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Medicine (Baltimore). 2017 Aug;96(32):e7661. doi: 10.1097/MD.0000000000007661.

Effects of calcium on the incidence of recurrent colorectal adenomas: A systematic review with meta-analysis and trial sequential analysis of randomized controlled trials.

Author information

1
aSchool of Pharmacy/School of Postgraduate Studies, International Medical University, Kuala Lumpur bDepartment of Family Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia cMalaysian Research Institute on Ageing, Universiti Putra Malaysia, Serdang, Malaysia dClinical School, Department of Surgery, International Medical University, Seremban, Negeri Sembilan, Malaysia eCenter of Health Outcomes Research and Therapeutic Safety (Cohorts), School of Pharmaceutical Sciences, University of Phayao, Thailand fSchool of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia gCenter of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok hUnit of Excellence on Herbal Medicine, School of Pharmaceutical Sciences, University of Phayao iDivision of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand jSchool of Pharmacy, University of Wisconsin, Madison, USA kAsian Centre for Evidence Synthesis in Population, Implementation and Clinical Outcomes (PICO), Health and Well-being Cluster, Global Asia in the 21st Century (GA21) Platform, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia.

Abstract

BACKGROUND:

Protective effects of calcium supplementation against colorectal adenomas have been documented in systematic reviews; however, the results have not been conclusive. Our objective was to update and systematically evaluate the evidence for calcium supplementation taking into consideration the risks of systematic and random error and to GRADE the evidence.

METHODS:

The study comprised a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized controlled trials (RCTs). We searched for RCTs published up until September 2016. Retrieved trials were evaluated using risk of bias. Primary outcome measures were the incidences of any recurrent adenomas and of advanced adenomas. Meta-analytic estimates were calculated with the random-effects model and random errors were evaluated with trial sequential analyses (TSAs).

RESULTS:

Five randomized trials (2234 patients with a history of adenomas) were included. Two of the 5 trials showed either unclear or high risks of bias in most criteria. Meta-analysis of good quality RCTs suggest a moderate protective effect of calcium supplementation on recurrence of adenomas (relative risk [RR], 0.88 [95% CI 0.79-0.99]); however, its effects on advanced adenomas did not show statistical significance (RR, 1.02 [95% CI 0.67-1.55]). Subgroup analyses demonstrated a greater protective effect on recurrence of adenomas with elemental calcium dose ≥1600 mg/day (RR, 0.74 [95% CI 0.56-0.97]) compared to ≤1200 mg/day (RR, 0.84 [95% CI 0.73-0.97]). No major serious adverse events were associated with the use of calcium, but there was an increase in the incidence of hypercalcemia (P = .0095). TSA indicated a lack of firm evidence for a beneficial effect. Concerns with directness and imprecision rated down the quality of the evidence to "low."

CONCLUSION:

The available good quality RCTs suggests a possible beneficial effect of calcium supplementation on the recurrence of adenomas; however, TSA indicated that the accumulated evidence is still inconclusive. Using GRADE-methodology, we conclude that the quality of evidence is low. Large well-designed randomized trials with low risk of bias are needed.

PMID:
28796047
PMCID:
PMC5556213
DOI:
10.1097/MD.0000000000007661
[Indexed for MEDLINE]
Free PMC Article

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