Calcium and α-tocopherol suppress cured-meat promotion of chemically induced colon carcinogenesis in rats and reduce associated biomarkers in human volunteers

Abstract

Background: Processed meat intake has been associated with increased colorectal cancer risk. We have shown that cured meat promotes carcinogen-induced preneoplastic lesions and increases specific biomarkers in the colon of rats.

Objectives: We investigated whether cured meat modulates biomarkers of cancer risk in human volunteers and whether specific agents can suppress cured meat-induced preneoplastic lesions in rats and associated biomarkers in rats and humans.

Design: Six additives (calcium carbonate, inulin, rutin, carnosol, α-tocopherol, and trisodium pyrophosphate) were added to cured meat given to groups of rats for 14 d, and fecal biomarkers were measured. On the basis of these results, calcium and tocopherol were kept for the following additional experiments: cured meat, with or without calcium or tocopherol, was given to dimethylhydrazine-initiated rats (47% meat diet for 100 d) and to human volunteers in a crossover study (180 g/d for 4 d). Rat colons were scored for mucin-depleted foci, putative precancer lesions. Biomarkers of nitrosation, lipoperoxidation, and cytotoxicity were measured in the urine and feces of rats and volunteers.

Results: Cured meat increased nitroso compounds and lipoperoxidation in human stools (both P < 0.05). Calcium normalized both biomarkers in rats and human feces, whereas tocopherol only decreased nitro compounds in rats and lipoperoxidation in feces of volunteers (all P < 0.05). Last, calcium and tocopherol reduced the number of mucin-depleted foci per colon in rats compared with nonsupplemented cured meat (P = 0.01).

Conclusion: Data suggest that the addition of calcium carbonate to the diet or α-tocopherol to cured meat may reduce colorectal cancer risk associated with cured-meat intake. This trial was registered at clinicaltrials.gov as NCT00994526.

Figures

FIGURE 1.

Clinical trial flowchart. The gray arrows correspond to medical visits. Bold lines correspond to periods of urine and feces collection.

FIGURE 2.

Effects (means ± SEMs) of cured-meat diets on nitrosated compound (ATNC, top graph) and fat peroxide (TBARS, bottom panel) formations in the FW of human volunteers at day 4 of each nutritional period. Design, diet composition, and analytic methods are given in Subjects and Methods. The following dietary periods were run in a random order for each volunteer and separated by washout periods—control: no red-meat period; DCNO: 4-d period during which each volunteer was given 180 g cured meat/d; DCNO + CaCO3: calcium carbonate capsules (1 g Ca/d) and 180 g cured meat/d; and DCNO + tocopherol: α-tocopherol–enriched cured meat (168 g/d, 0.05% tocopherol). n = 17. *Significantly different from the no-meat control period (P < 0.017; Wilcoxon's test); #significantly different from the DCNO period (P < 0.017; Wilcoxon's test). ATNC, apparent total N-nitroso compound; DCNO, dark cooked meat with nitrite, oxidized; FW, fecal water; eq.MDA, equivalent malondialdehyde; TBARS, thiobarbituric acid reactive substances.