Effects of curcumin on glycemic control and lipid profile in prediabetes and type 2 diabetes mellitus: A systematic review and meta-analysis
Effects of curcumin on glycemic control and lipid profile in prediabetes and type 2 diabetes mellitus: A systematic review and meta-analysis
Nalinee Poolsup 0 2
Naeti SuksomboonID 1 2
Putu Dian Marani Kurnianta 1 2
Kulchalee Deawjaroen 1 2
0 Department of Pharmacy, Faculty of Pharmacy, Silpakorn University , Nakhon-Pathom , Thailand
1 Department of Pharmacy, Faculty of Pharmacy, Mahidol University , Bangkok , Thailand
2 Editor: Stephen L. Atkin, Weill Cornell Medical College Qatar , QATAR
Data Availability Statement: All relevant data are
within the manuscript and its Supporting
Funding: This work was supported by Indonesia
Endowment Fund for Education (LPDP) to Ms.
Putu Dian Marani Kurnianta. The funders had no
role in study design, data collection and analysis,
decision to publish, or preparation of the
Competing interests: The authors have declared
that no competing interests exist.
Studies have demonstrated inconsistent effects of curcumin on glycemic outcomes and lipid
parameters in patients with prediabetes and type 2 diabetes mellitus (T2DM). This study
aimed to assess the effect of curcumin on glycemic control and lipid profile in prediabetes
Methods and results
A systematic search of randomized controlled trials (RCTs) was conducted from inception
to June 2018 in electronic sources including AMED, ANZCTR, BioMed Central, CENTRAL,
CINAHL, ClinicalTrials.gov, Expanded Academic Index, Google Scholar, ISRCTN, LILACS,
MEDLINE, NCCIH, Science Direct, Scopus, Web of Science, and WHO ICTRP. Hand
search was also performed. Of the total 486 records, four trials (N = 508) and eight trials (N
= 646) were eligible for the meta-analysis of individuals with prediabetes and T2DM,
respectively. Curcumin significantly reduced glycosylated hemoglobin (HbA1c) in prediabetics
(MD: -0.9%, 95% CI: -1.7 to -0.1%, p = 0.03). Furthermore, T2DM subjects gained favorable
reduction in both HbA1c (MD: -0.5%, 95% CI: -1.0 to -0.0%, p = 0.04) and fasting plasma
glucose (MD: -11.7 mg/dL, 95% CI: -22.1 to -1.3 mg/dL, p = 0.03). Tendency of lipid profile
improvement was also observed.
Our findings may encourage curcumin supplementation based on its meaningful effect on
glycemic control and positive trend on lipid outcomes in prediabetes and T2DM.
Diabetes is a metabolic disease presenting with elevated blood glucose level. This disease
accounted for not only 1.5 million deaths in 2012, but also an extra 2.2 million deaths for its
attribution to cardiovascular disease and other diseases. Accordingly, diabetes has become a
worldwide burden especially in less developed countries [
]. Furthermore, the global
prevalence of diabetes has been predicted to keep increasing to 13.5% of the total world population
in 2040 [
]. Among the growing number of people with diabetes, type 2 diabetes mellitus
(T2DM) is the most prevalent. In order to manage with the worldwide issues of diabetes,
effective prevention and management are entirely required.
T2DM is preventable disorder [
]. Prevention should also be initiated in people with
prediabetes or impaired glucose tolerance who are prone to T2DM. Lifestyle modification and
pharmacologic intervention are suggested [
]. However, single oral antidiabetic drug may poorly
control blood glucose at times. Consequently, additional insulin seems to take some cost and
patient preference issues. This may grow another problem as the economic burden of diabetes
treatment has affected many countries around the world [
]. Hence, the more affordable
alternative therapy for diabetes, either as additional supplement or as prevention is necessary.
