title: Role of methionine containing antioxidant combination in the management of pain in chronic pancreatitis: a systematic review and meta-analysis.
abstract: BACKGROUND
  Pain 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.
  
  
  METHODS
  Literature 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 I(2) measures; publication bias by Egger's test. Random-effect model (DerSimonian and Laird) was used if there was heterogeneity.
  
  
  RESULTS
  Eight 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.
  
  
  CONCLUSIONS
  Methionine 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.
authors: Department of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India; Asian Healthcare Foundation, Hyderabad, India. Electronic address: rup_talukdar@yahoo.com.
authors: Rupjyoti
authors: R
authors: Talukdar
authors: Department of Biostatistics, Asian Institute of Gastroenterology, Hyderabad, India.
authors: H V V
authors: HV
authors: Murthy
authors: Department of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India.
authors: D Nageshwar
authors: DN
authors: Reddy
mesh_terms: D000975:Antioxidants / Q000627:therapeutic use*; D002908:Chronic Disease; D006801:Humans; D008715:Methionine / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology*; D059408:Pain Management; D010195:Pancreatitis / Q000150:complications* / Q000188:drug therapy*
chemical_list: D000975:Antioxidants; D008715:Methionine
keywords: Antioxidant combination; Chronic pancreatitis; Meta-analysis; Methionine; Pain; Systematic review