Chronic magnesium deficiency causes reversible mitochondrial permeability transition pore opening and impairs hypoxia tolerance in the rat heart.

Chronic magnesium (Mg) deficiency induces and exacerbates various cardiovascular diseases. We previously investigated the mechanisms underlying decline in cardiac function caused by chronic Mg deficiency and the effectiveness of Mg supplementation on this decline using the Langendorff-perfused isolated mouse heart model. Herein, we used the Langendorff-perfused isolated rat heart model to demonstrate the chronic Mg-deficient rats (Mg-deficient group) had lower the heart rate (HR) and left ventricular pressure (LVDP) than rats with normal Mg levels (normal group). Furthermore, decline in cardiac function due to hypoxia/reoxygenation injury was significantly greater in the Mg-deficient group than in the normal group. Experiments on mitochondrial permeability transition pore (mPTP) using isolated mitochondria revealed that mitochondrial membrane was fragile in the Mg-deficient group, implying that cardiac function decline through hypoxia/reoxygenation injury is associated with mitochondrial function. Mg supplementation for chronic Mg-deficient rats not only improved hypomagnesemia but also almost completely restored cardiac and mitochondrial functions. Therefore, proactive Mg supplementation in pathological conditions induced by Mg deficiency or for those at risk of developing hypomagnesemia may suppress the development and exacerbation of certain disease states.

Migraine and Its Association with Hyperactivity of Cell Membranes in the Course of Latent Magnesium Deficiency-Preliminary Study of the Importance of the Latent Tetany Presence in the Migraine Pathogenesis.

So far, there is no consistent and convincing theory explaining the pathogenesis of migraines. Vascular disorders, the effect of oxidative stress on neurons, and the contribution of magnesium-calcium deficiencies in triggering cortical depression and abnormal glutaminergic neurotransmission are taken into account. However, there are no reliable publications confirming the role of dietary deficits of magnesium and latent tetany as factors triggering migraine attacks. The aim of the study was to evaluate the influence of latent magnesium deficiency assessed with the electrophysiological tetany test on the course of migraine. The study included: a group of 35 patients (29 women and six men; in mean age 41 years) with migraine and a control group of 24 (17 women and seven men; in mean age 39 years) healthy volunteers. Migraine diagnosis was based on the International Headache Society criteria, 3rd edition. All patients and controls after full general and neurological examination were subjected to a standard electrophysiological ischemic tetany test. Moreover, the level of magnesium in blood serum was tested and was in the normal range in all patients. Then, the incidence of a positive tetany EMG test results in the migraine group and the results in the subgroups with and without aura were compared to the results in the control group. Moreover, the relationship between clinical markers of spasmophilia and the results of the tetany test was investigated in the migraine group. As well as the relationship between migraine frequency and tetany test results. There was no statistically significant difference in the occurrence of the electrophysiological exponent of spasmophilia between the migraine and control group. Neither correlation between the occurrence of clinical symptoms nor the frequency of migraine attacks and the results of the tetany test was stated (p > 0.05). However, there was an apparent statistical difference between the subgroup of migraine patients with aura in relation to the control group (p < 0.05). The result raises hope to find a trigger for migraine attacks of this clinical form, the more that this factor may turn out to be easy to supplement with dietary supplementation.

Magnesium in joint health and osteoarthritis.

Osteoarthritis (OA) is a prevalent debilitating age-related skeletal disease. The hallmark of OA is the degradation of articular cartilage that cushions the joint during movement. It is characterized by chronic pain and disability. Magnesium, a critical trace element in the human body, plays a pivotal role in metabolism homeostasis and the energy balance. Humans obtain magnesium mainly from the diet. However, inadequate magnesium intake is not uncommon. Moreover, the magnesium status deteriorates with ageing. There has been a growing body of clinical studies pointing to an intimate relationship between dietary magnesium and OA although the conclusion remains controversial. As reported, the magnesium ion concentration is essential to determine cell fate. Firstly, the low-concentration magnesium ions induced human fibroblasts senescence. Magnesium supplementation was also able to mitigate chondrocyte apoptosis, and to facilitate chondrocyte proliferation and differentiation. In this literature review, we will outline the existing evidence in animals and humans. We will also discuss the controversies on plasma or intracellular level of magnesium as the indicator of magnesium status. In addition, we put forward the interplay between dietary magnesium intake and intestinal microbiome to modulate the inflammatory milieu in the conjecture of OA pathogenesis. This leads to an emerging hypothesis that the synergistic effect of magnesium and probiotics may open a new avenue for the prevention and treatment of OA.

