Introduction The long-term goal of our studies is to determine if, and to what extent, a multi-mineral product (Aquamin) could have beneficial impact on individuals with ulcerative colitis (UC). As a step toward achieving that goal, we carried out a 180-day biomarker trial in patients with UC in remission or at the mild stage.

Approach A total of 28 subjects were included in the study. Each was randomized to receive either Aquamin for 180 days or placebo for the first 90 days. At day-90, placebo subjects crossed over to Aquamin for the final 90 days. At days-0, −90 and −180, serum samples were assessed for alkaline phosphatase (ALP), intestine-specific ALP (ALPI), C-reactive protein (CRP) and for biomarkers of bone turnover (osteocalcin, TRAP5b and bone-specific ALP [e.g., BALP]). Stool specimens were assessed for fecal calprotectin at the same time points and colon biopsies were examined histologically. Each subject underwent DEXA scanning (day-0 and −180 only). In addition, a mass spectrometry-based proteomic assessment was performed using colon biopsy specimens obtained at each time point.

Results Subjects receiving Aquamin for the complete 180-day period (a total of 12) demonstrated improvement in all biomarkers; this was not seen in the placebo group (16 subjects). Subjects who received Aquamin for 90-days were intermediary in their responses. Subjects receiving Aquamin for 180-days also demonstrated increases in bone mineral density (BMD) and bone mineral content (BMC) resulting in a statistically-significant increase in the hip strength index over the period of treatment. This was accompanied by increases in osteocalcin and TRAP5b and by a decrease in BALP. The proteomic screen demonstrated up-regulation of multiple gut barrier proteins, cell surface transporter molecules and certain proteins with anti-inflammatory potential in response to Aquamin. Aquamin treatment also led to down-regulation of several proteins associated with the pro-inflammatory state.

Conclusion These findings suggest the potential value of multi-mineral intervention (Aquamin) as a low-cost, non-toxic adjuvant therapy for mild UC or for individuals with UC in remission.

The authors have declared no competing interest.

NCT03869905

This investigator-initiated trial was supported through discretionary funds (JV) provided by Marigot Inc. as a gift to the University of Michigan, as well as the University of Michigan Pandemic Research Recovery (PRR) funding awarded to MA, and funding from the American Society for Investigative Pathology (ASIP) Summer Research Opportunity Program in Pathology (SROPP) to MA. None of these entities played any role in or had any influence on the research activities (i.e., study design, recruitment, data collection, data interpretation, or data dissemination). This study also utilized services at the University of Michigan supported by NIH funding (UM1TR004404 to the Michigan Institute for Clinical and Health Research).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The interventional study was conducted with FDA approval of Aquamin as an Investigational New Drug (IND#141600) and with oversight by the Institutional Review Board at the University of Michigan Medical School (IRBMED).

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The mass spectrometry proteomics dataset generated as part of this study are uploaded to a data repository called MassIVE (Mass Spectrometry Interactive Virtual Environment). The dataset will be freely accessible on the MassIVE repository (https://massive.ucsd.edu/v08/MSV000095472/) after the publication. (MassIVE and ProteomeXchange identifiers: MSV000095472 and PXD054344).