Full Terms & Conditions of access and use can be found at
Critical Reviews in Food Science and Nutrition
ISSN: 1040-8398 (Print) 1549-7852 (Online) Journal homepage: http://www.tandfonline.com/loi/bfsn20
Curcumin, an active component of turmeric
(Curcuma longa), and its effects on health
Betül Kocaadam & Nevin Şanlier
To cite this article: Betül Kocaadam & Nevin Şanlier (2017) Curcumin, an active component of
turmeric (Curcuma longa), and its effects on health, Critical Reviews in Food Science and Nutrition,
57:13, 2889-2895, DOI: 10.1080/10408398.2015.1077195
To link to this article: https://doi.org/10.1080/10408398.2015.1077195
Accepted author version posted online: 03
Published online: 03 Nov 2015.
Submit your article to this journal
Article views: 2124
View related articles
View Crossmark data
Citing articles: 15 View citing articles
Curcumin, an active component of turmeric (Curcuma longa), and its effects on health
ul Kocaadam and Nevin ¸Sanlier
Faculty of Health Sciences, Nutrition and Dietetics Department, Gazi University, Ankara, Turkey
Turmeric (Curcuma longa) is a type of herb belonging to ginger family, which is widely grown in southern
and south western tropical Asia region. Turmeric, which has an importance place in the cuisines of Iran,
Malesia, India, China, Polynesia, and Thailand, is often used as spice and has an effect on the nature, color,
and taste of foods. Turmeric is also known to have been used for centuries in India and China for the
medical treatments of illnesses such as dermatologic diseases, infection, stress, and depression. Turmeric’s
effects on health are generally centered upon an orange-yellow colored, lipophilic polyphenol substance
called “curcumin,”which is acquired from the rhizomes of the herb. Curcumin is known recently to have
antioxidant, anti-inﬂammatory, anticancer effects and, thanks to these effects, to have an important role in
prevention and treatment of various illnesses ranging notably from cancer to autoimmune, neurological,
cardiovascular diseases, and diabetic. Furthermore, it is aimed to increase the biological activity and
physiological effects of the curcumin on the body by synthesizing curcumin analogues. This article reviews
the history, chemical and physical features, analogues, metabolites, mechanisms of its physiological
activities, and effects on health of curcumin.
Turmeric; curcumin; health;
Turmeric is acquired from Curcuma long L., a tuberous herba-
ceous perennial plant with yellow ﬂowers and wide leaves,
which is a member of ginger family and grows in tropical cli-
mate (Akpolat et al., 2010; Prasad et al., 2014). Unlike cinna-
mon, turmeric has not any different kinds. On the other hand,
geographical conditions of the region where it grows and the
features of its soil may affect the growth, nutrition composition,
and quality of this plant (Hossain and Ishimine, 2005; Haya-
kawa et al., 2011). While this plant is rather an important spice
in Iran, it is also an important component of curries to which it
gives the yellow color in Malesia, India, China, Polynesia, and
Thailand, and the mustard and sauces in the West (Gupta
et al., 2013a). Turmeric is also used to add ﬂavor and color to
rice, pasta, meat and vegetable dishes, and salads.
It is stated that turmeric has been widely used for medical
treatments of various diseases for at least 2500 years in Asian
countries mostly (Gupta et al., 2013a) and it has many beneﬁts
for prevention and treatment of many diseases in Ayurveda
and traditional Chinese medicine (Deogade and Ghate, 2015).
The importance of turmeric in medical treatment primarily
stems from orange-yellow colored curcumin, the most active
component. Curcumin is a lipophilic polyphenol substance
(Jurenka, 2009), which constitutes the 2–5% of turmeric
powder (Deogade and Ghate, 2015).
With the studies about curcumin, it has been determined
that the chemical structure of this polyphenol substance shows
antioxidant, antimicrobial, anti-inﬂammatory, antiangiogenic,
antimutagenic, and antiplatelet aggregation properties (Patil
et al., 2009; Shehzad et al., 2013; Prasad et al., 2014; Deogade
and Ghate, 2015). It is stated that, thanks to this properties,
curcumin has a protective and preventive effect against various
diseases such as cancer, autoimmune, neurological, metabolic,
lung, liver, and cardiovascular diseases (CVDs) (Gupta et al.,
2013b; Prasad et al., 2014).
Recently, substantial importance has been put on polyphe-
nol substances due to their effects on various degenerative dis-
eases, especially cancer (Sohrab et al., 2013). Examination of
the effects of curcumin on health, which is also a polyphenol
substance, is highly signiﬁcant.
Curcumin and its historical process
Curcumin was deﬁned as “substance that gives the yellow
color”by Vogel and Pelletier about 200 years ago. In 1842, it
was purely acquired by Vogel Jr. In the mid-1900, curcumin
was stated to be a biologically active component, to have
antibacterial property, and therefore, to be effective against
Staphylococcus aureus, Salmonella paratyphi, Mycobacterium
tuberculosis, and Trichophyton gypseum types. In 1953,
Srinivasan determined the existence of other components called
curcuminoids as well as curcumin with the analysis of turmeric
through chromatography (Patil et al., 2009; Prasad et al., 2014;
Deogade and Ghate, 2015).
Later, curcumin was said to have a cholesterol-lowering,
antidiabetic, anti-inﬂammatory, and antioxidant properties and
CONTACT Nevin ¸Sanlier, Professor email@example.com Gazi University, Faculty of Health Sciences, Nutrition and Dietetics Department, Emniyet Mahallesi,
Muammer Ya¸s ar BostancıCaddesi, No:16, 06500 Be¸sevler/Ankara, Turkey.
Color versions of one or more of the ﬁgures in the article can be found online at www.tandfonline.com/bfsn.
