Neuromuscular system and nutritional support
Neuromuscular disorders are implicated in a wide variety of conditions, including cardiovascular disorders, premenstrual symptoms & fibromyalgia. Magnesium, calcium & vitamins, particularly the B vitamins, can all be used to deal with such disorders.
Nutritional support for the neuromuscular system
Chronic fatigue syndrome
Coronary artery disease
Mitral valve prolapse
Elevated blood lipids
Congestive heart failure
Muscle cramping and spasms
Stress, anxiety, panic disorder
Free radical protection
Heavy metal toxicity
Premenstrual syndrome (PMS)
High fat, sugar, salt intake
Magnesium is an essential mineral, required in the biological function of at least 360 enzymes in the human body. It is intimately involved in most of the reactions involving the metabolism of carbohydrates, lipids, nucleic acids and proteins. Dietary magnesium deficiency is more prevalent than is generally suspected. It can impact on many biochemical processes and be expressed via a diverse range of clinical symptoms and signs.
Magnesium absorption and bioavailability
Oral magnesium sources are generally available as an ionically bound salt. These include magnesium chloride (MgCl), magnesium sulphate (MgSO4) and magnesium oxide (MgO). Other forms are the complexed minerals, like Mg aspartate and Mg orotate. All of these forms dissociate in solution to release Mg ions and are known to produce loose bowel motions when taken in therapeutic doses.
A covalently bound magnesium-glycine chelate is not hydrolysed by digestive processes, nor does it dissociate in solution. This form of magnesium is readily absorbed as an amino acid complex, to provide rapid serum delivery, while remaining intact. The intact chelate does not release magnesium, which would be bound to blood proteins and further reduce bioavailability. Rather, there is direct cellular uptake, again as an amino acid chelate and release of the magnesium ion due to lysosome cleavage of the glycine residues.
The magnesium-glycine chelate (magnesium diglycinate) is a significant advance in magnesium supplementation technology. Therapeutic levels of oral magnesium supplementation, which do not cause gastrointestinal upset and diarrhoea, can now be administered.
Determination of deficiency and laboratory findings
Total body magnesium levels are difficult to quantify, as no stable reservoir of magnesium exists. Serum magnesium level is known to be without significant value in determining Mg status. During acute deficiency states, serum levels may in fact rise as the ion fluxes out of cells into the serum. Only when there is serious depletion of cellular reserves do serum levels fall. Fluctuations in magnesium status can be seen in red blood cell magnesium levels due to a number of influences e.g. strenuous exercise. Nevertheless, red blood cell and leukocyte levels remain a useful marker of tissue Mg levels.
Therefore, the most reliable and accurate assessment of cellular magnesium reserves and requirements is the magnesium loading test. The test involves administration of Mg concurrent with urinary excretion determination. The balance between ingestion and excretion determines the amount of the ion retained and indicates repletion of any body store deficit. The test may also monitor biochemical and symptomatic responses to magnesium intake, as patients with low magnesium reserve often do not show classical deficiency signs, yet present with conditions associated with deficiency.
The recommended daily allowance (RDA) of magnesium is currently 320 mg/day for men and 270 mg/day for women. Pregnant and lactating women require an extra 30 and 70 mg/day respectively. It is questionable, though, that the recommended daily allowance (RDA) is currently achievable with a modern diet, or if it is sufficient for neutral magnesium balance.
Current research indicates that in most Western countries, a sufficient magnesium supply is difficult to achieve, particularly in view of the increased demand for magnesium associated with common diets and lifestyles. Environmental factors also affect the magnesium content of the food supply (soils, agriculture, acidic rain, air pollution).
Magnesium deficiency has been categorised into four stages related to the variety of presentations of magnesium insufficiency in clinical practice.
