Anti-inflammatory Properties of Curcumin, a Major Constituent of Curcuma longa: A Review of Preclinical and Clinical Research

Alternative Medicine Review Volume 14, Number 2 2009
Review Article
Anti-inflammatory Properties of
Curcumin, a Major Constituent
of Curcuma longa: A Review of
Preclinical and Clinical Research
Julie S. Jurenka, MT(ASCP)
Introduction
Turmeric (the common name for Curcuma
Abstract
longa) is an Indian spice derived from the rhizomes of
Curcuma longa (turmeric) has a long history of use in Ayurvedic
the plant and has a long history of use in Ayurvedic
medicine as a treatment for inflammatory conditions. Turmeric
medicine as a treatment for inflammatory conditions. C.
constituents include the three curcuminoids: curcumin
longa is a perennial member of the Zingiberaceae family
(diferuloylmethane; the primary constituent and the one
and is cultivated in India and other parts of Southeast
responsible for its vibrant yellow color), demethoxycurcumin,
Asia.1 The primary active constituent of turmeric and
and bisdemethoxycurcumin, as well as volatile oils (tumerone,
the one responsible for its vibrant yellow color is cur-
atlantone, and zingiberone), sugars, proteins, and resins. While
cumin, first identified in 1910 by Lampe and Milobed-
zka.2 While curcumin has been attributed numerous
numerous pharmacological activities, including antioxidant and
pharmacological activities, including antioxidant3 and
antimicrobial properties, have been attributed to curcumin,
antimicrobial properties,4 this article focuses on one of
this article focuses on curcumin’s anti-inflammatory properties
the best-explored actions, the anti-inflammatory effects
and its use for inflammatory conditions. Curcumin’s effect on
of curcumin. Curcumin’s effect on cancer (from an anti-
cancer (from an anti-inflammatory perspective) will also be
inflammatory perspective) is also discussed; however, an
discussed; however, an exhaustive review of its many anticancer
exhaustive review of its many anticancer mechanisms is
mechanisms is outside the scope of this article. Research has
outside the scope of this article. Based on early research
shown curcumin to be a highly pleiotropic molecule capable
conducted with cell cultures and animal models, pilot
of interacting with numerous molecular targets involved
and clinical trials indicate curcumin may have potential
in inflammation. Based on early cell culture and animal
as a therapeutic agent in diseases such as inflammatory
research, clinical trials indicate curcumin may have potential
bowel disease, pancreatitis, arthritis, and chronic ante-
as a therapeutic agent in diseases such as inflammatory bowel
rior uveitis, as well as certain types of cancer. Numerous
disease, pancreatitis, arthritis, and chronic anterior uveitis, as
clinical trials are currently in progress that, over the next
few years, will provide an even deeper understanding of
well as certain types of cancer. Because of curcumin’s rapid
the therapeutic potential of curcumin.
plasma clearance and conjugation, its therapeutic usefulness
has been somewhat limited, leading researchers to investigate
the benefits of complexing curcumin with other substances
Julie Jurenka, MT (ASCP) – Associate Editor, Alternative Medicine Review;
to increase systemic bioavailability. Numerous in-progress
technical assistant, Thorne Research, Inc. – the manufacturer of Meriva
Curcumin Phytosome
clinical trials should provide an even deeper understanding
Correspondence address: Thorne Research, Inc, PO Box 25, Dover, ID 83825
of the mechanisms and therapeutic potential of curcumin.
Email: juliej@thorne.com
(Altern Med Rev 2009;14(2):141-153)
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Alternative Medicine Review Volume 14, Number 2 2009
Curcumin
Active Constituents
Turmeric is comprised of a group of three cur-
Figure 1. Structures of Curcumin
cuminoids: curcumin (diferuloylmethane), demethoxy-
(Diferuloylmethane), Demethoxycurcumin, and
curcumin, and bisdemethoxycurcumin (Figure 1), as
Bisdemethoxycurcumin
well as volatile oils (tumerone, atlantone, and zingib-
erone), sugars, proteins, and resins. The curcuminoid
CH3O
OCH3
complex is also known as Indian saffron.5 Curcumin is
a lipophilic polyphenol that is nearly insoluble in water6
HO
CH=CHCOCH2COCH=CH
OH
but is quite stable in the acidic pH of the stomach.7
Curcumin
Absorption of Curcumin
Animal studies have shown curcumin is rapidly
OCH3
metabolized, conjugated in the liver, and excreted in the
feces, therefore having limited systemic bioavailability.
