Magnesium

Two authors, Alan Yuen from the Department of Clinical and Experimental Epilepsy plus Josemir Sander from SEIN-Epilepsy Institute of the Netherlands Foundation based in Heemstde, The Netherlands writing recently in the Journal of Epilepsy Research have written an interesting hypothesis about diet supplementation of magnesium to reduce seizures.

First a little background on magnesium. ” Magnesium is required for over 300 enzyme systems and is critical for many cellular functions including oxidative phosphorylation, glycolysis, DNA transcription and protein synthesis. Studies suggest that the modern Western diet and lifestyle may lead to magnesium deficiency, and this appears to be associated with a wide range of medical conditions. Magnesium deficiency decreases seizure thresholds in animal models of epilepsy and indeed low magnesium concentration in the perfusate is a common method of generating spontaneous epileptiform discharges from rat hippocampal slices. Magnesium is a potential modulator of seizure activity because of its ability to antagonize excitation through the N-methyl-D-aspartate receptor. Some studies have shown that people with epilepsy have lower magnesium levels than people without epilepsy. There are case reports of seizures being controlled with magnesium supplementation in people with specific conditions, and recently in an open randomized trial, children with infantile spasms responded better to adrenocorticotropic hormone (ACTH) plus magnesium than to ACTH alone.” These authors are drawing attention to the western lifestyle specifically with the diet. Where in our foods do we have magnesium?

This diagram is a molecule of chlorophyll, notice the Mg ++ in the middle, that’s from any green vegetable. Listen to how the authors describe things. ” There is much interest in the impact of diet and lifestyle on disease processes such as cancer, hypertension, diabetes and cardiovascular disease, and diet and lifestyle guidelines have been produced for these (e.g. reducing cardiovascular disease risk (Lichtenstein et al., 2006)). It is possible that dietary and lifestyle factors may also have an influence on seizures, and magnesium (Mg) is one such potential factor.”

Magnesium is important for many physiological processes

“Magnesium is the fourth most common mineral in the human body with approximately 25 g in a 70 kg man, and it is the second most common intracellular cation after potassium. Approximately 50% of the body’s store of Mg is found in
skeletal bone, with most of the rest in the intracellular compartment of muscle and soft tissues. Only 0.3% is located in serum, of which approximately 60% is in ionised form. The main physiological role of Mg relates to its function in enzyme systems and its influence on membrane properties. Over 300 enzyme systems are dependent on the presence of Mg (Fawcett et al., 1999). All enzymes utilizing
ATP (adenosine triphosphate) require Mg for substrate formation. Many critical enzyme systems, including adenylate cyclase, phospholipase C and Na/K-ATPase, are dependent on Mg. Therefore Mg is critical for a number of cellular
functions, including oxidative phosphorylation, glycolysis, DNA transcription and protein synthesis. The transport of potassium and calcium across membranes is thought to be dependent on Mg; hence Mg is also important for nerve conduction
(Rude, 1998).” Notice some common themes from previous essays? Like nerve conduction, that’s brain stuff, 50% of magnesium is stored in bone, should I say brain bone conversation ? Then there is the magnesium in muscle and all the other enzyme systems, so that’s the heart muscle which is brain heart conversation, looks like a story to me what do you think ?

The modern Western diet is deficient in magnesium

“One study estimated that 75% of Americans do not meet the recommended dietary allowance of Mg (Alaimo et al., 1994). Another assessment suggested that the mineral content of food in the UK has decreased in the last 60 years. It suggested that the Mg content in vegetables decreased by 24% and in fruits by 16% between 1940 and 1991. The Mg content appears to have reduced by 15% in meat and by 20% in cheeses between 1940 and 2002 (Thomas, 2007). Other lifestyle factors also appear to influence Mg status. Even moderate alcohol intake appeared to increase renal loss of Mg (Rylander et al., 2001). In a healthy volunteer study, physical stress with loud noise was shown to induce an increase in Mg excretion (Mocci et al., 2001).”

