Various lines of research have established a connection between hypomagnesemia and an extensive inventory of disease states (Gullestad et al., 1991-1992; Klein, 1994; White et al., 1992). Because the signs and symptoms of hypomagnesemia may be indistinct from those of other conditions, the deficiency is often difficult to identify clinically (Gullestad et al., 1991-1992). Moreover, body magnesium may be deficient even when serum values are normal, and the deficiency may be specific to a particular organ (Knochel, 1991). Studies have shown that between 6.9% and 11% of hospitalized patients and 65% of patients in intensive care units may have magnesium deficiency (Gullestad et al., 1991-1992; Klein, 1994).

Cardiovascular diseases -- heart failure, cardiac dysrhythmia and hypertension -- lead the list of disorders associated with hypomagnesemia. The relation of serum and dietary magnesium with coronary heart disease (CHD) incidence was examined in 13,922 middle-aged adults from four U.S. communities (Liao et al., 1998). Over four to seven years of follow-up, CHD developed in 223 men and 96 women. After adjusting for sociodemographic characteristics, waist/hip ratio, smoking, alcohol consumption, sports participation, use of diuretics, fibrinogen, total and high-density lipoprotein cholesterol levels, triglyceride levels, and hormone replacement therapy, the researchers concluded that magnesium deficiency has the potential to contribute to the pathogenesis of coronary atherosclerosis or acute thrombosis.

A randomized, double-blind, placebo-controlled trial in an acute-care hospital was conducted to determine whether magnesium administration would reduce morbidity and mortality after cardiac surgery (England et al., 1992). Over a six-month period, 100 patients electively scheduled for cardiac surgery involving cardiopulmonary bypass were studied. Fifty patients received an intravenous infusion of a magnesium supplement and 50 patients received a placebo after the termination of cardiopulmonary bypass. The magnesium-treated patients had a significantly decreased frequency of postoperative ventricular dysrhythmias compared to placebo-treated patients (p<0.04). Magnesium-treated patients also had significantly higher postoperative cardiac indices in the intensive care unit (p<0.02).

The effects of magnesium supplementation on office, home and ambulatory blood pressures were studied in 60 untreated or treated hypertensive Japanese patients (34 men and 26 women, aged 33 to 74 years) with office blood pressure >140/90 mmHg (Kawano et al., 1998). The patients were assigned to an eight-week magnesium supplementation period or an eight-week control period in a randomized crossover design. Magnesium supplementation lowered blood pressure in hypertensive patients, and this effect was greater in those with higher blood pressure. The results supported the usefulness of increasing magnesium intake as a lifestyle modification in the management of hypertension.

Hypomagnesemia has also been linked to chronic fatigue syndrome (CFS). The hypothesis that patients with CFS have low levels of red blood cell magnesium was tested in a British case-control study (Cox et al., 1991). In this study, patients with CFS had lower red cell magnesium concentrations than did healthy control subjects matched for age, sex and social class. In the clinical trial, patients with CFS were randomly given a magnesium supplement (n=15) or placebo (n=17). Patients treated with magnesium claimed to have improved energy levels, a better emotional state and less pain as judged by changes in the Nottingham health profile.

According to a 1998 review by Mauskop and Altura, "The importance of magnesium in the pathogenesis of migraine headaches has been clearly established by a large number of clinical and experimental studies." The exact role of low magnesium levels in migraine development is unknown, but magnesium concentration affects serotonin receptors, nitric oxide synthesis and release, N-methyl-D-aspartate (NMDA) receptors, and other migraine-related receptors and neurotransmitters. According to this review, as much as 50% of patients have lowered levels of ionized magnesium during an acute migraine attack. In these patients, an infusion of magnesium results in a rapid and sustained relief of an acute migraine (Mauskop and Altura, 1998).

It is probable that some conditions, such as CFS and migraine, are related to catecholamine release and a "spurious hypomagnesemia" as opposed to low magnesium levels per se. However, hypomagnesemia is a common problem in hyperthyroid patients. This is of particular concern in the elderly with their predilection to develop atrial fibrillation. In fact, alcoholics are probably the largest population at risk for hypomagnesemia as well as a whole host of other metabolic derangements.

Magnesium deficiency in conjunction with diabetes also has the potential to intensify some complications associated with the disease. A study of 23 children with diabetes found that their serum values of total and ionized calcium, magnesium, intact parathyroid hormone, calcitriol, and osteocalcin were lower than those of control subjects (Saggese et al., 1991). All patients were given 6 mg/kg daily (orally) of elemental magnesium for up to 60 days. During treatment, all concentrations increased significantly, reaching control values. These data suggested that magnesium deficiency plays a pivotal role in positively altering mineral homeostasis in insulin-dependent diabetes mellitus.

Poor nutritional status, impaired gastrointestinal (GI) status and polypharmacy are other factors that put the elderly at greater risk for magnesium deficiency (Klein, 1994). Therapy with thiazide or loop diuretics for hypertension or congestive heart failure -- and the consequent diuresis -- may further stress their mineral balance. Hypokalemia can be a problem in the elderly population, and Klein (1994) reported finding hypomagnesemia in 38% to 42% of hypokalemic patients. Because the correction of a potassium deficit may be difficult to achieve unless the magnesium deficit is also corrected, patients with hypokalemia should also be evaluated for magnesium deficiency. The elderly are also vulnerable to hypomagnesemia-induced malabsorption syndromes and nephrolithiasis (Lindberg et al., 1990; White et al., 1992).

