Mineral Biomarkers: Serum Magnesium

Optimal Takeaways

Magnesium is a critically important mineral as it has antioxidant and anti-inflammatory properties and is a cofactor for more than 600 metabolic enzymes. It is essential to cardiovascular health, neurological function, bone integrity, and glucose regulation. Low magnesium is associated with hypertension, cardiac arrhythmias, CVD, osteoporosis, glucose dysregulation, inflammation, headaches, depression, cognitive impairment, sleep disturbance, muscle cramps, and kidney stones. Hypermagnesemia is uncommon but can occur with excessive intake or reduced kidney excretion.

Standard Range: 1.50 - 2.50 mg/dL (0.62 - 1.04 mmol/L)

The ODX Range: 2.20 - 2.50 mg/dL (0.91 - 1.04 mmol/L)

Low magnesium is associated with inadequate intake, malnutrition, malabsorption, hypoparathyroidism, diabetic acidosis, chronic renal disease, cardiac irritability and arrhythmia, and pregnancy-related toxemia. Medications that can decrease levels include diuretics, insulin, and some antibiotics (Pagana 2021).

Low magnesium may also be associated with kidney stones (Wu 2020), metabolic syndrome (Rodríguez-Moran 2018), diabetes, insulin resistance (Fiorentini 2021), pancreatic exocrine insufficiency (Lindkvist 2012), depression, sleep disturbance (Micke 2021), headaches (Karim 2021), migraines (Samaie 2012), cognitive impairment (Sitzia 2020), a diet high in processed foods and low in leafy greens and whole grains, CVD, vascular calcification, endothelial dysfunction, poor glycemic control, oxidative stress, increased hip fracture risk, increased Alzheimer’s risk, gastrointestinal disorders, refeeding syndrome, sepsis, prolonged exercise, proton pump inhibitors, and epidermal growth factor inhibitors. Very low serum magnesium can be associated with tetany, seizures, psychosis, and nystagmus (Van Laecke 2019). Inflammation and oxidative stress associated with type 2 DM are also associated with low magnesium (Verma 2017).

High magnesium levels can be associated with magnesium-containing antacids, uncontrolled diabetes, hypothyroidism, renal insufficiency/decreased excretion, slower cardiac conduction, and Addison’s disease. Medications that increase magnesium include antacids, laxatives, lithium, loop diuretics, thyroid medication, and aminoglycoside antibiotics (Pagana 2021). Very high levels may be associated with tachycardia, hypotension, muscle weakness, and cardiac arrest (Van Laecke 2019). Excess hemolysis can also increase serum magnesium due to its release from red blood cells (Cascella 2022).

Overview

Magnesium is an essential mineral and the second most abundant intracellular element after potassium, assisting in maintaining a neutral electrical charge within the cell. Magnesium participates in numerous functions, and most organs depend upon it metabolically (Pagana 2021).

Magnesium’s effects are far-reaching as a cofactor for more than 600 enzymes. It has valuable antioxidant, anti-inflammatory, and anti-apoptotic properties. It participates in protein and DNA synthesis, oxidative phosphorylation, glycolysis, glycemic control, and signal transduction at the metabolic level. Most magnesium is found in the bone and soft tissue, and only 1-2% is found extracellularly. Therefore, a magnesium deficiency at the cellular level may be present even with normal serum magnesium. Metabolic complications are associated with a U-shaped curve for serum magnesium, with consequences occurring at high and low levels (Van Laecke 2019). Magnesium is also required to activate alkaline phosphatase, which can decrease with magnesium insufficiency (Ray 2017).

Magnesium and calcium compete for absorption and transport and share the same feedback mechanism. Therefore, an excess of one can contribute to a deficiency of the other (Dai 2007).

Subclinical magnesium deficiency is common in the general population, and signs may be as subtle as fatigue, weakness, and loss of appetite, with symptoms worsening as the deficiency progresses. Food sources of magnesium include nuts, seeds, legumes, cocoa, and whole grains. However, food processing, poor soil, and high concentrations of potassium and ammonium in fertilizer deplete magnesium (Fiorentini 2021). Insufficient intake is associated with hypertension, CVD, type 2 diabetes, osteoporosis, and neurological complications, reflecting a likely chronic latent magnesium deficit. Serum magnesium below 2.0 mg/dL (0.82 mmol/L) coupled with urinary magnesium of 40-80 mg/L indicates insufficient intake of less than 250 mg/day. Insufficiency should be addressed accordingly, as the body may compensate for lower serum magnesium by releasing magnesium from the bone (Costello 2016).

Physical symptoms of magnesium insufficiency may also include headache, muscle cramps, depression, sleep disturbances, hypertension, cardiac arrhythmias, electrolyte disorders such as hypocalcemia and hypokalemia, and deficiency of active vitamin D. Researchers note that assessment of magnesium status should include symptoms as well as serum levels, especially if below 2.1 mg/dL (0.85 mmol/L) (Micke 2021).

