Received: 18 August 2017 Revised: 21 December 2017 Accepted: 2 January 2018

DOI: 10.1002/ptr.6037

REVIEW

Effects of curcumin consumption on human chronic diseases: A

narrative review of the most recent clinical data
Maria Mantzorou | Eleni Pavlidou | George Vasios | Eftychia Tsagalioti |

Constantinos Giaginis

Department of Food Science and Nutrition,

School of Environment, University of the
Aegean, Myrina, Lemnos, Greece
Correspondence
Mantzorou Maria, PhD candidate, Department
of Food Science and Nutrition, University of
the Aegean, Mitropoliti Ioakim 2, Myrina,
Lemnos 81440, Greece.
Email: mantzorou.m@aegean.gr
Numerous clinical trials have investigated the potential beneficial effects of curcumin supplemen-
tation against several human chronic diseases. Up to now, it has been claimed that curcumin con-
sumption may exert beneficial effects against several chronic diseases by promoting human
health and preventing diseases. In this aspect, the present review aims to critically collect and
in‐depth summarize the most recent, well‐designed clinical studies evaluating the potential ben-
eficial effects of curcumin consumption on human health promotion and disease prevention.
According to recent and well‐designed clinical studies, curcumin consumption may benefit
against obesity, metabolic syndrome, and diabetes. Moreover, curcumin consumption seems to
exert a positive effect on people suffering from various types of cancer, fatty liver disease,
depression, arthritis, skin diseases, gut inflammation, and symptoms of premenstrual syndrome.
Due to the strong heterogeneity among the clinical studies concerning the exact effective
curcumin dose and formulation, as well as the recommended treatment duration for each chronic
disease, no precise and definitive conclusions could be drawn. Further large‐scale prospective
studies are strongly recommended, being well‐designed as far as follow‐up times, dosage, formu-
lation, and duration of curcumin supplementation are concerned. Moreover, potential con-
founders in each specific chronic disease should carefully be taken into account in future studies.

KEY W ORDS

cancer, chronic diseases, curcumin, diabetes, inflammation, metabolic syndrome, obesity

1 | I N T RO D U CT I O N diseases, as presented in Figure 1. In addition, curcumin has been

Curcumin (diferuloylmethane), a component of the golden spice tur-
meric (Curcuma longa), is a highly pleiotropic molecule that was first
shown to exhibit antibacterial activity in 1949 (Gupta, Patchva, &
Aggarwal, 2013). Since then, extensive clinical studies have shown that
this polyphenol exerts anti‐inflammatory, anticancer, hypoglycemic,
antioxidant, wound‐healing, antiviral, and antimicrobial activities, indi-
cating curcumin's therapeutic potential against a wide range of human
Abbreviations: BDNF, Brain‐Derived Neurotrophic Factor; BMI, Body Mass
Index; CAI, Clinical Activity Index; CBP, Chronic Bacterial Prostatitis; CRP, C‐
Reactive Protein; DLQI, Dermatology Life Quality Index; HAMD‐17, 17‐item
Hamilton Depression Rating Scale; HDL, High‐Density Lipoprotein; IDS‐SR30,
Inventory of Depressive Symptomatology self‐rated version; LDL, Low‐Density
Lipoprotein; MDD, Major Depressive Disorder; MGUS, Monoclonal
Gammopathy of Undetermined Significance; NAFLD, Nonalcoholic Fatty Liver
Disease; PSA, Prostate‐Specific Antigen; QoL, Quality of Life; SM, Sulphur
Mustard; TNF‐α, Tumor Necrosis Factor‐alpha; UC, Ulcerative Colitis
shown to directly interact with numerous cell signaling molecules, as
well as targets involved in inflammation, cancer, and other diseases
(Gupta et al., 2013; Kunnumakkara et al., 2017; Nabavi, Daglia,
Moghaddam, Habtemariam, & Nabavi, 2014; Perrone et al., 2015). It
has also been observed that curcumin can modulate the activity of var-
ious important transcription factors, growth factors, inflammatory
cytokines, protein kinase, and other enzymes (Milani, Basirnejad,
Shahbazi, & Bolhassani, 2017; Perrone et al., 2015; Stanic, 2012).
These activities of curcumin can lead to several biological effects,
including the inhibition of free radicals production, oxidative stress
reduction, and inhibition of the transcription of genes implicated in oxi-
dative stress and inflammatory responses (Darvesh, Aggarwal, &
Bishayee, 2012; de Oliveira, Jardim, Setzer, Nabavi, & Nabavi, 2016;
Nabavi et al., 2014; Perrone et al., 2015; Stanic, 2012).
Extensive clinical trials over the past quarter century have
addressed the pharmacokinetics, the exceptional pharmacological

Phytotherapy Research. 2018;1–19. wileyonlinelibrary.com/journal/ptr Copyright © 2018 John Wiley & Sons, Ltd. 1
2 MANTZOROU
FIGURE 1 The diseases, health states, and symptoms shown to be
improved after curcumin supplementation
safety, and efficacy of this nutraceutical against numerous human dis-
eases (Darvesh et al., 2012; de Oliveira et al., 2016; Gota et al., 2010;
Gupta et al., 2013; WHO, 1999). Some promising effects have been
observed in patients with obesity, metabolic syndrome, and diabetes,
as well as different types of cancer, depression, arthritis, skin diseases,
inflammatory bowel disease, muscle lesions, premenstrual syndrome
symptoms, gynecological diseases, and inflammation (Nabavi et al.,
2014; Perrone et al., 2015).
However, pharmacokinetic and bioavailability studies have
observed that curcumin is poorly absorbed and rapidly metabolized
and excreted from the body, limiting its clinical use (Siviero et al.,
2015). Hence, its bioavailability should be improved in order to be uti-
lized properly and efficiently in the human body. In clinical trials,
curcumin has been used either alone or in combination with other
agents. Various formulations of curcumin, including nanoparticles, lipo-
somal encapsulation, emulsions, capsules, tablets, and powder, have
been synthesized and examined (Douglass & Clouatre, 2015; Feng,
Wei, Lee, & Zhao, 2017; Jager et al., 2014; Schiborr et al., 2014).
Considering in vivo bioavailability, in a study examining curcumin
bioavailability, 2 g standard curcumin in humans resulted in a peak con-
centration of 149.8 ng/g at 2 hr and was then eliminated from the blood
by 4.5 hr (Antony et al., 2008). In another study, after 4, 6, and 8 g
curcumin, peak serum curcumin concentration were 0.51 ± 0.11,
0.64 ± 0.06, and 1.77 ± 1.87 μM, respectively, however, at lower
curcumin doses, systemic curcumin concentrations were almost unde-
tectable (Cheng et al., 2001). However, in patients with advanced colo-
rectal cancer that were given with 3.6 g curcuminoids per day had
mean plasma concentrations at 8.9 curcumin sulfate and 15.8 nmol/L
curcumin glucuronide, 1 hr after oral administration (Sharma et al., 2004).
In rats, oral bioavailability of curcumin was found to be 1% (K. Y.
Yang, Lin, Tseng, Wang, & Tsai, 2007). However, in an in vitro study
with rat intestines (Ravindranath & Chandrasekhara, 1981), it was
shown that when the rat intestine was treated with 50–750 μg of
curcumin in 10 ml incubation medium, 30–80% of the added curcumin
was absorbed, but curcumin was not detectable in the serosal fluid.
Less than 3% of the curcumin was found in the tissue at the highest
concentration, while using radioactive curcumin, 5–6% of added radio-
activity was found in the serosal side, and it was proposed that
curcumin undergoes biotransformation during absorption from the
intestine (Ravindranath & Chandrasekhara, 1981).
Although the effects of curcumin in human diseases have widely
been investigated, the exact underlying mechanisms remain unclear,
ET AL.
because of the complex nature of the diseases (Gupta et al., 2013;
Stanić, 2017). Newly described mechanisms of action have suggested
that curcumin may modulate inflammation in the gut by decreasing
topical inflammatory response in epithelial cells and by protecting nor-
mal function of the intestinal barrier (Cho & Park, 2015; Wang, Ghosh,
& Ghosh, 2017). Additionally, concerning curcumin's antiarthritic
effect, it has been suggested that curcumin can modulate signaling
pathways in the gut, inducing somatostatin secretion from endocrine
cells in small intestine (Y. Yang, Wu, et al., 2015). Moreover, it has been
proposed that curcumin may exert an effect on the gut–brain axis, reg-
ulating neurotransmitters that signal in the gut and the brain in a rat
irritable bowel syndrome model (Yu, Wu, et al., 2015). Thus, curcumin,
despite its low bioavailability, has targets in the gut, which affect the
rest of the body.
Systemic concentrations of curcumin in vivo and in vitro highlight
low bioavailability of curcumin in vivo.
In view of the above considerations, the present review aims to
critically collect and in‐depth summarize the most recent, well‐
designed clinical data concerning the potential beneficial effects of
curcumin consumption on human chronic diseases. For this purpose,
PubMed database was comprehensively searched by the use of vari-
ous relative keywords in order to identify well‐designed clinical studies
investigating the potential beneficial role of curcumin supplementation
against human chronic diseases.
2 | C U R C U M I N A N D OB E S I T Y , M E T A B O L I C
SYNDROME AND DIABETES
There were nine studies evaluating the role of curcumin supplementa-
tion, as far as obesity, metabolic syndrome, and diabetes are concerned
(Table 1).
2.1 | Curcumin and obesity and overweight
A randomized crossover trial aimed to investigate the efficacy of
curcumin on the serum levels of various cytokines and mediators in
obese individuals (Ganjali et al., 2014). More to the point, 30 obese
individuals were randomized to receive 1 g curcumin daily or placebo
for 4 weeks. Following a 2‐week wash‐out period, each group was
assigned to the alternate treatment regimen for another 4 weeks.
Notably, mean serum interleukin (IL)‐1β, IL‐4, and vascular endothelial
growth factor levels were significantly reduced after curcumin therapy.
Hence, curcumin may exert immunomodulatory effects via altering the
circulating concentrations of IL‐1β, IL‐4, and vascular endothelial
growth factor in obese subjects (Ganjali et al., 2014).
Franco‐Robles et al. (2014) evaluated the effects of curcumin
treatment on protein oxidation, lipid peroxidation, and brain‐derived
neurotrophic factor (BDNF) levels in the serum of obese humans.
Obese subjects were treated daily with 500 and 750 mg of curcumin
that was administered orally for 12 weeks. In the serum of obese
humans, the 500 mg curcumin dose decreased low‐density lipoprotein
(LDL) levels at Weeks 2 and 12, and lipid peroxidation and oxidized
LDL levels at 6 and 12 weeks when compared with baseline levels,
but the 750 mg dose did not have any effect. Moreover, both doses
MANTZOROU ET AL. 3

TABLE 1 Clinical studies assessing the effect of curcumin consumption on obesity, metabolic syndrome, and diabetes
Study population p
Study type Intervention period Follow up & treatment dose Outcomes value Ref.