Type I: Occult magnesium deficiency
Incidence very common
Investigation serum magnesium levels normal. RBC magnesium levels normal. Loading retention increase retention to IV load (>25%), indicating depletion of cellular store
Symptomatology: Fatigue, lethargy, difficulty concentrating
Type II: Subclinical magnesium deficiency
Investigation serum magnesium levels normal. RBC levels decreased. Loading retention approximately 25-50% retention
Symptomatology: Mood/behavioural changes, anxiety, irritability, premenstrual tension, migraines, fatigue, muscular aches and pains, poor memory
Type III: Acute magnesium deficiency
Incidence associated with acute trauma, MI, prolonged or strenuous exercise, surgery
Investigation serum levels low. RBC levels may be normal. Loading retention usually greater than 50%
Symptomatology: Acute fatigue, muscle spasms, arrhythmia, tetany
Type IV: Chronic magnesium deficiency
Incidence indicates negative magnesium balance over several months, present in 65% of intensive care patients and approximately 11% of general population. Investigation serum magnesium level low. RBC level low
Loading retention at least 50% of loading dose is retained, indicating severe depletion of total body store
Symptomatology/Associated conditions indicated in degenerative disease processes, including cardiovascular diseases, diabetes, Alzheimer's disease, multiple sclerosis, asthma, osteoporosis, infertility, chronic fatigue and fibromyalgia
Pathologies associated with magnesium deficiency include:
Acute and chronic pancreatitis
Renal tubular acidosis
Chronic glomerular nephritis
Primary and secondary aldosteronism
Medications associated with magnesium deficiency
Diuretics (especially loop and thiazide diuretics)
Fibromyalgia is a common clinical feature of chronic fatigue syndrome (CFS) and is associated with the presence of multiple tender points and depression. Approximately 20% of patients presenting to rheumatology clinics have fibromyalgia.
Chronic tissue hypoxia seems to be the responsible biochemical process in this condition and magnesium deficiency is a likely contributor. Patients with fibromyalgia often suffer from myalgias, fatigue, sleep disturbances and anxiety. These same symptoms are also found in patients with low magnesium levels.
Clinical trials of magnesium in fibromyalgia
Clinical studies have indeed found sufferers of fibromyalgia to be deficient in magnesium and to benefit from supplementation. Another more recent study on the treatment of subjects diagnosed with fibromyalgia show marked improvement with supplementation. Patients took 1200-2400 mg of malic acid and 300-600 mg magnesium daily for 8 weeks on the combination.
Subjective improvement in pain score on ingestion of a magnesium/malic acid combination resulted within 48 hours. Their tender point index scores decreased from an average 19.6 to 8 and 6.5 after 4 and 8 weeks respectively. On cessation of supplementation the fibromyalgia patients noted a subsequent subjective worsening of their condition.
A similar study using both malic acid and magnesium has confirmed the previous results. The randomised placebo-controlled study found no clear treatment advantage when low dosage (1200 mg malic acid and 300 mg magnesium) was used for 4 weeks as a pilot trial. Doubling the dose for 6 months in the main trial showed significant reductions in primary pain and tenderness measures in the fibromyalgia patients. The researchers commented that the treatment appeared to be safe, although required to be taken for at least two months before positive effects began.
Chronic fatigue syndrome
Magnesium deficiency signs and symptoms are similar to those expressed by chronic fatigue syndrome (CFS) sufferers and these patients are known to be magnesium deficient.
Cox et al examined red blood cell magnesium of CFS patients and found every subject to be lower than controls. These same patients were treated with magnesium sulphate injections every week for 6 weeks. Those treated with magnesium had improved energy levels, better emotional state and less pain. Minimal changes were noted in the controls. All of those patients receiving magnesium supplementation achieved normal red blood cell magnesium before the end of the study, whereas only one of the magnesium deficient controls was found to have normal levels at trial termination.
Takahashi et al have reported a case of CFS, which was unresponsive to NSAIDs, minor tranquillisers and antidepressant drugs. Weekly intravenous magnesium for 6 weeks resulted in reduced fatigue and after 7 months in hospital, the patient was able to return home.
