Monographs


Magnesium

Nutritional therapy

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Description

Magnesium is the seventh most abundant element in the earth’s crust, the third most abundant cation in the body and after potassium is the second most common intracellular cation. The human body contains about 24 grams (1 mol) of magnesium, which is approximately 0.034% of the total body weight. Magnesium is mainly stored in bone (60%), muscle (20%) and in soft tissues (20%). Less than 1% is found in the blood. 
   

Magnesium is an activator of more than 300 metabolic responses, including energy production, protein synthesis and nucleic acid, cell growth and division and protection of cell membranes. As a calcium antagonist it regulates the neurotransmitters, muscle contraction and relaxation and therefore has an effect on mental function, (cardiac) muscle function, neuromuscular control, muscle tone and blood pressure. It is therefore self-evident that a deficiency will lead to dysfunction of the body. A magnesium deficiency can go hand in hand with arrhythmia, thromboembolic disease and abnormalities in metabolism, the immune system and the autonomic nervous system. However, the symptoms of a deficiency can vary in nature and scope. Sometimes latent symptoms are present, but over time they can even become life-threatening. 
   

Magnesium status
95% of magnesium is intracellular. In the blood, particularly in the erythrocytes, the concentration is three times higher than in serum. Usually serum magnesium levels are tested (extracellular magnesium), whilst it is actually the intracellular magnesium that is indicative for the magnesium status. Because of that, test results will not give a proper picture of the magnesium status. Because too much trust is usually placed on analysis of serum magnesium, a magnesium deficiency often goes unnoticed.
For a more accurate reading of the magnesium status, the level of magnesium in erythrocytes and urine should be tested. The “magnesium load test” (24-hour urine test) is probably the most accurate diagnosis, but the test is difficult to perform. Testing the level of calcium and potassium in blood and urine can help to provide an understanding of the magnesium status. 
    

A differential diagnostic parameter to determine the magnesium status is whether or not abdominal pain occurs caused by increased peristalsis (diarrhoea can sometimes also occur). This is a sign that the cells are saturated with magnesium and that supplementation is not necessary. 
    

Magnesium absorption
When magnesium levels are normal, 40-50% of the magnesium from the food is absorbed in the entire digestive tract, but mainly in the duodenum. Various factors in the food can affect the absorption. 
   

Magnesium competes with other minerals to be absorbed. Absorption can take place actively and passively. When only small amounts are consumed with the food, the concentration in the lumen is low and absorption is mainly through saturable active transcellular transport, with an increased concentration through unsaturated passive diffusion. Approximately 80% of the plasma magnesium is filtered through the kidneys, of which 95% is reabsorbed, the remainder is eliminated. Unbound (bivalent) magnesium easily binds to phytate (from grain), oxalate (from, among other things, rhubarb), phosphates and methylamines, meaning it can no longer be absorbed. Especially the high consumption of grains can interfere with a good magnesium status.
   

Organically bound magnesium (such as magnesium citrate, magnesium gluconate, magnesium lactate and magnesium aspartate) is absorbed more easily than inorganic forms of magnesium, such as magnesium chloride, magnesium hydroxide and magnesium sulphate. (Inorganic) magnesium oxide, still commonly used in food supplements, is insoluble and is therefore almost not absorbed. 
    

Magnesium chelates are the most readily absorbable forms of magnesium. A magnesium chelate is a covalent bond between 1 molecule of soluble magnesium salt and 1, 2 or 3 (preferably 2) molecules of an amino acid. As it is small, glycine is the most suitable amino acid. A covalent bond of 2 glycine molecules with 1 molecule of magnesium salt, magnesium bisglycinate is found to be the most optimal magnesium chelate. There are various reasons why magnesium bisglycinate is known as the most readily absorbable compound: 

    

  1. Several minerals use the same transporters, so absorption of one mineral can decrease absorption of another, but this compound is not seen as a mineral but as an amino acid. This prevents the minerals from competing;
  2. The absorption of amino acids is higher than that of metals and that of glycine is extra high because of its limited size;

    

Magnesium deficiency
On average a human needs 5 mg of magnesium per kg of body weight a day. A deficiency can arise from insufficient intake, but also from disrupted magnesium regulation. Consider, for example, intestinal hypoabsorption, loss via the urine, reduced bone absorption, insulin resistance and stress. Intake is low, because the Western diet is relatively deficient in magnesium. Meat and dairy contain less magnesium than green leafy vegetables, partly because magnesium is the main component of chlorophyll. There is a significant amount in grains and nuts, but unfortunately refined flour is often used which contains little magnesium. Furthermore, intensive farming and (artificial) fertilizer with a low magnesium content is depleting the soil, so levels in plant-based food are falling. Tap water is also a source of magnesium. The harder the water, the greater the levels of magnesium salt dissolved in the water (max. 50 mg/L). 
    

