Table 1.
Summary of Clinical Studies Using Antioxidants in IBD Patients
| Trial characteristic | Population | Subjects | Intervention; duration | Concomitant therapy | Outcome summary | Conclusion | Reference, year |
|---|---|---|---|---|---|---|---|
| Randomized, placebo-controlled pilot study | UC patients; age: 18–70 y | n =37 | Oral NAC (0.8 g/day); 4 weeks | Mesalamine | Clinical remission rate (MTWSI ≤ 2) 63% in treated vs 50% in placebo; clinical response (MTWSI ≥ 2) 66% in treated vs 44% in placebo; reduced interleukin 8 and MCP-1 level; no adverse effect | NAC as combination therapy with mesalamine resulted in clinical improvement in UC patients | 87, 2008 |
| Randomized pilot study | UC patients | n=42 | Intravenous PC-SOD (40 or 80 mg/day); 4 weeks | Immunosuppressants (azathioprine, mercaptopurine) and/or anti-UC agents (mesalazine, salazosulfapyridine) | Decreased Ulcerative Colitis-Disease Activity Index (UC-DAI) in both 40 mg and 80 mg groups; no severe side effects with any of the doses | PC-SOD improved UC more rapidly than previously existing drugs | 58, 2008 |
| Randomized double-blind placebo-controlled | Mild to moderate UC patients; age: 18–75 y | n=121 | Oral tablets of PLC (ST 261; 1 g or 2 g/day); 4 weeks | Aminosalicylates or thiopurine | Clinical/endoscopic response in 75% of patients with 1 g/day and 69% in patients with 2 g/day; remission rates were 55%, 49%, and 35% in PLC (1 g/day), PLC (2 g/day), and placebo groups, respectively. | PLC could be potent treatment modality for mild to moderate UC patients | 89, 2011 |
| Open-label, proof-of-concept pilot study | Mild to moderate IBD patients; age: 16–80 y | N=14 | Oral PLC (ST 261; 2 g/day); 4 weeks | Aminosalicylates, mercaptopurine, or azathioprine | Reduction of Disease Activity Index (DAI) in both UC and CD patients; improvement in Histological Index (HI); no adverse effects | PLC improved endoscopic and histologic activity of mild to moderate UC | 88, 2012 |
| Case-control study | IBD patients; age: 15–34 y | n=219; 111 (UC) + 128 (CD) | VitC from food source, calculated from FFQ collected; 5 y | None | Low risk of UC development with vitC intake | Intake of vitC was negatively associated to UC risk | 96, 2005 |
| Randomized double-blind placebo-controlled | CD patients; age: 38.3 ± 2.9 y (treated); 36.5 ± 1.7 y (placebo) | n=57 | Oral vitC (1000 mg) and vitE (800 IU) daily; 4 weeks | None | Reduction in oxidant burden (measured by breath pentane and ethane output, plasma lipid peroxides, and F2-isoprostane; no change in disease activity | Significant reduction in oxidant burden, but disease activity remained stable in vitC-treated group | 93, 2003 |
| Randomized double-blind placebo-controlled | UC patients; age: 20–45 y | n=150 | Oral vitA (25,000 IU/day); 2 mo | Mesalamine | Decreased DAI and higher clinical response and mucosal healing in vitA group | VitA had positive clinical and endoscopic effects in UC patients | 129, 2018 |
| Open-label study | Mild and moderately active UC patients; age: 21–55 y | n=15 | Enema of α-tocopherol (8000 U/day); 12 weeks | Mesalamine | Decreased average DAI, remission in 64% of patients of treated group | α-tocopherol decreased disease severity in patients with active UC | 92, 2008 |
| Randomized double-blind placebo-controlled multicentric | Patients with quiescent UC; age: 13–65 y | n=89 | Oral curcumin (1 g twice a day); 6 mo | Sulfasalazine or mesalamine | Improved Clinical Activity Index (CAI) and endoscopic index (EI), and suppression in morbidity associated with UC in curcumin group | Curcumin could be a promising and safe medication for maintaining remission in patients with quiescent UC | 130, 2006 |