HO
CH=CHCOCH2COCH=CH
OH
A 40 mg/kg intravenous dose of curcumin given to rats
resulted in complete plasma clearance at one hour post-
Demethoxycurcumin
dose. An oral dose of 500 mg/kg given to rats resulted
in a peak plasma concentration of only 1.8 ng/mL, with
the major metabolites identified being curcumin sulfate
HO
CH=CHCOCH
OH
and curcumin glucuronide.8
2COCH=CH
Data on the pharmacokinetics, metabolites,
and systemic bioavailability of curcumin in humans,
mainly conducted on cancer patients, are inconclusive.
A phase I clinical trial conducted on 25 patients with
1/45 of the levels reported by Cheng et al, who used
various precancerous lesions demonstrated oral doses
a similar dose of curcumin (4 g).9 The reason for the
of 4, 6, and 8 g curcumin daily for three months yielded
discrepancy is unclear.
serum curcumin concentrations of only 0.51 ± 0.11,
While systemic distribution of curcumin tends
0.63 ± 0.06, and 1.77 ± 1.87 μM, respectively, indicat-
to be low, Garcea et al demonstrated that 3.6 g curcu-
ing curcumin is poorly absorbed and may have limited
min given to 12 patients with varying stages of colorec-
systemic bioavailability. Serum levels peaked between
tal cancer for seven days resulted in pharmacologically
one and two hours post-dose and declined rapidly. This
efficacious levels of curcumin (12.7 ± 5.7 nmol/g) in
study did not identify curcumin metabolites and urinary
both malignant colorectal tissue and normal colorectal
excretion of curcumin was undetectable.9
tissue (7.7 ± 1.8 nmol/g), perhaps accounting for the
Another phase I trial, involving 15
anti-inflammatory benefits of curcumin observed in
patients with advanced colorectal cancer, used cur-
diseases of the gastrointestinal tract.11
cumin at doses between 0.45 and 3.6 g daily for four
Although research on curcumin pharmacoki-
months. In three of six patients given the 3.6 g dose,
netics in healthy subjects is limited, one study using high
mean plasma curcumin measured after one hour on day
doses (10 and 12 g in a single oral dose) in 12 healthy
1 was 11.1 ± 0.6 nmol/L. This measurement remained
subjects measured serum curcumin as well as its sulfate
relatively consistent at all time points measured during
and glucuronide metabolites at various time points up
the first month of curcumin therapy. Curcumin was not
to 72 hours post-dose. As in previous studies, curcumin
detected in the plasma of patients taking lower doses.
was rapidly cleared (only one subject had detectable
Glucuronide and sulfate metabolites of curcumin were
free curcumin in the serum) and subsequently conju-
detected in plasma of all six patients in the high-dose
gated in the gastrointestinal tract and liver. Area under
group at all measurement points in the study.10 Cur-
cumin levels reported in this study are approximately
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Alternative Medicine Review Volume 14, Number 2 2009
Review Article
Figure 2. Absorption of Curcumin Phytosome (Meriva) Compared to Non-complex
Curcumin in Humans
450mg MERIVA curcuminoids vs 4g curcuminoids
45.00
l
] 40.00
450mg MERIVA curcuminoids
35.00
4.0g non-complexed curcuminoids
30.00
i
n

[
n
g
/
m
25.00
20.00
15.00
10.00
5.00
T
o
t
a
l

C
u
r
c
u
m
0.00
0
2
4
6
8
10
12
14
16
18
20
22
24
Time after supplementation [hours]
the curve (AUC) for curcumin conjugates was surpris-
more bioavailable than unbound curcumin. In rats,
ingly higher (35.33 ± 3.78 μg/mL) for the 10-g dose
peak plasma concentration and AUC were five times
than for the 12-g dose (26.57 ± 2.97 μg/mL), perhaps
higher for Meriva than for unbound curcumin.14 One
indicating saturation of the transport mechanism in
small unpublished, single-dose trial demonstrated
the gut for free curcumin. Maximum serum concentra-
450 mg of Meriva curcuminoids complexed with
tion (C ) for the 10-g dose was 2.30 ± 0.26 μg/mL
phosphatidylcholine was absorbed as efficiently as 4 g
max
compared to 1.73 ± 0.19 μg/mL for the 12-g dose.12
unbound Curcuma longa (95% curcumin), re-
Because of curcumin’s rapid plasma clearance