Normalization of magnesium deficiency attenuated mechanical allodynia, depressive-like behaviors, and memory deficits associated with cyclophosphamide-induced cystitis by inhibiting TNF-α/NF-κB signaling in female rats.

BACKGROUND: Bladder-related pain symptoms in patients with bladder pain syndrome/interstitial cystitis (BPS/IC) are often accompanied by depression and memory deficits. Magnesium deficiency contributes to neuroinflammation and is associated with pain, depression, and memory deficits. Neuroinflammation is involved in the mechanical allodynia of cyclophosphamide (CYP)-induced cystitis. Magnesium-L-Threonate (L-TAMS) supplementation can attenuate neuroinflammation. This study aimed to determine whether and how L-TAMS influences mechanical allodynia and accompanying depressive symptoms and memory deficits in CYP-induced cystitis. METHODS: Injection of CYP (50 mg/kg, intraperitoneally, every 3 days for 3 doses) was used to establish a rat model of BPS/IC. L-TAMS was administered in drinking water (604 mg·kg-1·day-1). Mechanical allodynia in the lower abdomen was assessed with von Frey filaments using the up-down method. Forced swim test (FST) and sucrose preference test (SPT) were used to measure depressive-like behaviors. Novel object recognition test (NORT) was used to detect short-term memory function. Concentrations of Mg2+ in serum and cerebrospinal fluid (CSF) were measured by calmagite chronometry. Western blot and immunofluorescence staining measured the expression of tumor necrosis factor-α/nuclear factor-κB (TNF-α/NF-κB), interleukin-1ß (IL-1ß), and N-methyl-D-aspartate receptor type 2B subunit (NR2B) of the N-methyl-D-aspartate receptor in the L6-S1 spinal dorsal horn (SDH) and hippocampus. RESULTS: Free Mg2+ was reduced in the serum and CSF of the CYP-induced cystitis rats on days 8, 12, and 20 after the first CYP injection. Magnesium deficiency in the serum and CSF correlated with the mechanical withdrawal threshold, depressive-like behaviors, and short-term memory deficits (STMD). Oral application of L-TAMS prevented magnesium deficiency and attenuated mechanical allodynia (n = 14) and normalized depressive-like behaviors (n = 10) and STMD (n = 10). The upregulation of TNF-α/NF-κB signaling and IL-1ß in the L6-S1 SDH or hippocampus was reversed by L-TAMS. The change in NR2B expression in the SDH and hippocampus in the cystitis model was normalized by L-TAMS. CONCLUSIONS: Normalization of magnesium deficiency by L-TAMS attenuated mechanical allodynia, depressive-like behaviors, and STMD in the CYP-induced cystitis model via inhibition of TNF-α/NF-κВ signaling and normalization of NR2B expression. Our study provides evidence that L-TAMS may have therapeutic value for treating pain and comorbid depression or memory deficits in BPS/IC patients.

Effect of teduglutide on restoring oral autonomy for magnesium in two patients with short bowel.

It is not known whether Teduglutide can allow patients with Short bowel syndrome, previously dependent on continuous or periodic intravenous (IV) magnesium, to attain oral autonomy with or without supplementation. Here, we report on two patients previously dependent on continuous or intermittently administered IV magnesium to achieve autonomy from IV, one with and one without oral supplementation that was previously ineffective in both patients.

Dietary magnesium deficiency impairs hippocampus-dependent memories without changes in the spine density and morphology of hippocampal neurons in mice.

Magnesium (Mg2+) is an essential mineral for maintaining biological functions. One major action of Mg2+ in the brain is modulating the voltage-dependent blockade of N-methyl-d-aspartate type glutamate receptors, thereby controlling their opening, which is crucial for synaptic plasticity. Therefore, Mg2+ has been shown to play critical roles in learning and memory, and synaptic plasticity. However, the effects of dietary Mg2+ deficiency (MgD) on learning and memory and the morphology of neurons contributing to memory performance have not been examined in depth. Here, we show that MgD impairs hippocampus-dependent memories in mice. Mice fed an MgD diet showed deficits in hippocampus-dependent contextual fear, spatial and social recognition memories, although they showed normal amygdala- and insular cortex-dependent conditioned taste aversion memory, locomotor activity, and emotional behaviors such as anxiety-related and social behaviors. However, MgD mice showed normal spine density and morphology of hippocampal neurons. These findings suggest that MgD impairs hippocampus-dependent memory without affecting the morphology of hippocampal neurons.

Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial.

Background: Previous in vitro and in vivo studies indicate that enzymes that synthesize and metabolize vitamin D are magnesium dependent. Recent observational studies found that magnesium intake significantly interacted with vitamin D in relation to vitamin D status and risk of mortality. According to NHANES, 79% of US adults do not meet their Recommended Dietary Allowance of magnesium. Objectives: The aim of this study was to test the hypothesis that magnesium supplementation differentially affects vitamin D metabolism dependent on baseline 25-hydroxyvitamin D [25(OH)D] concentration. Methods: The study included 180 participants aged 40-85 y and is a National Cancer Institute independently funded ancillary study, nested within the Personalized Prevention of Colorectal Cancer Trial (PPCCT), which enrolled 250 participants. The PPCCT is a double-blind 2 × 2 factorial randomized controlled trial conducted in the Vanderbilt University Medical Center. Doses for both magnesium and placebo were customized based on baseline dietary intakes. Subjects were randomly assigned to treatments using a permuted-block randomization algorithm. Changes in plasma 25-hydroxyvitamin D3 [25(OH)D3], 25-hydroxyvitamin D2 [25(OH)D2], 1,25-dihydroxyvitamin D3, 1,25-dihydroxyvitamin D2, and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] were measured by liquid chromatography-mass spectrometry. Results: The relations between magnesium treatment and plasma concentrations of 25(OH)D3, 25(OH)D2, and 24,25(OH)2D3 were significantly different dependent on the baseline concentrations of 25(OH)D, and significant interactions persisted after Bonferroni corrections. Magnesium supplementation increased the 25(OH)D3 concentration when baseline 25(OH)D concentrations were close to 30 ng/mL, but decreased it when baseline 25(OH)D was higher (from ∼30 to 50 ng/mL). Magnesium treatment significantly affected 24,25(OH)2D3 concentration when baseline 25(OH)D concentration was 50 ng/mL but not 30 ng/mL. On the other hand, magnesium treatment increased 25(OH)D2 as baseline 25(OH)D increased. Conclusion: Our findings suggest that optimal magnesium status may be important for optimizing 25(OH)D status. This trial was registered at clinicaltrials.gov as NCT03265483.

El síndrome de realimentación. Importancia del fósforo / The refeeding syndrome. Importance of phosphorus

El síndrome de realimentación es una enfermedad compleja que ocurre cuando se inicia el soporte nutricional después de un periodo de ayuno. La característica principal es la hipofosfatemia, sin embargo, también son comunes otras alteraciones bioquímicas como la hipomagnesemia, el déficit de tiamina y las alteraciones hídrico-electrolíticas. Su incidencia es desconocida, ya que no existe una definición universalmente aceptada, pero con frecuencia está infradiagnosticado. El síndrome de realimentación es un trastorno potencialmente fatal pero prevenible. Identificar a los pacientes en riesgo es crucial para mejorar su manejo. Si se diagnostica existen unas guías (NICE 2006) para orientar su tratamiento (pero basadas en un bajo grado de evidencia). Los objetivos de esta revisión son: destacar la importancia de este problema en pacientes desnutridos, discutir su fisiopatología y características clínicas y dar una serie de recomendaciones finales para disminuir el riesgo de desarrollarlo y facilitar su tratamiento

Refeeding syndrome (RS) is a complex disease that occurs when nutritional support is initiated after a period of starvation. The hallmark feature is the hypophosphataemia, however other biochemical abnormalities like hypokalaemia, hypomagnesaemia, thiamine deficiency and disorder of sodium and fluid balance are common. The incidence of RS is unknown as no universally accepted definition exists, but it is frequently underdiagnosed. RS is a potentially fatal, but preventable, disorder. The identification of patients at risk is crucial to improve their management. If RS is diagnosed, there is one guideline (NICE 2006) in place to help its treatment (but it is based on low quality of evidence). The aims of this review are: highlight the importance of this problem in malnourished patients, discuss the pathophysiology and clinical characteristics, with a final series of recommendations to reduce the risk of the syndrome and facilitate the treatment

Dietary Magnesium and Chronic Disease.