| Randomized double-blind placebo-controlled | Mild to moderate UC patients; age: 18–70 y | n=70 | Oral curcumin (500 mg capsule 3 times a day); 8 weeks | Salicylates and/or immunomodulators and/or corticosteroids | Significant improvement in Clinical Colitis Activity Index, significantly higher score of quality of life, reduced serum hs-CRP and ESR in curcumin group than placebo | Curcumin supplementation along with traditional drug was associated with improved clinical outcome in mild to moderate UC patients | 131, 2020 |
| Randomized double-blind placebo-controlled | Mild to moderate UC patients; age: 18 y and older | n=56 | Oral curcuminoids nanomicelles (80 mg 3 times a day); 4 weeks | Mesalamine | Decreased SCCAI score in curcuminoid group; reduced frequency of urgent defecation; improved patient’s self-reported well-being | Curcuminoids nanomicelles treatment significantly improved clinical activity of UC patients | 132, 2018 |
| Randomized double-blind placebo-controlled | Mild to moderate UC patients; age: 18–70 y | n=50 | Oral curcumin capsules (1000 mg capsule twice a day); 4 weeks | Mesalamine | Clinical remission in 53.8% and endoscopic remission in 38% of curcumin group compared with 0% in placebo | Addition of curcumin to drug (mesalamine) therapy was superior in inducing clinical and endoscopic remission in UC patients | 133, 2015 |
| Randomized double-blind placebo-controlled pilot study | Patients with mild to moderate distal UC; age: >18 y | n=45 | Enema of NCB-02 (standardized curcumin preparation) ie, equivalent to 140 mg curcumin once daily; 8 weeks | Mesalamine | Significantly better response in NCB-02 compared with placebo in terms of clinical response (92.9% vs 50%), clinical remission (71.4% vs 31.3%), and improvement in endoscopic activity (85.7% vs 50%) | NCB-02 enema improved disease activity in patients with mild to moderate distal UC | 134, 2014 |
| Randomized double-blind placebo-controlled multicentric | Mild to moderate Crohn’s disease patients; age: 21–65 y | n=30 | Theracurmin (a new curcumin derivative with increased absorption rate; 360 mg/day); 12 weeks | Mesalamine (90% of patients), immunomodulators (33.3% of patients), steroids (3.3% of patients), and anti-TNFα (6.7% of patients) | Reduction in clinical disease activity; 40% clinical remission rate and 15% endoscopic remission rate in the Theracurmin group compared with 0% in placebo; better healing of anal lesion with no adverse effect in Theracurmin-treated group | Theracurmin treatment showed significant clinical and endoscopic efficacy with favorable safety profile in mild to moderate Crohn’s disease | 135. 2020 |
| Randomized double-blind placebo-controlled pilot study | Mild to moderate UC patients; age: >18 y | n=56 | Oral resveratrol capsule (500 mg pure trans-resveratrol/day); 6 weeks | — | Decreased disease activity, increased quality of life, increased serum SOD and TAC, and decreased serum MDA in resveratrol group | Supplementation of resveratrol reduced oxidative damage and improved quality of life and disease activity of UC patients | 136, 2016 |
| Randomized double-blind placebo-controlled pilot study | Mild to moderate UC patients; age: >18 y | n=50 | Oral resveratrol capsule (500 mg pure trans-resveratrol/day); 6 weeks | — | Reduction in plasma levels of TNFα and hs-CRP; suppression of NF-kB in peripheral blood mononuclear cells, decrease in clinical colitis activity index score and increase in IBDQ-9 in resveratrol group | Supplementation of resveratrol reduced inflammation and improved quality of life and colitis activity of UC patients | 137, 2015 |
ESR, erythrocyte sedimentation rate; FFQ, food frequency questionnaire; hs-CRP, high sensitivity C-reactive protein; IBDQ-9, inflammatory bowel disease questionnaire-9; MCP-1, monocyte chemoattractant protein-1; MDA, malondialdehyde; MTWSI, Modified Truelove-Witts Severity Index; PC-SOD, lecithinized superoxide dismutase; PLC, propionyl-L-carnitine; SCCAIQ, Simple Clinical Colitis Activity Index Questionnaire; SOD, superoxide dismutase; TAC, total antioxidant capacity.