Magnesium

This section was compiled by Frank M. Painter, D.C.
Send all comments or additions to:   Frankp@chiro.org

If there are terms in these articles you don't understand, you can get a definition from the Merriam Webster Medical Dictionary. If you want information about a specific disease, you can access the Merck Manual. You can also search Pub Med for more abstracts on this, or any other health topic.

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	Magnesium Status and Stress: The Vicious Circle Concept Revisited Nutrients 2020 (Nov 28);   12 (12):   pii: E3672 To conclude, while there is good evidence from animal and human studies of the bi-directional link between magnesium and stress, further research is needed to better understand the impact of this correlation and the benefit of magnesium supplementation on general health. Additional studies should apply standard methodologies (e.g., magnesium load test) to evaluate the magnesium status in well-characterized stressed population. These studies would help to demonstrate the increased need of magnesium supplementation during stress periods, and further strengthen our initial hypothesis. Further, in line with the GUTS model, repetitive negative thinking could be considered as a cognitive indicator of stress and evaluated in relation to blood magnesium levels in a cohort of subjects exposed to chronic stress. Given the strong association of stress with mental and physical diseases, these studies are fundamental to further support adequate magnesium dietary needs.
	Effect of Oral Magnesium Supplementation On Physical Performance in Healthy Elderly Women Involved in a Weekly Exercise Program: A Randomized Controlled Trial pii: ajcn.080168. [Epub ahead of print] At baseline, the SPPB scores did not differ between the 2 groups. After 12 wk, the treated group had a significantly better total SPPB score (Δ = 0.41 ± 0.24 points; P = 0.03), chair stand times (Δ = -1.31 ± 0.33 s; P < 0.0001), and 4-m walking speeds (Δ = 0.14 ± 0.03 m/s; P = 0.006) than did the control group.
	Can Magnesium Cure Migraines? About 18 million women and some 5 million men in the United States suffer from migraine headaches. Only about a third are satisfied with their treatments, which can range from over-the-counter headache remedies to serotonin receptor antagonists, beta-blockers and calcium antagonists. Many of these prescription drugs come with an array of side effects. But what if a mineral could make a difference for migraine sufferers?

General Magnesium Information:

Consequences of Magnesium Deficiency on the Enhancement of Stress Reactions; Preventive and Therapeutic Implications (A Review)


Magnesium Metabolism in Health and Disease

Magnesium and Pregnancy:

Vitamin and Mineral Deficiencies Which May Predispose to Glucose Intolerance of Pregnancy


The Pathogenesis of Eclampsia: The 'Magnesium Ischaemia' Hypothesis


Effects of a Combination of Evening Primrose Oil (Gamma linolenic acid) and Fish Oil (Eicosapentaenoic + Docahexaenoic acid) versus Magnesium, and versus Placebo in Preventing Pre-eclampsia

Intakes of Vitamins and Minerals by Pregnant Women with Selected Clinical Symptoms

Magnesium and Premenstrual Syndrome:

Clinical and Biochemical Effects of Nutritional Supplementation on the Premenstrual Syndrome


Plasma Copper, Zinc and Magnesium Levels in Patients with Premenstrual Tension Syndrome


Oral Magnesium Successfully Relieves Premenstrual Mood Changes

Magnesium and Heart Disease:

Magnesium and Sudden Death


An Expanded Concept of "Insurance": Supplementation--Broad-spectrum Protection from Cardiovascular Disease


Magnesium in Supraventricular and Ventricular Arrhythmias


Trace Elements in Prognosis of Myocardial Infarction and Sudden Coronary Death

Magnesium and ADD/ADHD:

Deficiency of Certain Trace Elements in Children With Hyperactivity

Magnesium and Glucose Regulation:

Daily Magnesium Supplements Improve Glucose Handling in Elderly Subjects


Magnesium and Carbohydrate Metabolism


Magnesium Intake and Risk of Type 2 Diabetes in Men and Women


Magnesium and Potassium in Diabetes and Carbohydrate Metabolism. Review of the Present Status and Recent Results


Hypertension, Diabetes Mellitus, and Insulin Resistance: The Role of Intracellular Magnesium

Magnesium and Asthma:

Skeletal Muscle Magnesium and Potassium in Asthmatics Treated with Oral Beta2-agonists


Bronchial Reactivity and Dietary Antioxidants


See also:    Research Perspectives in Asthma:   A Rationale for the Therapeutic Application of Magnesium, Pyridoxine, Coleus forskholii and Ginkgo biloba in the Treatment of Adult and Pediatric Asthma
The Internist 1998;   5 (3) Sept:   14–16 ~ FULL TEXT

Magnesium and Chronic Fatigue Syndrome aka Fibromyalgia:

Complementary and Alternative Medical Therapies in Fibromyalgia


Magnesium Deficit in a Sample of the Belgian Population Presenting with Chronic Fatigue


Selenium and Magnesium Status in Fibromyalgia

Magnesium and Osteoporosis:

Magnesium Deficiency: Possible Role in Osteoporosis Associated with Gluten-sensitive Enteropathy

Magnesium Supplementation and Osteoporosis


Calcium, Phosphorus and Magnesium Intakes Correlate with Bone Mineral Content in Postmenopausal Women

Magnesium and Other Ailments:

Magnesium Taurate and Fish Oil for Prevention of Migraine


Prophylaxis of Migraine with Oral Magnesium: Results from a Prospective, Multi-center, Placebo-controlled and Double-blind Randomized Study


Electromyographical Ischemic Test and Intracellular and Extracellular Magnesium Concentration in Migraine and Tension-type Headache Patients

Experimental and Clinical Studies on Dysregulation of Magnesium Metabolism and the Aetiopathogenesis of Multiple Sclerosis


Amyotrophic Lateral Sclerosis--Causative Role of Trace Elements


Nutrient Intake of Patients with Rheumatoid Arthritis is Deficient in Pyridoxine, Zinc, Copper, and Magnesium

General Magnesium Information:

Consequences of Magnesium Deficiency on the Enhancement of Stress Reactions; Preventive and Therapeutic Implications (A Review)
J Am Coll Nutr 1994 (Oct); 13 (5): 429-446

Stress intensifies release of catecholamines and corticosteroids that increase survival of normal animals when their lives are threatened. When magnesium (Mg) deficiency exists, stress paradoxically increases risk of cardiovascular damage including hypertension, cerebrovascular and coronary constriction and occlusion, arrhythmias and sudden cardiac death (SCD). In affluent societies, severe dietary Mg deficiency is uncommon, but dietary imbalances such as high intakes of fat and/or calcium (Ca) can intensify Mg inadequacy, especially under conditions of stress. Adrenergic stimulation of lipolysis can intensify its deficiency by complexing Mg with liberated fatty acids (FA), A low Mg/Ca ratio increases release of catecholamines, which lowers tissue (i.e. myocardial) Mg levels. It also favors excess release or formation of factors (derived both from FA metabolism and the endothelium), that are vasoconstrictive and platelet aggregating; a high Ca/Mg ratio also directly favors blood coagulation, which is also favored by excess fat and its mobilization during adrenergic lipolysis. Auto-oxidation of catecholamines yields free radicals, which explains the enhancement of the protective effect of Mg by anti-oxidant nutrients against cardiac damage caused by beta-catecholamines. Thus, stress, whether physical (i.e. exertion, heat, cold, trauma--accidental or surgical, burns), or emotional (i.e. pain, anxiety, excitement or depression) and dyspnea as in asthma increases need for Mg. Genetic differences in Mg utilization may account for differences in vulnerability to Mg deficiency and differences in body responses to stress.

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Magnesium Metabolism in Health and Disease
DIS. MON. (USA), 1988, 34/4 (166-218)

Magnesium is an important element for health and disease. Magnesium, the second most abundant intracellular cation, has been identified as a cofactor in over 300 enzymatic reactions involving energy metabolism and protein and nucleic acid synthesis. Approximately half of the total magnesium in the body is present in soft tissue, and the other half in bone. Less than 1% of the total body magnesium is present in blood. Nonetheless, the majority of our experimental information comes from determination of magnesium in serum and red blood cells. At present, we have little information about equilibrium among and state of magnesium within body pools. Magnesium is absorbed uniformly from the small intestine and the serum concentration controlled by excretion from the kidney. The clinical laboratory evaluation of magnesium status is primarily limited to the serum magnesium concentration, 24-hour urinary excretion, and percent retention following parenteral magnesium. However, results for these tests do not necessarily correlate with intracellular magnesium. Thus, there is no readily available test to determine intracellular/total body magnesium status. Magnesium deficiency may cause weakness, tremors, seizures, cardiac arrhythmias, hypokalemia, and hypocalcemia. The causes of hypomagnesemia are reduced intake (poor nutrition or IV fluids without magnesium), reduced absorption (chronic diarrhea, malabsorption, or bypass/resection of bowel), redistribution (exchange transfusion or acute pancreatitis), and increased excretion (medication, alcoholism, diabetes mellitus, renal tubular disorders, hypercalcemia, hyperthyroidism, aldosteronism, stress, or excessive lactation). A large segment of the U.S. population may have an inadequate intake of magnesium and may have a chronic latent magnesium deficiency that has been linked to atherosclerosis, myocardial infarction, hypertension, cancer, kidney stones, premenstrual syndrome, and psychiatric disorders. Hypermagnesemia is primarily seen in acute and chronic renal failure, and is treated effectively by dialysis.

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Magnesium and Pregnancy:

Vitamin and Mineral Deficiencies Which May Predispose to Glucose Intolerance of Pregnancy
Journal of the American College of Nutrition 1996 (Feb); 15(1):14-20

There is an increased requirement for nutrients in normal pregnancy, not only due to increased demand, but also increased loss. There is also an increased insulin resistant state during pregnancy mediated by the placental anti-insulin hormones estrogen, progesterone, human somatomammotropin; the pituitary hormone prolactin; and the adrenal hormone, cortisol. If the maternal pancreas cannot increase production of insulin to sustain normoglycemia despite these anti-insulin hormones, gestational diabetes occurs. Gestational diabetes is associated with excessive nutrient losses due to glycosuria. Specific nutrient deficiencies of chromium, magnesium, potassium and pyridoxine may potentiate the tendency towards hyperglycemia in gestational diabetic women because each of these four deficiencies causes impairment of pancreatic insulin production. This review describes the pathophysiology of the hyperglycemia and the nutrient loss in gestational diabetes and further postulates the mechanism whereby vitamin/mineral supplementation may be useful to prevent or ameliorate pregnancy-related glucose intolerance.

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The Pathogenesis of Eclampsia: The 'Magnesium Ischaemia' Hypothesis
Med Hypotheses 1993 (Apr); 40 (4): 250-256

'Magnesium ischaemia' is a term used to denote the functional impairment of the ATP-dependent sodium/potassium and calcium pumps in the cell membranes and within the cell itself. The production of ATP and the functioning of these pumps is magnesium-dependent and is critically sensitive to acidosis. Zinc and iron deficiencies may secondarily impair these pumps and thus contribute to 'magnesium ischaemia' (as does acidosis). This term is two-dimensional at its simplest; it refers to a functional magnesium deficiency, whether actual or induced. It is argued that chronic acidosis is the most common inducing factor. This simple hypothesis can begin to unify diverse pathophysiologies: some spontaneous abortions, aspects of Type II and gestational diabetes and the curious observation that heroin addicts become diabetic. It can also unify clinical thinking about pregnancy-induced hypertension, pre-eclampsia/eclampsia and acute fatty liver of pregnancy, as well as the coagulopathy of pregnancy. It makes important predictions about perinatal morbidity and suggests that early supplementation might prevent much pregnancy-induced disease.

