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Curcumin Maintenance Therapy for Ulcerative Colitis: Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial

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  • Hamamatsu South Hoapital, Hamamatsu, Japan

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Curcumin is a biologically active phytochemical substance present in turmeric and has pharmacologic actions that might benefit patients with ulcerative colitis (UC). The aim in this trial was to assess the efficacy of curcumin as maintenance therapy in patients with quiescent ulcerative colitis (UC). Eighty-nine patients with quiescent UC were recruited for this randomized, double-blind, multicenter trial of curcumin in the prevention of relapse. Forty-five patients received curcumin, 1g after breakfast and 1g after the evening meal, plus sulfasalazine (SZ) or mesalamine, and 44 patients received placebo plus SZ or mesalamine for 6 months. Clinical activity index (CAI) and endoscopic index (EI) were determined at entry, every 2 months (CAI), at the conclusion of 6-month trial, and at the end of 6-month follow-up. Seven patients were protocol violators. Of 43 patients who received curcumin, 2 relapsed during 6 months of therapy (4.65%), whereas 8 of 39 patients (20.51%) in the placebo group relapsed (P=.040). Recurrence rates evaluated on the basis of intention to treat showed significant difference between curcumin and placebo (P=.049). Furthermore, curcumin improved both CAI (P=.038) and EI (P=.0001), thus suppressing the morbidity associated with UC. A 6-month follow-up was done during which patients in both groups were on SZ or mesalamine. Eight additional patients in the curcumin group and 6 patients in the placebo group relapsed. Curcumin seems to be a promising and safe medication for maintaining remission in patients with quiescent UC. Further studies on curcumin should strengthen our findings.
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Curcumin Maintenance Therapy for Ulcerative Colitis: Randomized,
Multicenter, Double-Blind, Placebo-Controlled Trial
HIROYUKI HANAI,*
,‡
TAKAYUKI IIDA,
KEN TAKEUCHI,
FUMITOSHI WATANABE,
§
YASUHIKO MARUYAMA,
§
AKIRA ANDOH,
TOMOYUKI TSUJIKAWA,
YOSIHIHIDE FUJIYAMA,
KEIICHI MITSUYAMA,
MICHIO SATA,
MASAMI YAMADA,
#
YASUSHI IWAOKA,
#
KAZUNARI KANKE,** HIDEYUKI HIRAISHI,** KAZUHISA HIRAYAMA,
††
HAJIME ARAI,
‡‡
SHIGEHITO YOSHII,
‡‡
MASATO UCHIJIMA,
§§
TOSHI NAGATA,
§§
and YUKIO KOIDE
§§
*Department of Endoscopic and Photodynamic Medicine and
§§
Department of Microbiology and Immunology, Hamamatsu University School of Medicine,
Hamamatsu;
Center for Gastroenterology, Hamamatsu South Hospital, Hamamatsu;
§
Department of Gastroenterology, Fujieda Municipal General Hospital,
Shizuoka;
Department of Internal Medicine, Shiga University of Medical Science, Shiga;
Second Department of Medicine, Kurume University School of Medicine,
Kurume;
#
Department of Gastroenterology, Hamamatsu Medical Center, Hamamatsu; **Department of Gastroenterology, Dokkyo University School of Medicine,
Tochigi;
††
Department of Surgery, Hamamatsu Social Insurance Hospital, Hamamatsu; and
‡‡
Hamamatsu Mikatahara Seirei Hospital, Hamamatsu, Japan
Background & Aims: Curcumin is a biologically active
phytochemical substance present in turmeric and has pharma-
cologic actions that might benefit patients with ulcerative co-
litis (UC). The aim in this trial was to assess the efficacy of
curcumin as maintenance therapy in patients with quiescent
ulcerative colitis (UC). Methods: Eighty-nine patients with
quiescent UC were recruited for this randomized, double-blind,
multicenter trial of curcumin in the prevention of relapse.
Forty-five patients received curcumin, 1g after breakfast and 1g
after the evening meal, plus sulfasalazine (SZ) or mesalamine,
and 44 patients received placebo plus SZ or mesalamine for 6
months. Clinical activity index (CAI) and endoscopic index (EI)
were determined at entry, every 2 months (CAI), at the conclu-
sion of 6-month trial, and at the end of 6-month follow-up.
Results: Seven patients were protocol violators. Of 43 patients
who received curcumin, 2 relapsed during 6 months of therapy
(4.65%), whereas 8 of 39 patients (20.51%) in the placebo group
relapsed (P.040). Recurrence rates evaluated on the basis of
intention to treat showed significant difference between curcumin
and placebo (P.049). Furthermore, curcumin improved both
CAI (P.038) and EI (P.0001), thus suppressing the morbidity
associated with UC. A 6-month follow-up was done during which
patients in both groups were on SZ or mesalamine. Eight addi-
tional patients in the curcumin group and 6 patients in the
placebo group relapsed. Conclusions: Curcumin seems to be
a promising and safe medication for maintaining remission in
patients with quiescent UC. Further studies on curcumin
should strengthen our findings.
Ulcerative colitis (UC) is a debilitating, chronic, relapsing-
remitting IBD that afflicts millions of individuals
throughout the world and produces symptoms that impair
quality of life and ability to function.
1
Although factors like
smoking cessation,
2
use of nonsteroidal anti-inflammatory
drugs,
3
and stress
4
are known to provoke an exacerbation,
clinical relapses are often unpredictable.
Currently, several drugs including sulfasalazine (SZ), me-
salamine, corticosteroids, immunomodulators, and remicade
are used to treat patients with active IBD.