© 2017 Taylor & Francis Group, LLC
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
2017, VOL. 57, NO. 13, 2889–2895
to have an anticancer activity in both in vitro and in vivo mod-
els. Then, with the clinical studies conducted with humans, it
was determined that curcumin was safe and effective. Food and
Drug Administration (FDA) conﬁrmed curcumin as a com-
pound “generally recognized as safe”(Patil et al., 2009; Prasad
et al., 2014).
Chemical and physical characteristic of curcumin
The compound of turmeric contains carbohydrate (69.4%),
protein (6.3%), fat (5.1%), mineral (3.5%), and moisture
(13.1%) (Prasad et al., 2014). The essence of turmeric roots,
pulverized by drying, also contains curcuminoids consisting of
curcumin components. Curcuminoids consist of curcumin
(77%), demethoxycurcumin (DMC; 17%), and bidemethoxy-
curcumin (BDMC; 3%) (Goel et al., 2008). It is stated that even
if studies focus on curcumin, other curcuminoid components
also have biological activities (Shehzad et al., 2010).
Chemical denotation of curcumin is 1,7-bis-(4-hydroxy-3-
methoxyphenyl)-hepta-1,6-diene-3,5-dione or dipheruloylme-
thane; while its chemical formula is C
(Fig. 1) (Deogade
and Ghate, 2015; Pubchem Open Chemistry Data Base, 2015).
Curcumin is not soluble in water at acidic and neutral pH.
However, it is soluble in acetone, methanol, and ethanol (Goel
et al., 2008; Jurenka, 2009). It is stated that curcumin is sensi-
tive to light and, therefore, it is recommended that biological
samples containing curcumin are to be protected from light
(Prasad et al., 2014).
Curcumin’s natural, synthetic analogues and
Due to its insufﬁcient absorption by the body, high metabolism
speed, and high elimination from the body, curcumin has a
limited bioavailability in the body. The low bioavailability of
curcumin limits signiﬁcantly the therapeutics effects of this
component (Devassy et al., 2015). Now, new methods have
been developed to increase the bioavailability of curcumin. One
of these methods is to use piperine with curcumin. It has been
shown that piperine increases the bioavailability of curcumin
on humans and rats by decreasing glucuronidation of curcumin
(Aggarwal and Harikumar, 2009). Use of liposomal curcumin,
curcumin nanoparticles, and phospholipid complexes are
among other methods. Besides, it is stated that use of structural
analogues of curcumin also increases bioavailability (Shehzad
et al., 2010; Devassy et al., 2015).
It is stated that DMC and BDMC, natural analogues of cur-
cumin, have biological activity like curcumin. A study has
found that inﬂammatory transcription factor nuclear factor
kappaB (NF-kB) suppression of curcumin is much more effec-
tive than others (curcumin >DMC >BDMC). It is thought
that this result may stem from the important role of methoxy
groups on the phenyl ring of curcumin (Sandur et al., 2007).
DMC and BDMC have been determined to suppress Inos
and COX-2, which are NF-kB onset inﬂammatory molecules
(Guo et al., 2008). Curcumin and DMC have been shown to be
effective for decreasing AGEs-originated reactive oxygen types
(ROS) in mesangial cells curcumin and DMC have also been
determined to increase signiﬁcantly the advanced glycosylation
end products (AGEs) decreasing superoxide dismutase activity
and malondialdehyde component in the surface of cell culture.
It is also stated that these two components provide protection
against AGEs-originated apoptosis, and due to these effects,
they may provide protection against diabetic neuropathy (Liu
et al., 2012).
There are many metabolites of curcumin such as dihydro-
curcumin, tetrahydrocurcumin (THC), octahydrocurcumin
(OHC), hexahydrocurcumin (HHC), curcumin glucuronide,
and curcumin sulfate (Prasad et al., 2014). After many
researches on curcumin metabolites, it has been determined
that THC shows antioxidant (Murugan and Pari, 2006), anti-
inﬂammatory (Lai et al., 2011), and anticancer (Wu et al.,
2011) effects; that HHC has anticancer (Srimuangwong et al.,
2012), antioxidant and anti-inﬂammatory (Li et al., 2012), and
platelet aggregation epistasis (Dong et al., 2012) properties; that
OHC has anti-inﬂammatory and antioxidant effects (Somparn
et al., 2007; Prasad et al., 2014).
Furthermore, synthetic derivatives of curcumin can be
acquired with such chemical modiﬁcations as phenolic
hydroxyl groups, acylation, alkylation, glycosylation, and
amino acylation (Prasad et al., 2014).
Biological activities and molecular targets of curcumin
and related diseases
In ancient times, curcumin appeared in the Ayurveda medical
treatment methods applied in India, used in treatment of inju-
ries, skin diseases, eye infections, ambustions, and acne
(Hatcher et al., 2008). Curcumin is also an important compo-
nent of traditional treatment methods called Jiawei-Xiaoyao in
China, and it has been used for the treatment of various dis-
eases like dyspepsia, stress, and depression for thousands of
years (Qin et al., 2009). In the last 30 years, curcumin was
shown to have a therapeutic effect against cancer, autoimmune
diseases, metabolic diseases, neurological diseases, CVDs, lung
diseases, liver diseases, and a variety of other inﬂammatory dis-
eases (Aggarwal and Harikumar, 2009; Kannappan et al., 2011).
Curcumin is thought to be effective on pathogenesis of
molecular targets with the purpose of prevention and treatment
of diseases. It is stated that the modulation of these molecular
targets that have a role in the formation process of the disease
can be achieved. It has been proven, for instance, that tumor
development can be suppressed by suppressing cancer cell sig-
nal pathway (Devassy et al., 2015). Curcumin, with its polyphe-
nol structure, is shown to be able to effectively modulate
Figure 1. Chemical structure of curcumin.
