Curcumin Therapy in Inflammatory Bowel Disease: A Pilot Study

Abstract

Curcumin, a natural compound used as a food additive, has been shown to have anti-inflammatory and antioxidant properties in cell culture and animal studies. A pure curcumin preparation was administered in an open label study to five patients with ulcerative proctitis and five with Crohn's disease. All proctitis patients improved, with reductions in concomitant medications in four, and four of five Crohn's disease patients had lowered CDAI scores and sedimentation rates. This encouraging pilot study suggests the need for double-blind placebo-controlled follow-up studies.

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Digestive Diseases and Sciences, Vol. 50, No. 11 (November 2005), pp. 2191–2193 (
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DOI: 10.1007/s10620-005-3032-8
Curcumin Therapy in Inflammatory Bowel
Disease: A Pilot Study
PETER R. HOLT, MD,* SEYMOUR KATZ, MD,† and ROBERT KIRSHOFF†
Curcumin, a natural compound used as a food additive, has been shown to have anti-inflammatory
and antioxidant properties in cell culture and animal studies. A pure curcumin preparation was
administered in an open label study to five patients with ulcerative proctitis and five with Crohn’s
disease. All proctitis patients improved, with reductions in concomitant medications in four, and four
of five Crohn’s disease patients had lowered CDAI scores and sedimentation rates. This encouraging
pilot study suggests the need for double-blind placebo-controlled follow-up studies.
KEY WORDS: curcumin; ulcerative proctitis; Crohn’s disease; inflammatory bowel disease.
Curcumin is a natural compound found in the plant Cur-
cuma longa which is used as a food additive known as
turmeric. The major pigment in turmeric is curcumin
(chemical name diferuloymethane), which possesses both
anti-inflammatory (1, 2) and antioxidant properties (3, 4)
Topical application of curcumin inhibits carcinogen-
induced DMA adduct formation and the development of
skin tumors. Curcumin also strongly inhibits proliferation
of HT-29 and HCT-15 human colon cancer cell lines (5).
Dietary administration of curcumin suppresses the devel-
opment of chemically induced cancers. These properties
have led to studies of the chemopreventive effects of cur-
cumin which also showed that the agent reduces colonic
inflammatory responses (6). The background for such anti-
inflammatory activity rests in in vitro and animal model
studies. We report here our experience with curcumin ther-
apy in 10 patients with inflammatory bowel disease.
MATERIALS AND METHODS
Five consecutive patients with ulcerative proctitis or proc-
tosigmoiditis who agreed to participate in this study were en-
tered (Table 1). There were three women and two men, aged 28
Manuscript received March 21, 2004; accepted August 10, 2004.
From *St. Luke’s Roosevelt Hospital Center, Columbia University
and Strang Cancer Center Research Laboratory, New York, New York,
and †Long Island Clinical Research Associates, Great Neck, New York,
USA.
Address for reprint requests: Peter R. Holt, MD,15 West 81 Street,
New York, New York 10024, USA; pholt@chpnet.org.
to 54 years, who had complained of proctitis symptoms for 1 to
32 years. All had been previously treated with 5-aminosalicyclic
acid (5ASA) compounds by mouth and/or rectum, three had re-
ceived corticosteroid therapy at some time, and one subject was
taking prednisone, 10 mg per day, at study entry.
They were treated with 550 mg of curcumin (DFM 100; 99.5%
pure
1
) twice daily for 1 month and then 550 mg three times daily
for another month. All had blood taken for hematologic and bio-
chemical analysis and for indexes of inflammation (sedimenta-
tion rate and C-reactive protein [CRP]) and had sigmoidoscopies
and biopsies both at baseline and 2 months later when the study
ended.
Symptoms were assessed by a standard questionnaire at the
start and conclusion of the study and by a daily symptom dairy.
The endoscopic evaluation was not blinded since the investigator
wasaware of the timing of the procedure, however, the biopsies
were obtained and evaluated for the degree of inflammation with-
out knowledge of their timing.
Five subjects, three men and two women, with an established
diagnosis of Crohn’s disease were entered in this pilot study to
determine whether the addition of curcumin to existing treat-
ments for Crohn’s disease would result in a reduction of in-
flammation with the ability to reduce other concomitant anti-
inflammatory agents (Table 1). The subjects were treated with
curcumin, 360 mg (1 capsule) three times daily for 1 month
and then 360 mg (4 capsules) four times daily for the remaining
2 months. Crohn’s Disease Activity Index (CDAI), CRP, ery-
throcyte sedimentation rate (ESR), complete blood counts, and
