The typical Western diet has a sub-optimal concentration of calcium, as well as a generalized deficiency in inorganic trace elements. Calcium supplementation is known to have chemopreventive activity against colon polyp formation. However, the effects of calcium alone are modest. Based on our past studies in cell culture and results from our long-term dietary intervention studies in rodents, it is hypothesized that dietary supplementation with a multi-mineral-rich natural product will regulate growth and differentiation in the human colonic epithelium more effectively than calcium alone. The end result will be more effective colon polyp prevention. The studies presented here will address this hypothesis. We just finished a 90-day dietary intervention study in human subjects. Individuals at risk for colon cancer were randomized to receive a calcium-rich, seaweed-derived multi-mineral-supplement (Aquamin®), a comparable level of calcium alone (800 mg/day) or placebo. Prior to ingesting the study agents and following the course of treatment, colon biopsies and stool samples were obtained by sigmoidoscopy. Colon biopsies will be quantitatively examined for markers of growth and differentiation. Proteomic analysis and quantitative immunohistochemistry will be used for this. In parallel, we will conduct a microbiome and metabolomic analysis of fecal specimens and colon mucosal biopsies obtained at the start and conclusion of this study. The overall goal of this pilot phase I trial is to determine if the multi-mineral supplement is more effective than calcium alone in modulating biomarker changes in human colon tissue and to correlate changes in biomarker expression with changes in the gut microbial population and in the metabolomic signature. In a separate study, the same calcium-rich, multi-mineral supplement was compared to calcium alone and control for the ability to modulate growth and differentiation in human colon adenomatous tissue maintained in colonoid culture. Proliferation marker expression was reduced and markers of differentiation were increased. Additional proteins associated with differentiation / growth control (including histone-1 family members, certain keratins, NF-2 [merlin], olfactomedin-4 and metallothionines) were altered as assessed by proteomics. These findings support the conclusion that providing additional trace elements along with calcium is more effective than calcium alone at promoting differentiation in human colon adenomas grown in colonoid culture. The inclusion of multiple trace elements along with calcium may provide more effective colon polyp chemopreventive activity than achievable with calcium alone.