Davies has reported magnesium deficiencies in CFS patients and suggests that this is responsible for the muscle pain they experience. Muscle relaxation is a magnesium dependent process and in magnesium deficient states, myofibrillar relaxation may be impaired. The contraction of an antagonist against a partly contracted protagonist will result in myofibrillar damage, muscle pain and tenderness with easy fatigability of the muscles.
Folic acid is required for the maturation of many cell types, including most immune cells. Research has found chronic fatigue patients to be deficient in folic acid, suggesting supplementation may be of benefit to these patients.
Hypertension - Clinical hypotensive effects of magnesium therapy
A large range of processes are affected by magnesium with respect to blood pressure regulation, so it is not surprising that magnesium supplementation has demonstrated substantial reductions in blood pressure in subjects with mild to severe hypertension.
Further, low magnesium levels are associated with increased risk of hypertension. A double-blind placebo controlled cross-over study found a dose dependent effect of magnesium on hypertension.
Effect of antihypertensive medication on magnesium
Interestingly, antihypertensive therapy and diuretics often contribute to the common magnesium deficiency seen in hypertensive patients. Supplementation with oral magnesium appears to reduce both the high blood pressure and subsequently, the requirement for these antihypertensive/magnesium-depleting treatments.
Coronary Artery Disease / Atherosclerosis
The physiological features of coronary artery disease (CAD) strongly suggest that the influence of magnesium deficiency and supplementation has shown significant effects in this serious pathology.
"Magnesium deficiency alone has been shown to cause cardiac and arterial lesions in every species of animal in which it has been induced. High fat/low magnesium intakes appear to be conjoint pathogenic factors. The arterial lesions of high fat diets in several species are intensified by simultaneous Mg deficiency and protected against by Mg repletion."
At the mitochondrial level, magnesium activates various enzymes and preserves both function and structure. The heart has a high mitochondrial density and enzyme activity, which makes it particularly vulnerable to magnesium deficiency.
Substantial evidence now suggests chronic magnesium deficiency causes functional cardiovascular abnormalities. Magnesium is an effective calcium channel blocker. Cellular calcium toxicity is known to be contributory to atherogenesis and calcium channel blocking agents have demonstrated preventive effects in atherosclerosis.
The atherosclerotic process appears to be dependent on free radical oxidation of LDL's and vascular epithelial tissue and antioxidants have been demonstrated to arrest atherosclerotic progression.
A magnesium deficient state is undeniably linked to exaggerated free radical tissue injury and several mechanisms are known to explain how magnesium deficiency leads to enhanced peroxidation and decreased oxidative defence processes. The role of magnesium as a cofactor in glutathione production (a powerful antioxidant) and the presence of high levels of copper and iron in magnesium deficient states support the role of magnesium to augment antioxidant defences against atherosclerosis.
Cardiac ischaemia and reperfusion are responsible for myocardial tissue damage during and immediately after myocardial infarction (MI).
Several trials have demonstrated a protective effect of magnesium against heart muscle injury due to myocardial infarct and they also show a reduction in subsequent mortality in those patients receiving magnesium.
Levels of magnesium and zinc are notably reduced in patients experiencing MI. The Leicester Intravenous Magnesium Trial (LIMIT-2), a double-blind, placebo controlled study was undertaken by randomising 2,316 patients with suspect acute myocardial infarction. The 28-day mortality from all causes showed a 24% reduction in the magnesium group. There was also a 25% reduction in the incidence of heart failure, a benefit conferred equally on thrombolysed and non-thrombolysed patients. The effects of magnesium sulphate therapy on early mortality are reported to be comparable to, but independent of, thrombolytic therapy.
The effects on the myocardium of myocardial infarct patients receiving magnesium are multiple. They include a reduction in afterload by decreasing vascular resistance, improving coronary blood flow, protection of mitochondria against calcium influx and inhibition of postinfarctional dysrhythmias.
