Low Magnesium Status Research Articles

Examining the Effects of Supplemental Magnesium on Self-Reported Anxiety and Sleep Quality: A Systematic Review.

Self-treatment with vitamin, mineral, and herbal supplements has become increasingly common among patients for the treatment of psychiatric disorders. Magnesium, in particular, is popular on social media for the treatment of anxiety and insomnia. Meanwhile, preclinical studies support associations between magnesium status, sleep quality, and symptoms of anxiety. The extent to which these claims are evidence-based is unclear. Therefore, a systematic review was performedto provide an updated examination of the clinical evidence on the use of magnesium for the treatment of the above conditions given the popularity of such supplements among patients and the public at large. A thorough search of the PubMed database was performed and results were systematically reviewed using PRISMA guidelines. The search was limited to anxiety disorders and sleep disorders and included interventional trials only.Exclusion criteria included insufficient (<50 mg/12.5% of recommended daily allowance (RDA)) or unknown magnesium dose, >3 other potentially active compounds present in the formulation, and articles in languages other than English. This query returned 860 articlesof which 15 met full inclusion criteria. Eight measured sleep-related outcomes, seven measured anxiety-related outcomes, and one examined both. Sleep quality was measured most frequently using the Pittsburg Sleep Quality Index (PSQI). Anxiety measures included self-reported measures such as the Hamilton Anxiety Scale. The majority of included studies demonstrated improvement in at least one sleep- or anxiety-related parameter. Five out of eight sleep-related studies reported improvements in sleep parameters, while two studies reported no improvements, and one reported mixed results. Five out of seven studies measuring anxiety-related outcomes reported improvements in self-reported anxiety. Firm conclusions were limited by the heterogeneity of the data and the small numberof participants involved in most of the studies. The dosages, formulations, and durations of the magnesium interventions used also differed across studies. Furthermore, some studies included additional, potentially activeingredients, further complicating interpretations. Given the generally positive results across studies, the preponderance of preclinical evidence, and minimal side effects, however, supplemental magnesiumis likely useful in the treatment ofmild anxiety and insomnia, particularly in those with low magnesium status at baseline. Notably, both negative anxiety trials featured populations withunderlying endocrine factors likely contributing to their symptoms (patients with premenstrual symptoms and post-partum women). Nonetheless, larger, randomized clinical trials are needed to confirm efficacy and to establish the most effective forms and dosages of magnesium for the treatment of insomnia and anxiety disorders.

Recommendation on an updated standardization of serum magnesium reference ranges.

PurposeSerum 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.MethodsWe gathered and compared serum magnesium reference range values from our institutions, hospitals, and colleagues worldwide.ResultsSerum 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.ConclusionsWidely 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).

Magnesium Status and Stress: The Vicious Circle Concept Revisited.

Magnesium deficiency and stress are both common conditions among the general population, which, over time, can increase the risk of health consequences. Numerous studies, both in pre-clinical and clinical settings, have investigated the interaction of magnesium with key mediators of the physiological stress response, and demonstrated that magnesium plays an inhibitory key role in the regulation and neurotransmission of the normal stress response. Furthermore, low magnesium status has been reported in several studies assessing nutritional aspects in subjects suffering from psychological stress or associated symptoms. This overlap in the results suggests that stress could increase magnesium loss, causing a deficiency; and in turn, magnesium deficiency could enhance the body’s susceptibility to stress, resulting in a magnesium and stress vicious circle. This review revisits the magnesium and stress vicious circle concept, first introduced in the early 1990s, in light of recent available data.

Magnesium and inflammation: Advances and perspectives

Magnesium is an essential element of life, involved in the regulation of metabolism and homeostasis of all the tissues. It also regulates immunological functions, acting on the cells of innate and adaptive immune systems. Magnesium deficiency primes phagocytes, enhances granulocyte oxidative burst, activates endothelial cells and increases the levels of cytokines, thus promoting inflammation. Consequently, a low magnesium status, which is often underdiagnosed, potentiates the reactivity to various immune challenges and is implicated in the pathophysiology of many common chronic diseases. Here we summarize recent advances supporting the link between magnesium deficiency, inflammatory responses and diseases, and offer new hints towards a better understanding of the underlying mechanisms.