5–12
However, these
medications are associated with side effects that add to the
disease complications when used either to induce remission or
to prevent a recurrence.
9–15
Furthermore, given that the major-
ity of patients with UC (approximately 70%) have a clinical
course that is either relapsing-remitting or chronic continuous,
there is a need for novel safe medications to maintain remission
in patients with UC in whom the disease has reverted to a
quiescent state.
Curcumin is a natural substance present in turmeric, the
spice that gives food an exotic yellow color. Curcumin seems to
have a broad spectrum of pharmacologic actions including
antitumor, anti-inflammatory, and antioxidant effects.
16–20
The pleiotropic effects of curcumin are attributable in part
to the inhibition of the transcriptional nuclear factor–
B
(NF-
B).
21–23
In line with this background, recently we demon-
strated that treatment with curcumin can prevent murine ex-
perimental colitis by inhibiting N
˜F-
B activation and CD4
T-cell infiltration into the colonic mucosa.
24
This study aimed
to assess the efficacy of curcumin as a maintenance therapy in
patients with quiescent UC.
Patients and Methods
Patients
Between April 2004–July 2005, 8 centers in Japan en-
rolled a total of 89 patients. The study protocol was reviewed
and approved by the Committees on Ethics of clinical trials
involving human subjects at each institution, and the trial was
conducted in accord with the Declaration of Helsinki. Inclusion
criteria were (1) patient had a diagnosis of UC as confirmed by
radiologic, endoscopic, or histologic criteria that are established
by the Research Committee of Inflammatory Bowel Disease,
the Japan Ministry of Health; (2) age between 13–65 years;
(3) patient’s UC had a clinical activity index (CAI) 4, stable for
the previous 4 weeks; (4) patient had achieved remission with a
corticosteroid 20 mg/day prednisolone or an alternative med-
ication and had successfully ceased steroid therapy; and
(5) patient had a hemoglobin of 10 g/dL. Exclusion criteria
were (1) patient was receiving an immunomodulator like aza-
Abbreviations used in this paper: CAI, clinical activity index; EI,
endoscopic index; MAPK, mitogen-activated protein kinase; NF-B,
nuclear factor-B; NOS, nitric oxide synthase; SZ, sulfasalazine; TNBS,
trinitrobenzene sulfonic acid; UC, ulcerative colitis.
©2006 by the AGA Institute
1542-3565/06/$32.00
doi:10.1016/j.cgh.2006.08.008
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2006;4:1502–1506
thioprine, 6-mercaptopurine, or cyclosporine; (2) patients with
severe cardiovascular diseases; (3) patients with laboratory ab-
normalities indicating anemia (hemoglobin 9 g/dL), leukope-
nia, thrombocytopenia, or abnormal coagulation; (4) patients
with renal or liver disease, chronic pancreatitis, diabetes melli-
tus, or gallstone; (5) patients with infection, sepsis, or pneumo-
nia; and (6) pregnant or nursing women. Dropout criteria were
(1) patient exhibits complications during the study; (2) patient
decides to withdraw from the trial at will; and (3) patient
requires additional drug therapy that violates the inclusion
criteria. Any adverse symptom was recorded in the diary kept by
patients during the study. Laboratory investigations including a
complete blood count and blood chemistry were performed 3
times, at baseline, at 3 months, and at the end of the treatment.
Methods
This study was to be a randomized, multicenter (8
hospital institutions), double-blind, and placebo-controlled
clinical trial. Assignment to curcumin or placebo was according
to a computer-generated randomization scheme done by the
clinical pharmacist. Patients were given SZ (1.0–3.0 g/day; me-
dian, 2.0 g/day) or mesalamine (1.5–3.0 g/day; median, 2.25
g/day) plus 2 g curcumin, 1 g taken after breakfast and 1 g after
the evening meal, or placebo for 6 months (Figure 1). Patients
were then followed for an additional 6 months, during which
either SZ or mesalamine was continued. All medications except
SZ or mesalamine were discontinued 4 weeks before starting
this study. All study personnel and participants were blinded to
treatment assignment for the duration of the study. Only the
study statisticians and the data monitoring committee could
see unblinded data, but none had any contact with the study
patients. Curcumin and placebo were made to have identical
appearance (yellow), prepared by API Co, Ltd (Gifu, Japan). The
compositions of curcumin and placebo are shown in Table 1.
Clinical Assessment
CAI was measured at entry (within 2 weeks before
randomization), every 2 months, and then at the conclusion of
the clinical trial, whereas endoscopic index (EI) was determined
at entry and at the conclusion of the trial. Both CAI and EI were
according to Rachmilewitz.
25
Patients who had a CAI 4 were
considered to be in clinical remission, whereas relapse was
defined as CAI 5.
Statistical Analysis
Data are presented as the mean standard deviation
values and ranges unless indicated otherwise. For determining
statistical significance, comparisons were made by using the
Fisher exact test or the
2test. Pvalue .05 was considered
significant in all statistical evaluations.
Results
Clinical Outcomes
Seven patients (2 in the curcumin group and 5 in the
placebo group) were excluded in line with patients’ wishes.
Hence, 43 patients in the curcumin group and 39 patients in
the placebo group completed the study. Study groups were
well-matched with respect to gender, age, duration of UC,
recurrences during the past 2 years, clinical course, CAI, and EI
(Table 2). Recurrent rates evaluated in all patients (intention to
treat) also showed significant differences between the curcumin
and the placebo groups (P.049, Table 3). Relapses in the 2
groups during the 6-month study period together with the
Figure 1. Summary of the study design, randomization, and clinical
outcomes of the 6 months of treatment.