flecting a significant increase in bioavailability for
and conjugation, its therapeutic usefulness has been
Meriva complex (Figure 2).15
somewhat limited, leading researchers to investigate the
benefits of complexing curcumin with other substances
Anti-inflammatory Mechanisms
to increase systemic bioavaility. One substance that has
Research shows curcumin is a highly pleiotropic
been studied is the alkaloid piperine, a constituent from
molecule capable of interacting with numerous molecu-
black pepper and long pepper (Piper nigrum and Piper
lar targets involved in inflammation. Curcumin modu-
longum, respectively). In humans 20 mg piperine given
lates the inflammatory response by down-regulating the
concomitantly with 2 g curcumin increased serum cur-
activity of cyclooxygenase-2 (COX-2), lipoxygenase,
cumin bioavailability 20-fold, which was attributed to
and inducible nitric oxide synthase (iNOS) enzymes;
piperine’s inhibition of hepatic glucuronidation and in-
inhibits the production of the inflammatory cytokines
testinal metabolism.13
tumor necrosis factor-alpha (TNF-a), interleukin
Another method currently being investigated
(IL) -1, -2, -6, -8, and -12, monocyte chemoattractant
is complexing curcumin with a phospholipid, known
protein
(MCP),
and
migration
inhibitory
as a phytosome. The phosphatidylcholine-curcumin
protein; and down-regulates mitogen-activated and
complex (Meriva) is more readily incorporated into
Janus kinases.16,17
lipophilic cell membranes, making it significantly
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Alternative Medicine Review Volume 14, Number 2 2009
Curcumin
COX-2 and iNOS inhibition are likely accom-
cancer cell lines;23 and (4) down-regulation of enzymes,
plished via curcumin’s suppression of nuclear factor-
such as protein kinase C, that mediate inflammation
kappa B (NF-κB) activation.18 NF-κB, a ubiquitous
and tumor-cell proliferation.24
eukaryotic transcription factor, is involved in regulation
of inflammation, cellular proliferation, transformation,
Animal Research on Curcumin and
and tumorigenesis. Curcumin is thought to suppress
Inflammation
NF-κB activation and proinflammatory gene expres-
sion by blocking phosphorylation of inhibitory factor
Inflammation and Edema
I-kappa B kinase (IκB). Suppression of NF-κB activa-
Several animal studies have investigated the
tion subsequently down-regulates COX-2 and iNOS
anti-inflammatory effects of curcumin. Early work by
expression, inhibiting the inflammatory process and
Srimal et al demonstrated curcumin’s anti-inflamma-
tumorigenesis.18,19 In an animal model of inflammation,
tory action in a mouse and rat model of carrageenan-
curcumin also inhibited arachidonic acid metabolism
induced paw edema. In mice, curcumin inhibited edema
and inflammation in mouse skin epidermis via down-
at doses between 50-200 mg/kg. A 50-percent reduc-
regulation of the cyclooxygenase and lipoxygenase
tion in edema was achieved with a dose of 48 mg/kg
pathways.20
body weight, with curcumin nearly as effective as cor-
Curcumin’s inhibition of inflammatory
tisone and phenylbutazone at similar doses. In rats, a
cytokines is achieved through a number of mechanisms.
lower dose of 20-80 mg/kg decreased paw edema and
In vitro studies indicate curcumin regulates activa-
inflammation. Curcumin also inhibited formaldehyde-
tion of certain transcription factors such as activating
induced arthritis in rats at a dose of 40 mg/kg, had a
protein-1 (AP-1) and NF-κB in stimulated monocytes
lower ulcerogenic index (0.60) than phenylbutazone
and alveolar macrophages, thereby blocking expres-
(1.70) (an anti-inflammatory drug often used to treat
sion of cytokine gene expression. Down-regulation of
arthritis and gout), and demonstrated no acute toxicity
intercellular signaling proteins, such as protein kinase
at doses up to 2 g/kg body weight.25
C, may be another way in which curcumin inhibits
cytokine production.
Ulcerative Colitis
Curcumin has also been shown to reduce mu-
Curcumin’s Anti-inflammatory
cosal injury in mice with experimentally-induced colitis.