Cadmium toxicity degree on tomato development is associated with disbalances in B and Mn status at early stages of plant exposure.

Cadmium (Cd) toxicity is frequently coupled to its accumulation in plants, but not always the highest Cd concentration triggers the worst damages, indicating that additional events influence the magnitude of Cd side-effects. We investigated the early mechanisms behind the differential Cd-induced impacts on plant development of four tomato accessions with contrasting tolerance to Cd toxicity. At organ level, the highest Cd concentration was not associated with the largest biomass losses. In leaves, changes in superoxide dismutase and catalase activities were not related to differences in Cd concentration, which was unable to provoke H2O2 overproduction on the sixth day of plant exposure to this metal. Further investigation in the mineral profile revealed that magnitude of Cd toxicity depends probably on synergic effects from increased B status, in addition to the own Cd accumulation. Furthermore, disbalances in Mn status (i.e., excess in leaves and deficiency in roots) may enhance Cd toxicity degree. According to data, however, the low magnesium (Mg) status can be linked to tomato tolerance against Cd toxicity. In conclusion, the tomato tolerance degree under short-Cd exposure depends on actively, finely regulation of mineral homeostasis that results in different development of plant organs. The better understanding on the mode of action of Cd toxicity in plants can help in the establishment of strategies to mitigate its impacts on crop yield.

Abstract 4258: Magnesium intake and mortality due to liver cancer and other liver diseases: Results from the Third National Health and Nutrition Examination Survey Cohort

Abstract People with fatty liver disease are at high risk of magnesium deficiency. Meanwhile, low magnesium status is linked to both chronic inflammation and insulin resistance. However, no study has investigated the association between intake of magnesium and risk of mortality due to liver cancer and other liver diseases. We evaluated the association between total magnesium intake and mortality due to liver cancer and other liver diseases in the Third National Health and Nutrition Examination Study (NHANES III) cohort, which included 13,504 participants who completed liver ultrasound examination for hepatic steatosis. Overall magnesium intake was associated with a reduced risk of mortality due to liver cancer and other liver disease at borderline significance (P=0.05). In multi-variable adjusted models, every 100 mg increase in intake of magnesium was associated with a 49% reduction in the risk for mortality due to liver cancer and other liver diseases. Although interactions between magnesium intake and alcohol use and hepatic steatosis at baseline were not significant (P&amp;gt;0.05), inverse associations between magnesium intake with liver cancer and other liver disease mortality were stronger among alcohol drinkers and those with hepatic steatosis. Our novel findings suggest higher intakes of magnesium may be associated with a reduced risk of mortality due to liver cancer and other liver disease particularly among alcohol drinkers and those with hepatic steatosis. Further studies are warranted to confirm the findings. Citation Format: Zhu Xiangzhu, Lijun Wu, Lei Fan, Edmond K Kabagambe, Yiqing Song, Menghua Tao, Xiaosong Zhong, Lifang Hou, Martha J. Shrubsole, Jie Liu, Qi Dai. Magnesium intake and mortality due to liver cancer and other liver diseases: Results from the Third National Health and Nutrition Examination Survey Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4258.

Magnesium and Progression of Chronic Kidney Disease: Benefits Beyond Cardiovascular Protection?

Experimental and clinical studies have demonstrated that magnesium deficiency leads to hypertension, insulin resistance, and endothelial dysfunction, and is associated with an increased risk of cardiovascular events. Given that cardiovascular disease and CKD share similar risk factors, the low magnesium status may also contribute to CKD progression. In fact, lower serum magnesium levels and lower dietary magnesium intake are associated with an increased risk of incident CKD and progression to end-stage kidney disease. Because these associations are independent of traditional risk factors, other pathways might be involved in the relationship between magnesium deficiency and the risk of CKD progression. Recent evidence has shown thatmagnesium suppresses phosphate-induced vascular calcification. Magnesium impairs the crystallization of calcium phosphate-more specifically, the maturation of calciprotein particles. Considering that phosphate overload causes kidney damage, magnesium might counteract the phosphate toxicity to the kidney, as in the case of vascular calcification. This hypothesis is supported by an invitro observation that magnesium alleviates proximal tubular cell injury induced by high phosphate. Potential usefulness of magnesium as a treatment option for phosphate toxicity in CKD should be further investigated by intervention studies.