Table 1. Compositions of Medications (%)
Curcumin Placebo
Curcumin 50.0 Microcrystalline cellulose 25.0
Microcrystalline
cellulose
42.5 Dextrin 29.6
Malitol 7.5 Cornstarch 10.0
Malitol 35.0
FD & C Yellow No. 5 0.15
FD & C Yellow No. 6 0.04
Caramel color 0.2
Total 100 100
Table 2. Demography of Patients at Baseline
Demography Curcumin Placebo Pvalue
Male/female 23/22 26/18 .52
Age, mean (y) 45.2 15.8 39.7 14.2 .11
Range (18–75) (21–68)
Duration of UC (mo) 98.6 74.2 93.5 74.2 .77
Range (11–305) (5–336)
No. of recurrences during
past 2 y
1.6 1.2 1.5 1.0 .78
Range (0–5) (0–4)
Clinical course (cases)
First attack 5 4
Relapsing-remitting 29 28
Chronic continuousa10 8 .89
CAI before study 1.3 1.1 1.0 1.1 .23
Range (0–4) (0–4)
EI before study 1.3 0.8 1.3 1.0 .60
Range (0–3.0) (0–3.6)
Mean standard deviation values and (ranges) are presented.
aPatients with chronic continuous UC had a CAI 4 for at least 4
weeks before entry. “Chronic continuous” is commonly used in Japan
to indicate a CAI that oscillates between fully quiescent (0 –1) and
clinical remission (4) in some patients.
December 2006 CURCUMIN FOR MAINTENANCE THERAPY 1503
follow-up data are presented in Figures 1 and 2. Of the 43
patients who received curcumin, 2 patients (4.55%) relapsed
during 6 months, whereas 8 of 39 patients (20.51%) in the
placebo group relapsed (P.040) (Table 4).
We also determined the mean CAI and EI values before and
after the treatment (Table 5). The mean CAI in the curcumin
group was improved from 1.3 1.1 at baseline to 1.0 2.0 at
6 months (P.038). In contrast, CAI in the placebo group
showed significant deterioration; mean CAI increased from
1.0 1.1 to 2.2 2.3 (P.0003). Furthermore, patients in the
curcumin group had significantly improved EI, 1.3 0.8 vs
0.8 0.6 (P.0001). The EI values in the placebo group
showed no significant difference between baseline and post-
treatment.
Follow-up Observations
A 6-month follow-up was done after the end of the
6-month study period. As shown in Figure 2, 8 additional
patients in the curcumin group and 6 patients in the placebo
group relapsed during the 6-month follow-up while being on
SZ or mesalamine. There was no significant difference between
the 2 groups with respect to relapse rates during the 6-month
follow-up.
Safety Evaluation
A total of 9 mild and transient side effects in 7 of 89
patients were observed during curcumin maintenance therapy.
Some patients experienced more than 1 event. The side effects
included sensation of abdominal bulging, nausea, transient
hypertension, transient increase in the number of stools,
and elevated
guanosine triphosphate level. The elevated
guanosine triphosphate was observed in a patient who was a
regular alcohol drinker. No patient discontinued curcumin
therapy as a result of side effects, except 1 patient with hyper-
tension.
Discussion
The clinical outcomes of this double-blind, placebo-
controlled trial of curcumin therapy to sustain remission in
patients with quiescent UC might be briefly summarized as
follows: (1) 2 g/day curcumin in combination with SZ or me-
salamine had significantly better clinical efficacy in the preven-
tion of relapse compared with placebo plus SZ or mesalamine;
(2) curcumin significantly improved both CAI and EI; and
(3) curcumin was well-tolerated and was not associated with
any serious side effect.
Most currently available conventional drugs used to treat UC
are associated with unpleasant side effects. For example, nausea,
vomiting, headaches, rash, fever, hepatitis, pancreatitis, nephri-
tis, agranulocytosis, and male infertility are reported in approx-
imately 30% of patients who take SZ.
1
The sulfa moiety of the
drug is known to interfere with folic acid absorption. Even the
mesalamine derivatives that lack the sulfa moiety are associated
with fever, diarrhea, and abdominal discomfort. In contrast,
none of these side effects were observed when patients were
given curcumin. Curcumin is a diferulolymethane, a natural
plant product extracted from the root of Curcuma longa Linn.It
Table 4. Recurrence Status at 6 Months
Curcumin Placebo Pvalue
No. of patients treated 43 39
No. of patients with
recurrence
28
% with recurrence 4.65 20.51 .040
95% confidence interval 0.56–15.47 9.30–36.46
Analysis is based on the number of eligible patients who completed
the study, excluding the 7 patients who became protocol violators
during the study.
Table 3. Recurrence Rates at 6 and 12 Months Based on
Intention to Treat
Curcumin Placebo Pvalue
No. of patients randomized 45 44
No. of patients with
recurrence at 6 mo
28
% with recurrence at 6 mo 4.44 15.15 .049
95% confidence interval (%) 0.54–15.15 8.19–32.71
No. of patients with
recurrence at 12 mo
10 14
% with recurrence at 12 mo 22.2 31.8 .433
95% confidence interval (%) 11.2–37.1 18.6–47.6
Figure 2. The Kaplan-Meier curves showing the efficacy outcomes during the 6 months of therapy and 6 months of follow-up.
