Perspective: The Case for an Evidence-Based Reference Interval for Serum Magnesium: The Time Has Come

Abstract

The 2015 Dietary Guidelines Advisory Committee indicated that magnesium was a shortfall nutrient that was underconsumed relative to the Estimated Average Requirement (EAR) for many Americans. Approximately 50% of Americans consume less than the EAR for magnesium, and some age groups consume substantially less. A growing body of literature from animal, epidemiologic, and clinical studies has demonstrated a varied pathologic role for magnesium deficiency that includes electrolyte, neurologic, musculoskeletal, and inflammatory disorders; osteoporosis; hypertension; cardiovascular diseases; metabolic syndrome; and diabetes. Studies have also demonstrated that magnesium deficiency is associated with several chronic diseases and that a reduced risk of these diseases is observed with higher magnesium intake or supplementation. Subclinical magnesium deficiency can exist despite the presentation of a normal status as defined within the current serum magnesium reference interval of 0.75-0.95 mmol/L. This reference interval was derived from data from NHANES I (1974), which was based on the distribution of serum magnesium in a normal population rather than clinical outcomes. What is needed is an evidenced-based serum magnesium reference interval that reflects optimal health and the current food environment and population. We present herein data from an array of scientific studies to support the perspective that subclinical deficiencies in magnesium exist, that they contribute to several chronic diseases, and that adopting a revised serum magnesium reference interval would improve clinical care and public health.

Serum Magnesium Concentrations in the Canadian Population and Associations with Diabetes, Glycemic Regulation, and Insulin Resistance

“…Between 9.5% and 16.6% of the adult sex-age groups were hypomagnesaemic (serum Mg < 0.75 mmol·L −1 ) in relation to a population-based reference interval [14]. There is a need to establish an evidence-based reference interval (or at minimum a lower cut-off value) for health that will allow more accurate assessment of the prevalence of Mg deficiency in Canada and related health risk based on results from this study [61]. Among demographic factors, age was the strongest predictor of serum Mg concentration.…”

Low serum magnesium and 1‐year mortality in alcohol withdrawal syndrome

“…18,19 Most epidemiological studies have defined concentrations below 0.70 mmol/L as "very low" 20 below 0.75 mmol/L as "low". However, there is ongoing debate as to the serum magnesium concentration threshold below which a patient may be considered to be deficient.…”

Interpreting magnesium status to enhance clinical care

“…In addition, mild and moderate Mg deficiencies (subclinical Mg deficiency) are mostly asymptomatic [2*]. As a result, subclinical Mg deficiency has not been routinely recognized in healthy population groups.…”

“…Significant dose and time responses of serum Mg concentration to oral Mg supplementation increased gradually until reaching a steady state at 300 mg/day after approximately 20 weeks (P-nonlinearity <0.001). High baseline serum Mg concentrations were associated with less or no changes in serum Mg. A recent extensive review found that serum Mg in relation with risk factors for chronic disease such as glucose intolerance, inflammation, and elevated blood pressure indicated that many individuals had what has been termed chronic latent Mg deficiency as defined by serum concentrations in the range of 0.75–0.85 mmol/L [2*]. These findings indicate that many physicians may assume that patients have “normal” Mg status when they may actually have chronic or subclinical deficiency.…”

“…In the Atherosclerosis Risk in Communities Study, a low serum Mg (<70 mmol/L) was associated with a 70% higher risk of incident heart failure [21]. An extensive review of cohort studies of cardiovascular disease outcomes found that the risk of mortality and morbidity of several cardiovascular diseases decreased as Mg status markers improved (dietary intake >250 mg/day; serum concentration >0.75 mmol/L; urinary excretion >100 mg/day) [2*]. …”