Randomized, 4 weeks intervention At the end of 30 obese individuals Curcumin may exert <.05 Ganjali et al.,
double blind, and 2 weeks each treated with 1 g/day immunomodulatory 2014
crossover, wash‐out period, intervention curcumin (n = 15) or effects by reducing
placebo‐ followed by 4 weeks placebo (n = 15) the circulating
controlled trial intervention concentrations of
IL‐1β, IL‐4, and VEGF.
Single‐blind, 12 weeks 2, 6, and 40 obese males treated 500 mg dose: ↓ LDL at <.05 Franco‐Robles
randomized trial 12 weeks with 500 mg/day (n = 20) Weeks 2 and 12, ↓ lipid et al., 2014
or 750 mg/day (n = 20) peroxidation levels at
curcumin Weeks 6 and 12, ↓ oxidised
LDL at Weeks 6 and 12. ↓
protein oxidation at Weeks
2, 6, and 12.
750 mg dose: ↓ protein oxidation
at Weeks 2, 6, and 12.
Randomized, 12 weeks 12 weeks 65 metabolic syndrome Lipid‐lowering effect. ↑HDL and <.05 Y. S. Yang et al.,
double‐blind, patients treated with ↓LDL. 2014
placebo‐ 1,890 mg/day curcumin ↓triglycerides
controlled trial (n = 33) or placebo Lack of weight and glucose
(n = 32) homeostasis improvement.
Randomized 8 weeks 8 weeks 75 acute coronary Low‐dose curcumin showed a NS Alwi et al.,
double blind syndrome patients non‐significant trend of 2008
placebo‐ treated with 45 mg/day reduction in total cholesterol
controlled trial (n = 15), 90 mg/day and LDL cholesterol levels.
(n = 15), 120 mg/day
(n = 15) or placebo
(n = 30)
Placebo‐ 4 weeks 4 weeks 25 diabetic patients treated Improvement in microangiopathy. <.05 Appendino
controlled trial with 200 mg/day Improvement in the venoarteriolar et al., 2011
curcumin (Meriva; n = 25) response. Edema decrease.
or placebo (n = 25)
Placebo‐ 4 weeks 4 weeks 77 diabetic patients treated Improvements on microcirculation <.05 Steigerwalt
controlled trial with 200 mg/day and retinal flow. Improvement et al., 2012
curcumin (Meriva; n = 34) on retinal oedema in the
or placebo (n = 33) curcumin treatment group.
Randomized, 36 weeks 12, 18, and 209 prediabetic individuals After 9 months of curcumin <.05 Chuengsamarn
double‐blinded, 36 weeks treated with 1,500 mg/ supplementation, no participant et al., 2012
placebo‐ day curcumoid content developed diabetes.
controlled study (n = 112) or placebo Improvement of the overall
(n = 97) function of β‐cells, ↓lHOMA‐IR
and ↑adiponectin levels.
Intervention 15–30 days 15–30 days 36 diabetic patients treated Attenuation of urinary excretion of <.05 H. Yang, Xu,
clinical trial with 500 mg/day albumin. Enhancement of et al., 2015
curcumin nuclear factor erythroid‐derived
2‐like 2 (Nrf2) system. Decrease
of inflammatory signaling
efficacies.
An open‐label, 11 days 1 and 11 days Eight diabetic patients Improved glycemic and lipid <.05 Neerati et al.,
randomized cotreated with 5 mg/day control (improvements on 2014
controlled trial glyburide and 475 mg/ glucose levels, LDL, HDL, VLDL,
day curcumin triglycerides).

Note. VEGF = vascular endothelial growth factor; LDL = low‐density lipoprotein; HDL = high‐density lipoprotein.

