Magnesium is important to health – March 2021

Magnesium: Biochemistry, Nutrition, Detection, and Social Impact of Diseases Linked to Its Deficiency
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Magnesium: Biochemistry, Nutrition, Detection, and Social Impact of Diseases Linked to Its Deficiency

Nutrients 2021, 13(4), 1136; https://doi.org/10.3390/nu13041136
Diana Fiorentini , Concettina Cappadone +, Giovanna Farruggia Correspondence: giovanna.farruggia at unibo.it and Cecilia Prata 0
Department of Pharmacy and Biotechnology, Alma Mater Studiorum—University of Bologna,
40126 Bologna, Italy; diana.fiorentini at unibo.it (D.F.); concettina.cappadone at unibo.it (C.C.); cecilia.prata at unibo.it (C.P.)

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Mg Recommended intake

Mg Deficiency and Toxiocity

Magnesium plays an important role in many physiological functions. Habitually low intakes of magnesium and in general the deficiency of this micronutrient induce changes in biochemical pathways that can increase the risk of illness and, in particular, chronic degenerative diseases. The assessment of magnesium status is consequently of great importance, however, its evaluation is difficult. The measurement of serum magnesium concentration is the most commonly used and readily available method for assessing magnesium status, even if serum levels have no reliable correlation with total body magnesium levels or concentrations in specific tissues. Therefore, this review offers an overview of recent insights into magnesium from multiple perspectives. Starting from a biochemical point of view, it aims at highlighting the risk due to insufficient uptake (frequently due to the low content of magnesium in the modern western diet), at suggesting strategies to reach the recommended dietary reference values, and at focusing on the importance of detecting physiological or pathological levels of magnesium in various body districts, in order to counteract the social impact of diseases linked to magnesium deficiency.

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Diabetes Mellitus

It is well known that magnesium acts as an insulin sensitizer by inducing autophosphorylation of insulin receptors and regulating tyrosine kinase activity on these receptors [63,153,294,295]. In addition, magnesium may directly affect the activity of the glucose transporter 4 (GLUT4) and help to regulate glucose uptake into the cell [21]. Consequently, diets with higher amounts of magnesium are related to a significantly lower risk of diabetes [296]. Several studies report that a reduced intracellular magnesium level can lead to increased insulin resistance [93,297]. The incidence of hypomagnesemia in patients with type 2 diabetes is wide, ranging from 13.5-47.7% [298].
A 100 mg/day increase in total magnesium intake is reported to decrease the risk of diabetes by a statistically significant 15% [299]. Moreover, a meta-analysis of eight prospective cohort studies, involving 271,869 men and women over 4 to 18 years, showed a significant inverse association between magnesium intake from food and risk of type 2 diabetes; the relative risk reduction was 23% when the highest to lowest intakes were compared [300]. According to this, Dong et al. reported a meta-analysis of prospective cohort studies of magnesium intake and risk of type 2 diabetes included 13 studies with a total of 536,318 participants and 24,516 cases of diabetes. It was demonstrated that the magnesium intake is inversely associated with risk of contracting the disease in a dose-response manner [301]. The same conclusion was drawn from a prospective study on high risk population, involving 2582 community-dwelling participants followed up for 7 years [302]. Moreover, in a randomized controlled trial involving 116 adults with prediabetes and hypomagnesemia, the reduction of plasma glucose levels and the improvement of the glycemic status by oral magnesium supplementation were also demonstrated [303]. Additionally, a very recent trial sequential analysis confirmed that magnesium intake has an inverse dose-response association with type 2 diabetes incidence, and magnesium supplementation appears to be advisable in terms of glucose parameters in high-risk individuals [304].
Interestingly, some studies documented that hypomagnesemia could have an impact on many dysfunctions indicated in the pathophysiology of diabetes, such as diabetic nephropathy, poor lipid profile, and high risk of atherosclerosis, even indicating hypomagnesemia as a marker [103,305].