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Effects of a Combination of Evening Primrose Oil (Gamma linolenic acid) and Fish Oil (Eicosapentaenoic + Docahexaenoic acid) versus Magnesium, and versus Placebo in Preventing Pre-eclampsia
Women Health 1992; 19 (2-3): 117-131

In a placebo controlled, partially double-blinded, clinical trial, a combination of evening primrose oil and fish oil was compared to Magnesium Oxide, and to a Placebo in preventing Pre-Eclampsia of Pregnancy. All were given as nutritional supplements for six months to a group of primiparous and multiparous pregnant women. Some of these women had personal or family histories of hypertension (21%). Only those patients who received prenatal care at the Central Maternity Hospital for Luanda were included in the study. Compared to the Placebo group (29%), the group receiving the mixture of evening primrose oil and fish oil containing Gamma-linolenic acid (GLA), Eicosapentaenoic acid (EPA), and Docosahexaenoic acid (DHA) had a significantly lower incidence of edema (13%, p = 0.004). The group receiving Magnesium Oxide had statistically significant fewer subjects who developed hypertension of pregnancy. There were 3 cases of eclampsia, all in the Placebo group.

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Intakes of Vitamins and Minerals by Pregnant Women with Selected Clinical Symptoms
J Am Diet Assoc 1981 (may); 78 (5): 477-482

Toxemia in pregnancy is characterized by a combination of at least two of the following clinical symptoms: hypertension, edema, and proteinuria. In this study the dietary intakes of young pregnant women attending a Maternal and Infant Care Program at Tuskegee Institute were evaluated for selected vitamins and minerals. Women with toxemia were identified, and women without toxemia served as controls. The toxemia group generally consumed lesser amounts of vitamins and minerals than the controls. However, both groups were deficient (less than two-thirds RDA) in calcium, magnesium, vitamin B6, vitamin B12, and thiamin. Milk, meat, and grains supplied an appreciable proportion of each vitamin except vitamin A, which was found primarily in the two vegetable groups. Meat and grains contained the greatest quantities of minerals, but milk provided a relatively good proportion of potassium, calcium, magnesium, and phosphorus. Anemia was not related to the incidence of toxemia. Women exhibiting anemia consumed smaller amounts of vitamins studied than did women without anemia.

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Magnesium and Premenstrual Syndrome:

Clinical and Biochemical Effects of Nutritional Supplementation on the Premenstrual Syndrome
J Reprod Med1987 (Jun); 32 (6): 435-441

Many different treatments have been suggested for the premenstrual syndrome (PMS), including such nutritional supplements as vitamins, minerals and essential fatty acids. There is little agreement about the causes or treatments of the syndrome. The effect of a nutritional supplement, at high and low dosage, on premenstrual symptoms was assessed in a double-blind, placebo-controlled study. Also, the nutritional state of 11 women with PMS was evaluated. There was laboratory evidence of significant deficiencies in vitamin B6 and magnesium; other deficiencies occurred frequently, also. The multivitamin/multimineral supplement was shown to correct some of these deficiencies and, at the appropriate dosage, to improve the symptoms of premenstrual tension.

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Plasma Copper, Zinc and Magnesium Levels in Patients with Premenstrual Tension Syndrome
Acta Obstet Gynecol Scand 1994 (Jul); 73 (6): 452-5

We measured plasma Cu, Zn and Mg levels in 40 women suffering from premenstrual tension syndrome (PMTS) and in 20 control subjects by atomic absorption spectrophotometer. Mean plasma Cu, Zn and Mg levels, the Zn/Cu ratio were 80.2 plus or minus 6.00 microg/dl, 112.6 plus or minus 8.35 microg/dl, 0.70 plus or minus 0.18 mmol/l, and 1.40 plus or minus 0.10 in the PMTS group; and 77.0 plus or minus 4.50 microg/dl, 117.4 plus or minus 9.50 microg/dl, 0.87 plus or minus 0.10 mmol/l, and 1.51 plus or minus 0.05 in the control group respectively. The mean Mg level and the Zn/Cu ratio were significantly lower in PMTS patients than in the control group. Plasma Mg and Zn levels were diminished significantly during the luteal phase compared to the follicular phase in PMTS group. Mg deficiency may play a role in the etiology of PMTS.

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Oral Magnesium Successfully Relieves Premenstrual Mood Changes
Obstet Gynecol 1991 (Aug); 78 (2): 177-81

Reduced magnesium (Mg) levels have been reported in women affected by premenstrual syndrome (PMS). To evaluate the effects of an oral Mg preparation on premenstrual symptoms, we studied, by a double-blind, randomized design, 32 women (24-39 years old) with PMS confirmed by the Moos Menstrual Distress Questionnaire. After 2 months of baseline recording, the subjects were randomly assigned to placebo or Mg for two cycles. In the next two cycles, both groups received Mg. Magnesium pyrrolidone carboxylic acid (360 mg Mg) or placebo was administered three times a day, from the 15th day of the menstrual cycle to the onset of menstrual flow. Blood samples for Mg measurement were drawn premenstrually, during the baseline period, andin the second and fourth months of treatment. The Menstrual Distress Questionnaire score of the cluster 'pain' was significantly reduced during the second month in both groups, whereas Mg treatment significantly affected both the total Menstrual Distress Questionnaire score and the cluster 'negative affect'. In the second month, the women assigned to treatment showed a significant increase in Mg in lymphocytes and polymorphonuclear cells, whereas no changes were observed in plasma and erythrocytes. These data indicate that Mg supplementation could represent an effective treatment of premenstrual symptoms related to mood changes.

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Magnesium and Heart Disease:

Magnesium and Sudden Death
S Afr Med J 1983 (Nov 12); 64 (21): 820-2

Magnesium deficiency may result from reduced dietary intake of the ion increased losses in sweat, urine or faeces. Stress potentiates magnesium deficiency, and an increased incidence of sudden death associated with ischaemic heart disease is found in some areas in which soil and drinking water lack magnesium. Furthermore, it has been demonstrated experimentally that reduction of the plasma magnesium level is associated with arterial spasm. Careful studies are required to assess the clinical importance of magnesium and the benefits of magnesium supplementation in man.

