Magnesium Limitation Leads to Transcriptional Down-Tuning of Auxin Synthesis, Transport, and Signaling in the Tomato Root

Magnesium (Mg) deficiency is becoming a widespread limiting factor for crop production. How crops adapt to Mg limitation remains largely unclear at the molecular level. Using hydroponic-cultured tomato seedlings, we found that total Mg2+ content significantly decreased by ∼80% under Mg limitation while K+ and Ca2+ concentrations increased. Phylogenetic analysis suggested that Mg transporters (MRS2/MGTs) constitute a previously uncharacterized 3-clade tree in planta with two rounds of asymmetric duplications, providing evolutionary evidence for further molecular investigation. In adaptation to internal Mg deficiency, the expression of six representative MGTs (two in the shoot and four in the root) was up-regulated in Mg-deficient plants. Contradictory to the transcriptional elevation of most of MGTs, Mg limitation resulted in the ∼50% smaller root system. Auxin concentrations particularly decreased by ∼23% in the Mg-deficient root, despite the enhanced accumulation of gibberellin, cytokinin, and ABA. In accordance with such auxin reduction was overall transcriptional down-regulation of thirteen genes controlling auxin biosynthesis (TAR/YUCs), transport (LAXs, PINs), and signaling (IAAs, ARFs). Together, systemic down-tuning of gene expression in the auxin signaling pathway under Mg limitation preconditions a smaller tomato root system, expectedly stimulating MGT transcription for Mg uptake or translocation.

Increased Provision of Bioavailable Mg through Vegetables Could Significantly Reduce the Growing Health and Economic Burden Caused by Mg Malnutrition

Magnesium (Mg) is an essential mineral nutrient for human health and its deficiency associated with many diseases, including stroke, heart failure, and type 2 diabetes. Vegetables are an important source of dietary Mg for humans. In this study, we quantified vegetable Mg content by a global meat analysis, analyzed human health, and economic impact caused by Mg deficiency. Results revealed that vegetable Mg content showed a large variation with an average value of 19.3 mg 100 g−1 FW. Variation in per capita vegetable-Mg supply in different continents is largely ascribed to continental difference in the amount and the type of vegetables produced. The health and economic loss attributed to Mg deficiency are estimated to be 1.91 million disability-adjusted life years (DALYs) and 15.8 billion dollars (0.14% of GDP), respectively. A scenario analysis indicated that the increasing vegetable production (increased by 8.9% and 20.7% relative to 2017 in 2030 and 2050) and vegetable Mg content (increased by 22% through biofortification) could significantly reduce DALYs (1.24 million years) and economic burden (0.09% of GDP). This study could guide a major re-balance of production practices, species cultivated, and Mg biofortification to provide sufficient vegetable Mg for better human Mg nutrition.

Abstract P310: Mitochondrial Electron Transport Chain Dysfunction Is Associated With Mg Deficiency Induced Diastolic Dysfunction

Introduction: The prevalence of heart failure with preserved ejection fraction (HFpEF) is increasing, although there is no specific treatment for HFpEF yet because of poor understanding of the underlying pathophysiology. Our previous studies show that hypomagnesemia contributes to diastolic dysfunction and HFpEF by regulation of mitochondrial function and that Mg supplementation improves diastolic function. In this study, we investigated how mitochondria were affected by Mg deficiency. Methods: C57BL/6J mice were fed with a low-Mg diet (HypoMg mice, 15-30 mg/kg Mg) or a normal Mg diet (control mice, 600 mg/kg Mg) for 6 weeks. Mg repletion was achieved by feeding HypoMg mice with normal diet for another 6 weeks. Results: HypoMg mice showed significantly decreased serum Mg (0.38±0.03 mM vs. 1.14±0.03 mM of control, P<0.0001), diastolic dysfunction (E/e’=21.1±1.1 vs. 15.4±0.4 of control, P=0.011), increased mitochondrial ROS (1.9±0.2-fold of control, P<0.0001), decreased total mitochondrial Mg content (3.6±1.8 vs. 18.3±4.7 μM total Mg/mg mitochondrial protein of control, P=0.019), decreased ATP production in hearts (1.2±0.2 vs. 2.7±0.2 μmol/g heart tissue of control, P=0.0002), decreased complex I activity (ΔOCR NADH-rotenone =0.27±0.10 vs. 1.02±0.04 of control, P=0.0004 measured with Seahorse), and decreased complex I protein levels (50.2% reduction compared with control mice, P=0.009). Mg repletion reversed all these changes. Conclusion: HypoMg-induced diastolic dysfunction likely results from HypoMg-induced electron transport chain dysfunction resulting from a decrease in mitochondrial Mg content. Mg repletion reverses these changes, reinforcing the known correlation of increased Mg intake and reduced heart failure symptoms. In deficiency states, Mg supplementation may represent a novel treatment for diastolic heart failure by improving mitochondrial function.