Magnesium deficiency is associated with a wide range of medical conditions

Mg is known to be required for maintenance of genomic stability. In an ongoing study, the occurrence of lung cancer decreased with increasing quartiles of dietary Mg intake. The rate was approximately halved in the highest quartile
compare to the lowest (Mahabir et al., 2008). In a large cohort of Finnish male smokers, a high Mg intake was associated with a statistically significant lower risk of cerebral infarction, whilst intake of calcium, potassium, and sodium was not significantly associated with risk (Larsson et al., 2008). In a large cohort of middle-aged adults, those in the highest quartile of serum Mg at baseline had less than half the risk of coronary heart disease than those in the lowest quartile (Liao et al., 1998). The Framingham Offspring Study showed a greater frequency of ventricular premature complexes with decreasing quartiles of serum Mg concentrations (Tsuji et al., 1994). In a large cohort study, those with the
highest quintile of Mg intake had approximately two thirds the risk of developing type 2 diabetes than those with the lowest intake (Lopez-Ridaura et al., 2004). In 14 consecutive people with type 2 diabetes admitted for critical care, the
nine who died had significantly lower Mg levels on admission than the five who survived (Curiel-Garcia et al., 2008). In a cross-sectional study in people aged 70—79, dietary intake of Mg was positively associated with bone mineral density
(Ryder et al., 2005). Erythrocyte Mg levels were reported to be significantly lower in people with major depression than in controls, and treatment with antidepressants appeared to raise Mg concentrations (Nechifor, 2009). In a study of relatively healthy, adult women without psychiatric disorders, the risk of depressive mood disorder was approximately four times higher in the lowest tertile of serum Mg than in the highest tertile (Jung et al., 2010).”

Hence, Mg deficiency appears to be associated with increased risk of cancer, cerebral infarction, coronary heart disease, diabetes, osteoporosis and mood disorder.” The metabolic triangle of brain bone heart conversation comes into notice.

Magnesium supplementation appears efficacious in a variety of medical conditions

It has been observed that a number of tachy arrhythmias appear to respond favorably to Mg sulphate infusion; these arrhythmias include intractable ventricular tachycardia and fibrillation (whether hypo- or normomagnesemic),
torsades de pointes (a variant of ventricular tachycardia), digitalis-toxic ventricular tachyarrhythmia, multifocal atrial tachycardia and hypomagnesemic atrial tachyarrhythmia  (Iseri et al., 1989). A meta-analysis of 20 trials, including
1220 individuals, showed a dose-dependent effect of Mg, with reductions of 4.3 mm Hg in systolic BP and of 2.3 mm Hg in diastolic BP for each 10 mmol/day increase in Mg supplementation (Jee et al., 2002). A meta-analysis of nine randomised trials including 1743 women with eclampsia and 2390 women with pre-eclampsia showed that Mg sulphate is superior to phenytoin and diazepam in preventing the recurrence of seizures in eclampsia and superior to phenytoin in seizure prophylaxis in pre-eclampsia (Chien et al., 1996). A meta-analysis of 24 studies showed that intravenous Mg sulphate was effective in improving respiratory function and reducing hospital admission in children with severe asthma (Mohammed and Goodacre, 2007). Magnesium salts are included in many over-the-counter and prescription treatments for constipation and dyspepsia. It
is accepted as standard care for these conditions despite limited evidence (Guerrera et al., 2009).
Hence, there is evidence for the use of Mg supplementation in various arrhythmias, hypertension, prevention of seizures in eclampsia and pre-eclampsia, and in severe asthma.” That’s heart brain conversation for sure, so to query the brain you listen to the bone conversation or the heart bone conversation, do you follow our logic?  The authors also cited a bunch of reports on the ability of magnesium given in mice experiments in a dose dependent manner to inhibit convulsions and that low blood Mg concentration levels are associated with seizures. Here’s another of their musings: ” It has been suggested that low Mg can reduce surface charge of neuronal membrane, thereby increasing neuronal hyper-excitability (Isaev et al., 2012)” I’m noticing the descriptive term, surface, here are we getting into any sort of tensegrity tension net activity with magnesium?