Although official magnesium (Mg) dietary reference intakes are open to question, a significant number of adults likely have intakes that are in the range of 50%-99% of the requirement. This moderate or marginal (subclinical) deficient Mg intake generally is asymptomatic. Animal studies, however, indicate that moderate or subclinical Mg deficiency primes phagocytic cells for the release of proinflammatory cytokines leading to chronic inflammatory and oxidative stress. Human studies have found that dietary Mg is inversely related to serum or plasma C-reactive protein (CRP). Individuals with apparently deficient Mg intakes have an increased likelihood of serum or plasma CRP ≥3.0 mg/L, considered an indicator of chronic inflammatory stress that increases the risk for chronic disease. In addition, elevated serum or plasma CRP in individuals with chronic disease is decreased by Mg supplementation, which suggests that Mg decreases the risk for chronic disease. The importance of dietary Mg intake on the risk for chronic disease through affecting inflammatory and oxidative stress is supported by numerous meta-analyses and systematic reviews that have found dietary Mg is inversely associated with chronic diseases such hypertension, ischemic heart disease, stroke, metabolic syndrome, diabetes, and colorectal cancer.

Magnesium and Blood Pressure: A Physiology-Based Approach.

Hypertension is an important public health challenge because of its high prevalence and strong association with cardiovascular disease and premature death. Hypertension is a major cause of CKD, is present in more than 80% of CKD patients, and contributes to CKD progression. Risk factors for hypertension include, but are not limited to, age, race, family history, obesity, physical inactivity, tobacco use, and inadequate intake of minerals such as calcium, potassium, and magnesium. Magnesium is the second most abundant intracellular cation in the human body and plays an important role in insulin and adenosine triphosphate metabolism. Low dietary magnesium intake has been associated with an increased risk of developing hypertension in prospective cohort studies. Moreover, clinical trials suggest that magnesium supplementation has blood pressure-lowering effects. In addition, emerging data reveal potential mechanisms by which magnesium may influence blood pressure. Here, we will review these mechanisms, using a physiology-based approach, focusing on the effects of magnesium on total peripheral resistance and cardiac output.

Magnesium and Cardiovascular Disease.

Magnesium is the most abundant intracellular divalent cation and essential for maintaining normal cellular physiology and metabolism, acting as a cofactor of numerous enzymes, regulating ion channels and energy generation. In the heart, magnesium plays a key role in modulating neuronal excitation, intracardiac conduction, and myocardial contraction by regulating a number of ion transporters, including potassium and calcium channels. Magnesium also has a role in regulating vascular tone, atherogenesis and thrombosis, vascular calcification, and proliferation and migration of endothelial and vascular smooth muscle cells. As such, magnesium potentially has a major influence on the pathogenesis of cardiovascular disease. As the kidney is a major regulator of magnesium homeostasis, kidney disorders can potentially lead to both magnesium depletion and overload, and as such increase the risk of cardiovascular disease. Observational data have shown an association between low serum magnesium concentrations or magnesium intake and increased atherosclerosis, coronary artery disease, arrhythmias, and heart failure. However, major trials of supplementation with magnesium have reported inconsistent benefits and also raised potential adverse effects of magnesium overload. As such, there is currently no firm recommendation for routine magnesium supplementation except when hypomagnesemia has been proven or suspected as a cause for cardiac arrhythmias.

Magnesium as a Calcification Inhibitor.

Vascular calcification (VC) is associated with elevated cardiovascular mortality rates in patients with CKD. Recent clinical studies of patients with advanced CKD have observed an association between low serum magnesium (Mg) levels on one hand and elevated VC and cardiovascular mortality on the other. These findings have stimulated interest in understanding Mg's impact on CKD in general and the associated VC in particular. In vitro and preclinical in vivo data indicate that Mg has the potential to protect vascular smooth muscle cells against calcification via several different molecular mechanisms. Accordingly, data from pilot interventional studies in the clinic suggest that oral Mg supplementation reduces VC in patients with CKD. The present review provides an overview of our current understanding of the impact of Mg on the development of VC in patients with CKD.

The Role of Elements in Anxiety.