Infarct size reduction by magnesium
The size of infarction also appears to be strongly influenced by magnesium supplementation. Two recent studies performed on porcine models demonstrated a significant reduction in infarct size. Prophylactic administration of magnesium in high-risk individuals is expected to provide significant protection against myocardial infarction.
Lowered magnesium levels have been associated with an increased risk of cardiovascular disease. The raised lipid profile in magnesium deficient subjects appears to be contributory to this process.
Clinical trials on magnesium and blood lipids
Triglyceride levels were examined in a controlled study of 69 patients with hyperlipidaemia. Thirty-seven received 500 mg oral magnesium daily. A significant reduction in triglycerides was seen in the supplemented patients. Mean triglycerides fell from 198.17 +/- 47.01 to 163.2 +/- 40.55. Erythrocyte magnesium concentration increased in these patients, although without significant changes in plasma concentration.
Yamaguchi et al examined the effects of various levels of magnesium intake on serum lipids and aortic cholesterol deposition in mice. The levels of both serum total cholesterol and lipid peroxides decreased relative to increases in the dose of magnesium. They also found that adequate magnesium intake prevented cholesterol deposition in the arteries of the mice fed on an atherogenic diet. The atherogenic potential of LDL and VLDL appears to be dependent on oxidation of these particles.
Several studies have shown considerable peroxidation of these lipoproteins under magnesium deficient conditions. Two recent studies demonstrate that magnesium deficiency in rats is significantly associated with increased peroxidation of triglycerides, VLDL and HDL.
Magnesium deficiency further increases the atherogenic potential by increasing the uptake by the arterial endothelium of oxidised cholesterol and LDL. In vitro studies suggest that the uptake of LDL by the vascular wall and its subsequent oxidation is markedly enhanced in magnesium deficient states. Rabbits fed a low magnesium diet were seen to accumulate oxidised cholesterol in their artery walls much more readily than those fed a magnesium sufficient diet.
An in vivo study of several potential antithrombotic agents, including heparin and aspirin, found poor efficacy, while magnesium demonstrated surprising capability without complications. The researchers reported profound modification of thrombus formation with parenteral magnesium administration. Excessive bleeding was not associated with the thrombus- preventing qualities of magnesium.
The effect of magnesium on blood homeostasis contributes toward our understanding of the capacity of magnesium to prevent myocardial infarct. Platelet aggregation is a calcium dependent process, whereas magnesium is required for deaggregation and maintenance of platelet shape. Further, release of serotonin by aggregated platelets is calcium dependent and inhibited by magnesium.
Thus the net effect of a raised Ca:Mg ratio is an elevated risk of thrombosis. The concern is that women may be consuming high levels of calcium, without ensuring that the magnesium deficiencies, which are so prevalent, are addressed.
Mitral valve prolapse
Several researchers have documented an association between magnesium deficiency and the incidence of mitral valve prolapse (MVP).
Coghlan et al prospectively studied 94 patients with MVP and found 59 (62.7%) to have low erythrocyte magnesium, while only 35 (37.3%) had normal levels. The deficient patients were also noted to experience more muscle cramps and migraines. Forty-one of the 59 hypomagnesaemic patients were assigned to a randomised double-blind study of magnesium supplementation. Subjects were given between 250 and 1200 mg oral magnesium oxide or 128 to 256 mg magnesium chloride for up to four months. Four patients stopped because of diarrhoea. In the remaining subjects, magnesium treatment resulted in marked symptomatic improvement.
Low magnesium status is now well recognised as an electrolyte abnormality that relates to cardiac arrhythmia, ventricular tachyarrhythmia and sudden cardiac death. Some reports have demonstrated significant antiarrhythmic effects of magnesium, which are not associated with low serum levels of magnesium.
The effect of magnesium on supraventricular arrhythmias was evaluated and compared to a calcium antagonist (Verapamil) in a recent randomised blind study. The efficacy of magnesium for conversion to sinus rhythm was at least as effective as Verapamil and its action more rapid. No side effects were noted with magnesium, whereas six patients receiving Verapamil had to be withdrawn from the study due to symptomatic side effects (hypotension in three, cardiac failure in three).