of curcumin decreased protein oxidation levels at 2, 6, and 12 weeks of
treatment when compared with baseline levels. On the other hand,
curcumin did not have any effect on the serum BDNF levels of obese
humans. The above results suggested a therapeutic potential of
curcumin to decrease oxidation caused by obesity in humans
(Franco‐Robles et al., 2014).
In view of the above studies, it should be speculated that curcumin
supplementation may exert positive effects in obese humans, enhanc-
ing weight and fat loss, as well as decreasing inflammatory cytokine
levels and oxidation due to obesity. However, as expected, curcumin
supplementation cannot result in weight or fat loss without dietary
restrictions (Franco‐Robles et al., 2014).
2.2 | Curcumin and metabolic syndrome
The effect of daily curcumin extract consumption for 12 weeks on
weight, glucose, and lipid profiles of patients with metabolic syndrome
was evaluated in a study by Y. S. Yang et al. (2014). In particular, 65
patients were randomized into two groups, where 33 patients received
curcumin extract capsule and 32 patients received a placebo capsule,
thrice daily for 12 weeks. At 12 weeks after curcumin extract con-
sumption, the levels of high‐density lipoprotein (HDL) cholesterol were
significantly increased, while the levels of LDL cholesterol were signif-
icantly decreased, and triglycerides were also lowered. In subgroups
analysis, curcumin supplementation exerted a lowering total
4 MANTZOROU
cholesterol effect in male patients and an increasing HDL effect in
female patients, resulting in a decrease of total cholesterol/HDL ratio.
Thus, 1,890 mg/day of curcumin extract for 12 weeks may have lipid‐
lowering effect, despite the lack of improvement of weight and glucose
homeostasis in patients with metabolic syndrome (Y. S. Yang et al.,
2014). In contrast, another interventional randomized double‐blind
controlled study that assessed the effects of curcumin on total choles-
terol, LDL, HDL, and triglycerides in 75 acute coronary syndrome
patients (Alwi et al., 2008) did not find any significant improvement
after lower doses of curcumin supplementation (45–180 mg per day).
2.3 | Curcumin and diabetes
Appendino et al. (2011) evaluated the potential improvement of dia-
betic microangiopathy in patients suffering from this condition for at
least 5 years and whose disease was managed without insulin.
Meriva®, a highly bioavailable, lecithinised formulation of curcumin
was administered at the dosage of two tablets per day (200 mg
curcumin per day) to 25 diabetic patients for 4 weeks, whereas a
matched group received standard care. In the treatment group, at
4 weeks, significant improvements on microangiopathy were
observed, as skin flux at foot surface was decreased, and edema score
was also significantly decreased, along with a corresponding improve-
ment in venoarteriolar response. Also, a significant increase of PO2
was associated with a decrease in skin edema, allowing a better PO2
exchange and diffusion into the skin. Meriva® was also well tolerated
and there were no dropouts (Appendino et al., 2011). In a similar study
by Steigerwalt, the improvement of diabetic microangiopathy and ret-
inopathy was evaluated in 38 diabetic patients treated with Meriva®
(Steigerwalt et al., 2012). Diabetes was diagnosed at least 5 years
before enrolment, and all patients had signs of retinal edema and
peripheral microangiopathy. Meriva® was administered at the dosage
of two tablets per day (200 mg curcumin per day) for at least 4 weeks,
in addition to the standard care. Moreover, a comparable group of 39
subjects followed the standard care alone. There were no dropouts
and Meriva® showed an optimal tolerability. At 4 weeks, the evalua-
tion showed significant improvements on microcirculation (edema
score and venoarteriolar response) and retinal flow (retinal peak sys-
tolic flow velocity), as well as an improvement on retinal edema in
the Meriva® treated group (Steigerwalt et al., 2012). Hence, it was
speculated that 200 mg curcumin in bioavailable form may play a valu-
able role in the management of diabetic microangiopathy and
retinopathy.
Another randomized, double‐blinded, placebo‐controlled study
was performed to assess the efficacy of curcumin in delaying develop-
ment of Type 2 diabetes mellitus in prediabetic population
(Chuengsamarn, Rattanamongkolgul, Luechapudiporn, Phisalaphong,
& Jirawatnotai, 2012). This study included 240 subjects that met the
criteria of prediabetes. All participants were randomly assigned to
receive either 1,500 mg/day curcumin or placebo capsules for
9 months. Changes in β‐cell function, insulin resistance, anti‐inflamma-
tory cytokines, and other parameters were monitored at baseline and
at 3, 6, and 9 months during the intervention. After 9 months of treat-
ment, 16.4% of participants in the placebo group were diagnosed with
Type 2 diabetes, whereas none were diagnosed with Type 2 diabetes in
ET AL.
the curcumin‐treated group. In addition, the curcumin‐treated group
showed a significantly better overall function of β‐cells, lower levels
of HOMA‐IR, and higher adiponectin levels, and no serious adverse
effects were reported. Therefore, this study demonstrated that
curcumin intervention in a prediabetic population may exert beneficial
effects (Chuengsamarn et al., 2012).
In a study by H. Yang, Xu, et al. (2015), curcumin intervention was
applied in patients with Type 2 diabetes mellitus by oral intake of
curcumin at the dose of 500 mg/day for a period of 15–30 days.
Curcumin was found to reduce plasma malondialdehyde levels,
enhancing the Nrf2 system regulated protein and NAD(P)H quinone
oxidoreductase 1, together with other antioxidative enzymes in
patients' blood lymphocytes. Finally, the authors observed reduced
plasma lipopolysaccharide content and increased IκB, an inhibitory
protein on inflammatory signaling, in patient's lymphocytes after
curcumin administration. However, there was no control group in this
study in order to make firm conclusions (H. Yang, Xu, et al., 2015).
In addition, another study aimed to assess the possible beneficial
effects of curcumin capsules on lowering blood lipids, and as a perme-
ability glycoprotein inhibitor on the pharmacokinetics and pharmaco-
dynamics of glyburide, and as a permeability glycoprotein substrate
with glyburide in patients with Type 2 diabetes mellitus (Neerati,
Devde, & Gangi, 2014). This open‐label, randomized control trial was
carried out for 11 days on eight Type 2 diabetic patients on glyburide
therapy. On the first day of the study, following the administration of
5 mg of glyburide, blood patients' samples were collected at various
time intervals. Blood sampling was repeated on the 11th day after
treating the patients with curcumin for 10 consecutive days. Glyburide
bioavailability was enhanced in the curcumin cotreatment group, and
glucose concentrations were also decreased in this group, and no
patient experienced hypoglycemia. In the treatment group, LDL cho-
lesterol, very LDL cholesterol, and triglycerides were decreased signif-
icantly, and HDL cholesterol was significantly increased. Thus, the
coadministration of 5 mg/day glyburide and 475 mg/day curcumin
may exert positive impact on the glycemic and lipid control of patients
with Type 2 diabetes (Neerati et al., 2014). However, a larger scale
study with longer study period is necessary in order to replicate these
results.
Taking the above results into account, curcumin supplementation
may exert beneficial effects on the management of diabetic complica-
tions, glycemic and lipid control, as well as enhancing prevention of
diabetes on prediabetic patients.
3 | CURCUMIN AND FATTY LIVER DISEASE
There are two randomized‐controlled trials evaluating the role of
curcumin supplementation on nonalcoholic fatty liver disease
(NAFLD). Panahi et al. (2017) recently undertook a randomized‐con-
trolled trial to investigate the potential benefit and safety of curcumin
in patients with NAFLD. Along with diet and lifestyle advice, 50
patients were randomized to receive 1 g of a bioavailable form of
curcumin (Meriva®), and 52 were randomized to receive placebo for
8 weeks. Curcumin supplementation was associated with significant
reductions on body mass index and waist circumference, serum levels
MANTZOROU ET AL.
of aspartate aminotransferase, and alanine aminotransferase. Ultra-
sounds also showed a significant response on the curcumin‐treated
group. Additionally, curcumin was deemed safe and well‐tolerated
(Panahi et al., 2017). Another randomized double‐blind placebo‐con-
trolled trial aimed to investigate the effects of bioavailable curcumin
in an amorphous dispersion formulation on liver fat content and on
biochemical and anthropometric measures in patients with NAFLD
(Rahmani et al., 2016). Patients were randomized to receive 70 mg
curcumin or placebo for 8 weeks. Curcumin was associated with a sig-
nificant reduction in liver fat content, body mass index, serum levels of
total cholesterol, LDL, triglycerides, aspartate aminotransferase, ala-
nine aminotransferase, glucose, and glycated hemoglobin compared
with the placebo group. Curcumin was safe and well tolerated in this
study as well (Rahmani et al., 2016).
Curcumin supplementation at a dosage of 70 mg and 1 g curcumin
per day for 8 weeks has significant beneficial effect on the treatment
of NAFLD, while being safe and well‐tolerated.
4 | CURCUMIN AND CANCER
There are 13 clinical studies on the effect of curcumin supplementa-
tion in cancer (Table 2). In fact, one studies were on prostate cancer,
two on breast cancer, four on pancreatic cancer, three on colorectal
cancer, one on multiple types of cancer, and two on smoldering multi-
ple myeloma and monoclonal gammopathy of undetermined signifi-
cance (MGUS).
4.1 | Curcumin and prostate cancer
A recent pilot Phase II clinical study assessed the efficacy of the coad-
ministration of docetaxel and curcumin in chemotherapy‐naive
patients with metastatic castration‐resistant prostate cancer
(Mahammedi et al., 2016). In this study, 30 patients with progressing
castration‐resistant prostate cancer and rising prostate‐specific anti-
gen levels received docetaxel/prednisone in standard conditions for
six cycles, in combination with per os curcumin, at a daily dose of
6,000 mg. A prostate‐specific antigen response was observed in 59%
of patients, being achieved within the first three cycles for 88% of
the responders, and partial response reached to 40% of evaluable
patients. The regimen was well tolerated, with 89% of patients being
compliant, and the adverse effects were attributed to docetaxel, and
the dropouts were due to disease progression and death. Thus, this
study supported curcumin supplementation, as a complementary treat-
ment for prostate cancer, with a high response rate, good tolerability,
and patient acceptability, and the authors are conducting a follow‐up
multicenter, randomized Phase II study (Mahammedi et al., 2016).
4.2 | Curcumin and breast cancer
A randomized, double‐blind, placebo‐controlled clinical trial was per-
formed to assess the ability of curcumin to reduce radiation dermatitis
severity in 30 breast cancer patients (Ryan et al., 2013). Adult females
with noninflammatory breast cancer or carcinoma in situ were pre-
scribed to undergo radiotherapy without concurrent chemotherapy.
Randomized patients took 2 g of curcumin or placebo orally 3 times
5
per day, throughout the course of radiotherapy. Curcumin was found
to significantly reduce radiation dermatitis severity and moist desqua-
mation at the end of the treatment compared with placebo in women
who did not underwent total mastectomy prior to radiation therapy.
Thus, the above study provided evidence that 6 g per day curcumin
per os reduced the severity of radiation dermatitis in breast cancer
patients, however, the optimal dosage for severe radiation dermatitis
was not studied (Ryan et al., 2013). In another open‐label Phase I
study, Bayet‐Robert et al. (2010) investigated the feasibility and toler-
ability of the combination of docetaxel and curcumin in 14 advanced,
metastatic breast cancer patients. The primary aim of this study was
to determine the maximal tolerated dose of the combination of dose‐
escalating curcumin and standard docetaxel dose. Curcumin was orally
given at 500 mg/day for 7 consecutive days by cycle, and escalated
until a dose‐limiting toxicity occurred. At the last dose level of
curcumin, three dose‐limiting toxicities were observed and two out
of three patients at this dose level refused to continue treatment,
leading Bayet‐Robert et al. (2010) to define the maximal tolerated daily
dose of curcumin at 8,000 mg, even though other studies have
reported higher doses to be safe, without serious adverse effects.
However, as it was reported in this study, some patients believed that
the amount of capsules per day was unacceptable. Considering the
antitumor effects, despite the small study group, docetaxel combined
with curcumin response rate was expected to be up to 50%. The rec-
ommended dose of curcumin was defined to 6,000 mg/day for 7 con-
secutive days every 3 weeks in combination with a standard dose of
docetaxel (Bayet‐Robert et al., 2010).
In breast cancer, curcumin supplementation could reduce radiation
dermatitis severity and moist desquamation, while possibly exerting
antitumor effect, at a proposed dose of 6,000 mg/day.
4.3 | Curcumin and pancreatic and biliary tract
cancer
A study by Kanai et al. (2013) was performed to evaluate the safety of
repetitive administration of Theracurmin in pancreatic or biliary tract
cancer patients who failed standard chemotherapy. Theracurmin is a
highly bioavailable form of curcumin that contains 10 w/w% of
curcumin, which is produced using a microparticle and surface‐con-
trolled drug delivery system and has over 30 times higher bioavailabil-
ity than conventional curcumin in rats (Kanai et al., 2013). Based on
their previous pharmacokinetic study in healthy subjects that showed
that 210 mg curcumin can be safely administered, without saturating
the absorption system (Kanai et al., 2012), the authors selected
Theracurmin containing 200 mg of curcumin as a starting dose, and
the dose was safely escalated to 400 mg of curcumin. Theracurmin
was orally administered every day with standard gemcitabine‐based
chemotherapy. Ten patients were assigned for low curcumin dose
(200 mg) and six patients for high dose (400 mg). Peak plasma
curcumin levels after Theracurmin administration were 324 ng/ml for
low curcumin dose and 440 ng/ml for high curcumin dose. Adverse
side effects, which were expected and observed in other studies,
concerning the gut were observed in this study, and three patients
safely continued Theracurmin administration for more than 9 months.
Repetitive systemic exposure to high concentrations of curcumin
 6

TABLE 2 Clinical studies assessing the effect of curcumin consumption on cancer

Intervention p
Study type period Follow up Study population & treatment dose Outcomes value Ref.

A pilot Phase II study 6 cycles 6 cycles 26 patients A high response rate <.05 Mahammedi
chemotherapy‐naive on PSA after curcumin et al., 2016
metastatic castration‐ supplementation, good
resistant prostate tolerability and patient
cancer with 6,000 acceptability.
mg/day completed
the study
A randomized, 24 weeks 24 weeks 30 breast cancer patients Curcumin reduced the <.05 Ryan et al., 2013
double‐blind, with 6 g of curcumin or severity of radiation
placebo‐controlled placebo orally dermatitis and moist
clinical trial desquamation in
women who had not
underwent total
mastectomy.
An open‐label 6 cycles 6 cycles Eight patients with Some improvements as <.05 Bayet‐Robert
Phase I trial advanced or biological and clinical et al., 2010
metastatic breast responses were
cancer with observed in most
escalating dose of patients.
curcumin (500 mg‐
8,000 mg/day)
A Phase I study Until toxicity Over 52 weeks 16 pancreatic or biliary Did not increase the Kanai et al., 2013
tract cancer patients incidence of adverse
with 200 mg curcumin events in cancer
(Level 1) as a starting patients receiving
dose, and the dose gemcitabine‐based
was safely escalated chemotherapy.
to Level 2, which
contained 400 mg
curcumin
Prospective study 4 weeks 4 weeks 17 patients with Curcumin exerted a Epelbaum et al.,
advanced pancreatic potent antiproliferative 2010
cancer with 8 g/day activity, potentiating
curcumin concurrently the antitumor effect
with gemcitabine 1 g/day of gemcitabine.
Dosage lowered after
2 weeks at 4 g/day
due to adverse effects
A Phase I/II study 52 weeks 52 weeks 21 patients with Combination therapy Kanai et al., 2011
pancreatic cancer using oral curcumin
treated with 8 g/day daily with gemcitabine‐
curcumin based chemotherapy
was safe and feasible.
A Phase II trial Until disease Every 8 weeks 25 patients with Oral curcumin was well <.05 Dhillon et al.,
progression pancreatic cancer tolerated and, despite 2008
treated with its limited absorption,
8 g/day curcumin exerted biological activity.
MANTZOROU