Magnesium intake and mortality due to liver diseases: Results from the Third National Health and Nutrition Examination Survey Cohort

People with fatty liver disease are at high risk of magnesium deficiency. Meanwhile, low magnesium status is linked to both chronic inflammation and insulin resistance. However, no study has investigated the association between intake of magnesium and risk of mortality due to liver diseases. We evaluated the association between total magnesium intake and mortality due to liver diseases in the Third National Health and Nutrition Examination Study (NHANES III) cohort, which included 13,504 participants who completed liver ultrasound examination for hepatic steatosis. Overall magnesium intake was associated with a reduced risk of mortality due to liver disease at borderline significance (P = 0.05). In fully-adjusted analyses, every 100 mg increase in intake of magnesium was associated with a 49% reduction in the risk for mortality due to liver diseases. Although interactions between magnesium intake and alcohol use and hepatic steatosis at baseline were not significant (P > 0.05), inverse associations between magnesium intake and liver disease mortality were stronger among alcohol drinkers and those with hepatic steatosis. Our findings suggest higher intakes of magnesium may be associated with a reduced risk of mortality due to liver disease particularly among alcohol drinkers and those with hepatic steatosis. Further studies are warranted to confirm the findings.

Ionized magnesium in plasma and erythrocytes for the assessment of low magnesium status in alcohol dependent patients

BackgroundStudies on the homeostasis of magnesium in alcohol-dependent patients have often been characterized by low hypomagnesemia detection rates. This may be due to the fact that the content of magnesium in blood serum constitutes only 1% of the average magnesium level within the human body. However, the concentration of ionized magnesium is more physiologically important and makes up 67% of the total magnesium within a human organism. There are no data concerning the determination of the ionized fraction of magnesium in patients addicted to alcohol and its influence on mental health status. MethodsThis study included 100 alcohol-dependent patients and 50 healthy subjects. The free magnesium fraction was determined using the potentiometric method by means of using ion-selective electrodes. The total magnesium level was determined by using a biochemical Indiko Plus analyzer. In this study, different psychometric scales were applied. ResultsOur results confirm the usefulness of ionized magnesium concentrations in erythrocytes and plasma as a diagnostic parameter of low magnesium status in alcohol-dependent patients. ConclusionsThe lower the concentration of ionized magnesium, the worse the quality of life an alcohol-dependent person might experience. In the case of total magnesium, no such correlation was determined.

Burning magnesium, a sparkle in acute inflammation: gleams from experimental models.

Magnesium contributes to the regulation of inflammatory responses. Here, we focus on the role of magnesium in acute inflammation. Although present knowledge is incomplete to delineate an accurate scenario and a schedule of the events occurring under magnesium deficiency, it emerges that low magnesium status favors the induction of acute inflammation by sensitizing sentinel cells to the noxious agent, and then by participating to the orchestration of the vascular and cellular events that characterize the process.

Abstract P146: Serum Magnesium and Mortality in the General US Population: Results From the NHANES I Epidemiologic Follow-up Study

