Mg Water

The Magnesium Web Site


Healthy Water
  The Magnesium
  Online Library

The Magnesium Online Library
The Magnesium Online Library More

Center for Magnesium Education & Research, LLC

Magnesium Symposium at Experimental Biology 2010

Program Announcement, April 24, 2010, Anaheim Convention Center

Featured Editorial from Life Extension Magazine, Sept. 2005:

How Many Americans Are Magnesium Deficient?

Complete Book by
Dr. Mildred S. Seelig:

Mg Deficiency in the Pathogenesis
of Disease

Free ebook
edited by Robert Vink and Mihai Nechifor
University of Adelaide Press

Magnesium in the Central Nervous System

John Libbey Eurotext

Magnesium Research
Archives, 2003-Present

The legal battle for recognition of the importance of dietary magnesium:

Legal documents

Healthy Water Association

HWA Button Healthy Water Association--USA
AHWA Button Arab Healthy Water Association



Paul Mason, Librarian
P.O. Box 1417
Patterson, CA 95363

Send Email to The Magnesium Online Library
Go to our Main Menu



In Journal of the American College of Nutrition, Vol. 12, NO. 4, 442-458 (1993)


Mildred S. Seelig, M.D., M.P.H., F.A.C.N.,

Adjunct Professor: Community and Preventive Medicine, New York Medical College, Valhalla, New York, and Nutrition, School of Public Health, University of North Carolina, Chapel Hill

The section headers of this paper are as follows:


The anticonvulsive and antihypertensive values of magnesium (Mg) in eclampsia, and its antiarrhythmic applications in a variety of cardiac diseases, have caused Mg to be considered only for parenteral administration by many physicians. In contrast, nutritionists have long recognized Mg as an essential nutrient, because severe deficiencies elicit neuromuscular manifestations similar to those justifying its use in eclampsia. More recently, this element has been used to favorably influence latent tetany with and without thrombotic complications, to delay preterm birth, to influence premenstrual syndrome, and to ameliorate migraine headaches. Most of these disorders exclusively or largely afflict women. The lesions of arteries and heart caused by experimental Mg deficiency have been well documented and may contribute to human cardiovascular disease. Estrogen's enhancement of Mg utilization and uptake by soft tissues and bone may explain resistance of young women to heart disease and osteoporosis, as well as increased prevalence of these diseases when estrogen secretion ceases. However, estrogen-induced shifts of Mg can be deleterious when estrogen levels are high and Mg intake is suboptimal. The resultant lowering of blood Mg can increase the CA/Mg ratio, thus favoring coagulation. With Ca supplementation in the face of commonly low Mg intake, risk of thrombosis increases.


AMI=acute myocardial infarction Ca=calcium cAMP-cyclic adenosine monophosphate DM=diabetes mellitus EDRF=endothelial derived relaxing factor HDL=high density lipoprotein IHD=ischemic heart disease i.v.=intravenous IUGR=intrauterine growth retardation LDL=low density lipoprotein MAP=mean arterial pressure Mg=magnesium mmol=millimole OCA=oral contraceptive agent PGI=prostacyclin potassium=K PMS=premenstrual syndrome PTH=parathyroid hormone RDA=recommended dietary allowances TBX=thromboxane VLDL=very low density lipoprotein


In physiologic amounts, estrogen protects against cardiovascular and bone diseases. In excess, especially in those with marginal or deficient magnesium (Mg) intake, estrogen may create problems. The observation that young women retaining Mg better than do young men has led to speculation that this might contribute to the sex difference in prevalence of ischemic heart disease (IHD). Lower dietary Mg intake in the West compared to the East may contribute to the relatively higher prevalence of IHD in Western populations [1]. Experimental and epidemiologic evidence implicating Mg deficiency in arteriosclerosis and IHD has been reviewed elsewhere [2-8]. The much greater prevalence of IHD in postmenopausal compared to young women, approaching that of men, reflects the protective effect of estrogen. The benefits of estrogen may be mediated in part by its effects on Mg distribution [9-11]. Estrogen replacement therapy during menopause is usually accompanied by increased intakes of calcium (Ca). Rarely considered is fact that Mg increases bone elasticity through formation and maintenance of bone matrix [5,9,12]. Development of osteoporosis in conditions of Mg malabsorption or urinary wasting provides evidence that Mg deficiency can be contributory to this disease [9].

Estrogen is deleterious at high levels. Thromboembolic events have complicated synthetic estrogen treatment of prostatic carcinoma [13], use as an oral contraceptive agent (OCA) [9,14,15] and use to inhibit lactation [9,16,17]. High estrogen secretion has been implicated in complications of pregnancy, for which parenteral Mg is effective and protective [18-34]. Correction of underlying Mg deficiency, and pharmacologic effects of Mg contribute to usefulness of Mg in cardiovascular disease and eclampsia. Mg deficiency is associated with thrombogenesis and arterioconstriction, which are pathogenic and complicating factors in both conditions. At pharmacologic levels, the anti-arrhythmic effects, formation of antiplatelet-aggregating, vasodilating factors: prostacycline (PGI) and endothelial derived relaxing factor (EDRF), and inhibition of formation of platelet-aggregating, vasoconstricting factors: thromboxane (TXB) and endothelin, were cited as justification of its use in a large study to test Mg's efficacy in reducing mortality in acute myocardial infarction (AMI) [35] . When estrogen is used to prevent osteoporosis, and Mg intake is marginal or low, high dosage Ca, which increases Mg needs [2-6], can keep the pro-coagulative effects of Ca from being countered by the normal anticoagulative effect of Mg in the circulation [5,9].


Preeclampsia, Eclampsia and Preterm Labor

Treating toxemic pregnancy with intravenous (i.v.) Mg was reported in 1925 [36]. In 1932, i.v. Mg was found to control bovine hypocalcemic postpartum convulsions, to correct arrhythmia caused by i.v.Ca, and to prevent or cure neuromuscular irritability terminating in convulsions of lactating cows consuming forage poor in Mg and rich in potassium (K) [37]. Diuretics and anti-convulsants displaced Mg for a time, in treatment of eclampsia, until it was shown, in 1965, that Mg treatment achieved better fetal salvage than did the new drugs [38]. Accordingly, the position of parenteral Mg as treatment of choice, has endured [39]. Mg is used now, as adjunct to tocolytic therapy, or alone, to prevent premature uterine contractions and preterm births (40-49).

Hypomagnesemia and Coagulopathy

Increased blood coagulability causes complications of toxemic pregnancies: embolic events, phlebothrombosis, and microthrombosis of glomeruli, and placental scarring that interferes with fetal blood supply, thus resulting in intrauterine growth retardation [IUGR]) [5,9,50-53]. Pulmonary embolism may cause death during pregnancy and postpartum [51], which suggests that naturally high estrogen secretion increases intravascular coagulation. The latter may be mediated by estrogen-induced shift of Mg from the blood into cells in the face of marginal or low intake [9-11]. Hypomagnesemic pregnant ewes had three-fold more platelets clumping than did normal ewes [27]. In another study [54], hypomagnesemic cows and ewes exhibited abnormal platelet activation. It has been postulated that Mg deficiency in pregnant women increases coagulability. Therefore use of Mg in eclampsia may reduce fetal and infant complications [22,27,54].


The production of glomerular microthrombi and lowered platelet counts in pregnant Mg deficient ewes developing preeclampsia called attention to the lowered ratio of PGI (vasodilator and anti-platelet-aggregating prostanoid) to thromboxane (vasoconstrictive, platelet-aggregating prostanoid) [27], that is seen in Mg deficiency [27,55,56, infra vide] and implicated in toxemias of pregnancy [57]. Furthermore, Mg increases formation of PGI by human umbilical endothelial cells [58] and cord vessel preparations [59]; endothelial cells from eclamptic patients who had received Mg treatment produced 2-5 times more PGI than did those not so treated [58]. Another potent circulating, naturally occurring vasoconstrictor (endothelin), produced by vascular endothelium, is more elevated in preeclamptic women before than after Mg treatment. Umbilical venous endothelin of toxemic patients was 10 times higher than in normal pregnant women [60]. Thus, not only has the use of Mg in eclampsia been scientifically justified, there is now laboratory evidence that Mg deficiency enhances intravascular blood coagulation and increases hypertension, both directly and indirectly via resultant increase in TXB and endothelin and decreases in EDRF and PGI.

