ArticlePDF AvailableLiterature Review

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


Abstract and Figures

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.
Content may be subject to copyright.
Metabolic benefits of curcumin supplementation in patients
with metabolic syndrome: A systematic review and meta
analysis of randomized controlled trials
Maryam Azhdari
|Majid Karandish
|Anahita Mansoori
Nutrition and metabolic Diseases Research
Center, Ahvaz Jundishapur University of
Medical Sciences, Ahvaz, Iran
Department of clinical biochemistry, Faculty
of Medicine, Shahid Sadoughi University of
Medical Sciences and Health Services, Yazd,
Health Research Institute, Diabetes Research
Center, Ahvaz Jundishapur University of
Medical Sciences, Ahvaz, Iran
Anahita Mansoori, PhD (Nutrition Sciences),
Assistant Professor, Nutrition Department,
Faculty of Paramedicine, Ahvaz Jundishapur
University of Medical Sciences, P.O. Box
6135715794, Ahvaz, Iran.
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.
curcumin, metabolic syndrome, turmeric
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, 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.
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., MEDLINE (source: PubMed; https://www., 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
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
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
. Heterogeneity was considered
low if I
< 30%, moderate if I
=3075%, and high if I
> 75%.
FIGURE 1 Flow diagram for selection of trials [Colour figure can be viewed at]
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).
3.1 |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
= 0.0%; p= 0.59;
Figure 2, Table 2).
TABLE 1 Characteristics of trials included in the metaanalysis
criteria Location
No. of
Type of
Dose of
of study
(weeks) Side effects Outcome
Panahi et al.
Iran 44.13 50/50 50/50 Curcuminoid
1000 8 Gastrointestinal LDLC, HDLC, Lp(a), sdLDL, TG, T.chol
Yang et al.
Taiwan 59.32 30/29 36/23 Supplement of curcumin
1890 12 Stomach pain,
mild diarrhea,
Weight, BMI, FBG, HbA1c, LDLC, HDLC,
nonHDLC, TG, T.chol, T.chol/HDL, VLDL
Panahi et al.
Iran 44.13 50/50 50/50 Curcuminoid
1000 8 Gastrointestinal FBG, HbA1c, SBP, DBP, SOD, MDA
Pierro et al.
Italy 40.47 22/22 27/17 Curcumin supplement/
800 4 None Weight, BMI, WC, HC, FAT%
Amin et al.
Pakistan 44 56/52 0/108 Supplement of turmeric
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)
Iran 48 10/10 0/20 Curcumin supplement/
20 mg/kg 8 None Weight, BMI, WC, FBG, FAT%, BP, HDLC, TG
et al.
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.
Overall (I-squared = 0.0%, p = 0.595)
DI Pierro F et al (2015)
Salimi Avansar M et al (2017)
Saberi-Karimian M et al (2018)
Amin F et al (2015)
-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)
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]
NOTE: Weights are from random effects analysis
Overall (I-squared = 90.1%, p = 0.000)
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)
-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]
Overall (I- squared = 48.2%, p = 0.145)
Panahi Y et al (2015)
Amin F et al ( 2015)
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]
Overall (I-squared = 48.7%, p = 0.142)
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
-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]
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)
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)
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]
Overall (I-squared = 98.6%, p = 0.000)
Salimi Avansar M et al (2017)
Amin F et al (2015 )
Panahi Y et al (2014)
Yi-Sun Yang (2014)
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)
0 105-5-10
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]
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
= 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
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
= 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
= 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
= 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).
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);
(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
Quantitative data synthesis Heterogeneity analysis
WMD 95% CI Zvalue pvalue df (Q)I
(%) pvalue
Overall effect 124/120 4 0.409 1.951, 1.132 0.52 0.60 3 0.0 0.59
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
Overall effect 142/138 3 1.68 4.68, 1.30 1.11 0.269 2 48.2 0.14
Overall effect 142/138 3 2.96 5.09, 0.82 2.72 0.007 2 48.7 0.142
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
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.