2890 B. KOCAADAM AND N. ¸SANLIER
molecular targets that have a role in the pathogenesis of many
diseases (Fig. 2). Curcumin has been determined to play an
important role regulating cytokines, kinases, enzymes, tran-
scription factors, growth factors, receptors, metastatic, and apo-
ptotic molecules in almost all phases of the development of
many diseases (Shehzad and Lee, 2010; Baliga et al., 2012; Pra-
sad et al., 2014). The fact that its structure is inclined to high-
level methoxylation and low-level hydrogenation and gives cur-
cumin a property that increases free radicals scavenging activ-
ity. It is stated that this structure probably enables curcumin to
have an anticancer, anti-inﬂammatory, and antioxidant effect
(Devassy et al., 2015)(Fig. 2).
Even curcumin has already been shown to have a positive effect
against many diseases; its effect against cancer is the most
under-researched topic (Devassy et al., 2015). Curcumin has
been found to be effective in many phases of cancer develop-
ment, to suppress transformation, beginning, development and
invasion of tumor, angiogenesis, and metastasis. Curcumin has
been determined to suppress the growth of tumor cells via cell
proliferation pathway (cyclin D1, c-myc), cell survival pathway
(Bcl-2, Bcl-xL, cFLIP, XIAP, and cIAP1), caspase activation
pathway (caspase ¡8, ¡3, and ¡9), tumor suppressor pathway
(p53, p21), death receptor pathway (DR4, DR5), and many cell
signal pathways that contain protein kinase pathway (c-Jun
N-terminal kinases (JNK), protein kinase B (PKB), also known
as Akt, and 50adenosine monophosphate-activated protein
kinase (AMPK)) (Ravindran et al., 2009). It is stated that,
thanks to these effects of curcumin, it is effective for decreasing
or preventing various cancer types including multiple myeloma
and colon, pancreas, breast, prostates, and lung cancers (Anand
et al., 2008; Devassy et al., 2015). It is also stated that curcumin
increases the effectiveness of radiotherapy and thus, it may
open a quicker path to treatment (Akpolat et al., 2010).
In a study dealing with monocarbonyl analogue of B63
acquired through some chemical modiﬁcations of curcumin’s
structure, this component has been shown to have a higher
antiproliferative effect than curcumin on colon cancer cells. At
the same time, with the use of less B63 (50 mg/kg B63, 100 mg/
kg curcumin), suppression of tumor growth has been achieved
like curcumin (Zheng et al., 2014).
Anti-inﬂammatory and antioxidant effects
Curcumin has been determined to be an anti-inﬂammatory and
antioxidant agent (Deogade and Ghate, 2015). It is thought that
curcumin has these properties due to hydroxyl and methoxy
groups (Rahman and Biswas, 2009). Curcumin enables negative
regulation of proinﬂammatory interleukins (IL-1, ¡2, ¡6, ¡8,
and ¡12), cytokines (tumor necrosis factor-alpha (TNF-a),
monocyte chemoattractant protein-1) by causing down-regula-
tion of janus kinase and signal transducer and activator of tran-
scription (JAK/STAT) signaling pathway. It is also stated that
curcumin regulates the inﬂammatory response by down-regu-
lating enzymes of inducible nitric oxide synthase (iNOS), cyclo-
oxygenase-2 (COX-2), lipoxygenase, and xanthine oxidase
activity; and thus, it may cause to suppress activation of NF-kB
(Rahman and Biswas, 2009).
Curcumin is stated to show its effectiveness by inhibiting
inﬂammatory cell proliferation, metastasis, and angiogenesis
through various molecular targets (Shehzad et al., 2013). Large-
scale studies have shown that inﬂammation changes the signal
pathways; and thus it is related to the increase of inﬂammatory
biomarkers, lipid peroxides, and free radicals. Acute and chron-
ical inﬂammation is an important risk factor for cardiovascular,
neurodegenerative, and metabolic diseases, obesity, type 2
Figure 2. Related molecular targets and diseases of curcumin.
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 2891
diabetes, and some cancer types (Dantzer et al., 2008; Medzhi-
tov, 2008). Curcumin is stated to be effective for the treatment
of various inﬂammatory diseases such as obesity, diabetes,
CVDs, neurological diseases, and inﬂammatory bowel disease
(IBD) (Shehzad et al., 2013; Prasad et al., 2014; Deogade and
Curcumin exhibits strong antioxidant effect through free-
radical-scavenging activity (Deogade and Ghate, 2015). Even
though curcumin shows antioxidant effect, in order to increase
its antioxidant capacity, analogues of curcumin are focused on.
Dolai et al. (2011) showed that the synthetic sugar analogue of
curcumin is a stronger antioxidant. It has been determined that
while curcumin suppresses tau peptides aggregation and amy-
loid-bat micromolar concentrations, sugar-curcumin conju-
gate shows suppressing effect for this aggregation even in
Inﬂammation has been determined to play a great role in devel-
opment of cardiovascular diseases (CVD). Curcumin treatment
is stated to have an anti-inﬂammatory effect against CVD, by
means of various mechanisms. Curcumin is stated to enable
HO-1 expression by actuating Nrf2-dependent antioxidant
response element. It is also stated that curcumin suppress
TNF-ain vascular and aortic smooth muscle cells; and that it
increases p21 expression through HO-1 (Pae et al., 2007;
Wongcharoen and Phrommintikul, 2009). Curcumin treatment
on animals has been determined to decrease ischemia through
activation of JAK2/STAT3 signal pathway (Duan et al., 2012).
