The kinetics of colorectal epithelial cell proliferation (CECP) have been found to be altered in patients at increased risk for colon cancer. Altered CECP kinetics include an increase within the colon crypts of the overall proportion of proliferating cells (labeling index; LI) and the proportion of proliferating cells that are in the upper 40% of the crypts (phi h). Use of CECP as a biomarker to measure effects of calcium interventions on the colon has been reported in five small uncontrolled clinical trials, nine small randomized placebo-controlled trials, and three full-scale randomized placebo-controlled trials. All five uncontrolled trials indicated substantial and significant decreases in proliferation. Of the nine small controlled trials, three found statistically significant decreases in the LI, and the remainder were inconclusive because of insufficient sample size. Of the three full-scale trials, one found a decrease in, or normalization of, the phi h but no effect on the LI; a second found an increase in the phi h but no effect on the LI; and the third, which did not measure the phi h, also found no effect on the LI. Differences between the two full-scale trials that measured the phi h were that the negative trial was multicentered, used multiple types of bowel-cleansing preparations, had no baseline measurements of CECP, and had low intrareader reliability for CECP scoring. The positive trial was single centered, used no bowel-cleansing preparations, measured CECP prior to, and at three precise intervals after, randomization, and had high intrareader reliability for CECP scoring. The current literature indicates that in humans, it is unlikely that calcium supplementation can substantially lower CECP rates, but it may normalize the distribution of proliferating cells within colon crypts.

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