Herbal medicine is an interesting approach for diabetes treatment. Some evidence has
conclusively demonstrated the efficacy of medicinal plants in prediabetes and type 2 diabetes mellitus
Curcumin is an active ingredient contained in the rhizome of Curcuma longa plant or
turmeric. This natural substance has purported anti-inflammatory, anti-depressant, and
anti-diabetic effects [
]. Animal study revealed that curcumin and its analogues resembled the action
of antidiabetic drug namely thiazolidinedione group through activation of peroxisome
proliferator-activated receptor-? (PPAR-?) [
]. Thus, curcumin may correct the responsible targets
relating to glucose and lipid control in the body [
] which play an important part in diabetes
]. Curcumin?s effects on glycemic outcomes and lipid parameters have been
translated in human through several randomized controlled trials enrolling subjects with
] and T2DM [
]. The inconsistency among the results of those studies has
raised a question regarding the role of curcumin in diabetes management. Therefore, we
performed this systematic review and meta-analysis to assess the effect of curcumin on glycemic
control and lipid profile in prediabetes and T2DM.
Materials and methods
We conducted a systematic review and meta-analysis according to the Preferred Reporting
Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines [
Search strategy and study selection
We carried out a systematic search through bibliographic databases or search engines
including Allied and Complementary Medicine Database (AMED), BioMed Central, Cochrane
Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied
Health Literature (CINAHL), Dissertation Abstracts International (DAI), ProQuest
Dissertations and Theses (PQDT), Expanded Academic Index, Google Scholar, Latin American and
Caribbean Health Sciences Literature (LILACS), MEDLINE (Pubmed), National Center for
Complementary and Integrative Health (NCCIH), Science Direct, Scopus, and Web of
Science. We also searched clinical trial registry databases including Australian New Zealand
Clinical Trials Registry (ANZCTR), ClinicalTrials.gov, World Health Organization International
Clinical Trial Registry Platform (WHO ICTRP), and International Standard Randomized
Controlled Trial Number (ISRCTN). MeSH terms were used to include diabetes mellitus,
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prediabetic state, curcumin, curcuma, hypoglycemic agents, placebos, blood glucose, glycated
hemoglobin A, triglycerides, (cholesterol, HDL), (cholesterol, LDL), insulin resistance,
hyperglycemia. We applied the following keywords: curcum , curcumin extract, curcuma extract,
turmeric, turmeric extract, curcuminoid(s), HbA1c, lipid, lipid profile(s), prediabetes,
antidiabetic, and type 2 diabetes. The search strings were combined by using Boolean operators.
Additionally, hand search was performed to find relevant cited articles from reference list of
the identified articles. We conducted all the searches from respective inceptions until the end
of June 2018.
We included the studies if they met the following criteria: (i) randomized controlled trials
(RCTs) comparing the effect of curcumin preparation or turmeric powder to placebo; (ii)
involved participants with prediabetes or type 2 diabetes mellitus (T2DM); (iii) reported
glycemic parameters used in clinical practice such as, glycosylated hemoglobin (HbA1c) or fasting
plasma glucose (FPG) [
] with or without the report of lipid outcomes including total
cholesterol (TC), triglycerides (TG), HDL, or LDL; and (iv) treatment duration of at least 8 weeks.
Eight-week duration was considered sufficient to obtain meaningful effect since we decided
HbA1c as our primary outcome [
]. FPG and lipid profile were determined as secondary
outcomes. We did not restrict the publication language, so we had the non-English articles
translated into English. We independently screened the records based on their titles and abstracts.
PDMK further reviewed and selected the obtained full-text articles according to the inclusion
criteria. NS and NP finalized the eligibility for meta-analysis.
Data extraction and quality assessment
Two reviewers (PDMK, NP) independently extracted the data for meta-analysis, evaluated the
quality of qualified studies, and performed double-check. NS resolved the disagreements, if
necessary. The following data were extracted in standardized form: (i) studies? characteristics,
including authors, year, design, location, duration, and intervention arms; (ii) subjects?
information, including inclusion criteria, age, and gender; (iii) outcomes assessed, including
baseline and endpoint values of main outcomes of interest (HbA1c, FPG, TG, TC, LDL, and HDL).