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An Expanded Concept of "Insurance": Supplementation-- Broad-spectrum Protection from Cardiovascular Disease
Med Hypotheses 1981 (Oct); 7 (10): 1287-1302

The preventive merits of "nutritional insurance" supplementation can be considerably broadened if meaningful doses of nutrients such as mitochondrial "metavitamins" (coenzyme Q, lipoic acid, carnitine), lipotropes, and key essential fatty acids, are included in insurance supplements. From the standpoint of cardiovascular protection, these nutrients, as well as magnesium, selenium, and GTF-chromium, appear to have particular value. Sophisticated insurance supplementation would likely have a favorable impact on many parameters which govern cardiovascular risk--serum lipid profiles, blood pressure, platelet stability, glucose tolerance, bioenergetics, action potential regulation--and as a life-long preventive health strategy might confer substantial benefit.

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Magnesium in Supraventricular and Ventricular Arrhythmias
Zeitschrift fur Kardiologie 1996; 85 Suppl 6: 135-145

The use of magnesium as an antiarrhythmic agent in ventricular and supraventricular arrhythmias is a matter of an increasing but still controversial discussion during recent years. With regard to the well established importance of magnesium in experimental studies for preserving electrical stability and function of myocardial cells and tissue, the use of magnesium for treating one or the other arrhythmia seems to be a valid concept. In addition, magnesium application represents a physiologic approach, and by this, is simple, cost-effective and safe for the patient. However, when one reviews the available data from controlled studies on the antiarrhythmic effects of magnesium, there are only a few types of cardiac arrhythmias, such as torsade de pointes, digitalis-induced ventricular arrhythmias and ventricular arrhythmias occurring in the presence of heart failure or during the perioperative state, in which the antiarrhythmic benefit of magnesium has been shown and/or established. Particularly in patients with one of these types of cardiac arrhythmias, however, it should be realized that preventing the patient from a magnesium deficit is the first, and the application of magnesium the second best strategy to keep the patient free from cardiac arrhythmias.

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Trace Elements in Prognosis of Myocardial Infarction and Sudden Coronary Death
Journal of Trace Elements in Experimental Medicine (USA), 1996, 9/2 (57-62)

Ca, Cu, Mg, Mn, and Zn concentrates were measured in plasma, RBC, and hair of 350 men aged 40-59 years with myocardial infarction (MI) and/or who died from sudden cardiac death (SCD), as compared with normal controls. Analyses were done by flame atomic absorption spectrophotometry. Cu in plasma of MI patients was significantly higher than the controls'. Plasma Mn was significantly lower in SCD than in MI subjects. No other consistent and significant changes were observed. Past and present evidence indicates that high plasma Cu levels may be associated with heart failure and rhythm disorders. The low plasma Mn levels may be an indicator of decreased parasympathetic tonus thus favouring myocardial desynchronization and A-V block. Cu inhibits phosphodiesterase activity and Mn inhibits andenylate cyclase activity thus exerting an influence on the contractility of cardiomyocites and of smooth muscle cells in coronary arteries. Cu and Mn analyses may thus have a prognostic significance for MI and SCD.

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Magnesium and ADD/ADHD:

Deficiency of Certain Trace Elements in Children with Hyperactivity
Psychiatr Pol (POLAND) May-Jun 1994, 28 (3) p345-53

The magnesium, zinc, copper, iron and calcium level of plasma, erythrocytes, urine and hair in 50 children aged from 4 to 13 years with hyperactivity, were examined by AAS. The average concentration of all trace elements was lower compared with the control group-healthy children from Szczecin. The highest deficit was noted in hair. Our results show that it is necessary to supplement trace elements in children with hyperactivity.

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Magnesium and Glucose Regulation:

Daily Magnesium Supplements Improve Glucose Handling in Elderly Subjects
Am J Clin Nutr 1992 (Jun); 55 (6): 1161-1167

We demonstrated similar plasma concentrations and urinary losses but lower erythrocyte magnesium concentrations (2.18 +/- 0.04 vs 1.86 +/- 0.03 mmol/L, P less than 0.01) in twelve aged (77.8 +/- 2.1 y) vs 25 young (36.1 +/- 0.4 y), nonobese subjects. Subsequently, aged subjects were enrolled in a double-blind, randomized, crossover study in which placebo (for 4 wk) and chronic magnesium administration (CMA) (4.5 g/d for 4 wk) were provided. At the end of each treatment period an intravenous glucose tolerance test (0.33 g/kg body wt) and a euglycemic glucose clamp with simultaneous [D-3H]glucose infusion and indirect calorimetry were performed. CMA vs placebo significantly increased erythrocyte magnesium concentration and improved insulin response and action. Net increase in erythrocyte magnesium significantly and positively correlated with the decrease in erythrocyte membrane microviscosity and with the net increase in both insulin secretion and action. In aged patients, correction of a low erythrocyte magnesium concentration may allow an improvement of glucose handling.

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Magnesium and Carbohydrate Metabolism
THERAPIE (France), 1994, 49/1 (1-7)

The interrelationships between magnesium and carbohydrate metabolism have regained considerable interest over the last few years. Insulin secretion requires magnesium: magnesium deficiency results in impaired insulin secretion while magnesium replacement restores insulin secretion. Furthermore, experimental magnesium deficiency reduces the tissues sensitivity to insulin. Subclinical magnesium deficiency is common in diabetes. It results from both insuficient magnesium intakes and increase magnesium losses, particularly in the urine. In type 2, or non-insulin-dependent, diabetes mellitus, magnesium deficiency seems to be associated with insulin resistance. Furthermore, it may participate in the pathogenesis of diabetes complications and may contribute to the increased risk of sudden death associated with diabetes. Some studies suggest that magnesium deficiency may play a role in spontaneous abortion of diabetic women, in fetal malformations and in the pathogenesis of neonatal hypocalcemia of the infants of diabetic mothers. Administration of magnesium salts to patients with type 2 diabetes tend to reduce insulin resistance. Long-term studies are needed before recommending systematic magnesium supplementation to type 2 diabetic patients with subclinical magnesium deficiency.

