Updated publication reference for PubMed record(s): 33799486. The overall goal of this study was to determine if Aquamin®, a multi-mineral natural product, would alter the expression of proteins involved in growth-regulation and differentiation in the colon. Thirty healthy human subjects (at risk for colorectal cancer) were enrolled in a three-arm, 90-day interventional trial in which Aquamin® was compared to calcium alone and placebo. Before and after the interventional period colonic biopsies were obtained. Biopsies were evalu-ated by immunohistology for expression of Ki67 (proliferation marker) and for CK20 and p21 (differentiation markers). Tandem mass tag-mass spectrometry-based detection was used to as-sess levels of multiple proteins. As compared to placebo or calcium, Aquamin® reduced the level of Ki67 expression. Neither intervention altered CK20 expression, while a trend toward in-creased p21 was observed with calcium and Aquamin®. In the proteomic screen, Aquamin® treatment resulted in many more proteins being upregulated (including cytokeratins, cell-cell adhesion molecules and components of the basement membrane) or downregulated (prolifera-tion and nucleic acid metabolism) than placebo. Calcium alone also altered the expression of many of the same proteins but not to the same extent as Aquamin®. We conclude that daily Aquamin® ingestion alters protein expression profile in the colon that could be beneficial to colonic health.