The outcomes values were managed in the same unit for HbA1c (%), FPG (mg/dL), and lipid
profile (mg/dL). If we found the other treatment arms than curcumin and placebo, we only
extracted the data from curcumin and placebo groups for prediabetes or T2DM studies. The
studies? quality was evaluated using Cochrane Risk of Bias Tool [
]. We considered the
methodological domains of individual studies as low risk, high risk, or unclear risk of bias. The
seven domains in the assessment involved random sequence generation, allocation
concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete
outcome data, selective outcome reporting, and other risk of bias.
Meta-analysis was performed for prediabetes and T2DM using Review Manager Software
(RevMan version 5.3.5). We estimated the treatment effects on HbA1c, FPG, TC, TG, LDL,
and HDL by pooling mean and SD of endpoint values in the treatment and control groups.
Final values were decided for these data based on assumption of similar direction given by the
effect magnitude. In the absence of both data, we converted the available statistical data into
mean and SD by applying appropriate formula [
]: Mean = median; SD = range/6 (when
n > 70); SD = SEM ? n (values within group); or SD = IQR/1.35 (symmetrical data
distribution), where SD is the standard deviation, n is group size, SEM is standard error of the mean,
and IQR is interquartile range, consecutively. The pooled data were computed using inverse
variance-weighted method and presented as weighted mean difference (MD) with 95% CI.
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The degree of heterogeneity was defined based on I-squared statistic. The heterogeneity was
substantially significant when the Cochrane?s test showed I2 greater than 50% with p-value
<0.1. Data with significant heterogeneity were analyzed using DerSimonian and Laird
random-effect model, otherwise, a fixed-effect model was applied. The results of meta-analysis
were statistically significant at the level of 0.05 based on Z-score of overall effects [
Sensitivity analysis was undertaken to observe if curcumin is effective for the treatment with short
duration according to the duration criteria in this systematic review. Publication bias was
evaluated based on funnel plot and Egger?s regression test [
Summary of selected studies
Fig 1 represents the search process. We retrieved a total of 486 records from the electronic
sources and manual search. There were 35 full-texts of RCTs qualified for further eligibility
assessment following title and abstract screening. Among these articles, we excluded 23 trials
by the following reasons: four were conducted in other populations [
]; nine trials tested
curcumin as combination [
]; two trials were not controlled trials [34, 35]; six trials did
not provide our outcomes of interest [36?41]; and the rest two trials were less than 8 weeks
duration [42, 43]. Hence, we finally included 12 studies [
] for the systematic
review and meta-analysis. Of these, there were 2 non-English articles which were translated
into English [
Studies? characteristics and risk of bias
The summary of the main features of the included studies is shown in Table 1. We obtained
four trials in prediabetes involving 508 participants in Asian countries [
10, 11, 44, 45
participants seemed to have similar characteristics. However, one study  recruited only
male subjects. All studies in prediabetes, except one add-on study , tested curcumin as
single supplementation. Adverse events (AEs) were assessed in all prediabetes studies along with
outcomes of interest and the other varied outcomes. The remaining eight studies were
conducted in 646 subjects with T2DM [
]. All of these studies were performed in
Asian countries, except one study  in Mexico. The background characteristics of subjects
Fig 1. PRISMA flow diagram of the study selection.
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aArrows represent relative comparison of change from baseline between treatment group and control group (opposite direction or similar direction with control group).
bAnthropometric assessments were varied such as body weight, body mass index, waist circumference, or hip circumference.
with T2DM were more varied than those of subjects with prediabetes. These attributes were
for example, diabetic nephropathy, chronic kidney disease, and suspected coronary artery
disease. All studies in T2DM were add-on trials, except two studies [
]. One study was
conducted in Na?ve T2DM participants and tested curcumin without background therapy . A
study did not clearly mention the background medication [
]. Only 3 studies in T2DM
assessed AEs. The preparation forms of curcumin studied in all trials of both prediabetes and
T2DM included curcuminoid extract 300 mg to 1.8 g per day, turmeric powder 1.5 g to 2.4 g
per day, curcumin amorphous dispersion 500 mg per day, standardized curcuminoids
preparation 600 mg per day, and nano-curcumin 80 mg per day.
