Table 5.

Details of clinical trials of curcumin in the treatment of inflammatory bowel disease.

S. No	Author/Year	Study Title	Dose and Duration	Population and Study Design	Main Findings
1	Cheng, 2001 [132]	Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-the risk or pre-malignant lesions	500–8000 mg/day, three months	Twenty-five patients with the risk of premalignant lesions in Taiwan. Patients with resection of bladder cancer, oral leukoplakia, stomach metaplasia, cervical intraepithelial neoplasm, and Bowen’s disease enrolled in this clinical trial.	Curcumin could not be measured in lower doses. Serum concentration varied from 0.5 ± 0.11 mM and 1.77 ± 1.87 mM at 4000 mg/day. Curcumin could not produce any adverse effects when taken by oral administration for three months, up to 8000 mg/day.
2	Sharma et al., 2004 [133]	Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance	0.45 to 3.6 g/day, four months	Fifteen patients with colorectal cancer resistant to chemotherapy participated in this clinical trial	Supplementation of curcumin was associated with mild diarrhea, and uptake of 3.6 g/day of curcumin results in a noticeable amount of the compound and conjugates in the urine and plasma. Curcumin supplementation obstructs the PGE2 production in blood leukocytes. Study results lead us to conclude that the systemic pharmacological properties of a daily dose of 3.6 g of curcumin are appropriate for its evaluation in the prevention of malignancies at sites other than the gastrointestinal tract and also help to optimize the clinical evaluation of curcumin in a Phase II chemoprevention or chemotherapy trial.
3	Holt et al., 2005 [129]	Curcumin therapy in inflammatory bowel disease: a pilot study	Curcumin (550 mg and 360 mg/day) two times for the first month and three times for the second month	Five CD patients; pilot study	CD activity index dropped, and the condition improved in the majority of the patients
4	Hanai et al., 2006 [123]	Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial	Curcumin (capsules) (2 g) + 1.5–3 g 5-ASA or 1–3 g sulfasalazine/day (n = 45) or placebo + 5-ASA/sulfasalazine (n = 44) (six months)	89 patients participated in this clinical trial. Multicenter, randomized, double-blind, placebo-controlled study	Seven patients did not complete the trial. After six months, the relapse rate was 2/43 (4.65%) in the curcumin group and 8/39 (20.51%) in the placebo group Curcumin improved the clinical activity index (p < 0.038). In the curcumin-treated group, it improved from 1.3 to 1.0. In contrast, it raised from 1.0 to 2.2 in the placebo group. Furthermore, patients who consumed curcumin had a considerably enhanced endoscopic index (p < 0.0001). Curcumin was well-tolerated and not associated with any side effects.
5	Singla et al., 2014 [124]	Induction with NCB-02 (curcumin) enema for mild-to-moderate distal ulcerative colitis—a randomized, placebo-controlled, pilot study	140 mg NCB-02 (curcumin extract) enema + oral 1.6 g 5-ASA/day (n = 28) or placebo enema + oral 1.6 g5-ASA/day (n = 22), eight weeks	Mild to moderate UC patients (n = 45). Pilot, double-blind, randomized, placebo-controlled study	Two and six patients from the NCB-02 group and the placebo group, respectively, did not finish the trial. Treatment response was seen in 56.5% of patients in the NCB-02 group compared with 36.4% (p = 0.175) in the placebo group. In the NCB-02 group, the clinical remission was observed in 43.4% of the patients whereas and in 22.7% of the patients in the placebo group (p = 0.14). After eight weeks, clinical response was 92.9% in the NCB-02 group versus 50% in the placebo group (p = 0.01). Clinical remission: 71.4% in the NCB-02 group versus 31.3% in the placebo group. Improvement of endoscopic activity: 85.7% in the NCB-02 group versus 50% in the placebo group (p = 0.04). No side effects.
6	Lang et al., 2015 [125]	Curcumin in combination with mesalamine induces remission in patients with mild-to-moderate ulcerative colitis in a randomized controlled trial	Curcumin (capsules) (3 g) + 4 g 5-ASA/day (n = 26) or placebo + 4 g 5-ASA/day (n = 24), one month	Mild or moderate UC patients (n = 50). Multicenter, randomized, double-blind, placebo-controlled study	Clinical remission: 54% in the curcumin group versus 0% in the placebo group. Clinical response: 65.3% in the curcumin group versus 12.5% in the placebo group. Endoscopic remission: 38% in the curcumin group versus 0% in the placebo group. No adverse effects.
7	Kedia et al., 2017 [134]	Low dose oral curcumin is not effective in induction of remission in mild to moderate ulcerative colitis: results from a randomized double a blind placebo-controlled trial	Curcumin (450 mg/day) + 2.4 g 5-ASA/day (n = 29) or placebo + 2.4 g 5-ASA/day (n = 33), eight weeks	Mild or moderate UC patients (n = 62). Single-center, double-blind, randomized, placebo-controlled study	The minimum dose of curcumin (450 mg/daily) was ineffective in UC patients. No significant changes were observed between the clinical remission and endoscopic remission rates of curcumin- and placebo-treated groups. Twenty-one patients withdrew from the study.