The average amount of magnesium needed is a need that is sufficient for half of the population. The “Dutch National Food Consumption Survey 2007-2010” shows that 16 to 35% of adults have a magnesium intake below the average need, for adolescents this is 57 to 72%, for children aged 13 to 19 years, 10 to 19%. Only in children aged 7 and 8 years were no intakes below the average need seen. Because of their diet, patients suffering from renal insufficiency have a low intake of magnesium and elderly people are at a higher risk of a magnesium deficiency. On the one hand this is because of the difficulties experienced with buying and preparing food and because of a reduced appetite owing to loss of taste or sense of smell or because of loneliness. On the other hand, elderly people are at a higher risk of magnesium deficiency because absorption reduces with age, whilst urinary elimination increases. Long-term use of diuretics or gastric acid suppressants (proton pump inhibitors) can also lead to a magnesium deficiency.
    

A magnesium deficiency has a negative effect on the gastrointestinal tract, the skeleton and the central nervous system. 
    

A magnesium deficiency often manifests itself by muscle cramps and fatigue. Other early symptoms of a magnesium deficiency are nausea, reduced appetite, vomiting, weakness, tingling, numbness, seizures, personality changes, abnormal cardiac rhythm and coronary spasms. These can therefore all be indicators for the use of magnesium, but magnesium can also help to improve various symptoms. In general, a magnesium deficiency results in a stress response, furthermore it also results in an increased risk of cardiac disease, elevated blood pressure, a stroke and complications in pregnancy.

Action

Electrolyte balance
Magnesium is an endogenous regulator of various electrolytes. Magnesium is needed for activation of the sodium-potassium pump that pumps sodium out of the cell and potassium into the cell. Therefore, magnesium influences the membrane potential. When there is a magnesium deficiency, insufficient magnesium and potassium are present in the cells, which can seriously disrupt the cellular functions.
   

Magnesium reduces the absorption and distribution of calcium by activation of sodium-calcium exchangers, also because as a non-competitive inhibitor it blocks the calcium channels, as well as the release from the endoplasmic reticulum. Even so, magnesium can restore hypocalcaemia. That is because the homeostasis of calcium is partly regulated by formation of parathyroid hormone (PTH), for which magnesium is required (magnesium converts vitamin D into its active form).
   

Therefore a magnesium deficiency obviously goes hand in hand with a changed electrolyte balance. The potassium level in the cells falls whilst the sodium and calcium levels rise because Magnesium ATP pumps work less and the membrane potential is changed. Because of this a magnesium deficiency is linked to muscle cramps, high blood pressure and coronary and cerebral artery stenoses, caused by cramps (vasospasms). 

   
Calcium antagonism
Magnesium and calcium metabolism are closely linked. Magnesium is a calcium antagonist: various enzymes that are activated by magnesium are, to the contrary, inhibited by calcium. As a calcium antagonist, magnesium regulates the neurotransmitter release, muscle contraction and relaxation. The consequence of this is that magnesium plays a crucial role in cardiac muscle function, neuromuscular functions, muscle contraction, blood pressure and other important body functions.

   
Energy metabolism
Magnesium also plays a role in (an)aerobic energy production; directly because it is part of magnesium-ATP-complex and indirectly as an enzyme activator of ATP-generated enzymes in the glycolyse and oxidative phosphorylation. 

    
Hormone homeostasis 
Magnesium regulates the activity of the sympathetic nervous system. It behaves as an antagonist of the N-methyl-D-aspartic (NMDA) receptor and inhibitor of sympathetic neurotransmitters. Various hormones, such as thyroxin, angiotensin, glucocorticoids, glucagon, calcitonin, and the sympathetic neurotransmitters have an effect on the absorption of magnesium. A normal to high magnesium level: 