All trials were randomized trials, but half number of studies did not appropriately describe
the method of randomization and allocation concealment. Consequently, the risk of selection
bias remained unclear across those studies. All studies demonstrated low risk of performance
bias by performing double-blinded method. However, one study  did not specify the
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blinding method. We considered this study as having high risk of performance bias since we
found its interventions were distinguishable. These interventions probably affect the outcome
assessment, therefore we judged the risk of detection bias of the referred study as high.
Meanwhile, majority of the other studies had unclear risk in detection bias. There was no remarkable
attrition bias, reporting bias, and other bias across studies. Nevertheless, one study 
revealed high risk of attrition bias. Two studies had high risk in reporting bias [
] and one
study likely showed high risk of other bias due to imbalance baseline values [
The risk of bias evaluation is provided in Fig 2 and S1 Fig.
Meta-analysis on glycemic control and lipid profile in prediabetes
Random-effect model was performed in pooling the data on glycemic outcomes in prediabetes
due to the significantly high heterogeneity (I2 = 92%, p<0.00001). Four studies [
10, 11, 44, 45
in prediabetes with 496 subjects contributed for the meta-analysis on FPG. However, one
study  did not provide HbA1c leaving the analysis on this outcome with only three studies
of 370 subjects. The results revealed that the mean differences between curcumin and placebo
groups were -0.89% (95% CI: -1.70 to -0.08%, p = 0.03) on HbA1c and -10.77 mg/dL (95% CI:
-22.65 to 1.12 mg/dL, p = 0.08) on FPG, respectively. These findings indicated the significant
effect of curcumin in reducing HbA1c in prediabetes (Fig 3).
The meta-analysis on all lipid outcomes in prediabetes consisted of three studies [
] with 262 participants. Positive effects on lipid outcomes were explained as a decrease in
TG, TC, and LDL, but an increase in HDL. Regardless of the varied heterogeneity (I2 =
0?92%) and analysis model, curcumin demonstrated non-significant effects on lipid profile
Sensitivity analysis regarding the duration of the treatment by removing study with far
longer duration  was planned. However, due to the limited number of studies after removal,
we did not proceed with the analysis.
Meta-analysis on glycemic control and lipid profile in T2DM
The data of glycemic outcomes in T2DM demonstrated significant heterogeneity (I2 = 68?
72%, p = 0.003). Based on the meta-analysis of six trials (N = 546) [
12?14, 46, 49, 50
curcumin offered benefit of HbA1c reduction by up to -0.49% (95% CI: -0.96 to -0.02%, p = 0.04).
Consistently, the result on FPG from eight trials (N = 637) [
] offered favorable
lowering effect (MD: -11.68 mg/dL, 95% CI: -22.11 to -1.25 mg/dL, p = 0.03). Therefore,
curcumin contributed to significant improvement on glycemic control in T2DM (Fig 3).
Significant heterogeneity was also found in the meta-analysis on lipid outcomes in T2DM
(I2 = 71?89%, p 0.002). Random effect model was applied to pool the data in both TG and TC
involving seven trials (N = 593) [
]. By removing one study [
] which did not
provide outcomes on LDL and HDL, we performed the analysis for the remaining six trials
(N = 542) under the same model. Curcumin seemed to have greater effect in lipid outcomes
including TG, TC, and HDL toward T2DM population than prediabetes population.
Nevertheless, the overall effect on all lipid outcomes in T2DM again did not indicate significant
results (S3 Fig).