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Magnesium Intake and Risk of Type 2 Diabetes in Men and Women
Diabetes Care 2004 (Jan); 27 (1): 134-140

OBJECTIVE: To examine the association between magnesium intake and risk of type 2 diabetes.

RESEARCH DESIGN AND METHODS: We followed 85,060 women and 42,872 men who had no history of diabetes, cardiovascular disease, or cancer at baseline. Magnesium intake was evaluated using a validated food frequency questionnaire every 2-4 years. After 18 years of follow-up in women and 12 years in men, we documented 4,085 and 1,333 incident cases of type 2 diabetes, respectively.

RESULTS: After adjusting for age, BMI, physical activity, family history of diabetes, smoking, alcohol consumption, and history of hypertension and hypercholesterolemia at baseline, the relative risk (RR) of type 2 diabetes was 0.66 (95% CI 0.60-0.73; P for trend <0.001) in women and 0.67 (0.56-0.80; P for trend <0.001) in men, comparing the highest with the lowest quintile of total magnesium intake. The RRs remained significant after additional adjustment for dietary variables, including glycemic load, polyunsaturated fat, trans fat, cereal fiber, and processed meat in the multivariate models. The inverse association persisted in subgroup analyses according to BMI, physical activity, and family history of diabetes.

CONCLUSIONS: Our findings suggest a significant inverse association between magnesium intake and diabetes risk. This study supports the dietary recommendation to increase consumption of major food sources of magnesium, such as whole grains, nuts, and green leafy vegetables.

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Magnesium and Potassium in Diabetes and Carbohydrate Metabolism. Review of the Present Status and Recent Results
Magnesium. 1984. 3(4-6). P 315-23

Diabetes mellitus is the most common pathological state in which secondary magnesium deficiency occurs. Magnesium metabolism abnormalities vary according to the multiple clinical forms of diabetes: plasma magnesium is more often decreased than red blood cell magnesium. Plasma Mg levels are correlated mainly with the severity of the diabetic state, glucose disposal and endogenous insulin secretion. Various mechanisms are involved in the induction of Mg depletion in diabetes mellitus, i.e. insulin and epinephrine secretion, modifications of the vitamin D metabolism, decrease of blood P, vitamin B6 and taurine levels, increase of vitamin B5, C and glutathione turnover, treatment with high levels of insulin and biguanides. K depletion in diabetes mellitus is well known. Some of its mechanisms are concomitant to those of Mg depletion. But their hierarchic importance is not the same: i.e., insulin hyposecretion is more important versus K+ than versus Mg2+. Insulin increases the cellular inflow of K+ more than that of Mg2+ because there is more free K+ (87%) than Mg2+ (30%) in the cell. The consequences of the double Mg-K depletion are either antagonistic: i.e. versus insulin secretion (increased by K+, decreased by Mg2+) or agonistic i.e. on the membrane: (i.e. Na+K+ATPase), tolerance of glucose oral load, renal disturbances. The real importance of these disorders in the diabetic condition is still poorly understood. Retinopathy and microangiopathy are correlated with the drop of plasma and red blood cell Mg. K deficiency increases the noxious cardiorenal effects of Mg deficiency. The treatment should primarily insure diabetic control.

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Hypertension, Diabetes mellitus, and Insulin Resistance: The Role of Intracellular Magnesium
Am J Hypertens (UNITED STATES) Mar 1997, 10 (3) p346-55

Magnesium is one of the most abundant ions present in living cells and its plasma concentration is remarkably constant in healthy subjects. Plasma and intracellular magnesium concentrations are tightly regulated by several factors. Among them, insulin seems to be one of the most important. In fact, in vitro and in vivo studies have demonstrated that insulin may modulate the shift of magnesium from extracellular to intracellular space. Intracellular magnesium concentration has also been shown to be effective on modulating insulin action (mainly oxidative glucose metabolism), offset calcium-related excitation-contraction coupling, and decrease smooth cell responsiveness to depolarizing stimuli, by stimulating Ca2+-dependent K+ channels. A poor intracellular magnesium concentration, as found in non-insulin-dependent diabetes mellitus (NIDDM) and in hypertensive (HP) patients, may result in a defective tyrosine-kinase activity at the insulin receptor level and exaggerated intracellular calcium concentration. Both events are responsible for the impairment in insulin action and a worsening of insulin resistance in non-insulin-dependent diabetic and hypertensive patients. By contrast, in NIDDM patients daily magnesium administration, restoring a more appropriate intracellular magnesium concentration, contributes to improve insulin-mediated glucose uptake. Similarly, in HP patients magnesium administration may be useful in decreasing arterial blood pressure and improving insulin-mediated glucose uptake. The benefits deriving from daily magnesium supplementation in NIDDM and HP patients are further supported by epidemiological studies showing that high daily magnesium intake to be predictive of a lower incidence of NIDDM and HP. In conclusion, a growing body of studies suggest that intracellular magnesium may play a key role on modulating insulin-mediated glucose uptake and vascular tone. We further suggest that a reduced intracellular magnesium concentration might be the missing link helping to explain the epidemiological association between NIDDM and hypertension.

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Magnesium and Asthma:

Skeletal Muscle Magnesium and Potassium in Asthmatics Treated with Oral Beta2-agonists
European Respiratory Journal (Denmark), 1996, 9/2 (237-240)

Dietary magnesium has been shown to be important for lung function and bronchial reactivity. Interest in electrolytes in asthma has so far mainly been focused upon serum potassium, especially linked to beta2-agonist treatment. It is known that serum levels of magnesium and potassium may not correctly reflect the intracellular status. We therefore investigated whether asthmatics treated with oral beta2-agonists had low magnesium or potassium in skeletal muscle and serum, and whether withdrawal of the oral beta2-agonists would improve the electrolyte levels. Magnesium and potassium levels in skeletal muscle biopsies, serum and urine were analysed in 20 asthmatics before and 2 months after withdrawal of long-term oral beta2-agonists, and for comparison in 10 healthy subjects. Skeletal muscle magnesium in the asthmatics was lower both before (3.62plus or minus0.69 mmol-100 g-1 (meanplus or minusSD)) and after (3.43plus or minus0.60 mmol.100 g-1) withdrawal of oral beta2-agonists compared with the controls (4.43plus or minus0.74 mmol-100 g-1) Skeletal muscle potassium and serum magnesium did not differ between the groups. Serum potassium was significantly lower both before (4.0plus or minus0.2 mmol.L-1) and after (3.9plus or minus0.2 mmol.L-1) the withdrawal of oral beta2-agonists compared with the control group (42plus or minus0.2 mmol.L-1). The asthmatics had lower skeletal muscle magnesium and lower serum potassium than the healthy controls, both with and without oral beta2-agonists. Whether the findings are related to asthma pathophysiology or treatment is currently being investigated.