Prophylaxis for Preeclampsia, Eclampsia and Preterm Birth

Several investigators have suggested that low Mg intake and tissue stores may contribute to eclampsia [18-34,41-46,61]. Mg supplements have prevented premature uterine contractions and reduced occurrence of calf cramps and sensations of numbness [25,30,42]. A double-blind study disclosed fewer complications in normal pregnant women given supplemental Mg than in controls [29]. Mg deficiency, alone, caused preeclamptic hypertension in pregnant triplet-bearing ewes [27]. Mg supplementation during pregnancy also was not only associated with fewer preterm deliveries, but fewer cases of IUGR [23,25,29-31,34,44,61]. In Hungary, where the prevalence of preterm deliveries is very high, a significant correlation was discerned between preterm delivery rates and Mg concentration in drinking water [62]. Two groups of pregnant women were randomly selected for a double blind study concerning prophylactic Mg supplementation [63]. Among 255 expectant mothers who received 300 mg/day from diagnosis of pregnancy to delivery, the preterm birth rate was 8.5%.; among 280 mothers given placebo but similarly managed prenatally, the preterm birth rate was 10.9%, a significant difference. There were too few spontaneous abortions to statistically evaluate the difference observed (1.6% in Mg-group; 3.6% in controls). However, supporting the premise that low Mg can contribute to spontaneous abortion was the observation from Italy that significantly lower Mg levels (and higher Ca/Mg ratios) were found in women whose pregnancies had aborted than in those whose pregnancies came to term [64]. Although a study in the United States has not confirmed the protection afforded by Mg against adverse outcomes of pregnancy [65]. routine Mg supplementation of pregnant women, is increasingly being recommended overseas [23,25,29-31,34,44,61].


With the foregoing data that support the premise that the efficacy of high dose Mg treatment in complications of pregnancy might be explained by repair of gestational Mg deficiency, as well as by its pharmacologic activity, what evidence is there that pregnant women are likely to be Mg deficient?

Metabolic Balance Evidence

We must rely principally on the early long-term metabolic balance studies to estimate the amount of Mg required by pregnant women for formation of new maternal and fetal tissue [66-69]. These extensive studies suggested that at least 450 mg/day was required to maintain the strong positive balance needed for maternal and fetal health. Of particular interest are data from a multipara who had had repeated uncomplicated pregnancies and healthy infants [68]. Intakes as high as 600 mg/day during the last half of her pregnancy resulted in cumulative retentions of 15.5 grams. Daily Mg intakes below 300 mg resulted in negative balance or bare equilibrium in an adolescent primipara [69]. Only two Mg balance studies of pregnant women have been found, since the studies of the 1930s [66-69]. One, a study of Ca requirements during pregnancy, showed that three teen-age primiparas, on Ca intakes of 2 g/day, had Mg balances of -14, +1 and +24, with mean urinary Mg output of 124 mg/day in a six day balance period [70]. The only long-term metabolic balance study during pregnancy, to provide data on Mg, was conducted in 10 healthy pregnant white, middle class women [71]. With a mean Mg intake of 269 +/- 55 mg, they had positive Mg balance in only 3 of 47 balance periods. Their mean Mg balance was -40 +/- 50 mg; their mean urinary loss was 94 +/- 28 mg, reflecting failure of renal conservation.

Renal Magnesium Excretion Studies

To examine whether inadequate Mg intake is related to toxemia of pregnancy [72], the urinary Mg output (in mEq/g creatinine) from 117 white, middle class women (aged 14-39 yrs, 10-42 weeks gestation) was compared with their mean arterial pressure (MAP: 2 x diastolic pressure + systolic pressure divided by 3; normal = about 90). There was significant negative correlation between MAP and Mg excretion when it was less than 7.0 mEq/g creatinine, both in 25 multiparous mothers and 32 primiparas. Four women had values less than 2.0 mEq/g creatinine; all had hypertension, with MAP > 105. In this study, those with the poorest Mg status had the highest blood pressure. Percentage retention of Mg loads, by measuring urinary Mg before and 24 hours after a parenteral Mg load, is a practical means of determining Mg status; retention of >20-25% has long been accepted as an index of Mg deficiency [5,73]. Three studies have employed this test to demonstrate Mg deficiency in normal pregnancies, and in those complicated by hypertension or diabetes [21,74,75].

Dietary Surveys and Estimates

Dietary surveys of American pregnant women show that their Mg intakes generally fall far short of needs. A 1976 report of the Mg intake of pregnant women, estimated from food record diaries from the fifth month of pregnancy until delivery [76] showed the average intake to be 204 mg +- 54 (S.D.) mg/d (103 to 333 mg). Almost 80% consumed less than 248 mg Mg in their normal diets. There was a positive correlation between Mg intake and birthweight of infants. Dietary estimates from 24-hour recall of low income pregnant women indicated Mg intakes of 102, and 124 mg/1000 kcal for adolescent and older women; 97.3 and 92.1% of the younger and older women, respectively, had Mg intakes less than 100% of the 1980 RDA [77]. A 1987 review of mean dietary Mg of pregnant women showed intakes to be 35-58% of the amount deemed desirable: 450 mg/day [78]. Low income women consumed 97-100 mg Mg/1000 kcal; higher income women consumed an average of 120 mg Mg/1000 kcal, not taking into account the Mg in drinking water. A 1991 report of 212 pregnant women and their infants showed that maternal Mg intake was inversely related to six month infant systolic pressure [79].

Recommended Dietary Allowances for Magnesium

The 9th edition of the RDA [80] lists 450 mg/day as the requirement of pregnant women, i.e. 150 mg/day is added to the amount recommended for non-pregnant women. The current edition [81] lowered the base daily requirement to 4.5 mg/kg/day, discounting the extensive metabolic studies showing negative Mg balances during most periods on intakes of less than 5 mg/kg/day [1,82]. This also ignores a more recent study of young women on controlled diets providing 265-305 mg/day of Mg (4-5 mg/kg/day), who remained in strong negative Mg balance over three consecutive 20-day balance periods [83]. The current RDA of only 40 mg of Mg more per day during pregnancy than the amount for girls 15-18 (300 mg) or those 19-24 (280 mg) is inappropriate and possibly dangerous. This is especially true for pregnant adolescents, whose requirements for growth and development may compete with those of the fetus. The current RDA for Mg was based in part on the erroneous assumption that half the ingested Mg is absorbed and that renal conservation can prevent deficiency, a conclusion not substantiated by the metabolic studies. Accordingly, the increased need of Mg for anabolic processes of gestation seems to justify prophylactic Mg administration to pregnant women to lower the risk of maternal and infant complications, while awaiting results of further investigation. [84,85].


The interrelationship between Mg and estrogen may be the basis for a strong association of migraine and eclampsia [86-88]. Migraine has been found to occur far more frequently in women who have had preeclampsia than in those who have not, and 2.5 times as often in patients with preeclampsia before the 34th week of pregnancy, than in those with normal pregnancy [88]. Favorable results have been reported in 80% of 3,000 women, given 200 mg/day of Mg for prophylaxis of eclampsia and migraine, when they were taking OCA or were pregnant [56,87]. The higher incidence of migraine among those prone to hypomagnesemia [25,89] and the influence of Mg on prostanoids and thrombogenesis, support the premise that Mg deficiency is involved in the pathogenesis of migraine [56,87,89].

Additional factors that may be involved in the role played by Mg deficiency in migraine relate, not only to prostaglandin metabolism [90], but to serotonin release and vascular reactivity to serotonin. In vitro studies have shown that platelets from migraine sufferers release more serotonin than normal, which may contribute to cerebral vasospasms [91]. Spasms of canine cerebral arteries induced by serotonin have been reduced by Mg [92]. Release of serotonin from platelets is enhanced by Ca and inhibited by Mg [93]. Serotonin levels are increased in Mg deficient animals [24,94]. Ca-channel blockers are effective in prophylaxis of migraine [95], and Mg is a physiologic Ca-channel blocker [96]. The latter further supports Mg treatment for migraine [97].


Mg deficiency has been associated with the premenstrual syndrome (PMS) alone [98-101], or in combination with inadequacies of zinc, linoleic acid and B vitamin (predominantly pyridoxine) [102-104] and high Ca intake [103]. The condition has been reported to respond to Mg supplements alone [101,104,105] or in combination with trace minerals and vitamins [106,107]. Mechanisms that may explain the explain the development of PMS, and its response to nutritional therapy, entail interrelations of Mg with estrogen and B vitamins in prostanoid, catecholamine, and serotonin synthesis and release [102].



Disturbances in cardiac rhythm caused by Mg deficiency were first described in rats in 1932 and 1938 [108, 109]. The nature of electrocardiogram changes caused by severe acute Mg deficiency was related to K deficiency in rats [110] and dogs [111], and then extended to longer-term subacute Mg deficiencies in dogs and monkeys [112-115]. Additional details of experimental evidence of the nature of Mg deficiency-induced dysrhythmias in cows and in humans have been presented elsewhere [3,5,8]. Additional evidence of Mg deficiency induced dysrhythmias in cows and humans has been presented elsewhere [3,5,8]. In addition, the therapeutic efficacy of i.v Mg was reported in cows with complications from i.v. Ca treatment) [37]. In the 1930 arrhythmias were also recognized as a risk of rapid i.v. Ca injections, used as an adjunct to digitalis treatment or to measure circulation time [116]. In contrast, i.v. Mg was recommended for circulation time determinations as it was relatively free of deleterious effect on the heart [117].