Properties and Carcinogenesis
A dose of 50 mg/kg curcumin for 10 days prior to in-
duction of colitis with 1,4,6-trinitrobenzene sulphonic
It is well understood that proinflammatory
acid resulted in a significant amelioration of diarrhea,
states are linked to tumor promotion.21,22 Consequently,
improved colonic architecture, and significantly reduced
phytochemicals like curcumin that exert a strong anti-
neutrophil infiltration and lipid peroxidation in colonic
inflammatory effect are anticipated to have some degree
tissue. Reduced levels of nitric oxide and O radicals
of chemopreventive activity. Preclinical cancer research
2
and suppressed NF-κB activation in colonic mucosa,
using curcumin has shown it inhibits carcinogenesis in a
all indicators of reduced inflammation and symptom
number of cancer types, including colorectal, pancreatic,
improvement, were also reported.26
gastric, prostate, hepatic, breast, and oral cancers, and
leukemia, and at various stages of carcinogenesis.6 Anti-
inflammatory mechanisms implicated in the anticarci-
Rheumatoid Arthritis
nogenic potential of curcumin include: (1) inhibition
In an animal model of streptococcal cell
of NF-κB and COX-2 (increased levels of COX-2 are
wall-induced rheumatoid arthritis, a turmeric extract
associated with many cancer types);18,20 (2) inhibition
devoid of essential oils was given to Wistar female
of arachidonic acid metabolism via lipoxygenase and
rats. Intraperitoneal injection of an extract containing
scavenging of free radicals generated in this pathway;20
4 mg total curcuminoids/kg/day for four days prior to
(3) decreased expression of inflammatory cytokines IL-
arthritis induction significantly inhibited joint inflam-
1b, IL-6, and TNF-a, resulting in growth inhibition of
mation in both the acute (75%) and chronic (68%)
phases. To test efficacy of an oral preparation, a 30-fold
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Alternative Medicine Review Volume 14, Number 2 2009
Review Article
higher dose (to allow for possible low gastrointestinal
days postoperatively. Parameters measured were spermatic
absorption) of the curcuminoid preparation, given to
cord edema, spermatic cord tenderness, operative site pain,
rats four days prior to arthritis induction, significantly
and operative site tenderness (0: absent, 1: mild, 2: mod-
reduced joint inflammation by 48 percent on the third
erate, 3: severe) and reflected by intensity score (TIS) of
day of administration.27
0-12. TIS on day 6 decreased in Group A (curcumin) by
84.2 percent, by 61.8 percent in Group B (placebo), and by
Pancreatitis
86 percent in Group C (phenylbutazone). Although TIS
In two rat models of experimental y-induced
scores for curcumin and phenylbutazone were similar on
pancreatitis, curcumin decreased inflammation by
day 6, curcumin proved to be superior by reducing all four
markedly decreasing activation of NF-κB and AP-1 as
parameters of inflammation. Phenylbutazone did not re-
well as inhibiting mRNA induction of IL-6, TNF-a, and
duce tenderness at the operative site.41
iNOS in the pancreas. In both cerulein- and ethanol-in-
duced pancreatitis, curcumin’s inhibitory effect on inflam-
Rheumatoid Arthritis
matory mediators resulted in improvement in disease se-
In a preliminary double-blind, randomized,
verity as measured by histology, serum amylase, pancreatic
controlled trial (RCT), curcumin was compared to phe-
trypsin, and neutrophil infiltration.28
nylbutazone in patients with rheumatoid arthritis. Cur-
cumin given at 1200 mg daily was effective in improv-
Cancer
ing joint swelling, morning stiffness, and walking time.
Numerous animal studies have explored cur-
Although phenylbutazone provided an even great-
cumin’s anti-inflammatory mechanisms and their influ-
er benefit, dosages, study size, and details were not
ence on carcinogenesis; however, discussion of these
available in English full text.42
studies in detail is beyond the scope of this paper.
Table 1 lists animal studies in which oral or dietary cur-
Osteoarthritis
cumin inhibited carcinogenesis via anti-inflammatory
A crossover RCT examined the effect of tur-
mechanisms.
meric extract (50 mg/capsule) in combination with zinc
complex (50 mg/capsule) and other botanicals – With-
Clinical Trials Exploring Curcumin’s Anti-
ania somnifera (450 mg/capsule) and Boswel ia serrata
inflammatory Benefits
(100 mg/capsule) in 42 patients with osteoarthritis.
Curcumin’s potent anti-inflammatory properties
Patients were given 2 capsules of test formula or pla-
have lead to active research on its use for a variety of inflam-
cebo three times daily for three months; then, after a
matory conditions, including postoperative inflammation,
two-week washout period, switched to the opposite
arthritis, uveitis, inflammatory pseudotumors, dyspepsia,
treatment for another three months. Assessment every
irritable bowel syndrome, inflammatory bowel disease,
two weeks during the study demonstrated significant
pancreatitis, and Helicobacter pylori infection. Most studies
improvements in pain severity (p<0.001) and disability
are promising and further exploration of curcumin’s thera-
scores (p<0.05), but no statistically significant changes
peutic value for inflammatory conditions is warranted.
in other parameters. Curcumin’s role in this improve-
ment cannot be confirmed due to the other botanicals
Post-surgery
and zinc in the treatment compound.43
Satoskar et al examined the effects of curcumin
compared to phenylbutazone or placebo for spermatic
Ocular Conditions
cord edema after surgery for inguinal hernia or hydrocele.
