Magnesium Treatment on Vitamin D Metabolism in Participants Completed Personalized Prevention of Colorectal Cancer Trial

One striking observation is that a large portion of the inter-person variation in serum 25-hydroxyvitamin D (25(OH)D) levels is unexplained. In vitro and in vivo studies indicate vitamin D synthesizing and metabolizing enzymes are Mg-dependent. Magnesium (Mg) supplementation substantially reversed the resistance to vitamin D treatment in patients with magnesium-dependent vitamin-D-resistant rickets. The investigators reported in 2013 from observational studies conducted in the general US population that Mg intake significantly interacted with vitamin D intake in affecting vitamin D status as well as interacted with serum 25(OH)D in risk of cardiovascular disease mortality and, maybe, colorectal cancer mortality. The potential interaction between Mg and vitamin D was supported by two subsequent studies, including a Finnish cohort study and a mouse study. In the parent study (Personalized Prevention of Colorectal Cancer Trial, NCT01105169), the investigators proposed to measure blood concentration of total 25(OH)D as a secondary aim using Elisa approach. However, following the novel finding of Mg-vitamin D interaction published by the investigators in 2013, they submitted a separate grant application to NCI which was funded in 2014. In the new study, the investigators proposed to use a LC-MS approach, which is more accurate and specific than an Elisa method, to measure 5 vitamin D metabolites. This new ancillary study allows the investigators to evaluate whether Mg supplementation differentially affects vitamin D synthesis and metabolism dependent on baseline serum 25(OH)D levels using existing biospecimens collected in our double-blind placebo-controlled randomized chemoprevention trial.

Sex

All

Minimum age

40 Years

Maximum age

85 Years

Inclusion Criteria:

1. Participants from our parent study (Personalized Prevention of Colorectal Cancer Trial, NCT#01105169, IRB#100106);
2. Participants who had completed the above study before the time of the sample selection (October 2015);
3. Participants consent to store/share samples for future research in colorectal tumors.

Exclusion Criteria:

1\. Participants cannot provide their blood samples in the parent study.

• DERIVEDSun E, Zhu X, Ness RM, Murff HJ, Sun S, Yu C, Fan L, Azcarate-Peril MA, Shrubsole MJ, Dai Q. Magnesium treatment increases gut microbiome synthesizing vitamin D and inhibiting colorectal cancer: results from a double-blind precision-based randomized placebo-controlled trial. Am J Clin Nutr. 2025 Nov;122(5):1185-1194. doi: 10.1016/j.ajcnut.2025.09.011. Epub 2025 Sep 12. PMID 40946805
• DERIVEDZhu X, Borenstein AR, Zheng Y, Zhang W, Seidner DL, Ness R, Murff HJ, Li B, Shrubsole MJ, Yu C, Hou L, Dai Q. Ca:Mg Ratio, APOE Cytosine Modifications, and Cognitive Function: Results from a Randomized Trial. J Alzheimers Dis. 2020;75(1):85-98. doi: 10.3233/JAD-191223. PMID 32280092
• DERIVEDDai Q, Zhu X, Manson JE, Song Y, Li X, Franke AA, Costello RB, Rosanoff A, Nian H, Fan L, Murff H, Ness RM, Seidner DL, Yu C, Shrubsole MJ. Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial. Am J Clin Nutr. 2018 Dec 1;108(6):1249-1258. doi: 10.1093/ajcn/nqy274. PMID 30541089