Magnesium depletion causes a neuron to become oversensitive and can result in tremors, muscle spasms, rapid or irregular heartbeat, and, in extreme cases, convulsions, confusion and weakness.

Seventy-eight-year-old Mrs. Jones goes to the doctor complaining of weakness and lack of energy during the past several days. Her breathing is slow. The doctor measures her blood pressure; it is very low. He tests her deep tendon reflexes and finds they are depressed. Questioned about her health and activities over the last few weeks, Mrs. Jones reveals that several weeks ago she had stomach upset and since has taken milk of magnesia several times a day.

What's the matter with Mrs. Jones? A blood test shows her serum magnesium to be 6.5 milli-equivalents/liter (normal is nearer 1.5 mEq/liter). Mrs. Jones has magnesium toxicity, a relatively undiagnosed condition.

Several doses of milk of magnesia each day can provide 1,000 to 2,000 mg magnesium (Mg), depending on the dosages chosen from the manufacturer's recommended range. The magnesium RDA for women is 280 mg/day (for men, 350 mg). The main route for elimination of magnesium is the kidney. A young person with healthy kidneys might be able to deal with several days of excess magnesium intake, but Mrs. Jones, like many elderly people, has reduced kidney function (renal insufficiency) and can't get rid of the overload.

Magnesium has many functions in the body. One of the things it does is to relax nerve impulses and muscle contractions, working in opposition to calcium (Ca). That's why Mrs. Jones felt weak and had depressed deep tendon reflexes.

Magnesium is mainly an intracellular ion (i.e., inside the cells). The majority of magnesium in the body is in the skeleton, 20 percent to 30 percent is in muscle, and only about 2 percent is outside of cells (extracellular). Magnesium regulates cellular ion balance--keeping potassium in the cells and sodium out. It also regulates cellular glucose metabolism, protein digestion and certain hormone receptor signal transmissions. In heart tissue, magnesium behaves as a calcium channel blocker, preventing influx of calcium into cells; calcium influx can be precipitated by ischemia (lack of oxygen to the cells). It does all these, and many other actions, by being an enzyme activator and by its role as a part of an activated ATP complex--the all-important organic compound that transfers its energy to other molecules in oxidative enzymatic reactions. In fact, magnesium is involved in more than 300 different enzyme reactions.

Two things are evident: 1) magnesium is needed for so many bodily functions that we wouldn't want to be short of it, and 2) too much magnesium can cause toxic effects--like Mrs. Jones had.

Magnesium Deficiency So, what happens when we don't get enough magnesium? Metabolic systems--digestion, for example--can be sluggish, presenting only subtle and hard-to-pin-down symptoms. Magnesium depletion also reduces the threshold for nerve stimulation and can result in increased irritability. Typical findings include tremors, muscle spasms, twitching of facial muscles, rapid heartbeat, irregular heartbeat, and, in extreme cases, convulsions, confusion, hallucinations, weakness, anorexia, nausea and vomiting.

Of course, none of these problems is specific to magnesium deficiency. There is no symptom that waves the single flag of magnesium deficiency. For a physician to suspect it, there would most likely have to be a recognized potential cause such as a bowel re-section, a recent severe case of diarrhea, a suspected GI malabsorption problem, alcoholism or use of a medication such as a thiazide diuretic that could cause excessive loss of magnesium through the urine.

Part of the reason for the lack of recognition of magnesium deficiency is that only lately have good measures of intracellular magnesium been developed, and they are not commonly available. Serum magnesium is a notably poor indicator of magnesium status, since it is possible to have low cellular magnesium while at the same time having low, normal, or even high serum magnesium. Likewise, low serum magnesium doesn't always mean that intracellular magnesium (where it matters) is abnormal. Two new methods, nuclear magnetic resonance (NMR) spectroscopy and magnesium-specific ion-selective electrodes, are a major advance in detection. Because of the cost and difficulty of operation, however, the NMR method is likely to continue to be limited to research, but the magnesium-selective electrode has recently been commercially developed and may become routine in clinical use.

Research using these two techniques has demonstrated consistently that deficient levels of magnesium accompany hypertension and diabetes mellitus. These results support findings in large population studies that magnesium intake is an independent predictor of the prevalence of hypertension. (Magnesium levels appear to be a better predictor of disease risk than calcium or sodium.)1

It is not known whether the magnesium deficiency associated with hypertension and diabetes mellitus is the result of low magnesium intake or if magnesium loss is a result of the disease process--the old chicken-and-the-egg problem.

It does appear that a higher-than-normal magnesium intake can benefit many who have either of these problems. The findings for diabetes have led to the recommendation that the adult diabetic should include 300 to 400 mg of dietary Mg per day and a supplement of 100 to 600 mg/day, according to each person's degree of deficiency.2

For the "normal" person, however, nutritionists think the amount of magnesium in an ordinary diet is sufficient. In one analysis of the average American diet, primary sources of magnesium included dairy products (20 percent); flours and cereals (20 percent); vegetables, particularly tomatoes (16 percent); meat and poultry (15 percent); and legumes and nuts (13 percent).

Rich sources of magnesium include soybean flour, wheat germ, wheat bran, sesame seeds, peanut flour and cocoa powder. Nuts, whole grains and yeast are considered good sources while meats and dairy products and most green leafy vegetables provide small amounts. (Magnesium is a structural part of the chlorophyll molecule.)