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Bronchial Reactivity and Dietary Antioxidants
Thorax (United Kingdom), 1997, 52/2 (166-170)

BACKGROUND - It has been postulated that dietary antioxidants may influence the expression of allergic diseases and asthma. To test this hypothesis a case-control study was performed, nested in a cross sectional study of a random sample of adults, to investigate the relationship between allergic disease and dietary antioxidants.

METHODS - The study was performed in rural general practices in Grampian, Scotland. A validated dietary questionnaire was used to measure food intake of cases, defined, firstly, as people with seasonal allergic-type symptoms and, secondly, those with bronchial hyperreactivity confirmed by methacholine challenge, and of controls without allergic symptoms or bronchial reactivity.

RESULTS - Cases with seasonal symptoms did not differ from controls except with respect to the presence of atopy and an increased risk of symptoms associated with the lowest intake of zinc. The lowest intakes of vitamin C and manganese were associated with more than five-fold increased risks of bronchial reactivity. Decreasing intakes of magnesium were also significantly associated with an increased risk of hyperreactivity.

CONCLUSIONS - This study provides evidence that diet may have a modulatory effect on bronchial reactivity, and is consistent with the hypothesis that the observed reduction in antioxidant intake in the British diet over the last 25 years has been a factor in the increase in the prevalence of asthma over this period.

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Magnesium and Chronic Fatigue Syndrome aka Fibromyalgia:

Complementary and Alternative Medical Therapies in Fibromyalgia
Curr Pharm Des 2006; 12 (1): 47-57

This article describes the studies that have been performed evaluating complementary or alternative medical (CAM) therapies for efficacy and some adverse events fibromyalgia (FM). There is no permanent cure for FM; therefore, adequate symptom control should be goal of treatment. Clinicians can choose from a variety of pharmacologic and nonpharmacologic modalities. Unfortunately, controlled studies of most current treatments have failed to demonstrate sustained, clinically significant responses. CAM has gained increasing popularity, particularly among individuals with FM for which traditional medicine has generally been ineffective. Some herbal and nutritional supplements (magnesium, S- adenosylmethionine) and massage therapy have the best evidence for effectiveness with FM. Other CAM therapies such as chlorella, biofeedback, relaxation have either been evaluated in only one randomised controlled trials (RCT) with positive results, in multiple RCTs with mixed results (magnet therapies) or have positive results from studies with methodological flaws (homeopathy, botanical oils, balneotherapy, anthocyanidins and dietary modifications). Another CAM therapy such as chiropractic care has neither well-designed studies nor positive results and is not currently recommended for FM treatment. Once CAM therapies have been better evaluated for safety and long-term efficacy in randomised, placebo-controlled trials, they may prove to be beneficial in treatments for FM. It would then be important to assess studies assessing cost-benefit analyses comparing conventional therapies and CAM.

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Magnesium Deficit in a Sample of the Belgian Population Presenting with Chronic Fatigue
Magnes Res 1997 (Dec); 10 (4): 329-337

97 patients (25 per cent males, ages ranging from 14 to 73 years, median 38 years) with complaints of chronic fatigue (chronic fatigue syndrome, fibromyalgia or/and spasmophilia) have been enrolled in a prospective study to evaluate the Mg status and the dietary intake of Mg. An IV loading test (performed following the Ryzen protocol) showed a Mg deficit in 44 patients. After Mg supplementation in 24 patients, the loading test showed a significant decrease (p = 0.0018) in Mg retention. Mean values of serum Mg, red blood cell Mg and magnesuria showed no significant difference between patients with or without Mg deficiency. No association was found between Mg deficiency, CFS or FM. However serum Mg level was significantly lower in the patients with spasmophilia than in the other patients.

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Selenium and Magnesium Status in Fibromyalgia
Magnes Res 1994 (Dec); 7 (3-4): 285-288

Muscle pain has been associated with magnesium (Mg) and selenium (Se) deficiency: magnesium and selenium status were investigated in fibromyalgia (FM). Erythrocyte (E), leucocyte (L) and serum (S) magnesium, serum selenium and zinc, and vitamin B1, B2, A or E status were assessed in 22 patients with fibromyalgia and in 23 age-matched healthy controls. LMg is significantly increased (P < 0.05) and EMg slightly decreased in fibromyalgia. These magnesium abnormalities are associated with previously-reported impairment of thiamin metabolism. Antioxidant status (as well as plasma malondialdehyde) is unchanged in fibromyalgia and serum selenium levels, slightly but not significantly correlated with serum magnesium, is normal.

