Copyright ©2009 The WJG Press and Baishideng.
World J Gastroenterol. Sep 28, 2009; 15(36): 4481-4490
Published online Sep 28, 2009. doi: 10.3748/wjg.15.4481
Table 1 Controlled clinical trials of antioxidants in patients with acute or chronic pancreatitis
Study/Ref.Drug/supplementsStudy designJadadscoreParticipants
Treatment (intervention)
Outcome (results)
Adverse effects/events
Bhardwaj et al[16] 2009Combined antioxidant (organic selenium, vitamin C, β-carotene, α-tocopherol and methionine)Randomized; double blind; placebo-controlled5147 patients with CP71 patients; combined antioxidants: 600 μg organic selenium, 0.54 g ascorbic acid, 9000 IU β-carotene, 270 IU α-tocopherol and 2 g methionine; per day; for 6 mo76 patients; placeboNumber of painful days per month2 Numbers of oral analgesic tablets and parenteral analgesic injections per month2 Hospitalization2 Percentage of patients become pain-free2 Number of man-days lost per month2Lipid peroxidation (TBARS)2 Serum SOD2 Total antioxidant capacity (FRAP)1 Serum vitamin A1 Serum vitamin C1 Serum vitamin E1 Erythrocyte superoxide dismutase2Headache & constipation (all during the first month of treatment)
Xue et al[17] 2008GlutamineRandomized180 patients with severe AP38 patients; 100 mL/d of 20% AGD intravenous infusion; for 10 d; starting on the day 1 (Early treatment)38 patients; 100 mL/d of 20% AGD intravenous infusion/for 10 d starting on the day 5 (Late treatment)Infection rate2 Operation rate2 Mortality2 Hospitalization2 Duration of ARDS2 Renal failure2 Acute hepatitis2 Encephalopathy2 Enteroparalysis2 Duration of shock2 15-d APACHE II core2-
Fuentes-Orozco et al[18] 2008GlutamineRandomized; double blind; controlled444 patients with AP22 patients; 0.4 g/kg per day of L-alanyl-L-Glutamine in standard TPN; 10 d22 patients; standard TPN; 10 dInfectious morbidity2 Hospital stay day3 Mortality3Serum IL-101 Serum IL-62 CRP2 Ig A1 Protein1 Albumin1 Leucocyte2 Total lymphocyte1 Nitrogen balance was (+) in treated group vs (-) in control group-
Siriwardena et al[19] 2007Combined antioxidant (N-acetylcysteine, selenium, vitamin C)Randomized; double blind; placebo- controlled543 patients with severe AP22 patients; N-acetylcysteine, selenium and vitamin C; for 7 d21 patients; placeboOrgan dysfunction3 APACHE-II3 Hospitalization3 All case mortality3Serum vitamin C3 Serum selenium3 GSH/GSSG ratio3 CRP3-
Kirk et al[4] 2006Combined antioxidant (selenium, β-carotene, L-methionine, vitamins C and E)Randomized; double-blind; placebo-controlled; crossover436 patients with CP36 patients; Antox tablet: 75 mg of selenium, 3 mg β-carotene, 47 mg vitamin E, 150 mg vitamin C, and 400 mg methionon; four times per day; for 10 wk36 patients; placebo; four times per day; for 10 wkQuality of life1 Pain2 Physical and social functioning1 Health perception1 Emotional functioning, energy, mental health3Plasma selenium1 Plasma vitamin C1 Plasma vitamin E1 Plasma β-carotene1Two patients complained of nausea and one of an unpleasant taste during treatment with Antox
Durgaprasad et al[20] 2005CurcuminRandomized; single blind; placebo- controlled320 patients of tropical pancreatitis (CP)Eight patients; capsule: 500 mg curcumin (95%) with 5 mg of piperine; three times per day; for 6 wkSeven patients; placebo (lactose)Pain3Erythrocyte MDA2 GSH level3-
Du et al[21] 2003Vitamin CRandomized; controlled384 patients with AP40 patients; IV vitamin C; 10 g/d; for 5 d44 patients; IV vitamin C; 1 g/d; for 5 dHospitalization2 Deterioration of disease2 Improvement of disease1 Cure rate1Tnf-α2 IL-12 IL-82 CRP2 Serum interleukin-2 receptor2 Plasma vitamin C1 Plasma lipideroxide1 Plasma vitamin E1 Plasma β-carotene1 Whole blood glutathione1 Activity of erythrocyte superoxide dismutase1 Erythrocyte catalase1-
Ockenga et al[22] 2002GlutamineRandomized, double blind; controlled428 patients with APStandard TPN which contains 0.3 g/kg per day L-alanine-L-glutamine; at least 1 wkStandard TPNHospitalization2 Duration of TPN2 Cost of TPN3Cholinesterase1 Albumin1 lymphocyte count1 CRP2-
de Beaux et al[23] 1998GlutamineRandomized; double-blind; controlled514 patients with APSix patients; 0.22 g/kg per day of glycyl-glutamine in standard TPN; for 7 dSeven patients; standard TPN-Lymphocytic proliferation (by DNA synthesis)1 TNF3 IL-63 IL-82-