Introduction: Low magnesium (Mg) intake and/or status has been associated with increased risk of chronic disease, including cardiovascular disease (CVD) and cancer. However, whether and to what extent low serum Mg levels are associated with all-cause or cause-specific mortality in the general population is uncertain. Hypothesis: We aimed to quantify the dose-response associations between low concentrations of serum Mg and mortality from all causes, cancer, CVD, and stroke in the general US population. Methods: We analyzed prospective data on 14,353 participants aged 25-74 years with baseline measures of serum Mg concentrations from the National Health and Nutrition Examination Survey Epidemiologic Follow-up Study 1971-2006. We estimated the mortality hazard ratios (HRs) for participants within predefined and clinically meaningful categories of serum Mg levels, including &lt;0.7, 0.7-0.74, 0.75-0.79, 0.8-0.9 (normal reference), 0.9-0.94, 0.95-0.99, and ≥1.0 mmol/L, using Cox proportional hazards models. Restricted cubic spline models were applied to examine potentially nonlinear relationships between serum Mg and mortality. Results: During a mean follow-up of 27.6 years, 7,072 deaths occurred, 3,310 (47%) CVD deaths, 1,533 (22%) cancer deaths, and 281 (4%) stroke deaths. Twenty-one percent of all participants had low levels of serum Mg (&lt;0.8 mmol/L) and 1.5% had extremely low serum Mg (&lt;0.7 mmol/L). Age-adjusted all-cause mortality rates were 3845, 3491, 3471, 3400 (normal reference), 3531, 3525, and 3836 per 100,000 person-years for increasing categories of serum Mg; the HRs and 95% confidence intervals for increasing serum Mg were 1.32 (1.02-1.72), 0.93 (0.74-1.16), and 1.06 (0.96-1.18), 1.07 (0.97-1.18), 0.94 (0.77-1.13), and 0.93 (0.72-1.21), compared to the reference group (0.8-0.9 mmol/L). An L-shaped association between serum Mg concentrations and all-cause mortality was observed after adjusting for potential confounders (Figure). No statistically significant associations were observed between serum Mg and cancer, CVD, or stroke mortality. Conclusions: Very low serum Mg levels were significantly associated with all-cause mortality in the general US population. Our findings support the hypothesis that Mg deficiency as defined by very low serum Mg may have an important influence on mortality.

Magnesium: Nutrition and Homoeostasis.

The essential mineral magnesium is involved in numerous physiological processes. Recommended dietary intake is often not met and a low magnesium status increases the risk for various diseases. Magnesium status is regulated by several magnesium transport systems either in cellular or paracellular pathways. Numerous drugs either interfere with magnesium absorption in the intestines or the reabsorption from primary urine in the kidney. Low magnesium status has been identified as a significant risk factor for several diseases, including type-2 diabetes, cardiovascular diseases, arrhythmias, as well as general muscular and neurological problems. Therefore, an adequate magnesium supply would be of special benefit to our overall health.

Essential Nutrient Interactions: Does Low or Suboptimal Magnesium Status Interact with Vitamin D and/or Calcium Status?

Although much is known about magnesium, its interactions with calcium and vitamin D are less well studied. Magnesium intake is low in populations who consume modern processed-food diets. Low magnesium intake is associated with chronic diseases of global concern [e.g., cardiovascular disease (CVD), type 2 diabetes, metabolic syndrome, and skeletal disorders], as is low vitamin D status. No simple, reliable biomarker for whole-body magnesium status is currently available, which makes clinical assessment and interpretation of human magnesium research difficult. Between 1977 and 2012, US calcium intakes increased at a rate 2–2.5 times that of magnesium intakes, resulting in a dietary calcium to magnesium intake ratio of >3.0. Calcium to magnesium ratios <1.7 and >2.8 can be detrimental, and optimal ratios may be ∼2.0. Background calcium to magnesium ratios can affect studies of either mineral alone. For example, US studies (background Ca:Mg >3.0) showed benefits of high dietary or supplemental magnesium for CVD, whereas similar Chinese studies (background Ca:Mg <1.7) showed increased risks of CVD. Oral vitamin D is widely recommended in US age-sex groups with low dietary magnesium. Magnesium is a cofactor for vitamin D biosynthesis, transport, and activation; and vitamin D and magnesium studies both showed associations with several of the same chronic diseases. Research on possible magnesium and vitamin D interactions in these human diseases is currently rare. Increasing calcium to magnesium intake ratios, coupled with calcium and vitamin D supplementation coincident with suboptimal magnesium intakes, may have unknown health implications. Interactions of low magnesium status with calcium and vitamin D, especially during supplementation, require further study.