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.
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.
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.
The authors declare no conflict of interest.
Maryam Azhdari
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.
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.
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.
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.
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),
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.
Cicero, A. F., & Colletti, A. (2016). Role of phytochemicals in the manage-
ment of metabolic syndrome. Phytomedicine,23(11), 11341144.
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.
Colalto, C. (2018). What phytotherapy needs: Evidencebased guidelines
for better clinical practice. Phytotherapy Research,32(3), 413425.
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),
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.
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.
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
Pharmacology,658(1), 4148.
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.
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),
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.
Gonzales, A. M., & Orlando, R. A. (2008). Curcumin and resveratrol inhibit
nuclear factorκBmediated cytokine expression in adipocytes. Nutri-
tion & Metabolism,5(1), 17.
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,
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.
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.
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.
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.
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.
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),
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.
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.
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.
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.
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),
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.
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),
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.
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.
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.
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.
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.
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://
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.
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
by decreasing serum free fatty acids: A doubleblind, placebo
controlled trial. Molecular Nutrition & Food Research,57(9),
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.
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
mice. Journal of Agricultural and Food Chemistry,
53(4), 959963.
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.
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.
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.
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.
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.
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
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.
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),
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://
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.
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.
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.
Sahebkar, A. (2014a). Curcuminoids for the management of
hypertriglyceridaemia. Nature Reviews Cardiology,11(2), 123. https://
Sahebkar, A. (2014b). Lowdensity lipoprotein is a potential target for
curcumin: novel mechanistic insights. Basic & Clinical Pharmacology &
Toxicology,114(6), 437438.
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),
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.
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.
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.
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.
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.
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),
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.
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.
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.
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.
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.
... 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). ...
Full-text available
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. ...
Full-text available
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. ...
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. ...
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]. ...
Full-text available
Abstract Background We aim to identify the molecular mechanisms behind curcumin's therapeutic benefits for metabolic syndrome (MetS) and its components. Methods The Comparative Toxicogenomics Database, MIENTURNET, Metascape, GeneMania, and Cytoscape software were critical analytic tools. Results Curcumin may have therapeutic effects on MetS and its components via the following genes: NOS3, IL6, INS, and ADIPOQ, particularly PPARG. Curcumin has higher docking scores than other genes with INS and PPARG (docking scores: −8.3 and −5.8, respectively). Physical interactions (56%) were found to be the most prevalent for dyslipidemia, co-expression for hypertension, obesity, T2DM, and MetS. “Galanin receptor pathway”, “lipid particles composition”, “IL-18 signaling pathway”, “response to extracellular stimulus”, and “insulin resistance” were listed in the first of the key pathways for MetS, dyslipidemia, hypertension, obesity, and diabetes, respectively. The protein-protein interaction enrichment analysis study also identified “vitamin B12 metabolism,” “folate metabolism,” and “selenium micronutrient network” as three major molecular pathways linked to MetS targeted by curcumin. PPARG was the key transcription factor that regulated practically all curcumin-targeted genes linked to MetS and its components. Curcumin targets hsa-miR-155-5p, which has been linked to T2DM, hypertension, and MetS, as well as hsa-miR-130b-3p and hsa-miR-22-3p, which have been linked to dyslipidemia and obesity, respectively. In silico, sponges that regulated hsa-miR-155-5p were developed and evaluated. Curcumin, MetS, and its components have been found to target adipocytes, cardiac myocytes, smooth muscle, the liver, and pancreas. Curcumin's physicochemical properties and pharmacokinetics are closely connected with its therapeutic advantages in MetS and its components due to its high gastrointestinal absorption, drug-likeness, water solubility, and lipophilic nature. Curcumin is a CYP1A9 and CYP3A4 inhibitor. Although curcumin has a low bioavailability, it can be synthesized and administered to increase its pharmacokinetic features. Conclusions Curcumin needs to undergo therapeutic optimization and further study into its pharmacological structure before it can be used to treat MetS and its components.
