisms. Journal of Cellular Physiology,
233(1), 141152. https://doi.org/10.1002/jcp.25756
Panahi, Y., Hosseini, M., Khalili, N., Naimi, E., Majeed, M., & Sahebkar, A.
(2015). Antioxidant and antiinflammatory effects of curcuminoid
piperine combination in subjects with metabolic syndrome: A random-
ized controlled trial and an updated metaanalysis. Clinical Nutrition,
34(6), 11011108. https://doi.org/10.1016/j.clnu.2014.12.019
Panahi, Y., Khalili, N., Hosseini, M. S., Abbasinazari, M., & Sahebkar, A.
(2014). Lipidmodifying effects of adjunctive therapy with
curcuminoidspiperine combination in patients with metabolic syn-
drome: Results of a randomized controlled trial. Complementary
Therapies in Medicine,22(5), 851857. https://doi.org/10.1016/j.
ctim.2014.07.006
Panahi, Y., Khalili, N., Sahebi, E., Namazi, S., Karimian, M. S., Majeed, M., &
Sahebkar, A. (2017a). Antioxidant effects of curcuminoids in patients
with type 2 diabetes mellitus: A randomized controlled trial.
Inflammopharmacology,25(1), 2531. https://doi.org/10.1007/
s1078701603014
Panahi, Y., Khalili, N., Sahebi, E., Namazi, S., Reiner, Z., Majeed, M., &
Sahbekar, A. (2017b). Curcuminoids modify lipid profile in type 2 diabe-
tes mellitus: A randomized controlled trial. Complementary Therapies in
Medicine,33,15. https://doi.org/10.1016/j.ctim.2017.05.006
Patti, A. M., AlRasadi, K., Giglio, R. V., Nikolic, D., Mannina, C., Castellino,
G., Toth, P. P. (2018). Natural approaches in metabolic syndrome
management. Archives of Medical Science: AMS,14(2), 422441.
https://doi.org/10.5114/aoms.2017.68717
Pierro, F., Bressan, A., Ranaldi, D., Rapacioli, G., Giacomelli, L., &
Bertuccioli, A. (2015). Potential role of bioavailable curcumin in weight
loss and omental adipose tissue decrease: Preliminary data of a ran-
domized, controlled trial in overweight people with metabolic
syndrome. Preliminary study. European Review for Medical and Pharma-
cological Sciences,19(21), 41954202.
Prasad, S., Tyagi, A. K., & Aggarwal, B. B. (2014). Recent developments in
delivery, bioavailability, absorption and metabolism of curcumin: The
golden pigment from golden spice. Cancer Research Treatment,46(1),
218. https://doi.org/10.4143/crt.2014.46.1.2
Qin, S., Huang, L., Gong, J., Shen, S., Huang, J., Ren, H., & Hu, H. (2017).
Efficacy and safety of turmeric and curcumin in lowering blood lipid
levels in patients with cardiovascular risk factors: A metaanalysis of
randomized controlled trials. Nutrition Journal,16(1), 6878. https://
doi.org/10.1186/s129370170293y
Rachmawati, H., Soraya, I. S., Kurniati, N. F., & Rahma, A. (2016). In vitro
study on antihypertensive and antihypercholesterolemic effects of a
curcumin nanoemulsion. Scientia Pharmaceutica,84(1), 131140.
https://doi.org/10.3797/scipharm.ISP.2015.05
Rahimi, H. R., Mohammadpour, A. H., Dastani, M., Jaafari, M. R., Abnous,
K., Mobarhan, M. G., & Kazemi Oskuee, R. (2016). The effect of
nanocurcumin on HbA1c, fasting blood glucose, and lipid profile in
diabetic subjects: A randomized clinical trial. Avicenna Journal of
Phytomedicine,6(5), 567577.
Rahmani, S., Asgary, S., Askari, G., Keshvari, M., Hatamipour, M., Feizi, A., &
Sahebkar, A. (2016). Treatment of nonalcoholic fatty liver disease with
curcumin: A randomized placebocontrolled trial. Phytotherapy
Research,30(9), 15401548. https://doi.org/10.1002/ptr.5659
Rezaianzadeh, A., Namayandeh, S.M., & Sadr, S.M. (2012). National cho-
lesterol education program adult treatment panel III versus
international diabetic federation definition of metabolic syndrome,
which one is associated with diabetes mellitus and coronary artery dis-
ease? International Journal of Preventive Medicine,3(8), 552558.