The efficacy of i.v Mg in controlling a variety of arrhythmias was shown in both men and women in 1935 [118], but received little attention until the 1975 evaluation of the role of Mg deficiency and replacement in cardiac rhythmicity [119]. The antiarrhythmic activity of Mg has since received widespread attention. Cited here are only a few key papers that consider prior Mg depletion as a pathogenic factor [120-123]. Use of Mg in victims of acute myocardial infarction (AMI), has been clearly demonstrated worldwide to improve survival [124-138]. The anti-arrhythmic effect of Mg is credited here; in the improved survival of AMI patients treated with Mg infusions; however its anti-thrombotic and anti-vasoconstrictive effects may also participate in the favorable outcome [5,8,35].

Ischemic Heart Disease

It has been recognized for many years that, with the menopause, the death rate from ischemic heart disease (IHD) increases, gradually rising by the seventh decade to about that of men (Table 1 [139].

Estrogen Table 1

However, low dosage estrogen replacement therapy has decreased the incidence of IHD in elderly women [140-143]. In a 1978 report, female to male ratios for pulmonary embolism death rates were higher from 20 to about 40 years of age; thereafter they were approximately the same [144]. A good question is whether the higher female:male ratio of this coagulative disorder reflects the use of OCA. OCA contained higher doses of estrogen 20 years ago. Thrombophlebitic events in women on high dosage estrogen-containing OCA [14-16], and in women given estrogen to inhibit lactation [16,17], led to studies examining whether estrogen increased coagulation. Synthetic estrogens, especially in high doses, but not low dose conjugated estrogens were shown to enhance blood coagulability [145-148]. In this regard, OCAs have been found to lower serum Mg levels [149-151] and Mg prophylaxis has been deemed protective for women on these agents [152].

Regarding eclampsia, intravascular coagulation that is seen with high levels of estrogen is described above. Men treated with estrogens for prostatic carcinoma had more thrombosis-associated cardiac disease than those not so treated [13] although the degree of atherosclerosis seems not to have been affected [153]. OCA users who smoke have increased platelet aggregation and decreased prostacyclin levels [154]. The interrelationships of Mg with PGI provide an additional mechanism through which estrogen may affect blood coagulation. It has been advised that during long-term estrogen therapy, Mg status should be monitored and deficits corrected to reduce the risk of phlebothrombosis [9,155].


Marginal Clinical Magnesium Deficiency

Women are more subject than men to latent tetany of marginal Mg deficiency. Many developed thromboses and emboli with this condition, yet new events have been prevented by Mg supplementation. However, these conditions often recurred when supplements were discontinued [152,156-158].

Magnesium/Calcium in Blood Coagulation

That Mg antagonizes activation Ca-induced blood clotting has been known since 1944 [159]. By many steps, Ca leads to fibrin formation and polymerization in clot formation has been defined [160,161]. Interestingly, Mg counteracts Ca stimulation of coagulation and enhances fibrinolysis [162,163] (Table 2).

Estrogen Table 2

Platelet aggregation requires both Mg and Ca, but is largely Ca-dependent. Mg is needed for deaggregation and to maintenance of platelet shape [9,164-167]. Aggregating platelets release serotonin, which participates in vasoconstriction (supra vide). The release is dependent on Ca and inhibited by Mg [93,168]. Serotonin-induced vascular muscle contraction is also inhibited by Mg [92,169,170].

Partial thromboplastin and thrombin clotting times were significantly shortened in Mg deficient calves, but prothrombin time, platelet counts and aggregation were unaffected [171]. Increasing serum Mg only to 2.1 mEq before partial occlusion (by suture) of coronary arteries of animals markedly diminished platelet aggregation at the site of injury and distal to it. This finding suggests that Mg might protect against thrombosis formation on atherosclerotic plaques and against formation of microthrombi associated with arteriospasms [172].

Magnesium and Experimental Lipidemic, Atherogenic, and Thrombogenic Diets

High blood levels of Ca increase risk of arrhythmias, and enhance blood coagulability (supra vide). Increased Mg levels counter both. Animal experiments demonstrating the anticoagulative, cardiovascular and renal protective effects of adding Mg to diets designed to be thrombogenic, hyperlipidemic, or infarctoid [3-5,173-175]. High-fat diets also have also been shown to increase Mg requirements. The atherogenicity of high fat diets is increased when the diets are also low in Mg [175-179]. How mechanisms involved in Mg/lipid interactions affect coagulation and vascular disease are being elucidated [180-186]. Of significance, in relating the effects of Mg on blood lipids to interrelationships with the effect of estrogen, is that both estrogen and Mg function to maintain levels of high-density lipoproteins (HDL).

Magnesium and Clinical Thrombotic Diseases

Ischemic Heart Disease. Increased platelet adhesiveness has long been recognized in patients with IHD [187] or AMI [188]. Adhesiveness is known to be intensified by hyperlipemia caused by high intake of saturated fatty acids [189-191]. As long recognized as the adverse effects of saturated fats on blood coagulation in patients with IHD, was the favorable response to Mg treatment of several hundred patients with IHD with and without recent AMI [192,193]. Their reduction in angina persisted as long as the Mg treatment was maintained, and tended to recur when it was discontinued. A 1959 report on patients with IHD correlated the efficacy of Mg with changes in blood lipids and coagulation factors and thrombolysis [194]. A recent double-blind study [195] of 47 IHD and MI patients compared the effects of 3 months of treatment with oral Mg (15 mmol/d) with placebo. Those receiving Mg had a 13% increase in molar ratio of apolipoprotein A1 to apolipoprotein B, vs a 2% increase in the placebo group. Triglycerides and very low density lipoproteins (VLDL) decreased by 27% after Mg treatment (from 2.41 to 1.76 mmol/L, and from 1.1 to 0.79 mmol/L, respectively). Decrements were much smaller with placebo. There was also a trend toward increased HDL and HDL/LDL/VLDLC ratio after Mg.

Magnesium, Prostacycline and Thromboxane. It has been hypothesized that the accelerated platelet-clumping produced by platelet-active collagen from damaged vascular intima in Mg deficient lambs is mediated by diminished production of PGI [196]. The release of more arachidonic acid, the precursor of prostanoids, from thymocytes of Mg deficient rats [197], led to study of the effect of Mg deficiency on these derivatives of phospholipid metabolism [198]. PGI, as measured by its stable metabolite 6-keto-PGFa1, increased 2-fold; PGE2 increased 3-fold, but TXB2 increased more than 10-fold. These increases were attributed to increased Ca levels of Mg deficient rats, since the enzyme responsible for liberation of arachidonic acid is Ca-activated phospholipase A2 [199]. The depression of cyclic adenosine monophosphate (cAMP) seen in Mg deficiency, also may participate directly in the markedly increased TXB2 synthesis of Mg deficiency, since cAMP inhibits TXB2 production by platelets [200]. Mg deficiency alters fatty acid metabolism, with arachidonic acid production diminished as a result of slowed conversion of linoleic acid to arachidonic acid [201]. This finding is pertinent to the role of prostanoids in blood coagulation. Dietary Mg depletion of humans has been shown to increase platelet aggregation and TXB2 release; effects that were reversed by Mg infusion [202].


Magnesium Deficiency and Decreased Bone Magnesium

Since osteoporosis is associated with disorders in which Mg loss occurs, estrogen deficiency may cause loss of tissue Mg. Postmenopausal osteoporosis is the most common form of this bone-wasting disease. Estrogen also interacts with other hormones that influence mineral utilization (infra vide) - both directly and possibly through its effects on Mg [9].

Evidence suggests a low Mg state in post menopausal women with osteoporosis. Significant retention of Mg after a parenteral Mg load - a practical means to detect Mg deficiency [5,9,73-75] has been found in postmenopausal patients with osteoporosis [203,204]. Serum Mg of 10 elderly osteoporotic women was marginally low (1.64 mEq/L) vs osteoporosis-free age-matched women (1.74 mEq/L). Biopsied bone Mg of the osteoporotic women (1.54 +- 0.29 mg/g) was lower than necropsy specimens from sudden death victims (1.75 +- 0.25) (205). Mg malabsorption was diagnosed in 12 of 20 post-menopausal osteoporotics [206]. Loss of trabecular bone (in which the bone crystals are abnormal [203,206]), is associated with decreased trabecular bone Mg in postmenopausal and senile osteoporosis [203,204,206,207], in alcohol-associated osteoporosis [208], and in diabetic osteoporosis (208,209]. Interestingly, the same abnormalities were not seen in estrogen treated women [203]. Patients with non-alcoholic cirrhosis (without osteoporosis), had low Mg in bone cortex rather than in trabecular bone [210]. The acidity of bone extracellular fluid, postulated to fall when Mg deficiency depresses the Mg-dependent adenosine triphosphatase H+-K+ pump in osteocytes, may result in decline in octacalcium phosphate formation in bone. The latter may explain the mechanism through which long-term Mg deficiency causes osteoporosis [[211].

Conditions that Increase Magnesium Needs in Osteoporosis

Magnesium Malabsorption and Renal Wasting. Patients with malabsorption caused by sprue, steatorrhea, inflammatory bowel disease, intestinal resections or genetic isolated Mg malabsorption manifest low bone Mg and low bone Mg/Ca ratios, as well as negative Mg balance [212-220]. Malabsorption was associated with slight generalized bone thinning in a 67 year old man [215], and with evidence of demineralization in a 56 year old black woman [219]. Vertebral osteoporosis was seen in a young man with Mg deficiency secondary to intestinal resection [213]. Juvenile osteoporosis has been reported in Bartter's syndrome, a genetic renal Mg wasting condition [220]. Malabsorption of Mg [207] and renal Mg wasting [221] have been diagnosed in postmenopausal osteoporosis.