Currently, a large amount of experimental data has been accumulated, which confirm that the main component of turmeric, curcumin, has a high biological activity and a wide spectrum of action. Curcumin is used in the practice of clinical medicine as an effective anti-inflammatory, antioxidant, neuroprotective, detoxifying and antiseptic agent. Based on numerous reviews of clinical studies, it seems possible to use this biologically active substance in therapy as a universal remedy for the prevention of the development and complex treatment of many pathological conditions.
The elaboration of therapeutic protocols using natural compounds can help in improving the outcomes of many human conditions such as malignant disorders, neurodegenerative diseases, and systemic disorders. Recently, the attention of scientists was more focused on nutraceuticals as potential candidates that can be administered in the management strategy of various pathologies. This rise in nutraceutical applications is due to their relative safety and their pleiotropic effects. Several studies suggest the use of dietary regimens and food-derived substances for the prevention and treatment of many metabolic disorders that affect the central nervous system. The neuroprotective actions offered by these substances are mediated by their pertinent antiapoptotic, antiinflammatory, and antioxidative potentials. Some compounds may also intervene in the promotion of individuals’ health via the regulation of the process of autophagy and via the enhancement of the functionality of intracellular organelles such as mitochondria. Furthermore, healthy diet and the use of dietary supplements can directly influence the functions and the progeny of neural stem cells and the metabolism of microglial cells and can influence the polarization of macrophages in the nervous tissue resulting in better outcomes in some pathologic situations. In this chapter, we review the different roles and applications of nutraceuticals in the treatment of the major brain disorders that can affect human beings.
Metabolic diseases are devastating abnormalities that address human lives toward death if they are not correctly managed. Obesity and diabetes mellitus are the prime factors that induce insulin resistance to signaling pathways and increase the risk of cardiovascular diseases. Phytonutrients are the biologically active agents derived from natural sources such as vegetables, fruits, grains, cereals, and medicinal plants, and present the ability to boost the immune system of patients with metabolic disease and also enhance the conditions by the management of lipid profiles, insulin resistance and glucose homeostasis, and chemopreventive events in case of cancer disease. This chapter highlights some phytonutrients that may have issues with the gene and produce healthy and unhealthy interactions. However, the interaction between genetic and environmental factors such as intake of particular healthy and sufficient diet plans with a good lifestyle encourages the development and pathogenesis of diseases of polygenic dietary components. Phytonutrients are critical tools for the modulation of gene expressions involved in signaling pathways and phenotypes linked with metabolic diseases. It is also noted that human health is also affected by dietary nutrients having carcinogens and aflatoxin attached with them and influence the genetic variants. As the knowledge of carcinogen and anticarcinogen increases, nutritional science leads to promising therapeutics for cancer management by healthy diet plans. This chapter has depicted essential aspects of phytonutrients and their interactions with genes in metabolic disease prevention and treatments.
In spite of the advanced researches, preventive measures, and treatment options, cancer remains a growing ailment all over the world and its prevalence is estimated to increase in future. Cellular metabolic alterations have been documented as a hallmark of cancer. Metabolic regulation is an intricately coupled process whose deregulation leads to tumor progression as well as metastasis. In order to thrive in the living system, cancer cells adapt different metabolic pathways (bioenergetics and biosynthesis). They replenish their metabolic demands by switching from normal metabolism to cancer metabolism by the process of metabolic rewiring. Recent researches suggest that starving cancer cells by the use of nontoxic chemical entities can give promising results regarding cancer proliferation. Natural products, especially those of plant origin, offer different chemical scaffolds to target cancer via modulation of multiple cell signaling cascades. Phytonutrients, the secondary metabolites from the plants, constitute edible phytochemicals which are abundantly found in vegetables, whole grains, and fruits. The growing numbers of evidences suggest that phytonutrients exhibit anticancer as well as chemopreventive activities of these bioactive molecules against several cancers by targeting the various significant enzymes of glycolysis, the PPP pathway, TCA cycle, and serine metabolism. This book chapter presents an update for the scientific community about targeting the cancer metabolism by phytonutrients. The alterations in the cancer metabolism in the context of bioenergetics, biosynthesis, and mitochondrial functions have been discussed while presenting the impact of phytonutrients as modulators of potential metabolic effectors in the cancer metabolism.