(Continues)
ET AL.
TABLE 2 (Continued)

Intervention p
Study type period Follow up Study population & treatment dose Outcomes value Ref.
MANTZOROU

Decreased COX‐2,
phosphorylated signal
ET AL.

transducer and activator

Double‐blind
placebo‐controlled,
randomized study
A prospective study
A Phase I clinical trial
A Phase I study
A randomized,
double‐blind
placebo‐controlled
cross‐over study
A single‐blind,
cross‐over pilot study
of transcription 3.
10 to 30 days 10 to 30 days 126 patients with colorectal ↑ body weight, ↓serum <.05 He et al., 2011
cancer, of whom 63 were TNF‐α levels, ↑ apoptotic
administered 360 mg tumor cells, enhanced
curcumin, thrice/day expression of p53 molecule
during the period ahead in tumor tissue, and
of surgery, between modulated tumor cell
10 and 30 days apoptotic pathway.
1 week 1 week 12 patients with colorectal ↓M1G with 3.6 g curcumin <.05 Garcea et al., 2005
cancer treated with 3,600,
1,800, or 450 mg/day
curcumin
16 weeks 16 weeks 15 patients with advanced 3.6 g of curcumin is <.05 Sharma et al.,
colorectal cancer treated advocated for Phase II 2004
with 450 mg‐ 3,600 /day evaluation in the
curcumin prevention or treatment of
cancers outside the
gastrointestinal tract.
↓inducible PGE.
12 weeks 12 weeks 25 patients with either Curcumin was not toxic up Cheng et al., 2001
recently resected urinary to 8,000 mg/day when
bladder cancer or arsenic taken by mouth for
Bowen's disease of the 3 months.
skin or uterine cervical Potential biologic effect
intraepithelial neoplasm in the chemoprevention
or oral leucoplakia or of cancer.
intestinal metaplasia of
the stomach with the
starting dose was
500 mg/day, the dose
was then escalated
to1,2
4, 8, and 12 g/day
curcumin
12 weeks for 12 weeks (at the end 36 patients with MGUS Delay of the disease process. <.05 Golombick et al.,
each intervention of each intervention) and SMM treated with At the dosage of 2012
4 g curcumin or 4 g placebo, 8 g, free light‐chain
followed by open label ratio, total protein,
8 g dose extension study. random urinary
protein and PTH
were decreased.
12 weeks for 12 weeks for each 26 patients with MGUS Decreased paraprotein load. <.05 Golombick et al.,
each intervention intervention treated with 4 g/day 2009
curcumin

Note. PSA = Prostate‐specific antigen; COX‐2 = cycloox‐ygenase‐2; TNF‐α = tumor necrosis factor‐alpha; MGUS = monoclonal gammopathy of undetermined significance; SMM = smoldering multiple myeloma.
7
8 MANTZOROU
achieved by Theracurmin did not increase the incidence of adverse
events in patients receiving gemcitabine‐based chemotherapy. How-
ever, concerning efficacy, no response was observed in this study
(Kanai et al., 2013). In another study evaluating the activity and feasi-
bility of gemcitabine in combination with curcumin in patients with
advanced pancreatic cancer (Epelbaum, Schaffer, Vizel, Badmaev, &
Bar‐Sela, 2010), 17 patients were enrolled and received 8,000 mg of
curcumin per os daily, concurrently with gemcitabine 1,000 mg/m2
IV, thrice weekly for 4 weeks. In this study, five patients discontinued
curcumin after a few days to 2 weeks due to intractable abdominal full-
ness or pain, and curcumin dose was reduced to 4,000 mg/day
because of abdominal complaints in two other patients. One of 11
evaluable patients had partial response, 4 had stable disease, and 6
had tumor progression. The authors concluded that low curcumin com-
pliance at a dose of 8,000 mg/day, when taken together with systemic
gemcitabine, may prevent the use of high doses of oral curcumin
needed to achieve systemic effect. However, it should be noted that
a strong limitation of this study is the lack of control group (Epelbaum
et al., 2010). On the other hand, it should be emphasized that Bayet‐
Robert et al. (2010) defined optimal dosages at 6,000 mg/day, with
maximal tolerated dosage at 8,000 mg/day in contrast to other studies
reporting that higher doses were safe.
Kanai et al. (2011) also evaluated the safety and feasibility of com-
bination therapy using curcumin with gemcitabine‐based chemother-
apy. Twenty‐one gemcitabine‐resistant pancreatic cancer patients
received 8 g oral curcumin daily in combination with gemcitabine‐
based chemotherapy. The primary endpoint was safety for Phase I
and feasibility of oral curcumin for Phase II study. In contrast to the
previous study, no dose‐limiting toxicities were observed in Phase I
study and 8 g/day oral curcumin was selected as the recommended
dose for Phase II study. Also, no patients were withdrawn due to
curcumin intolerability. However, 81% of the patients died during the
study period, while no one responded to the treatment, and five
patients continued on having stable disease. Plasma curcumin levels
ranged from 29 to 412 ng/ml in the five patients tested. Thus, this
study suggested that combination therapy using 8 g oral curcumin daily
with gemcitabine‐based chemotherapy was safe and feasible in
pancreatic cancer patients (Kanai et al., 2011).
Dhillon et al. (2008) also evaluated the potential beneficial effects
of curcumin in advanced pancreatic cancer. More to the point, 25
patients received 8 g curcumin per os daily until disease progression,
with restaging every 2 months. Serum cytokine levels for IL‐1, IL‐6,
IL‐8, and IL‐10 receptor antagonists and peripheral blood mononuclear
cells' expression of nuclear factor‐kappa B and cyclooxygenase‐2
(COX‐2) were monitored. Two patients showed clinical biological
activity. One had ongoing stable disease for more than 18 months.
Interestingly, one additional patient had a brief, but marked, tumor
regression accompanied by significant increase in serum cytokine
levels. Curcumin down‐regulated the expression of nuclear factor‐
kappa B (p = .1/non‐significant), COX‐2 (p < .05), and phosphorylated
signal transducer and activator of transcription 3 (p < .05) in peripheral
blood mononuclear cells. Hence, it was speculated that oral curcumin
was well tolerated, with no toxicities being observed, despite its low
bioavailability, it may exert biological activity in some patients with
pancreatic cancer (Dhillon et al., 2008).
ET AL.
In pancreatic and billiard tract cancer, high doses of curcumin can
be safely used along with gemcitabine‐based therapy, despite few
adverse effects. However, due to the limited number of participants,
no firm conclusion can be drawn on the efficacy of curcumin
supplementation.
4.4 | Curcumin and colorectal cancer
A double‐blind randomized controlled study by He et al. (2011) exam-
ined the inhibitory mechanisms of curcumin on tumor cells in patients
with colorectal cancer. One hundred twenty‐six patients were random-
ized to receive either 360 mg curcumin (n = 63) or placebo (n = 63) for
10–30 days before surgery. Specimens were taken for biopsy at diag-
nosis and during surgery. The results showed that 360 mg per day
curcumin after 10–30 days administration significantly increased body
weight, decreased serum tumor necrosis factor‐alpha (TNF‐α) levels,
increased apoptotic tumor cells, enhanced p53 expression in tumor tis-
sue, and modulated tumor cell apoptotic pathway. The authors con-
cluded that curcumin treatment improved the general health of
colorectal cancer patients, through induction of apoptosis by increas-
ing p53 expression in tumor cells (He et al., 2011). Another study
tested the hypothesis whether pharmacologically active curcumin
levels could be achieved in the colorectum of humans as measured
by effects on M(1)G and COX‐2 protein levels, and comparisons were
made between cancerous and normal tissue (Garcea et al., 2005).
Patients with colorectal cancer were given 450 mg (n = 4), 1,800 mg
(n = 4), or 3,600 mg (n = 4) of curcumin daily for 7 days before surgery.
M(1)G levels were significantly decreased for the highest dose of
3,600 mg curcumin per day, but COX‐2 protein levels in malignant
colorectal tissues were not affected. These findings supported evi-
dence that a daily dose of 3,600 mg curcumin may achieve pharmaco-
logically efficacious levels in the colorectum, despite its low
bioavailability (Garcea et al., 2005).
Sharma et al. (2004) designed a dose‐escalation study to explore
the pharmacology of curcumin in humans. In particular, 15 patients
with advanced colorectal cancer refractory to standard chemother-
apies consumed Glutathione S‐transferase activity, levels of M(1)G,
and PGE(2), production induced ex vivo were measured in the
participants' leukocytes. Curcumin and its glucuronide and sulfate
metabolites were detected in both plasma and urine. A daily dose of
3.6 g curcumin led to significant decreases in inducible PGE(2) produc-
tion in blood samples taken 1 hr after curcumin supplementation on
Days 1 and 29 of treatment, compared with the levels observed imme-
diately predose. A daily oral dose of 3.6 g of curcumin was advocated
for Phase II evaluation in the prevention or treatment of cancers out-
side the gastrointestinal tract. This study also suggested that the levels
of curcumin and its metabolites in the urine could be used to assess
general compliance. Considering side‐effects, although dose‐limiting
toxicity was not observed, some cases were reported. Two patients
suffered from diarrhea, and another one from nausea, and increased
serum alkaline phosphatase level was observed in four patients and
serum lactate dehydrogenase increased more than 1.5‐fold of pre-
treatment values in three patients (Sharma et al., 2004).
Considering colorectal cancer, preoperative curcumin supplemen-
tation of 3,600 mg/day increased body weight, decreased serum
MANTZOROU ET AL.
TNF‐α levels, increased apoptotic tumor cells, enhanced p53 expres-
sion in tumor tissue, and modulated tumor cell apoptotic pathway.
Moreover, 3.6 g curcumin per day may contribute to a decrease in
M(1)G levels and PGE(2) production. However, the need for well‐
designed Phase II and randomized‐controlled trials is apparent.
4.5 | Curcumin and other types of cancer
A prospective Phase I clinical study evaluated several issues of
curcumin administration in patients with high‐risk conditions (recently
resected urinary bladder cancer, arsenic Bowen's disease of the skin,
uterine cervical intraepithelial neoplasm, oral leucoplakia, or intestinal
metaplasia of the stomach; Cheng et al., 2001). Biopsies of the lesion
sites were done at enrolment and 3 months after starting curcumin
treatment, with starting dose at 500 mg/day. One of the four patients
with cervical intraepithelial neoplasm and one of the seven patients
with oral leucoplakia proceeded to develop cancer. In contrast, histo-
logic improvement of precancerous lesions was seen in one out of
two patients with recently resected bladder cancer, two out of the
seven patients with oral leucoplakia, one out of the six patients with
intestinal metaplasia of the stomach, one out of the four patients with
cervical intraepithelial neoplasm, and two out of the six patients with
Bowen's disease. Thus, this study demonstrated that curcumin was
not toxic to humans up to 8,000 mg/day per os or 3 months, and the
number of capsules taken was deemed acceptable by the participants.
These findings also suggested a potential biologic effect of curcumin in
cancer chemoprevention (Cheng et al., 2001).
Administrating a 4 g dose of curcumin, Golombick, Diamond,
Manoharan, and Ramakrishna (2012) performed a randomized, dou-
ble‐blind placebo‐controlled cross‐over study, followed by an open‐
label extension study using an 8 g curcumin dose. This study aimed
to assess the effect of curcumin on free light‐chain response and bone
turnover in patients with MGUS and smoldering multiple myeloma
(Golombick et al., 2012). Thirty‐six patients were randomized into
two groups: one received 4 g curcumin and the other 4 g placebo. At
completion of the 4 g arm, all patients were given the option of enter-
ing an open‐label 8 g dose extension study. Twenty‐five patients com-
pleted the 4 g cross‐over study and 18 completed the 8 g extension
study. The reasons reported for dropping out were progressive disease
(n = 5), low compliance (n = 4), and diarrhea (n = 2). Four grams
curcumin therapy decreased random urinary protein and serum creat-
inine levels. At the dose of 8 g free light‐chain ratio, total protein, ran-
dom urinary protein, and PTH were significantly decreased. These
findings suggested that curcumin might exert the potential to slow
down disease progression in patients with MGUS and smoldering mul-
tiple myeloma (Golombick et al., 2012).
Golombick, Diamond, Badmaev, Manoharan, and Ramakrishna
(2009) carried out another clinical trial to determine the effect of
curcumin on plasma cells and osteoclasts in patients with MGUS.
Twenty‐six patients with MGUS were enrolled and received 4 g/day
oral curcumin (n = 17) or placebo (n = 9) and crossed over at 3 months
after enrollment. Blood and urine samples were collected at specified
visits after initiating therapy. It was found that 4 g curcumin supple-
mentation decreased paraprotein load in patients with greater
paraprotein levels (<20 g/L; Golombick et al., 2009).
9
According to the above, curcumin supplementation may exert
anticancer effects on precancerous conditions, while it may slow down
disease progression in patients with MGUS and smoldering multiple
myeloma.
5 | C U R C U M I N A N D D E P R E S SI O N
There are six clinical trials evaluating the effect of curcumin on depres-
sion (Table 3). A recent study investigated the impact of curcumin on
the frequency of symptoms of anxiety and depression in obese individ-
uals (Esmaily et al., 2015). In this double blind, cross‐over trial, 30
obese subjects were randomized to receive either 1 g curcumin or pla-
cebo for 30 days. Following a wash‐out interval of 2 weeks, each par-
ticipant was crossed over to the alternative regimen for another
30 days. The Beck Anxiety Inventory and Beck Depression Inventory
scales were used to measure the severity of anxiety and depression.
Mean Beck Anxiety Inventory score was found to be significantly
reduced following curcumin treatment, supporting evidence that
curcumin may exert a potential antianxiety effect in individuals with
obesity. On the other hand, curcumin supplementation did not exert
any significant impact on Beck Depression Inventory scores (Esmaily
et al., 2015). In another study, 108 male adults were enrolled to study
the antidepressant actions of curcumin (Yu, Pei, Zhang, Wen, & Yang,
2015). Subjects were evaluated by the Chinese version of 17‐item
Hamilton Depression Rating Scale and Montgomery‐Asberg Depres-
sion Rating Scale that measured different scores of depressive symp-
toms. After 6 weeks of 2 g curcumin supplementation or placebo,
along with antidepressant therapy, it was found that curcumin
decreased ratings of depressive symptoms, as well as inflammatory
cytokines IL‐1b and TNF‐α levels and salivary cortisol concentrations,
while increasing plasma BDNF levels compared with placebo group.
These findings indicated a potential beneficial effect of curcumin on
the management of major depressive disorder (MDD; Yu, Pei, et al.,
2015).
A recent randomized, double‐blind, placebo controlled study by
Lopresti et al. (2015) evaluated the efficacy of supplementation with
a patented curcumin extract for 8 weeks in reducing depressive symp-
toms in people with MDD, using the Depressive Symptomatology self‐
rated version (IDS‐SR30) as the primary depression outcome measure.
One gram curcumin supplementation for 8 weeks significantly
decreased urinary thromboxane B2 and substance P levels compared
with placebo. Higher baseline plasma endothelin‐1 and leptin in
curcumin‐treated individuals was associated with greater reductions
in IDS‐SR30 score. Curcumin's mechanism of action on depression
might be associated with the measured biomarkers, with leptin and
endothelin‐1 playing an important role (Lopresti et al., 2015). In
another study by Lopresti, Maes, Maker, Hood, and Drummond
(2014), the effectiveness of 1 g curcumin on the management of
depressive symptoms in 56 individuals with MDD for a period of
8 weeks was examined. From baseline to Week 4, both curcumin and
placebo were associated with improvements in most outcome mea-
sures. However, from Weeks 4 to 8, curcumin was significantly more
effective than placebo in improving IDS‐SR30 total and DS‐SR30
mood score. Moreover, greater efficacy from curcumin treatment
 Clinical studies assessing the effect of curcumin on depression
10