In a study done on rats, it has been proven that applying
50 mg/kg curcumin to rats with salt-sensitivity and hyperten-
sive heart disease develops systolic function and prevents coro-
nary failure (Morimoto et al., 2008). In a study on the
effectiveness of curcumin on cardiovascular risk factors in indi-
viduals with coronary artery disease, it has been determined
that serum triglyceride, LDL and VLDL cholesterol levels
decrease considerably in the group of individuals taking curcu-
min. Even though effects of curcumin on blood lipid proﬁle
have been proven, no considerable effect has been determined
on inﬂammatory markers (Mirzabeigia et al., 2015). In a study
conducted in Turkey, the consumption prevalence of plant-
based alternative treatments and supplementary foods of indi-
viduals with CVDs was researched; and it was found out that
turmeric is one of the most popular herbal foods. Also, hyper-
tension and hyperlipidemia are found to be the most important
reasons for patients to use alternative products (
Ipek et al.,
Diabetes mellitus is a health problem affecting liver, heart,
brain, and kidneys. It has been determined that inﬂammation
is the primary cause of type II diabetes development and that
various inﬂammatory cytokines, transcription factors, and
enzymes have an important role in the outset and progression
of diabetes (Choudhary et al., 2011; Shehzad et al., 2013).
Ghorbani et al. (2014) pointed out that curcumin has proper-
ties such as decreasing hepatic glucose production, suppressing
inﬂammatory response stemming from hyperglycemia, increas-
ing GLUT2, GLUT3, and GLUT4 gene expression, increasing
glucose intake of cells, and activating AMPK; and thus, that it
may decrease blood glucose decreasing insulin resistance. They
also stated that, for these reasons, curcumin has an increasing
effect on antihyperglycemic and insulin sensitivity.
One study conducted on type 2 diabetic KK-Ay mice found
that curcumin suppresses the increase in blood glucose level via
peroxisome proliferator-activated receptor-gamma (PPAR-g)
activation (Kuroda et al., 2005). Studies have been conducted
on derivatives of curcumin with the aim of increasing the anti-
diabetic effect of curcumin. For instance, as a result of a study
researching whether a new curcumin derivative (NCD),
acquired by covalent modiﬁcation of curcumin molecule,
shows hypoglycemic effect on diabetic rats, it has been proven
that NCD decreases plasma glucose level at the rate of 27.5%,
and that it increases plasma insulin up to 66.67%. It is stated
that NCD shows this effect by inducing HO-1 gene (Aziz et al.,
2012; Aziz et al., 2013).
Curcumin has been shown to suppress mitogen-activated
protein kinase (MAPK, extracellular signal-regulated kinases
(ERK), JNK, and p38), which is associated with differentiation
of 3T3-L1 cells into adipocytes and activates Wnt/b-catenin
signaling in differentiated adipocytes., which are closely related
to obesity (Ahn et al., 2010). It is stated that curcumin decreases
the macrophage inﬁltration, leptin, and leptin receptor level
(Ob-R) in the white adipose tissue; that it increases the adipo-
nectin expression in inﬂammation-related obesity. It is pointed
out that the adiponectin production, which increases due to
effect of curcumin, may have a positive effect against obesity by
decreasing NF-kB activity (Shehzad et al., 2011).
Inﬂammatory bowel disease
IBD is an immune impairment including Crohn disease and
ulcerative colitis, commonly characterized with digestion sys-
tem chronical inﬂammation (Shehzad et al., 2013). Studies
indicate that curcumin is useful in prevention and treatment of
IBD (Holt et al., 2005; Ali et al., 2012). Curcumin inhibit the
activity of activated protein-1 (AP-1), STAT proteins, PPAR-g,
b-catenin, COX-2, 5-LOX, and iNOS expression which play a
key role in inﬂammation (Taylor and Leonard, 2011). There-
fore, it can reduce colitis. It has been proven that curcumin, at
the same time, suppress TLR4-based NF-kB activation; and
thus, it may be effective for recovery of bowel inﬂammation
(Lubbad et al., 2009; Ali et al., 2012; Baliga et al., 2012).
A pilot study done with Crohn or ulcerative patients by Sus-
kind et al. (2013) indicated that recovery in disease symptoms
is achieved as a result of using curcumin as 500 mg capsules
twice a day during three weeks. Researchers have suggested
that using curcumin as an adjunctive therapy for the individu-
als seeking combination of traditional and alternative treat-
ment. Likewise, Taylor and Leonard (2011) have stated that
curcumin becomes more effective when used with traditional
medicines for the treatment of IBD; and that this combination
is a cheaper alternative method.
Aging is a signiﬁcant risk factor for neurodegenerative diseases.
It is considered that curcumin may be effective on aging
2892 B. KOCAADAM AND N. ¸SANLIER
mechanisms; thus, it may prevent the changes in the cell pro-
teins which occur due to aging. Therefore, it is indicated that
curcumin may help to maintain protein homeostasis and it
may be effective for prevention of aging-associated diseases
(Monroy et al., 2013). Besides, curcumin has scavenge oxygen
derived free-radical property; and thus, curcumin is stated to
be a potential neuroprotective agent (Nabiuni et al., 2011).
In neurodegenerative diseases such as Alzheimer character-
ized with inﬂammation and oxidative injury, abnormal protein
development causes such gene mutations as human amyloid
precursor protein or presenile 1 or 2 (Smith et al., 2007). In
Alzheimer disease, curcumin as an antioxidant, anti-inﬂamma-
tory properties can improve the cognitive functions, and also it
is stated to bring various therapeutic beneﬁts through decreased
b-amyloid plaques and microglia formation, delayed deteriora-
tion of neurons in patients. (Mishra and Palanivelu, 2008).
Parkinson’s disease (PD), one of the most common neuro-
degenerative diseases, is characterized by loss of dopaminergic
neurons in the substantia nigra. The most important biological
effect of curcumin, related to neuroprotection, is its antioxidant
function (Mythri and Srinivas Bharath, 2012). Thus, it protects
substantia nigra neurons, ameliorates dopamine levels in the 6-
OHDA rat model of PD. It is pointed out that curcumin pro-
tects many tyrosine hydroxylase-positive cells in substantia
nigra; and that it maintains the dopamine levels in striatum
probably because of this effect (Zbarsky et al., 2005).