1504 HANAI ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 4, No. 12
is a common food additive popular for its pleasant mild aroma
and exotic yellow color, not likely to cause side effects. In India
and China, for centuries curcumin has been known as a medic-
inal plant. It is very likely that curcumin has several biochemical
actions that are not yet elucidated. Recently, curcumin was
reported to block the upstream of NF-
B and I
B kinase.
26
NF-
B is suspected to promote the expression of human
IBD.
26–28
Consistent with this assertion, recently we demon-
strated that curcumin can suppress colonic inflammation in-
duced by trinitrobenzene sulfonic acid (TNBS) in a mice model
of colitis.
24
In the present study, only 2 of 43 patients treated with
curcumin in combination with SZ or mesalamine relapsed
during the 6 months of therapy, whereas 8 of 39 patients who
received placebo with SZ or mesalamine relapsed during the
same period. It is appropriate to mention that mesalamine
alone when used as maintenance therapy during a 6-month
period has an efficacy similar to that of SZ, which is equal to the
placebo group in our study.
29,30
In addition, in this study, we
added a 6-month follow-up to the 6-month treatment time
during which patients received SZ or mesalamine only. Clinical
assessment at the end of the follow-up showed no significant
difference between the 2 groups. This supported our impression
that curcumin, in fact, does suppress relapse.
The 2-g curcumin per day in this study is similar to the dose
reported to have antitumor effect.
31
However, we admit that the
dose of curcumin used in this study might not be the optimum
and the most effective regimen. This could be viewed as one
major limitation of our data. With this in mind, we believe that
future studies in larger cohorts of patients should use multiple
doses of curcumin, because a dose higher than 2 g/day might
appear superior to 2 g/day.
Aminosalicylates have been reported to be inhibitors of
NF-
B.
4
However, curcumin has broader effects on the NF-
B
signal transduction pathways. In addition, curcumin inhibits
mitogen-activated protein kinase (MAPK),
32
c-Fos, and nitric
oxide synthase (NOS) activity,
33
thus potentially having a
broader spectrum of anti-inflammatory effects compared with
aminosalicylates (not to mention its safety).
In our study, both the clinical and endoscopic evaluation
scores were significantly improved by curcumin therapy. Espe-
cially the endoscopic score was substantially improved com-
pared with the placebo. Nine of the curcumin-treated patients
reported some mild side effects such as abdominal bloating and
nausea. Because the patients were also receiving SZ or me-
salamine as well, we could not with certainty attribute these
complaints to curcumin. A phase I human trial with 25 subjects
using up to 8 g curcumin per day found no toxicity or serious
side effects related to curcumin.
34
Therefore, we conclude that
curcumin therapy is both effective and safe in maintaining UC
remission.
In conclusion, the results of this study indicate that the
turmeric component, curcumin, is potentially a promising med-
ication for the treatment of IBD. In the near future, we plan to
undertake a multiple-dose (including a high-dose) curcumin
trial without an aminosalicylate as maintenance therapy in
patients with quiescent UC.
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Address requests for reprints to: Yukio Koide, MD, PhD, Department
of Microbiology and Immunology, Hamamatsu University School of
Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan. e-mail:
koidelb@hama-med.ac.jp; fax: 81-53-435-2335.
Supported by the Broad Medical Research Program (IBD-0069) from
The Eli and Edythe L. Broad Foundation.
1506 HANAI ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 4, No. 12
... However, some CAMs do not have explicit and conclusive evidence based on clinical trials [35] or have sideeffects and adverse reactions [49][50][51][52][53]. For example, homeopathy has no direct evidence of clinical or endoscopic efficacy in treating IBD patients, while curcumin and cannabis are reported to have mild side-effects despite exhibiting clinical or endoscopic efficacy [49][50][51][52]. ...
... However, some CAMs do not have explicit and conclusive evidence based on clinical trials [35] or have sideeffects and adverse reactions [49][50][51][52][53]. For example, homeopathy has no direct evidence of clinical or endoscopic efficacy in treating IBD patients, while curcumin and cannabis are reported to have mild side-effects despite exhibiting clinical or endoscopic efficacy [49][50][51][52]. This could be attributed to various reasons including formulation and dosage in addition to other drawbacks of the study which are discussed below. ...
... & ): CAMs with prior evidence in inducing and/or maintaining clinical remission of IBD. (~): CAMs with prior evidence in inducing and/or maintaining endoscopic remission of IBD. ( + ): CAMs with prior evidence in inducing decreased expression of proinflammatory biomarkers or increased expression of anti-inflammatory biomarkers[42,47,49,50,54,56,57,[64][65][66][67][68]. ...
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Background. Complementary and alternative medicines (CAMs) are used by patients with chronic disorders, such as inflammatory bowel disease (IBD), with a desire to manage their disease. Methods. Patients visiting an IBD outpatient clinic and infusion unit in a tertiary referral center were surveyed through an anonymized Dutch version of the international questionnaire to measure the use of CAMs. Results. Of the 467 IBD patients who responded to the survey, 41.8% ( n = 195 ) reported the use of CAMs. Gender ( p = 0.03 , higher in females), educational qualification ( p = 0.02 , higher in more educated patients), and number of prior IBD medical treatments ( p = 0.05 , higher in patients having received more than one therapy) were significantly associated with CAM usage. Overall, there was no significant difference in CAM-usage between UC (45.3%) and CD (38.2%) patients. Over two-thirds of patients reported using CAMs to alleviate IBD-related symptoms. The most prevalent reason for CAM-usage was to minimize stress and symptoms. The top five nonsupplemental CAMs used by IBD patients included probiotics, curcumin, yoghurt, homeopathy, and yoga. Among CAMs with a minimum of 25 users, yoga (93.5%), cannabis (87.5%), and mindfulness (84.6%) had high self-reported efficacy indices. Fifty-six percent of the patients who affirmed the economic worthiness of CAMs expressed their interest to consult with their gastroenterologist about CAM-conventional therapy interactions. Conclusion. CAM usage in IBD patients is highly prevalent, and consultation of the patients with the gastroenterologist about the use of CAMs is warranted. Since CAMs can interact with conventional therapies, a debate could help optimizing CAM use, eventually resulting in better disease management.