TABLE 3

Intervention Follow‐ p
Study type period up Study population & treatment dose Outcomes value Ref.

A double blind, 30 days for each intervention, 4, 6, and 10 weeks 30 obese subjects treated ↓mean Beck anxiety inventory score .03 Esmaily et al., 2015
cross‐over trial 2 weeks wash‐out period with 1 g/day curcumin
A randomized, 6 weeks 6 weeks 108 male adults with ↓HAMD‐17 and ↓Montgomery‐Asberg <.05 Yu, Pei, et al., 2015
double‐blind, MDD treated with 2,000 mg depression rating scales.
placebo‐controlled curcumin or placebo soybean Reduction of inflammatory cytokines.
pilot study powder daily
A randomized, 8 weeks 8 weeks 50 participants diagnosed with ↓urinary thromboxane B2, and ↓substance <.05 Lopresti et al., 2015
double‐blind, MDD treated with 1 g/day P levels compared with placebo. Higher
placebo‐controlled curcumin baseline plasma endothelin‐1 and leptin
trial in curcumin‐treated individuals was
associated with greater reductions in
IDS‐SR30 score
A randomized, 8 weeks 4 and 8 weeks 56 individuals with MDD treated From Weeks 4 to 8, curcumin was more <.05 Lopresti et al., 2014
double‐blind, with 1 g/day curcumin or placebo effective than placebo in improving a
placebo‐controlled significant group × time interaction for
study IDS‐SR30 total score and IDS‐SR30
mood score. Greater efficacy from
curcumin in individuals with atypical
depression.
A randomized 6 weeks 6 weeks 60 patients with MDD treated Comparable results in all groups. Curcumin NS Sanmukhani et al., 2014
controlled trial with 20 mg fluoxetine and was safely used in the treatment plan.
1 g curcumin individually or
their combination
A randomized, 5 weeks Each visit up to 5 weeks 40 patients with a first episode of No difference between curcumin and NS Bergman et al., 2013
double‐blind, depression treated with 500 mg/day placebo. Curcumin group demonstrated
placebo‐controlled, curcumin or placebo together with a trend to a more rapid recovery from
pilot clinical study antidepressants (escitalopram or depressive symptoms.
venlafaxine)

Note. MDD = major depressive disorder; HAMD‐17 = 17‐item Hamilton Depression Rating Scale; IDS‐SR30 = Inventory of Depressive Symptomatology self‐rated version.
MANTZOROU
ET AL.
MANTZOROU ET AL. 11

was observed in individuals with atypical depression. In view of the
above, it was speculated that the antidepressant effects of curcumin
were exerted after 4 weeks of treatment (Lopresti et al., 2014).
The objectives of another clinical trial were to compare the efficacy
and safety of curcumin cotreated with fluoxetine in MDD patients
(Sanmukhani et al., 2014). Herein, 60 patients diagnosed with MDD were
randomized for 6 weeks observer‐masked treatment with 20 mg fluoxe-
tine and 1 g curcumin either individually or in combination. Interestingly,
the mean change in HAM‐D17 score at the end of 6 weeks was compa-
rable in all three groups. Because curcumin was well tolerated, it can be
as considered as an effective and safe treatment for MDD patients with-
out concurrent suicidal ideation or other psychotic disorders
(Sanmukhani et al., 2014). Bergman et al. (2013) evaluated the efficacy
of curcumin as an antidepressive agent, in combination with other anti-
depressants in patients with major depression. Forty patients with a first
episode of depression participated in this 5‐week, double‐blind, random-
ized, placebo‐controlled study. The participants were treated with either
500 mg/day curcumin or placebo together with antidepressants. Signifi-
cant positive changes in both groups from baseline to the end of the
study in all scales of measurement were recorded. These changes
became significant after 7 days of treatment. Although no difference
between curcumin and placebo was found, the patients in curcumin
group demonstrated a nonstatistically significant trend to recover faster
from depressive symptoms, in comparison with those in the placebo
group (Bergman et al., 2013).
Considering depression, the above studies concluded to mixed
results, despite the comparable doses of curcumin and the comparable
follow‐up times in some of the studies. Some studies showed a posi-
tive effect on the reduction of depressive symptoms, and a potential
mechanism of action of curcumin might involve the modulation of
plasma endothelin‐1 and leptin.
6 | CURCUMIN AND ARTHRITIS
There are five clinical trials on the impact of curcumin supplementation
on arthritis (Table 4). Nakagawa et al. (2014) examined the clinical effects
of orally administered Theracurmin in patients with knee osteoarthritis
during 8 weeks of treatment. Fifty patients with knee osteoarthritis of
Kellgren–Lawrence Grade II or III were enrolled in this randomized, dou-
ble‐blind, placebo‐controlled, prospective clinical study. Placebo or
Theracurmin containing 180 mg/day curcumin was administered orally.
At 8 weeks after treatment initiation, knee pain visual analog scale scores
were significantly lower in Theracurmin group compared with placebo
group, among those with higher pain score, and Theracurmin significantly
lowered celecoxib dependence. In view of the above, Theracurmin

TABLE 4 Clinical studies assessing the effect of curcumin on arthritis

Intervention Follow p
Study type period up Study population & treatment dose Outcomes value Ref.