SaberiKarimian, M., Parizadeh, S. M. R., GhayourMobarhan, M.,
Salahshooh, M. M., Dizaji, B. F., Safarian, H., Ahmadinejad, M.
(2018). Evaluation of the effects of curcumin in patients with metabolic
syndrome. Comparative Clinical Pathology,27(3), 555563. https://doi.
org/10.1007/s005800172624y
Sahebkar, A. (2014a). Curcuminoids for the management of
hypertriglyceridaemia. Nature Reviews Cardiology,11(2), 123. https://
doi.org/10.1038/nrcardio.2013.140c1
Sahebkar, A. (2014b). Lowdensity lipoprotein is a potential target for
curcumin: novel mechanistic insights. Basic & Clinical Pharmacology &
Toxicology,114(6), 437438. https://doi.org/10.1111/bcpt.12212
Salimi Avansar, M. (2017). The effects of eight weeks interval training and
curcumin consumption on TNFαand BDNF levels in men with meta-
bolic syndrome. Journal of Ardabil University of Medical Sciences,17(3),
299310.
Santos, C. M. D. C., Pimenta, C. A. D. M., & Nobre, M. R. C. (2007). The
PICO strategy for the research question construction and evidence
search. Revista LatinoAmericana de Enfermagem,15(3), 508511.
SantosParker, J. R., Strahler, T. R., Bassett, C. J., Bispham, N. Z., Chonchol,
M. B., & Seals, D. R. (2017). Curcumin supplementation improves vascu-
lar endothelial function in healthy middleaged and older adults by
increasing nitric oxide bioavailability and reducing oxidative stress. Aging
(Albany NY),9(1), 187205. https://doi.org/10.18632/aging.101149
Selmanovic, S., Beganlic, A., Salihefendic, N., Ljuca, F., Softic, A., & Smajic,
E. (2017). Therapeutic effects of curcumin on ultrasonic morphological
characteristics of liver in patients with metabolic syndrome. Acta
Informatica Medica,25(3), 169174. https://doi.org/10.5455/
aim.2017.25.169174
Seo, K. I., Choi, M. S., Jung, U. J., Kim, H. J., Yeo, J., Jeon, S. M., & Lee, M. K.
(2008). Effect of curcumin supplementation on blood glucose, plasma
insulin, and glucose homeostasis related enzyme activities in diabetic
db/db mice. Molecular Nutrition & Food Research,52(9), 9951004.
https://doi.org/10.1002/mnfr.200700184
ShaoLing, W., Ying, L., Ying, W., YanFeng, C., LiXin, N., SongTao, L., &
ChangHao, S. (2009). Curcumin, a potential inhibitor of upregulation
of TNFalpha and IL6 induced by palmitate in 3T3L1 adipocytes
through NFkappaB and JNK pathway. Biomedical and Environmental
Sciences,22(1), 3239.
Soetikno, V., Sari, F. R., Veeraveedu, P. T., Thandavarayan, R. A., Harima,
M., Sukumaran, V., Watanabe, K. (2011). Curcumin ameliorates mac-
rophage infiltration by inhibiting NFκB activation and proinflammatory
cytokines in streptozotocin induceddiabetic nephropathy. Nutrition &
Metabolism,8(1), 35. https://doi.org/10.1186/17437075835
12 AZHDARI ET AL.
Soleimani, V., Sahebkar, A., & Hosseinzadeh, H. (2018). Turmeric (Curcuma
longa) and its major constituent (curcumin) as nontoxic and safe sub-
stances. Phytotherapy Research,32(6), 985995. https://doi.org/
10.1002/ptr.6054
Suryanarayana, P., Satyanarayana, A., Balakrishna, N., Kumar, P. U., &
Reddy, G. B. (2007). Effect of turmeric and curcumin on oxidative
stress and antioxidant enzymes in streptozotocininduced diabetic rat.
Medical Science Monitor,13(12), BR286BR292.
Tariq, S., Imran, M., Mushtaq, Z., & Asghar, N. (2016). Phytopreventive
antihypercholesterolmic and antilipidemic perspectives of zedoary
(Curcuma zedoaria Roscoe.) herbal tea. Lipids in Health and Disease,
15(1), 39.
