Abstract
A double-blind cross-over study was undertaken in 16 patients after panproctocolectomy and ileoanal pouch reconstruction to compare supplementary calcium (1.5 g/day) with placebo over 2 months with a 2-week washout period. Stool frequency was recorded and the eflects on pouch mucosal crypt cellular proliferation were determined using an in vitro stathmokinetic technique which measures the crypt cell production rate (CCPR) and an immunohistochemical method using the Ki67 monoclonal antibody for proliferating nuclei. The median (interquartile range) diurnal stool frequency was reduced by calcium (4 (3โ5) per day) compared with values obtained before treatment (7 (5โ10) per day, P < 0.002) and with placebo (7 (6โ9) per day, P = 0.002). Similarly, calcium reduced nocturnal stool frequency (1 (0โ1)per night) compared with pretreatment and placebo (both 2 (1โ3) per night, P < 0.05) values. Calcium reduced the mean(s.e.m.) CCPR to 1.88(0.41) cells per crypt per hour compared with pretreatment (3.63(0.53), P = 0.01) and placebo (3.24(0.43), P = 0.002) values. Median (interquartile range) Ki67 activity was also reduced by calcium (13.2 (9.7โ16.7) per cent), compared with values obtained before treatment (27.3 (14.3โ30.2) per cent, P = 0.001) and with placebo (26.0 (17.2โ32.0) per cent, P = 0.001). Stool frequency was significantly correlated with the CCPR (diurnal: r = 0.37; nocturnal: r = 0.31, both P < 0.05). Nine patients used antidiarrhoeal medication while receiving placebo compared with four patients receiving calcium (P = 0.032). This study has shown that supplementary oral calcium significantly reduced stool frequency in patients with pouches, a reduction that was associated with reduced cell proliferation. The mechanisms for this eflect are not known.