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Magnesium and Osteoporosis:

Magnesium Deficiency: Possible Role in Osteoporosis Associated with Gluten-sensitive Enteropathy
Osteoporosis International (United Kingdom), 1996, 6/6 (453-461)

Osteoporosis and magnesium (Mg) deficiency often occur in malabsorption syndromes such as gluten-sensitive enteropathy (GSE). Mg deficiency is known to impair parathyroid hormone (PTH) secretion and action in humans and will result in osteopenia and increased skeletal fragility in animal models. We hypothesize that Mg depletion may contribute to the osteoporosis associated with malabsorption. It was our objective to determine Mg status and bone mass in GSE patients who were clinically asymptomatic and on a stable gluten-free diet, as well as their response to Mg therapy. Twenty-three patients with biopsy-proven GSE on a gluten-free diet were assessed for Mg deficiency by determination of the serum Mg, red blood cell (RBC) and lymphocyte free Mg2+, and total lymphocyte Mg. Fourteen subjects completed a 3-month treatment period in which they were given 504-576 mg MgCl2 or Mg lactate daily. Serum PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and osteocalcin were measured at baseline and monthly thereafter. Eight patients who had documented Mg depletion (RBC Mg2+ < 150 microM) underwent bone density measurements of the lumbar spine and proximal femur, and 5 of these patients were followed for 2 years on Mg therapy. The mean serum Mg, calcium, phosphorus and alkaline phosphatase concentrations were in the normal range. Most serum calcium values fell below mean normal and the baseline serum PTH was high normal or slightly elevated in 7 of the 14 subjects who completed the 3-month treatment period. No correlation with the serum calcium was noted, however. Mean serum 25-hydroxyvitamin D, 1,25-dihydroxy vitamin D and osteocalcin concentrations were also normal. Despite only 1 patient having hypomagnesemia, the RBC Mg2+ (153 + or - 6.2 microM; mean plus or minus SEM) and lymphocyte Mg2+ (182 plus or minus 5.5 microM) were significantly lower than normal (202 + or - 6.0 microM, P < 0.001, and 198 + or - 6.8 microM, p < 0.05, respectively). Bone densitometry revealed that 4 of 8 patients had osteoporosis of the lumbar spine and 5 of 8 had osteoporosis of the proximal femur (T-scores less than or equal to -2.5). Mg therapy resulted in a significant rise in the mean serum PTH concentration from 44.6 + or - 3.6 pg/ml to 55.9 plus or minus 5.6 pg/ml (p < 0.05). In the 5 patients given Mg supplements for 2 years, a significant increased in bone mineral density was observed in the femoral neck and total proximal femur. This increase in bone mineral density correlated positively with a rise in RBC Mg2+. This study demonstrates that GSE patients have reduction in intracellular free Mg2+, despite being clinically asymptomatic on a gluten-free diet. Bone mass also appears to be reduced. Mg therapy resulted in a rise in PTH, suggesting that the intracellular Mg deficit was impairing PTH secretion in these patients. The increase in bone density in response to Mg therapy suggests that Mg depletion may be one factor contributing to osteoporosis in GSE.

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Magnesium Supplementation and Osteoporosis
Nutrition Reviews 1995; 53 (3): 71-74

Among other things, magnesium regulates active calcium transport. As a result, there has been a growing interest in the role of magnesium (Mg) in bone metabolism. A group of menopausal women were given magnesium hydroxide to assess the effects of magnesium on bone density. At the end of the 2-year study, magnesium therapy appears to have prevented fractures and resulted in a significant increase in bone density.

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Calcium, phosphorus and magnesium intakes correlate with bone mineral content in postmenopausal women
GYNECOL. ENDOCRINOL. (United Kingdom), 1994, 8/1 (55-58)

Qualitative and quantitative differences in the dietary habits of postmenopausal women were studied to assess their influence on bone health and osteoporosis. A total of 194 postmenopausal women were studied with forearm DEXA densitometry. 70 were osteoporotic and 124 served as controls. Women had been menopausal for 5-7 years and had never been treated with hormone replacement or drug therapy. A 3-day dietary recall was completed on Sunday, Monday and Tuesday after the examination: the results were processed by computer and daily calcium, phosphorus and magnesium intakes were related to bone mineral content (BMC). Data were compared with Student's t-test and significance was assessed at p < 0.05. Regression analysis was performed to correlate BMC and intake levels. The dietary intake of calcium phosphorus and magnesium was significantly reduced in osteoporotic women and correlated with BMC. Calcium and magnesium intakes were lower than the recommended daily allowance even in normal women. The results suggest that nutritional factors are relevant to bone health in postmenopausal women, and dietary supplementation may be indicated for the prophylaxis of osteoporosis. Adequate nutritional recommendations and supplements should be given before the menopause, and dietary evaluation should be mandatory in treating postmenopausal osteoporosis.

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Magnesium and Other Ailments:

Magnesium taurate and fish oil for prevention of migraine
Med Hypotheses (ENGLAND) Dec 1996, 47 (6) p461-6

Although the pathogenesis of migraine is still poorly understood, various clinical investigations, as well as consideration of the characteristic activities of the wide range of drugs known to reduce migraine incidence, suggest that such phenomena as neuronal hyperexcitation, cortical spreading depression, vasospasm, platelet activation and sympathetic hyperactivity often play a part in this syndrome. Increased tissue levels of taurine, as well as increased extracellular magnesium, could be expected to dampen neuronal hyperexcitation, counteract vasospasm, increase tolerance to focal hypoxia and stabilize platelets; taurine may also lessen sympathetic outflow. Thus it is reasonable to speculate that supplemental magnesium taurate will have preventive value in the treatment of migraine. Fish oil, owing to its platelet-stabilizing and antivasospastic actions, may also be useful in this regard, as suggested by a few clinical reports. Although many drugs have value for migraine prophylaxis, the two nutritional measures suggested here may have particular merit owing to the versatility of their actions, their safety and lack of side-effects and their long-term favorable impact on vascular health

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Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study
Cephalalgia (NORWAY) Jun 1996, 16 (4) p257-63

In order to evaluate the prophylactic effect of oral magnesium, 81 patients aged 18-65 years with migraine according to the International Headache Society (IHS) criteria (mean attack frequency 3.6 per month) were examined. After a prospective baseline period of 4 weeks they received oral 600 mg (24 mmol) magnesium (trimagnesium dicitrate) daily for 12 weeks or placebo. In weeks 9-12 the attack frequency was reduced by 41.6% in the magnesium group and by 15.8% in the placebo group compared to the baseline (p < 0.05). The number of days with migraine and the drug consumption for symptomatic treatment per patient also decreased significantly in the magnesium group. Duration and intensity of the attacks and the drug consumption per attack also tended to decrease compared to placebo but failed to be significant. Adverse events were diarrhea (18.6%) and gastric irritation (4.7%). High-dose oral magnesium appears to be effective in migraine prophylaxis.

