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

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...

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Main Authors: Veettil, Sajesh K., Ching, Siew Mooi, Lim, Kean Ghee, Saokaew, Surasak, Phisalprapa, Pochamana, Chaiyakunapruk, Nathorn
Format: Article
Language:English
Published: Lippincott, Williams & Wilkins 2017
Online Access:http://psasir.upm.edu.my/id/eprint/61635/1/Effects%20of%20calcium%20on%20the%20incidence%20of%20recurrent.pdf
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author Veettil, Sajesh K.
Ching, Siew Mooi
Lim, Kean Ghee
Saokaew, Surasak
Phisalprapa, Pochamana
Chaiyakunapruk, Nathorn
author_facet Veettil, Sajesh K.
Ching, Siew Mooi
Lim, Kean Ghee
Saokaew, Surasak
Phisalprapa, Pochamana
Chaiyakunapruk, Nathorn
author_sort Veettil, Sajesh K.
collection UPM
description 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 ≥1600mg/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.
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spelling upm.eprints-616352018-10-10T08:02:56Z http://psasir.upm.edu.my/id/eprint/61635/ Effects of calcium on the incidence of recurrent colorectal adenomas: a systematic review with meta-analysis and trial sequential analysis of randomized controlled trials Veettil, Sajesh K. Ching, Siew Mooi Lim, Kean Ghee Saokaew, Surasak Phisalprapa, Pochamana Chaiyakunapruk, Nathorn 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 ≥1600mg/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. Lippincott, Williams & Wilkins 2017-08 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/61635/1/Effects%20of%20calcium%20on%20the%20incidence%20of%20recurrent.pdf Veettil, Sajesh K. and Ching, Siew Mooi and Lim, Kean Ghee and Saokaew, Surasak and Phisalprapa, Pochamana and Chaiyakunapruk, Nathorn (2017) Effects of calcium on the incidence of recurrent colorectal adenomas: a systematic review with meta-analysis and trial sequential analysis of randomized controlled trials. Medicine, 96 (32). pp. 1-9. ISSN 0025-7974; ESSN: 1536-5964 https://insights.ovid.com/pubmed?pmid=28796047 10.1097/MD.0000000000007661
spellingShingle Veettil, Sajesh K.
Ching, Siew Mooi
Lim, Kean Ghee
Saokaew, Surasak
Phisalprapa, Pochamana
Chaiyakunapruk, Nathorn
Effects of calcium on the incidence of recurrent colorectal adenomas: a systematic review with meta-analysis and trial sequential analysis of randomized controlled trials
title Effects of calcium on the incidence of recurrent colorectal adenomas: a systematic review with meta-analysis and trial sequential analysis of randomized controlled trials
title_full Effects of calcium on the incidence of recurrent colorectal adenomas: a systematic review with meta-analysis and trial sequential analysis of randomized controlled trials
title_fullStr Effects of calcium on the incidence of recurrent colorectal adenomas: a systematic review with meta-analysis and trial sequential analysis of randomized controlled trials
title_full_unstemmed Effects of calcium on the incidence of recurrent colorectal adenomas: a systematic review with meta-analysis and trial sequential analysis of randomized controlled trials
title_short Effects of calcium on the incidence of recurrent colorectal adenomas: a systematic review with meta-analysis and trial sequential analysis of randomized controlled trials
title_sort effects of calcium on the incidence of recurrent colorectal adenomas a systematic review with meta analysis and trial sequential analysis of randomized controlled trials
url http://psasir.upm.edu.my/id/eprint/61635/1/Effects%20of%20calcium%20on%20the%20incidence%20of%20recurrent.pdf
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