title: Calcium supplementation for the prevention of colorectal adenomas: A systematic review and meta-analysis of randomized controlled trials.
abstract: OBJECTIVE
  To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas.
  
  
  METHODS
  We conducted a systematic review and meta-analysis of published studies. We searched PubMed, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the ClinicalTrials.gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were eligible for inclusion. Two reviewers independently selected studies based on predefined criteria, extracted data and outcomes (recurrence of colorectal adenomas, and advanced or "high-risk" adenomas), and rated each trial's risk-of-bias. Between-study heterogeneity was assessed, and pooled risk ratio (RR) estimates with their 95% confidence intervals (95%CI) were calculated using fixed- and random-effects models. To express the treatment effect in clinical terms, we calculated the number needed to treat (NNT) to prevent one adenoma recurrence. We also assessed the quality of evidence using GRADE.
  
  
  RESULTS
  Four randomized, placebo-controlled trials met the eligibility criteria and were included. Daily doses of elemental calcium ranged from 1200 to 2000 mg, while the duration of treatment and follow-up of participants ranged from 36 to 60 mo. Synthesis of intention-to-treat data, for participants who had undergone follow-up colonoscopies, indicated a modest protective effect of calcium in prevention of adenomas (fixed-effects, RR = 0.89, 95%CI: 0.82-0.96; random-effects, RR = 0.87, 95%CI: 0.77-0.98; high quality of evidence). The NNT was 20 (95%CI: 12-61) to prevent one colorectal adenoma recurrence within a period of 3 to 5 years. On the other hand, the association between calcium treatment and advanced adenomas did not reach statistical significance (fixed-effects, RR = 0.92, 95%CI: 0.75-1.13; random-effects, RR = 0.92, 95%CI: 0.71-1.18; moderate quality of evidence).
  
  
  CONCLUSIONS
  Our results suggest a modest chemopreventive effect of calcium supplements against recurrent colorectal adenomas over a period of 36 to 60 mo. Further research is warranted.
authors.affiliation: Stefanos Bonovas, Gionata Fiorino, Alberto Malesci, Silvio Danese, Department of Gastroenterology, Humanitas Clinical and Research Center, 20089 Rozzano, Milan, Italy.
authors.forename: Stefanos
authors.initials: S
authors.lastname: Bonovas
authors.affiliation: Stefanos Bonovas, Gionata Fiorino, Alberto Malesci, Silvio Danese, Department of Gastroenterology, Humanitas Clinical and Research Center, 20089 Rozzano, Milan, Italy.
authors.forename: Gionata
authors.initials: G
authors.lastname: Fiorino
authors.affiliation: Stefanos Bonovas, Gionata Fiorino, Alberto Malesci, Silvio Danese, Department of Gastroenterology, Humanitas Clinical and Research Center, 20089 Rozzano, Milan, Italy.
authors.forename: Theodore
authors.initials: T
authors.lastname: Lytras
authors.affiliation: Stefanos Bonovas, Gionata Fiorino, Alberto Malesci, Silvio Danese, Department of Gastroenterology, Humanitas Clinical and Research Center, 20089 Rozzano, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Malesci
authors.affiliation: Stefanos Bonovas, Gionata Fiorino, Alberto Malesci, Silvio Danese, Department of Gastroenterology, Humanitas Clinical and Research Center, 20089 Rozzano, Milan, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Danese
mesh_terms: D000236:Adenoma / Q000453:epidemiology / Q000517:prevention & control*; D000368:Aged; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002118:Calcium / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000517:prevention & control*; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D065840:Protective Factors; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012307:Risk Factors; D055502:Secondary Prevention / Q000379:methods*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D016588:Anticarcinogenic Agents; D002118:Calcium
keywords: Calcium; Cancer chemoprevention; Colorectal adenoma; Colorectal cancer; Meta-analysis; Polyp; Recurrence; Systematic review