Chronic Organic Magnesium Supplementation Enhances Tissue-Specific Bioavailability and Functional Capacity in Rats: A Focus on Brain, Muscle, and Vascular Health

Magnesium (Mg) is crucial in numerous physiological functions, including neuromuscular activity, energy metabolism, and cognitive processes. Despite its significance, the bioavailability and functional impact of different Mg formulations remain underexplored. This study investigates the long-term effects of chronic organic Mg supplementation (citrate, glycinate, malate) on tissue-specific Mg distribution and functional outcomes in rats. Thirty-eight adult Sprague Dawley rats were allocated into control and Mg-supplemented groups, receiving 35.4 mg/kg/day of elemental Mg for eight weeks. Cognitive and behavioral assessments were conducted to evaluate learning, memory, and anxiety-like behavior, including the Morris water maze, open field test, and elevated plus maze. Neuromuscular function was assessed via the grip strength and rotarod performance tests. Biochemical analyses of brain regions, skeletal muscle, and vascular tissue were performed to determine Mg levels, brain- derived neurotrophic factor (BDNF), and corticosterone concentrations. Results demonstrated that Mg-malate supplementation significantly increased Mg levels in skeletal muscle and whole-brain tissue, correlating with enhanced neuromuscular performance. Mg-citrate selectively elevated hippocampal BDNF levels, improving spatial learning and memory, while Mg-glycinate exhibited anxiolytic properties by reducing thigmotaxis behavior. Interestingly, despite increased aortic Mg levels, vascular relaxation responses were diminished in Mg-malate and Mg-citrate groups, suggesting a complex interplay between Mg accumulation and vascular reactivity. These findings highlight the formulation-dependent bioavailability and functional effects of Mg, emphasizing the necessity of targeted supplementation strategies for neurological, muscular, and cardiovascular health. Further clinical studies are warranted to validate these effects in human populations.