  • Inhibits excess activity of the central nervous system, which prevents spastic symptoms.
  • Blocks the N-type calcium channels at nerve endings, resulting in changed secretion of noradrenaline. This combats elevated blood pressure.
  • Regulates the activity of renin and therefore the formation of angiotensin II, which prevents vasoconstriction and elevated blood pressure. 
  • Inhibits the release of mediators from mastocytes and regulates T-cell activity, helping to prevent an excessive inflammatory response.
  • Inhibits the release of acetylcholine, which inhibits the sensitivity of the motor nerve endings in the muscle fibre. 
  • Stimulates the synthesis of nitrogen monoxide and prostacyclin, resulting in vasodilation and inhibition of thrombosis. 
  • Inhibits the secretion of noradrenaline, acetylcholine, serotonin and potassium, which prevents vasoconstriction.
  • Is probably needed to keep purines and pyrimidines at the required level, needed for the formation of nucleotides, from which RNA and DNA are formed
  • Along with the NMDA receptor could influence pain perception. 
  • Prevents susceptibility to stress and therefore prevents a fall in the level of magnesium-saving hormones and loss of magnesium via the urine by hypersecretion of adrenal cortex hormones, antidiuretic hormones and thyroid gland hormones.
  • Enables the synthesis of parathyroid hormone (PTH), an increase in PTH results in increased absorption of magnesium via the intestines and increased reuptake via the kidneys.
  • As secondary transporter enables the transport of insulin. In turn, insulin regulates the intracellular magnesium. 
     

Taking into account hormone homeostasis, a magnesium deficiency can lead to spasms, thrombosis, elevated blood pressure, inflammatory responses, stress and ischemia as a result of vasoconstriction. Furthermore a magnesium deficiency disrupts the action of the PTH, which in turn can lead to hypocalcaemia and sometimes to hypokalaemia.

Indications

Improvement in sports performance
After exercise, athletes suffer from hypomagnesaemia. In athletes, this means that a magnesium intake of less than 260 and 220 mg a day for men and women respectively can already result in a deficiency. A significant number of athletes, particularly those who practice sports for which they have to keep their weight low (for example, ballet), have been found to have a magnesium intake that can result in a deficiency. Physical exercise ensures that magnesium is redistributed within the body in order to meet the metabolic need. During physical exercise, not only is magnesium consumed, but an increased loss also occurs through sweat and urine, increasing the need by 10-20%. In combination with a limited intake, these two factors can have a negative effect on energy metabolism, the electrolyte balance, the immune system, the oxygen intake and therefore on the muscle function and performance. A long period of excessive training or short, very intense exertion can magnify these negative effects. A magnesium deficiency leads to immunopathological changes, which lead to inflammatory responses. During long-term exertion, hormonal changes take place that could be the cause of this; secretion of antidiuretic hormones, aldosterone, sympathetic neurotransmitters, thyroid stimulating hormone and adrenal cortex hormones increase. 
    

Magnesium supplementation can improve the sporting performance of athletes with a (threatened) magnesium deficiency and can help to prevent immunosuppression, oxidative damage and cardiac arrhythmias. 

   
Perinatal
Pre-eclampsia occurs in 3 to 10% of pregnancies. The cause is unknown, but it can lead to serious illness and even death of the mother and foetus. After the 20th week of the pregnancy, the mother will suffer from elevated blood pressure and protein in the urine, there can also be thrombosis and increased susceptibility to inflammations. When unconsciousness or coma also occurs, this is known as eclampsia. Symptoms of pre-eclampsia and eclampsia improve because magnesium causes direct and indirect vasodilation in (amongst other things) the brain and uterus. Indirectly by boosting the secretion of vasodilators and by weakening vasoconstrictors. Furthermore, magnesium helps prevent premature contractions and premature birth. Magnesium deficiency has been linked to muscular weakness in babies, however there is insufficient evidence that it can lead to sudden infant death syndrome (SIDS). 
    

An improved magnesium intake can help to prevent and heal (pre-)eclampsia. Two Cochrane reviews have assessed magnesium therapy as being more effective than treatment using phenytoin.