Serum Magnesium Levels in Patients with Obstructive Sleep Apnoea: A Systematic Review and Meta-Analysis

Purpose: Obstructive sleep apnoea (OSA) affects patients&rsquo; quality of life and health. Magnesium (Mg) is an essential mineral and a potent antioxidant. Mg deficiency can worsen oxidative stress caused by sleep deprivation or disorders. The impact of OSA on serum Mg levels and its health consequences remain unclear. Methods: This study systematically reviewed clinical studies investigating the serum Mg levels of OSA patients and the potential relationships with other biomarkers.Results: Six articles were included for qualitative synthesis; five were used in quantitative analysis. Two out of four studies that compared OSA patients to healthy controls found them to have significantly lower serum Mg levels. Our meta-analysis with three studies shows that patients with OSA had significantly lower serum Mg with an effect size of -1.22 (95% CI: -2.24, -0.21). However, the mean serum Mg level of OSA patients (n=251) pooled from five studies (1.90 mg/dL, 95% CI: 1.77, 2.04) does not differ significantly from the normal range. OSA severity appears to affect serum Mg negatively. Serum Mg levels generally improve after treatment, coincide with the improvement of OSA severity. Low serum Mg levels correlate with worsening of cardiovascular risk biomarkers of C-reactive protein, ischaemia-modified albumin, and carotid intima-media thickness. The serum Mg levels also potentially correlate with biomarkers for lipid profile, glucose metabolism, calcium and heavy metals. Conclusions: Sleep deprivation appears to deplete Mg levels of OSA patients, making them at risk of Mg deficiency, which potentially increases systemic inflammation and the risk of cardiovascular and metabolic diseases.

The possible correlation between magnesium deficiency and SARS-CoV-2 infection

Magnesium (Mg) is an essential electrolyte for living organisms. It is the fourth most abundant mineral in the body. Although Mg is usually found in hard water and high-fiber diets, wide use of soft water and refined flour impose people at risk of Mg deficiency. Imbalances in Mg status and Mg deficiency may result in a variety of complications associated with the immune, cardiovascular, urinary, nervous, and respiratory systems. Because of the important roles of magnesium in the prevention and treatment of many diseases, several studies are focusing on the correlation between Mg status and Coronavirus disease 2019 (COVID-19). The present study reviewed several types of research to indicate the importance of monitoring of Mg status as well as the possible role of Mg supplementation for supportive treatment in COVID-19 patients. The results indicated that Mg deficiency could be a risk factor for multi-organ dysfunction in COVID-19 infection. Mg supplementation improves functions of the immune, cardiovascular, nervous, urinary, and respiratory systems through different mechanisms. Suppression of cytokine storm, bronchodilation, antithrombotic function, a decrease of arterial blood pressure, preventing electrolyte imbalance, increase stress resistance are some of the related mechanisms. These findings may provide a reference regarding the possible beneficial effects of the Mg supplement as an inexpensive, safe, and easily available drug for supportive treatment in COVID-19 patients.

Magnesium Deficiency Causes a Reversible, Metabolic, Diastolic Cardiomyopathy

Background Dietary Mg intake is associated with a decreased risk of developing heart failure, whereas low circulating Mg level is associated with increased cardiovascular mortality. We investigated whether Mg deficiency alone could cause cardiomyopathy. Methods and Results C57BL/6J mice were fed with a low Mg (low‐Mg, 15–30 mg/kg Mg) or a normal Mg (nl‐Mg, 600 mg/kg Mg) diet for 6 weeks. To test reversibility, half of the low‐Mg mice were fed then with nl‐Mg diet for another 6 weeks. Low‐Mg diet significantly decreased mouse serum Mg (0.38±0.03 versus 1.14±0.03 mmol/L for nl‐Mg; P <0.0001) with a reciprocal increase in serum Ca, K, and Na. Low‐Mg mice exhibited impaired cardiac relaxation (ratio between mitral peak early filling velocity E and longitudinal tissue velocity of the mitral anterior annulus e, 21.1±1.1 versus 15.4±0.4 for nl‐Mg; P =0.011). Cellular ATP was decreased significantly in low‐Mg hearts. The changes were accompanied by mitochondrial dysfunction with mitochondrial reactive oxygen species overproduction and membrane depolarization. cMyBPC (cardiac myosin‐binding protein C) was S ‐glutathionylated in low‐Mg mouse hearts. All these changes were normalized with Mg repletion. In vivo (2‐(2,2,6,6‐tetramethylpiperidin‐1‐oxyl‐4‐ylamino)‐2‐oxoethyl)triphenylphosphonium chloride treatment during low‐Mg diet improved cardiac relaxation, increased ATP levels, and reduced S ‐glutathionylated cMyBPC. Conclusions Mg deficiency caused a reversible diastolic cardiomyopathy associated with mitochondrial dysfunction and oxidative modification of cMyBPC. In deficiency states, Mg supplementation may represent a novel treatment for diastolic heart failure.

