Role of methionine containing antioxidant combination in the management of pain in chronic pancreatitis: A systematic review and meta-analysis

Abstract

BackgroundPain in CP results from inflammation and neuroimmune alterations that are associated with oxidative stress, among other mechanisms. This is marked by depletion of antioxidant defenses including methionine, which is a donor of methyl moieties that maintains the acinar transsulfuration pathway. We performed a systematic review and meta-analysis of trials evaluating methionine-containing antioxidants in CP. Patient and methodsLiterature search was conducted in Medline/Pubmed, EMBASE, and Cochrane databases. Systematic review and meta-analysis was performed per PRISMA guidelines. Main study outcome was pain relief. GRADE system was used for quality assessment. Heterogeneity was assessed by the Q and I2 measures; publication bias by Egger's test. Random-effect model (DerSimonian and Laird) was used if there was heterogeneity. ResultsEight studies (n = 411) were identified that used methionine-containing antioxidants. The study duration ranged from 10 wks to 12 months. All studies used methionine, organic selenium, ascorbate, beta-carotene and alpha-tocoferol. Four studies (including two RCTs) that reported change in pain scores were metaanalyzed. Though overall effect [standardized difference in means (95% CI)] on pain score reduction was −0.95 (−1.738 to −0.160) (z = −2.36; p = 0.018), the significance was lost when the two RCTs were meta-analyzed. RCTs that reported the number of pain free patients had a statistically significant overall effect of −3.204 (p = 0.001). Though more patients on methionine containing antioxidants had adverse events, majority of them were mild. ConclusionMethionine containing antioxidants appear to result in pain reduction in a significant proportion of CP patients. Further randomized controlled trials with homogeneous outcome measures are needed.