Alcoholism. Many reasons exist for alcoholics to be hypomagnesemic. The chronic alcoholic has poor food intake and malabsorption. Alcohol causes a diuresis which increases urinary Mg output (seen even when consumed in moderate amounts [222-224]), and which can cause severe enough Mg deficiency leading to tremors, hallucinations, convulsions and arrhythmia, all of which respond to Mg therapy [224-226]. Accordingly, chronic Mg deficiency of alcoholism may contribute to development of osteoporosis [208].

Pregnancy. Pregnancy increases the need for both Mg and Ca [2,5,9,227, supra vide]. Therefore osteoporosis can be a risk among women who have experienced multiple pregnancies. In such women, repeated drains on Mg, as well as on Ca, may contribute to hyperparathyroidism of pregnancy (infra vide) This state is so common as to be termed "physiologic" [5,9,228].

Diabetes Mellitus. Mg depletion has long been associated with decompensated diabetes mellitus (DM) [229]. Osteoporosis is a frequent complication of insulin-dependent DM [203,230]. Subnormal serum Mg levels have been shown in juvenile diabetics [231,232]. Contributory to Mg deficiency is glycosuria, which increases Mg output in the urine even in normal subjects given glucose loads [224,233]. Because insulin is important in cellular uptake of Mg [234,235], chronic deficiency of this hormone may diminish tissue Mg, including bone. In fact, low bone Mg has been detected in diabetics [203,209], and low free ionic Mg has been detected in erythrocytes of DM patients [236].

Old Age. The elderly, who are prone to involutional osteoporosis, often have reduced food intake [237,238], impaired intestinal Mg absorption [207,239] and increased urinary Mg excretion [240], all factors that increase the likelihood of Mg deficiency. Also their hormonal changes can contribute to Mg loss [5,9,238]. Previously a dietary Ca/Mg ratio of 2/1, but with the frequently advised intake of 1200 mg/day of Ca or more, for the elderly, the ratio may be at least 4/1.

Calcium/Magnesium Imbalances

Effect of Increased Calcium Intakes on Magnesium. To compensate for the loss of Ca from osteoporotic bones, oral treatment with Ca is common. Rarely considered is the effect of high Ca intakes on Mg requirements [5-7], or the importance of Mg in maintaining normal bone matrix [5,9,12]. High dietary Ca/Mg ratios interfere with Mg absorption (Figure 1),

Estrogen Figure 1

partially because Ca and Mg share a common intestinal absorption pathway [217,241,242]. Metabolic studies have shown interference by high dietary Ca with Mg retention of normal young women [1,82], and of patients with osteopathies (Figure 2) [217,243-245].

Estrogen Figure 2

Moderately high Ca intake (1270 to 2360 mg/day) had little effect on the Mg balance of elderly men [246]. Similarly, increasing the Ca intake of young men from 700 to 1600 mg of Ca had little effect on Mg balance [247]. However, plasma Mg levels fell in the young men even though Mg balance was not affected when they were given up to 2 g/day of Ca [248].

Early experimental studies of Mg deficiency in rats employed diets with high Ca/Mg dietary ratios that were rich in vitamin D, resulting in hypermineralized, brittle bones [249-251]. This may be pertinent to the current encouragement of women to consume substantial amounts of Ca; regard is not given to probable low dietary Mg, as indicated by dietary surveys [252-258] and the inadequate current RDA for Mg [81].

Effect of Magnesium Deficiency and Calcium Supplementation. Diets low in Mg, or hypomagnesemia from other causes [259-263] have resulted in Mg-responsive hypocalcemia. Increasing Mg intake increased Ca absorption in normal young men on adequate Ca intake [264]. Refractoriness of hypocalcemia associated with Mg deficiency to Ca replacement, can be caused by impaired release of parathyroid hormone (PTH) and by resistance of target organs (bone and kidneys) to PTH [265-270], and/or by failure of to form hormonally active metabolites of vitamin D [271,272]. Treatment with Mg has long been known to restore responsiveness to vitamin D and PTH, and to correct hypocalcemia and hypomagnesemia [214,216,243].

Magnesium/Estrogen Interactions with Parathyroid Hormone and Vitamin D

Loss of estrogen's antagonism of PTH activity can be inferred by the development of postmenopausal hyperparathyroidism [273,274], and greater severity of osteoporosis in hyper- than in hypoparathyroid women [275]. Estrogen antagonizes PTH-induced bone resorption [276,277], and bone of ovariectomized rats has increased sensitivity to PTH as measured by Ca and hydroxyproline content and decreased bone thickness [278]. Loss of estrogen, which adversely affects Mg utilization [supra vide], is associated with greater bone responsiveness to the Ca-mobilizing effect of PTH, and with decreased formation of calcitriol. Both effects enhance Ca loss [279,280]. Thus, estrogen may protect bone via its influence on PTH release and its demineralization effects [5,9]. Whether estrogen's influence on the parathyroids might be mediated by Mg is not clear. As pointed out above, response to the PTH is impaired with severe Mg deficiency, and repair deficiency restores normal function. Paradoxically, deficiencies of Mg insufficient to suppress release of PTH or response of the target organs, have resulted in parathyroid hyperplasia and bone damage typical of hyperparathyroidism in normocalcemic calves [281] and increased PTH secretion by goat and sheep parathyroids perfused with hypomagnesemic, normocalcemic solutions [282-284].

Low calcitriol levels, and low activity of enzymes involved in its formation, are associated with old age and with involutional osteoporosis [285-290]. Nevertheless, response of the disease to its administration is inconsistent [289]. The need for more parathyroid stimulation for normal vitamin D metabolism by women with osteoporosis, and the lesser response of the elderly to calcitriol [290], has been correlated with possible Mg deficiency [291]. Calcitriol concentration has been raised during physiologically increased estrogen, during pregnancy [292], and during use of estrogen [293]. It has been suggested that impaired activation of 1-alpha-hydroxylase might be responsible for the estrogen deficiency-induced decreased formation of the active vitamin D metabolite [294]. On the grounds that low levels of the active form of vitamin D were found in Mg deficiency [295], that Mg administration (for 20 days) raised the level of PTH (the trophic hormone for alpha-hydroxylation [296], and that estrogen increases Mg retention (supra vide), estrogen-induced increase of calcitriol formation might be mediated by increased tissue Mg.


It is proposed that interrelationships between estrogen and Mg influence both women's resistance and vulnerability to certain diseases. When present in physiologic amounts, estrogen enhances Mg utilization, favoring its uptake by soft and hard tissues. Since there is substantial evidence that Mg is protective against cardiovascular disease, it is plausible that a contributory factor to the sex difference in prevalence of IHD in countries where the Mg intake is marginal or low might be estrogen's maintenance of adequate Mg levels in heart and arteries. On the other hand, high estrogen levels - whether secreted as in pregnancy, administered to prevent conception or lactation, or used in the treatment of prostatic cancer - have caused thrombotic complications. Ironically, hypercoagulability may also be a consequence of estrogen's shift of Mg from one compartment to another - in this case, lowering blood Mg in those with suboptimal Mg intakes. This results in diminution of counteraction by Mg of Ca-stimulating steps in the coagulation cascade. Lowered blood Mg also functions to increase levels of TXB and endothelin, and to decrease levels of PGI and EDRF. Calcemic prophylactic therapy of osteoporosis further increases the Ca/Mg ratio, creating a greater risk of thrombogenesis and arterial spasms.

Mg inadequacy may play a role in migraine and premenstrual tension, with and without participation of high estrogen levels. That estrogen is needed for maintenance of normal bone Mg levels is indicated by low bone Mg in post-menopausal osteoporotic bone. Mg is needed for maintenance of normal bone structure, both directly for matrix formation and indirectly for mineralization through its requirement for normal parathyroid and vitamin D metabolism. Estrogen also interacts with PTH and vitamin D, possibly in part through its effect on Mg. Development of osteoporosis in diseases associated with Mg loss is additional evidence of the importance of Mg in postmenopausal women.


1. Seelig MS: The requirement of magnesium by the normal adult. Am J Clin Nutr 14:342-390, 1964.

2. Seelig MS : Human requirements of magnesium. Factors that increase needs. Proc First Intl Sympos on Mg Deficit in Human Pathology, Ed J Durlach, Vittel, France 1:11-38, 1971. (privately printed)

3. Seelig MS, Heggtveit HA: Magnesium interrelationships in ischemic heart disease: A review. Am J Clin Nutr 27:59-79, 1974.

4. Seelig MS, Haddy FJ: Magnesium and the Arteries: I. Effects of magnesium deficiency on arteries and on retention of sodium, potassium, and calcium. In Magnesium in Health and Disease, eds M Cantin, MS Seelig, Spectrum, NY,NY, 1980, pp 605-638. (2nd Intl Mg Sympos, Quebec, Canada, 1976).