Study of Magnesium Level as an Indicator of Diabetic Complications

Background: Type 2 diabetes has become a leading cause of morbidity and mortality world over. Magnesium depletion has a negative impact on glucose homeostasis and insulin sensitivity in patients with Type 2 diabetes. Magnesium deficiency can lead to development of complications such as retinopathy, nphropathy, thrombosis and hypertension. Material and Methods: The case control type of study was carried out on 50 age and sex matched healthy controls and 50 type 2 diabetic patients who attended the outpatient and inpatient department of medicine in tertiary care medical institute. All patients and controls underwent thorough clinical examination and estimation of serum magnesium, FBS, PPBS, lipid profile and urea, creatinine levels. Results: 46% of diabetic patients had low serum magnesium levels (Mg2+ level<1.5mg/dL) and 6% of controls had low serum magnesium levels (Mg2+ level<1.5mg/dL). The mean serum magnesium levels were 1.79±0.34mg/dL and 2.12±0.29mg/dL, in diabetics and controls respectively (p value < 0.0001 highly significant). In this study hypomagnesaemia (Mg2+ level < 1.5mg/dl) was correlating with neuropathy and retinopathy, and the results were highly significant. Conclusion: This study demonstrated that Low Magnesium status is common in Type 2 diabetes mellitus patients when compared to non diabetic controls. It may be prudent in clinical practice to periodically monitor plasma magnesium concentration in diabetic patients. If plasma magnesium is low, an intervention to increase dietary intake of magnesium maybe beneficial.

Magnesium: The fifth electrolyte

Among cations of biologic importance, Magnesium (Mg) is the forgotten member, often labeled as fifth electrolyte and sometimes even as the body's 'orphan ion', because of an apparent lack of a specific endocrine control. Magnesium is an important co-factor in many enzymatic reactions involving energy metabolism, protein and nucleic acid synthesis. Ionized Mg is the physiologically active form of the element. It has been mentioned in various epidemiological and correlation studies that low Magnesium status is widely prevalent. Data from many studies indicate that in about 60% of adults the Magnesium intakes from food do not meet the estimated average requirement. Recommended dietary allowance especially for Indians are still undefined.

Gestational glucose intolerance modifies the association between magnesium and glycemic variables in mothers and daughters 15 years post-partum

Gestational diabetes mellitus (GDM) and low magnesium (Mg) intake and status are associated with an increased risk of type 2 diabetes. However, Mg homeostasis may be modified by GDM. We sought to determine if a history of GDM prospectively modifies associations between Mg and glycemic variables in mothers and their offspring. Plasma and dietary Mg, anthropometric, lifestyle and glycemic variables were assessed in mothers affected by GDM during 1989-1990, a comparative group of normoglycemic women, pregnant during the same time period, and the 15-year-old, nondiabetic daughters of affected and unaffected pregnancies (n = 332). Multivariate regression analyses evaluated the cross-sectional association between plasma and dietary Mg with glycemic variables in mothers and daughters. Plasma Mg was lower in mothers with a history of GDM in comparison to control mothers after adjustment for current type 2 diabetes, race and body mass index (0.90 ± 0.01 versus 0.96 ± 0.01 mmol/L; p = 0.002). Plasma Mg was significantly associated with insulin sensitivity and was inversely associated with fasting insulin in GDM mothers only (p<0.05). Plasma and dietary Mg were significantly inversely associated with glycated hemoglobin and fasting glucose, respectively, in nondiabetic teenage daughters. For fasting glucose, plasma Mg was inversely associated in GDM-born daughters only. Associations between plasma Mg and some glycemic variables may be stronger in mothers and offspring with a history of GDM.

Suboptimal magnesium status in the United States: are the health consequences underestimated?

In comparison with calcium, magnesium is an "orphan nutrient" that has been studied considerably less heavily. Low magnesium intakes and blood levels have been associated with type 2 diabetes, metabolic syndrome, elevated C-reactive protein, hypertension, atherosclerotic vascular disease, sudden cardiac death, osteoporosis, migraine headache, asthma, and colon cancer. Almost half (48%) of the US population consumed less than the required amount of magnesium from food in 2005-2006, and the figure was down from 56% in 2001-2002. Surveys conducted over 30 years indicate rising calcium-to-magnesium food-intake ratios among adults and the elderly in the United States, excluding intake from supplements, which favor calcium over magnesium. The prevalence and incidence of type 2 diabetes in the United States increased sharply between 1994 and 2001 as the ratio of calcium-to-magnesium intake from food rose from <3.0 to >3.0. Dietary Reference Intakes determined by balance studies may be misleading if subjects have chronic latent magnesium deficiency but are assumed to be healthy. Cellular magnesium deficit, perhaps involving TRPM6/7 channels, elicits calcium-activated inflammatory cascades independent of injury or pathogens. Refining the magnesium requirements and understanding how low magnesium status and rising calcium-to-magnesium ratios influence the incidence of type 2 diabetes, metabolic syndrome, osteoporosis, and other inflammation-related disorders are research priorities.

