Abstract CT093: Bimodal relationship between magnesium supplementation and vitamin D status and metabolism: Results from a randomized trial
Authors: Dai Qi , Zhu Xiangzhu , Manson JoAnn E. , Song Yiqing , Li Xingnan , Franke Adrian , Costello Rebecca B. , Rosanoff Andrea , Nian Hui , Fan Lei , Murff Harvey , Ness Reid M. , Seidner Douglas L. , Yu Chang , Shrubsole Martha J. 
Published: August 2018

Abstract
Background: There is inconsistent evidence from epidemiologic studies and randomized trials on the role of vitamin D on colorectal adenoma recurrence, colorectal cancer incidence, and total cancer incidence. Previous in vitro and in vivo studies indicate vitamin D synthesizing and metabolizing enzymes are Mg-dependent. The 2015 Dietary Guidelines Advisory Committee determined that magnesium (Mg) is under consumed relative to the Estimated Average Requirement (EAR) in the US population. In a single study, patients with Mg-dependent vitamin-D-resistant rickets received intramuscular infusion with vitamin D up to 600,000 IU which did not lead to any improvements in vitamin D deficiency. However, supplementation with Mg substantially reverse the resistance to vitamin D treatment. We previously reported from observational studies that Mg intake significantly interacted with vitamin D in affecting vitamin D status and risk of mortality. In this first randomized trial examining the interaction between Mg and vitamin D, we tested our hypothesis that Mg supplementation alters vitamin D synthesis and metabolism depending upon baseline circulating 25(OH)D concentration.
Methods: The Personalized Prevention of Colorectal Cancer Trial (PPCCT) is a double-blind 2×2 factorial randomized controlled trial which enrolled 250 participants and randomized them to placebo or a customized dose of Mg supplementation based on background dietary intakes levels. The current study is an NCI-independently funded ancillary study nested in the PPCCT. High-resolution accurate-mass (LCMS) was used to measure plasma levels of 25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 1,25(OH)2D2, 24,25(OH)2D3.
Results: All but one participant in this trial had normal plasma Mg at baseline. We found treatment with Mg significantly interacted with baseline plasma concentrations of 25(OH)D in altering plasma concentrations of 25(OH)D3, 25(OH)D2 and 24,25(OH)2D3. The test for interactions were statistically significant after Bonferroni corrections. 25(OH)D3 increased
after Mg supplementation when baseline 25(OH)D concentrations were below around 30 ng/ml, but reduced in a dose-response manner when baseline 25(OH)D levels were greater (from about 30 to 50 ng/ml). The bimodal relationship between Mg treatment and 24,25(OH)2D3 was very similar to the pattern found for 25(OH)D3. Conversely, Mg treatment elevated 25(OH)D2 as baseline 25(OH)D levels increased.
Conclusions: We provided the first evidence that Mg has bimodal relationships with 25(OH)D3 and 24,25(OH)2D3. Also, we found the association between Mg treatment with 25(OH)D2 differed from that with 25(OH)D3. Thus, optimal Mg status may be crucial for optimizing 25(OH)D status and metabolism. These findings may help to explain some of the previously inconsistent role of vitamin D in risks of colorectal neoplasia and total cancer.
Citation Format: Qi Dai, Xiangzhu Zhu, JoAnn E. Manson, Yiqing Song, Xingnan Li, Adrian Franke, Rebecca B. Costello, Andrea Rosanoff, Hui Nian, Lei Fan, Harvey Murff, Reid M. Ness, Douglas L. Seidner, Chang Yu, Martha J. Shrubsole. Bimodal relationship between magnesium supplementation and vitamin D status and metabolism: Results from a randomized trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT093.