Magnesium

James Meschino DC, MS, ROHP

General Features
The adult human body contains approximately 20-28 grams of Magnesium.  Approximately 60 percent is found in bone, 28 percent in muscle, and the remainder in soft tissue and body fluids.  It is second to potassium as an intracellular cation.

Magnesium is essential for energy production, protein synthesis, muscle contraction, nerve excitability and conduction and as a cofactor in numerous enzyme systems (more than 300 enzymes).

Magnesium and calcium tend to antagonize each other’s effects on muscle contraction and depolarization.  Calcium activates muscle contraction whereas Magnesium is a relaxer of muscles.  This effect on decreasing muscle cell excitability may be of importance in the treatment of acute phase ischemic heart disease, fibromyalgia, asthma and other conditions discussed below.  Magnesium is important (along with calcium, sodium, potassium and phosphorous) in nervous activity and muscle contraction.  At certain stages of neuromuscular activity, the interaction between Magnesium and calcium is antagonistic; at others, synergistic (enhancing).

In nature, Magnesium is the core atom of chlorophyll, the green pigment that enables plants, in the presence of light, to transform carbon dioxide and water into carbohydrates.  It thus has the claim to being, after carbon, the element most important to life.¹

Magnesium deficiency is extremely common in Americans, particularly in the geriatric population and in women during the premenstrual period.  Deficiency is often secondary to factors that reduce absorption or increase excretion of Magnesium, such as high calcium intake, alcohol, diuretics (including caffeine and nicotine), and oral contraceptive use.²

Recommended Daily Allowance (Magnesium)

Supplementation Studies and Clinical Applications

1. High Blood Pressure

Several intervention trials have revealed that Magnesium supplementation at 480 mg or 600 mg per day may lower blood pressure in hypertensive patients (mild to moderate cases).  The lowering effect has been shown to be mild to moderate and may require other interventions to achieve a normotensive state.^2,3,4

2. Cardiomyopathy

Cardiomyopathy describes any disease of the heart muscle that causes a reduction in the force of heart muscle contraction (e.g., congestive heart failure, cardiac arrhythmias, and angina).

Several studies show that Magnesium supplementation produces improvements in heart function in patients with a variety of cardiomyopathies.  However, these patients are often on medications for their condition and the attending physician must be made aware of any additional supplementation program targeted at cardiac function.^5-11

3. Diabetes

Magnesium levels are often low in diabetics and lowest in those with severe retinopathy.^1,2   Diabetics may need twice the RDA level for Magnesium to achieve optimal nutritional status.  A Magnesium deficiency may increase insulin resistance.^13,14,15   Magnesium supplementation in diabetics has been shown to increase insulin sensitivity and provide other benefits to these patients.¹⁵  As of yet, the American Diabetes Association has not recommended widespread use of Magnesium supplements for diabetics.¹⁴

4. Eosinophilia – Myalgia Syndrome (EMS)

EMS causes severe muscle pain, inflammation and in some cases neural and visceral involvement.  Contamination of L-tryptopan caused the most recent outbreak of this condition.

Magnesium supplementation has been shown to be a useful therapeutic agent in these conditions at doses of 1,000 mg, injected intramuscularly, twice weekly.²

5. Fibromyalgia and Chronic Fatigue Syndrome (CFS)

Preliminary evidence suggests that Magnesium supplementation at 300-600 mg per day can reduce the number and severity of tender points in patients suffering from fibromyalgia.¹⁵  Intramuscular injections of Magnesium sulfate (1,000 mg in 2 ml injectable water) has been shown to improve energy levels, pain levels and the emotional state of patients with CFS in a placebo controlled trial.¹⁶

Earlier trials with oral Magnesium supplementation demonstrated improvement in patients with CFS during the 1960s.  The total daily oral dosage was 1,000 mg per day.^17,18

6. Premenstrual Syndrome (PMS)

Magnesium supplementation, especially in conjunction with vitamin B6, has been shown to decrease certain PMS symptoms.  Reductions in nervousness, breast tenderness, and weight gain, and PMS-related mood swings have been the most consistently reported positive benefits in this regard.  Magnesium supplementation as high as 350 mg, three times daily has been employed in these studies.  A high potency multivitamin and mineral containing Magnesium and high dose Vitamin B6 (50-75 mg) has demonstrated improvement in relieving PMS symptoms.^19,20