Multiple sclerosis (MS) is a chronic inﬂammatory autoim-
mune disease, characterized with oligodendrocyte in central
nervous system and degradation of myelin sheath. Curcumin
has been shown to inhibit autoimmune diseases by regulating
inﬂammatory cytokines and associated JAK-STAT, AP-1, and
NF-kB signaling pathways (Bright, 2007; Tegenge et al., 2014).
Th17 cells are important factor for the pathophysiological pro-
cess of MS. Curcumin suppresses the differentiation and devel-
opment of Th17 cells through the down-regulation of IL-6,
TGF-b,IL-1b, IL-23, and STAT3-phosphorylation (Xie et al.,
2011). Furthermore, it has been determined that curcumin
inhibits channel Kv1.3, which is mainly effective on T(EM)
cells; and at the same time it suppress the cytokine secretion
and proliferation of T(EM) cells which are isolated from MS
patients (Lian et al., 2013).
The use of curcumin for treatment of skin diseases dates back
to ancient times. Due to its role in treatment of skin diseases in
India, turmeric is used in production of cream and soap in
Ayurveda, the ancient Indian medical system, turmeric is
widely used as an easy treatment method for eye infections,
treat bites, burns, and acne (Hatcher et al., 2008; Akpolat et al.,
Now, it is indicated that curcumin may be effective against
various skin diseases such as dermatitis, psoriasis, and sclero-
derma. It is pointed out that psoriasis, a chronical skin disease,
which is characterized with hyperproliferation and abnormal
differentiation of keratinocyte, can be treated by curcumin
(Prasad et al., 2014). Curcumin can protect skin by scavenging
free radicals and reducing inﬂammation through nuclear fac-
tor-kB inhibition and cytokines (Thangapazham et al., 2007). A
study conducted on mice indicates that curcumin diminished
psoriasis-like inﬂammation by reducing cytokines such as IL-
1band IL-6 (Sun et al., 2013).
Allergy and asthma
Allergy and asthma are proinﬂammatory diseases, stemming
from inﬂammatory cytokines (Shehzad et al., 2013). Turmeric
rhizomes have been long used for treatment of allergy and
asthma in Asia, especially in India; for treatment of itching and
other skin diseases in Thailand (Tewtrakul and Subhadhirasa-
kul, 2007; Viswanath and Christy, 2008). Yano et al. (2000)
have indicated that turmeric exhibits antiallergic activity by
suppressing the 48/80-induced histamine release from mast
cells. The hydroxyl groups of curcumin are indicated to
decrease the allergic reactions and to have a positive effect
against asthma by broadening the narrowed air pathway and
increasing the antioxidant capacity (Viswanath and Christy,
2008; Shehzad et al., 2013). Curcumin has been determined to
cause Th2 response down-regulation by decreasing the produc-
tion of IgE antibodies and cytokine, and enabling the formation
of less inﬂammatory response (Viswanath and Christy, 2008).
The safe dosage and toxicology of curcumin
Curcumin has been conﬁrmed as a “generally recognized as
safe”compound by FDA, and it is stated not to have any toxic
effect. According to Joint FAO/WHO Expert Committee on
Food Additives (JECFA) and European Food Safety Authority
(EFSA) reports, adequate daily intake (ADI) value of curcumin
is 0–3 mg/kg (JECFA, 2004; EFSA, 2014) Lao et al. (2006)
applied 500–12,000 mg curcumin to healthy individuals so as
to examine the maximum tolerance dosage and safety of curcu-
min. As a result, up to 12 g/day intake of curcumin has been
shown to have no harmful effects on individuals. There are
some concerns about the relationship between inhibition of
some enzymes working in drug metabolism, potential DNA
impairment, iron chelation, and curcumin intake. However,
more studies need to be conducted to examine these relation-
ships (Devassy et al., 2015).
Conclusion and suggestions
In conclusion, the effects of curcumin on health are rather
complex as in many other natural products. The results of clini-
cal studies on in vitro, in vivo, and human indicate that curcu-
min may be effective in prevention and treatment of many
diseases, particularly cancer, by affecting various molecular tar-
gets. Safety, active ingredients, interactions, and dosage of the
medicine are highly important in treatment of diseases. For this
reason, the fact that curcumin is a safe natural product and its
cost is lower than drugs may give rise to the thought that curcu-
min can be used in treatment and prevention of diseases.
Because it prevents formation and progression of various dis-
eases, and has positive effects on health, a healthy individual
with a 70 kg body weight can consume 4–10 g turmeric powder
in accordance with JECFA and EFSA’s suggestion that curcu-
min’s ADI value should be 0–3 mg/kg. Oral intake of curcumin
exhibits poor bioavailability, so it limits signiﬁcantly the thera-
peutic effects of this component. Other structural analogues of
curcumin are more bioavailable and effective, and they could
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 2893
be designed as to be combined with large and well-controlled
clinical trials. It will be good to conduct more studies in order
to determine the effectiveness of curcumin, its analogues and
metabolites, interaction of drug-food and drug-nutrient more
ﬁrmly; to clarify the other possible biological activities; to
develop suggestions; to provide evidence about its relations
with other diseases.
Aggarwal, B. B. and Harikumar, K. B. (2009). Potential therapeutic effects
of curcumin, the anti-inﬂammatory agent, against neurodegenerative,
cardiovascular, pulmonary, metabolic, autoimmune, and neoplastic
diseases. Int J Biochem Cell Biol. 41:40–59.
Ahn, J., Lee, H., Kim, S. and Ha, T. (2010). Curcumin-induced suppression
of adipogenic differentiation is accompanied by activation of Wnt/
beta-catenin signaling. Am. J. Physiol. Cell. Physiol. 298:1510–1516.
