• Usama Ahmed Ali, Sjoerd Jens, Olivier R C Busch, Frederik Keus, Harry van Goor, Hein G Gooszen, and Marja A Boermeester.
• Department of Surgery, University Medical Center Utrecht, Heidelberglaan 100, P.O. Box 85500, Utrecht, Utrecht, Netherlands, 3508 GA.
• Cochrane Db Syst Rev. 2014 Aug 21; 2014 (8): CD008945CD008945.

BackgroundReduced intake and absorption of antioxidants due to pain and malabsorption are probable causes of the lower levels of antioxidants observed in patients with chronic pancreatitis (CP). Improving the status of antioxidants might be effective in slowing the disease process and reducing pain in CP.ObjectivesTo assess the benefits and harms of antioxidants for the treatment of pain in patients with CP.Search MethodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Conference Proceedings Citation Index from inception to October 2012. Two review authors performed the selection of trials independently.Selection CriteriaWe included all randomised controlled trials (RCTs) evaluating antioxidants for treatment of pain in CP. All trials were included irrespective of blinding, numbers of participants randomly assigned and language of the article.Data Collection And AnalysisTwo review authors extracted data independently. The risk of bias of included trials was assessed. Study authors were asked for additional information in the case of missing data.Main ResultsTwelve RCTs with a total of 585 participants were included. Six trials were double-blinded, placebo-controlled studies, and the other six trials were of less adequate methodology. Most trials were small and had high rates of dropout. Eleven of the 12 included trials described the effects of antioxidants on chronic abdominal pain in chronic pancreatitis. Pain as measured on a visual analogue scale (VAS, scale range 0 to 10) after one to six months was less in the antioxidant group than in the control group (mean difference (MD) -0.33, 95% confidence interval (CI) -0.64 to -0.02, P value 0.04, moderate-quality evidence). The number of pain-free participants was not statistically significantly different (risk ratio (RR) 1.73, 95% CI 0.95 to 3.15, P value 0.07, low-quality evidence). More adverse events were observed in the antioxidant group, both in the parallel trials (RR 4.43, 95% CI 1.60 to 12.29, P value 0.0004, moderate-quality evidence) and in the cross-over trials (RR 5.80, 95% CI 1.56 to 21.53, P value 0.0009, moderate-quality evidence). Adverse events occurred in 16% of participants and were mostly mild (e.g. headache, gastrointestinal complaints), but were sufficient to make participants stop antioxidant use. Other important outcomes such as use of analgesics, exacerbation of pancreatitis and quality of life were rarely reported. One trial from 1991 evaluated the effects of antioxidants on acute pain during exacerbation of chronic pancreatitis and found that a significantly higher proportion of participants in the antioxidant group experienced pain relief. This trial was conducted more than 25 years ago and has not been reproduced since that time. Therefore, additional trials are needed before reliable conclusions can be drawn.Authors' ConclusionsCurrent evidence shows that antioxidants can reduce pain slightly in patients with chronic pancreatitis. The clinical relevance of this small reduction is uncertain, and more evidence is needed. Adverse events in one of six patients may prevent the use of antioxidants. Effects of antioxidants on other outcome measures, such as use of analgesics, exacerbation of pancreatitis and quality of life remain uncertain because reliable data are not available.

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