Mitochondria are the main organelles responsible for generating cellular energy. The common symptom of mitochondrial disorders is extreme fatigue. The lowered mitochondrial activity owing to lack of chemical transmembrane capacity, changes in the electron transport chain’s function, the maintenance of the inner mitochondrial membrane’s electrical and decrease in essential metabolites transport to the mitochondria. The change in mitochondrial activity is brought about by the reduction of adenosine-5′-triphosphate (ATP) and oxidative phosphorylation. The mitochondrial activity needs regular replacement of natural phytochemicals and supplementations that help to maintain the energy level. The efficacy of oral alternative nutrients like reduced nicotinamide adenine dinucleotide (NADH), alpha-lipoic acid, coenzyme Q10, alpha-lipoic acid carnitine, membrane phospholipids, and other supplements was evaluated in clinical studies and were found effective against mitochondrial disorders. Combinations of these supplements can substantially alleviate weakness and other symptoms associated with mitochondrial disorders in patients. The frequent intake of these nutrients can also help to reduce the onset of various neurological disorders along with mitochondrial dysfunction. These results have significant effects on the welfare of both the civilian and military communities.
Full-text available
Curcumin is a yellow pigment derived from rhizomes of turmeric (Curcuma longa L.) and can affect multiple components metabolic syndrome (MetS). In the current study, we aimed to evaluate the effects of curcumin on several CVD risk factors, including indices of depression and anxiety in individuals with MetS. This randomized clinical trial was undertaken in the Nutrition Clinic of the Ghaem Hospital. One hundred and twenty subjects (18–65 years old) were randomly assigned to one of three treatment groups: a group receiving phospholipidated curcumin (PC) capsules (1 g/day) for 6 weeks )n = 40), a group receiving unformulated curcumin (UC) capsules (1 g/day) for 6 weeks (n = 40), and a control group who received a placebo capsule (n = 40). Socio-demographic status of all participants was documented using a self-administered questionnaire. Blood samples were collected after a 12-h fasting. All biochemical factors and anthropometric indices were measured in all patients at baseline and after 6 weeks intervention. Complete blood count (CBC), serum levels of FBG, lipid profile, apolipoproteins, and hs-CRP were assessed. Physical activity level was measured using a standard questionnaire. At the beginning and end of study, Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) were completed by all volunteers. According to the self-reported adverse effects, one subject in the PC-treated group reported hypersensitivity. Also, there were reports of cold sore (n = 1) and nausea (n = 1) in the UC group. Statistical analyses were performed using SPSS software. A total of 109 subjects completed the study. There were no significant differences between the three study groups for any of the variables at baseline, nor after the 6 weeks intervention, including anthropometric indices, serum biochemical factors, systolic and diastolic blood pressures, and CBC. However, subjects with severe anxiety appeared to be significantly improved by treatment with the PC and UC compared with the placebo group (p = 0.01). Curcumin supplementation did not improve any of the cardiovascular risk factors associated with MetS.
Full-text available
Curcumin is an active component derived from Curcuma longa L. which is a traditional Chinese medicine that is widely used for treating metabolic diseases through regulating different molecular pathways. Here, in this study, we aimed to comprehensively investigate the effects of curcumin on glycolipid metabolism in vivo and in vitro and then determine the underlying mechanism. Male C57BL/6 J obese mice and 3T3-L1 adipocytes were used for in vivo and in vitro study, respectively. Our results demonstrated that treatment with curcumin for eight weeks decreased body weight, fat mass and serum lipid profiles. Meanwhile, it lowered fasting blood glucose and increased the insulin sensitivity in high-fat dietinduced obese mice. In addition, curcumin stimulated lipolysis and improved glycolipid metabolism through upregulating the expressions of adipose triglyceride lipase and hormonesensitive lipase, peroxisome proliferator activated receptor γ/α (PPAR γ/α) and CCAAT/enhancer binding proteinα (C/EBP α) in adipose tissue of the mice. In differentiated 3T3-L1 cells, curcumin reduced glycerol release and increased glucose uptake via upregulating PPAR γ and C/EBP α. We concluded that curcumin has the potential to improve glycolipid metabolism disorders caused by obesity through regulating PPAR γ signalling pathway.