5. Seelig MS: Magnesium Deficiency in the Pathogenesis of Disease. Early Roots of Cardiovascular, Skeletal, and Renal Abnormalities. NY, NY, Plenum Medical Book Co. 1980

6. Seelig MS: Magnesium requirements in human nutrition. Magnesium Bull 1a:26-47, 1981.

7. Seelig MS: Nutritional Status and Requirements of Magnesium. Magnesium Bull 8:170-185, 1986.

8. Seelig MS: Cardiovascular consequences of magnesium deficiency and loss: pathogenesis, prevalence and manifestations- magnesium and chloride Loss in refractory potassium repletion. Am J Cardiol 63:4G-21G, 1989

9. Seelig MS: Increased need for magnesium with the use of combined oestrogen and calcium for osteoporosis treatment. Magnesium Res:3:197-215, 1990.

10. Goldsmith NF: Physiologic relationship between magnesium and the female reproductive apparatus. Serum magnesium variations in normal subjects; the effect of estrogen on magnesium distribution. Proc First Intl Sympos Mg, Ed J Durlach, Vittel, France, 1:439-458, 1971.

11. Goldsmith NF, Johnston JO: Magnesium-estrogen hypothesis: thromboembolic and mineralization ratios. in "Magnesium in Health and Disease", Eds M Cantin, MS Seelig, pp 313-323, 1980. Spectrum, New York. (Proc 2nd Intl Mg Sympos, Quebec, Canada, 1976).

12. Miller ER, Ullrey DE, Zutaut CL, Baltzer BV, Schmidt DA, Hoefer JA, Lurcke RW: Magnesium requirements of the baby pig. J Nutr 85:13-20, 1965.

13. Blackard CE, Doe RP, Mellinger GT, Byar DP: Incidence of cardiovascular disease and death in patients receiving diethylstilbestrol for carcinoma of the prostate. Cancer 26:249-256, 1970.

14. Cole M: Strokes in young women using oral contraceptives. Arch Intern Med 120:551-555, 1967.

15. Inman WHW, Vessey MP, Westerholm B, Engelund A: Thromboembolic disease and the steroidal content of oral contraceptives. A report to the committee on safety of drugs. Brit Med J 2:203-209. 1970.

16. Jeffcoate TNA, Miller J, Roos RF, Tindall VR: Puerperal thromboembolism in relation to the inhibition of lactation by oestrogen therapy. Brit Med J 4:19-25, 1968.

17. Unsigned Editorial: Thrombosis and inhibition of lactation. Brit Med J 4: 1-2, 1968.

18. Hall DG: Serum magnesium in pregnancy. Obstet Gynec 9:158-162, 1957.

19. Flowers Jr CE: Magnesium sulfate in obstetrics. Am J Obstet Gynec 91:763- 772, 775-776, 1965.

20. McGanity WJ (discussion). Magnesium sulfate in Obstetrics Am J Obstet Gynec 91:774-775, 1965.

21. Kontopoulos V, Seelig MS, Dolan J, Berger AR, Ross RS: Influence of parenteral administration of magnesium sulfate to normal pregnant and preeclamptic women. In Magnesium in Health and Disease, eds M Cantin, MS Seelig, Spectrum, NY, NY, 1980, pp 839-848. (2nd Intl Mg Sympos, Quebec, Canada, 1976).

22. Weaver K: A possible anticoagulant effect of magnesium in preeclampsia. In In Magnesium in Health and Disease,eds M Cantin, MS Seelig, Spectrum, NY, NY, 1980, pp 833--838. (2nd Intl Mg Sympos, Quebec, Canada, 1976).

23. Kuti V, Balazs M, Morvay F, Varenka Z, Szekly A, Szucs M: Effect of Maternal Magnesium Supply on Spontaneous Abortion and Premature Birth and on Intrauterine Foetal Development: Experimental Epidemiological Study. Magnesium Bull 3:73-79, 1981.

24. Altura BM, Altura BT, Carella A: Magnesium deficiency-induced spasms of umbilical vessels: relation to preeclampsia, hypertension, growth retardation. Science 221:376-378, 1983.

25. Fehlinger R, Kemnitz C, Dreibig P, Egert M, Seidel K: [Prematurity, latent tetany and magnesium deficiency: a retrospective study with 132 mothers.] Magnesium Bull 6:52-59, 1984. (in German)

26. Bartl W, Riss P: [Magnesium serum levels and magnesium deficiency in pregnancy.] Magnesium Bull 6:60-62, 1984. (in German)

27. Weaver K: Pregnancy-Induced Hypertension and Low Birth Weight in Magnesium-Deficient Ewes. Magnesium 5: 191-200, 1986.

28. Valenzuela GJ, Munson LA: Magnesium and Pregnancy. Magnesium 6:128-135, 1987.

29. Spaetling L, Spaetling G: Magnesium supplementation in pregnancy; a double-blind study; after treatment with intravenous MgSO4: a preliminary report. Br J Obstet Gynec 95:120-125, 1988.

30. De Ridder G, Gossen D: Magnesium in pregnancy--relationship to prophylaxis and therapy of early contractions and threatening premature birth. Magnesium Res. 1:247, 1988.

31. Kovacs L, Molnar BG, Huhn E, Bodis L: [Magnesium substitution in pregnancy. A prospective, randomized double-blind study]. Geburtshilfe-Frauenheilkd. 48:595-600, 1988. (in German)

32. Sjogren A, Gennser G, Rymark P: Reduced concentrations of magnesium, potassium and zinc in skeletal muscle from women during normal pregnancy or eclampsia. J Amer Coll Nutr 7:408, 1988.

33. LeBouedec G, Begon E, Monteillard C, Gioanni G, Pignide L, Bruhat MA: [Magnesium and the threat of premature labor]. J Gynecol Obstet Biol Reprod Paris 18: 53-60, 1989. (in French)

34. Molnar BG, Kovacs L: Experiences with magnesium substitution during pregnancy. Magnesium Res 2:230-231, 1989.

35. Woods K.L.: Possible pharmacological actions of magnesium in acute myocardial infarction. Br J Clin Pharmacol 32:3-10, 1991.

36. Lazard EM: A preliminary report on the intravenous use of magnesium sulphate in puerperal eclampsia. Am J Obstet Gynec, 9:178-188, 1925.

37. Sjollema B: Nutritional and metabolic disorders in cattle. Nutr Abstr Rev 1:621-632, 1932.

39. Sibai BM: Magnesium sulfate is the ideal anticonvulsant in preeclampsia- eclampsia. Am J Obstet Gynecol 162:1141-1145, 1990.

40. Elliott JP: Magnesium sulfate as a tocolytic agent. Am J Obstet Gynecol 147:277-284. 1983.

41. Valenzuela G, Hayashi RH, Johns A: Effect of magnesium sulfate upon uterine contractility in humans. Magnesium 2:120-124, 1983.

42. Classen HG, Helbig J: [Magnesium in obstetrics and gynecology.] Magnesium Bull 6:45-51, 1984.

43. Spaetling L, Schneider H, Huch R, Huch A: [Magnesium as an additional therapy to tocolysis.] Magnesium Bull 6:63-67, 1984.

44. Conradt A, Weidinger H, Algayer H: Magnesium therapy decreased the rate of intrauterine fetal retardation, premature rupture of membranes and premature delivery in risk pregnancies treated with betamimetics. Magnesium 4:20-28, 1985.

45. Wischnik A, Weidinger H: [Magnesium Aspartate and Magnesium Sulfate in Obstetrics.] Magnesium Bull 7:96-101, 1985. (In German)

46. Spaetling L: Magnesium deficiency and premature labour. Magnesium Bull 7: 81-86, 1985.

47. Spaetling L: Magnesium deficiency and preterm labor. In Magnesium in Health and Disease, eds Y Itokawa, J Durlach. J. Libbey, London, 1989, pp 363-366 (5th Intl Mg Sympos, Kyoto, 1988).

48. Hatjis CG, Swain M, Nelson LH, Meis PJ, Ernest JM: Efficacy of combined administration of magnesium sulfate and ritodrine in the treatment of premature labor. Obstet Gynecol 69(3 Pt 1): 317-322, 1987.

49. Hollander DI, Nagey DA, Pupkin MJ: Magnesium sulfate and ritodrine hydrochloride: a randomized comparison. Am J Obstet Gynec 156:631-637, 1987.

50. Bonnar J, McNicol GP, Douglas AS: Coagulation and fibrinolytic systems in preeclampsia and eclampsia. Brit J Med 3:12-16, 1971.

51. Unsigned Editorial: Antenatal thromboembolism. Brit Med J 1:249-250, 1970.

52. Warkany J, Monroe BB, Sutherland BS: Intrauterine growth retardation, J Dis Child 102:249-279, 1961.

53. McKay DG, Goldenberg V, Kaunitz H, Csvassy I: Experimental eclampsia. An electron microscopic study and review. Arch Path 84:557-597, 1967.