A randomized, 8 weeks 8 weeks 50 patients with knee osteoarthritis Modest potential for the <.05 Nakagawa et al.,
double‐blind, of Kellgren–Lawrence Grade II treatment of human knee 2014
placebo‐controlled, or III treated with placebo or osteoarthritis.
clinical study Theracurmin containing 180 ↓knee pain scores in the
mg/day of curcumin Theracurmin group.
An exploratory, 12 weeks 12 weeks 22 patients with knee osteoarthritis ↓serum Coll2–1 levels. <.05 Henrotin et al.,
noncontrolled treated with 252 mg/day curcumin ↓the global assessment 2014
clinical trial (6 caps/day Flexofytol®) of disease activity.
A registry study 12 weeks 12 weeks 50 patients with OA treated with Meriva® was clinically <.05 Belcaro et al.,
200 mg/day curcumin effective in the 2010b
management and
treatment of osteoarthritis,
reducing global WOMAC
score and prolonging
walking distance in the
treadmill test.
A study with patients 32 weeks 32 weeks 100 osteoarthritis patients, of whom Meriva® could be a <.05 Belcaro et al.,
from an open, 50 were treated with the standard promising option for 2010a
product evaluation treatment and 50 with standard the long‐term
registry for the treatment plus curcumin, with complementary
complementary 200 mg curcumin/ day (two 500 mg management of
management of Meriva® tablets daily) osteoarthritis,
osteoarthritis improving clinical
and biochemical
measures.
A randomized, 8 weeks 8 weeks 45 patients diagnosed with Curcumin group showed <.05 Chandran &
single‐blinded, rheumatoid arthritis treated the highest percentage Goel, 2012
pilot study with 500 mg curcumin and of improvement in overall
50 mg diclofenac sodium disease activity score and
alone or combination American College of
Rheumatology criteria for
reduction in tenderness and
swelling of joint scores.
Safety and superiority of
curcumin treatment in patients
with active RA.

Note. WOMAC = Western Ontario and McMaster Universities.

12 MANTZOROU ET AL.

showed modest potential for the treatment of knee osteoarthritis
(Nakagawa et al., 2014). The aim of an exploratory, noncontrolled clinical
trial was to evaluate the effects of curcumin on serum levels of specific
biomarkers in knee osteoarthritis patients (Henrotin et al., 2014).
Twenty‐two patients with knee osteoarthritis were enrolled to take six
capsules per day of a bioavailable form of curcumin (Flexofytol®;
Appelboom, Maes, & Albert, 2014), containing 42 mg curcumin mixed
with polysorbate (Tween 80®) for 3 months. Curcumin was well toler-
ated, and after 84 days, it significantly reduced serum Coll2–1 levels, a
cartilage specific biomarker, as well as patient's global assessment of dis-
ease activity (Henrotin et al., 2014). However, it is important to note that
this study was partially sponsored by the manufacturer of the curcumin
supplement, Tilman S.A.
Another highly bioavailable from of curcumin (Meriva®) was
evaluated in a registry study to define its efficacy in 50 patients with
osteoarthritis at daily dosages corresponding to 200 mg curcumin
(Belcaro et al., 2010b). After 3 months of treatment, the global
Western Ontario and McMaster Universities score was decreased
by 58%, walking distance in the treadmill test was prolonged from
76 m to 332 m, and CRP levels was also decreased in patients with
high baseline CRP. Moreover, the treatment costs were reduced
significantly in the treatment group. These findings supported
evidence that a bioavailable form of curcumin (Meriva®) was clinically
effective in the management and treatment of osteoarthritis (Belcaro
et al., 2010b).
Meriva® was further investigated in 100 osteoarthritis patients
for 8 months (Belcaro et al., 2010a). Fifty patients were treated with
the standard treatment and 50 with standard treatment plus 200 mg
curcumin/day. Significant improvements were observed on several
clinical and biochemical measures, such as Western Ontario and
McMaster Universities scores, pain, stiffness, physical, emotional and
social function, and on treadmill walking performance. In addition,
painkiller use was reduced in the Meriva® treated group compared
with control group. These findings supported evidence that Meriva®
could be considered as a promising option for the long‐term comple-
mentary management of osteoarthritis (Belcaro et al., 2010a).
Furthermore, another pilot clinical study evaluated the safety and
effectiveness of no bio‐optimized curcumin alone, and in combination
with diclofenac sodium in rheumatoid arthritis patients (Chandran &
Goel, 2012). Forty‐five patients diagnosed with rheumatoid arthritis
were randomized into three groups, which included patients receiving
500 mg of curcumin or 50 mg of diclofenac sodium alone, or their com-
bination. Disease Activity Score scores were significantly improved in
all groups. Interestingly, patients in the curcumin group showed signif-
icantly better improvement in overall Disease Activity Score and Amer-
ican College of Rheumatology criteria scores, compared with the group
receiving diclofenac sodium alone. Hence, it was speculated that
curcumin may exert significant antiarthritis effects, without serious
adverse effects (Chandran & Goel, 2012).
Curcumin was shown to have positive effect on the management
and therapy of osteoarthritis and rheumatoid arthritis, either in a highly
bioavailable form or not, highlighting it as a promising and safe comple-
mentary therapy method.
7 | CU RC U M I N A N D SKI N D I S EA S ES
There are four studies on the role of curcumin supplementation on skin
diseases (Table 5). A randomized, double‐blind, placebo‐controlled
clinical trial assessed the effectiveness of Meriva® in the treatment
of psoriasis (Antiga, Bonciolini, Volpi, Del Bianco, & Caproni, 2015).
More to the point, 63 patients with mild‐to‐moderate psoriasis vulgaris
were randomly divided into two groups treated with topical steroids
and Meriva® at a dosage of 2 g of curcumin per day, or with topical
steroids alone, both for 12 weeks. At 12 weeks, both groups achieved
a significant reduction of Psoriasis Area and Severity Index values,
however, the improvement was markedly greater in patients treated
with both topical steroids and oral curcumin compared with patients

TABLE 5 Clinical studies assessing the effect of curcumin on skin diseases

Intervention Follow Study population & treatment p

Study type period up dose Outcomes value Ref.

A randomized, 12 weeks 12 weeks 63 patients with mild‐to‐moderate ↓psoriasis area and severity <.05 Antiga et al.,
double‐blind, psoriasis vulgaris treated with index values for arm 1. 2015
placebo‐controlled 2 g/day curcumin and topical ↓ IL‐22 serum in patients
clinical trial steroids (arm 1), or with topical treated with oral curcumin.
steroids alone (arm 2)
A Phase II, open‐label, 12 weeks 12 weeks 18 patients with plaque psoriasis The response rate was low and N/A Kurd et al., 2008
Simon's two‐stage treated with 4.5 g/day of oral possibly caused by a placebo
clinical trial curcuminoid C3 complex effect or the natural history of
psoriasis.
A randomized, 4 weeks 4 weeks 96 male Iranian veterans with Anti‐inflammatory effect, as <.05 Panahi,
double‐blind trial chronic SM‐induced pruritic IL‐8 and hs‐CRP were reduced. Sahebkar,
skin lesions treated with Pruritus alleviation and QoL Parvin, &
curcumin (1 g/d, n = 46) or improvement. Saadat, 2012
placebo (n = 50)
A randomized, 4 weeks 4 weeks 96 male Iranian veterans with ↓substance P, ↓activities of <.05 Panahi,
double‐blind, pruritus treated with curcumin superoxide dismutase, Sahebkar,
placebo‐controlled (1 g/day, n = 46) or placebo glutathione peroxidase and catalase. Amiri, et al.,
trial (n = 50) ↓ pruritus severity, ↓ examined scores 2012
and ↓ DLQI's first question.
Greater reduction of DLQI scores in
the curcumin group.