... Positive effects of curcumin therapy have also been demonstrated in patients with inflammatory bowel diseases. The use of curcumin in these patients reduced clinical symptoms and resulted in healing of endoscopic lesions [22,23]. In one randomized Japanese study with patients suffering from ulcerative colitis, it was shown that administration of curcumin in combination with 5-ASA preparations caused reduced recurrences of the disease. ...
... In patients taking only 5-ASA preparations during the course of the study (6 months), exacerbation was more frequent compared to patients taking additionally curcumin at a dose of 2 g/day (20.51% vs. 4.65%; p = 0.04). Moreover, in the group of patients taking curcumin, a significant improvement in endoscopic lesions was found, assessed based on the Rachmilewitz endoscopic index [22]. It is particularly important due to the neuroinflammatory hallmark of IBS pathogenesis and reports on overlap between IBS and inflammatory bowel diseases [24]. ...
... In our study, we did not observe any significant adverse effects of curcumin. In the previously mentioned Japanese study with curcumin at a dose of 2 g/day, no serious side effects were reported, and only a few patients reported mild bloating or nausea [22]. In the study carried out by Bandy et al., there were only mild side effects reported, such as flatulence and dry mouth [8]. ...
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Introduction Irritable bowel syndrome (IBS) is the cause of numerous gastroenterological consultations. Due to multifactorial pathogenesis, treatment of IBS is difficult. Even the management with new medications appears unsatisfactory. Recent reports on IBS therapy highlight the possible beneficial effect of curcumin. The aim of the study was to assess the efficacy and safety of curcumin in IBS patients. Materials and Methods Our non-controlled study included 51 patients: 30 (58.8%) women and 21 (41.2%) men diagnosed with IBS based on Roman Criteria IV, 35 patients with diarrhea-predominant (IBS-D) variant and 16 with constipation-predominant (IBS-C) variant. The quality of life and severity of symptoms were assessed with the IBS Symptom Severity Score (IBS-SSS) and IBS Quality of Life Instrument (IBS-QoL) questionnaires in all patients at: 0, 4, and 12-week time points. Results A statistically significantly lower IBS-SSS score was found after 4 and 12 weeks of using curcumin (p < 0.01), especially in the category of bloating and severity of abdominal pain. After 4 weeks of using curcumin, a reduction in the mean IBS-SSS score decreased from 279.7 to 202.2 points (p < 0.05). There was a significant increase in the overall score obtained with IBS-QoL questionnaire after the first 4 weeks of taking curcumin compared to baseline visit (41,9 vs. 53,4; p < 0.05). No side effects have been reported associated with the curcumin use. Conclusions In summary, curcumin is effective in reducing the IBS clinical symptoms and improving the patients’ quality of life. It also has a high safety profile.
... The anti-inflammatory activity of curcumin, including the support of IBD therapy, is based on the inhibition of effective myeloperoxidase function, prevention of NF-kappaB kinase and IKB activation, as well as the reduction of interleukin-1 production and neutrophil infiltration [46]. Studies have shown that combining pharmacological treatment for patients with UC with curcumin supplementation can improve disease activity indices, reduce the risk of recurrent exacerbation, and alleviate disease symptoms, chief among which are improved mood and minimized urgency of bowel movements [47][48][49][50][51]. Despite the promising results of curcumin supplementation in supporting the treatment of UC, researchers note that there is a need for more studies to confirm the efficacy and safety of its higher doses, but a small addition of curcumin can add variety to daily meals [46][47][48]. ...
... Studies have shown that combining pharmacological treatment for patients with UC with curcumin supplementation can improve disease activity indices, reduce the risk of recurrent exacerbation, and alleviate disease symptoms, chief among which are improved mood and minimized urgency of bowel movements [47][48][49][50][51]. Despite the promising results of curcumin supplementation in supporting the treatment of UC, researchers note that there is a need for more studies to confirm the efficacy and safety of its higher doses, but a small addition of curcumin can add variety to daily meals [46][47][48]. ...
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Ulcerative colitis (UC) belongs to the group of inflammatory bowel diseases (IBD). UC is an incurable, diffuse, and chronic inflammatory process of the colonic mucosa with alternating periods of exacerbation and remission. This review aimed to analyze the scientific research conducted to date to determine what impact different nutritional plans and dietary supplements may have on the course of UC. The latest 98 articles about nutrition and supplementation in ulcerative colitis were used to prepare the work. Certain components in food can greatly influence the course of UC, inducing changes in the composition and function of the gut microbiome. This activity may be an important part of therapy for people with IBD. The Mediterranean diet has shown the most promising results in the treatment of patients with UC due to its high content of biologically active foods. Patients with UC may benefit from the UC Exclusion Diet (UCED); however, it is a new nutritional plan that requires further research. Patents frequently resort to unconventional diets, which, because of their frequent elimination of nutrient-rich foods, can worsen the health and nutritional status of those who follow them. The benefits of omega-3 fatty acids and probiotics supplementation may have additional therapeutic effects; however, the evidence is not unequivocal.