Anterior uveitis is a condition characterized by
Forty-five patients (ages 15-68) received 400 mg curcumin
inflammation of the uveal tract of the eye (including the
(Group A), 250 mg lactose powder placebo (Group B), or
iris) and if untreated can result in blurred vision and
100 mg phenylbutazone (Group C) three times daily for six
permanent damage. Although the exact cause of ante-
rior uveitis is not certain, it has been known to occur
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Alternative Medicine Review Volume 14, Number 2 2009
Curcumin
Table 1. Animal Studies Investigating the Anti-inflammatory Effects of Curcumin
in Cancer Models29-40
Author
Animal Model
Route of Curcumin
Dose
Administration
Chan et al 199829
Murine (liver) iNOS production
Oral by gavage, Intravenous 0.5 mL of 10µM solution
0.5 µg/g body weight
Rao et al 199930
Rat colonic aberrant crypt foci
Oral (diet), Subcutaneous
50-2,000 ppm
15 mg/kg body weight
Rao et al 199531
Rat colon cancer
Oral (diet)
2,000 ppm
Perkins et al 200232
Murine familial adenomatous
Oral (diet), Intraperitoneal
0.1-, 0.2-, 0.5-% diet
polyposis
100 mg/kg body weight
Shpitz et al 200633
Rat colonic aberrant crypt foci
Oral (diet)
0.6-% diet
Kwon et al 200934
Rat colonic apoptosis
Oral
0.6-% diet
Dujic et al 200935
Murine xenograft tumor
Intraperitoneal
200 µL of 0.2-1.0 µg/mL-
curcumin suspension
Garg et al 200836
Murine liver, lung tumor initiation Oral (diet)
0.01- or 0.0-% diet
Kawamori et al 199937 Rat colonic apoptosis
Oral
0.2- or 0.6-% diet
Huang et al 199838
Murine lymphomas/leukemias
Oral (diet)
2-% diet
Aggarwal et al 200539 Murine breast cancer
Oral (diet)
2-% diet
with lung metastasis
Tomita et al 200640
Murine T-cell leukemia
Oral (gavage)
300 mg/kg body weight
with trauma to the eye, other eye diseases, tuberculosis,

compared to 86 percent in the curcumin/antitubercular
rheumatoid arthritis, measles, or mumps. Treatment is
therapy group (n=14). Improvements were observed in
usually aimed at decreasing inflammation.44
visual acuity and aqueous flare and were accompanied
In a clinical trial involving 32 patients (ages
by a decrease in keratic precipitates.45
19-70) with anterior uveitis, 375 mg curcumin was
Curcumin has been used for idiopathic orbital
administered alone or with antitubercular therapy (to
inflammatory pseudotumors (IOIP). Orbital pseudo-
those patients demonstrating a positive PPD skin prick
tumors include ocular lesions that are non-neoplastic in
test) three times daily for 12 weeks. Of those in the
nature for which there is no clearly defined cause. The
curcumin-only group (n=18), 100 percent reported
condition is an immunological inflammatory condi-
marked improvement after two weeks of therapy,
tion characterized by a hard mass in the orbit, inflam-
mation of the conjunctiva, and decreased visual acuity.
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Alternative Medicine Review Volume 14, Number 2 2009
Review Article
Conventional treatment consisting of corticosteroids is
Inflammatory Bowel Disease
often ineffective.46 In a small study of eight patients with
Crohn’s disease (CD) and ulcerative colitis
IOIP, 375 mg curcumin three times daily was given for
(UC) are the two primary forms of inflammatory bowel
6-22 months, until complete regression of symptomol-
disease (IBD). The primary difference between the two
ogy was achieved. Patients were followed for two years
is nature and location of inflammatory changes in the
and assessed at three-month intervals. Only five pa-
gastrointestinal tract. CD can affect any part of the gas-
tients completed the study, but four completely recov-
trointestinal tract and affects the entire bowel wall. In
ered on curcumin therapy. One patient was asymptom-
contrast, UC is restricted to the colon and the rectum
atic but continued to have some restriction of ocular
and disease is confined to the intestinal epithelium.
movement.47
Although very different in scope, both diseases may
present with abdominal pain, vomiting, diarrhea, bloody
Gastrointestinal Conditions
stools, weight loss, and secondary sequelae such as
Curcumin’s anti-inflammatory properties and
arthritis, pyoderma gangrenosum, and primary scleros-
therapeutic benefit have been demonstrated for a vari-
ing cholangitis.52
ety of gastrointestinal conditions, including dyspepsia,
Holt et al conducted a pilot study to examine
Helicobacter pylori infection, peptic ulcer, irritable bowel
the effect of curcumin therapy in 10 patients with IBD
syndrome, Crohn’s disease, and ulcerative colitis.