We undertook sensitivity analysis in T2DM by removing one studies conducted in much
longer duration [
] than the majority of the studies. We summarized the results of sensitivity
analysis on glycemic outcomes and lipid outcomes in S1 Table. The results on glycemic
parameters were affected to become non-significant. Meanwhile, the results on lipid outcomes did
not change regardless of the treatment duration.
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Fig 2. Risk of bias summary for each included study. (+) low risk of bias, (-) high risk of bias, (?) unclear risk of bias.
We tested the risk of publication bias by funnel plot and Egger?s regression test in the presence
of at least five studies. We planned to evaluate the publication bias of studies in prediabetes
and T2DM separately. However, there were only four studies [
10, 11, 44, 45
] in prediabetes. In
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Fig 3. Meta-analysis of glycemic outcomes in prediabetes and type 2 diabetes mellitus.
CI, confidence interval; HbA1, glycosylated hemoglobin; FPG, fasting plasma glucose; TG, triglyceride; TC, total
cholesterol; LDL, low density lipoprotein cholesterol; HDL, high density lipoprotein cholesterol
aRisk of publication is considered high if the intercept deviates significantly from zero with p-value <0.05.
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consequence, we only examined the studies [
] in T2DM. We did not detect any
significant risk of publication bias in every outcome reported by those studies. The results of
Egger?s regression test are summarized in Table 2. The funnel plots are illustrated in
Supporting Information (S4 Fig).
The proposed mechanisms of curcumin antidiabetic effects were demonstrated through a
whole picture of insulin resistance inhibition and some highlighted mechanisms. Curcumin
improves insulin sensitivity by affecting three processes. Firstly, curcumin ameliorates glucose
homeostasis by triggering glucokinase activity in the liver. Secondly, it induces lipid
metabolism by raising lipoprotein lipase activity to reduce triglyceride. Thirdly, curcumin affects
insulin pathway independently by inducing glucose transporter-4 (GLUT4) expression to increase
peripheral glucose uptake. [
]. Additionally, curcumin attenuates tumor necrosis
factoralpha, plasma free fatty acid, and thiobarbituric acid reactive substances level as well as the
activity of sorbitol dehydrogenase [
]. Interestingly, antihyperglycemic effect of curcumin
and its analogues might be compared to the approved antidiabetic agent namely
thiazolidinedione group. Curcumin activating PPAR-? appears to offer good combination effect which
improves insulin secretion, lipid metabolism, and free fatty acid receptor expression [
Thus, all of these mechanisms may reflect glucose and lipid lowering effects in human.
The results of this investigation revealed the effect of curcumin on glycemic outcomes in
both prediabetes and T2DM participants. The primary outcome on glycemic control in this
research was HbA1c. We considered this outcome due to its representative measurement of
long-term glycemic control in diabetes management. The trend of the glucose level is more
reliably predicted by HbA1c than FPG which only demonstrates the blood glucose
concentration at certain time. However, both HbA1c and FPG may be taken together since these
parameters had a strong correlation [
]. Therefore, we set FPG as the secondary outcome.
Assessment of 2-hours postprandial plasma glucose (2HPP) was supposed to be combined
with those outcomes to achieve the target in management of both prediabetes and diabetes
]. Despite this, we did not manage to perform meta-analysis on 2HPP. Respectively only
one study in prediabetes  and the other in T2DM  provided this outcome data.
Nevertheless, curcumin demonstrated meaningful effect on HbA1 reduction and tended to improve
FPG in prediabetes. Furthermore, curcumin supplementation offered excellent effects on both
HbA1c and FPG reductions in T2DM.