7. Osteoporosis

During the 1990s several studies have shown that Magnesium supplementation in postmenopausal women can help to increase bone density, whether administered alone or in combination with calcium or hormone replacement therapy.  Supplementation of Magnesium in these studies ranged from 500 mg to 750 mg.^21,22,23  Thus, Magnesium is emerging as a mineral that may be important in the prevention of osteoporosis, as a synergistic nutrient with calcium and Vitamin D.²¹

As well, the lower circulating levels of 1,25 dihydroxyvitamin D in aging may be a result of poor Magnesium status.  The enzyme that converts 25 hydroxyvitamin D to the 5-times more potent 1,25 dihydroxyvitamin D, is dependent upon Magnesium as a cofactor to drive this biochemical pathway.²⁴

8. Pregnancy and Preeclampsia (elevated blood pressure, fluid retention, protein loss in urine)

During pregnancy, Magnesium needs increase from 300 mg to 450 mg per day.  Magnesium deficiency during pregnancy is linked to the development of preeclampsia.  The appropriate supplementation of Magnesium during pregnancy decreases the incidence of these complications.  Several double-blind studies confirm this finding.^25-29

9. Kidney Stone Prevention

Intervention trials suggest that Magnesium supplementation significantly reduces the recurrence of kidney stones.  Magnesium increases the solubility of calcium in the urine, helping to prevent its precipitation with oxalate or urate, in stone formation.  Magnesium used in conjunction with vitamin B6 may yield an even greater preventive effect (e.g., 200 mg Magnesium plus 10 mg Vitamin B6 or 300 mg Magnesium as a single agent).

It is estimated that one million Americans now living will die from causes related to kidney stones.^30-35

Dosage Ranges

Side Effects and Toxicity
Magnesium exhibits low toxicity, even at high doses (3,000-5,000 mg per day).  However, people with kidney disease or severe heart disease should not take Magnesium (or potassium) except by physician’s orders.²

Drug-Nutrient Interactions
Drugs such as insulin and digitalis decrease Magnesium nutritional status.  Magnesium supplementation may decrease the absorption of digoxin, tetracycline and phenyltoin (dilantin) if taken at the same time.^36,37

The following drugs have been shown to deplete Magnesium status:

1. Penacillamine – this drug binds to Magnesium, reducing absorption of the drug and the mineral³⁸
2. Tetracycline Antibiotics – these drugs bind to Magnesium reducing absorption of the drug and the mineral³⁹
3. Aminoglycosides – increase urinary excretion of Magnesium^40,41
4. Amphotericin B – increases urinary excretion of Magnesium⁴²
5. Cholestyramine – increases urinary excretion of Magnesium⁴³
6. Corticosteroid drugs⁴⁴
7. Hormone Replacement Therapy^45,46
8. Foscarnet – increases urinary excretion of Magnesium⁴⁷
9. Digoxin – increases urinary excretion of Magnesium⁴⁸
10. Loop Diuretics – increase urinary excretion of Magnesium⁴⁹
11. Oral contraceptives⁴⁵
12. Pentamidine⁴⁹
13. Thiazide Diuretics. – increase urinary excretion of Magnesium⁴⁹

Nutrient-Nutrient Interactions

1. Calcium – high intake of calcium may reduce Magnesium absorption.⁵⁰
2. Phosphate – high intake of phosphorous may decrease Magnesium absorption.⁵¹

