Mild magnesium deficiency affects the urinary metabolome in rats

Low magnesium (Mg) intake increases the risk of various diseases such as anxiety disorder, depression, and diabetes. However, a reliable biomarker of mild Mg deficiency due to low Mg intake has not yet been identified. We speculate that metabolomics will be effective for biomarker discovery because Mg can affect various metabolic processes in the body. In the present study, we evaluated whether mild Mg deficiency affects growth, behaviour, and plasma and urinary metabolomes in rats. Mg levels in plasma and the femur, and urinary Mg excretion decreased by consuming a mildly low Mg diet, whereas body weight and food intake were not affected. Also, anxiety- and depression-like behaviours were not affected by Mg deficiency. These results indicate that the negative effects observed here are milder than those for severe Mg deficiency, as previously reported. Of the 93 annotated metabolites in plasma, only glycylglycine was moderately affected. Of the 122 annotated metabolites in urine, 29 were affected. A marked decrease in urinary excretion of some organic acids of the tricarboxylic acid cycle, particularly citric acid, was noticed. This study identifies urinary metabolites that may be useful biomarkers of mild Mg deficiency.