The optimal daily intake of magnesium for an adult is 15 mmol to 20 mmol (30 mEq to 40 mEq), and normal magnesium serum levels range from 0.7 mmol/L to 1.0 mmol/L (Knochel, 1991; White et al., 1992). Foods that are rich in magnesium include legumes, whole grains, green leafy vegetables, nuts, coffee, chocolate and milk. Although these foods are readily available, some individuals do not consume adequate quantities to satisfy the daily nutritional requirement. Furthermore, expanded consumption of processed foods, which tend to contain less magnesium, may account for the perceptible decline in dietary magnesium in the United States during the past century (Klein, 1994). Thus, continued use of an oral magnesium supplement that offers reliable absorption and bioavailability is recommended for people with magnesium deficiency (White et al., 1992). Oral magnesium supplements are available in a number of formulations that utilize a different anion or salt -- such as oxide, gluconate, chloride or lactate dihydrate (Klein, 1994). However, these preparations are not interchangeable because they have differences in absorption and bioavailability.

Magnesium is absorbed primarily in the distal small intestine, and healthy people absorb approximately 30% to 40% of ingested magnesium (Knochel, 1991; White et al., 1992). Since magnesium is predominately an intracellularcation, the effectiveness of the oral supplement is assessed by its solubility and rate of uptake from the small intestine into the bloodstream and by its transfer into the tissues. Magnesium balance is regulated by the kidneys (White et al., 1992). When magnesium levels in the blood are high, the kidneys will rapidly excrete the surplus. When magnesium intake is low, on the other hand, renal excretion drops to 0.5 mmol to 1 mmol (1 mEq to 2 mEq) per day (Knochel, 1991). A caveat: patients with renal failure receiving magnesium salts need to be carefully monitored for the potential of magnesium intoxication.

The in vitro solubility and in vivo GI absorbability of magnesium oxide and magnesium citrate were compared (Lindberg et al., 1990). The simulated gastric fluids represented five different concentrations of hydrochloric acid. Magnesium citrate was significantly more soluble than magnesium oxide in all levels of acid secretion, but reprecipitation from magnesium oxide and magnesium citrate did not occur when the hydrochloric acid was titrated to a pH between 6 and 7, which is the pH of the distal small intestine where magnesium anions are absorbed. Absorption of the two magnesium formulations was also compared in vivo by measuring the rise in urinary magnesium levels, and the citrate form was absorbed to a much greater extent than the oxide.

The study just described involved healthy individuals with normal magnesium serum levels. In contrast, another study focused on the effects of magnesium supplementation in 40 elderly magnesium-deficient patients and compared oral versus intravenous administration (Gullestad et al., 1991-1992). The oral magnesium lactate-citrate preparation was given for six weeks at a daily dose of 15 mmol; the IV magnesium sulfate formulation was given at a daily dose of 30 mmol as an infusion in 1000 mL of saline for seven days. The two routes of magnesium administration yielded comparable results. The authors termed bioavailability of oral magnesium lactate citrate "satisfactory" and concluded that oral delivery of magnesium supplements for six weeks may restore magnesium levels in magnesium-deficient patients.

A non-randomized clinical trial evaluated the absorption of sustained-release magnesium lactate dihydrate in 24 patients (Kann, 1989). The patients received 21 mEq of the sustained-release preparation at 8 a.m. and 2 p.m. on the third day of the study after consuming a low-magnesium diet for two days. Blood samples were collected on day 2 and after the initial dose (day 3), and urine was collected for four continuous days. Statistical data showed that the participants absorbed 41% of the oral dose with no serious adverse reactions. In a study with dogs, magnesium L-lactate dihydrate proved to be highly soluble at a neutral pH with a readily absorbed anion, and decreased acidity did not impair its bioavailability (Robbins et al., 1989).

Magnesium deficiency has been linked to a growing number of disease states. When hypomagnesemia is detected, the appropriate course of action consists of addressing the underlying cause (if identifiable) and reversing the depleted state. Oral magnesium supplements constitute an effective form of replacement therapy, but not all formulations are equal. Absorption and bioavailability of preparations vary, as do concomitant side effects. Various investigators have reported that magnesium L-lactate dihydrate, which is available in a sustained-release formulation, ensures maximal absorption in the distal small intestine. The solubility and bioavailability of magnesium L-lactate dihydrate are higher than those of other magnesium formulations, and the low incidence of side effects and a bid dosing schedule may provide the additional benefit of patient compliance.

Dr. Bernstein is chief medical officer for Jewish Geriatric Services in Longmeadow, Mass. He is responsible for patients in the nursing home, subacute care, assisted living, adult day care, home care and office practice settings.

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Robbins TL, Imondi AR, Murphy PE et al. (1989), Magnesium lactate bioavailability in dogs is not impaired by decreased gastric acidity. J Am Coll Nutr 8:462. Abstract 144.

Saggese G, Federico G, Bertelloni S et al. (1991), Hypomagnesemia and the parathyroid hormone-vitamin D endocrine system in children with insulin-dependent diabetes mellitus: effects of magnesium administration. J Pediatr 118(2):220-225 [see comment].

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Improving Magnesium Absorption and Bioavailability