Andrea Rosanoff

Background and Aims: Magnesium deficiency is associated with poor outcomes in patients with heart failure (HF), but less is known about the impact of oral magnesium therapy. This study aimed to examine the association of oral magnesium with outcomes in patients with HF and whether it depends on baseline serum magnesium. Methods: Of 54 696 Veterans with HF (2001–2023) and hypomagnesemia (serum magnesium <1.7 mg/dL), 10 695 were initiated on oral magnesium (median dose, 420 mg/day). A propensity score-matched cohort of 21 098 patients (treated, n = 10 549) balanced on 71 baseline characteristics was assembled while remaining outcome-blinded. This process was repeated to assemble a matched cohort of 11 634 patients (treated, n = 5817) with normomagnesemia (serum magnesium, 1.7–2.3 mg/dL). Hazard ratios (HR) (95% confidence intervals [CIs]) for one-year outcomes associated with oral magnesium were estimated. Results: In the hypomagnesemia cohort, HF hospitalization or death occurred in 21.7% of patients not receiving and 20.1% receiving oral magnesium (HR: 0.91; 95% CI: 0.86–0.97). Respective HRs (95% CIs) in subgroups with serum magnesium 1.6 (n = 5929), 1.3–1.5 (n = 11 293) and <1.3 (n = 3876) mg/dL were 0.99 (0.88–1.12), 0.91 (0.84–0.98; interaction P = .20), and 0.81 (0.71–0.93; interaction P = .03). Respective rates in the normomagnesemia cohort were 17.8% and 19.5% (HR: 1.11; 95% CI: 1.02–1.21). Spline regression analysis revealed that HRs were lower at serum magnesium 1.8 mg/dL, and not significant at 1.5–1.8 mg/dL. Conclusions: Oral magnesium therapy was associated with a lower risk of HF hospitalization or death in patients with HF and hypomagnesemia. Future clinical trials need to confirm these findings.

Background/Objectives: Reliable markers of human magnesium (Mg) status are needed. Methods: Current Mg studies report ratios between serum Mg and calcium (Ca) using four interchangeable expressions (i.e., molar or weight calculations of Mg/Ca or Ca/Mg). We propose a scale using ratios of serum Mg and Ca to assess Mg status, unified for all four expressions. We explore its application for case studies and published research. Results: Case Studies (4)—the proposed serum Mg/Ca scale showed better Mg diagnostic value than serum Mg alone. Published Studies—A. The proposed Mg/Ca scale’s “depleted Mg” status predicted mortality among hospitalized COVID-19 patients in ROC/AUC analyses. B. The serum Ca/Mg proposed scale, when applied to “healthy” adults with “normal” serum Mg, exposed a “seriously depleted” to “adequate” range of Mg status. C. In a study of periodontal disease, patients designated “adequate” or “mild” Mg depletion by the proposed scale showed greater 5-year improvement than those with scale’s “moderate to serious” Mg depletion status. D. Finally, the proposed scale demonstrated appropriate diagnostic value of serum Ca/Mg in acute coronary syndrome patients only when “corrected Ca” was NOT used in ratio calculation. Conclusions: The proposed scale needs both total serum Ca and Mg measures in identical units, i.e., mg/dL or mg% (for weight ratios); mmol/L or mEq/L (for molar ratios). Authors/reviewers/editors need to take care when reporting units/methodology of serum Mg and Ca ratios for clear reporting as to weight or molar ratio and use of total or corrected values. Future trials and statistical testing are needed to determine whether ratios between serum Mg and Ca yield more precise measures of physiological Mg status than serum Mg alone. Our findings indicate the proposed scale is worthy of further study as a marker of Mg deficit.

Background/Objectives: Calcium (Ca) and magnesium (Mg) are mutual antagonists that interact in a majority of physiological processes. Thus, maintaining a balance between these two minerals is essential for functional homeostasis. Mg deficiency plays a role in the course and severity of a wide range of chronic health conditions. This knowledge, however, has not translated into active incorporation of serum Mg determination as a reliable diagnostic tool for physiological Mg deficit. Methods: Pioneering work by von Ehrlich and Rosanoff has prompted development of a simple algorithm and scale for using serum Ca and Mg determinations to identify subclinical (i.e., “hidden”) physiological Mg deficiencies. This novel serum Mg/Ca–Ca/Mg scale uses determinations of total serum Ca and Mg and their ratios to alert clinicians to avoidable risks associated with chronic latent Mg deficiency. This review applies this scale to 10 published clinical studies reporting the serum (or plasma) ratio between Mg and Ca. Results: In all 10 studies, application of the serum Mg/Ca–Ca/Mg scale diagnosed deficit Mg status more reliably than serum Mg alone. Conclusions: This review provides both illustrations of the value of the novel scale and support for its consideration in clinical practice and Mg research.