   
Cardiovascular
The incidence of cardiovascular disease (strokes, ischemic heart disease) is reciprocally equal to the level of magnesium in the water or in the ground. Cardiac excitability, neuromuscular transmission, blood pressure, vasodilation and vasoconstriction are all related to the magnesium status, which is important for patients with cardiac disease. When there is a magnesium deficiency, arterial fibrillation and ventricular tachycardia and fibrillation are more common. Magnesium has a positive effect in “torsades de pointes tachycardia” (a special type of ventricular tachycardia). A deficiency has also been found to pave the way for the occurrence and development of coronary risk factors such as diabetes mellitus, hypertension, atherosclerosis, hyperlipidaemia, cardiac arrhythmias, damage to the cardiac muscle and ischemic heart disease. An improved magnesium status can prevent ischemia of the heart by reducing the intracellular calcium levels, dilation of the coronary arteries, reduction in the peripheral resistance and inhibition of thrombosis. Magnesium supplementation reduces the frequency of asymptomatic ventricular arrhythmia in heart failure and has a blood pressure regulating effect; it can also be used preventatively for atherosclerosis and ischemic disease. When magnesium is administered directly intravenously for a suspected cardiac infarction, there is an increased chance of survival. Magnesium supplementation seems to have a positive effect on all kinds of cardiovascular complications, especially in “torsades de points” tachycardia and blood pressure regulation.

    
Mitral valve prolapse
Approximately 5% of adults, of which more women than men, suffer from mitral valve prolapse. It is one of the most common heart abnormalities in young people. As far as the prevalence is concerned, there is an idiopathic similarity between symptoms and the latent nature and mitral valve prolapse (dysfunction of the valves of the left atrium) to a form of latent tetany caused by a magnesium deficiency. Mitral valve prolapse is common in patients with latent tetany caused by magnesium deficiency and latent tetany caused by magnesium deficiency almost always occurs in patients with mitral valve prolapse. A magnesium deficiency can lead to abnormalities in the synthesis of collagen, connective tissue and cardiac muscle, resulting in mitral valve prolapse. An early diagnosis and magnesium supplementation can reduce the symptoms of mitral valve prolapse and can prevent asymptomatic patients from suffering symptoms of latent tetany. 
Mitral valve prolapse is closely linked to latent tetany caused by magnesium deficiency, symptoms of both can be relieved or prevented when the magnesium status normalises.

    
Metabolic syndrome 
The effect of metabolic syndrome on public health has increased significantly. Metabolic syndrome is a combination of risk factors for cardiovascular disease, including: insulin resistance, elevated blood pressure, reduced glucose tolerance, abdominal obesity, reduced coagulation, inflammatory disorders, oxidative stress and dyslipidaemia, leading to arteriosclerosis. The magnesium balance in the cells and the serum is usually regulated by hormones that, in patients with metabolic syndrome, are different than those in people who do not suffer from this syndrome. There is a negative connection between magnesium intake and the occurrence of metabolic syndrome and the individual symptoms. Metabolic syndrome and its sub-symptoms could improve through an improved magnesium status. 

   
Type 2 diabetes 
Depending on the seriousness of the illness, type 2 diabetes causes a changed magnesium status. The level of magnesium in the cells and in the serum is lower in diabetics than in the rest of the population and lower still in untreated diabetics. A magnesium deficiency could arise because glucose in the urine impedes reuptake by the kidneys, resulting in insulin resistance and reduced insulin release. Furthermore, there appears to be a negative connection between magnesium intake/serum magnesium and insulin resistance and between magnesium intake/serum magnesium and the incidence of type 2 diabetes. The aforementioned connection is strongest when there is a magnesium deficiency. Furthermore, potassium deficiencies occur in diabetics which paves the way for a magnesium deficiency. Magnesium supplementation has a positive effect on the glucose metabolism, the insulin sensitivity and the serum potassium level, therefore it can help to keep diabetes under control, thereby preventing complications involving the vessels. Glucose and endogenous insulin secretion have an effect on the plasma magnesium. 
    

Magnesium and insulin levels show an interaction, supplementation of the magnesium that is lost can improve the clinical picture in diabetics.
    

Noise-induced hearing loss
Acoustic trauma is one of the main causes of noise-induced hearing loss, ringing in the ear (tinnitus) and sound hypersensitivity. Hearing loss can be permanent or temporary; temporary loss is when the stereocilia are not irreparably damaged. Not only does acoustic trauma result in direct mechanical damage, but also indirect metabolic processes. Exposure to noise results in vasoconstriction and oxygen deficiency in the cochlea of the ear. Vasoconstriction leads to oxidative stress and the death of neurons caused by an excess of glutamate. Upon exposure to noise, the cilia in the ear become overactive, releasing large amounts of glutamate in the synapses of the inner ear. This causes the NMDA receptors to be overstimulated.
   