liver and renal function studies were obtained in all patients. All
patients signed a consent form and IRB permission was obtained
for this study.
1
Kindly provided by R. Kane Products, Pennsauken, New Jersey.
Digestive Diseases and Sciences, Vol. 50, No. 11 (November 2005)
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HOLT ET AL.
T
ABLE 1. DATA ON ULCERATIVE PROCTOSIGMOIDITIS AND CROHN’S DISEASE PATIENTS
Length of disease Medications at
Patient No. Age/sex Extent of disease history (yr) study entry
A. Ulcerative proctosigmoiditis
1. RK 52/F Proctitis 32 5ASA suppositories
Sulfasalazine, 2g 1d
2. EJ 30/F Proctitis 01 5ASA enemas and
suppositories
3. PM 28/M Proctitis 05 5ASA enemas
4. JM 29/M Proctitis 07 Sulfasalazine, 2g 1d
5ASA suppositories
5. RP 54/F Proctosigmoiditis 06 Prednisone, 10 mg
5ASA and enemas
Azathiopine, 100 mg
B. Crohn’s disease
1. JD 43/M lleocolitis 22 Colestid, 3/day
6MP, 75 mg
2. RK 47/M Crohn’s colitis 26 6MP, 75 mg
3. BE 65/F lleocolitis 11 6MP, 75 mg
4. JR 50/M lleojejunal colitis 23 Flagyl, 500 mg
Budesonide, 9 mg
5. JWP 33/F Ileitis 22 None
Note. 5ASA, 5-aminosalicylic acid; 6MP, 6-methylprednisone.
RESULTS
Overall, all five subjects with proctitis improved by the
end of the study as judged by a global score (P < 0.02;
Table 2). The major changes found were in the number and
quality of stools. Two subjects eliminated their prestudy
5ASA medications, two subjects reduced their medica-
tions (including termination of the prednisone therapy in
one subject), and one continued taking 5ASA supposito-
ries. In these patients with limited ulcerative colitis, sero-
logic indexes of inflammation, sedimentation rate, and
CRP returned to within normal limits at the conclusion
of the study.
The CDAI scores for all completed subjects fell, with
a mean reduction of 55 points; sedimentation rate fell
as well, with a mean reduction of 10 mm/hr (Table 3).
CRP was reduced by a mean of 0.1 mg/dl. There were no
changes in indexes of liver or renal function. Visits oc-
TABLE 2. EFFECTS OF CURCUMIN ADMINISTRATION IN ULCERATIVE PROCTITIS PATIENTS
General No. of Stool Stool Abdominal Rectal pain Global
Subject No. well-being stools quality blood pain urgency Medication Endoscopy score
1. Before 1 2–3 2 1 0 1 Eliminated 3 11
After 0 1 0 1 0 0 2 4
2. Before 1 4+ 13 02Unchanged 2 13
After 0 2–3 1 3 0 2 2 11
3. Before 0 2–3 1 0 0 0 Eliminated 0 4
After 0 1 0 0 0 0 0 1
4. Before 1 4+ 23 11Reduced++ 315
After 1 2–3 0 3 0 0 1 8
5. Before 4+ 1–2 1 0 1 Reduced 1 9
After 1–2 1–2 1 0 1 1 7
Note. Numbers represent semiquantitative scores ranging from 1 to 3. The higher the score, the worse the status.
curred every month, at which the four completed subjects
reported improvement in clinical symptoms as follows:
more formed stools, less frequent bowel movements, and
less abdominal pain and cramping. One subject reported
decreased muscle soreness, commonly felt after his exer-
cise routine. Of the five subjects, four successfully com-
pleted and one discontinued due to lack of treatment effect,
with a slight worsening of fistula output.
DISCUSSION
Curcumin has a profound immunosuppressive effect via
inhibition of IL-2 synthesis as well as IL-2 and mitogen
activation of human leukocytes. This immunosuppressive
effect may be mediated by NFκB inhibition (7).
Further support is offered by data indicating that cur-
cumin effectively inhibited tumor necrosis factor α and
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CURCUMIN THERAPY IN INFLAMMATORY BOWEL DISEASE
T
ABLE 3. EFFECTS OF CURCUMIN ADMINISTRATION IN CROHN’S
DISEASE PATIENTS
CDAI Sedimentation rate
Subject No. Index Change % change Rate Change % change
1. Before 225 23
After 196 −29 −12.9 19 −4 −17.4
2. Before 253 11
After 155 −98 −38.7 6 −5 −45.5
3. Before 250 24
After 239 −11 −44 7 −17 −70.8
4. Before 302 42
After 220 −82 −27.2 28 −14 −33.3
Note.CDAI, Crohn’s Disease Activity Index. Data for the four subjects
who completed the study.
phorbol ester-induced binding of NFκ B transcription
factors to sites located on the GSTP1-1 (glutathione
S-transferase P1-1) gene promoter. These results indi-
cate that curcumin could thereby induce apoptosis by its
ability to inhibit GSTP1-1 expression at the transcription
level (8).
In animal colitis models, curcumin has been shown to
attenuate or prevent DNB or trinitrobenzene sulfonic acid-
induced colitis in mice by suppressing CD4(+)T-cell in-
filtration and NHκ B activation as well as reducing p38
MAPX activity (9, 10). Based on these reports we have
shown that curcumin appears to have reduced the inflam-
matory response in four of five ulcerative colitis patients
and four of five Crohn’s disease patients.
Conclusion
The results of this pilot study indicate that further stud-
ies are warranted. A larger scale, double-blind, placebo-
controlled trial is indicated.
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