54. Miller JK, Schneider MD, Ramsey N, White PK, Bell MC: Effects of hypomagnesemia on reactivity of bovine and ovine platelets: possible relevance to infantile apnea and sudden infant death syndrome. J Am Coll Nutr 9: 58-64, 1990.

55. Weaver K: Magnesium and its role in vascular reactivity and coagulation. Contemp Nutr 12:1-2, 1987.

56. Weaver K: Magnesium and migraine: reversible hypomagnesemic coagulative angiopathy. Hypothesis and preliminary clinical data. J Am Coll Nutr 1:187-188, 1983.

57. Ogburn PL, Williams PP, Johnson SB, Holman RT: Serum arachidonic levels in normal and preeclamptic pregnancies. Am J Obstet Gynecol 148:5-9, 1984.

58. Watson KV, Moldow CF, Ogburn PL, Jacob HS: Magnesium sulfate: rationale for its use in preeclampsia. Proc Natl Acad Sci USA 83:1075-1078, 1986.

59. Briel RC, Lippert TH, Zahradnik HP: [Changes in blood coagulation, thrombocyte function and vascular prostacyclin synthesis caused by magnesium sulfate]. Geburtshilfe Frauenheilkd 47:332-336, 1987. (in German)

60. Mastrogiannis DS, O'Brien WF, Krammer J, Benoit R: Potential role of endothelin-1 in normal and hypertensive pregnancies. Am J Obstet Gynecol 165(6 Pt 1):1711-1716, 1991.

61. Wynn A, Wynn M: Magnesium and other nutrient deficiencies as possible causes of hypertension and low birthweight. Nutr Health. 6:69-88, 1988.

62. Losonczy J, Adorjan G, Novak M, Toth MO: Correlation between the incidence of preterm delivery and the concentration of magnesium in drinking water in Szabolcs-Szatmar County, Northeast Hungary. Magnesium Res 2:229-230, 1989.

63. Novak M, Losonczy J, Kornafeld J, Toth MO: Experiences on giving magnesium citrate to pregnant mothers. Magnesium Res 2:230, 1989.

64. Borella P, Szilagyi A, Than G, Csaba I, Giardino A, Facchinetti F: Maternal plasma concentrations of magnesium, calcium, zinc and copper in normal and pathological pregnancies. Sci Total Environ 99:67-76, 1990.

65. Sibai BM, Villar MA, Bray E: Magnesium supplementation during pregnancy: a double-blind randomized controlled clinical trial. Am J Obstet Gynecol 161:115-119, 1989.

66. Coons C, Blunt K: retention of nitrogen, calcium, phosphorus, and magnesium by pregnant women. J Biol Chem 86:1-16, 1930.

67. Coons CM, Schiefelbusch AT, Marshall BB, Coons RR: Studies in metabolism during pregnancy. Oklahoma Agric Mech Coll Agric Exp Sta Bull #223: 1-113, 1935.

68. Hummel F, Sternberger H, Hunscher H, Macy I: Metabolism of women during the reproductive cycle. VII. Utilization of inorganic elements (a continuous case study of a multipara). J Nutr 11:235-255, 1936.

69. Hummel FC, Hunscher HA, Bates MF, Bonner P, Macy IC, Johnston JA: A consideration of the nutritive state in the metabolism of women during pregnancy. J Nutr 13:263-278, 1937

70. Duggin GG, Dale NE, Lyneham RC, Evans RA, Tiller DJ: Calcium balance in pregnancy. Lancet (Oct): 926-927, 1974.

71. Ashe JR, Schofield FA, Gram MR: The retention of calcium, iron, phosphorus, and magnesium during pregnancy: the adequacy of prenatal diets with and without supplementation. Am J Clin Nutr 32:286-291, 1979.

72. Franz KB: Correlation of Urinary Magnesium Excretion with Blood Pressure of Pregnancy. Magnesium Bull 4:73-78, 1982.

73. Elin R.J. (1988): Magnesium metabolism in health and disease. Disease-a- Month 34:161-219

74. Palla GP, Giaquinto P, Moro PR, Maniccia E, Carelli G, Mancuso S: Magnesium Load Test in Pregnancy Hypertension. Clin Exp Hypertens Pregn B7:159-163, 1988.

75. Palla GP, Castaldo F, Moro P R, Giaquinto P, Carelli G, Caruso A, Lanzone A, Mancuso S: Intravenous magnesium load test in normal and diabetic pregnant women. Magnesium Res 2:91-92, 1989.

76. Johnson NE, Philipps C: Magnesium content of diets of pregnant women. In Magnesium in Health and Disease. eds M Cantin, MS Seelig, Spectrum, New York, 1980, pp 827-831. (2nd Intl Sympos on Magnesium, Quebec, 1976) 77. Endres J, Dunning S, Poon S, Welch P, Duncan H: Older pregnant women and adolescents: Nutrition data after enrollment in WIC. J Amer Dietetic Assc 87:1011-1019, 1987.

78. Franz KB: Magnesium intake during Pregnancy Magnesium 6:18-27, 1987.

79. McGarvey ST, Zinner SH, Willett WC, Rosner B: Maternal prenatal dietary potassium, calcium, magnesium, and infant blood pressure. Hypertension 17:218-224, 1991.

80. Food and Nutr Bd: Recommended Dietary Allowances, 9th Ed, Natl Acad Press, pp 134-136, 1980.

81. Food and Nutr Bd: Recommended Dietary Allowances, 10th Ed, Natl Acad Press, pp 187-194, 1989.

82. Hathaway M: Magnesium in human nutrition. Home Econ Res Rep 19, Agric Res Serv, USDA, 1962.

83. Irwin MI, Feeley RM: Frequency and size of meals and serum lipids, nitrogen and mineral retention, fat digestibility and urinary thiamine and riboflavin in young women. Am J Clin Nutr 20:816-824, 1967.

84. Seelig MS: Magnesium in pregnancy: special needs for the adolescent mother. J Am Coll Nutr 10:566, 1991.

85. Seelig MS, Franz K, Weaver K: Poor outcomes of adolescent pregnancy; relationship to magnesium deficiency. (in preparation)

86. Rotton WN, Sachtleben MR, Friedman EA: Migraine and eclampsia. Obstet Gynecol 14:322-330, 1959.

87. Weaver K (letter to editor): Migraine and magnesium. Perspect Biol Med 33:150-151, 1989.

88. Moore MP, Redman CWG: Case control study of severe eclampsia of early onset. Brit Med J 287:580-583, 1983.

89. Swanson DR: Migraine and magnesium; eleven neglected connections. Perspect Biol Med 31:526-557, 1988.

90. Horrobin DF: Hypothesis: prostaglandins and migraine. Headache 17:113-117, 1977.

91. Anthony M: Serotonin and cyclic nucleotides in migraine. Adv Neurol 33:45-49, 1982.

92. Allen GS, Gross CJ, Henderson LM, Chou SN: Cerebral arterial spasm. IV. In vitro effects of temperature, serotonin analogues, large nonphysiologic concentrations of serotonin, and extracellular calcium and magnesium on serotonin-induced contractions of the canine basilar artery. J Neurosurg 44:585-593, 1976.

93. Sneddon JM, Willimas KI: Effect of cations on the platelet release reaction. J Physiol (Lond) 235:625-637, 1973.

94. Itokawa Y, Tanaka C, Kimura M: Effect of thiamine on serotonin levels in magnesium-deficient animals. Metabolism 21:375-379, 1972.

95. Olesen J: Role of calcium-entry blockers in the prophylaxis of migraine. Europ Neurol 25 (suppl 1):72-79, 1986.

96. Iseri LT, French JH: Magnesium: nature's physiologic calcium blocker. Am Heart J 108:188-193, 1984.

97. Altura BM (editorial): Calcium antagonist properties of magnesium; implication for antimigraine actions. Magnesium 4:269-275, 1985.

98. Abraham GE, Lubran MM: Serum and red cell magnesium levels in patients with premenstrual tension. Am J Clin Nutr 34:2364-2366, 1981.

99. Abraham GE: Magnesium deficiency in premenstrual tension. Magnesium Bulletin 4:68-73, 1982.

100. Facchinetti F, Borella P, Valentini M, Pironti T, Ficroni L, Genazzani A: Magnesium variability in blood cells throughout the normal and pathological menstrual cycle. in Magnesium in Health and Disease eds Y Itokawa, J Durlach, Publ: J Libbey, London, 1989, pp. 163-170 (Fifth Intl Mg Sympos, Kyoto, Japan 1988)

101. Stewart A, Howard J: Magnesium and potassium deficiencies in women with pre-menstrual syndrome. Magnesium Bull 8:314-316, 1986.

102. Abraham GE: Nutritional factors in the etiology of the premenstrual syndrome tension syndromes. J Reprod Med 28:446-464, 1983.

103. Abraham GE: Nutrition and the premenstrual tension syndromes. J Appl Nutr 36:103-124, 1984.

104. Gallant MP, Bowering J, Short SH, Turkki PR: Pyridoxine and Magnesium Status of Women with Premenstrual Syndrome. Nutrition Research 7:243-252, 1987.