Magnesium and potassium regulation
Magnesium appears to be an important ionic regulator at the cellular membrane and in patients with low potassium, normal levels cannot be restored without magnesium repletion and often, magnesium supplementation alone is effective in restoring potassium levels. The effect of magnesium on potassium and calcium regulation is thought to mediate the antiarrhythmic ability of magnesium.
The pain of angina is due to ischaemia in the cardiac muscle. The blood supply to the heart muscle through the coronary vessels is obviously inadequate and this may be due to atheroma, thrombosis or vasospasm, all of which are affected by magnesium status.
Clinical trial of magnesium diglycinate and angina
Research on magnesium diglycinate has demonstrated remarkable effects on angina pain. Sanvad et al studied patients with angina pectoralis to determine the effect of magnesium diglycinate on myocardial performance and requirement of nitroglycerine. Patients receiving 50 mg/day Mg experienced a 25% increase in myocardial performance. Controls required an average of 29% more nitroglycerine to fend off anginal attacks through the trial.
Coronary vasospasm appears to be a significant contributor to anginal symptoms and cardiac ischaemia. Considering the effect of magnesium deficiency on smooth muscle irritability, it is assumed that magnesium deficiency predisposes to the spasm of coronary vessels.
This has been demonstrated by Mori et al. They studied 264 patients with mild coronary sclerosis who underwent a detailed coronary angiography to determine the effect of magnesium on acute myocardial infarction and angina. Provocative testing for coronary vasospasm using acetylcholine demonstrated a protective effect of magnesium.
Magnesium loading testing demonstrated that magnesium deficiency induces abnormal lipid metabolism, which is a promoter of coronary lesions and increases coronary vasospasm. The researchers commented on the possibility that vasospasm may promote coronary lesions by disrupting blood flow characteristics in the vessels.
The authors concluded that the results of this study could be taken as the pathological relationship between coronary artery disease and magnesium. Magnesium deficiency is an important and poorly recognised risk factor for heart disease, which requires more clinical attention. A state of magnesium deficiency can be inferred in our society and is a strong contributor to the high mortality associated with cardiovascular pathology.
Stress, trauma and surgery
Stress = low magnesium
Any significant stressor has a dramatic effect on body magnesium homeostasis. Stress generates an increase in stress hormone (catecholamine) release, which initiates movement of cellular magnesium into the plasma, with associated renal magnesium loss. Catecholamines also induce lipolysis, resulting in increased free fatty acid levels in blood. These fatty acids are able to bind magnesium, resulting in a further reduction in available magnesium and increased renal loss.
These changes in magnesium levels can be brought about by stress from diverse circumstances including traumatic injury, inflammation and unusual environmental conditions.
Complicating the magnesium depleting effect of stress is the exaggerated release of stress hormones during magnesium deficiency. Thus, a vicious cycle can develop where stress increases cellular magnesium loss causing renal magnesium wastage, resulting in an exaggerated stress response.
Stress leads to magnesium depletion, which also exacerbates stress
A French study separated subjects into personality types A and B. Exposure to stress of the type A personalities produced substantial decreases in intracellular magnesium in comparison to the type B subjects. The authors propose that the dramatic magnesium depletion response to elevated stress hormones in the type A personalities is a contributory factor in the higher incidence of stress related disorders and cardiovascular disease observed in these people.
Classen et al examined the magnesium status of 130 children with nervous complaints related to psychosocial and school stresses. They found 16% had hypomagnesaemia, 41.5% had hypocalcaemia and 62% of the children improved with oral magnesium supplementation.
Another French study of children with similar complaints plus latent tetany and respiratory alkalosis, achieved satisfactory improvement in 56% with oral magnesium. There was a partial amelioration in 32% of the children.
