1. 2013;16;521-532Antioxidant Therapy for Pain Relief in Patients with Chronic Pancreatitis: Systematic Review and Meta-analysis
   Systematic Review
   Sheng-Xi Wu, MD, PhD, Wen Wang, MD, PhD, Yun-Qing Li, MD, PhD, Yu-Lin Dong, MD, PhD, Howard S. Smith, MD, Huang-Hui Wu, MD, Jing Chen, MD, Yan Zhao, MD, Jing Huang, MD, PhD, and Guo-Hong Cai, MD.

BACKGROUND: Currently, there is no specific therapy for chronic pancreatitis (CP). The treatment of micronutrient antioxidant therapy for painful CP has been sporadically used for more than 30 years, however, its efficacy are still poorly understood.

OBJECTIVE: The purpose of this meta-analysis is to investigate the safety and efficacy of antioxidant therapy for pain relief in patients with CP.

SETTING: University Hospital in China

STUDY DESIGN: Systematic review and meta-analysis

METHODS: Two authors independently reviewed the search results and extracted data and disagreements were resolved by discussion. Effects were summarized using standardized mean differences (SMDs), weighted mean differences, or odds ratio (OR) according to the suitable effect model. MEDLINE, PsycINFO, Scopus, EMBASE, and the Cochrane Central Register of Controlled Trials  were searched from 1980 through December 2012. Randomized controlled trials (RCTs) that studied antioxidant supplementation for pain relief in patients with CP were analyzed.

RESULTS: Nine randomized controlled trials (RCTs) involving 390 patients were included. Overall, there was no association of antioxidant therapy with pain reduction in CP patients (SMD, -0.55; 95% CI, -1.22 to 0.12; P = 0.67). However, antioxidant therapy significantly increased blood levels of antioxidants in CP patients versus the placebo group (SMD, 1.08; 95% CI, 0.74 to 1.43; P < 0.00001). Interestingly, combined antioxidant (selenium, ?-carotene, vitamin C, vitamin E, methionine) therapy was found to be associated with pain relief (SMD, -0.93; 95% CI, -1.72 to -0.14; P = 0.02), while the trials in which a single antioxidant was used revealed no significant pain relief (SMD, -0.12; 95% CI, -1.23 to 0.99; P = 0.83) in CP patients. Strong evidence was obtained that the antioxidants increased adverse effects (OR, 6.09; 95% CI, 2.29 to 16.17, P < 0.01); nevertheless, none was serious.

LIMITATIONS: Because of the small sample, a consolidated conclusion cannot be reached based on current RCTs. Large-sample RCTs are needed to clarify the analgesic effect of antioxidants in CP patients.

CONCLUSIONS: Combined antioxidant therapy seems to be a safe and effective therapy for pain relief in CP patients. Measures of total antioxidant status may not help to monitor the efficacy of antioxidant therapy for patients with CP.