Osteoporosis

The most common bone disease in humans is osteoporosis, which represents a major public health problem and is more common in Caucasians, women, and older people [306].
It is well accepted that magnesium deficiency might represent a risk factor for osteoporosis [80,91]. Both dietary intake and supplementation of magnesium were investigated in relation to osteoporosis and risk of fractures in humans. Early works examining the effect of oral supplementation of magnesium in postmenopausal women evidenced a significant increase in BMD (bone mineral density), but the little number of enrolled subjects limited the conclusions that could be drawn [307,308]. According to one short-term study, 290 mg/day of elemental magnesium for 30 days in 20 postmenopausal women with osteoporosis counteract bone turnover and thus decreased bone loss compared with placebo [309]. Other investigations found a positive association between dietary magnesium, BMD, and lower risk of osteoporosis, suggesting that increasing magnesium intakes from food or supplements might increase BMD in postmenopausal and elderly patients [310,311].
A recent meta-analysis evidenced a positive slightly significant correlation between magnesium intake and BMD only for the femoral neck and total hip, but not for the lumbar spine [312].
Fractures and in particular osteoporotic fractures are widespread causes of disability and morbidity, especially among the aging population, and increase the burden on health systems [306]. The prevention of fractures and the evaluation of putative risk factors could be very important for the public health: serum magnesium, which may have predictive or causal relevance to the risk of fractures, could help to personalize preventive and therapeutic interventions [219]. Although several studies evidenced a positive correlation between BMD and magnesium intake, the relation to fracture outcomes is yet unclear. A prospective cohort study on 73,684 postmenopausal women showed that a lower magnesium intake is linked to decreased bone density in the hip and whole body. However this does not relate to an increase of fracture risks [313]. On the other hand, data from a large perspective study [314] and cross-sectional analysis [315] showed that by satisfying the recommended magnesium intake, the risk of fractures is lower. Accordingly, a strong association between low serum magnesium and increased risk of fractures was reported in a prospective cohort study of 2245 middle-aged Caucasian men over a 25-year period [219].