The effect of curcumin on glycemic level in both prediabetes and T2DM should reflect their
corresponding influence on lipid profile. In fact, both glucose and lipid encounter such
complex metabolism in the body. The abnormality of either glucose or lipid probably leads to a
causal relationship [
]. Furthermore, glycemic control, particularly HbA1c, might estimate
the presence of dyslipidemia in T2DM. This possible prediction is by the reason of the linear
correlation between HbA1c and TC, TG, LDL, and HDL. Higher level of HbA1c tends to
represent higher level of TC, TG, and LDL but lower level of HDL [
]. Lipid abnormality can be
noticed not only in T2DM, but also in prediabetes. Again, this characterization might occur
when HbA1c is involved in the prediction [
]. The results on lipid parameters in this study
did not completely decline from this concept. Notwithstanding the non-statistically significant
results on lipid parameters, the results were positive and consistent with those of glycemic
parameters in both prediabetes and T2DM. Of these results on lipid outcomes, tendency of
greater magnitude was seen in T2DM population. An important issue was bioavailabilty of
curcumin. Several studies found that the levels of curcumin and its in vivo metabolites are low
in serum and tissues [
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We confirmed our findings in this meta-analysis by conducting sensitivity analysis. As we
established strict criteria of treatment duration regarding appropriate period for HbA1c to be
morethan 8 weeks, we found that most of the included studies were undertaken within eight
weeks until three months. However, there were studies conducted much longer, respectively
up to nine months in prediabetes  and six months in T2DM [
]. Therefore, we decided to
exclude these studies in respective analyses to observe the estimated effects on both glycemic
control and lipid outcomes in the majority of the studies length. The limited number of studies
led us to perform the sensitivity analysis only in T2DM. Engaging with sample-size factor,
there was likely small-trial effect of curcumin on glycemic control in T2DM. Some smaller
individual studies [
] seemed to contribute for significant reduction in the whole
meta-analysis together with the larger trial in longer duration . However, when the larger
trial was removed, we found that treatment with curcumin within 2 until 3 months might not
be sufficient for glycemic control in T2DM. Meanwhile, the sensitivity analysis in lipid
outcomes has confirmed the robustness pertaining that study duration did not affect changes on
Potential bias from the included studies might become another contributing factor for the
results. Overall studies had low risk of bias, but half of studies unclearly described the
concealment and assessment processes. Also, one study was not double-blinded. It should be
recognized that trials conducted without adequate concealment and blinding might overestimate
the treatment effects. Recent evidence proved that the average risk of bias of these sources
probably exaggerated the results of trials, particularly greater in trials with subjective outcomes
than trials with objective outcomes [
]. However, the present study assessed objective
outcomes including laboratory-based values in both glycemic control and lipid profiles.
Therefore, these issues should be negligible in general evaluation. Additionally, apparent publication
bias of the included studies was not found in this study. Language of publication also seemed
not to affect the publication bias since two of those studies were published in non-English
]. Thus, the minimized bias among the included trials should support the results
in this study to establish the role of curcumin supplementation in clinical relevance.
This present systematic review and meta-analysis may strengthen the available evidences of
curcumin becoming alternative adjunctive therapy to better control glycemic targets and lipid
parameters. Some previous meta-analyses of RCTs of curcumin have been undertaken to
assess the effects of curcumin on blood glucose and/ or lipid profile [
]. On the one hand,
one meta-analysis has successfully demonstrated curcumin?s effective FPG reduction in
dysglycemia comprising prediabetes, metabolic syndrome, and diabetic subjects [
curcumin was proposed to affect more significantly both FPG and HbA1c reduction than turmeric
preparation disregarding either in diabetic or non-diabetic subjects. Another meta-analysis
has assessed not only glycemic parameters, but also lipid profile involving similar population
with metabolic syndrome and related disorders [
]. Since this meta-analysis was published,
we found 2 additional studies and therefore included in our meta-analysis. Concerningtheir
several subgroup analyses [
], such as based on diseases (T2DM, obese and overweight) or
short duration of treatment (included 4 weeks duration) curcumin was considered to affect
glycemic parameters, lipid profile, and insulin resistance. The HbA1c test tells an average level
of blood glucose over the past 2 to 3 months, therefore including more than 8 weeks duration
was rather appropriate.
