Four weeks of Low Magnesium Consumption can Dysregulate Whole‐body Metabolism and Body Composition in Mice
Authors: Duke Brian , Challburg Jessica , Smith Alexander J , Grover Grant , Walker Edward , Symons J. David , Jalili Thunder 
Published: November 2023

Nearly 60% of adults in the United States do not meet their dietary magnesium (Mg) recommendation. Mg facilitates over 300 enzymatic reactions, stabilizes ATP during phosphorylation / dephosphorylation, and may aid in blood pressure regulation by influencing vascular tone. While the general symptoms of a long term Mg deficient diet in animals has been described, the impact of a low Mg diet upon whole‐body metabolism is unknown. Our aim was to quantify the metabolic and vascular impact of a low Mg diet since this is more clinically relevant than a Mg deficient diet. We hypothesized that low Mg diets would reduce metabolic rate, impair vascular function and glucose tolerance, and that acute supplementation of Mg back into the diet could rescue these changes. To test this we used 3 groups of 8‐week old male C57BLK6J mice; Group 1 consumed a low Mg diet for 4 weeks (L‐Mg, n=12, 100mg Mg Oxide/ kg chow), Group 2 consumed the Low Mg diet for 3 weeks, followed by 1 week Mg supplementation (L‐Mg+S, n=12, 500mg Mg Bisglycinate / kg chow), Group 3 consumed a control diet for 4 weeks (Con, n=8, 500mg MgO/ kg chow).

Mg status was impaired in L‐Mg vs. L‐Mg+S mice as evidenced by lower (p<0.05) Mg concentrations (Mg mg/g tissue) in bone (2367±82 vs. 2682±64) and heart (177±18 vs. 236±20). O2 consumption (mL/kg/hr) was greater (p<0.05) in L‐Mg (3105±51) vs. Con (2880±62), and further increased in L‐Mg+S (3349±51). CO2 production was similar between L‐Mg (2967±58) and Con (2856±71), but increased (p<0.05) in L‐Mg+S (3246±58). Respiratory exchange ratio (O2 consumed : CO2 produced) was similar among all groups. Heat production (Cal/hr) was lower (p<0.05) in L‐Mg (398±8) vs. Con (426±8), but was normalized in L‐Mg+S (442±8). The changes in O2, CO2 and heat production were not due to any differences in food intake, water intake, or physical activity. All groups had similar lean body mass (% of body mass). Body fat (% of body mass) trended (p=0.088) to be greater in L‐Mg (12.6±0.96%) vs. Con (10.0±1.08%), which was subsequently normalized (p<0.05) in L‐Mg+S (8.3±1.15%). Fasting glucose levels and glucose tolerance tests were similar among groups. Arterial function was assessed in two femoral artery segments (150 μm i.d.) per mouse using isometric tension procedures. Vasorelaxation to endothelium‐dependent (acetylcholine) and –independent (sodium nitroprusside) agonists, and vasocontraction to receptor‐mediated (phenylephrine) and non‐receptor‐mediated (potassium chloride) agonists were similar among groups.

Our study demonstrates that short‐term low Mg consumption leads to dysregulation of whole‐body metabolism that is characterized by reduced heat production and increased body fat. However, both are rapidly reversed after 1‐week of Mg supplementation. Metabolic data gathered in our study provide proof of concept that long‐term consumption of low Mg diets may precipitate weight gain and development of obesity. This is a novel finding with potential public health relevance since the majority of Americans are overweight and have documented low Mg intake.

Support or Funding Information

This work was support by a Research Grant from Albion Labs