Terrin, N., Schmid, C. H., Lau, J., & Olkin, I. (2003). Adjusting for publication
bias in the presence of heterogeneity. Statistics in Medicine,22(13),
21132126. https://doi.org/10.1002/sim.1461
VázquezVela, M. E. F., Torres, N., & Tovar, A. R. (2008). White adipose tis-
sue as endocrine organ and its role in obesity. Archives of Medical
Research,39(8), 715728. https://doi.org/10.1016/j.arcmed.2008.
09.005
Wilborn, C., Beckham, J., Campbell, B., Harvey, T., Galbreath, M., La
Bounty, P., Kreider, R. (2005). Obesity: Prevalence, theories, medical
consequences, management, and research directions. Journal of the
International Society of Sports Nutrition,2(2), 431. https://doi.org/
10.1186/15502783224
Wu, K. L., Chan, S. H., & Chan, J. Y. (2012). Neuroinflammation and oxida-
tive stress in rostral ventrolateral medulla contribute to neurogenic
hypertension induced by systemic inflammation. Journal of Neuroin-
flammation,9(212), 115.
Yang, Y., Su, Y., Yang, H., Lee, Y., Chou, J., & Ueng, K. (2014). Lipidlower-
ing effects of curcumin in patients with metabolic syndrome: A
randomized, doubleblind, placebocontrolled trial. Phytotherapy
Research,28(12), 17701777. https://doi.org/10.1002/ptr.5197
Zorofchian Moghadamtousi, S., Abdul Kadir, H., Hassandarvish, P., Tajik, H.,
Abubakar, S., & Zandi, K. (2014). A review on antibacterial, antiviral,
and antifungal activity of curcumin. BioMed Research International,
2014, 2014,112. https://doi.org/10.1155/2014/186864
SUPPORTING INFORMATION
Additional supporting information may be found online in the
Supporting Information section at the end of the article.
How to cite this article: Azhdari M, Karandish M, Mansoori A.
Metabolic benefits of curcumin supplementation in patients
with metabolic syndrome: A systematic review and metaanal-
ysis of randomized controlled trials. Phytotherapy Research.
2019;113. https://doi.org/10.1002/ptr.6323
AZHDARI ET AL.13
... Curcumin (CUR), a component of Curcuma longa, is a polyphenolic compound that has long been reputed for its anti-inflammatory, anti-oxidative, and anti-hyperlipidemic potentials (Ahmed-Farid et al., 2017;Azhdari et al., 2019;Manzoni et al., 2019;Nasr et al., 2022). ...
... (Pongchaidecha et al., 2009). In addition, CUR has been formerly used at doses ranging from 40 to 500 mg/kg in various models and proved to be effective in reducing serum ALT, AST levels, ameliorating oxidative stress, inflammation as well as decreasing 8-OHdG level in several organs and counteracting metabolic syndrome (Aggarwal et al., 2013;Azhdari et al., 2019;Cao et al., 2018;Elmansi et al., 2017;Khan et al., 2019;Kim et al., 2015Kim et al., , 2019. It was also demonstrated that CUR nanoparticles at a dose of 15 mg/kg in rats counteracted nano-hydroxyapatite-induced decreased testicular oxidative stress and 8-OHDG level (Yousef et al., 2021). ...
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The relationship between the incidence of cardiovascular abnormalities and non‐alcoholic fatty liver disease (NAFLD) has long been postulated. Curcumin (CUR) is a potential anti‐atherosclerotic agent but its poor water solubility hinders its pharmacological use. Therefore, the present study aimed to investigate the effect of formulation of CUR nanoemulsion prepared using the spontaneous emulsification technique on high fat high fructose (HFHF)‐induced hepatic and cardiac complications. Fifty Wistar rats were divided into five groups. CUR nanoemulsion at doses of 5 and 10 mg/kg and conventional powdered CUR at a dose of 50 mg/kg were orally administered daily to rats for two weeks, and compared with normal control and HFHF control. Results revealed that the high dose level of CUR nanoemulsion was superior to conventional CUR in ameliorating the HFHF‐induced insulin resistance status and hyperlipidemia, with beneficial impact on rats' recorded electrocardiogram (ECG), serum aspartate aminotransferase (ALT) and alanine aminotransferase (AST) levels, leptin, adiponectin, creatine phosphokinase, lactate dehydrogenase and cardiac troponin‐I. In addition, hepatic and cardiac oxidative and nitrosative stresses, oxidative DNA damage and disrupted cellular energy statuses were counteracted. Results were also confirmed by histopathological examination. Practical applications The use of curcumin nanoemulsion could be beneficial in combating hepatic and cardiac complications resulting from HFHF diets.
