Systematic Reviews
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2016; 22(18): 4594-4603
Published online May 14, 2016. doi: 10.3748/wjg.v22.i18.4594
Calcium supplementation for the prevention of colorectal adenomas: A systematic review and meta-analysis of randomized controlled trials
Stefanos Bonovas, Gionata Fiorino, Theodore Lytras, Alberto Malesci, Silvio Danese
Stefanos Bonovas, Gionata Fiorino, Alberto Malesci, Silvio Danese, Department of Gastroenterology, Humanitas Clinical and Research Center, 20089 Rozzano, Milan, Italy
Theodore Lytras, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain
Theodore Lytras, Centre for Research in Environmental Epidemiology, 08003 Barcelona, Spain
Theodore Lytras, Hellenic Center for Disease Control and Prevention, 15123 Athens, Greece
Alberto Malesci, Department of Medical Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy
Silvio Danese, Department of Biomedical Sciences, Humanitas University, 20089 Rozzano, Milan, Italy
Author contributions: Bonovas S, Fiorino G, Lytras T, Malesci A and Danese S designed the research; Bonovas S and Lytras T collected and analyzed the data; Bonovas S, Fiorino G, Lytras T, Malesci A and Danese S interpreted the data; Bonovas S wrote the article; Bonovas S, Fiorino G, Lytras T, Malesci A and Danese S critically revised the article for important intellectual content and gave final approval to be published.
Conflict-of-interest statement: No potential conflicts of interest exist.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Stefanos Bonovas, MD, MSc, PhD, Department of Gastroenterology, Humanitas Clinical and Research Center, Via Manzoni 56, 20089 Rozzano, Milan, Italy. sbonovas@gmail.com
Telephone: +39-31-3542327 Fax: +39-31-3542327
Received: January 13, 2016
Peer-review started: January 15, 2016
First decision: March 21, 2016
Revised: April 7, 2016
Accepted: April 15, 2016
Article in press: April 15, 2016
Published online: May 14, 2016
Abstract

AIM: 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).

CONCLUSION: 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.

Keywords: Calcium, Colorectal adenoma, Recurrence, Cancer chemoprevention, Colorectal cancer, Systematic review, Meta-analysis, Polyp

Core tip: To assess the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas, we conducted a systematic review and meta-analysis of randomized, placebo-controlled trials. We found 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). On the other hand, the association between calcium treatment and advanced (“high-risk”) colorectal adenomas was not statistically significant (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). Further targeted research is warranted.