This study was one of the largest and the most comprehensive real-world studies of magnesium deficiency in women. The study cohorts consisted of pregnant women and women with hormone-related conditions from multiple cities and regions of the Russian Federation, providing wide geographical coverage and a large sample size (a total of 10,427 women).
The prevalence of magnesium deficiency in the studied population was extremely high, reaching 78.9% in pregnant women and 54.8% in women with hormone-related conditions. These rates are among the highest cited in literature; however, one should keep in mind that participants of MAGIC and MAGIC2 studies were enrolled based on clinical suspicion of magnesium deficiency. Furthermore, the analysis of MAGYN and MAGYN2 study included only women with serum magnesium level assessment at Visit 1, i.e. those with suspected magnesium deficiency. Nevertheless, these results complement other studies, including those assessing magnesium levels in general adult populations of Germany, Mexico, Taiwan and the USA that found higher prevalence of hypomagnesemia in women (21.0–40.0%) than in men (1.5–35.4%) [23, 24, 2, 25]. In these studies, magnesium deficiency was determined using cut-offs between 0.76 mmol/L and 0.85 mmol/L [23, 24, 2, 25]. High rates of hypomagnesemia have been reported in pregnant women in India (43.6%) and Sudan (57.2%); both studies used a cut-off of 0.74 mmol/L [26, 27]. The results of the present study confirm the general observations that pregnant women, women receiving oral contraceptives, postmenopausal women and women with osteoporosis are at a particular risk of hypomagnesemia [16, 9, 17]. The multifactorial reasons for the increased risk during pregnancy have been discussed in detail elsewhere and include fetal demand, altered tissue distribution and an increased renal output of magnesium [9]. High estrogen levels may also influence magnesium utilization in tissues and may account for subnormal serum magnesium levels in young women receiving oral contraceptives, with multiple gender-specific physiological ageing processes accounting for low magnesium in women with osteoporosis [4, 17]. Irrespective of the underlying cause, there is an argument for the use of magnesium supplementation in women who are at risk of hypomagnesemia, including pregnant women and women with hormone-related conditions. Notably, among various subgroups of women with hormone-related conditions, women with osteoporosis had the highest incidence of hypomagnesemia (28.0%/58.3% using cut-off < 0.66/0.8 mmol/L), but also had the highest rate of achieving target serum magnesium level with magnesium supplementation (88.1%/58.8% using cut-off < 0.66/0.8 mmol/L). These results emphasize a possible role for magnesium supplementation in the prevention or treatment of various gynecological conditions that could be explored in future studies.
Several risk factors associated with low magnesium levels have been identified in the studied cohorts. The broad variety of conditions and comorbidities found in this study are in line with the previous studies in pregnant women and the general population (e.g. cardiovascular comorbidities) and further expand the current knowledge of the effect of hypomagnesemia on women’s health. In pregnant women, risk factors for both 0.66 mmol/L and 0.8 mmol/L cut-offs included increased diastolic blood pressure, previous pregnancy complications, such as preeclampsia, placental insufficiency and intrauterine growth retardation, viral infections in general medical history and edema. Previous studies have identified placental insufficiency, preeclampsia, miscarriage, premature birth and gestational diabetes as conditions and outcomes associated with low magnesium levels [9]. Magnesium sulphate is recommended by the WHO for the prevention and treatment of eclampsia [28]. However, despite its wide use in clinical practice, the dosing regimens vary across countries and are often inconsistent with the international recommendations [29]. Our results further strengthen the clinical evidence supporting a direct link between magnesium supplementation and risk of preeclampsia and may help facilitate the uptake of the WHO guidelines throughout the world. It may also be interesting to test in further clinical studies whether the use of over-the-counter magnesium supplements in pregnant women decreases the risk of preeclampsia and the need for intravenous magnesium administration.
In women with hormone-related conditions, risk factors for both 0.66 mmol/L and 0.8 mmol/L cut-offs included age and BMI, all studied symptoms of magnesium deficiency, and a large number of previous gynecological conditions and general comorbidities. Our analysis found significant associations between the risk of low magnesium and various general comorbidities, including immune system-related conditions (infections, asthma, allergies) and with general stress (various laboratory and hormone values) in women with hormone-related conditions. These observations support previous reports linking immune dysfunction and general stress to magnesium deficiency [30, 31]. The large number of risk factors associated with hypomagnesemia in this study confirms the status of magnesium as one of the essential elements in health and supports further clinical research investigating the role of magnesium in various neurological, gastrointestinal and cardiovascular conditions.
This study has several limitations. The observational studies MAGIC and MAGIC2 collected data on pregnant women with suspected magnesium deficiency, and it is not possible to generalize these results to the overall population. However, the study generated an important insight into hypomagnesemia in a larger cohort of women with hormone-related conditions (MAGYN and MAGYN2). Because of the retrospective observational design of this study, no causal links can be established between magnesium deficiency and associated conditions.
Nonetheless, this is one of the largest and representative analyses of magnesium deficiency in pregnant women and women with hormone-related conditions. The study provided an estimate of the prevalence of hypomagnesemia in these cohorts and identified multiple risk factors and associated comorbidities, providing unique insights into the epidemiology of magnesium deficiency in the Russian Federation.