Elements (bioelements) are necessary factors required for the physiological function of organisms. They are critically involved in fundamental processes of life. Extra- and intracellular message and metabolic pathway factors as well as structural components include one or many elements in their functional structure. Recent years have seen an intensification in terms of knowledge gained about the roles of elements in anxiety disorders. In this chapter we present a review of the most important current data concerning the involvement of zinc, magnesium, copper, lithium, iron, and manganese, and their deficiency, in the pathophysiology and treatment of anxiety.

Role of Magnesium in Oxidative Stress in Individuals with Obesity.

Adipose tissue is considered an endocrine organ that promotes excessive production of reactive oxygen species when in excess, thus contributing to lipid peroxidation. Magnesium deficiency contributes to the development of oxidative stress in obese individuals, as this mineral plays a role as an antioxidant, participates as a cofactor of several enzymes, maintains cell membrane stability and mitigates the effects of oxidative stress. The objective of this review is to bring together updated information on the participation of magnesium in the oxidative stress present in obesity. We conducted a search of articles published in the PubMed, SciELO and LILACS databases, using the keywords 'magnesium', 'oxidative stress', 'malondialdehyde', 'superoxide dismutase', 'glutathione peroxidase', 'reactive oxygen species', 'inflammation' and 'obesity'. The studies show that obese subjects have low serum concentrations of magnesium, as well as high concentrations of oxidative stress marker in these individuals. Furthermore, it is evident that the adequate intake of magnesium contributes to its appropriate homeostasis in the body. Thus, this review of current research can help define the need for intervention with supplementation of this mineral for the prevention and treatment of disorders associated with this chronic disease.

Dietary intake of calcium and magnesium and the metabolic syndrome in the National Health and Nutrition Examination (NHANES) 2001-2010 data.

Higher dietary intakes of Mg and Ca, individually, have been associated with a decreased risk for the metabolic syndrome (MetSyn). Experimental studies suggest that a higher intra-cellular ratio of Ca:Mg, which may be induced by a diet high in Ca and low in Mg, may lead to hypertension and insulin resistance. However, no previous epidemiological studies have examined the effects of the combined intake of Mg and Ca on MetSyn. Thus, we evaluated the association between dietary intakes of Ca and Mg (using 24-h recalls), independently and in combination, and MetSyn in the National Health and Nutrition Examination Study 2001-2010 data, which included 9148 adults (4549 men and 4599 women), with complete information on relevant nutrient, demographic, anthropometric and biomarker variables. We found an inverse association between the highest (>355 mg/d) v. the lowest (<197 mg/d) quartile of Mg and MetSyn (OR 0.70; 95% CI 0.57, 0.86). Women who met the RDA for both Mg (310-320 mg/d) and Ca (1000-1200 mg/d) had the greatest reduced odds of MetSyn (OR 0.59; 95% CI 0.45, 0.76). In men, meeting the RDA for Mg (400-420 mg/d) and Ca (1000-1200 mg/d), individually or in combination, was not associated with MetSyn; however, men with intakes in the highest quartile for Mg (≥ 386 mg/d) and Ca (≥ 1224 mg/d) had a lower odds of MetSyn (OR 0.74; 95% CI 0.59, 0.93). Our results suggest that women who meet the RDA for Mg and Ca have a reduced odds of MetSyn but men may require Ca levels higher than the RDA to be protected against MetSyn.

Familial Hypomagnesemia with Secondary Hypocalcemia Mimicking Neurodegenerative Disorder.

BACKGROUND: Familial hypomagnesemia with secondary hypocalcemia is a genetic disorder of magnesium metabolism that presents with refractory seizures in infancy. CASE CHARACTERISTICS: We herein report an infant with familial hypomagnesemia who presented as medically-refractory seizures and had cerebral atrophy on neuroimaging. Interestingly he had lost previous two siblings because of lack of correct diagnosis. INTERVENTION: Child was given oral magnesium supplementation and the seizures got controlled. MESSAGE: Familial hypomagnesemia should be considered in any child with recurrent or refractory hypocalcemic seizures.

Hypomagnesaemia in kidney transplantation.