Full-text available
Background: Dyslipidemia is an important and common cardiovascular risk factor in the general population. The lipid-lowering effects of turmeric and curcumin are unconfirmed. We performed a meta-analysis to assess the efficacy and safety of turmeric and curcumin in lowering blood lipids in patients at risk of cardiovascular disease (CVD). Methods: A comprehensive literature search was conducted on PubMed, Embase, Ovid, Medline and Cochrane Library databases to identify randomized controlled trials (published as of November 2016) that assessed the effect of turmeric and curcumin on blood lipid levels including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Pooled standardized mean difference (SMD) with 95% confidence interval (CI) was used to assess the effect. Results: The analysis included 7 eligible studies (649 patients). Turmeric and curcumin significantly reduced serum LDL-C (SMD = -0.340, 95% confidence interval [CI]: -0.530 to -0.150, P < 0.0001) and TG (SMD = -0.214, 95% CI: -0.369 to -0.059, P = 0.007) levels as compared to those in the control group. These may be effective in lowering serum TC levels in patients with metabolic syndrome (MetS, SMD = -0.934, 95% CI: -1.289 to -0.579, P < 0.0001), and turmeric extract could possibly have a greater effect on reducing serum TC levels (SMD = -0.584, 95% CI: -0.980 to -0.188, P = 0.004); however, the efficacy is yet to be confirmed. Serum HDL-C levels were not obviously improved. Turmeric and curcumin appeared safe, and no serious adverse events were reported in any of the included studies. Conclusions: Turmeric and curcumin may protect patients at risk of CVD through improving serum lipid levels. Curcumin may be used as a well-tolerated dietary adjunct to conventional drugs. Further research is required to resolve uncertainties related to dosage form, dose and medication frequency of curcumin.
Full-text available
Introduction Metabolic syndrome (METS) represent a simultaneous presence of multiple metabolic disorders in one person. Prevalence is increasing worldwide, which is probably related to increased obesity and sedentary lifestyle. Non-alcoholic steatosis or “fatty liver” is a metabolic disease caused by fat dysfunction. It can be a sign of some other disease, and can often be found in patients with metabolic disorders. Ultrasound is an acceptable method for the identification of fatty steatosis. There is evidence that when turmeric is used as a herbal diet, with its active metabolite of curcumin, can repair fatty acidosis and thus prevent progression of fatty steatosis complications such as cirrhosis and liver cancer. Goal. The aim of the study was to determine the effects of 400 mg curcuminaddition to the nutrition on ultrasound morphological characteristics of the liver in METS patients. Methodology A prospective cohort study was conducted on 100 subjects with METS, treated in the family medicine practice of the Tuzla Canton, aged 35-70 years. The therapeutic effects of 400 mg curcumin on ultrasound-morphological characteristics of the liver were followed, validated by ultrasound in 50 respondents of experimental groups with METS. The data were processed by the IBM SPSS Statistics 21 statistical analysis program using parametric techniques andStudent’s t-test for paired samples. Results There were 65% of women in the study. There were no statistically significant differences in the age of respondents within the analyzed groups. The use of 400 mg curcumin per day was statistically significantly improved ultrasound morphological characteristics of the liver in subjects with METS. Conclusion All respondents with METS who used curcumin had beneficial effects on the morphological characteristics of the liver. Curcumin had stronger effects on subjects with METS and DM type 2 than others.
Full-text available
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.
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.
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.
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.
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.
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.