Interventional studies have shown that calcium supplementation reduces the risk of colon adenoma formation in at risk subjects, although this protection is modest and inconsistent. In our animal models, there is evidence that calcium in combination with trace elements (from Aquamin – a multi-mineral seaweed extract) may be more effective at decreasing colon polyp incidence, progression and/or inflammation. The overall goal of our research is to correlate dietary calcium or calcium and trace element supplementation with particular gastrointestinal microbial and metabolomic profiles that may be protective against colorectal cancer (CRC) in humans. We have previously demonstrated that Aquamin®, a seaweed-derived, multi-mineral product, is protective against high fat diet-induced colonic or hepatic neoplasia in mice. Additionally, we have demonstrated that calcium and trace minerals inhibit proliferation and favor differentiation in human colon cancer cell lines. We hypothesize that the protective effects of calcium and calcium/mineral supplementation against CRC are mediated in part by supplement-induced alterations in gut microbes and microbially-derived metabolites, which in turn influence colonic enterocyte proliferation and metabolic state. In the ongoing studies, metabolomic and microbial profiles will be generated from fecal and colon mucosal samples taken at baseline and study endpoint in our FDA-approved, double-blinded interventional 90-day clinical study. In this study 30 human subjects at increased risk for colon cancer will be randomized to three groups – placebo, calcium alone, or Aquamin®, which provides calcium as part of a mixture of 72 trace minerals.
The utility of calcium supplementation for colon cancer prevention is somewhat limited by the finding that higher levels also correlate with increased cardiovascular risk and other complications. Thus, the demonstration of a synergistic protective effect by a multi-mineral supplement containing moderate calcium levels may be of clinical benefit. Little is currently known, mechanistically, about the observed beneficial effects of calcium supplementation on colonic epithelial health. The proposed study will identify candidate metabolic pathways influenced by diet supplementation in clinically-derived samples. Diet-correlated microbial and metabolic profiles thus identified may serve as potential biomarkers of preventative intervention in future clinical trials.
Sponsored by the Host Microbiome Initiative