Cardiovascular Diseases

Increasing evidence from epidemiological studies, randomized controlled trials, and meta-analyses has shown inverse relationship between magnesium intake and cardiovascular disorders (CVD) [316]. Indeed, high magnesium intake is related to lower probability of major CV risk factors (such as hypertension and diabetes), stroke, and total CVD. In addition, a reduced risk of ischemic and coronary heart disease is related to higher levels of circulating magnesium [317].
It is well known that hypertension is an important risk factor for heart disease and stroke. As stated by A. Rosanoff, "Magnesium status has a direct effect upon the relaxation capability of vascular smooth muscle cells and the regulation of the cellular placement of other cations important to blood pressure—cellular sodium: potassium ratio and intracellular calcium. As a result, nutritional magnesium has both direct and indirect impacts on the regulation of blood pressure and therefore on the occurrence of hypertension" [318]. Early studies have shown that a magnesium deficiency could impact blood pressure, leading to hypertension. Oral magnesium supplementation may exert a moderate antihypertensive effect [319]. Afterwards, a meta-analysis of 12 clinical trials found that magnesium supplementation for 8-26 weeks in 545 hypertensive subjects obtained only a slight reduction in diastolic blood pressure with magnesium supplementation, ranging from nearly 243 to 973 mg/day [320]. Next, Kass et al. analyzed 22 studies with 1173 normotensive and hypertensive adults concluding that magnesium supplements for 3-24 weeks reduced both systolic and diastolic blood pressure, albeit to a small extent [321]. Other authors have pooled six prospective cohort studies including 20,119 cases and 180,566 participants. They found a statistically significant inverse association between dietary magnesium and hypertension risk without apparent evidence of heterogeneity between studies. The range of dietary magnesium intake among the included studies was 96-425 mg/day, and the follow-up ranged from 4 to 15 years [322]. Additionally, a meta-analysis on 11 randomized controlled trials counting 543 participants with preclinical or non-communicable diseases who were monitored for a range of 1-6 months, showed that the group supplemented with oral magnesium had a considerably greater decrease in blood pressure. An average reduction of 4.18 mmHg in systolic blood pressure and 2.27 mmHg in diastolic blood pressure was found after magnesium supplementation [323].
Magnesium deficiency reduces cardiac Na-K-ATPase, determining greater levels of sodium and calcium and lower levels of magnesium and potassium in the heart. Consequently, the vasoconstriction in the coronary arteries increases, inducing coronary artery spasms, heart attack, and cardiac arrhythmia [18]. Higher magnesium serum levels were significantly linked to a lower risk of CVD, as shown by a systematic review and metaanalysis of prospective studies, involving 313,041 individuals with 11,995 cardiovascular diseases, 7534 ischemic heart diseases, and 2686 fatal ischemic heart disease. Moreover, higher dietary magnesium intakes (up to approximately 250 mg/day) were correlated with a substantially lower risk of ischemic heart disease caused by a lowered blood supply to the heart muscle. Circulating serum magnesium (per 0.2 mmol/L increment) was associated with a 30% lower risk of CVD and trends toward lesser risks of ischemic heart disease and fatal ischemic heart disease [324]. In a monocentric, controlled, double-blind study, 79 patients with severe chronic heart failure under optimal medical cardiovascular treatment were randomized to receive either magnesium orotate or placebo. The two groups were similar in demographic data, duration of heart failure, and pre- and concomitant treatment. The survival rate was 75.7% compared to 51.6% under placebo, after 1 year of treatment. Clinical symptoms improved in 38.5% of patients under magnesium orotate, whereas they worsened in 56.3% of patients under placebo [325].
Additionally, magnesium has a well-established role in the management of torsade de pointes, a repetitive polymorphous ventricular tachycardia with prolongation of QT interval of the electrocardiogram. The guideline of the American Heart Association and the American College of Cardiology recommends intravenous administration of magnesium and potassium for the prevention and treatment of torsade de pointes, and tachycardia [326,327].
Low magnesium levels can also enhance endothelial cell dysfunction, potentially increasing the risk of atherosclerosis and thrombosis, stimulating a proatherogenic phenotype in endothelial cells [328]. The Atherosclerosis Risk in Communities study evaluated heart disease risk factors and concentrations of serum magnesium in a cohort of 14,232 white and African American men and women aged 45 to 64 years at baseline. Over an average of 12 years of follow-up, individuals with a normal physiologic range of serum magnesium (at least 0.88 mmol/L) had a 38% reduced risk of sudden cardiac death in comparison with individuals with 0.75 mmol/L or less. Nevertheless, dietary magnesium intakes did not show any risk of sudden cardiac death [329].
In an updated meta-analysis involving more than 400,000 adults from different cohorts, who were followed for 5 to 28 years, the summary estimate comparing individuals at the higher versus the lowest categories of dietary magnesium intake demonstrated a protection of 14% against the risk of CVD death. Additional assessment of the subtypes of CVD death indicated that dietary magnesium intake was inversely and significantly associated with a lower risk for heart failure and sudden cardiac death. Further dose-response analysis showed a protection of 25% in women for the increment of 100 mg/day of magnesium intake [322]. Another prospective population study of 7664 adults aged 20 to 75 years without cardiovascular disease verified the protective action of magnesium in this context: it was found that low urinary magnesium excretion levels (an indicator for low dietary magnesium intake) were related to a superior risk of ischemic heart disease over a median follow-up period of 10.5 years [330].