On the other hand, the results from the other three meta-analyses evaluating lipid outcomes
were inconsistent. Two meta-analyses shared common evaluation approaches including varied
population backgrounds and trial duration within seven days to six months [
only the larger study  has succeeded to present remarkable TG reduction and HDL
elevation regardless of treatment duration. The third meta-analysis [
] analyzed the effect in
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population with high risk of cardiovascular diseases pooling metabolic syndrome and T2DM
together. The results revealed significant decrease in LDL and TG. Subgroup analysis on TC
convinced each particular benefit of turmeric extract and curcumin in metabolic syndrome.
However, these significant results seemed to introduce bias due to some unexplained removals
of study in the analysis.
Compared to previous studies, this current meta-analysis considers some more suitable
approaches to investigate curcumin effects in specific population namely prediabetes and
T2DM, respectively. For example, both glycemic and lipid outcomes were observed
simultaneously; trial conducted for less than two months was not allowed; and more searches were
conducted including non-English articles. Instead of performing sub-analyses with certain criteria
under such broad population group of metabolic diseases, we defined strict criteria right at the
beginning of the search. Hence, our systematic review and meta-analysis may grant more robust
evidence to assist the application of curcumin supplementation in prediabetes and T2DM.
Our findings should be taken with caution. Heterogeneity should be considered and may
be due to varied participants? and studies? characteristics. For example, studies? duration,
participants? comorbidities, curcumin doses and preparations, co-medication, and lifestyle
influence involved in each study might be influenced. However, looking further into individual
studies suggested the following considerations. Firstly, under the same amount of
administration, curcumin extract either pure curcumin or curcuminoids may be more beneficial than
powdered turmeric to produce effects. This suggestion should concern that curcuminoids
content in turmeric powder is only around 2?6% [
]. Thus, turmeric powder has very low dose
of curcumin. Secondly, eight weeks seemed to be sufficient as minimum length of curcumin
supplementation to start gaining benefit on glycemic control [
]. Meanwhile, duration
longer than eight weeks may be required to obtain obvious results on lipid outcomes.
Nonetheless, duration of curcumin treatment might require to follow the other contributing factors
due to the finding of small-trial effect in our meta-analysis.
The other consideration concerning heterogeneity is co-medication during the treatment
with curcumin. Co-medication may associate with the individual?s stage of the disease either
prediabetes or diabetes. Our finding suggest that curcumin supplementation may be helpful in
prediabetes without co-medication, but not in T2DM. However, the greater effects magnitude
was mostly seen in T2DM than in prediabetic population. Thus, suggestion for taking
curcumin in clinical practice should be concerned case by case following individual?s stage of
disease. Also, the individual should be encouraged to keep maintaining healthy lifestyle while
consuming curcumin. The data available draw mainly from Asian studies. This is because the
majority of the studies included in this meta-analysis involved Asians.
Curcumin and its preparations demonstrated tolerable safety profile. Serious adverse events
(AEs) were not found during the supplementation with curcumin, although some minor AEs
were reported [
10, 11, 14, 44?47
]. A separate meta-analysis has been performed to confirm
this safety consideration (S5 Fig). Curcumin might be related to rare AEs. However, the
probability of curcumin-related AEs should not be ignored without attention. According to a
computational study in regard to animal studies, prolonged consumption of curcumin was
predicted to have tendency of dose-dependent hepatotoxicity in human [
]. Despite some
included studies have reported insignificant harmful alteration in liver function [
11, 13, 14,
], clinical decision should be carefully concerned for long term curcumin administration in
prone subjects. Safe dose of curcumin intake was mentioned up to 12 g/day as standardized
curcuminoids extract in healthy people [
]. Nevertheless, based on the findings in this
systematic review and meta-analysis, effective and safe administration of curcumin in prediabetes
and T2DM are likely to be achieved with dose up to 1.8 g/day of curcuminoids extract and
nine months of duration.