1. Standard Textbooks of Nutritional Science:
   • – Shils M, Shike M, Olson J, Ross C. Modern Nutrition in Health and Disease. 9^th Baltimore, MD: Lippincott Williams & Wilkins; 1993.
   • – Escott-Stump S, Mahan LK, editors. Food, Nutrition and Diet Therapy. 10^th Philadelphia, PA: W.B. Saunders Company; 2000.
   • – Bowman B, Russell RM, editors. Present Knowledge in Nutrition, 8^th Washington, DC:.ILSI Press; 2001.
   • – Kreutler PA, Czajka-Narins DM, editors. Nutrition in Perspective. 2^nd Upper Saddle River, NJ: Prentice Hall Inc.; 1987.
2. Murray M. Encyclopedia of Nutritional Supplements.  Rocklin, CA: Prima Publishing; 1996.
3. Witterman JCM, et al. Reduction of blood pressure with oral magnesium supplementation in women with mild to moderate hypertension.  Am J Clin Nutr 1994; 60:129-35.
4. Motoyama T, Sano H, Fukuzaki H. Oral Magnesium supplementation in patients with essential hypertension.  Hypertension 1989;13:227-32.
5. McLean RM. Magnesium and its therapeutic uses:  a review.  Am J Med 1994;96:63-76.
6. Altura BM. Basic biochemistry and physiology of Magnesium: a brief review.   Magnes Trace Elem 1991;10:167-71.
7. Purvis JR, Movahed A. Magnesium disorders and cardiovascular disease.  Clin Cardiol 1992;15:556-68.
8. Altura BM. Ischemic heart disease and Magnesium.  Magnesium 1988;7:57-67.
9. Perticone F, Borelli D, Ceravolo R, Mattioli PL. Antiarrhythmic short-term protective Magnesium treatment in ischemic dilated cardiomyopathy.  J Am Coll Nutr 1990;9:492-9.
10. Galland LD, Baker SM, McLellan RK. Magnesium deficiency in the pathogenesis of mitral valve prolapse.  Magnesium 1986;5:165-74.
11. Fernandes JS, et al. Therapeutic effect of a Magnesium salt in patients suffering from mitral valvular prolapse and latent tetany.  Magnesium 1985:4:283-9.
12. White JR, Campbell RK. Magnesium and diabetes:  a review.  Ann Pharmacother 1993;27:775-80.
13. Djurhuus MS, Skott P, Hother NO, Klitgaard NA, Beck NH. Insulin increases renal Magnesium excretion: a possible cause of Magnesium depletion in hyperinsulinaemic states.  Diabetic Med 1995;12:664-9.
14. Consensus Statement, Magnesium supplementation in the treatment of diabetes. Diabetes Care 1996;19(Suppl. 1):S93-5.
15. Paolisso G, Sgambato S, Gambardella A, Pizza G, Tesauro P, Varricchio M, et al. Daily Magnesium supplements improve glucose handling in elderly subject.  Am J Clin Nutr 1992;55:1161-7.
16. Clauw DJ, et al. Magnesium deficiency in the eosinophilia-myalgia syndrome.  Arth Rheum 1994;9:1331-4.
17. Hicks JT. Treatment of fatigue in general practice: a double-blind study.  Clin Med J 1964:85-90.
18. Friedlander HS. Fatigue as a presenting symptom:  management in general practice.  Curr Ther Res 1962;4:441-9.
19. Facchinetti F, Borella P, Sances G, et al. Oral Magnesium successfully relieves premenstrual mood changes.  Obstet Gynecol 1991;78:177-81.
20. Goei GS, Abraham GE. Effect of nutritional supplement, Optivite, on symptoms of premenstrual tension.  J Repro Med 1983;28;527-31.
21. Tucker K, et al. Magnesium intake is associated with bone mineral density in elderly women.  J Bone Mineral Res 1995;(Suppl):10S-46S.
22. Abraham, GE, Grewal, H. A total dietary program emphasizing Magnesium instead of Calcium effect on the mineral density of calcaneous bone in postmenopausal women on hormonal therapy.  J Reprod Med 1990;5:503-7.
23. Stendig-Lindberg G, Tepper R, Leichter I. Trabecular bone density in a two-year controlled trial of peroral Magnesium in osteoporosis.  Magnes Res 1993;2:155-63.
24. Rude RK, Adams JS, Ryzen E, Endres DB, Niimi H. Low serum concentration of 1,25-dihydroxyvitamin D in human Magnesium deficiency.  J Clin Endo Metabol 1985;61:933-40.
25. Conradt A, Weidinger H, and Algayer H. ON:  The role of Magnesium in fetal hypertrophy, pregnancy-induced hypertension, and preeclampsia.  Mag Bull 1984;6:68-76.
26. Kiss V, et al. Effect of maternal Magnesium supply on spontaneous abortion and premature birth and on intrauterine fetal development: experimental epidemiological study.  Mag Bull 1981; 3:73-9.