Low magnesium status in plants enhances tolerance to cadmium exposure

In a transcriptomic study of magnesium (Mg) starvation in Arabidopsis, we identified several genes that were differentially regulated which are involved in the detoxification process of nonessential heavy metals such as cadmium (Cd). We further tested the impact of low Mg status on Cd sensitivity in plants. Interestingly, a -Mg pretreatment of 7 d alleviated the bleaching of young leaves caused by Cd. No or little difference in Cd tissue concentration between the +Mg and -Mg plants was observed, suggesting that lower Cd toxicity was probably not attributable to modified root to shoot translocation. Mg deficiency also promoted an increase in the iron (Fe) concentration (up to one-fourth) in Cd-treated leaves. Because high Fe concentrations have previously been reported to prevent the harmful effects of Cd, we explored whether Fe homeostasis plays a role in the Mg-Cd interaction. A protective effect of -Mg pretreatment was also observed on Fe starvation. However, Fe foliar spray partially alleviated Cd-induced chloroses, while it almost completely restored chlorophyll content in Fe-deficient leaves. In conclusion, the protective effect of Mg against Cd toxicity could be attributable partly to the maintenance of Fe status but also to the increase in antioxidative capacity, detoxification and/or protection of the photosynthetic apparatus.

Magnesium, inflammation, and obesity in chronic disease

About 60% of adults in the United States do not consume the estimated average requirement for magnesium, but widespread pathological conditions attributed to magnesium deficiency have not been reported. Nevertheless, low magnesium status has been associated with numerous pathological conditions characterized as having a chronic inflammatory stress component. In humans, deficient magnesium intakes are mostly marginal to moderate (approximately 50% to <100% of the recommended dietary allowance). Animal experiments indicate that signs of marginal-to-moderate magnesium deficiency can be compensated or exacerbated by other factors influencing inflammatory and oxidative stress; recent studies suggest a similar happening in humans. This suggestion may have significance in obesity, which is characterized as having a chronic low-grade inflammation component and an increased incidence of a low magnesium status. Marginal-to-moderate magnesium deficiency through exacerbating chronic inflammatory stress may be contributing significantly to the occurrence of chronic diseases such as atherosclerosis, hypertension, osteoporosis, diabetes mellitus, and cancer.

Relationship between low magnesium status and TRPM6 expression in the kidney and large intestine

The body maintains Mg(2+) homeostasis by renal and intestinal (re)absorption. However, the molecular mechanisms that mediate transepithelial Mg(2+) transport are largely unknown. Transient receptor potential melastatin 6 (TRPM6) was recently identified and shown to function in active epithelial Mg(2+) transport in intestine and kidney. To define the relationship between Mg(2+) status and TRPM6 expression, we used two models of hypomagnesemia: 1) C57BL/6J mice fed a mildly or severely Mg(2+)-deficient diet, and 2) mice selected for either low (MgL) or high (MgH) erythrocyte and plasma Mg(2+) status. In addition, the mice were subjected to a severely Mg(2+)-deficient diet. Our results show that C57BL/6J mice fed a severely Mg(2+)-deficient diet developed hypomagnesemia and hypomagnesuria and showed increased TRPM6 expression in kidney and intestine. When fed a Mg(2+)-adequate diet, MgL mice presented hypomagnesemia and hypermagnesuria, and lower kidney and intestinal TRPM6 expression, compared with MgH mice. A severely Mg(2+)-deficient diet led to hypomagnesemia and hypomagnesuria in both strains. Furthermore, this diet induced kidney TRPM6 expression in MgL mice, but not in MgH mice. In conclusion, as shown in C57BL/6J mice, dietary Mg(2+)-restriction results in increased Mg(2+) (re)absorption, which is correlated with increased TRPM6 expression. In MgL and MgH mice, the inherited Mg(2+) status is linked to different TRPM6 expression. The MgL and MgH mice respond differently to a low-Mg(2+) diet with regard to TRPM6 expression in the kidney, consistent with genetic factors contributing to the regulation of cellular Mg(2+) levels. Further studies of these mice strains could improve our understanding of the genetics of Mg(2+) homeostasis.