(five with CD and five with UC, ages 28-54) who had
previously received standard UC or CD therapy. Five
Dyspepsia and Gastric Ulcer
patients with proctitis (UC of the rectal area) received
In a phase II clinical trial involving 45 sub-
550 mg curcumin twice daily for one month and then
jects (24 males, 21 females, ages 16-60 years), 25 with
were given the same dose three times daily for an ad-
endoscopically diagnosed peptic ulcers were given 600
ditional month. Hematological and biochemical blood
mg curcumin five times daily 30-60 minutes before
analysis, erythrocyte sedimentation rate (ESR), C-reac-
meals, at 4:00 pm, and at bedtime for 12 weeks. Ulcers
tive protein (CRP) (the latter two inflammatory indica-
were absent in 12 patients (48%) after four weeks, in
tors), sigmoidoscopy, and biopsy were all performed at
18 patients after eight weeks, and in 19 patients (76%)
baseline and at the study end. Symptoms were assessed
after 12 weeks. The remaining 20 patients, also given
by questionnaire and daily symptom diary. The other
curcumin, had no detectable ulcerations at the start of
five patients, with Crohn’s disease, received 360 mg three
the study, but were symptomatic – erosions, gastritis,
times daily for one month and then four times daily for a
and dyspepsia. Within 1-2 weeks abdominal pain and
second month. Crohn’s Disease Activity Index (CDAI),
other symptoms had decreased significantly.48
CRP, ESR, hematological blood analysis, and kidney
function was assessed in all patients at baseline and end
Irritable Bowel Syndrome
of study. In the proctitis group all five patients improved
In patients with irritable bowel syndrome
by study’s end as indicated by a global score, two elimi-
(IBS) the most common symptoms are abdominal pain,
nated prestudy medications, two decreased their medi-
bloating, altered bowel habits, and increased stool fre-
cations, and all five subjects demonstrated normal ESR,
quency.49 It is thought that low-grade inflammation of
CRP, and serologic indices of inflammation after two
the intestinal mucosa is responsible for some sympto-
months. In the CD group, CDAI scores decreased by
mology.50 In an eight-week pilot study of IBS patients,
an average of 55 points, and CRP and ESR decreased
either 72 mg or 144 mg of a standardized turmeric
in four of five patients.53
extract was administered to a group of 102 or 105 sub-
Another clinical trial was conducted to assess
jects, respectively. After four weeks, those in the 72-mg
the efficacy of curcumin as a maintenance therapy in 82
group experienced a 53-percent reduction in IBS preva-
patients with quiescent UC. Subjects were randomized
lence, while the 144-mg group experienced a 60-percent
to receive 1 g curcumin twice daily plus sulfasalazine
decrease. In post-study analysis, abdominal pain and
or mesalamine (n=43), or placebo plus sulfasalazine
discomfort scores were reduced by 22 percent in the 72-
or mesalamine (n=39) for six months. Subjects were
mg group and 25 percent in the 144-mg group.51
assessed at baseline, every two months for six months,
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Alternative Medicine Review Volume 14, Number 2 2009
Curcumin
and again at the end of a six-month follow-up period
Renal Graft Rejection
via the Clinical Activity Index (CAI) and Endoscopic
An RCT investigated the effect of a com-
Index (EI). Only two of 43 patients (4.7%) receiving
bination of 480 mg curcumin and 20 mg quercetin
curcumin plus sulfasalazine/mesalamine experienced a
(per capsule) on delayed graft rejection (DGR) in 43
relapse during the six-month study, compared to eight
kidney transplant patients. Subjects were randomized
of 39 subjects (20.5%) in the placebo plus sulfasalazine/
to low-dose (one capsule), high-dose (two capsules), or
mesalamine group. Subjects in the curcumin group
placebo (one capsule twice daily) groups for one month
also demonstrated significant improvement in CAI
post-surgery. Of 39 participants who completed the
(p=0.038) and EI scores (p=0.001), indicating a de-
study, two of 14 in the control group experienced DGR
crease in UC-associated morbidity. Interestingly, at the
compared to zero in either treatment group. Early func-
end of the six-month follow-up period, during which
tion (significantly decreased serum creatinine 48 hours
all patients took only sulfasalazine or mesalamine, eight
post-transplant) was achieved in 43 percent of subjects
additional patients from the curcumin group relapsed
in the control group, 71 percent of those in the low-
(total of 23.3%) compared to six additional patients in
dose treatment group, and 93 percent in the high-dose
the placebo group (total of 35.9%). The authors con-
group. Since the amount of quercetin in the compound
cluded that curcumin plus standard therapy was more
was minimal, the majority of benefit is thought to be
effective in maintaining remission than placebo plus
due to curcumin’s anti-inflammatory and antioxidant
standard UC treatment.54
activity.57
Likely mechanisms for improved early func-
Pancreatitis
tion of transplanted kidneys include induction of the
Clinical research on curcumin’s therapeutic
hemeoxygenase enzyme, inhibition of NF-κB and pro-
benefit for pancreatitis is limited and has primarily fo-
inflammatory cytokines, and scavenging of free radicals
cused on its antioxidant properties. However, research
associated with tissue damage.57
indicates the inflammatory response plays a critical
In addition to the research presented here,
role in development of pancreatitis and subsequent tis-
there are a number of ongoing clinical trials explor-
sue damage.28,55 For this reason, it seems likely an anti-
ing the effects of curcumin in various inflammatory
inflammatory agent like curcumin, effective against a
conditions (Table 2).
