Magnesium: Why Standard Ranges Are Suboptimal

Accurate assessment of magnesium status is another prime example of where standard lab ranges can fall short. Magnesium is an essential mineral required by most organs for a wide variety of metabolic functions. Its insufficiency contributes to hypertension, atherosclerosis, cardiovascular disease, insulin resistance, type 2 diabetes, neurological dysfunction, osteoporosis, low-grade inflammation, and electrolyte imbalance among other dysfunctions.[i]

Insufficiency may be subtle but widespread as less than half of the population in the United States consumes adequate magnesium. Not surprisingly, subclinical magnesium deficiency was suspected even at “acceptable” serum magnesium levels of 1.82 - 2.3 mg/dL (0.75–0.95 mmol/L) based on 1974 NHANES I data.[ii]

Unfortunately, some standard lab ranges for magnesium currently have an even lower acceptable cut-off, making it more difficult to identify suboptimal status:

Researchers suggest magnesium deficiency is likely with serum magnesium of less than 2 mg/dL (0.82 mmol/L), especially coupled with decreased urinary magnesium. Urinary magnesium of 40-80 mg/day reflects intake of less than 250 mg/day while excretion of 80-160 mg/day reflects intakes of more than 250 mg/day.[vii]

Maintaining a serum magnesium level of 2.2-2.5 mg/dL (0.91-1.04 mmol/L) can help maintain optimal cardiovascular health.

Magnesium insufficiency is suspected in primary hypertension, the most common form of high blood pressure. A 2021 systematic review of the literature noted the cardiovascular benefits of magnesium supplementation: [viii]

• 240 mg/day or more successfully reduced blood pressure in uncontrolled medicated hypertensives.
• 600 mg/day or more were needed to reduce blood pressure in uncontrolled untreated hypertensives.
• Supplementation in normotensive subjects didn’t lower blood pressure further but significantly improved serum magnesium, lipoprotein levels, CRP, fasting glucose, insulin resistance, sodium excretion, and retinal vasospasm.
• The current US tolerable upper limit (UL) for supplemental magnesium was set at 350 mg/day based on limited evidence.
• The potential for mild diarrhea in a minority of subjects at levels of 360-380 mg/day prompted the limited UL.
• Exceedingly high doses of 5000 mg/day or more can cause serious side effects.

Clinicians must look beyond standard reference intervals and not wait for a pathological diagnosis, if we are to help patients improve their metabolic profile now to prevent disease later.

References

[i] Kostov, Krasimir, and Lyudmila Halacheva. “Role of Magnesium Deficiency in Promoting Atherosclerosis, Endothelial Dysfunction, and Arterial Stiffening as Risk Factors for Hypertension.” International journal of molecular sciences vol. 19,6 1724. 11 Jun. 2018, doi:10.3390/ijms19061724

[ii] 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

[iii] Quest Diagnostics. Magnesium.

[iv] Labcorp. Magnesium.

[v] Pagana, Kathleen Deska; Pagana, Timothy J.; Pagana, Theresa N. Mosby's Diagnostic and Laboratory Test Reference - E-Book. Elsevier Health Sciences. 2019..

[vi] Merck Manual Professional Version. Overview of Disorders of Magnesium Concentration.

[vii] 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

[viii] Rosanoff, Andrea et al. “Effectively Prescribing Oral Magnesium Therapy for Hypertension: A Categorized Systematic Review of 49 Clinical Trials.” Nutrients vol. 13,1 195. 10 Jan. 2021, doi:10.3390/nu13010195