Akpolat, M., Tarlada¸calı¸sır, Y., Uz, Y., Metin, M. and Kızılay, G. (2010).
Kanser tedavisinde curcuminin yeri. Yeni Tıp Dergisi 27:142–147.
Ali, T., Shakir, F. and Morton, J. (2012). Curcumin and inﬂammatory
bowel disease: Biological mechanisms and clinical implication. Diges-
Anand, P., Sundaram, C., Jhurani, S., Kunnumakkara, A. B. and Aggarwal,
B. B. (2008). Curcumin and cancer: An “old-age”disease with an “age-
old”solution. Cancer Lett. 267:133–164.
Aziz, M. T., El-Asmar, M. F., El-Ibrashy, I. N., Rezq, A., Al-Malki, A., Was-
sef, M. A., Fouad, H. H., et al. (2012). Effect of novel water soluble cur-
cumin derivative on experimental type-1 diabetes mellitus (short term
study). Diabetology Metab. Synd. 4:30.
Aziz, M. T., El Ibrashy, I. N., Mikhailidis, D. P., Rezq, A. M., Wassef, M. A.,
Fouad, H. H., Ahmet, H. H., et al. (2013). Signaling mechanisms of a
water soluble curcumin derivative in experimental type 1 diabetes with
cardiomyopathy. Diabetol Metab Syndr. 5:13.
Baliga, M. S., Joseph, N., Venkataranganna, M. V., Saxena, A., Ponemone,
V. and Fayad, R. (2012). Curcumin, an active component of turmeric
in the prevention and treatment of ulcerative colitis: Preclinical and
clinical observations. Food Funct 3:1109–1117.
Bright, J. (2007). Curcumin and autoimmune disease. Adv Exp Med Biol.
S., et al. (2011). NF-kB-inducing kinase (NIK) mediates skeletal muscle
insulin resistance: Blockade by adiponectin. Endocrinol. 152:3622–3627.
Dantzer, R., O’Connor, J. C., Freund, G., Johnson, W. and Kelley, W.
(2008). From inﬂammation to sickness and depression: When the
immune system subjugates the brain. Nat. Rev. Neurosci. 9:46–56.
Devassy, J., Nwachukwu, I. and Jones, P. (2015). Curcumin and cancer:
Barriers to obtaining a health claim. Nutr. Rev. 73(3):155–165.
Deogade, S. and Ghate, S. (2015). Curcumın: Therapeutıc applıcatıons in
systemıc and oral health. Int. J. Biol. Pharm. Res. 6(4):281–290.
Dolai, S, Shi, W, Corbo, C, Sun, C, Averick, S, Obeysekera, D, et al. (2011).
“Clicked”sugar-curcumin conjugate: Modulator of amyloid-beta and
tau peptide aggregation at ultralow concentrations. ACS Chem Neuro-
Dong, H. P., Yang, R. C., Chunag, I. C., Huang, L. J., Li, H. T., Chen, H. L.
and Chen, C. Y. (2012). Inhibitory effect of hexahydrocurcumin on
human platelet aggregation. Nat. Prod. Commun. 7(7):883–884.
Duan, W., Yang, Y., Yan, J., Yu, S., Liu, J., Zhou, J., et al. (2012). The effects
of curcumin post-treatment against myocardial ischemia and reperfu-
sion by activation of the JAK2/STAT3 signaling pathway. Basic Res
European Food Safety Authority. (2014). Reﬁned exposure assessment for
curcumin (E 100). EFSA J. 12(10):3876
Ghorbani, Z., Hekmatdoost, A. and Mirmiran, P. (2014). Antihyperglyce-
mic and insulin sensitizer effects of turmeric and its principle constitu-
ent curcumin. Int J Endocrinol Metab. 12(4):e18081.
Guo, L. Y., Cai, X. F., Lee, J. J., Kang, S. S., Shin, E. M., Zhou, H. Y., et al.
(2008). Comparison of suppressive effects of demethoxycurcumin and
bisdemethoxycurcumin on expressions of inﬂammatory mediators in
vitro and in vivo. Arch Pharm Res 31:490–496.
Gupta, S. C., Sung, B., Kim, J. H., Prasad, S., Li, S. and Aggarwal, B. B.
(2013a). Multitargeting by turmeric, the golden spice: From kitchen to
clinic. Mol Nutr Food Res. 57(9):1510–1528.
Gupta, S. C., Kismali, G. and Aggarwal, B. B. (2013b). Curcumin, a compo-
nent of turmeric: From farm to pharmacy. Biofactors. 39(1):2–13.
Goel, A., Kunnumakkara, A. B. and Aggarwal, B. B. (2008). Curcumin as
“curecumin”: From kitchen to clinic. Biochem Pharmacol. 75:787–809.
Hatcher, H., Planalp, R., Cho, J., Torti, F. M. and Torti, S. V. (2008). Cur-
cumin: From ancient medicine to current clinical trials. Cell Mol Life
Hayakawa, H., Kobayashi, T., Minamiya, Y., Ito, K., Miyazaki, A., Fukuda,
T. and Yamamoto, Y. (2011). Development of a molecular marker to
identify a candidate line of turmeric (Curcuma longa L.) with a high
curcumin content. Am. J. Plant Sci. 2(1):5–26.
Holt, P., Katz, S. and Kirshoff, R. (2005). Curcumin therapy in inﬂamma-
tory bowel disease: A pilot study. Digest. Dis. Sci. 50(11):2191–2193.
Hossain, A. and Ishimine, Y. (2005). Growth, yield, and quality of turmeric
(Curcuma longa L.) cultivated on dark-red soil, gray soil, and red soil in
Okinawa, Japan. Plant. Prod. Sci. 8(4):482–486.