Background: Magnesium (Mg) deficiency is associated with many common chronic conditions and potentially severe health care outcomes, including cardiovascular disease, cardiovascular risk factors, and diabetes. However, Mg deficiency is underdiagnosed and often underrecognized in the ambulatory health care setting, and nutrition education and training are often limited for health care providers (HCPs). Methods: A clinical guideline for detecting and treating Mg deficiency in the ambulatory care setting was developed. A pilot study was conducted in which HCPs received education on Mg and completed pre-test and post-test questionnaires to assess the intervention efficacy of the guideline. Results: Ten HCPs participated in the pilot study via telephone or face-to-face session. In general, there was a statistically significant increase in Mg knowledge among HCPs, due to the intervention of presentation of the guideline, with a nonsignificant increase in clinical practice application. However, the 1-month follow-up survey results showed that HCPs were likely to incorporate Mg assessment and treatment tools from the guideline in their future practice. Conclusions: These findings suggest that the use of the proposed clinical guideline may increase HCP knowledge and improve the diagnosis and treatment of Mg deficiency. Further use, development, and evaluation of this guideline is warranted.

Background: Magnesium (Mg) deficiency is associated with many common chronic conditions and potentially severe health care outcomes, including cardiovascular disease, cardiovascular risk factors, and diabetes. However, Mg deficiency is underdiagnosed and often underrecognized in the ambulatory health care setting, and nutrition education and training are often limited for health care providers (HCPs). Methods: A clinical guideline for detecting and treating Mg deficiency in the ambulatory care setting was developed. A pilot study was conducted in which HCPs received education on Mg and completed pre-test and post-test questionnaires to assess intervention efficacy of the guideline. Results: Ten HCPs participated in the pilot study via telephone or face-to-face session. There was a statistically significant increase in general Mg knowledge among HCPs, due to the intervention of presentation of the guideline, with a nonsignificant increase in clinical practice. However, 1-month follow-up survey results showed that HPCs were likely to incorporate Mg assessment and treatment tools from the guideline in their future practice. Conclusions: These findings suggest that use of the proposed clinical guideline may increase HCP knowledge and improve the diagnosis and treatment of Mg deficiency.

A large amount of published research points to the interesting concept (hypothesis) that magnesium (Mg) status may have relevance for the outcome of COVID-19 and that Mg could be protective during the COVID disease course. As an essential element, Mg plays basic biochemical, cellular, and physiological roles required for cardiovascular, immunological, respiratory, and neurological functions. Both low serum and dietary Mg have been associated with the severity of COVID-19 outcomes, including mortality; both are also associated with COVID-19 risk factors such as older age, obesity, type 2 diabetes, kidney disease, cardiovascular disease, hypertension, and asthma. In addition, populations with high rates of COVID-19 mortality and hospitalization tend to consume diets high in modern processed foods, which are generally low in Mg. In this review, we review the research to describe and consider the possible impact of Mg and Mg status on COVID-19 showing that (1) serum Mg between 2.19 and 2.26 mg/dL and dietary Mg intakes > 329 mg/day could be protective during the disease course and (2) inhaled Mg may improve oxygenation of hypoxic COVID-19 patients. In spite of such promise, oral Mg for COVID-19 has thus far been studied only in combination with other nutrients. Mg deficiency is involved in the occurrence and aggravation of neuropsychiatric complications of COVID-19, including memory loss, cognition, loss of taste and smell, ataxia, confusion, dizziness, and headache. Potential of zinc and/or Mg as useful for increasing drug therapy effectiveness or reducing adverse effect of anti-COVID-19 drugs is reviewed. Oral Mg trials of patients with COVID-19 are warranted.

Purpose Serum magnesium is the most frequently used laboratory test for evaluating clinical magnesium status. Hypomagnesemia (low magnesium status), which is associated with many chronic diseases, is diagnosed using the serum magnesium reference range. Currently, no international consensus for a magnesemia normal range exists. Two independent groups designated 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L) as the low cut-off point defining hypomagnesemia. MaGNet discussions revealed differences in serum magnesium reference ranges used by members’ hospitals and laboratories, presenting an urgent need for standardization. Methods We gathered and compared serum magnesium reference range values from our institutions, hospitals, and colleagues worldwide. Results Serum magnesium levels designating “hypomagnesemia” differ widely. Of 43 collected values, only 2 met 0.85 mmol/L as the low cut-off point to define hypomagnesemia. The remainder had lower cut-off values, which may underestimate hypomagnesemia diagnosis in hospital, clinical, and research assessments. Current serum magnesium reference ranges stem from “normal” populations, which unknowingly include persons with chronic latent magnesium deficit (CLMD). Serum magnesium levels of patients with CLMD fall within widely used “normal” ranges, but their magnesium status is too low for long-term health. The lower serum magnesium reference (0.85 mmol/L) proposed specifically prevents the inclusion of patients with CLMD. Conclusions Widely varying serum magnesium reference ranges render our use of this important medical tool imprecise, minimizing impacts of low magnesium status or hypomagnesemia as a marker of disease risk. To appropriately diagnose, increase awareness of, and manage magnesium status, it is critical to standardize lower reference values for serum magnesium at 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L).