105. Facchinetti F, Borella P, Sances G, Fioroni L, Nappi RE, Genazzani AR Oral magnesium successfully relieves premenstrual mood changes. Obstet Gynecol 78:177-181, 1991.

106. Abraham GE, Rumley RE: Role of nutrition in managing the premenstrual tension syndromes. J Reprod Med 32:405-422, 1987.

107. London RS, Bradley L, Chiamori NY: Effect of a nutritional supplement on premenstrual symptomatology in women with premenstrual syndrome: a double-blind longitudinal study. J Am Coll Med 10:494-499, 1991.

108. Kruse HD, Orent ER, McCollum V: Studies on magnesium deficiency in animals. Symptomatology resulting from magnesium deprivation. J Biol Chem 96:519-539, 1932.

109. Greenberg D, Tufts E: The nature of magnesium tetany. Am J Physiol 121:269-300, 1938.

110. Seta K, Hellerstein E, Vitale JJ: Myocardium and plasma electrolytes in dietary magnesium and potassium deficiency in the rat. J Nutr 87:179-188, 1965.

111. Seta K, Kleiger R, Hellerstein EE, Lown B, Vitale JJ: Effect of potassium and magnesium deficiency on the electrocardiogram and plasma electrolytes of pure-bred beagles. Am J Cardiol 17:516-519, 1966.

112. Syllm-Rapaport I, Strassburger I, Gruneberg D, Zirbel C: Electrocardiographic studies in dogs with experimental magnesium deficiency. J Paediat 60:801-804, 1962.

113. Wener J, Pintar K, Simon MA, Motola R, Friedman R, Mayman A, Schucher R: The effects of prolonged hypomagnesemia on the cardiovascular system in young dogs. Am Heart J 67:221-231, 1964.

114. Vitale JJ, Hellerstein EE, Nakamura M, Lown B: Effects of magnesium deficient diet upon puppies. Circ Res 9:387-394, 1961.

115. Vitale JJ, Velez H, Guzman C, Correa P: Magnesium deficiency in the cebus monkey. Circ Res 12:642-650, 1963.

116. Berliner K: Then effect of calcium injections on the human heart. Am J Med Sci 191:117-121, 1936.

117. Bernstein M, Simkins S: Magnesium; effects of intravenous injections on human heart. J Lab Clin Med 25:131-141, 1939.

118. Zwillinger L: [About magnesium's effect on the heart]. Klin Wschr 14:1429-1433, 1935. (in German)

119. Iseri LT, Freed J, Bures AB: Magnesium deficiency and cardiac disorders. Am J Med 58:837-846, 1975.

120. Dyckner T, Wester PO: Ventricular extrasystoles and intracellular electrolytes before and after potassium and magnesium infusions in patients on diuretic treatment. Am Heart J 97:12-18, 1979.

121. Dyckner T, Wester PO: Potassium/Magnesium Depletion in Patients with Cardiovascular Disease. Am J Med 82(3A):11-17, 1987.

122. Charbon GA: Magnesium treatment of arrhythmia: drug or nutritional replenishment? pitfalls for the experimental design. In Magnesium in Health and Disease, eds Y Itokawa J Durlach, Publ J Libbey, London, 1989, pp 223-228. (Fifth Intl Mg Sympos, Kyoto, Japan,1988).

123. Iseri LT: Role of magnesium in cardiac tachyarrhythmias. Am J Cardiol 65: 47K-50K, 1990.

124. Morton BC, Nair RC, Smith FM, McKibbon TG, Poznanski WJ: Magnesium in therapy in acute myocardial infarction - a double-blind study. Magnesium 3:346-352, 1984.

125. Smith LF, Heagerty AM, Bing RF, Barnett DB: Intravenous infusion of magnesium sulphate after acute myocardial infarction: effects on arrhythmias and mortality. Intl J Cardiol 12:175-183, 1986.

126. Rasmussen HS: Justification for intravenous magnesium therapy in acute myocardial infarction. Magnesium Res 1:59-73, 1988.

127. Rasmussen HS, Gronbaek M, Cintin C, Balslov S, Norregard P, McNair P: One-year death rate in 270 patients with suspected acute myocardial infarction, initially treated with intravenous magnesium or placebo. Clin Cardiol 11: 377-381, 1988.

128. Golf SW, Temme H, Moebius T, Greaf V, Roka L, Homann J: magnesium therapy after acute myocardial infarction: chronologic sequence of biochemical blood parameters. Magnesium Bull 10:"119-123, 1988.

129. Bertschat F, Ising H, Guenther T, Sorgenfrei J, Wollitz M, Ibe K: Antiarrhythmic effects of magnesium infusions in patients with acute myocardial infarction. Magnesium Bull 11:155-158, 1989.

130. Rasmussen HS: Clinical intervention studies on magnesium in myocardial infarction. Magnesium 8:316-325, 1989.

131. Sheehan J: Importance of magnesium chloride repletion after myocardial infarction. Am J Cardiol 53:35G-38G, 1989.

132. Abraham AS: Treatment of patients with acute myocardial infarction with intravenous magnesium. Magnesium Trace Elem 9:177-185, 1990.

133. Pereira D, Pereira TG, RabaÝal C, Carvalho E, Linder J, Afonso JS, Pereira JN, Halpern MJ, Fernandes JS: [Effect of intravenous administration of SO4Mg in the acute phase of myocardial infarct]. Rev Port Cardiol 9:205-210, 1990.

134. Shechter M: Beneficial Effect of magnesium in acute myocardial infarction. A Review of the Literature. Magnesium Bull 12: 1-6, 1990.

135. Shechter M, Hod H, Marks N, Behar S, Kaplinsky E, Rabinowitz B: Beneficial effect of magnesium sulfate in acute myocardial infarction. Am J Cardiol 66:271-274, 1990.

136. Singh RB, Sircar AR, Rastogi SS, Garg V: Magnesium and potassium administration in acute myocardial infarction. Magnesium Trace Elem 9:198-204, 1990.

137. Teo KK, Usuf S, Collins R, Held PH, Peto R: Effects of intravenous magnesium in suspected acute myocardial infarction: overview of randomized trials. Brit Med J 303:1499-1503, 1991.

138. Rebentisch E, Ising H,Bertschat F, Sorgenfrei J: (Magnesium treatment during arrhythmias following myocardial infarction - therapeutic efficacy and electrolyte status.) Magnesium Bull 14:111-121, 1992. (in German)

139. Stamler JS: The relationship of sex and gonadal hormones to atherosclerosis. in Atherosclerosis and its Origin. eds M Sandler, GH Bourne, Academic Press, NY, 1963, pp 231-262.

140. Bush TL, Barrett-Connor E: Noncontraceptive estrogen use and cardiovascular disease. Epidemiol Rev 7:80-104, 1985.

141. Stampfer MJ, Willet WC, Coldita GA, Rosner B, Speizer FE, Henekens CH: A prospective study of postmenopausal estrogen therapy and coronary heart disease. New Engl J Med 313:1044-1049, 1985.

142. Knopp RH: Arteriosclerosis risk. The roles of oral contraceptives and postmenopausal estrogens. J Reprod Med 31:913-921, 1986.

143. Henderson BE, Paganini-Hill A, Ross RK: Estrogen replacement therapy and protection from acute myocardial infarction. Am J Obstet Gynec 159: 312-317, 1988.

144. Anderson TW: The changing pattern of ischemic heart disease. New Scientist 9:374-376, 1978.

145. Bolton CH, Hampton JR, Mitchell JRA: Effect of oral contraceptive agents on platelets and plasma phospholipids. Lancet 1:1336-1341, 1960.

146. Robinson RW, LeBeau R, Maschouf C: Effect of conjugated equine estrogens on the clotting mechanism. Circulation 28:670 (abstr), (1963.

147. Caspary EA, Peberdy M: Oral Contraception and Blood Platelet Adhesiveness. Lancet 1: 1142-1143, 1965.

148. Paganini-Hill A, Ross RK, Henderson BE: Postmenopausal oestrogen treatment and stroke: a prospective study. Brit Med J 297:519-522, 1988.

149. Goldsmith NF, Pace N, Baumberger JP, Ury H: Magnesium and citrate during the menstrual cycle. Effect of an oral contraceptive on serum magnesium. Fertil Steril 21:292-300, 1970.

150. Goulding A, McChesney R: Oestrogen-progestogen oral contraceptives and urinary calcium excretion. Clin Endocr 6:449-454, 1977.

151. Olatunbosun DA, Adeniyi FA, Adadevoh BK: Effect of oral contraceptives on serum magnesium levels. Intl J Fert 19:224-226, 1974.

152. Durlach J: The pill and thrombosis; platelets, estrogen and magnesium. Rev Franc Endocr Clin 11:45-54, 1970. (in French)

153. Hanash KA, Taylor WF, Greene LF, Koeke BA, Titus JL: Relationship of estrogen therapy for carcinoma of the prostate to atherosclerotic cardiovascular disease: a clinicopathologic study. J urol103:467-470, 1970.

154. Mileikowsky GN, Nadler JL, Francis R, Roy S: Evidence that smoking alters prostacyclin formation and platelet aggregation in women who use oral contraceptives. Am J Obstet Gynecol 159:1547-1552, 1988.