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Some limitations in this systematic review and meta-analysis exist. We found one study
] in prediabetes providing significantly different baseline in HbA1c and TG between the
curcumin and placebo groups. This may introduce bias, although the pooled result was not
dominated by this study. Next, more sample size might add more statistical power into the
analysis. However, the available RCTs are lacking regarding curcumin?s effects on glycemic
control and lipid profile in prediabetes and T2DM. Regardless of the small number of the
included studies, heterogeneity could not be avoided. Also, studies which assessed pure
curcumin are limited, so this meta-analysis still involved some differed preparations of curcumin.
Taking all of these together, further and larger clinical trials evaluating the effects of curcumin
or its specific dosage form on glycemic and lipid outcomes are expected, particularly in
prediabetes and T2DM.
In conclusion, the findings of this systematic review may encourage supplementation of
curcumin and its preparation specifically in Asian population with prediabetes and T2DM
patient. Curcumin appears to offer meaningful effect on glycemic control, particularly HbA1c.
Lack of effects in lipid outcomes were observed, but there was tendency of improvement in
these outcomes with greater effect in T2DM. Curcumin and its preparation also demonstrate
tolerable safety concern in the administration for eight weeks up to nine months. Hence, this
evidence may uphold the role of curcumin including prevention and management in diabetes.
Nevertheless, the application of curcumin supplementation in clinical practice should be taken
with individual?s contributing factors.
S1 Checklist. PRISMA 2009 checklist.
S1 Fig. Risk of bias graph across all included studies.
S2 Fig. Forest plots of effects of curcumin compared to placebo on lipid outcomes in
S3 Fig. Forest plots of effects of curcumin compared to placebo on lipid outcomes in type 2
S4 Fig. Funnel plots of publication bias on glycemic and lipid outcomes in type 2 diabetes
mellitus. Publication bias was assessed by Egger?s regression test and generated by StatDirect
version 3. A, glycosylated hemoglobin; B, fasting plasma glucose; C, triglyceride; D, total
cholesterol; E, LDL cholesterol; F, HDL cholesterol.
S5 Fig. Meta-analysis of adverse events in prediabetes and type 2 diabetes mellitus
involving curcumin and placebo groups.
S1 Table. Summary of sensitivity analysis in type 2 diabetes mellitus. HbA1c, glycosylated
hemoglobin; FPG, fasting plasma glucose; TG, triglyceride; TC, total cholesterol; LDL,
lowdensity lipoprotein; HDL, high-density lipoprotein; N, sample size; MD, mean difference.
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Indonesia Endowment Fund for Education (LPDP) to Ms. Putu Dian Marani Kurnianta. The
funders had no role in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
Conceptualization: Nalinee Poolsup, Naeti Suksomboon, Putu Dian Marani Kurnianta.
Data curation: Nalinee Poolsup, Naeti Suksomboon, Putu Dian Marani Kurnianta.
Formal analysis: Nalinee Poolsup, Naeti Suksomboon, Putu Dian Marani Kurnianta,
Investigation: Nalinee Poolsup, Naeti Suksomboon, Putu Dian Marani Kurnianta.
Methodology: Nalinee Poolsup, Naeti Suksomboon, Putu Dian Marani Kurnianta.
Project administration: Nalinee Poolsup, Naeti Suksomboon.
Resources: Nalinee Poolsup, Naeti Suksomboon, Putu Dian Marani Kurnianta.
Supervision: Nalinee Poolsup, Naeti Suksomboon.
Validation: Nalinee Poolsup, Naeti Suksomboon, Putu Dian Marani Kurnianta, Kulchalee
Visualization: Nalinee Poolsup, Naeti Suksomboon, Putu Dian Marani Kurnianta.
Writing ? original draft: Nalinee Poolsup, Naeti Suksomboon, Putu Dian Marani Kurnianta,
Writing ? review & editing: Nalinee Poolsup, Naeti Suksomboon, Putu Dian Marani
Kurnianta, Kulchalee Deawjaroen.
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