variety of inflammatory molecular targets and shown to
decrease inflammatory markers in an animal model of
Cancer Chemoprevention and Treatment
pancreatitis,28 might prove to be effective in humans.
with Curcumin
One pilot study examined the effect of cur-
The impact of curcumin’s anti-inflammatory
cumin for tropical pancreatitis in 15 patients. Subjects
effects on carcinogenesis in humans remains to be de-
received 500 mg curcumin with 5 mg of piperine to en-
termined. However, animal research demonstrates in-
hance absorption (n=8) or placebo (n=7) for six weeks.
hibition at all three stages of carcinogenesis – initia-
Treatment effect on pain patterns as well as erythrocyte
tion, promotion, and progression. During initiation and
malonylaldehyde (MDA; an indicator of lipid peroxida-
promotion, curcumin modulates transcription factors
tion) and glutathione (GSH) were assessed at baseline
controlling phase I and II detoxification of carcino-
and after six weeks. In the curcumin group there was
gens;36 down-regulates proinflammatory cytokines, free
a significant reduction in MDA levels (from 14.80 ±
radical-activated transcription factors, and arachidonic
1.19 to 6.02 ± 0.95). There was no significant change in
acid metabolism via cyclooxygenase and lipoxygenase
either GSH or pain value scores between the curcu-
pathways; and scavenges free radicals.59-61 In the promo-
min and placebo groups. Further research is needed to
tion and progression stages of carcinogenesis curcumin
determine the role of lipid peroxidation in pain and
decreases frequency and size of tumors and induces
other symptomology associated with pancreatitis.56
apoptosis via suppression of NF-κB and AP-1 in sev-
eral cancer types.20,37
Page 148
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Alternative Medicine Review Volume 14, Number 2 2009
Review Article
Table 2. Ongoing Clinical Trials Exploring Curcumin’s Benefits in Inflammatory Conditions58
Clinic Trial
Condition
Trial Site
Intervention
Trial Phase
Completion
Identifier
Date
NCT00752154
Rheumatoid arthritis University of California, Curcumin, 4-12 g daily
Pilot Study
September 2009
Los Angeles
NCT00792818
Knee osteoarthritis
Mahidol University,
Curcuma longa extracts, Phase III
November 2009
National Research
Ibuprofen
Council of Thailand
NCT00793130
Ulcerative colitis
Tel-Aviv Sourasky
Coltect – (curcumin
Unknown
November 2009
Medical Center
1 g daily, green tea,
selenium)
NCT00779493
Irritable bowel
Kaiser Permanente
Curcumin, 900 mg
Phase IV
November 2009
syndrome
twice daily
NCT00528151
Leber’s hereditary
Mahidol University
Curcumin, 250 mg
Phase III
Unknown
optical neuropathy
twice daily
NCT00595582
Mild cognitive
Louisiana State
Curcumin + Bioperine,
Unknown
January 2009
impairment
University
5.4 g daily
Clinical trials published in peer-reviewed lit-
(equivalent to 36-180 mg curcumin) for up to four
erature utilizing curcumin for chemoprevention or as a
months. In one patient, measurement of serum tumor
cancer therapy are somewhat limited. A phase I clinical
marker levels revealed a decrease of carcinoembryonic
trial investigated the use of curcumin as a chemopreven-
antigen levels from 310 ± 15 μg/L to 175 ± 9 μg/L
tive agent in 25 patients with various types of high-risk
after two months of treatment with 440 mg Curcuma
or pre-malignant lesions. After an initial dose of 500 mg
extract. Stable disease via CT scan was observed in five
curcumin daily, the dose was increased to as much as
of 15 patients – one taking 440 mg extract, one taking
8 g daily for three months. Histological improvement
880 mg, and one taking 1,760 mg for three months, and
of precancerous lesions was observed in one of four
in one taking 880 mg and one taking 1,320 mg for four
patients with cervical intraepithelial neoplasm (signifi-
months.62
cant decreases in hyperkeratosis, parakeratosis), one of
In the second trial, researchers used a higher
six patients with intestinal metaplasia of the stomach
potency curcuminoid preparation, each capsule con-
(fewer goblet cells), one of two patients with recently re-
taining 450 mg curcumin, 40 mg demethoxycurcumin,
sected bladder cancer (decreased dysplasia and inflam-
and 10 mg bisdemethoxycurcumin. Fifteen patients
mation), two of seven patients with oral leukoplakia,
with advanced colorectal cancer were given curcumi-
and two of six patients with Bowen’s disease.9
noid doses of 450-3,600 mg daily for up to four months.