Ipek, E., G€
uray, Y., Demirkan, B., G€
uray, (., Kafes, H. and Ba¸syi
(2013). Kardiyoloji poliklini
gine ba¸svuran hastalarda bitkisel k€
alternatif tedavilerin ve tamamlayıcıbesin (r€
lansı.Arch Turk Soc Cardiol. 41(3):218–224.
JECFA. (2004). Curcumin. (Prepared by Ivan Stankovic). Chemical and
Technical Assessment Compendıum Addendum 11/Fnp 52 Add.11/29;
Monographs 1 Vol.1/417.
Jurenka, J. S. (2009). Anti-inﬂammatory properties of curcumin, a maj€
constituent of Curcuma longa: A review of preclinical and clinical
research. Altern Med Rev. 14(2):141–153.
Kannappan, R., Gupta, S. C., Kim, J. H., Reuter, S. and Aggarwal, B. B.
(2011). Neuroprotection by spice-derived nutraceuticals: You are what
you eat! Mol Neurobiol. 44:142–159.
Kuroda, M., Mimaki, Y., Nishiyama, T., Mae, T., Kishida, H., Tsukagawa,
M., Takahashi, K., Kawada, T., Nakagawa, K. and Kitahara, M. (2005).
Hypoglycemic effects of turmeric (Curcuma longa L. rhizomes) on
genetically diabetic KK-Ay mice. Biol Pharm Bull. 28(5):937–939.
Lai, C. S., Wu, J. C., Yu, S. F., Badmaev, V., Nagabhushanam, K., Ho, C. T.
and Pan, M. H. (2011). Tetrahydrocurcumin is more effective than cur-
cumin in preventing azoxymethane-induced colon carcinogenesis. Mol
Nutr Food Res. 55:1819–1828.
Lao, C. D., Rufﬁn, M. T., Normolle, D., Heath, D. D., Murray, S. I., et al.
(2006). Dose escalation of a curcuminoid formulation. BMC. Complem.
Altern. Med. 6:10.
Li, F., Nitteranon, V., Tang, X., Liang, J., Zhang, G., Parkin, K. L. and Hu,
Q. (2012). In vitro antioxidant and anti-inﬂammatory activities of 1-
dehydro--gingerdione, 6-shogaol, 6-dehydroshogaol and hexahy-
drocurcumin. Food Chem. 135:332–337.
Lian, Y. T., Yang, X. F., Wang, Z. H., Yang, Y., Yang, Y., Shu, Y. W., Cheng,
L. X. and Liu, K. (2013). Curcumin serves as a human kv1.3 blocker to
inhibit effector memory T lymphocyte activities. Phytother Res.
Liu, J. P., Feng, L., Zhu, M. M., Wang, R. S., Zhang, M. H., Hu, S. Y., et al.
(2012). The in vitro protective effects of curcumin and demethoxycur-
cumin in Curcuma longa extract on advanced glycation end products-
induced mesangial cell apoptosis and oxidative stress. Planta Med.
Lubbad, A., Oriowo, A. and Khan, I. (2009). Curcumin attenuates inﬂam-
mation through inhibition of TLR-4 receptor in experimental colitis.
Mol. Cell. Biochem. 322:127–135.
Medzhitov, R. (2008). Origin and physiological roles of inﬂammation.
Mirzabeigia, P., Mohammadpour, A. H., Salarifar, M., Gholami, K., Mojta-
hedzadeh, M. and Javadi, M. R. (2015). The effect of curcumin on
some of traditional and nontraditional cardiovascular risk factors: A
pilot randomized, double-blind, placebo-controlled trial. Iran. J.
Pharm. Res. 14(2):479–486.
Mishra, S. and Palanivelu, K. (2008). The effect of curcumin (turmeric) on
Alzheimer’s disease: An overview. Ann Indian Acad Neurol. 11(1):13–19.
2894 B. KOCAADAM AND N. ¸SANLIER
Morimoto, T., Sunagawa, Y., Kawamura, T., Takaya, T., Wada, H., Naga-
sawa, A., et al. (2008). The dietary compound curcumin inhibits p300
histone acetyltransferase activity and prevents heart failure in rats. J.
Clin. Invest. 118:868–878.
Monroy, A., Lithgow, G. J. and Alavez, S. (2013). Curcumin and neurode-
generative diseases. Biofactors. 39(1):122–132.
Murugan, P. and Pari, L. (2006). Antioxidant effect of tetrahydrocurcumin
in streptozotocin–nicotinamide induced diabetic rats. Life Sciences. 79
Mythri, R. B. and Srinivas Bharath, M. M. (2012). Curcumin: A potential
neuroprotective agent in Parkinson’sdisease.Curr. Pharm. Des. 18:91–99.
Nabiuni, M., Nazari, Z., Abdolhamid Angaji, S. and Nejad, S. (2011). Neuro-
protective effects of curcumin. Aust.J.BasicAppl.Sci.5(9):2224–2240.
Pae, O., Jeong, S., Jeong, O., Kim, S., Kim, A., et al. (2007). Roles of heme
oxygenase-1 in curcumin-induced growth inhibition in rat smooth
muscle cells. Exp. Mol. Med. 39:267–277.
Patil, P., Jayaprakasha, G. K., Chidambara Murthy, K. N. and Vıkram, A.
(2009). Bioactive compounds: Historical perspectives, opportunities,
and challenges. J. Agric. Food Chem. 57:8142–8160.
Pubchem Open Chemistry Data Base, “Curcumin”. (2015). Access Date:
Prasad, S., Gupta, S., Tyagi, A. and Aggarwal, B. (2014). Curcumin, a com-
ponent of golden spice: From bedside to bench and back. Biotechnol.
Qin, F., Huang, X., Zhang, H. M. and Ren, P. (2009). Pharmacokinetic
comparison of puerarin after oral administration of Jiawei-Xiaoyao-
San to healthy volunteers and patients with functional dyspepsia: Inﬂu-
ence of disease state. J. Pharm. Pharmacol. 61:125–129.
