Magnesium Balance

INTRAVENOUS LOW-DOSE MAGNESIUM TOLERANCE TEST

The most effective way to evaluate Mg deficiency in the presence of normal serum Mg is to do and intravenous load test.(6) First, a 24-hour urine collection is made in three 8-hourly aliquots. An infusion of 0.2 mEq Mg/kg lean body weight is given over 4 hours, followed by a 24-hour collection timed from the beginning of the intravenous load. Normal patients with positive Mg balance retain only 40% of the load, whereas those in negative Mg balance (Mg deficient) retain up to 77 ± 7%. In this study conducted by Ryzen et al., those with normal serum Mg, mean 2.17± 0.05 mg/dl, still retained 63± 4%. Thus, normomagnesemic Mg deficiency exists.

ADVANTAGES OF MAGNESIUM GLUCONATE

Gluconates are formed vivo and in vitro from glucose. They are absorbed from the gastrointestinal tract along the same pathways as glucose. Although it is generally agreed that Mg is absorbed primarily in the ileum, it is said to begin in 1 hour and to continue at a uniform rate for 2 to 8 hours.(2) Absorption during the fasting state would favor early and more complete absorption. Nicar and Pak showed that after giving 25 mmol (608 mg) of Mg (with 555 mg in the form of magnesium gluconate) as an oral load test, the urinary Mg concentration peaked during the first or second 2 hours postcollection period and declined thereafter. The Mg was increased in the serum at 2 and 4 hours (p=0.001). There was no significant difference between the 2 and 4-hour serum levels.(11) Investigators from the same laboratory studied Mg citrate and Mg oxide in an identical experiment.(12) No Mg from either the citrate or oxide formulations was present in the urine at 2 hours and only from the citrate formulation at 4 hours. Thus, the delay in absorption of oxide strongly supports the fact that Mg from this preparation is absorbed in the ileum. All of this illustrates the absorptive advantages of Mg gluconate, in which the Mg is known to be chelated between 2 molecules of gluconate and is absorbed early.

Mg chloride, Mg sulfate, and Mg citrate all have, in addition to the Mg ions, a component anion that could very easily lead to diarrhea because of the additional osmotic action of the anions. Mg oxide eventually dissociates in the presence of hydrochloric acid to form Mg chloride, yet no Mg is absorbed in the first 4 hours.

ADMINISTRATION OF MAGNESIUM SUPPLEMENT

Each tablet of Magonate ® (Fleming & Co., Inc.), a formulation of Mg gluconate USP, contains 27 mg of Mg, and each teaspoon of Magonate ® liquid contains 54 mg of Mg. Human daily mineral supplementation should be satisfied with one to three tablets every 8 or 6 hours. The beginning dose in most individuals should be one tablet every 8 hours, slowly increasing the number of tablets every day or so up to the point that a soft stool is produced. This titration method is used to prevent diarrhea and has proven to be very successful. If the stools become firmer, the dose can be increased about 20%, or if the stools remain or become loose, it should be reduced 25% to 50%, then slowly increased to the point of a soft stool. It should be noted that starvation diarrhea associated with a fasting diet will take longer to correct and require more Mg. Moreover, in such patients, breakthrough diarrhea should be expected, and the patient should be warned not to be discouraged and not to stop the Mg supplementation. Note that an oral loading dose up to 555 mg of Mg as Mg gluconate has been well tolerated,(11) after which the Mg could be supplemented with smaller amounts as described.

TIMING OF MAGNESIUM SUPPLEMENTATION

The data obtained in the fasting state suggest that Magonate should be taken 2 hours after a meal and at least 1/2 an hour before eating. I prefer 1 hour before a meal for maximum absorption, and my experience indicates that subsequently there is less Mg available in the ileum to produce the very loose stools so often seen with Mg supplementation. Six hour administration, including bedtime and 6 hours later, seems optimal. Mg supplementation would deliver 81 mg if one tablet were given every 8 hours (27% of RDA), 108 mg if one tablet were given every 6 hours (72% of RDA). These amounts are based on the assumption that the RDA is 300 mg/day. The schedule of supplementation suggested by the physician would be over and above the individual’s established routine of daily dietary intake of Mg from food and water.

THE VULNERABLE AMERICAN FEMALE

Dieting

Dieting begins very early, since about 70% of teenage girls diet. This astounding percentage appeared in a recent Time magazine article, which called self-perfection, that is, thinness, virtually the state religion of our American Society.(13) This article by Toufexis discusses the fact that “the pursuit of sylphlike thinness is not only futile for most men and women, it can be down right unhealthy.” Yo-yo dieters run a 70% higher risk of dying from heart disease than those with a stable weight. Lissner et al.(14) believe that this may be most important for those trying to shed the last 5 or 10 pounds. The Time article points out that women are “captives of this damaging aesthetic standard.”

Dieting has a profound effect on Mg balance. Not only is the Mg content of the dieter’s food significantly reduced, but Mg is also lost in the secondary diarrhea. This may actually be produced by the binding of Mg ions to phosphates, which are very high in some diet soda. We are not just talking about one soda per day, but many. How many people do you know who have soda for breakfast instead of Mg-rich cereals? In 2 months, the body can lose as much as 20% of its total amount of Mg.(2)

Pregnancy

There is a large burden on the mother’s Mg balance during pregnancy because of the baby’s needs, as pointed out by Dr. Caddell in this issue (p 191). Table 2 lists the possible consequences to the fetus and newborn because of the mother’s having chronic negative Mg balance. Reference lists are available on Mg and each of these diseases from the author.

Lactation

This is another way for mothers to become Mg deficient.(2) In addition, the mother must be in Mg balance if the infant is to receive sufficient Mg during breastfeeding. Unfortunately, many Mg-deficient mothers breastfeed their full-term babies, who subsequently develop sudden infant death syndrome (SIDS) during a time when their own Mg needs have increased during rapid growth of the baby.

TABLE 2. POSSIBLE CONSEQUENCES OF MATERNAL NEGATIVE MAGNESIUM BALANCE


    1. Miscarriage
    2. Stillbirth
    3. Sudden infant death in utero
    4. Premature neonate
    5. Apnea neonatorum
    6. Bronchopulmonary dysplasia
    7. Fetal alcohol syndrome
    8. Sudden infant death syndrome

Repletion

The Mg-deficient woman can have a most difficult time because repletion can take a year or more. Repeated, rapid-sequence pregnancies only compound the negative Mg balance. Oral supplementation very often will sustain the serum level in the normal range and also prevent symptoms, such as weakness, tremors, agitation, depression, and leg cramps. Leg cramps often are improved in a few days. Many times, other diseases, such as premenstrual syndrome(2) (PMS), may improve due to the correction of the chronic latent Mg deficiency. Moreover, this type of association needs to be made, as illustrated by the following example. One hundred six selected patients with transient cerebral ischemic attacks (TIA) were studied.(15)p value was 0.001, whereas in group B, those with TIA and tetanic syndrome, the p In group A, comparison of the outcome of Mg-supplemented vs Mg-unsupplemented patients with TIA and tetanic syndrome, the value was 0.05. The tetanic syndrome was an additional pathogenic factor postulated as an electrolyte imbalance appearing clinically as tetany. Since tetany in Mg deficiency appears later and is associated with more advanced deficiency, one would expect a lower Mg level. All diseases suspected to be associated with Mg deficiency need such correlations, but I am not surprised by these findings. It is very likely that there are significant genetic differences in the handling of Mg in the human race and differences in the disease state or symptomology will be manifested. Thus, it would appear that in the presence of two risk factors, TIA and migraine, the negative Mg balance may be greater in one or the other.

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