Magnesium deficiency in people with epilepsy

“In the 1920—1960s there were a number of reports of low blood Mg concentrations in people with epilepsy, and these have been reviewed (Canelas et al., 1965). More recently, case reports have described seizures due to hypomagnesemia in infants and adults (Fagan and Phelan, 2001;
Weisleder et al., 2002). These seizures were controlled with Mg supplementation. Recent studies have also shown that people with epilepsy have lower Mg levels than people without epilepsy. In a study of 45 people with epilepsy and 35 healthy controls, plasma Mg concentrations were significantly lower in those with epilepsy (mean = 0.98 mmol/L) than in controls (mean = 1.15 mmol/L) (Oladipo et al., 2003). In another study, serum ionized Mg was significantly lower in 49 people with epilepsy than in 32 racially matched controls (Sinert et al., 2007). In a study in 50 people with epilepsy and 25 healthy controls, there was a significant fall in serum Mg levels in those with epilepsy on days 1 and 4 of seizures as compared to controls. The fall was greater in people with status epilepticus and severe epilepsy than in those with mild and moderate epilepsy (Gupta et al., 1994). In a study of 100 people with epilepsy and 95 healthy controls, there were significantly lower serum, CSF and RBC Mg levels and higher serum and CSF calcium levels in those
with epilepsy. Post ictal (within 24 h of seizure) serum and CSF Mg levels were significantly lower and calcium levels significantly higher compared with interictal levels (4 weeks after seizure). Low CSF Mg levels correlated with increased seizure frequency, poor control and longer duration of seizures (Sood et al., 1993).”

Magnesium supplementation in people

Infants with primary hypomagnesaemia have seizures that can be controlled with oral Mg supplementation (Prebble, 1995; Unachak et al., 2002; Visudhiphan et al., 2005). The use of Mg sulphate infusion has been used successfully to treat refractory status epilepticus in a subject with normal MRI (Pandey et al., 2010), and subjects with juvenile onset Alpers syndrome (caused by mutation of mtDNA polymerase gamma, POLG1) (Visser et al., 2011). In a randomised open study of 38 children with infantile spasms, treatment with adrenocorticotropic hormone
(ACTH) plus Mg intravenously for 3 weeks was compared with treatment with ACTH alone. The results suggest that the addition of Mg improved the response; at 8 weeks, 79% of those who also received Mg were seizure-free compared with 53% of those receiving ACTH alone (Zou et al., 2010).”

Previous essays have focused on the cardiac effects of seizures, bone micro fractures associated with cardiac arrhythmias, magnesium metabolism appears as the window into the conversation/communication that the observer should lean against the window to listen in on. Right now its like a foreign language so its not easy to follow, but the major observation is that it is there.

But what about breaking the conversation at bone does this help understand the foreign communication within the bone does this tell us any thing about the communication to shape? In other words is the size of magnesium important to shape and/or tension net as visible from a tensegrity window? Lets explore that question.

I will be quoting from the recent article Increased new bone formation with a surface magnesium-incorporated deproteinized porcine bone substitute in rabbit calvarial defects in the Society for Biomaterials published on line 12 January 2012 from the Kyungpook National University, Daegu, republic of Korea authored by Jin-Woo Park, Hyuk-Jin Ko, Je-Hee Jang, Hochang Kang and Jo-Young Suh.