Cancer

Hypomagnesemia is also a common medical problem that contributes to the morbidity of cancer patients. Cancer is the leading cause of death worldwide; over 1.7 million people were diagnosed with cancer and over 600,000 deaths have resulted from this disease in 2018 alone [331,332].
The effects of diet in cancer metabolism are certainly an area of popular interest. A recent review highlights the mechanisms underlying magnesium disturbances due to cancer and/or its treatment [333]. Hypomagnesemia can be due to these physio-pathological mechanisms: (i) decreased intake, (ii) transcellular shift, (iii) gastrointestinal losses, and (iv) kidney losses. Moreover, cancer patients are at risk for opportunistic infections, cardiovascular complications, and are treated with classes of medications that cause or emphasize hypomagnesemia, like platinum-based chemotherapy, anti-EGFR monoclonal antibodies, and human epidermal growth factor receptor-2 target inhibitors (HER2) [334].
Several epidemiologic studies demonstrated that a diet poor in magnesium increases the risk of developing cancer, evidencing its importance in the field of hematology and oncology. Being an enzyme cofactor involved in the DNA repair mechanisms, magnesium plays a major role in maintaining genomic stability and fidelity, modulating cell cycle progression, cell proliferation, differentiation, and apoptosis. Thus, magnesium deficiency could affects these systems, leading to DNA mutations, which may result in tumorigenesis and in both the risk and prognosis of cancers [78,335]. Moreover, a protective effect of magnesium against chemical carcinogenesis has been recently reported [27].
Some studies have focused on the effect of dietary magnesium on breast cancer prognosis, suggesting that higher dietary intake is inversely associated with mortality among breast cancer patients [336]. The effect of magnesium intake on breast cancer risk has been explored, both directly and indirectly via its effect on inflammatory markers C-reactive protein and interleukin-6 [337].
Liu et al. in a recent review evidenced that magnesium supplementation can protect the liver and reduce the morbidity and mortality associated also with liver cancer. Furthermore, the risk of cancer metastasis to the liver increases in cancer patients with magnesium deficiency [338]. According to this, an in vitro study has shown that magnesium canthari- date has an inhibitory effect on human hepatoma SMMC-7721 cell proliferation by blocking the MAPK signaling pathway [339]. Moreover, magnesium administration can increase the expression of protein phosphatase magnesium dependent 1A (PPM1a), blocking TGF-p signaling by dephosphorylating of p-Smad2/3, and thus preventing the transcription of specific genes necessary for hepatocellular cancer growth [340].
The association between magnesium and calcium intake and colorectal cancer (CRC) recurrence and all-cause mortality was also reported. It has been observed that 25(OH)D3 and magnesium may work synergistically in decreasing the risk of all-cause mortality in these patients [341]. Higher concentrations of 25-hydroxyvitamin D3 at diagnosis are associated with a lower mortality risk in CRC patients. This is expected given the crucial roles of magnesium in several biochemical processes involved in the synthesis and metabolism of vitamin D [85,342]. In addition, in a meta-analysis that involved 3 case- control studies of colorectal adenomas and six prospective cohort studies of carcinomas, every 100 mg (4.11 mmol)/d increase in magnesium intake was associated with a 13% lower risk of colorectal adenomas and 12% lower risk of colorectal tumors [343]. Moreover, epidemiological studies have linked a magnesium deficiency with high Ca:Mg intake ratios to a higher incidence of colon cancer and mortality [342]. It has been proposed that this kind of magnesium deficiency increases intracellular calcium levels in part by increasing TRPM7 expression and unblocking the gating effect of magnesium on intracellular calcium entry. Increased intracellular calcium levels promote reactive oxygen species (ROS) generation and magnesium deficiency likely blunts cell-associated antioxidant capacity to further promote oxidative stress. This study also sheds some insight on the epidemiological findings that link high Ca:Mg ratios with increased incidence of cancer [344-346] and increased mortality among colon cancer patients [347].
Observational studies evidenced that elevated magnesium content in drinking water is linked with a reduced risk of esophageal cancer and decreased mortality due to prostate and ovarian cancers. Higher dietary intake of magnesium decreases the risk beyond of above-mentioned colorectal cancer, also of pancreatic cancer and lung cancer [348-353].
Although most of the literature regards solid tumors, hypomagnesemia has also been correlated with a higher viral load of the Epstein Barr virus, a virus associated with a multitude of hematologic malignancies. Studies of patients with a rare primary immunodeficiency known as XMEN disease (x-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection, and Neoplasia disease) elucidated the role of magnesium in the immune system. These patients have a mutation in the MAGT1 gene, which codes for a magnesium transporter. The mutation leads to impaired T cell activation and an increased risk of developing hematologic malignancies. Furthermore, magnesium replacement may increase the immune system's ability to target and destroy cancer cells through this mechanism highlighted in patients with XMEN [27]. On the other hand, a very recent study has redefined MagT1 as a non-catalytic subunit of the oligosaccharyltransferase complex that facilitates Asparagine (N)-linked glycosylation of specific substrates. The authors proposed updating XMEN to "X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect". However, the precise mechanism by which MAGT1 is involved in the homeostasis of magnesium and how this affects the glycosylation defect requires further investigation [354].
Moreover, a very recent work assessed the disturbance of electrolyte in leukemia. In particular, a significantly higher concentration of calcium and a lower content of magnesium in the serum and whole blood of Acute leukemia children were found, as compared to healthy subjects. Furthermore, magnesium is replaced by calcium and harmful metals (As, Cd, and Pb) which results in its deficiency, producing physiological disorders, which may be involved in acute leukemia. The level of magnesium in normal children had the range of 150-279% than AL patients [355]. This finding is consistent with other previously reported data, which indicates an association between insufficiency of magnesium and development of malignant disorders [224,356-359]. These studies highlight that a diet enriched with magnesium can decrease the incidence of cancers and the possibility that hypomagnesemia is associated with poor outcomes in cancer patients undergoing treatment.