... Based on the current evidence from RCTs, curcumin stands out with four of the six studies showing a positive impact on clinical and endoscopic remission [86][87][88][89] (figure 1, figure 2A). Three of the four aforementioned studies also displayed a consistent trend showing a positive influence on clinical and endoscopic remission (figure 2B, online supplemental table 2) while having an insignificant impact on modulation of biomarkers and QoL. ...
Article
Inflammatory bowel disease (IBD) is an emerging global disease characterised by chronic inflammation of the gastrointestinal tract. However, IBD is also manifested by several extraintestinal symptoms which, along with the intestinal symptoms, impact on the mental and emotional well-being of patients. Despite therapeutic advancements, only one-third of the diagnosed patients receiving approved medical treatments achieve short-term to medium-term remission. Consequently, patients who do not get successfully treated might resort to using complementary and alternative approaches to manage their symptoms, with or without consulting their treating clinician. Despite their possible potential, such approaches have various risks stemming from unknown adverse reactions and possible interference with medically approved therapies. In this study, we present the results of a well-performed literature review where we included randomised clinical trials which have assessed the efficacy of complementary approaches and dietary therapy on at least one of the following four outcomes: clinical remission, endoscopic remission, modulation of molecular biomarkers or quality of life metrics. By pointing out intraoutcome and interoutcome concordance, we identified possible candidates for clinical adoption and further study in larger randomised clinical trials covering the broad spectrum of IBD heterogeneity. We finally proposed a patient-centric clinical care model and a series of recommendations for stakeholders, with special attention to complementary approaches and dietary strategies, aimed at achieving holistic remission.
... A randomized, double-blind trial in patients with ulcerative colitis suggested that consumption of 2 g/ day of curcumin reduced recurrence rates and improved the clinical activity index. Curcumin was also found to have anti-Helicobacter pylori activity Bundy et al., 2004;Hanai et al., 2006;Di Mario et al., 2007;De et al., 2009;Zaidi et al., 2009;Khonche et al., 2016;Rahmani et al., 2016 Brain health and cognitive function-curcumin enhanced Abeta clearance and reduced Abeta and plaque burden in animal studies Yang & Lim, 2005;Gingadze et al., 2008;Cashman et al., 2008;Ahmed & Gilani, 2009;Ishrat et al., 2009;Wakade et al., 2009;Ng et al., 2006;Rainey-Smith et al., 2016 Anti-inflammatory-curcumin may help maintain healthy joint function, effective in preventing joint inflammation and can act an analgesic and an anti-inflammatory agent Kuptniratsaikul et al., 2009;Panahi et al., 2016a;Amalraj et al., 2017 ;Haroyan et al., 2018; Blood glucose control-turmeric supplementation has been shown to improve glucose indexes as shown by a randomized clinical trial with patients with Type 2 diabetes mellitus. In another clinical trial, patients given turmeric in capsules per day for 12 week and there was a decreased in serum levels of glucose, insulin, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Usharani et al., 2008;Cheng et al., 2009;Navekar et al., 2017;Panahi et al., 2016bPanahi et al., , 2016c Weight loss due to bioavailable curcumin Ejaz et al., 2009;Di Pierro et al., 2015 Fenugreek Steroidal saponins (diosgenin, trigogenin), flavonoids and alkaloids ( gentianine and trigonelline), 4-hydroxyisoleucine Lipid metabolism and vascular health-can decrease total plasma cholesterol Petit et al., 1995;Bordia et al., 1997;Boban et al., 2006;Narender et al., 2006;Srichamroen et al., 2008 Blood glucose metabolism-4-hydroxyisoleucine supports glucose and lipid metabolism based on animal and in vitro studies; ...
... A randomized, double-blind trial in patients with ulcerative colitis suggested that consumption of 2 g/ day of curcumin reduced recurrence rates and improved the clinical activity index. Curcumin was also found to have anti-Helicobacter pylori activity Bundy et al., 2004;Hanai et al., 2006;Di Mario et al., 2007;De et al., 2009;Zaidi et al., 2009;Khonche et al., 2016;Rahmani et al., 2016 Brain health and cognitive function-curcumin enhanced Abeta clearance and reduced Abeta and plaque burden in animal studies Yang & Lim, 2005;Gingadze et al., 2008;Cashman et al., 2008;Ahmed & Gilani, 2009;Ishrat et al., 2009;Wakade et al., 2009;Ng et al., 2006;Rainey-Smith et al., 2016 Anti-inflammatory-curcumin may help maintain healthy joint function, effective in preventing joint inflammation and can act an analgesic and an anti-inflammatory agent Kuptniratsaikul et al., 2009;Panahi et al., 2016a;Amalraj et al., 2017 ;Haroyan et al., 2018; Blood glucose control-turmeric supplementation has been shown to improve glucose indexes as shown by a randomized clinical trial with patients with Type 2 diabetes mellitus. In another clinical trial, patients given turmeric in capsules per day for 12 week and there was a decreased in serum levels of glucose, insulin, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Usharani et al., 2008;Cheng et al., 2009;Navekar et al., 2017;Panahi et al., 2016bPanahi et al., , 2016c Weight loss due to bioavailable curcumin Ejaz et al., 2009;Di Pierro et al., 2015 Fenugreek Steroidal saponins (diosgenin, trigogenin), flavonoids and alkaloids ( gentianine and trigonelline), 4-hydroxyisoleucine Lipid metabolism and vascular health-can decrease total plasma cholesterol Petit et al., 1995;Bordia et al., 1997;Boban et al., 2006;Narender et al., 2006;Srichamroen et al., 2008 Blood glucose metabolism-4-hydroxyisoleucine supports glucose and lipid metabolism based on animal and in vitro studies; ...
