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What is magnesium

Why is it so important clinically

Why is magnesium so important?

  • "Hypomagnesemia is probably the most underdiagnosed electrolyte deficiency in current medical practice170"
  • "More than half the population in developed countries may have an inadequate dietary intake171,172."

  • If we combine those two quotes, we have the makings of a clinical disaster in individuals who drink alcohol heavily, take diuretics, exercise and sweat excessively, are elderly with low dietary intakes, have gastrointestinal disorders causing subclinical or clinical malabsorption and the large number of people out there who suffer from insulin resistance (pre-diabetes) that are at risk for low intracellular magnesium levels.

  • Serum (blood) levels are a very poor marker for intracellular magnesium levels whereas red blood cell magnesium content is a better indicator171. Thus many individuals who are at significant risk for all the complications of low intracellular magnesium, will not be identified due to a false sense of security provided by normal (unreliable) blood magnesium levels. 

Some key points about magnesium129

  • Over 300 enzymes require magnesium to work
  • ALL the enzymes that create ATP for energy are dependent on magnesium
  • 20% of the body's magnesium stores are found in skeletal muscle. 
  • Deficiency: Magnesium deficiency is a significant problem in insulin resistance, hypertension, diabetes, cardiovascular disease, asthma, the use of some medications and osteoporosis.
  • Intracellular magnesium: 49% of magnesium is found inside the cells of other tissues (intracellular magnesium).
  • Blood: Only 1% of magnesium is found in blood.
  • Cereals and legumes are poor sources of magnesium: The amount of magnesium in grains and legumes may look impressive on paper, but the bioavailable (absorbable and useful) amount of magnesium is very poor due to the fact that minerals like magnesium are bound to phytates.

Clinical symptoms171

  • Myalgia, muscle spasms, tremors, cardiac arrhythmia (palpitations), lethargy, depression and decreased appetite (anorexia), muscle weakness, apathy, neuromuscular weakness.

  • Magnesium deficiency is a recognized risk factor for ischaemic heart disease, hypertension and arrhythmia - especially if associated with coronary vasospasm and nigh muscle cramps.

Insulin and the effect on intracellular magnesium

  • Insulin has a significant effect on intracellular magnesium stores as shown in numerous clinical studies looking at insulin and non-insulin dependent subjects129.

  • Magnesium depletion is common in both insulin resistance and type-1 diabetes mellitus129.

  • With normal insulin-insulin receptor function, a signal is sent to the Na2+/Mg2+ pump and this is thought to be the mechanism for magnesium transport into cells173.

Insulin resistance and intracellular magnesium

  • As discussed above in diabetic states, there is a significantly low magnesium intracellular level affecting anywhere from 25% to 38% of diabetics putting them at great risk from cardiovascular events like an arrhythmia, increased triglyceride levels and atherosclerosis163.

  • If this insulin signal is blocked to the Na2+/Mg2+ transporter, then the opposite to what you see above will happen, intracellular magnesium will diminish and importantly there will be in influx of calcium. This will increase vascular tone if this happens in the blood vessels and thus increase blood pressure.

How low intracellular magnesium can lead to worsening insulin resistance

  • Magnesium has a vital role in activating tyrosine kinase which in turn transfers a phosphate molecule to the insulin receptor allowing the activation of this receptor and the subsequent signalling cascade to be triggered enabling all the functions of this receptor.

  • Tyrosine kinase is simply an enzyme that transfers a phosphate group to a protein in a cell from adenosine triphosphate (ATP). This acts as an On/Off switch for these proteins.

  • Low intracellular magnesium levels will result in defective tyrosine kinase activation and reduced insulin receptor activation and signalling. This is in essence insulin resistance due to a mineral deficiency.

Magnesium as a calcium channel blocker

  • Calcium flooding into a blood vessel endothelial cell, will trigger off a signalling cascade that will lead to increased vascular tone (increased blood pressure)174.

  • With low intakes or magnesium or insulin resistance or both, extracellular (blood) and intracellular levels of magnesium will be compromised (see below).

  • Suboptimally low extracellular levels of magnesium will allow the calcium channels to stay open allowing an influx of calcium into cells. Having an optimal level of magnesium, allows this mineral to act as a calcium channel blocker.

Low magnesium levels and endothelial cell damage

  • As mentioned above, suboptimal intakes of magnesium will result in unopposed influx of calcium leading to increasing intracellular calcium levels.

  • High intracellular calcium levels result in numerous deleterious effects as shown in this following graphic175.

  • It is interesting to note that magnesium provides critical cell membrane stability to cellular and subcellular (organelle) structures. When magnesium binds to phospholipids, it decreases cell membrane permeability. However, when intracellular magnesium levels are low, there is an increase in cell membrane permeability putting all cells involved at jeopardy for damage183.

Low magnesium and asthma

  • The mechanism of smooth muscle contraction around airways (bronchoconstriction) has a similar mechanism to what is shown above with regard to increasing intracellular calcium levels.

  • Many studies have shown strong correlations between low intracellular magnesium levels and bronchial reactivity181, 182. One research group stated:

    "The salient finding of our study is that there is a strong positive correlation between bronchial reactivity and the level of intracellular magnesium181 "

  • Often patients may have refractory asthma - i.e. they have a poor response to their bronchodilator medications or preventers. Rarely, would a medical practitioner contemplate that a dietary component may be contributing to this refractory state when all membrane potentials or nerve transmissions or smooth muscle activity is due to influx/efflux of electrolytes derived from food.

Migraines and refractory depression

  • It is interesting to note how effective magnesium is in the treatment of both depression and migraine headaches.

  • Comparative head-to-head studies of intravenous or oral magnesium against tricyclic antidepressants that are known to be effective in the treatment of migraines, found an equivocal efficacy in the management of migraine headaches184, 185,186.

  • It is interesting to note once again that low magnesium levels decrease brain serotonin levels and that it is also a known fact that antidepressants have the effect of raising brain magnesium levels186.

  • The authors of one paper go on to say:

    "Intravenous and oral magnesium in specific protocols have been reported to rapidly terminate TRD safely and without side effects186. "
    (TRD = Treatment Resistant Depression which makes up 60% of all depression186)

  • Niacin and migraines - Low serotonin levels are implicated in migraines. Niacin acts on the kynurenine pathway to shunt tryptophan to serotonin. The addition of niacin to magnesium is definitely worth a try if a non-drug approach is what an individual is after or simply to test the effectiveness of this combination with very low potential for side-effects187.

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