A recent study on the effects of surgery on magnesium levels and fatigue demonstrated that surgery results in a significant loss of cellular magnesium and that this was contributory to the fatigue commonly experienced post-surgery.
Stressors, including surgery, increase the release of catecholamines and corticosteroids, both of which deplete cellular magnesium reserves. At the same time, magnesium deficiency results in an abnormal stress response and the release of high levels of catecholamines, which can be prevented with magnesium supplementation.
Without magnesium supplementation, intracellular reserves are depleted, resulting in the mood and behavioural changes commonly seen in these studies. Oral magnesium supplementation is implicated in all situations, which are stressful to patients. These situations include emotional and physically traumatic stressors and administration of magnesium prior to stress is likely to reduce the stress experienced, reduce fatigue and speed recovery.
Anxiety / Neurosis
Magnesium modulates neuronal excitability and decreases membrane fluidity by binding phospholipids and modulates calcium release. These effects are thought to be responsible for the psychological effects of magnesium deficiency: loss of concentration, disorientation, abstract thinking and memory loss.
Magnesium levels were studied in a population of psychiatric in-patients who were admitted with a range of conditions including schizophrenia, mania with depression and neurosis. All patients showed substantially lower magnesium levels than normal. The deviation of magnesium levels from the mean also correlated significantly with severity of symptoms. Supplementation with magnesium is expected to improve the status of psychiatric patients.
Although the pathogenesis of panic disorder is unknown, magnesium therapy offers valuable assistance in panic attacks and neuronal hyperexcitability syndrome. Magnesium supplementation has demonstrated clinically significant responses in panic disorder, by reducing the number of spontaneous attacks per month. There was also a concurrent reduction in noradrenalin secretion in these patients taking magnesium.
Bone tissue is acutely dependent on magnesium for normal metabolic growth and development. Under magnesium deficiency, all phases of bone metabolism, including osteoblast activity, bone formation and fragility, as well as bone response to parathyroid hormone and vitamin D have been altered and the risk of osteoporosis and/or osteomalacia is high.
Research suggests that magnesium is equally as important as calcium in osteoporosis, not least because calcium absorption and utilisation require magnesium. In animal models, magnesium deficiency clearly results in osteoporosis, whereas calcium deficiency generates osteomalacia.
Several studies have also shown that a high magnesium /calcium ratio in the diet of normal women is associated with a greater mean bone density. The only studies to show a positive effect of calcium alone on post-menopausal bone density were of women consuming less than 400 mg of calcium in their daily diet.
The prevalence of magnesium deficiency and its importance in bone mineral health emphasises the value of magnesium supplementation to all persons with any indication of poor bone integrity.
Magnesium deficit is associated with a wide range of complications of female and male reproductive systems. Deficiency increases infertility, risk of miscarriage and preterm birth, low birth weight babies and poor sperm function.
The essential requirement of magnesium for sex hormonal production and function underlies the importance of magnesium in infertility. It is known that oestrogen receptor binding is a magnesium-dependent process and magnesium modulates FSH binding to receptors on the ovary.
It is also known that Mg is important in governing the rate limiting steps in DNA synthesis and mitosis. Further, magnesium deficiency is associated with increased smooth muscle cell tone, which may reduce the patency of an otherwise normal fallopian tube.
Howard et al studied the effect of Mg supplementation on infertile women. All of the women in the study demonstrated low red blood cell magnesium levels, although not all subjects returned to normal, even when given 600 mg/day Mg for four months. Administration of selenium assisted the return of normal RBC Mg levels and all women subsequently fell pregnant within eight months of Mg repletion.
Approximately half of all infertility cases are thought to be wholly, or in part, due to suboptimal male fertility. Magnesium is an essential factor in many of the processes of sperm production and function.
Research on mammals has demonstrated magnesium deficiency to reduce semen volume, sperm count and motility, which can all be reversed with magnesium supplementation. Human research data from the beginning of the century reveals that semen plasma magnesium was then about 30% higher than in the middle of the century, at which time it was lower than normal in 44% of men. The researchers commented, "Accordingly, it seems to be proved that there is a positive correlation between magnesium supply and fertility."