Neurological Diseases

Neurological diseases are a substantial and wide spreading health burden worldwide, as shown in the Global Burden of Diseases (GBD) Study 2016. They represent the third most common cause of disability and premature death in the EU and their prevalence will presumably increase with the progressive ageing of the European population [293].
Numerous studies report the involvement of magnesium in these pathologies, the recurrent deficiency in the patients and the effectiveness of dietary integration [103,360,361]. The mechanisms by which magnesium can modulate these disorders are multiple and not fully understood. However, variation in the excitability of the central nervous system, spontaneous neuronal depolarization, and abnormal mitochondria functioning have been connected to most of them. Since glutamate is the most abundant excitatory neurotransmitter, it is often linked to etiology, prevention, and treatment of neuropathology [362,363]. For this reason, magnesium has been a potential strategy for neurological diseases mainly due to its negative modulation of the glutamatergic N-methyl-D-aspartate (NMDA) receptor. Furthermore, magnesium is a key metabolic factor in mitochondrial functioning, lowering membrane permeability and consequently reducing the possibility of spontaneous neuronal depression due to hyperexcitability [50].
A very exhaustive review describes "The Role of Magnesium in Neurological Disorders", summarizing the recent literature on the role played by magnesium in counteracting the onset and co-treating the most frequent neurological diseases: chronic pain, migraine, stroke, epilepsy, Alzheimer's, and Parkinson's, as well as the commonly comorbid conditions of anxiety and depression. The authors claim that "despite to a great number of publications in this field the amount of quality data on the association of magnesium with various neurological disorders differs greatly." Nevertheless, compelling evidence is reported about the role of magnesium in migraine and depression and for counteracting chronic pain conditions and in anxiety as well [50].
From the social impact point of view, it is worth noting that a migraine is a debilitating brain disorder with serious social and financial consequences for the individual and society. The economic impact of headache disorders is enormous in EU countries, with an annual cost of 111 billion Euros. A total of 93% of the costs are indirect and attributable to reduced productivity rather than absenteeism [364]. The serum level of magnesium in migraine patients is frequently lower than healthy subjects. Oral magnesium supplementation is prescribed for prophylaxis while intravenous magnesium administration is routinely suggested for acute migraine. The American Academy of Neurology has revealed the effectiveness of oral magnesium usage in migraine prevention [365]. The efficacy of magnesium in acute migraine treatment was confirmed by different studies [366-368].