Low serum magnesium is associated with metabolic syndrome and its components, parameters that improve with magnesium supplementation. One 16-week randomized, double-blind, placebo-controlled study of 198 individuals with metabolic syndrome and low serum magnesium found that providing 382 mg of elemental magnesium significantly decreased systolic and diastolic blood pressure, fasting plasma glucose, and triglyceride levels. Serum magnesium increased significantly from a mean basal level of 1.5 mg/dL (0.62 mmol/L) to 1.9 mg/dL (0.78 mmol/L) versus a slight increase to 1.6 mg/dL (0.66 mmol/L) in the placebo group (Rodríguez-Moran 2018).

Meta-analysis of 1,694 subjects in total revealed that magnesium supplementation improves metabolic parameters in type 2 diabetes as well. Daily supplementation with 300-400 mg of magnesium significantly improved fasting plasma glucose, LDL and HDL cholesterol, triglycerides, and blood pressure in subjects with type 2 diabetes (Verma 2017).

Hypermagnesemia can be seen with markedly elevated levels of 4-6 mg/dL (1.74-2.61 mmol/L) or above, and symptoms include hypotension, nausea, vomiting, hyporeflexia, skeletal muscle paralysis, bradyarrhythmia, and even cardiac arrest. Hypermagnesemia is uncommon and is most likely associated with excessive intake or renal insufficiency. In addition to renal compromise, magnesium excretion will decrease in magnesium deficiency when challenged with a magnesium load as the body attempts to retain what it needs (Musso 2009).

References

Cascella, Marco. and Sarosh Vaqar. “Hypermagnesemia.” StatPearls, StatPearls Publishing, 30 May 2022.

Costello, Rebecca B et al. “Perspective: The Case for an Evidence-Based Reference Interval for Serum Magnesium: The Time Has Come.” Advances in nutrition (Bethesda, Md.) vol. 7,6 977-993. 15 Nov. 2016, doi:10.3945/an.116.012765

Dai, Qi et al. “The relation of magnesium and calcium intakes and a genetic polymorphism in the magnesium transporter to colorectal neoplasia risk.” The American journal of clinical nutrition vol. 86,3 (2007): 743-51. doi:10.1093/ajcn/86.3.743

Fiorentini, Diana et al. “Magnesium: Biochemistry, Nutrition, Detection, and Social Impact of Diseases Linked to Its Deficiency.” Nutrients vol. 13,4 1136. 30 Mar. 2021, doi:10.3390/nu13041136

Karim, M R et al. “Relation between Serum Magnesium Level and Migraine.” Mymensingh medical journal : MMJ vol. 30,2 (2021): 301-306.

Lindkvist, Björn et al. “Serum nutritional markers for prediction of pancreatic exocrine insufficiency in chronic pancreatitis.” Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] vol. 12,4 (2012): 305-10. doi:10.1016/j.pan.2012.04.006

Micke, Oliver et al. “Serum magnesium: time for a standardized and evidence-based reference range.” Magnesium research vol. 34,2 (2021): 84-89. doi:10.1684/mrh.2021.0486

Musso, Carlos G. “Magnesium metabolism in health and disease.” International urology and nephrology vol. 41,2 (2009): 357-62. doi:10.1007/s11255-009-9548-7

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Rodríguez-Morán, Martha et al. “Oral Magnesium Supplementation and Metabolic Syndrome: A Randomized Double-Blind Placebo-Controlled Clinical Trial.” Advances in chronic kidney disease vol. 25,3 (2018): 261-266. doi:10.1053/j.ackd.2018.02.011

Samaie, Afshin et al. “Blood Magnesium levels in migraineurs within and between the headache attacks: a case control study.” The Pan African medical journal vol. 11 (2012): 46.

Sitzia, Clementina et al. “Intra-erythrocytes magnesium deficiency could reflect cognitive impairment status due to vascular disease: a pilot study.” Journal of translational medicine vol. 18,1 458. 3 Dec. 2020, doi:10.1186/s12967-020-02645-w

Van Laecke, Steven. “Hypomagnesemia and hypermagnesemia.” Acta clinica Belgica vol. 74,1 (2019): 41-47. doi:10.1080/17843286.2018.1516173

Verma, H, and R Garg. “Effect of magnesium supplementation on type 2 diabetes associated cardiovascular risk factors: a systematic review and meta-analysis.” Journal of human nutrition and dietetics : the official journal of the British Dietetic Association vol. 30,5 (2017): 621-633. doi:10.1111/jhn.12454

Wu, Jing et al. “Association Between Serum Magnesium and the Prevalence of Kidney Stones: a Cross-sectional Study.” Biological trace element research vol. 195,1 (2020): 20-26. doi:10.1007/s12011-019-01830-3