Note. IL = interleukin; SM = sulphur mustard; CRP = C‐reactive protein; QoL = Quality of Life; DLQI = dermatology life quality index.
MANTZOROU ET AL.
treated with topical steroids only. Moreover, IL‐22 serum levels were
significantly reduced in patients treated with oral curcumin. Hence,
bioavailable curcumin was demonstrated to be effective as an adjuvant
therapy for psoriasis treatment, reducing serum IL‐22 levels (Antiga
et al., 2015). Kurd et al. (2008) also determined the safety and efficacy
of oral curcumin treatment in patients with psoriasis. They conducted a
Phase II, open‐label, Simon's two‐stage trial of 4.5 g per day of oral
curcuminoid C3 complex in patients with plaque psoriasis. After
12 weeks, the response rate was 25%, as only two subjects that com-
pleted the trial had responded to curcumin, and maintained the
response up to Week 16. No serious adverse effects were reported,
despite the drop outs, and hence, curcumin was considered safe. How-
ever, the small sample size and the lack of control group was a strong
limitation of this study. Consequently, no firm conclusions could be
drawn on curcumin effectiveness. (Kurd et al., 2008). In view of the
above, curcumin supplementation could be safely used by psoriasis
patients as adjunct therapy. However, more randomized controlled tri-
als for longer study periods should be undertaken, in order to investi-
gate the potential benefits of curcumin supplementation in this
patient population.
Another study investigated the impact of curcumin on serum
inflammatory biomarkers and their association with pruritus severity
and QoL (Panahi, Sahebkar, Parvin, & Saadat, 2012). This study was a
randomized, double‐blind clinical trial conducted on 96 male Iranian
veterans who were suffering from chronic sulphur mustard (SM)‐
induced pruritic skin lesions. Forty‐six patients were randomly
assigned to 1 g/day curcumin and 50 to placebo group for 4 weeks.
Serum IL‐8 and hs‐CRP levels were significantly reduced in both
groups, with the magnitude of reduction being significantly greater in
the curcumin treated group. Serum calcitonin gene‐related peptide
was significantly decreased only in the curcumin treated group. There
were significant correlations between calcitonin gene‐related peptide
and IL‐6 changes, as well as between Dermatology Life Quality Index
(DLQI) and IL‐8 changes in curcumin treated group. Notably, in
curcumin treated group, changes in serum IL‐8 concentrations were
found as the significant predictor of DLQI scores. Thus, this study sup-
ported evidence that curcumin supplementation may effectively ame-
liorate inflammation in patients suffering from chronic SM‐induced
cutaneous complications, and possibly improving pruritus and QoL.
(Panahi, Sahebkar, Parvin, & Saadat, 2012). Another clinical trial inves-
tigated the efficacy of curcumin in the alleviation of SM‐induced
chronic pruritic symptoms (Panahi, Sahebkar, Amiri, et al., 2012). For
this purpose, 96 male Iranian veterans were randomized to receive
either 1 g curcumin or placebo for 4 weeks. Serum concentrations of
substance P as well as activities of superoxide dismutase, glutathione
peroxidase, and catalase were significantly reduced in the curcumin,
compared with placebo group. Curcumin supplementation was also
associated with significant reductions in measures of pruritus severity,
measured by the pruritus score, visual analog scale score, overall and
objective scoring Atopic Dermatitis, and DLQI's first question.
Although DLQI scores decreased in both groups, the magnitude of
reduction was significantly greater in curcumin compared with placebo
group. Hence, it was supported that curcumin may be considered as a
safe and inexpensive treatment for SM‐induced chronic pruritus
(Panahi, Sahebkar, Amiri, et al., 2012).
13
In SM‐induced chronic pruritus, 1 g curcumin supplement could be
safely used for 1 month, effectively reducing inflammation and improv-
ing QoL.
8 | CU RC UMIN AN D I N F L A MMATO RY
B O W EL D I S E A S E S
There are five clinical trials on the effect of curcumin supplementa-
tion on inflammatory bowel disease (Table 6). In fact, Lang et al.
(2015) investigated curcumin's efficacy on inducing remission in
patients with active mild‐to‐moderate Ulcerative Colitis (UC). For this
purpose, a multicenter, randomized, placebo‐controlled, double‐blind
study was undertaken. 50 mesalamine‐treated patients with active
mild‐to‐moderate UC who did not respond to an additional 2 weeks
of the maximum dose of mesalamine by oral and topical therapy took
part. Patients were randomly assigned to groups and were treated
with 3 g/day curcumin or placebo for 1 month, along with
mesalamine. Higher clinical response and remission, as well as endo-
scopic response and remission, at Week 4 was statistically significant
in the curcumin treated group compared with the control one. The
adjunctive mesalamine and curcumin treatment yielded better results
compared with the combination of placebo and mesalamine in induc-
ing clinical and endoscopic remission in patients with mild‐to‐moder-
ate active UC, with no adverse effects. Thus, it was suggested that
curcumin may be considered as a safe and promising agent for the
complementary treatment of UC (Lang et al., 2015). Another random-
ized, double‐blind, single‐center pilot clinical trial was conducted on
patients with distal UC and mild‐to‐moderate disease activity (Singla
et al., 2014). Forty‐five patients were randomized to receive either
NCB‐02 (standardized curcumin preparation enema) plus oral 5‐ASA
or placebo enema plus oral 5‐ASA. Each NCB‐02 enema contained
140 mg of NCB‐02 preparation dissolved in 20 ml of water. Signifi-
cant improvements on clinical response and remission and endoscopic
response were observed in the curcumin treated group compared
with placebo group. Thus, this study supported evidence that the
use of curcumin (NCB‐02) enema may benefit patients with mild‐to‐
moderate distal UC (Singla et al., 2014).
Hanai et al. (2006) assessed the efficacy of curcumin as mainte-
nance therapy in patients with quiescent UC. Specifically, 89 patients
with quiescent UC were recruited for this randomized, double‐blind,
multicenter clinical trial. In fact, 45 patients received 2 g curcumin
per day in addition to sulfasalazine or mesalamine. Another 44 patients
received placebo in addition to sulfasalazine or mesalamine for
6 months. Notably, recurrence rates were significantly lower in the
curcumin group compared with placebo one. Furthermore, curcumin
significantly improved both CAI and endoscopic index. At the end of
follow‐up, 6 months after the end of the trial, eight additional patients
in the curcumin group and six patients in placebo group were relapsed,
with the difference not being statistically significant. Hence, it was
speculated that curcumin may be a promising and safe supplement
for maintaining remission in patients with quiescent UC (Hanai et al.,
2006).
In a prospective tolerability study, 11 pediatric patients with
Crohn disease or UC in remission or with mild disease were evaluated
14 MANTZOROU ET AL.

TABLE 6 Clinical studies assessing the effect of curcumin on inflammatory bowel diseases
Intervention Follow Study population &
Study type period up treatment dose Outcomes p value Ref.

A multicenter randomized,
placebo‐controlled,
double‐blind study
A randomized, double‐blind, 8 weeks
single‐center pilot trial
A randomized, double‐blind, 24 weeks
multicenter trial
A forced dose titration
study
An open label study
4 weeks 4 weeks 50 patients with active mild‐to‐ Addition of curcumin to
moderate UC treated with
curcumin capsules (3 g/day,
n = 26) or an identical
placebo (n = 24)
8 weeks 45 patients with distal UC and Improvements on clinical
mild‐to‐moderate disease
activity treated with NCB‐02
(standardized curcumin
preparation) enema plus oral
5‐ASA, or placebo enema
plus oral 5‐ASA
24 weeks 89 patients with quiescent UC
treated with 2 g curcumin/
day plus sulfasalazine or
mesalamine, and placebo
plus SZ or mesalamine
9 weeks Every 3 weeks Six pediatric patients with
Crohn's disease and five with
UC treated with 1 g/day
8 weeks Every 4 weeks Five patients with ulcerative
proctitis or proctosigmoiditis
treated with 1,100 mg daily
for 1 month and then
1,650 mg daily for another
month
<.05 Lang
mesalamine therapy was et al.,
superior to the combination 2015
of placebo and mesalamine in
inducing clinical and
endoscopic remission, with
no adverse effects attributed
to curcumin.
<.05 Singla
response and remission and et al.,
endoscopic response were 2014
observed in the curcumin
treated group compared with
the placebo group.
Curcumin improved both CAI <.05 Hanai
and endoscopic index. et al.,
2006
All patients tolerated curcumin Suskind
well, with the only symptom et al.,
reported being an increase in 2013
flatulence, in two patients.
Three patients showed
improvement in Pediatric
ulcerative colitis activity
index/ pediatric Crohn's
disease activity index score.
All proctitis patients improved, .02 for the Holt
with reductions in improvement et al.,
concomitant medications in of proctitis 2005
four of them.
Four of five Crohn's disease
patients had lowered Crohn's
disease activity index scores
and sedimentation rates.

Note. UC = ulcerative colitis; CAI = clinical activity index.

(Suskind et al., 2013). All patients received curcumin in addition to
their standard therapy. Patients initially received 500 mg curcumin
twice per day for 3 weeks. Using the forced‐dose titration design,
doses were increased up to 1 g twice per day at Week 3 for a total
of 3 weeks and then titrated again to 2 g curcumin twice per day at
Week 6 for another 3 weeks. All patients tolerated curcumin well,
except for two patients who consistently reported flatulence. Three
of nine patients that completed the trial showed improvement in
Pediatric Ulcerative Colitis Activity Index/Pediatric Crohn's Disease
Activity Index score. This pilot study suggested that curcumin may
be considered as an adjunctive therapy for individuals seeking a com-
bination of conventional medicine and alternative medicine (Suskind
et al., 2013).
In an open label study, a pure curcumin preparation was
administered to five patients with ulcerative proctitis and to
another five patients with Crohn's disease (Holt, Katz, & Kirshoff,
2005). Patients were administered 550 mg of curcumin, twice daily
for 1 month and then 550 mg 3 times daily for another month. All
proctitis patients improved, with reductions in concomitant medica-
tions in four patients, and four of five Crohn's disease patients had
lowered Crohn's Disease Activity Index scores and sedimentation
rates (Holt et al., 2005). Curcumin supplementation or curcumin
enema could be safely used and improve treatment outcomes in
patients with inflammatory bowel disease, even in pediatric popula-
tions, however, clinical trials with longer study periods and more
participants are strongly required in order for more precise conclu-
sions to be drawn.
9 | CU RC UMIN AND P REMENS TRUAL
SYNDROME SYMPTOMS
A recent double‐blinded study evaluated the effects of curcumin on
the severity of premenstrual syndrome symptoms (Khayat et al.,
2015). In fact, 70 women suffering from premenstrual syndrome
symptoms were randomly allocated to placebo and curcumin groups.
Then each participant received 200 mg/day (two capsules daily) for
7 days before menstruation and for 3 days after menstruation for
three successive menstrual cycles. After three consecutive cycles of
curcumin treatment, total severity of premenstrual syndrome score
MANTZOROU ET AL. 15

TABLE 7 Clinical studies assessing the effect of curcumin on post‐menopausal health

Intervention Follow p
Study type period up Study population & treatment dose Outcomes value Ref.

