Magnesium supplementation alleviates corticosteroid-associated muscle atrophy in rats

PURPOSE: Corticosteroid (CS) therapy for infectious and rheumatological diseases showed to decrease serum magnesium (Mg(++)) level and induce muscle atrophy in patients. The present study investigated the effects of Mg(++) supplementation on preventing CS-induced muscle atrophy in an animal model, which provided experimental data for potential clinical translation. METHODS: Twelve 24-week-old male Sprague–Dawley rats were treated with lipopolysaccharide (LPS) and CS methylprednisolone (MPS) to induce muscle atrophy, with half of the rats also given daily 50 mg/kg Mg(++) oral supplementation. Additional six rats without LPS + CS treatments were used as normal controls. After treatment for 6 weeks, serum was collected for Mg(++) quantification, animal dual-energy X-ray absorptiometry (DXA) was performed for tissue composition, and the extensor digitorum longus (EDL) was collected for muscle functional test and histology including muscle fiber size, intramuscular fat infiltration and fiber typing. In vitro myotube atrophy model was used to study the in vitro effect associated with in vivo muscle atrophy. RESULTS: LPS + CS treatments induced hypomagnesemia while the serum Mg(++) level was in normal range after Mg(++) supplementation. DXA showed 53.0% lower fat percent and 29.7% higher lean mass in LPS + CS + Mg group when compared to LPS + CS group. Muscle functional test showed 22.2% higher specific twitch force and 40.3% higher specific tetanic force in LPS + CS + Mg group when compared to LPS + CS group. Histological analysis showed 4.1% higher proportion of muscle fibers area to total area and 63.6% lower intramuscular fat infiltration in EDL sections in LPS + CS + Mg group when compared to LPS + CS group. LPS + CS + Mg group had 33.0% higher area proportion and 29.4% higher cross-sectional area (CSA) of type IIb muscle fiber. Myoblast culture results showed that Mg(++) supplementation group had larger myotube diameter. The mRNA expressions of the muscle atrophy marker genes MuRF1 and MAFbx were lower in Mg(++) supplementation group both in vitro and in vivo. CONCLUSION: The current study demonstrated that Mg(++) supplementation successfully alleviated CS-associated muscle atrophy in rats at both functional and morphology levels, indicating a translational potential for patients undergoing CS therapy. This study provided the evidence for the first time that Mg(++) supplementation could prevent muscle atrophy—an adverse effect of CS therapy, currently also adopted for treating coronavirus disease 2019 (COVID-19).