In the era of calcineurin inhibitors, hypomagnesaemia is a very common finding in kidney transplant recipients. Especially the first weeks after transplantation it is the rule rather than the exception. Hypomagnesaemia or low magnesium intake have been associated with a higher mortality or more cardiovascular events in the general population, but this association has never been explored in kidney transplant recipients, despite their increased cardiovascular risk. Kidney transplant recipients with pre- or post-transplant hypomagnesaemia seem to have an aberrant glucose metabolism and develop diabetes mellitus more frequently. Moreover, observations from alternate study populations, animal experiments or in vitro studies suggest a possible role of magnesium deficiency in graft dysfunction, bone metabolism and transplant immunology. Future observational and especially interventional studies should further define whether and to what extent we should make effort to correct this electrolyte disturbance in transplant recipients. Considering the mechanism of renal magnesium wasting, normalizing the serum magnesium concentration by oral supplementation alone might turn out to be cumbersome in kidney transplant recipients.

Comparative angioprotective effects of magnesium compounds.

Magnesium (Mg) deficiency is implicated in the development of numerous disorders of the cardiovascular system. Moreover, the data regarding the efficacy of different magnesium compounds in the correction of impaired functions due to low magnesium intake are often fragmentary and inconsistent. The aim of this study was to compare the effects of the most bioavailable Mg compounds (Mg l-aspartate, Mg N-acetyltaurate, Mg chloride, Mg sulphate and Mg oxybutyrate) on systemic inflammation and endothelial dysfunction in rats fed a low Mg diet for 74 days. A low Mg diet decreased the Mg concentration in the plasma and erythrocytes, which was accompanied by a reduced concentration of eNOs and increased levels of endothelin-1 level in the serum and impaired endothelium-dependent vasodilatation. These effects increased the concentration of proinflammatory molecules, such as VCAM-1, TNF-α, IL-6 and CRP, indicating the development of systemic inflammation and endothelial dysfunction. The increased total NO level, which estimated from the sum of the nitrate and nitrite concentrations in the serum, may also be considered to be a proinflammatory marker. Two weeks of Mg supplementation partially or fully normalised the ability of the vascular wall to effect adequate endothelium-dependent vasodilatation and reversed the levels of most endothelial dysfunction and inflammatory markers (except CRP) to the mean values of the control group. Mg sulphate had the smallest effect on the endothelin-1, TNF-α and VCAM-1 levels. Mg N-acetyltaurate was significantly more effective in restoring the level of eNOS compared to all other studied compounds, except for Mg oxybutyrate. Taken together, the present findings demonstrate that all Mg compounds equally alleviate endothelial dysfunction and inflammation caused by Mg deficiency. Mg sulphate tended to be the least effective compound.

Serum magnesium, phosphorus, and calcium are associated with risk of incident heart failure: the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Heart failure (HF) is a major source of morbidity and mortality, particularly among the elderly. Magnesium, phosphorus, and calcium are micronutrients traditionally viewed in relation to bone health or chronic kidney disease. However, they also may be associated with risk of cardiovascular disease through a broad range of physiologic roles. OBJECTIVE: With the use of data from the Atherosclerosis Risk in Communities (ARIC) cohort, we tested the hypotheses that the incidence of HF is greater among individuals with low serum magnesium and those with high serum phosphorus and calcium. DESIGN: A total of 14,709 African Americans (27%) and whites from the ARIC cohort [aged 45-64 y at baseline (1987-1989)] were observed through 2009. Proportional hazards regression was used to explore associations between biomarkers and incident HF. Serum calcium was corrected for serum albumin. Models were adjusted for demographics, behaviors, and physiologic characteristics. RESULTS: A total of 2250 incident HF events accrued over a median follow-up of 20.6 y. Participants in the lowest (≤1.4 mEq/L) compared with the highest (≥1.8 mEq/L) category of magnesium were at greater HF risk (HR: 1.71; 95% CI: 1.46, 1.99). For phosphorus, there appeared to be a threshold whereby only those in the highest quintile were at greater HF risk [HR(Q5 vs Q1): 1.34; 95% CI: 1.16, 1.54]. Higher concentrations of calcium were also associated with greater risk of HF [HR(Q5 vs Q1): 1.24; 95% CI: 1.07, 1.43]. Results were not modified by race, sex, or kidney function and were similar when incident coronary heart disease was included as a time-varying covariate. CONCLUSIONS: Low serum magnesium and high serum phosphorus and calcium were independently associated with greater risk of incident HF in this population-based cohort. Whether these biomarkers will be useful candidates for HF risk prediction or targets for prevention remains to be seen.