Depression is a frequent and debilitating disorder that affects almost 11% of adults older than 60 and 18.8% of those younger than 60. Depression is linked to inadequate quality of life with severe impairments and is often associated with other comorbid disorders, such as anxiety and chronic pain. Interestingly, magnesium plays a role in many pathways involved in the pathophysiology of depression and it is important for the activity of several enzymes, hormones, and neurotransmitters [157,369]. Low magnesium status has been associated with increased depressive symptoms in several different age groups and ethnic populations [370,371]. Recently, it has been reported that there is a significant association between very low magnesium intake and depression, especially in younger adults [372]. Magnesium supplementation has been associated with the improvements of symptoms linked to major depression, premenstrual condition, postpartum depression, and chronic fatigue syndrome [373,374]. A recent open-label randomized trial with 126 adults comparing 248 mg of magnesium to a placebo over six weeks, showed a significant improvement of depression scores within the magnesium group within the first two weeks of treatment [375,376].
Epilepsy is a disease that affects 50 million people worldwide, characterized by seizures occurrence. Seizure activity has been strongly linked to excessive glutamatergic neurotransmission thus, magnesium could also modulate the excitotoxicity connected to epilepsy [377]. In fact, it is well known that severe hypomagnesaemia, itself, can cause seizure activity [378]. Interestingly, it has been reported that pre-eclampsia and eclampsia, conditions associated with symptomatic seizures, improved after magnesium supplementation [50].
Stroke is a cerebrovascular disease characterized by symptoms such as slurred speech, paralysis/numbness, and difficulty walking. A recent publication on stroke reviewed multiple meta-analyses and reported a dose-dependent protective effect of magnesium against stroke. Most of the meta-analyses reviewed found that each 100 mg/day increment of dietary magnesium intake provided between 2% and 13% protection against total stroke. Another updated meta-analysis, including 40 prospective cohort studies, found a 22% protection against the risk of stroke when comparing people with the highest to the lowest categories of dietary magnesium intake [322].
Alzheimer's and Parkinson's diseases (AD and PD) represent two aging disease of neurodegenerative character with higher social impact. The cost burden of these pathologies in European countries rises year by year, and by 2050 it will be almost two times higher in comparison with the year of 2010, estimated to reach 357 billion Euros [293,379].
AD is characterized by profound synapse loss and impairments of learning and memory. Excitotoxicity, neuroinflammation, and mitochondrial dysfunction have all been implicated in Alzheimer's disease, thus, hypomagnesaemia could further hinder neuronal activity [380]. The level of magnesium in a diet is critical to support synaptic plasticity, and the decline in hippocampal synaptic connections has been associated with impaired memory [381]. Recent findings in animal studies are encouraging and provide novel insights into the neuroprotective effects of magnesium. Magnesium treatment, in fact, at an early stage may decrease the risk of cognitive decline in AD [382]. This coincides with earlier studies proving that the increase in the concentration of magnesium in the extracellular fluid results in a permanent increase in synaptic plasticity of hippocampal neurons cultured in vitro and improves learning and memory in rats [383]. Moreover, recent research suggests that ionized magnesium, cerebral spinal fluid magnesium, hair magnesium, plasma magnesium, and red blood cell magnesium concentrations are significantly reduced in AD patients compared to healthy and medical controls [21,384]. Nevertheless, the exact role of magnesium in AD pathogenesis remains unclear.
Parkinson's disease is a common neurodegenerative disease that occurs in the substantia nigra and striatum. The exact cause of its pathological changes is still not very clear, although genetic, aging, and oxidative stress have been suggested to be linked to it. It has been shown that the concentration of magnesium in the cortex, white matter, basal ganglia, and brainstem of the PD brain is low [385,386]. However, the association between circulating magnesium and PD is still ambiguous and controversial. Human research of magnesium concentrations in PD is severely lacking, despite growing evidence implicating magnesium in animal studies [356]. The latest published study on magnesium and PD was a multicentered hospital-based case-control study that examined the dietary intake of metals in patients who were found to be within six years of onset for PD. The study found that higher magnesium concentrations were associated with a reduced risk of PD [387].
Furthermore, the involvement of magnesium in Attention-Deficit Hyperactivity Disorder (ADHD), a serious neurodevelopmental condition characterized by inattention, hyperactivity, and impulsivity, has been reported. The estimated prevalence of ADHD is between 5% and 7% in schoolchildren worldwide. Frequently, learning disorders are associated with this disease and these impairments can influence children's quality of life and impose substantial costs on their family, health-care services, and educational systems worldwide [388]. It is well accepted that magnesium might be useful as a therapeutic agent in the treatment of ADHD because it has been reported that the serum magnesium level in ADHD children was lower than the controls [389,390]. Moreover, magnesium supplementation (alone or in combination with vitamins or other metals) significantly improved ADHD symptoms [391,392]. Magnesium supplementation along with standard treatment ameliorated inattention, hyperactivity, impulsivity, opposition, and conceptual level in children with ADHD. A very recent paper assessed that magnesium and vitamin D supplementation in children with ADHD disorder was effective on conduct problems, social problems, and anxiety/shy scores compared with placebo intake [381,388].