8	Peterson et al., 2018 [126]	Effects of turmeric and curcumin dietary supplementation on human gut microbiota: a double-blind, randomized, placebo-controlled pilot study	Turmeric tablets (C. longa (1000 mg) + piperine (1.25 mg)) and curcumin tablets (curcumin (1000 mg) and piperine (1.25 mg)); the subjects were advised to take three tablets orally with food two times per day (total 6000 mg daily)	UC patients (n = 30). Randomized, double-blind, placebo-controlled study	Microbiota analyses showed that the individual reactions to treatment were different. The patterns within the groups were almost the same in the turmeric group and the curcumin group. Though in the control group the total decrease in bacterial species was 15%, in the turmeric and curcumin groups, this amount increased by 7% and 69%. The study results confirmed that curcumin and turmeric changed the gut microbiota in the same way and suggested that curcumin can effect most of the detected variations seen in turmeric-treated patients.
9	Shapira et al., 2018 [135]	Of mice and men: a novel dietary supplement for the treatment of ulcerative colitis	Two Coltect (500 mg curcumin, 250 mg green tea, and 100 µg selenium) tablets two times daily for eight weeks	Mild or moderate UC patients (n = 20)	Combined treatment with curcumin, green tea polyphenol, and selenium showed better outcomes with reduced inflammatory symptoms and disease activity index in patients. Among the 20 patients, 14 patients (70%) were improved; nine patients (45%) featured complete remission and four patients (20%) showed marked improvement. One patient (5%) featured moderate improvement. The clinical active index showed considerable reduction at four and eight weeks (p < 0.001). There was no improvement in symptoms for two patients, and one patient was excluded after eight weeks. Besides, the uncertain condition resulted in exclusion of three subjects from the study. In eleven patients (69%), endoscopic improvement was observed, and four patients (25%) attained complete remission.
10	Sadeghi et al., 2020 [127]	The effect of curcumin supplementation on clinical outcomes and inflammatory markers in patients with ulcerative colitis	Curcumin (1.500 mg/day) + routine drugs (n = 35) or placebo + routine drugs (n = 35), eight weeks	Mild or moderate UC patients (n = 70). Double-blind, randomized, placebo-controlled study	Four patients from the curcumin group and three patients from the placebo group were excluded from the study. Clinical remission: 83.9% (curcumin) vs. 43.8% (placebo). Significant decrease in high-sensitivity C-reactive protein concentrations and erythrocyte sedimentation rate in the curcumin group as compared to the placebo group. The mean inflammatory bowel disease questionnaire (IBDQ)-9 score was increased in the curcumin group in comparison with the placebo group. Furthermore, curcumin improved life quality of UC patients.
11	Sugimoto et al., 2020 [130]	Highly bioavailable curcumin derivative ameliorates Crohn’s disease symptoms: a randomized, double-blind, multicenter study	Theracurcumin (360 mg/day, n = 20) or placebo (n = 10), 12 weeks	Mild or moderate CD patients (n = 30). Randomized, double-blind, placebo-controlled, multicenter study	After 12 weeks, the theracurcumin-treated group showed a significant reduction in clinical disease activity. The clinical reduction observed at 4, 8, and 12 weeks was 35%, 40%, and 40%, respectively, which was considerably higher than in the placebo group. Theracurcumin also exhibited a decrease in the severity of CD and stronger endoscopic reduction in the theracurcumin group (15% as compared to 0% in the placebo-treated groups), suggesting the potential of using theracurcumin to ameliorate CD.
12	Bommelaer et al., 2020 [131]	Oral curcumin no more effective than placebo in preventing recurrence of crohn’s disease after surgery in a randomized controlled trial	2.5 mg/kg azathioprine; subjects were arbitrarily allocated to the oral curcumin (3 g/day; n = 31) group and the placebo (n = 31) group for six months	CD patients (n = 60). Multicenter, randomized, double-blind, placebo-controlled study	Endoscopic recurrence (score ≥ i2) was seen in 18 patients (58%) of the curcumin-treated group whereas and in 21 patients (68%) in the placebo group (p = 0.60). Forty-five percent of the patients featured clinical recurrence of CD in the placebo group as compared with 30% of the patients in the curcumin group (p = 0.80). The clinical trial was terminated after short-term examination because of futility. The study results stated that curcumin is not very effective in preventing CD recurrence post-surgery.
13	Banerjee et al., 2020 [128]	Novel bioenhanced curcumin with mesalamine for induction of clinical and endoscopic remission in mild-to-moderate ulcerative colitis: a randomized, double-blind placebo-controlled pilot study	The standard dose of mesalamine was randomized to either 50 mg bio-enhanced curcumin (BEC) or an identical placebo twice daily	Mild or moderately active UC patients (n = 69). Randomized, double-blind, placebo-controlled, pilot study	After six weeks, 44.1% (15/34) and 35.3% (14/34) of patients had clinical and endoscopic remission, correspondingly, compared to none in the placebo-treated group. BEC-treated patients’ clinical response was considerably higher (18/34, 52.9%) than that of placebo-treated patients (5/35, 14.3%) (p = 0.001). At three months, the endoscopic remission, clinical response, and clinical remission rates were 55.9% (19/34), 58.8% (20/34), 44% (16/34) in the BEC group and 5.7% (2/35), 28.6% (10/35), 5.7% (2/35) in the placebo group, respectively. After six and 12 months, 95% (18/19) and 84% (16/19) of the BEC-treated patients maintained clinical remission. No adverse effects.