... Tabrizi et al. reported that curcumin reduced fasting glucose, HbA1c, triglycerides, and total cholesterol in MS patients, although no changes in low density lipoprotein (LDL) and high density lipoprotein (HDL) levels were observed (27). In the other hand, Azhadri et al. found that curcumin improved fasting blood glucose, triglycerides, HDL, and diastolic blood pressure without affecting systolic blood pressure or waist circumference (28). Curcumin supplementation can increase circulating adiponectin in patients with MS, reducing the risk of cardiovascular diseases (29) and promote lipid metabolism and glycemic control in polycystic ovary syndrome (PCOS) patients with no significant adverse effects (30). ...
... Waist circumference was also significantly reduced but there was no clinical data regarding a clinical significance in the hip ratio (84). Azhdari et al. and Altobelli et al. also reported the insignificant effect of curcumin in reducing BMI and waist circumference (28,75), thus the effectiveness of curcumin in improving obesity is unclear. ...
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The metabolic syndrome (MS) is a multifactorial syndrome associated with a significant economic burden and healthcare costs. MS management often requires multiple treatments (polydrug) to ameliorate conditions such as diabetes mellitus, insulin resistance, obesity, cardiovascular diseases, hypertension, and non-alcoholic fatty liver disease (NAFLD). However, various therapeutics and possible drug-drug interactions may also increase the risk of MS by altering lipid and glucose metabolism and promoting weight gain. In addition, the medications cause side effects such as nausea, flatulence, bloating, insomnia, restlessness, asthenia, palpitations, cardiac arrhythmias, dizziness, and blurred vision. Therefore, is important to identify and develop new safe and effective agents based on a multi-target approach to treat and manage MS. Natural products, such as curcumin, have multi-modalities to simultaneously target several factors involved in the development of MS. This review discusses the recent preclinical and clinical findings, and up-to-date meta-analysis from Randomized Controlled Trials regarding the effects of curcumin on MS, as well as the metabonomics and a pharma-metabolomics outlook considering curcumin metabolites, the gut microbiome, and environment for a complementary personalized prevention and treatment for MS management.
... The mean age of participants was from 27 to 60 years. In addition, of these studies, six studies were performed in Iran [5,18,22,23,32,33], six in China [24,34e38], two in Mexico [39,40], one in Thailand [26], one in the USA [41], one in Taiwan [25], one in Malaysia [42] and one in Italy [43]. Supplementation with curcumin was administered from 80 to 1,140 mg/day for 2e14 weeks. ...
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Aims Several meta-analyses exist supporting the beneficial effects of curcumin supplementation on lipid profile parameters; however, some studies' findings are inconsistent. Therefore, the current umbrella of meta-analysis of clinical trials was performed to evaluate the findings of multiple meta-analyses on the efficacy of curcumin on lipid profiles in adults. Data synthesis A comprehensive systematic search of PubMed/Medline, Scopus, Embase, Web of Science and Google Scholar were carried out up to May 2022 (in English only). Random-effects model was employed to conduct meta-analysis. The quality assessment of the selected meta-analyses was measured using a measurement tool to assess multiple systematic reviews (AMSTAR). From 101 articles returned in the literature search, 19 articles were met the qualified for inclusion in the umbrella meta-analysis. The results revealed that the curcumin supplementation was effective on reduction of total cholesterol (TC) (ES= -0.81 mg/dl; 95% CI: -1.39, -0.24, p= 0.006; I²= 68.8%, p<0.001), triglycerides (TG) (ES: -0.84 mg/dl, 95% CI: -1.42, -0.27, p= 0.004; I²=84.2 %, p<0.001), and low-density lipoprotein cholesterol (LDL-C) levels (ES: -0.49 mg/dl, 95%CI: -0.85, -0.13, p=0.007; I² = 51.9%, p= 0.004). Beyond that, Curcumin intake significantly increased high-density lipoprotein cholesterol (HDL-C) levels (ES: 1.34 mg/dl, 95% CI: 0.37, 2.31, p= 0.007; I²= 97.8%, p< 0.001). Conclusion Curcumin have ameliorating effects on TC, TG, LDL-c, and HDL-c levels. Overall, Curcumin could be recommended as an adjuvant anti-hyperlipidemic agent. Registration number PROSPERO, CRD42021289500.