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Electromyographical ischemic test and intracellular and extracellular magnesium concentration in migraine and tension-type headache patients
Headache (UNITED STATES) Jun 1996, 36 (6) p357-61

Headache has often been described in the hyperexcitability syndrome which recognizes an alteration of calcium and magnesium status in its etiopathogenesis. Moreover, in migraine patients magnesium has been shown to play an important role as a regulator of neuronal excitability and, therefore hypothetically, of headache. The present research involves a neurophysiological evaluation and magnesium status assessment of a group of headache patients. Nineteen patients (15 women and 4 men) with episodic tension-type headache and 30 patients (27 women and 3 men) with migraine without aura were examined. An ischemic test was carried out on the right arm with electromyographic (EMG) recording of motor unit potential activity during the interictal period. The determination of extracellular (serum and saliva) and intracellular (red and mononuclear blood cells) magnesium was also performed. The EMG test was positive in 25 of 30 migraine patients and in 2 of 19 tension-type headache patients. Between the two patient groups, there were no significant variations in the concentration of extracellular and white blood cell magnesium, while the red blood cell concentration of this mineral in the group of migraineurs was significantly reduced with respect to that in the group of tension-type headache patients (P < 0.05). The positive EMG test was significantly associated with a low concentration of red blood cell magnesium (P < 0.0001). These results confirm previous findings by demonstrating different etiopathogenic mechanisms as the basis of migraine and tension-type headache. Migraine seems to be related to an altered magnesium status, which manifests itself by a neuromuscular hyperexcitability and a reduced concentration in red blood cells.

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Experimental and clinical studies on dysregulation of magnesium metabolism and the aetiopathogenesis of multiple sclerosis.
Magnes Res (ENGLAND) Dec 1992, 5 (4) p295-302

The proposed aetiologies of multiple sclerosis (MS) have included immunological mechanisms, genetic factors, virus infection and direct or indirect action of minerals and/or metals. The processes of these aetiologies have implicated magnesium. Magnesium and zinc have been shown to be decreased in central nervous system (CNS) tissues of MS patients, especially tissues such as white matter where pathological changes have been observed. The calcium content of white matter has also been found to be decreased in MS patients. The interactions of minerals and/or metals such as calcium, magnesium, aluminium and zinc have also been evaluated in CNS tissues of experimental animal models. These data suggest that these elements are regulated by pooling of minerals and/or metals in bones. Biological actions of magnesium may affect the maintenance and function of nerve cells as well as the proliferation and synthesis of lymphocytes. A magnesium deficit may induce dysfunction of nerve cells or lymphocytes directly and/or indirectly, and thus magnesium depletion may be implicated in the aetiology of MS. The action of zinc helps to prevent virus infection, and zinc deficiency in CNS tissues of MS patients may also be relevant to its aetiology. Magnesium interacts with other minerals and/or metals such as calcium, zinc and aluminium in biological systems, affecting the immune system and influencing the content of these elements in CNS tissues. Because of these interactions, a magnesium deficit could also be a risk factor in the aetiology of MS.

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Amyotrophic lateral sclerosis--causative role of trace elements
Nippon Rinsho (JAPAN) Jan 1996, 54 (1) p123-8

Although numerous hypotheses have been proposed for the cause of amyotrophic lateral sclerosis (ALS), conclusive decision still remains vague. Recent epidemiological investigation disclosed an aggregation of ALS cases in the Western Pacific, including the Kii Peninsula of Japan, the island of Guam in Marianas and West New Guinea. Extensive environmental studies in these foci indicated an important role of trace elements in ALS etiology. It is postulated that chronic environment deficiencies of calcium and magnesium may provoke secondary hyperparathyroidism, resulting in increased intestinal absorption of toxic metals under the presence of excess levels of divalent or trivalent cations and lead to the mobilization of calcium and metals from the bone and deposition of these elements in nervous tissue. This hypothesis, called metal-induced calcifying degeneration of CNS, has been supported by experimental studies using several animal species.

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Nutrient intake of patients with rheumatoid arthritis is deficient in pyridoxine, zinc, copper, and magnesium
Journal of Rheumatology (Canada), 1996, 23/6 (990-994)

OBJECTIVE: To determine nutrient intake of patients with active rheumatoid arthritis and compare it with the typical American diet (TAD) and the recommended dietary allowance (RDA). Methods. 41 patients with active RA recorded a detailed dietary history. Information collected was analyzed for nutrient intake of energy, fats, protein, carbohydrate, vitamins and minerals, which were then statistically compared with the TAD and the RDA.

RESULTS: Both men and women ingested significantly less energy from carbohydrates (women 47.4% (6.4) vs 55% RDA, p = 0.0001; men = 48.9% (7.4), p = 0.025) and more energy from fat (women = 36.8% (4.5) vs 30% RDA. p = 0.001 and men = 35.2% (5.9) p = 0.02). Women ingested significantly more saturated and mono-unsaturated fat than the RDA (p = 0.02 and p = 0.04 respectively) while men ingested significantly less polyunsaturated fat (PUFA)(p = 0.0001). Both groups took in less fiber (p = 0.0001). Deficient dietary intake of pyridoxine was observed vs the RDA for both sexes (men and women p = 0.0001). Deficient folate intake was seen vs the TAD for men (p = 0.02) with a deficient trend in women (p = 0.06). Zinc and magnesium intake was deficient vs the RDA in both sexes (p values less than or equal to 0.001) and copper was deficient vs the TAD in both sexes (p = 0.004 women and p = 0.02 men). Conclusion. Patients with RA ingest too much total fat and too little PUFA and fiber. Their diets are deficient in pyridoxine, zinc and magnesium vs the RDA and copper and folate vs the TAD. These observations, also documented in previous studies, suggest that routine dietary supplementation with multivitamins and trace elements is appropriate in this population.

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