The authors are from the Department of Periodontology, School of Dentistry. They are working on using outside animal sourced bone to graft onto rabbit bone at fracture sites to study the kind of addition of bone to people who for example may need a dental implant who may be osteoportic and need some extra bone in their mouth for the implant post to be inserted to allow these people to add missing teeth so that they can chew to eat better, improving their nutrition ingestion. implants tend to be metal so is there a better way to incorporate the implant into bone? Earlier studies have focused on, “.. the critical event during the early bone healing process occur in the very limited area of the interface between the boner and the grafted materials surface. Thus, certain osteoconductive surface properties of endosseous metallic implants and bone substitutes promote new bone growth formation by enhancing cellular adhesion and differentiation of osteoblastic cells on the grafted surface.” Notice some key terms in their descriptions, like, cellular adhesion or grafted surface. What are the key functions of a tension net as viewed from a tensegrity point of view? Terms like hubs of attachments its the interaction into the matrix of the bone shape. “After the implantation of bony substitutes in the boney defects, enhancement of the early adhesion of osteoblastic cells on the material surface is essentail for a favorable cell response subsequently, such as osteoblast differentiation, in order to promote new bone formation around grafted bone substitute. Magnesium ions (Mg) are known to enhance integrin-mediated cellular adhesion via ligand binding to
integrins.15–17 In this context, Mg has been frequently employed in the surface modification of titanium implants with the expectation of utilizing its integrin–ligand binding effect.18–23 Mg incorporation significantly increased the
attachment, spreading, and alkaline phosphatase activity of osteoblastic cells while notably upregulating the expression of osteoblastic phenotype genes,16,21,22 and enhanced the osseointegration of microrough surface implants.18–20,23
Recent studies have employed Mg in the modification of synthetic hydroxyapatite (HA) bone replacement materials in order to control biodegradation and improve osteoconductivity. 24–27 Such Mg-enriched synthetic HA reportedly supported favorable bone healing in extraction sockets and elevated sinus floor in human studies.25–27 In the attempts to modify xenografts of animal origin, deproteinized bovine bone materials have been modified with collagen, cell adhesion peptides, and bone morphogenetic proteins to improve their bone forming ability.13,14,28 However, to date there have been only limited studies on xenograft of porcine origin, i.e., deproteinized porcine cancellous bone.10,11 To our knowledge, there have not been any reported attempts to increase the osteoconductivity of xenografts of animal origin by incorporating Mg into them.” So it appears, the early cell adhesion effect of magnesium as the authors term is a critical enhancement for bone healing, which is the rationale for their experiments. once the defect healing zone was investigated a few weeks into the healing process this is the comment of the authors; “The surface of the MG sample was covered with nanostructures 100 nm in size.”  Now to explain things here this is at an exceedingly small scale at the healing junction.Yet when the Mg is present as a surface nano feature healing appears to improve.

The authors final considerations are the following: ” On the other hand, the surface nanostructure did apparently enhance the osteoconductivity of MG bone substitute. The release of Mg ions into biological fluids via the increased surface area seems to contribute to enhanced new bone formation, which may promote integrin-mediated attachment and a subsequent osteoblastic cell response
through a facilitation of integrin-mediated signaling pathways. 15,17,21,22 Thus, we suppose that MG particles supported better new bone formation than other bone substitutes with a chemically stable HA structure by enhanced cellular attachment and differentiation on the surface because of biological effects of the surface nanostructures and Mg ion chemistry. In addition, we cannot rule out a possible contribution of the surface micropores in the bone healing of MG bone substitute. These micropores may enhance ionic exchanges with body fluids and serve as nucleation sites for calcium phosphate precipitation,41,42 which is believed to contribute to enhanced bone healing, possibly by acting in a synergistic manner with the Mg chemistry and surface nanostructures.” Again the numbers in the paragraph are references which refer to the original artickle for those readers interested enough to further their own investigation.

Going back to my original question: In other words is the size or scale of added magnesium important to shape and/or tension net, if visible from a tensegrity window? Lets explore that question. It sure looks like the nano scale of Mg is promoting into the healing process. Here in Dentistry this is a big wish to get implants accepted or incorporated into bone better and faster is a major desire, by adding Mg that incorporation is engaged. Here’s what is fascinating: is this magnesium part of the language of a tension net of tensegrity, is this the scale of shape sensing that were observing?

 

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About cerebrovortex

Montreal Grandmother, Agnes Kent was saved by Raul Wallenberg from certain death, when he provided papers for her and her Mom to escape away from the Nazis. Today when asked what that escape meant, she replied,"Remind people, that while statesmen and whole countries remained silent and did nothing, a single individual chose to act, with ramifications that proved enormous. Similar choices confront us today. Write that simple truth she said, it can never be repeated often enough because the world keeps forgetting it."
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