Banks et al[24] 1997AllopurinolRandomized, double-blind, two-period crossover clinical trial413 patients with CP13 patients; 300 mg/d allopurinol; 4 wk13 patients; placeboPain3Uric acid level2-
Sharer et al[25] 1995Glutathione precursors (S-adenosyl methionine and N-acetylcysteine)Randomized-79 patients with APSAMe 43 mg/kg and N-acetylcysteine 300 mg/kg-APACHE II score reduction3 Complication rate3 Days in hospital3 Mortality3--
Bilton et al[26] 1994S-adenosyl methionine (SAMe)Randomized; double-blind; crossover; placebo- controlled520 patients with AP or CP20 patients; SAMe 2.4g/d; 10 wkPlaceboAttack rate and background pain3Free radical activity2 Serum selenium2 Serum β-carotene2 Serum vitamin E23 Serum vitamin C2 Serum SAMe1-
Selenium and β-carotene + SAMe20 patients; SAMe 2.4 g/d, Selenium 600 μg and β-carotene 9000 IU; 10 wkFree radical activity2 Serum selenium2 Serum β-carotene1 Serum vitamin E13 Serum vitamin C2 Serum SAMe1
Salim[27] 1991Allopurinol; dimethyl sulfoxideRandomized; double-blind; placebo- controlled478 patients with CP25 patients; allopurinol; 50 mg four times per day, with analgesic regimen (IM pethidine hydrochloride; 50 mg every 4 h, and IM metoclopramide hydrochloride; 10 mg every 8 h)27 patients; placebo with analgesic regimenPain2 Hospitalization2 Epigastric tenderness2WBC count2 Serum amylase2 Serum LDH2Allergies General malaise Headache Nausea Vomiting Dyspepsia Abdominal pain
26 patients; dimethyl sulfoxide; 500 mg four times per day; with analgesic regimen
Uden et al[28,29] 1992, 1990Combined antioxidant (selenium, β-carotene, vitamin C, vitamin E, methionine)Randomized; double-blind; crossover; placebo- controlled528 patients with CP23 patients; daily doses of 600 mg organic selenium, 9000 IU β-carotene, 0.54 g vitamin C, 270 IU vitamin E and 2 g methionine; 10 wk23 patients; placeboPain2Free radical activity2 Serum selenium1 Serum β-carotene1 Serum vitamin E1 Serum SAMe2-
Table 2 Controlled clinical trials of antioxidant therapy to prevent post-ERCP pancreatitis
Ref.Drug/supplementsStudy designJadadscorenTreatment (intervention)
Outcome (results)
Adverse effects/eventsOther comments
Romagnuolo et al[30] 2008AllopurinolRandomized; double blind; placebo-controlled4586293 patients; 300 mg oral allopurinol 60 min before ERCP293 patients; placeboRate of PEP3 (5.5% vs 4.1%)Disease-related adverse events3 Procedure-related complications3 Hospitalization3-In the non-high-risk group (n = 520), the crude PEP rates were 5.4% for allopurinol and 1.5% for placebo (P = 0.017), favoring placebo, indicating harm associated with allopurinol, whereas in the high-risk group (n = 66), the PEP rates were 6.3% for allopurinol and 23.5% for placebo (P = 0.050), favoring allopurinol
Milewski et al[31] 2006N-acetylcysteineRandomized; placebo-controlled210655 patients; 600 mg oral N-acetylcysteine 24 and 12 h before ERCP and 1200 mg IV for 2 d after the ERCP51 patients; isotonic IV saline twice for 2 d after the ERCPRate of PEP3 (7.3% vs 11.8%)Urine amylase activity3 Serum amylase activity3--
Katsinelos et al[32] 2005AllopurinolRandomized; double blind; placebo-controlled4250125 patients; 600 mg oral allopurinol 15 and 3 h before ERCP118 patients; placeboRate of PEP2 (3.2% vs 17.8%)Hospitalization2 Severity of pancreatitis2--
Katsinelos et al[33] 2005N-acetylcysteineRandomized; double-blind; placebo-controlled3256124 patients; 70 mg/kg 2 h before and 35 mg/kg at 4 h intervals for a total of 24 h after the procedure125 patients; placebo (normal saline solution)Rate of PEP3 Hospitalization3-Nausea; skin rash; diarrhea; vomiting-
Mosler et al[34] 2005AllopurinolRandomized; double blind; placebo- controlled4701355 patients; 600 mg 4 h and 300 mg 1 h oral allopurinol before ERCP346 patients; placeboRate of PEP3 (13.0% vs 12.1%)Severity of pancreatitis3--
Lavy et al[35] 2004Natural β-caroteneRandomized; double-blind; placebo-controlled5321141 patients; 2 g oral β-carotene 12 h before ERCP180 patients; placeboRate of PEP3 (10% vs 9.4%)Severe pancreatitis2--
Budzyńska et al[36] 2001AllopurinolRandomized; placebo-controlled330099 patients; 200 mg oral allopurinol 15 and 3 h before ERCP101 patients; placeboRate of PEP3 (12.1% vs 7.9%)Severity of pancreatitis3--
Table 3 Studies evaluating post-ERCP pancreatitis after allopurinol administration
Romagnuolo et al[30] 200816/29312/293
Katsinelos et al[32] 20054/12121/118
Mosler et al[34] 200546/35542/346
Budzyńska et al[36] 200112/998/101