Exposure to noise causes a magnesium deficiency in the body and magnesium supplementation has proven to be effective in treating and preventing noise-induced hearing loss. The cochlea is protected because locally magnesium protects the nerves and dilates the vessels. Magnesium combats the death of neurons caused by an excess of glutamate (glutamate antagonism). Various studies confirm the protective effect of magnesium in hearing damage and ringing in the ear.

    
Migraine
Patients who suffer from cluster headaches and (menstrual) migraine have all been found to have a magnesium deficiency. After supplementation with magnesium, the frequency reduces, however to achieve that a dose of 600 mg a day was taken. 

    
Perioperative
Perioperative shivering and hypomagnesaemia are prevented by perioperative supplementation of magnesium. It is also probable that magnesium supplementation reduces the sensitivity and sensibility and has a neuroprotective effect, however this latter has not been proven. After approximately 25 to 40% of cardiac surgery cases the patient suffers from atrial fibrillation. Magnesium supplementation reduces postoperative atrial fibrillation equally well as mainstream antiarrhythmics, but has fewer side effects.

   
Lungs
Because magnesium can help to relax the muscle cells and has anti-inflammatory properties, it can be expected that magnesium is effective in the treatment of asthma. Bronchospasms and bronchial reactivity reduce. In acute severe deterioration, magnesium therapy can have a restorative effect when conventional therapy fails.

    
Bone and cell tissue 
Magnesium deficiency has a negative impact on all bone tissue cells, resulting in poor new cells being produced and old cells being broken down. The bone tissue degenerates in structure and quantity and the bone is more likely to fracture. In postmenopausal women and elderly men, magnesium supplementation helps to prevent bone fractures and loss of bone and even increases the bone density.
    

A low level of magnesium also accelerates the ageing of the human endothelial cells and fibroblasts. It is therefore expected that increasing the magnesium intake can contribute to ageing more healthily and preventing age-related illnesses. 

    
Mental functioning
In the brain magnesium supports the cognitive functions, such as the memory and the ability to concentrate. The anxiety-inhibiting effect of magnesium is partially linked to the relaxant effect of magnesium on the muscular system and the regulatory effect on neurotransmitters. Various studies show a link between symptoms of anxiety and a decreased magnesium status. There are also signs that a decreased magnesium status worsens compulsive disorders.

Contra-indications

If possible, for impaired renal function, heart block (a disruption in the excitation conduction of the heart) and neuromuscular disorders, magnesium supplementation must only be given under medical supervision. 

Side effects

Intensive therapy with inorganic magnesium, particularly magnesium sulphate and magnesium chloride, can result in temporary osmotic diarrhoea. Therefore for constipation, regular and sometimes higher doses of magnesium are advised. Magnesium sulphate is more likely to cause diarrhoea than other magnesium salts because sulphate, as well as magnesium, has an osmotic effect. Amino acid bound magnesium form and most organic forms are readily absorbed with minimal laxative effect.

Interactions

Simultaneous use with tetracyclines, digoxin, penicillin, iron or ciprofloxacin can reduce the resorption of these medicines by complex formation and because magnesium inhibits stomach acid formation.

Dosage

The daily recommended amount of magnesium in the Netherlands is 300 mg, but the actual magnesium needs can vary significantly, depending on factors such as age, gender, pregnancy, occupation, sport, eating habits, lifestyle and medicines. In unfavourable circumstances, the need for magnesium can even increase to 600-700 mg a day. 

   
It will take some time before the effects of magnesium supplementation become evident. The relaxing effect on the muscles will already manifest itself after a few days or weeks, but to achieve a long-lasting effect, supplementation has to continue for a few months.
    

As a safe upper limit, between 300 and 400 milligrams of elementary magnesium each day should be maintained. For acute use, 400 mg and for chronic use 300 mg. For children from 1 to 3 years, a limit of 65 mg applies, from 4 to 8 years 110 mg, for older than 8 years 350 mg. However, for certain uses higher doses may have to be given provided these are given under supervision. 
    

Nevertheless, magnesium therapy is an extremely safe form of therapy. In some people, an extreme overdose can result in a feeling of warmth and flushing, but the occurrence of hypotension as a result of a magnesium overdose is extremely rare. Intensive therapy with oral magnesium (as discussed above) can cause osmotic diarrhoea.

Synergism

An important cofactor for magnesium is vitamin B6. Vitamin B6 helps transport magnesium in the body’s cells. Vitamin C, vitamin D, calcium and phosphorus also have a synergistic effect. Calcium, vitamin D and phosphorus are especially synergistic in relation to the metabolism of bones and teeth.

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