... A meta-analysis of randomized clinical trials' "metabolic benefits of curcumin supplementation in patients with metabolic syndrome" revealed a significant reduction in fasting blood glucose and TG levels, with a considerable increase in HDL levels, while the effects of curcumin on waist circumference and systolic blood pressure were not significant when compared to placebo [81]. It is worth mentioning that the efficacy and potency of curcumin has rarely been compared with the available antidiabetic agents, most probably due to the bioavailability issues of curcumin which may thus require higher doses to produce similar results. ...
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In the bi-hormonal model, insulin and glucagon are the two major glucoregulatory hormones responsible for glucose disappearance and glucose appearance, respectively. The metabolic imbalance triggered by chronic hyperglycemia and hyperlipidemia may result in the impairment of glucose-induced insulin secretion, eventually resulting in the development of diabetes mellitus (DM). Persistent or chronic cases of DM can silently lead to serious complications such as autonomic neuropathy, peripheral neuropathy, nephropathy, atherosclerotic cardiovascular disease, retinopathy, peripheral arterial disease, cerebrovascular events, and increased susceptibility to infections. A range of agents have been approved for the clinical management of DM, but certain limitations remain, including the incidence of adverse drug reactions (ADRs) for almost all antidiabetic medications and a high cost for certain drug classes. Phytonutrients can play a vital role in the maintenance of health and wellness by protecting against chronic degenerative disorders including DM. Having a favorable safety profile and a low cost, they can be used effectively in the form of extracts or as isolated compounds, allowing them to serve as alternate therapeutic agents in glucose metabolic disorders. Thousands of herbs have been suggested for the treatment of DM, and a plethora of combinations of these products are marketed for the purpose of lowering blood glucose levels and for the treatment of diabetes-associated comorbid conditions. With further developments in the available literature, it is possible that one or more of these agents may become a part of conventional antidiabetic therapies. The present chapter highlights the potential hypoglycemic roles of phytonutrients including phenolic compounds, alkaloids, sulfides, phytosterols, dietary fibers, and carotenoids.
... According to a literature review, curcumin can also possess antiinflammatory properties through combating lipopolysaccharide-induced inflammatory pathways. In terms of insulin resistance, a recent meta-analysis of randomized controlled studies reported that high dosages of curcumin or curcumin extract (1 g/day) can reduce glycemia, hypertriglyceridemia, and hypertension in MetS patients [64]. ...
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Metabolic syndrome (MetS) is characterized as a group of cardiometabolic risk factors that raise the risk for heart disease and other health problems, such as diabetes mellitus and stroke. Treatment strategies include phar-macologic interventions and supplementary (or " alternative ") treatments. Nutraceuticals are derived from food sources (isolated nutrients, dietary supplements and herbal products) that are purported to provide health benefits, in addition to providing basic nutritional value. Nutraceuticals are claimed to prevent chronic diseases, improve health, delay the aging process , increase life expectancy, and support the structure and function of the body. The study of the beneficial effects of nutraceuticals in patients with MetS, including product standardization, duration of supplementation and definition of optimal dosing, could help better define appropriate treatment. This review focuses on widely marketed nutraceuticals (namely polyphenols, omega-3 fatty acids, macroelements and vitamins) with clinically demonstrated effects on more than one component of MetS.
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Curcumin is the major constituent of turmeric (Curcuma longa). Turmeric has been widely used as a spice in foods and for therapeutic applications such as anti-inflammatory, antihyperlipidemic, and antimicrobial activities. Turmeric and curcumin are nonmutagenic and nongenotoxic. Oral use of turmeric and curcumin did not have reproductive toxicity in animals at certain doses. Studies on human did not show toxic effects, and curcumin was safe at the dose of 6 g/day orally for 4–7 weeks. However, some adverse effects such as gastrointestinal upsets may occur. Moreover, oral bioavailable formulations of curcumin were safe for human at the dose of 500 mg two times in a day for 30 days, but there are still few trials and more studies are needed specially on nanoformulations and it should be discussed in a separate article. In addition, curcumin is known as a generally recognized as safe substance. This review discusses the safety and toxicity of turmeric and curcumin in medicine. Turmeric and curcumin are nontoxic for human especially in oral administration. Turmeric and curcumin are also safe in animals. They are nonmutagenic and are safe in pregnancy in animals but more studies in human are needed.