27. Spatling L, Spatling G. Magnesium supplementation in pregnancy.  A double-blind study.  Br J Obstet Gynaecol 1988;95:120-5.
28. Rudnicki M, Frolich A, Rasmussen WF, McNair P. The effect of Magnesium on maternal blood pressure in pregnancy-induced hypertension.  A randomized double-blind placebo-controlled trial.  Acta Obstet Gynecol Scand 1991;70:445-50.
29. Martin RW, Morrison JC. Oral Magnesium for tocolysis.  Contemp Ob/Gyn 1987;30:111-8.
30. Johansson G, Backman U, Danielson BG, Fellstrom B, Ljunghall S, Wikstrom B. Biochemical and clinical effects of the prophylactic treatment of renal Calcium stones with Magnesium Hydroxide. J Urol 1980;124:770-4.
31. Wunderlich W. Aspects of the influence of Magnesium ions on the formation of calcium oxalate.  Urol Res 1981;9:157-60.
32. Hallson P, Rose G, Sulaiman SM. Magnesium reduces Calcium oxalate crystal formation in human whole urine.  Clin Sci 1982;62:17-9.
33. Johansson G, Backman U, Danielson B, et al. Magnesium metabolism in renal stone formers.  Effects of therapy with magnesium hydroxide.  Scand J Urol Nephrol 1980; 53:125-30.
34. Prien E, Gershoff S. Magnesium oxide-pyridoxine therapy for recurrent calcium oxalate calculi.  J Urol 1974:509-12.
35. Gershoff S, Prien E. Effect of daily MgO and Vitamin B₆ administration to patients with recurring Calcium Oxalate stones.  Am J Clin Nutr 1967;20:33-7.
36. Reavley N. The New Encyclopedia of Vitamins, Minerals, Supplements and Herbs.  New York, NY: M. Evans and Company Inc.; 1998.
37. Healthnotes 1998-2002. Available from: URL: http://www.healthnotes.com
38. Seelig MS. Auto-immune complications of D-penicillamine – a possible result of Zinc and Magnesium depletion and of Pyridoxine inactivation.  J Am Coll Nutr 1982;1(2):207-14.
39. Berton G, et al. Metal ion-tetracycline interactions in biological fluids. 2. potentiometric study of Magnesium complexes with tetracycline, oxytetracycline, doxycycline, and minocycline, and discussion of their possible influence on the bioavailability of these antibiotics in blood plasma.  J Inorg Biochem 1983;19(1):1-18.
40. Kes P, Reiner Z. Symptomatic hypomagnesemia associated with gentamicin therapy.  Magnes Trace Elem 1990;9(1):54-60.
41. Jacobson ED, Faloon WW. Malabsorptive effects of neomycin in commonly used doses.  A Am Med Assoc 1961;175:187-90.
42. Barton CH, Pahl M, Vaziri ND, Cesario T. Renal Magnesium wasting associated with amphotericin B therapy.  Am  J Med  1984;77(3):471-4.
43. Watkins DW, Khalafi R, Cassidy MM, Vahouny GV. Alterations in Calcium, Magnesium, Iron, and Zinc metabolism by dietary cholestyramine.  Dig Dis Sci 1985;30(5):477-82.
44. Rolla G, Bucca C, Bugiani M, Oliva A, Branciforte L. Hypomagnesemia in chronic obstructive lung disease: effect of therapy.  Magnes Trace Elem 1990;9(3):132-6.
45. Blum M, Kitai E, Ariel Y, et al. Oral contraceptive lowers serum Magnesium.  1991;121(10):363-4.
46. Seelig MS. Increased need for Magnesium with the use of combined estrogen and Calcium for osteoporosis treatment.  Magnes Res 1990;3(3):197-215.
47. Gearhart MO, Sorg TB. Foscarnet-induced severe hypomagnesemia and other electrolyte disorders.  Ann Pharmacother 1993;27(3):285-9.
48. Kupfer S, Kosovsky JD. Effects of cardian glycosides on renal tubular transport of Calcium, Magnesium, inorganic phosphate and glucose in the dog.  J Clin Invest 1965;44:1132-43.
49. Ghamdi SM, Cameron EC, Sutton RA. Magnesium deficiency: pathophysiologic and clinical overview.  Am J Kidney Dis 1994;24(5):737-52.
50. Norman DA, et al. Jejunal and ileal adaptation to iterations in dietary Calcium: changes in Calcium and Magnesium absorption and pathogenetic role of parathyroid hormone and 1,25-dihydroxyvitamin D.  J Clin Invest 1981;67(6):1599-603.
51. Spencer H, et al. Magnesium-phosphorus interactions in man. Trace substances in environmental health-XIII. Hemphill DD editor.  Columbia: Univ. Missouri; 1979.