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Culinary spices and herbs have been used in food and beverages to enhance aroma, flavor, and color. They are rich in phytochemicals that provide significant antioxidant and anti-inflammatory effects. There is growing interest in identifying compounds from spices and herbs responsible for modulating oxidative and inflammatory stress to prevent diet-related diseases. This contribution will provide an overview of culinary spices and herbs, their classification , their sources or origins and more importantly, their chemical composition, antioxidant activity and their impacts on human health based on important and recent studies.
... Researches have proven various therapeutic potentials of turmeric including anti-inflammatory, [26] antitumor, [27] antibacterial, [28] antiviral, [29] antioxidant, [30] antiseptic, [31] cardioprotective, [32] hepatoprotective, [33] and digestive activities. [34] Moreover, it also constitutes to an important spice in the Indian culinary and is used extensively in daily diet. Adulteration of turmeric with MY would be dangerous to the health of people at all ages. ...
Article
Introduction: The food products available in the market today are made attractive by adding food colors. Fruits, vegetables, spices, sweets, and even the commonest drugs used as medicine in day-to-day life are adulterated with nonpermitted colors. Haridra or turmeric is the most popularly used Vishaharadravya/antitoxic drug which is taken internally almost every day both in diet and as medicine. Metanil yellow (MY) is a “nonpermitted” food colorant used extensively as an adulterant in different spices, especially turmeric. Though the quantity of intake would be small, when taken continuously, it may lead to several adverse life-threatening effects in humans. Methods: 20 different samples of Haridra (Turmeric) were collected randomly from markets in and around Varanasi. The presence of nonpermitted food color-MY in these turmeric samples was first tested with preliminary color test followed by ultraviolet-visible spectroscopic studies. The color change and change in absorption spectra have been used to identify the contaminated samples. Results and Conclusion: Two out of twenty samples of Haridra were found to be adulterated with MY. Food adulteration in daily diet is a matter of great concern and is a strong cause for Garavisha. Mass awareness has to be raised on the issue. Our results suggest that special care has to be taken by the turmeric-based Ayurveda manufacturers to avoid the use of such contaminated turmeric.
Chapter
Gastrointestinal tract (GIT) is the one of the most essential organs of human body. In the GIT, infections may be painful, destructive, and humiliating. Substantial morbidity and mortality worldwide are responsible for infections in gastrointestinal (GI), especially diseases like diarrhea. GI infections are caused by a large variety of viral, pathogens, bacterial, and protozoa. Herbal medicines are herbs used in botany or phytomedicine for their medicinal and therapeutic properties. Accessible medications also have poor effectiveness, or many adverse effects are associated with them. Therefore, to treat GI problems, alternative drugs are essential. The aim of this chapter was to recognize herbal drugs that are used to treat GI infections. Herbal medicines are now used for the treatment or prevention of GI infections of Western population until 50 %, in large minority cases. Many bioactive compounds include herbal preparations with both potentially deleterious and beneficial effects. People with GI infections that cannot be treated using traditional drug treatment can benefit from herbal medicine. Such specific herbal plants are ginger, turmeric, and astragalus, which are used to treat GI infections. Herbal medication is a healthy, holistic option having no side effects that is usually adverse. Herbal medicines are used to treat a number of other conditions effectively as well. There is a strong need for greater information on herbal therapy for patients and physicians, as well as constitution in regulating consistency on herbal formulation for GI infection care.
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Objective To evaluate the randomized controlled trials (RCTs) of Curcumin and Curcuma longa Extract in the treatment of autoimmune diseases. Methods Databases such as Embase, Web of Science, PubMed and The Cochrane Library were searched from the database establishment to February 2022 to collect RCTs of Curcumin and Curcuma longa Extract in the treatment of autoimmune diseases. Then the literature was screened and the data were extracted. Meta-analysis was performed using RevMan 5.3 software. Results A total of 34 records were included, involving 31 RCTs and 10 types of autoimmune disease. Among them, ankylosing spondylitis (AS) involves one RCT, Behcet ‘s disease (BD) involves one RCT, Crohn ‘s disease involves two RCTs, multiple sclerosis (MS) involves two RCTs, oral lichen planus involves six RCTs, psoriasis involves two RCTs, rheumatoid arthritis (RA) involves five RCTs, systemic lupus erythematosus (SLE) involves two RCTs, arteritis involves one RCT, ulcerative colitis (UC) involves nine RCTs. Among them, most of the RCTs of ulcerative colitis (UC), oral lichen planus, RA showed that curcumin and curcumin extracts improved clinical or laboratory results. Crohn ‘ s disease, MS, SLE, psoriasis included two RCTs; they all showed improvements (at least one RCT reported improvements in clinical outcomes). AS, BD and arteritis included only one RCT, and the clinical results showed improvement. However, due to the small number of RCTs and the small number of patients involved in each disease, there is still a need for more high-quality RCTs. Conclusion Curcumin and Curcuma longa Extract had good clinical efficacy in the treatment of Psoriasis, UC and RA, so Curcumin and Curcuma longa Extract could be used in the treatment of the above diseases in the future. The results of Meta-analysis showed that Curcumin and Curcuma longa Extract did not show efficacy in the treatment of oral lichen planus, while Takayasu arteritis, SLE, MS, AS, BD and CD did not report sufficient clinical data for meta-analysis. Therefore, large-sample, multi-center clinical trials are still needed for revision or validation.