Conclusions

This multifaceted analysis of the importance of magnesium for maintaining a good state of health, starting from the tuning role played by this element at cellular level, revealed the importance of disseminating dietary strategies that satisfy the recommended daily value. Moreover, it is fundamental to have reliable and minimally invasive methods either to promptly identify magnesium deficiency in various body districts or to accurately monitor the efficacy of supplements to prevent and counteract diseases that correlate with magnesium deficiency. Indeed, magnesium has to be considered as a real metabolite instead of a simple electrolyte and its deficiency has a great impact on different physiological functions.
Data from many studies indicate that in about 60% of adults, magnesium intakes from the diet is insufficient and that subclinical magnesium deficiency is a widely diffused condition in the western population. Hence, more attention should be paid to the preventive role of magnesium for social pathologies, encouraging a more adequate dietary intake of the cation and supplementations. As extensively described above, magnesium is found in a wide variety of non-refined foods and is among the less expensive available supplements. Moreover, magnesium trials have shown that magnesium supplements are well tolerated and generally improve multiple markers of disease status.

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Slutsky, I.; Abumaria, N.; Wu, L.-J.; Huang, C.; Zhang, L.; Li, B.; Zhao, X.; Govindarajan, A.; Zhao, M.-G.; Zhuo, M.; et al. Enhancement of Learning and Memory by Elevating Brain Magnesium. Neuron 2010, 65,165-177. [CrossRef]
Veronese, N.; Zurlo, A.; Solmi, M.; Luchini, C.; Trevisan, C.; Bano, G.; Manzato, E.; Sergi, G.; Rylander, R. Magnesium Status in Alzheimer's Disease: A Systematic Review. Am. J. Alzheimers. Dis. Other Demen. 2016, 31, 208-213. [CrossRef] [PubMed]
Xue, W.; You, J.; Su, Y.; Wang, Q. The Effect of Magnesium Deficiency on Neurological Disorders: A Narrative Review Article. Iran. J. Public Health 2019, 48, 379-387. [CrossRef]
Barbiroli, B.; Martinelli, P.; Patuelli, A.; Lodi, R.; Iotti, S.; Cortelli, P.; Montagna, P. Phosphorus magnetic resonance spectroscopy in multiple system atrophy and Parkinson's disease. Mov. Disord. 1999,14, 430-435. [CrossRef]
Miyake, Y.; Tanaka, K.; Fukushima, W.; Sasaki, S.; Kiyohara, C.; Tsuboi, Y.; Yamada, T.; Oeda, T.; Miki, T.; Kawamura, N.; et al. Dietary intake of metals and risk of Parkinson's disease: A case-control study in Japan. J. Neurol. Sci. 2011, 306, 98-102. [CrossRef] [PubMed]
Hemamy, M.; Heidari-Beni, M.; Askari, G.; Karahmadi, M.; Maracy, M. Effect of Vitamin D and Magnesium Supplementation on Behavior Problems in Children with Attention-Deficit Hyperactivity Disorder. Int. J. Prev. Med. 2020,11, 4. [CrossRef] [PubMed]
Archana, E.; Pai, P.; Prabhu, B.K.; Shenoy, R.P.; Prabhu, K.; Rao, A. Altered Biochemical Parameters in Saliva of Pediatric Attention Deficit Hyperactivity Disorder. Neurochem. Res. 2012, 37, 330-334. [CrossRef]
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VitaminDWiki - Magnesium and Vitamin D contains

369 items in category, see also

Magnesium and Vitamin D

12+ VitaminDWiki Magnesium pages have MANY STUDIES in the title
The list is automatically updated

Items found: 12

Title		Modified
Magnesium and Cancer - many studies		18 Oct, 2024
Vitamin D, Omega-3, and Magnesium are synergistic - many studies		14 Sep, 2024
Less Calcification if less Calcium or more Vitamin K, Magnesium, etc. - many studies		26 May, 2024
Fluoridation results in lower IQ, Magnesium, and Vitamin D - many studies		01 May, 2024
Atrial Fibrillation decreased by Vitamin D or Magnesium - many studies		11 Jul, 2023
Diabetes, Metabolic Syndrome and Magnesium - many studies		13 Jan, 2023
Pregnancy helped by Magnesium - many studies		05 Jan, 2023
Low Magnesium associated with severe COVID – many studies		19 Nov, 2022
Magnesium Role in Health and Longevity - many studies		18 Oct, 2022
Calcium to Magnesium Ratio - many studies		08 Aug, 2022
Magnesium reduces pain - many studies		19 May, 2022
Vitamin D and Magnesium need each other - many studies		15 Apr, 2022