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Curcuma longa is a rhizomatous perennial herb that belongs to the family Zingiberaceae, native to South Asia and is commonly known as turmeric. It is used as herbal remedy due to the prevalent belief that the plant has medical properties. C. longa possesses different effects such as antioxidant, anti-tumor, antimicrobial, anti-inflammatory, wound healing, and gastroprotective activities. The recent studies have shown that C. longa and curcumin, its important active ingredient, have protective effects against toxic agents. In this review article, we collected in vitro and animal studies which are related to protective effects of turmeric and its active ingredient against natural and chemical toxic agents.
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Objective: This study was aimed to develop microhemodynamic indices to evaluate the effectiveness of herbal medicine in diabetic tissues. Methods: Male Sprague-Dawley rats were divided into four groups: normal control rats (Control), type 2 diabetic rats without (DM2) and with supplementation of alpha mangostin (DM2-MG) or curcumin (DM2-CUR). Alpha-mangostin or curcumin (200 mg/kg BW) were fed followed by i.p. injection of streptozotocin (STZ). Mean arterial pressure (MAP) and retinal blood flow (RBF) were measured and retinal flow resistance (RFR) was calculated. Three indices were developed to evaluate the effectiveness of herbal medicines in RFR-MAP diagram based on experimental data of MAP and RFR in type 2 diabetic rats. These indices are α, β, and γ where α is a ratio of reduction in MAP, β is a ratio of reduction in RFR increasing with MAP increase, and γ indicates a ratio of reduction in RFR. Results: The elevated MAP and RFR and decreased RBF were observed in DM2 rats.Interestingly, alpha-mangostin or curcumin supplementation significantly increased RBF while decreased MAP and RFR. Using α, β and γ indices, it was found that alpha-mangostin is more effective than curcumin in type 2 diabetic retina. Conclusions: These microhemodynamic indices may be useful to compare various herbal medicines in different tissues.
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In recent decades, the pharmacological properties of numerous medicinal plants and opportunities in phytotherapy have been explored through research projects, reviews, and monographs. These studies confirm that medicinal plants offer new approaches to tackling diseases. However, improvement of phytotherapy in clinical practice relies on a number of critical factors. In particular, the studies are very heterogeneous, and results and their interpretation by healthcare workers vary greatly, so preventing consistency in clinical practice. There is therefore a lost opportunity to improve phytotherapy practice, because the work being done and the related systematic reviews cannot act as a body of data on which to base clear clinical recommendations. Approaches such as the Grading of Recommendations Assessment, Development and Evaluation or the Scottish Intercollegiate Guidelines Network methodology could easily help standardise the use of phytotherapy in clinical practice. In this context, evidence-based phytotherapy guidelines could offer new healthcare approaches to the treatment of diseases.
Article
Background Type 2 diabetes (T2D) is an established risk factor for cardiovascular disease (CVD) and is associated with disturbed metabolism of lipids and lipoproteins. Curcuminoids are natural products with anti-diabetic and lipid-modifying actions but their efficacy in improving dyslipidemia in diabetic individuals has not been sufficiently studied. Objective To investigate the efficacy of supplementation with curcuminoids, plus piperine as an absorption enhancer, in improving serum lipids in patients with T2D. Methods In this 12-week randomized double-blind placebo-controlled trial, subjects with T2D (n = 118) were assigned to curcuminoids (1000 mg/day plus piperine 10 mg/day) or placebo plus standard of care for T2D. Serum concentrations of lipids including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), lipoprotein(a) [Lp(a)], and non-HDL-C were determined at baseline and at the end of trial. Results Between-group comparison of change in the study parameters revealed significant reductions in serum levels of TC (-21.86 ± 25.78 versus −17.06 ± 41.51, respectively; p = 0.023), non-HDL-C (-23.42 ± 25.13 versus −16.84 ± 41.42, respectively; p = 0.014) and Lp(a) (-1.50 ± 1.61 versus −0.34 ± 1.73, respectively; p = 0.001) and elevations in serum HDL-C levels (1.56 ± 4.25 versus −0.22 ± 4.62, respectively; p = 0.048) in the curcuminoids group as compared with the placebo group (p<0.05). Serum TG and LDL-C changes did not show any significant difference between the study groups (p>0.05). Conclusion Curcuminoids supplementation can reduce serum levels of atherogenic lipid indices including non-HDL-C and Lp(a). Therefore, curcuminoids supplementation could contribute to a reduced risk of cardiovascular events in dyslipidemic patients with T2D.