Magnesium and imidazole propionate

  • Lei Fan
    Affiliations
    Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA
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  • Danxia Yu
    Affiliations
    Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA
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  • Xiangzhu Zhu
    Affiliations
    Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA
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  • Xiang Huang
    Affiliations
    Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA
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  • Harvey J. Murff
    Affiliations
    Veterans Health Administration-Tennessee Valley Healthcare System Geriatric Research Education Clinical Center (GRECC), HSR&D Center, Vanderbilt University Medical Center, Nashville, TN, USA
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  • M.Andrea Azcarate-Peril
    Affiliations
    Department of Medicine, Division of Gastroenterology and Hepatology, and UNC Microbiome Core, Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina, Chapel Hill, NC, USA
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  • Martha J. Shrubsole
    Affiliations
    Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA
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  • Qi Dai
    Correspondence
    Corresponding author. Department of Medicine, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 800, Nashville, TN, 37203-1738, USA. Fax: +1 615 343 5938.
    Affiliations
    Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA
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Published:December 22, 2020DOI:https://doi.org/10.1016/j.clnesp.2020.12.011

      Summary

      Background & aims

      Circulating levels of imidazole propionate (ImP), a microbial metabolite of histidine, were higher in participants with type 2 diabetes (T2D) compared to those without and also induced insulin resistance. We hypothesize that low intake of magnesium (Mg) and/or low body Mg status in humans may lead to low Mg concentrations in gut microbiota, and, in turn, elevated microbial production of ImP and increased levels of circulating ImP.

      Methods

      We tested this hypothesis in the Personalized Prevention of Colorectal Cancer Trial (PPCCT) (registered at clinicaltrials.gov as NCT01105169), a double-blind 2 × 2 factorial randomized controlled trial enrolling 240 participants at high risk of Mg deficiency. Among 68 participants (34 each in the treatment and placebo arms), we measured plasma metabolites using the untargeted Metabolon's global Precision Metabolomics™ LC-MS platform.

      Results

      Mg treatment significantly reduced ImP by 39.9% compared to a 6.0% increase in the placebo arm (P = 0.02). We found the correlation coefficients were −0.12 (P = 0.32) and −0.31 (P < 0.01) between the change in ImP and changes in serum Mg and urinary Mg, respectively. In addition, we found Mg treatment increased circulating levels of indole propionate (InP) by 27.5% (P = 0.07) and reduced levels of glutarate by 17.9% (P = 0.04) compared to the placebo arm.

      Conclusions

      Further studies are needed to replicate these findings and to investigate whether Mg treatment specifically changes the production of ImP by microbiota. Also, future studies are warranted to confirm the effect of Mg treatment on glutarate and InP.

      Keywords

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