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Understanding Serum Magnesium Levels: Genetic Influences, Health Implications, and Reference Ranges
Genetic Influences on Serum Magnesium Levels
Genome-Wide Association Studies (GWAS) and Magnesium Levels
Recent genome-wide association studies (GWAS) have identified six loci that significantly influence serum magnesium levels. These loci are located in or near the genes MUC1, ATP2B1, DCDC5, TRPM6, SHROOM3, and MDS1. The study involved 15,366 participants of European descent and was validated in an additional 8,463 subjects. Variants in these genes were also associated with clinically defined hypomagnesemia, kidney function, bone mineral density, and fasting glucose levels. Additionally, common variants in the magnesium transporter genes CNNM2, CNNM3, and CNNM4 were linked to magnesium concentrations.
Health Implications of Serum Magnesium Levels
Magnesium and Chronic Diseases
Magnesium plays a crucial role in various physiological processes, including energy metabolism, nerve and muscle function, and fluid regulation. Low magnesium levels have been associated with several chronic conditions. A meta-analysis of prospective cohort studies found that higher circulating magnesium levels are inversely associated with the incidence of coronary heart disease (CHD), hypertension, and type 2 diabetes mellitus (T2DM). Specifically, every 0.1 mmol/L increase in magnesium levels was associated with a 4% reduction in hypertension incidence.
Magnesium and Type 2 Diabetes
Magnesium supplementation has shown potential benefits in improving metabolic control in patients with type 2 diabetes. A clinical trial involving 128 patients demonstrated that higher doses of magnesium oxide supplementation significantly increased plasma and cellular magnesium levels and improved glycemic control, as indicated by a reduction in fructosamine levels.
Magnesium and Neurological Conditions
Magnesium levels also appear to be linked to neurological conditions. A systematic review and meta-analysis found that patients with Alzheimer's disease (AD) had significantly lower serum and plasma magnesium levels compared to healthy controls, suggesting that magnesium deficiency may be a risk factor for AD. Similarly, lower magnesium levels were observed in patients with obstructive sleep apnea (OSA), which could exacerbate oxidative stress and increase the risk of cardiovascular and metabolic diseases.
Magnesium and Acute Conditions
In acute medical conditions, such as spontaneous intracerebral hemorrhage (ICH), higher admission magnesium levels were associated with better outcomes, including lower initial hematoma volume and lower ICH scores. This suggests that magnesium may have protective effects in acute neurological events.
Reference Ranges for Serum Magnesium Levels
General Population
Reference values for serum magnesium levels can vary based on population and methodology. In a study of young Iranian adults, the 95% reference values for serum magnesium were found to be 1.83-2.49 mg/dL for men, 1.79-2.48 mg/dL for women, and 1.83-2.55 mg/dL for the total population.
Pediatric and Neonatal Populations
In neonates, serum magnesium levels are generally higher than in adults. A systematic review and meta-analysis reported that magnesium levels in newborns increase during the first week of life before stabilizing to adult levels. Factors influencing these levels include prenatal magnesium supplementation, gestational age, birth weight, and renal maturity.
Ionized Magnesium
Ionized magnesium (iMg) is the physiologically active form of magnesium. A consensus reference range for iMg in healthy adults and children has been established, although further studies are needed to refine these ranges based on age, gender, and ethnicity. In patients with chronic kidney disease (CKD), iMg levels were found to be inversely correlated with estimated glomerular filtration rate (eGFR), indicating that kidney function significantly impacts magnesium homeostasis.
Conclusion
Serum magnesium levels are influenced by genetic factors and have significant implications for various health conditions, including cardiovascular diseases, diabetes, neurological disorders, and acute medical events. Establishing accurate reference ranges for different populations is crucial for effective diagnosis and management. Further research is needed to explore the potential benefits of magnesium supplementation and to refine reference ranges for specific demographic groups.
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