Rahman, I. and Biswas, S. K. (2009). In Regulation of Inﬂammation, Redox,
and Glucocorticoid Signaling by Dietary Polyphenols, Surh, Y. J., Dong,
Z., Cadenas, E., Packer, L. (Eds.), Boca Raton: CRC Press
Ravindran, J., Prasad, S. and Aggarwal, B. B. (2009). Curcumin and cancer cells:
How many ways can curry kill tumor cells selectively? AAPS J. 11:495–510.
Sandur, S. K., Pandey, M. K., Sung, B., Ahn, K. S., Murakami, A., Sethi, G.,
et al. (2007). Curcumin, demethoxycurcumin, bisdemethoxycurcumin,
tetrahydrocurcumin, and turmerones differentially regulate anti-
inﬂammatory and antiproliferative responses through a ROS indepen-
dent mechanism. Carcinogen. 28:1765–1773.
Shehzad, A., Ha, T., Subhan, F. and Lee, S. (2011). New mechanism and
anti-inﬂammatory role of curcumin in obesity and obesity related met-
abolic disease. Eur. J. Nutr. 50:151–161.
Shehzad, A., Khan, S., Shehzad, O. and Lee, Y. S. (2010). Curcumin thera-
peutic promises and bioavailability in colorectal cancer. Drugs Today
Shehzad, A. and Lee, Y. S. (2010). Curcumin: Multiple molecular targets medi-
ate multiple pharmacological actions –Areview.Drugs Fut. 35:113–119.
Shehzad, A., Rehman, G. and Lee, Y. (2013). Curcumin in inﬂammatory
diseases. Int. Union Biochem. Mol. Biology, Inc. 39(1):69–77.
Smith, G., Cappai, R. and Barnham, J. (2007). The redox chemistry of the
Alzheimer’s disease amyloid beta peptide. Biochim. Biophys. Acta.
Srimuangwong, K., Tocharus, C., Yoysungnoen Chintana, P., Suksamrarn,
A. and Tocharus, J. (2012). Hexahydrocurcumin enhances inhibitory
effect of 5-ﬂuorouracil on HT-29 human colon cancer cells. World J
Sohrab, G., Hosseinpour-Niazi, S., Hejazi, J., Yuzbashian, E., Mirmiran, P.
and Azizi, F. (2013). Dietary polyphenols and metabolic syndrome
among Iranian adults. Int J Food Sci Nutr. 64(6):661–667.
Somparn, P, Phisalaphong, C, Nakornchai, S., Unchern, S. and Morales, N.
P. (2007). Comparative antioxidant activities of curcumin and
its demethoxy and hydrogenated derivatives. Biol Pharm Bull. 30:
Sun, J., Zhao, Y. and Hu, J. (2013). Curcumin inhibits imiquimod-induced
psoriasis-like inﬂammation by inhibiting IL-1beta and IL-6 production
in mice. PLoS One. 8:e67078.
Suskind, D. L., Wahbeh, G., Burpee, T., Cohen, M., Christie, D. and Weber,
W. (2013). Tolerability of curcumin in pediatric inﬂammatory bowel
disease: A forced-dose titration study. J Pediatr Gastroenterol Nutr.
Taylor, R. A. and Leonard, M. C. (2011). Curcumin for inﬂammatory
bowel disease: A review of human studies. Altern Med Rev. 16:152–156.
Tegenge, M. A., Rajbhandari, L., Shrestha, S., Mithal, A., Hosmane, S. and
Venkatesan, A. (2014). Curcumin protects axons from degeneration in
the setting of local neuroinﬂammation. Exp Neurol. 253C:102–110.
Tewtrakul, S. and Subhadhirasakul, S. (2007). Antiallergic activity of some
selected plants in the Zingiberaceae family. J. Ethnopharmacol.
Thangapazham, R. L., Sharma, A. and Maheshwari, R. K. (2007). Beneﬁcial
role of curcumin in skin diseases. Adv Exp Med Biol. 595:343–357.
Viswanath, P. K. and Christy, S. B. (2008). Immunomodulatory effects of
curcumin in allergy. Mol. Nutr. Food Res. 52:1031–1039.
Wongcharoen, W. and Phrommintikul, A. (2009). The protective role of
curcumin in cardiovascular diseases. Int. J. Cardiol. 133:145–151.
Wu, J. C., Lai, C. S., Badmaev, V., Nagabhushanam, K., Ho, C. T. and Pan,
M. H. (2011). Tetrahydrocurcumin, a major metabolite of curcumin,
induced autophagic cell death through coordinative modulation of
PI3K/Akt-mTOR and MAPK signaling pathways in human leukemia
HL-60 cells. Mol Nutr Food Res. 55:1646–1654.
Xie, L., Li, A X. and Takahara, S. (2011). Curcumin has bright prospects
for the treatment of multiple sclerosis. Int. Immunopharmaco. 11:
Yano, S., Terai, M., Shimizu, K. L., Futagami, Y., Sekine, T., et al. (2000).
Antiallergic activity of Curcuma longa (II). Features of inhibitory
actions on histamine release from mast cells. Nat. Medicines.
Zbarsky, V., Datla, K. P., Parkar, S., Rai, D. K., Aruoma, O. I. and Dexter,
D. T. (2005). Neuroprotective properties of the natural phenolic antiox-
idants curcumin and naringenin but not quercetin and ﬁsetin in a 6-
OHDA model of Parkinson’s disease. Free Radic Res. 39(10):1119–
Zheng, A, Li, H., Wang, X., Feng, Z., Xu, J. and Cao, K., et al. (2014).
Anticancer effect of a curcumin derivative B63: ROS production and
mitochondrial dysfunction. Current Cancer Drug Targets 14:156–166.
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 2895