Differences in morphological and physiological features of citrus seedlings are related to Mg transport from the parent to branch organs

Background In this study, we aimed to test the hypothesis that magnesium (Mg) remobilization in citrus plants is regulated by Mg supply and contributes to differences in the growth of the parent and branch organs. Citrus seedlings were grown in sand under Mg deficient (0 mmol Mg2+ L−1, -Mg) and Mg sufficient (2 mmol Mg2+ L−1, + Mg) conditions. The effects on biomass, Mg uptake and transport, gas exchange and chlorophyll fluorescence, as well as related morphological and physiological parameters were evaluated in different organs. Results Mg deficiency significantly decreased plant biomass, with a decrease in total plant biomass of 39.6%, and a greater than twofold decrease in the branch organs compared with that of the parent organs. Reduced photosynthesis capacity was caused by a decreased in pigment levels and photosynthetic electron transport chain disruption, thus affecting non-structural carbohydrate accumulation and plant growth. However, the adaptive responses of branch leaves to Mg deficiency were greater than those in parent leaves. Mg deficiency inhibited plant Mg uptake but enhanced Mg remobilization from parent to branch organs, thus changing related growth variables and physiological parameters, including protein synthesis and antioxidant enzyme activity. Moreover, in the principal components analysis, these variations were highly clustered in both the upper and lower parent leaves, but highly separated in branch leaves under the different Mg conditions. Conclusions Mg deficiency inhibits the growth of the parent and branch organs of citrus plants, with high Mg mobility contributing to differences in physiological metabolism. These findings suggest that Mg management should be optimized for sustainable citrus production.

Extracellular and Intracellular Magnesium Deficiency Found in Pregnant Women with Preeclampsia and Gestational Diabetes Is Associated with Overexpression of Notch Proteins, Cytokines, p53, NF-kB and Proto-Oncogenes: Potential Importance in Growth Retardation, Stillbirths, Fetal Mutations and Increased Cardiovascular Risks and Stroke with Advancing Age in Pregnant Women

In 1983, three of us reported in “Science” that umbilical-placental arteries and veins, obtained from normal pregnant women at term delivery, when exposed in vitro to low concentrations of Mg2+ went into vasospasm; the lower the Mg2+, the greater the contractile force developed. These blood vessels also demonstrated amplified contractile force development when challenged with circulating amines and peptides (e.g., norepinephrine, 5-HT, angiotensin II, etc.). We suggested that severe Mg deficiency during pregnancy could in part be responsible for spontaneous abortions, loss of fetuses, stillbirths, and developmental alterations in infants. Using short-term dietary Mg deficient animals, we have noted a great many molecular and biochemical alterations in ventricular, atrial and somatic vascular smooth muscle alterations including DNA methylation and histone changes leading us to speculate that Mg deficiency may represent a genotoxin promoting mutations and causing epigenetic changes. Over the last 35 years, we have new data on severely preeclamptic and gestational diabetic pregnant women that gives credence to our original hypothesis and demonstrates that recently- discovered developmental proteins, originally found 100 years ago in Drosophila fruit flies termed the “Notch pathway”, due to effects on its wings, appears to be important in development of the umbilical-placental blood vessels in pregnant women. Along with the developmental molecule, p53, these Notch proteins clearly alter the behavior of the umbilical-placental vessels. We believe these new findings probably help to explain many of the genetic-toxicity effects seen in women later in life who develop strokes and cardiovascular diseases. Notch alterations could also play an important role in babies born with cardiac defects.

The Contribution of Dietary Magnesium in Farm Animals and Human Nutrition

Magnesium (Mg) is a mineral that plays an essential role as cofactor of more than 300 enzymes. Mg in farm animals’ and human nutrition is recommended to avoid Mg deficiency, ensure adequate growth and health maintenance. Mg supplementation above the estimated minimum requirements is the best practice to improve farm animals’ performances (fertility and yield) and food products’ quality, since the performance of farm animals has grown in recent decades. Mg supplementation in pigs increases meat quality and sows’ fertility; in poultry, it helps to avoid deficiency-related health conditions and to improve meat quality and egg production by laying hens; in dairy cows, it serves to avoid grass tetany and milk fever, two conditions related to hypomagnesaemia, and to support their growth. Thus, Mg supplementation increases food products’ quality and prevents Mg deficiency in farm animals, ensuring an adequate Mg content in animal-source food. These latter are excellent Mg sources in human diets. Sub-optimal Mg intake by humans has several implications in bone development, muscle function, and health maintenance. This review summarizes the main knowledge about Mg in farm animals and in human nutrition.