Only 30 percent to 50 percent of daily magnesium intake is absorbed. The percentage absorbed is determined partly by the molecular composition of a meal. Oxalic acid (as found in spinach and rhubarb), phytic acid (in whole grain cereals) and poorly digested fats interfere with magnesium absorption by forming insoluble (and therefore unabsorbable) compounds. Excess calcium and phosphate also interfere with magnesium absorption. (Thus, taking calcium supplements without adding magnesium could result in magnesium deficiency.) Promoters of magnesium absorption include protein, lactose and vitamin D.

Magnesium And Calcium Because magnesium and calcium compete for absorption, it is important when taking calcium supplements to ensure that magnesium and calcium intakes are balanced. The optimal ratio of calcium to magnesium is not known--and, indeed, the ideal ratio is assumed to vary with conditions--but the ratio of the RDAs for calcium and magnesium is roughly 2.5:1 (RDAs differ for age and sex) and can provide a rule of thumb to keep supplements in balance. When calculating the specific amounts of each supplement, element amounts should be used and not the weights of the compounds that contain them. And, of course, people taking a supplement to increase magnesium should also pay attention to calcium intake.

Magnesium And Salt Substitutes A reasonable way to increase magnesium levels may be the use of a salt substitute. In a double-blind study, 40 hypertensive, non-insulin-dependent diabetics were given either a salt substitute composed of 50 percent sodium chloride, 40 percent potassium chloride and 10 percent magnesium sulfate or ordinary table salt (sodium chloride) for nine months. Blood pressure, blood electrolytes, insulin and indicators of diabetes control were monitored every three months. By the third month and through to the end of the study, the salt-substitute group showed a significant decline in systolic blood pressure (10 mm Hg), whereas there was no change in the salt group.3 Unfortunately, cellular magnesium was not monitored in this study, and it is not known whether the improvement in blood pressure was a reflection of increased potassium and magnesium intake or of lower sodium intake. However, the overall effect was beneficial, and no deleterious side effects were observed.

Magnesium is used therapeutically for many things, including extreme conditions that require intravenous administration of a magnesium salt. Among such conditions are acute asthma attacks, life-threatening cardiac arrhythmias, toxemia from pregnancy and prevention of premature labor.

Magnesium And Kidney Stones

Magnesium can also be self-administered orally to prevent kidney stone formation and migraine headaches. In a study of 56 subjects with a history of calcium oxalate stones, supplementation with 200 mg of magnesium (as magnesium hydroxide) twice per day for two years reduced the mean stone episode rate from 0.8 stones/ year to 0.03 stones/year.4 It likely works by forming insoluble magnesium oxalate in the intestine, resulting in reduced oxalate absorption and, therefore, reduced concentration of oxalate in urine. (Calcium can do the same.) Hence, for this treatment to be effective, magnesium should be taken with meals that are likely to have the higher concentrations of oxalate. (American breakfasts are typically low in oxalates.)

Magnesium And Migraines Oral magnesium was effective in reducing the frequency of migraine headaches in a placebo-controlled, double-blind study of 81 subjects.5 During nine weeks of treatment, the frequency of headaches declined 16 percent in the 38-member placebo group and 42 percent in the 43-member magnesium-treated group (600 mg Mg/day as trimagnesium dicitrate). The number of migraine days, the average duration of an attack, and pain intensity were also reduced more in the magnesium group than in the placebo group. The major adverse effects of magnesium treatment were diarrhea and gastric irritation.

Magnesium is frequently used as a laxative. Adult dosages recommended for over-the-counter preparations (milk of magnesia, citrate of magnesia) can be large--8 to 17 g. Although their laxative action may greatly reduce the percentage absorbed, with such large amounts there is potential for absorbing toxic quantities with repeated or chronic use, and certainly for interfering with absorption of other minerals. Hence, such preparations should not be used heedlessly.

Magnesium is a mineral to pay attention to because it plays a critical role in so many metabolic processes and because sometimes, unexpectedly, it is a newly found remedy for an old problem. Users also should pay attention to dosage: Both excesses and deficiencies of magnesium can have undesirable health effects.

Oh, by the way; Mrs. Jones recovered from her magnesium toxicity by stopping the milk of magnesia treatments. Had her condition been more acute, her doctor might have given her intravenous calcium.

Stephanie Briggs, Ph.D., is a nutritional biochemist with more than 20 years experience in laboratory research. She is also a freelance writer.

REFERENCES

1. Resnick, L.M. "Magnesium in the pathophysiology and treatment of hypertension and diabetes mellitus: Where are we in 1997?" Am J Hyperten, 10:368-370, 1997.

2. Tosiello, L. "Hypomagnesemia and diabetes mellitus: a review of clinical implications," Arch Intern Med, 156:1143-1148, 1996.

3. Gilleran, G., O'Leary, M., et al. "Effects of dietary sodium substitution with potassium and magnesium in hypertensive Type II diabetics: a randomized blind, controlled parallel study," J Hum Hypertens, 10:517-521, 1996.

4. Johansson, G., Backman, U., et al. "Biochemical and clinical effects of the prophylactic treatment of renal calcium stones with magnesium hydroxide," J Urol, 124:770-774, 1980.

5. Peikert, A., Wilimzig, C., et al. "Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study," Cephalagia, 16:257-263, 1996.