Magnesium reduces pregnancy complications. The multiplicity of actions of magnesium is clearly demonstrable in the complications of pregnancy.
A double-blind study of magnesium supplementation during pregnancy found a significant reduction in complications over controls. Another German study, of over 4,000 women given magnesium during prenatal care, showed a significant decrease in intrauterine growth retardation, premature labour, premature rupture of membranes and hypertensive disorders.
A recent study compared magnesium and iron deficiencies in pregnant rats. It found a deficiency of both magnesium and iron resulted in foetotoxicity, indicating that a lack of magnesium exacerbated the iron deficiency and that "with respect to human pregnancy, magnesium supplementation has a higher priority over iron supplements. To improve tolerance and compliance, both minerals are suggested to be taken simultaneously."
The interrelationships between magnesium and oestrogen are thought to strongly influence the effects of magnesium deficiency and supplementation in conditions affecting women's health.
Leg cramps are common in pregnancy. Magnesium, because of its modulating effect on muscle cell reactivity, has demonstrated positive ameliorative effects.
A recent study found otherwise healthy pregnant patients had a negative magnesium balance, which the researchers noted as typical. These patients were experiencing leg cramps and were included in the double-blind randomised placebo controlled trial. Oral magnesium supplementation effectively reduced leg cramps in comparison to controls, although the magnesium levels of the patients remained suboptimal after three weeks.
Eclampsia remains one of the leading causes of maternal and perinatal mortality in many parts of the world. Magnesium sulphate is routinely used in current obstetrics as the primary therapy for the hypertensive crisis of pre-eclampsia. Present management of eclampsia aims to stop the convulsions and prevent recurrence, control the blood pressure and correct fluid and electrolyte imbalance.
As magnesium is a regulatory mineral in all of these processes, the result of clinical trials demonstrates the potential of supplementation to avert the crisis.
Several studies indicate a low magnesium intake or tissue store to be associated with a greater risk of developing pre-eclampsia. Favourable results have been reported in 80% of 3,000 women given 200 mg/day Mg for prophylaxis of pre-eclampsia, while they were pregnant. The supplementation resulted in marked reduction in pre-eclamptic episodes in patients taking prophylactic magnesium.
The uterine antispasmodic property of magnesium and the prevalence of its deficiency underlies the importance of supplementation during pregnancy, especially in those women at risk of early delivery. Magnesium is currently being used successfully either with tocolytic therapy or alone, to prevent premature uterine contractions and preterm births.
A study comparing the amount of fenoterol (a uterine antispasmodic) required either alone or in combination with magnesium in preterm mothers, found that the dosage could be reduced by 50%. Two hundred and fifty-five expectant mothers were randomly selected for a double-blind trial using 300mg/day prophylactic magnesium from diagnosis of pregnancy to delivery. Preterm delivery rate was significantly lower in the supplemental versus the control group.
Inadequate intake and deficiencies in magnesium are associated with the occurrence and severity of premenstrual syndrome. Magnesium supplementation has shown positive effects in women experiencing the condition.
A double-blind randomised study using 360 mg Mg three times daily resulted in significant improvement in the Moos Menstrual Distress Questionnaire. It was not until two months later that any change in lymphocyte or polymorphonuclear cell magnesium levels was noticed. Even after this time, no elevations were seen in serum or erythrocyte magnesium. This study demonstrates the degree of intracellular magnesium deficiency in many of these patients and the prolonged time necessary to correct cellular reserves with supplemental magnesium.
As magnesium is a natural calcium channel blocker, high doses of magnesium may demonstrate features similar to a magnesium deficiency. Indeed, research on premenstrual syndrome has found that a high calcium intake is associated with increased severity of symptoms.