VitaminDWiki - Overview Magnesium and vitamin D Has a venn diagram

	Magnesium	not Magnesium
Vitamin D	Magnesium or Vitamin D Aging, Amyotrophic Lateral Sclerosis, Alzheimer's Disease; Asthma, Attention Deficit Disorder, Autism, Cancer, Cerebrovascular, Chronic Fatigue, Diabetes, Hearing Loss, Heart Disease, Heart Attack, Atherosclerosis, Cardiovascular Disease, HIV, AIDS; Hypertension; Kidney Stones, Migraine Headache, Multiple Sclerosis, Obesity, Osteoporosis, Peripheral vascular disease; Pregnancy-related problems, Rheumatoid Arthritis, Sports-related problems,	Vitamin D only Acne, Allergy, Autoimmune, Bone, Breathing, Celiac, Cognition, Colds and Flu, Cystic Fibrosis, Dental, Fertility, hyperparathyroid, Immunity, Kidney, Liver, Lupus, Osteoarthritis, Pain - chronic, Parkinson, Psoriasis, Rickets, Strokes, Sarcoidosis, Thyroid, Parathyroid, Tuberculosis, Vision, Hair, Skin, Sports
Not Vitamin D	Magnesium only Aggressive Behavior, Alcoholism, Arrhythmia, Cerebral Palsy, Chemical Sensitivity, Cluster Headaches; Cocaine-related Stroke; Constipation, Cramps, Fluoride Toxicity, Head Injuries, Central Nervous System Injuries, Magnesium Deficiency; Menopause, Mitral Valve Prolapse, Nystagmus, Psychiatric Disorders; Repetitive Strain Injury, Sickle Cell Disease, SIDS, Stress, Stuttering, Tetanus; Tinnitus, Sound Sensitivity; TMJ; Toxic Shock; Violence	Neither ALL OTHER DISEASES

VitaminDWiki - 26 studies in both categories Virus and Magnesium

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ID	Name	Comment	Uploaded	Size	Downloads
17715	Mg Requirements.jpg		admin 01 Jun, 2022	174.31 Kb	414
17714	Mg Def, Tox.jpg		admin 01 Jun, 2022	68.18 Kb	443
17713	ToC Mg.jpg		admin 01 Jun, 2022	58.04 Kb	318
17712	Mg march 2021_CompressPdf.pdf	PDF 2021	admin 01 Jun, 2022	534.79 Kb	168

Magnesium is important to health – March 2021

Table of contents

Magnesium: Biochemistry, Nutrition, Detection, and Social Impact of Diseases Linked to Its Deficiency

PDF Table of Contents

Mg Recommended intake

Mg Deficiency and Toxiocity

Sections clipped from PDF

Diabetes Mellitus

Osteoporosis

Cardiovascular Diseases

Cancer

Neurological Diseases

Conclusions

References

VitaminDWiki - Magnesium and Vitamin D contains

VitaminDWiki - Overview Magnesium and vitamin D Has a venn diagram

VitaminDWiki - 26 studies in both categories Virus and Magnesium

Attached files

Health Problems and D

Magnesium is important to health – March 2021

Table of contents

Magnesium: Biochemistry, Nutrition, Detection, and Social Impact of Diseases Linked to Its Deficiency

PDF Table of Contents

Mg Recommended intake

Mg Deficiency and Toxiocity

Sections clipped from PDF

Diabetes Mellitus

Osteoporosis

Cardiovascular Diseases

Cancer

Neurological Diseases

Conclusions

References

VitaminDWiki - Magnesium and Vitamin D contains

VitaminDWiki - Overview Magnesium and vitamin D Has a venn diagram

VitaminDWiki - 26 studies in both categories Virus and Magnesium

Page actions

Attached files

Health Problems and D