A 3‐arm, 8 weeks 8 weeks 32 postmenopausal women assigned to Curcumin and aerobic exercise training <.05 Akazawa
controlled three groups: control, exercise, and ↑flow‐mediated dilation in et al.,
trial 150 mg/day curcumin (Theracurmin) postmenopausal women. Both may 2012
potentially improve the age‐related
decline in endothelial function.
A pilot, 8 weeks 8 weeks 45 postmenopausal women were assigned to Regular endurance exercise combined with <.05 Sugawara
randomized, four interventions: “placebo ingestion” daily curcumin ingestion may ↓left et al.,
double‐blind, (n = 11), “150 mg/day curcumin ingestion” ventricular afterload to a greater extent 2012
placebo‐ (n = 11), “exercise training with placebo than monotherapy.
controlled ingestion” (n = 11), or “exercise training
study with 150 mg/day curcumin” (n = 12)

was significantly reduced. Furthermore, significant differences 1 1 | C U R C U M I N A N D CH R O N I C A N T E R I O R

between mean changes were recorded. These results showed for
the first time a potential advantage of curcumin supplementation on
reducing PMS symptoms, possibly mediated via the modulation of
neurotransmitters and the anti‐inflammatory effects of curcumin
(Khayat et al., 2015).
10 | CURCUMIN AND POSTMENOPAUSAL
H E A LT H
There are two studies evaluating the role of curcumin in postmeno-
pausal health (Table 7). Akazawa et al. (2012) investigated the effects
of curcumin ingestion and aerobic exercise training on flow‐mediated
dilation, as an endothelial function indicator in postmenopausal
women. Thirty‐two postmenopausal women were assigned to three
groups: control, exercise, and curcumin groups. The curcumin group
ingested 150 mg highly bioavailable curcumin orally (Theracurmin),
and the exercise group underwent moderate aerobic exercise training
both for 8 weeks. Flow‐mediated dilation increased significantly and
similarly in both curcumin and exercise groups, whereas no changes
were observed in control group. Thus, this study indicated that
curcumin ingestion and aerobic exercise training enhanced flow‐
mediated dilation in postmenopausal women, potentially improving
the age‐related decline in endothelial function (Akazawa et al., 2012).
Furthermore, a randomized, double‐blind, placebo‐controlled pilot
study evaluated whether regular endurance exercise, combined with
150 mg daily curcumin ingestion may attenuate age‐related increase
in left ventricular afterload to a greater extent, compared with mono-
therapy (Sugawara et al., 2012). Forty‐five women were randomly
assigned to four interventions (placebo or curcumin ingestion, exercise
training with placebo or curcumin ingestion) for 8 weeks. After inter-
ventions, brachial systolic blood pressure significantly decreased in
both exercise‐trained groups, whereas aortic systolic blood pressure
significantly decreased only in the exercise and curcumin group. Heart
rate corrected aortic augmentation index significantly decreased only
in the combined‐treatment group. Hence, regular endurance exercise
combined with daily curcumin ingestion may reduce left ventricular
afterload to a greater extent than monotherapy in postmenopausal
women (Sugawara et al., 2012). Thus, 150 mg/day curcumin might
contribute to reduction of left ventricular afterload and endothelial
function in postmenopausal women.
UVEITIS
There is one study investigating the role of curcumin on chronic ante-
rior uveitis, Lal et al. (1999) performed a study in which curcumin was
orally administered to patients suffering from chronic anterior uveitis
at a dose of 1,125 mg/day (375 mg, 3 times a day) for 12 weeks.
Thirty‐two patients completed this study, being divided into two
groups. A group of 18 patients received curcumin alone, whereas the
other group of 14 patients, who had a strong purified protein deriva-
tive reaction, additionally received antitubercular treatment. All
patients showed signs of improvement after 2 weeks of treatment,
whereas the group receiving antitubercular therapy along with
curcumin had a response rate of 86%. Three‐year follow‐up of all
patients indicated a recurrence rate of 55% in the first group and of
36% in the second group. Four out of 18 patients in the curcumin
group and 3 out of 14 patients in the curcumin and antitubercular
treatment group lost their vision in the follow‐up period, due to vari-
ous complications in the eyes. The efficacy of curcumin and recur-
rences following treatment were comparable with corticosteroid
therapy, the only available standard treatment for chronic anterior
uveitis. Notably, the lack of side effects with curcumin was the
greatest advantage of this treatment, compared with corticosteroids
(Lal et al., 1999).
12 | CONCLUSIONS
There is currently substantial evidence that curcumin consumption
may exert beneficial effects against numerous chronic diseases by pro-
moting human health and preventing disease. Notably, several clinical
studies have evaluated the effectiveness of curcumin consumption in
patients suffering from obesity, metabolic syndrome, or diabetes. On
the basis of the results of these studies, it was found that curcumin
consumption exerted a positive effect on weight management of
obese individuals, lowering blood lipids and improving glycemic con-
trol. This result is in line with a recent meta‐analysis, which showed
that curcumin supplementation can lower plasma leptin levels (Atkin,
Katsiki, Derosa, Maffioli, & Sahebkar, 2017), and a systematic review
that documented a decrease in fasting glucose levels after 2 hr of oral
glucose tolerance test, glycosylated hemoglobin levels A1c, and insulin
resistance (HOMA‐IR; Demmers, Korthout, van Etten‐Jamaludin,
16
Kortekaas, & Maaskant, 2017). Moreover, curcumin administration in
patients suffering from various types of cancer, such as prostate,
breast, pancreatic, biliary tract, and colon cancer may improve overall
health, ameliorating the adverse side effects induced by common phar-
maceutical regimens and, in some cases, slowing down disease pro-
gression. Also, it has been documented that curcumin
supplementation may exert potential benefits in people suffering from
depression, leading to delay of disease progression and enhancing
common antidepressant treatment. Notably, curcumin was also con-
sidered as an effective and safe cotreatment for patients with MDD.
However, other clinical studies documented that there was no defini-
tive evidence on the beneficial effects of curcumin against depression,
reinforcing the need for further clinical studies conducted on larger
populations that need to be followed‐up for at least 24 months. None-
theless, a recent meta‐analysis by Al‐Karawi, Al Mamoori, and Tayyar
(2016) found that curcumin supplementation in middle‐aged people
with major depression may have a positive effect on their depressive
symptoms, when administered for the longest period of time
(≥6 weeks), at higher doses (1 g), either with standard or with highly
bioavailable supplement.
Furthermore, certain clinical studies presented encouraging results
concerning the beneficial effects of curcumin consumption in people
suffering from arthritis. Curcumin seems to be a safe treatment in
patients suffering from active rheumatoid arthritis. However, long‐
term studies are strongly recommended in order to assess the effec-
tiveness and safety of curcumin in these disease states. In fact, in the
meta‐analyses of both Del Grossi Moura et al. (2017) and Onakpoya,
Spencer, Perera, and Heneghan (2017), it was stated that well‐
designed studies are needed for firm conclusions concerning the effec-
tiveness of curcumin on osteoarthritis. Moreover, certain clinical stud-
ies evaluated whether curcumin consumption may exert beneficial
effects in people suffering from skin diseases. Most of these studies
provided evidence that curcumin could be considered as a supplemen-
tary, natural, safe, and inexpensive therapy to combat the obtrusive
symptoms of skin diseases, a finding, which is in accordance to a recent
meta‐analysis by Vaughn, Branum, and Sivamani (2016). However, one
study did not show evidence of effectiveness, probably due to the fact
that the relative sample size was quite small and there was no placebo
group to make the relative comparisons.
Furthermore, the curcumin consumption effects were examined in
people suffering from inflammatory bowel disease. These studies doc-
umented that curcumin may be used as adjunct therapy, because it led
to significant disease improvements, being also considered as a prom-
ising, safe, and potential pharmaceutical regimen, with promising
effects also noticed in recent systematic reviews (Langhorst et al.,
2015; Schneider, Hossain, VanderMolen, & Nicol, 2017). Finally, a
probable beneficial effect of curcumin in premenstrual syndrome
symptoms and postmenopausal endothelial function and left ventricu-
lar afterload was recorded. However, all the above studies are prelim-
inary and should be replicated by well‐designed, prospective, and
randomized placebo‐controlled clinical trials. Despite that, curcumin
is one of the 25 best‐selling nutraceuticals, as of 2015 (Andrew & Izzo,
2017). In fact, its retail sales, as of 2015, were 15.73 million US dollars,
showing a 117.7% increase on sales, when compared with 2014
(Smith, Kawa, Eckl, & Johnson, 2016).
MANTZOROU ET AL.
From the currently available findings of the completed clinical tri-
als, curcumin's effect in various chronic diseases is promising. How-
ever, this polyphenol has not yet been approved as medicine for
human use. This fact may mainly be ascribed to its poor bioavailability,
and therefore, further clinical studies evaluating more bioavailable
curcumin formulations, and studies assessing its role via the gut, are
strongly recommended. In addition to this, the fact that many studies
that used standard (not highly bioavailable) form of curcumin have
shown positive results, it could signify that other active compounds
of turmeric extract, other than curcumin, may enhance the activity
and/or bioavailability of the standard forms of curcumin (Braga, Leal,
Carvalho, & Meireles, 2003; Yue et al., 2010; Yue et al., 2012), whereas
the great use of highly bioavailable forms of curcumin may lead to the
underestimation of those compounds. Moreover, small sample sizes,
recall bias, and lack of placebo group in several clinical trials are major
limitations to verify the potential beneficial utility of curcumin against
chronic diseases. Furthermore, it should be noted that several studies
reported some dropouts due to curcumin effects, and others docu-
mented low compliance or progressive disease, or subjects that did
not come back for follow‐up. The results from ongoing clinical trials
will provide a better understanding of curcumin's beneficial effects
on human health promotion and disease prevention, reinforcing its
potential use as a requisite supplement in conjunction with the com-
mon therapy.
CONFLIC T OF IN TE RE ST
The authors have declared no conflict of interest.
FUNDING
This research did not receive any specific grant from funding agencies
in the public, commercial, or not‐for‐profit sectors.
ORCID
Maria Mantzorou http://orcid.org/0000-0002-2535-2841
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How to cite this article: Mantzorou M, Pavlidou E, Vasios G,
Tsagalioti E, Giaginis C. Effects of curcumin consumption on
human chronic diseases: A narrative review of the most recent
clinical data. Phytotherapy Research. 2018;1–19. https://doi.
org/10.1002/ptr.6037