The interaction of magnesium with oestrogen is likely to be a significant factor with respect to the pathogenesis of this common clinical problem and prophylactic magnesium supplementation is expected to provide relief to a large proportion of these women.
The higher incidence of migraine amongst those prone to cellular magnesium depletion and the influence of magnesium on prostanoids and thrombogenesis support the premise that magnesium deficiency is involved in the pathogenesis of migraine.
Additional factors suggesting a role of magnesium deficiency in migraines include the role of magnesium in serotonin release and in vascular reactivity to serotonin. Migraine sufferers are known to release more serotonin from platelets than non-sufferers, which may contribute to vasospasm.
Calcium channel blockers have been effective in reducing migraines and as magnesium is a natural Ca channel blocker, this may be a further mechanism to explain the clinical effectiveness of magnesium against migraines.
Menstrual migraine is a problem for many women. The association between magnesium and both migraines and premenstrual syndrome suggests supplementation will benefit those sufferers.
A double-blind placebo controlled study using 360 mg/day Mg found a reduction in number of migraines and also in their duration and intensity. The beneficial effects of magnesium in this study were seen in all of the patients taking magnesium. The authors suggest low magnesium levels may lower the migraine threshold. A significant rise in magnesium status indices was found in those patients taking supplementation.
Physical exertion and athletic performance are dependent on magnesium for ATP phosphorylation. Studies demonstrating a broad deficiency of magnesium in society, point to athletes as being at high risk of developing magnesium deficiency because of their higher metabolic demands and increased losses through sweating.
Hypomagnesaemia is associated with decreased physical performance and increased incidence of muscle cramps, which improve with magnesium supplementation. A study of swimmers taking 65 mg elemental magnesium found an 86% reduction in muscle cramps. The reductions occurred after only three days of supplementation.
The prevalence of magnesium deficiency and the high risk of depletion for athletes indicate that supplementation may benefit these individuals.
Several researchers have discovered improved performance with magnesium supplementation. Female endurance athletes taking magnesium supplementation (15 mmol/day) found they could run at maximal intensity for longer, that submaximal O2 uptake decreased by 10 per cent, whereas maximal oxygen uptake (VO2) increased with a parallel change in workload. They also found submaximal respiratory minute volume and CO2 formation decreased significantly, while maximal parameters increased. This data suggests an improvement in oxygen utilisation during magnesium supplementation, in female endurance athletes not exhibiting magnesium deficiency signs. The red blood cell magnesium content of the women taking magnesium increased significantly by 8%.
Fencing athletes and male soccer players demonstrated similar biochemical responses to magnesium supplementation, as well as a lowering of heart rate and lactate formation.
Magnesium plays an important role in protein synthesis and this function may be most sensitive to magnesium insufficiency. DNA transcription, RNA aggregation and protein synthesis are all dependent on optimal magnesium concentration. During strength training, a suboptimal magnesium level would be likely to hinder gains from training.
A double-blind, placebo controlled, 7-week strength training program in 26 untrained subjects receiving magnesium found those being supplemented derived greater benefit from the training over controls. Dietary records of the patients were analysed and these athletes were supplemented with magnesium to bring them up to 8 mg/kg/day. This resulted in significant difference in strength gains in these athletes.
Carcinogenic potential of heavy metals
The effect of magnesium on tumour growth in animal systems has been known for several years. Part of the tumour inhibitory activity of magnesium is proposed to be due to a chemopreventive effect of heavy metal carcinogenesis.
Heavy metals have several unique characteristics. Firstly, they have remarkable target site specificity and secondly, unlike organic carcinogens, they do not require metabolic activation. Metals are emerging as very important carcinogens, with research increasingly demonstrating their toxicity and an increase in their distribution by industry.
Protection against DNA damage and carcinogenesis may be possible with magnesium. Simultaneous administration of magnesium with nickel carcinogens has been shown to eliminate the DNA methylation and carcinogenic potential of this metal.
Physiological oral magnesium is associated with practically only one contraindication: overt renal failure.