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Purpose of review: Diet remains an important topic for patients with inflammatory bowel disease (IBD), yet few guidelines for dietary recommendations exist. There is a growing interest in the use of diet as treatment or adjuvant therapy for both ulcerative colitis and Crohn's disease. Here, we highlight the latest evidence on the use of diet for treatment of symptoms, active disease and maintenance of remission in ulcerative colitis and Crohn's disease. Recent findings: The Crohn's Disease Exclusion Diet (CDED) and the Specific Carbohydrate Diet (SCD) are studied diets that have gained popularity, but there is growing interest in the use and efficacy of less restrictive diets such as the Mediterranean diet. Recent data suggest healthful dietary patterns alone, with an emphasis on whole foods that are high in vegetable fibre and that promote less consumption of ultra-processed foods may also help achieve remission in patients with ulcerative colitis and Crohn's disease. Summary: In this review, we summarize the literature on diet as treatment for IBD. We highlight the latest clinical dietary studies, randomized clinical trials, as well as new and emerging diets for the treatment of IBD.
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Transcription factors of the nuclear factor kappaB (NF-kappaB) family play an important role in the regulation of genes involved in inflammation. In inflammatory bowel diseases, proinflammatory cytokines known to be regulated by NF-kappaB are involved. The aim of this study was to investigate the role of NF-kappaB activation during mucosal inflammation in situ. A monoclonal antibody, alpha-p65mAb, was applied for immunofluorescence and immunohistochemical analysis that recognizes activated NF-kappaB. Electrophoretic mobility shift assay was used to directly demonstrate the presence of active DNA-binding NF-kappaB. Using the alpha-p65mAb antibody, activated NF-kappaB could be found in biopsy specimens from inflamed mucosa but was almost absent in uninflamed mucosa. The number of cells showing NF-kappaB activation correlated with the degree of mucosal inflammation but was not significantly different between inflamed mucosa from patients with Crohn's disease, ulcerative colitis, and nonspecific colitis or diverticulitis. NF-kappaB activation was localized in macrophages and in epithelial cells as identified by double-labeling techniques. Electrophoretic mobility shift assay with isolated lamina propria mononuclear cells and epithelial cells confirmed these results. This study shows for the first time the activation of NF-kappaB during human mucosal inflammation in situ. In addition to macrophages, epithelial cells contained activated NF-kappaB, indicating an involvement in the inflammatory process.
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It is clear that sulfasalazine plays a major role in the medical therapy of ulcerative colitis and Crohn's disease. In ulcerative colitis, continued sulfasalazine therapy prevents relapses. It is also apparent that this medication can cause a varied spectrum of adverse effects in 10–45% of the people who are dependent upon it. From this review, we know that the toxic manifestations of sulfasalazine can involve almost any organ system, and more recently described side effects related to the medication such as male infertility are just being recognized. Awareness of the wide spectra of adverse effects of sulfasalazine and prompt appropriate measures might allow the patients to avoid major complications and obtain continued benefit from the drug. Although in some cases this may entail discontinuing the medication permanently, most often side effects can be remedied by temporary discontinuation of the drug and then reintroducing the drug very slowly up to a maintenance level not to exceed 2 g/day. A knowledge of the adverse effects of sulfasalazine as well as the indications for its use will allow physicians to provide better care for patients with inflammatory bowel disease.
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Levels of various serum proteins were found to change in adjuvant induced arthritis. Increased levels of a glycoprotein with an apparent molecular weight of 72 kDa (Gp A72) were observed in the sera of arthritic rats. Gp A72 is an acidic glycoprotein with a pI of 5.1. Gp A72 also showed antitryptic activity. The appearance of Gp A72 in the serum preceded the onset of paw inflammation in arthritic rats and persisted in the chronic phase. Oral administration of the antiinflammatory spice principles-capsaicin (from red pepper) and curcumin (from turmeric) lowered the levels of Gp A72 by 88 and 73% respectively with concomitant lowering of paw inflammation in arthritic rats.
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We have studied the effect of curcumin (diferuloylmethane), a major component of the food flavor turmeric, on the proliferation and cell cycle progression of human umbilical vein endothelial cells (HUVEC). Curcumin inhibited the DNA synthesis of HUVEC as revealed by [3H]thymidine incorporation in a dose-dependent manner without significantly affecting the viability of the cells. The growth of HUVEC stimulated with fibroblast growth factor (FGF) and endothelial growth supplement (ECGS) was also inhibited by curcumin. Addition of curcumin to HUVEC resulted in an accumulation of >46% of the cells in early S-phase, as determined by the FACS analysis. Pulse labeling studies with [3H]thymidine demonstrated that curcumin affected cells that were actively undergoing DNA synthesis. The de-novo synthesis of thymidine depends on thymidine kinase (TK) enzyme. Curcumin caused a significant loss of TK activity, which may be one of the possible mechanism(s) for the inhibition of DNA synthesis activity of HUVEC by curcumin. These studies have revealed a unique mode of action of curcumin whereby it effectively blocked the cell cycle progression during S-phase by inhibiting the activity of TK enzyme. The migration, proliferation and differentiation of HUVEC leads to angiogenesis, which facilitates the tumor initiation and promotion. Since curcumin inhibited the proliferation of HUVEC, it could turn out to be a very useful compound for the development of novel anti-cancer therapy.
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