Growth and Recurrence of Colorectal Polyps: A Double-Blind 3-Year Intervention with Calcium and Antioxidants

Abstract

Background: Dietary calcium and antioxidants have been suggested as protective agents against colorectal cancer. This has been supported by animal experimental studies, case control and cohort studies. Materials and Methods: In a prospective intervention study of colorectal adenomas, and intermediary stage in colorectal carcinogenesis, 116 polyp-bearing patients received a placebo-controlled daily mixture of β-carotene 15 mg, vitamin C 150 mg, vitamin E 75 mg, selenium 101 µg, and calcium (1.6 g daily) as carbonate for a period of 3 years with annual colonoscopic follow-up to test if the mixture was able to reduce polyp growth or recurrence. All polyps of <10 mm at enrolment or follow-up were left unresected until the end of the study. Results: 87–91% of the patients attended the annual endoscopic follow-up investigations, and 19% of the patients dropped out of the medical intervention. The rest consumed 85% of the total amount of tablets over the 3 years. The fecal calcium concentration was 2.3–2.7 times higher in patients taking active medication compared to the placebo group. Diet registration showed that, when adding the intake of antioxidants and calcium from diet and intervention, there was a significant difference between the intake of these substances in the active and the placebo group. No difference was detected in the growth of adenomas between the active and the placebo group from year to year and for the total study period. Moreover, there was no effect on polyps of <5 or 5–9 mm, or on polyps in the different colonic segments analyzed separately. A reduced growth of adenomas was found in patients <60 years of age taking active medication (n = 8) compared to those taking placebo (n = 6; mean difference 2.3 mm; 95% CI 0.26–4.36). There was a significantly lower number of patients free of new adenomas in the placebo group compared to those taking active medication as tested by logistic regression and Kaplan-Meier analysis (log-rank test p value 0.035). Subgroup analysis showed that only the group of patients with no family history of colorectal cancer, those with only one adenoma at inclusion, and those <65 years benefitted from the intervention medication. Conclusion: The study did not find an overall effect on polyp growth. Our data, however, may support a protective role of calcium and antioxidants on new adenoma formation.

Results from two repeated 5 day dietary records with a 1 y interval among patients with colorectal polyps

“…Any dropouts from the intervention study (Hofstad et al, 1998) was to be avoided. Weighing of foods and drinks is a demanding task, and we did not want to jeopardise the compliance of the 116 polyp patients by asking them all to perform a repeated 5 day food record by weighing.…”

“…All 116 polyp-bearing out-patients (50% men), aged 50 ± 76 y, who participated in a double-blind 3 y placebocontrolled intervention study against growth and recurrence of polyps (Hofstad et al, 1992(Hofstad et al, , 1998, performed a 5 day dietary record by weighing at inclusion. A subsample of 30 polyp patients was asked to perform a second 5 day dietary record by weighing after 1 y of intervention.…”

“…Since increasing size of polyps (above 1 cm) has been recognised as a risk factor for development of CRC (Morson, 1974), all large-sized polyps were removed, whereas the remainder and new discoveries of polyps 9 mm in diameter were left in situ for a follow-up period of 3 y with annual endoscopic examinations and polyp size measurements. At the end of the study, all polyps were removed and subjected to histology (Hofstad et al, 1998).…”

“…The aim of the present study was to examine potential changes in dietary habits by the use of repeated 5 day dietary records by weighing after 1 y of participation in a double-blind 3 y placebo-controlled endoscopic follow-up and intervention study with a daily mixture of vitamin C, a-tocopherol, b-carotene, selenium and calcium against growth and recurrence of polyps (Hofstad et al, 1998).…”

Colorectal cancer: influence of diet and lifestyle factors

“…Case-control and prospective epidemiological studies show moderate inverse association (a decrease around 25%) between calcium intake and CRC risk (60,61). There are also interesting data from randomized clinical trials that show that calcium supplementation (1,200-2,000 mg per day) produces a modest, but rapid decrease in the incidence of recurrent colorectal adenomas (62)(63)(64)(65)(66), although in one of the studies (66) such an effect was only observed in subjects with higher levels of vitamin D, suggesting that perhaps both calcium and adequate levels of vitamin D are required for the protective effect to be exerted. Different mechanisms have been proposed for calcium's potential to reduce the risk of colorectal cancer: from binding secondary bile acids and fatty acids, sequestering these mutagenic substances from contact with epithelial cells, to a direct action decreasing colonic epithelial cell proliferation and promoting its differentiation, through a calcium-sensing receptor (67)(68)(69).…”