Mineral Biomarkers: RBC Magnesium

Optimal Takeaways

Magnesium is required by every organ in the body, and insufficiency can compromise cardiovascular health, glucose regulation, neurological function, and bone health. Measuring magnesium levels in red blood cells gives us a better idea of what’s “in the pantry” and available intracellularly. Low magnesium can contribute to diabetes, CVD, inflammation, muscle cramps, kidney stones, sleep disturbance, cognitive impairment, headaches, and depression. High magnesium levels are not typical and are likely caused by excess supplementation or decreased kidney excretion.

Standard Range: 4.00 - 6.80 mg/dL (1.66 - 2.82 mmol/L)

The ODX Range: 6.00 - 6.80 mg/dL (2.48 - 2.82 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 pancreatic exocrine insufficiency (Lindkvist 2012), depression, sleep disturbance (Micke 2021), headaches, migraines (Karim 2021), 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 magnesium can be associated with tetany, seizures, psychosis, and nystagmus (Van Laecke 2019). The inflammation and oxidative stress associated with type 2 DM are related to low magnesium as well (Verma 2017)

High magnesium levels can be associated with magnesium-containing antacids, uncontrolled diabetes, hypothyroidism, renal insufficiency/decreased excretion, slower cardiac conduction, and Addison disease. Medications that increase magnesium include antacids, laxatives, lithium, loop diuretics, thyroid medication, and aminoglycoside antibiotics (Pagana 2021).

Overview

Magnesium insufficiency increases the risk of metabolic disorders, including CVD, hypertension, type 2 diabetes, osteoporosis, musculoskeletal, and neurological disorders (Costello 2016), including anxiety and depression. Although evaluation of serum magnesium assists in identifying insufficiency, measurement of red blood cell magnesium may provide additional information about what’s “in the pantry” and may better reflect body stores. Experts recommend a minimum RBC magnesium of 6 mg/dL (2.47 mmol/L) (Razzaque 2018). The magnesium concentration in red blood cells is three times that of serum. Therefore, in severe hemolysis, a significant amount of magnesium can be released into the blood, increasing serum levels (Cascella 2022).

Cognitive impairment may also be associated with suboptimal magnesium status. One pilot study of 27 subjects with cognitive impairment and 21 without found a mean RBC magnesium of 3.14 mg/dL (1.29 mmol/L) in patients and 3.7 mg/dL (1.52 mmol/L) in controls. Further investigation found that those with severe cognitive impairment had a significantly lower mean RBC magnesium at 2.95 mg/dL (1.21 mmol/L) compared to a mean of 3.59 mg/dL (1.48 mmol/L) in those with mild cognitive impairment. Researchers note that plasma magnesium did not identify magnesium deficiency despite a mean level of 2.24 mg/dL (0.92 mmol/L) in healthy subjects and 2.2 mg/dL (0.91 mmol/L) in the cognitive impairment group (Sitzia 2020).

RBC magnesium was measured in one cross-sectional study of 70 critically ill ICU patients. Results revealed a significantly increased risk of cardiac complications and mortality when RBC magnesium was below 4 mg/dL (1.65 mmol/L). Meta-analysis and systematic review of previous research on critically ill patients noted that hypomagnesemia significantly increased the risk of sepsis, mechanical ventilation, and mortality (Heidari 2020).

A low RBC magnesium reflects inadequate magnesium intake, an observation confirmed in a study of 115 university students in Brazil. A suboptimal dietary magnesium intake of 214.8 mg/day (8.84 mmol/day) was associated with a mean suboptimal RBC magnesium of 4.79 mg/dL (1.97 mmol/L) and a mean deficient plasma magnesium of 1.86 mg/dL (0.76 mmol/L). Using a cut-off for plasma magnesium of 2.07 mg/dL (0.85 mmol/L), 87% of the population would be diagnosed with magnesium deficiency (Hermes 2014).

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

Heidari, Zinat Zinat, Alireza Abdollahi, and Hossein Khalili. "Is Intra-Cellular Magnesium Concentration Correlate with Morbidity and Mortality in Critically Ill Patients? A Cross-Sectional Study." Journal of Pharmaceutical Care (2020).

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

Hermes Sales, Cristiane et al. “There is chronic latent magnesium deficiency in apparently healthy university students.” Nutricion hospitalaria vol. 30,1 200-4. 1 Jul. 2014, doi:10.3305/nh.2014.30.1.7510

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

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

Razzaque, Mohammed S. “Magnesium: Are We Consuming Enough?.” Nutrients vol. 10,12 1863. 2 Dec. 2018, doi:10.3390/nu10121863

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