Three other clinical trials have investigated the
Blood and imaging tests were performed at baseline and
use of curcumin therapy in patients with established
various points throughout the trial. In six patients giv-
colorectal cancer. Sharma et al conducted two sepa-
en the 3,600-mg dose, mean prostaglandin E (PGE )
2
2
rate clinical trials exploring curcumin’s effect on ma-
levels measured after 29 days of treatment decreased by
lignancies and tumor marker levels.10,62 In one trial, 15
46 percent compared to baseline.10 PGE is an end prod-
2
patients with advanced colorectal cancer were given
uct of cyclooxygenase that has been shown to stimulate
a low-dose (440-2,200 mg daily) Curcuma extract
growth of human colorectal cancer cells.63 In addition,
Page 149
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Alternative Medicine Review Volume 14, Number 2 2009
Curcumin
Table 3. Clinical Trials Investigating the Use of Curcumin in Cancer58
Clinical Trial
Condition
Site
Intervention
Trial Phase
Completion
Identifier
Date
Chao Family Comprehensive
NCT00365209
Colon cancer prevention
Curcumin
Phase II
Unknown
Cancer Center
Curcuminoid
NCT00118989
Colon cancer prevention
University of Pennsylvania
Phase II
June 2009
complex, 4 g daily
Familial adenomatous
Curcumin, 700 mg
NCT00641147
Johns Hopkins University
Phase II
March 2013
polyposis
twice daily
Curcumin, 4 g daily,
NCT00745134
Rectal cancer
MD Anderson Cancer Center
Phase II
July 2010
Capecitabine
Gemcitabine,
Tel-Aviv Sourasky Medical
NCT00486460
Pancreatic cancer
Curcumin, Celebrex
Phase III
Unknown
Center
(doses unknown)
NCT00094445
Pancreatic cancer
MD Anderson Cancer Center Curcumin, 8 g daily
Phase II
December 2009
Curcumin +
NCT00113841
Multiple myeloma
MD Anderson Cancer Center Bioperine, 2 g
Pilot Study
December 2008
twice daily
Curcumin and
NCT00689195
Osteosarcoma
Tata Memorial Hospital
Ashwagandha
Phase I and II
May 2012
(doses unknown)
Curcumin liquid
Oral mucositis – children Hadassah Medical
NCT00475683
extract, 10-30 drops Phase III
December 2009
on chemotherapy
Organization
3 times daily
two patients (one taking 900 mg, the other taking 1,800
In another clinical trial, curcumin stabilized
mg) demonstrated stable disease (determined via CT
disease progression in patients with advanced pan-
scan or MRI) after two months. The patient taking the
creatic cancer. Twenty-one patients received 8 g cur-
higher dose remained stable for four months but with-
cumin daily until disease progression. Serum cytokine
drew due to diarrhea thought to be treatment related.10
levels as well as NF-κB and COX-2 levels in peripheral
Another clinical trial investigated curcumin’s
blood mononuclear cells were monitored. One patient
effects in patients with colorectal cancer at doses of
achieved disease stabilization for 18 months. Interest-
450, 1,800, or 3,600 mg daily for seven days.11 The
ingly, a second patient experienced significant increases
aim of this study was to determine if these doses re-
in serum cytokine levels (4- to 35-fold) accompanied
sulted in pharmacologically active levels of curcumin in
by a brief, but marked tumor regression (73%). Down-

colorectal tissue or had any effect on tissue levels of the
regulation of NF-κB and COX-2 were also observed.64

oxidative DNA adduct pyrimido(1,2-a)purin-10(3H)-
Currently there are nine ongoing clinical trials
one (M G) (a mutagenic byproduct of lipid peroxida-
investigating the benefits of curcumin as a therapy for
1
tion) or COX-2 – markers of DNA damage and in-
various cancers. Of these, three are preventive trials on
flammation. The highest dose (3,600 mg) resulted in a
subjects with adenomatous polyps at risk for colorectal
significant decrease in M G adducts from 4.8 ± 2.9 to
cancer. The remaining seven trials are investigating the
1
2.0 ±1.8 per 107 nucleotides. No curcumin dose had an
effects of curcumin (both alone and with conventional
effect on tissue levels of COX-2 protein.
Page 150
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