155. Durlach J: Clinical aspects of chronic magnesium deficit. In Magnesium in Health and Disease, eds M Cantin, MS Seelig, Spectrum, NY, NY, 1980, pp 883--909. (2nd Intl Mg Sympos, Quebec, Canada, 1976).

156. Durlach J: [The antithrombotic physiology of magnesium; phlebothrombosis caused by magnesium deficiency.] Coeur Med Interne 6:213-232, 1967. (in French)

157. Dupont B, Pony JC, LeBihan G, Leborgne P: [Phlebothrombotic disease and magnesium.] Sem Hop Paris 45:3048-3054, 1969.

158. Maurat J-P, Debrand J, Kieffer Y, Cardot N : [Magnesium deficiency and platelet aggregability.] (French) Rev Franc Endocrinol Clin 15:505-508, 1974. (in French)

159. Greville GD, Lehmann H: Cation antagonism in blood coagulation. J Physiol 103:175-184, 1944.

160. Silver MJ: Role of calcium ions and phospholipids in platelet aggregation and plug formation. Am J Physiol 209:1128-1136, 1965.

161. Lorand L, Konishi K: Activation of the fibrin stabilizing factor of plasma by thrombin. Arch Biochem Biophys 105:58-67, 1964.

162. Zahnert R, Oloffs J: [Study of the role of magnesium coagulation factors and the thromboelastogram]. Dtsche-Gesundh 15:2343-2348, 1960 (in German)

163. Huntsman RG, Hurn BA, Lehmann H: Observations on the effect of magnesium on blood coagulation. J Clin Path 13:99-101, 1960.

164. Herrmann RG, Lacefield WB, Crowe VG: Effect of ionic calcium and magnesium on human platelet aggregation. Proc Soc Exp Biol Med 135: 100-103, 1970.

165. Born GVR, Cross MJ: Effects of inorganic ions and of plasma proteins on the aggregation of blood platelets by adenosine phosphate. J Physiol 170: 397-414, 1964.

166. Elin RJ: Role of magnesium in membranes: erythrocyte and platelet function and stability. In Magnesium in Health and Disease,eds M Cantin, MS Seelig, Spectrum, NY, NY, 1980, pp 113-124.(2nd Intl Mg Sympos, Quebec, Canada, 1976).

167. Hughes A, Tonks RS: Magnesium, adenosine diphosphate and blood platelets. Nature 210:106-107, 1966.

168. Penglis F, Michal F: The induction of blood platelet aggregation by divalent cations. Experimentia 25:745-746, 1969.

169. Altura BM, Altura BT: Mg, Na, and K interactions and coronary artery diseases. Magnesium 1:241-256, 1982.

170. Goldstein S, Zsoter TT: The effect of magnesium on response of smooth muscle to 5-hydroxytryptamine. Br J Pharmacol 62:507-514, 1978.

171. Stevenson MM, Yoder I: Studies of platelet aggregation, plasma adenosine diphosphate breakdown and blood coagulation in magnesium deficient calves and rats. Thromb Diath Hemorrh 23:299-305, 1979.

172. Gertz SD, Wajnberg RS, Kurgon A, Uretzky G: Effect of magnesium sulfate on thrombus formation following partial arterial constriction: implications for coronary vasospasm. Magnesium 6: 225-235, 1987.

173. Vitale J, Hellerstein E, Hegsted D, Nakamura M, Farbman A: Studies on the interrelationships between dietary calcium and magnesium in atherogenesis and renal lesions. Am J Clin Nutr 7:13-22, 1959.

174. Bunce G, Chiemchaisri Y, Phillips P: The mineral requirements of the dog. IV. Effect of certain dietary and physiologic factors upon the magnesium deficiency syndrome. J Nutr 76:23-29, 1962.

175. Sos J, Gati T, Kemeny T, Rigo J: Infarctoid cardiac lesions induced by dietetic factors in the dog. Acta Med Acad Sci Hung 20:1-8, 1964.

176. Vitale J, White P, Nakamura M, Hegsted D: Effect of feeding an atherogenic diet on magnesium requirement. Fed Proc 16:400-401, 1957.

177. Vitale J, White P, Nakamura M, Hegsted D, Zamcheck M, Hellerstein E: Interrelationships between experimental hypercholesterolemia, magnesium requirements and experimental atherosclerosis. J Exp Med 106:757-766, 1957.

178. Szelenyi I, Rigo J, Ahmed BO, Sos J: The role of magnesium in blood coagulation. Thromb Diath Haemorrh 18:626-633, 1967.

179. Savoie LL: [Role of magnesium, potassium, antikaluretics and hypocholesterolemics in development of cardiac lesions in the rat fed a thrombogenic diet with NaH2PO4.] Path Biol 20:19-20, 751-756, 1972.

180. Rayssiguier Y: Magnesium and lipid interrelationships in the pathogenesis of vascular diseases. Magnesium Bull 3:165-177, 1981.

181. Gueux E, Rayssiguier Y: The hypercholesterolaemic effect of magnesium efficiency following cholesterol feeding in the rat. Magnesium Bull 3: 126-129, 1981.

182. Rayssiguier Y, Gueux E: The reduction of plasma triglyceride clearance by magnesium-deficient Rats. Magnesium 2:132-138, 1983.

183. Gueux E, Rayssiguier Y, Piot M-C, Alcindor L: The reduction of plasma lecithin-cholesterol acyl-transferase activity by acute magnesium deficiency in the rat. J Nutr 114:1479-1483, 1984.

184. Rayssiguier Y: Magnesium, lipids and vascular diseases. Experimental evidence in animal models. Magnesium 5:182-190, 1986.

185. Rayssiguier Y, Gueux E: Magnesium and lipids in cardiovascular disease. J Am Coll Nutr 5:507-519, 1986.

186. Rayssiguier Y, Gueux E, Cardot P, Thomas G, Robert A, Trugnan G: Variations of fatty acid composition in plasma lipids and platelet aggregation in magnesium deficient rats. Nutr Res 6:233-240, 1986.

187. McDonald L, Edgill M: Dietary restriction and coagulability of the blood in ischaemic heart disease. Lancet 1:996-998, 1958.

188. Hughes A, Tonks RS: Platelets, magnesium, myocardial infarction. Lancet 1:1044-1046, 1965.

189. Horlick L: Platelet adhesiveness in normal persons and in subjects with atherosclerosis. Effect of high fat meals and anticoagulants in the adhesive Index. Am J Cardiol 8:459-470, 1961.

190. Mustard JF, Murphy EA: Effect of different dietary fats on blood coagulation, platelet economy, and blood lipids. Brit Med J 1: 1651-1655, 1962.

191. Connor WE: The acceleration of thrombus formation by certain fatty acids. J Clin Invest 41:1199-1205, 1962.

192. Malkiel-Shapiro B, Bershon I, Terner PE: Parenteral magnesium sulphate therapy in coronary heart disease. A preliminary report on its clinical and laboratory aspects. Med Proc 2:455-462, 1956.

193. Malkiel-Shapiro B: Further observations on parenteral magnesium sulphate therapy in coronary heart disease: a clinical appraisal. S African Med J 32:1211-1215, 1958.

194. Parsons RS, Butler TC, Sellars EP: The treatment of coronary artery disease with parenteral magnesium sulphate. Med Proc 5:487-498, 1959.

195. Rasmussen HS, Aurup P, Goldstein K, McNair P, Mortensen P, Larsen OG, Lawaetz H: Influence of magnesium substitution therapy on blood lipid composition in patients with ischemic heart disease. A double-blind, placebo controlled study. Arch Intern Med 149:1050-1053, 1989.

196. Schneider MD, Miller JK, White PK, Ramsey N: Life span and tissue distribution of 111indium-labeled blood platelets in hypomagnesemic lambs. Magnesium Bull 3:116-122, 1981.

197. Averdunk R, Guenther T: Phospholipid metabolism and concavalin. A stimulation of thymocytes from magnesium deficient rats and magnesium - deficiency induced lymphoma. Magnesium Bull 7:11-15, 1985.

198. Nigam S, Averdunk R, Guenther T: Alteration of prostanoid metabolism in rats with magnesium deficiency. Prostaglandins Leukotrienes Med 23:1-10, 1986.

199. Van den Busch H: Intracellular phospholipase A. Biochim Biophys Acta 604:191-246, 1980.

200. Malmsten C, Granstom E, Samuelsson B: Cyclic-AMP inhibits synthesis of prostaglandin endoperoxide (PGG2) in Human Platelets. Biochem Biophys Res Commun 68:569, 1976.

201. Mahfouz MM, Kummerow FA: Effect of magnesium deficiency on delta 6-desaturase activity and fatty acid composition of rat liver microsomes. Tech 13: . (1990) (In press)

202. Nadler J, Kuong H, Ehrlich L, Ryzen E, Frances R, Rude R: Magnesium plays an important role in the regulation of thromboxane release and platelet aggregation. presented: 1989 Natl Mtg Am Fed Clin Res, Washington DC 203. Cohen L, Laor A, Kitzes R: Bone magnesium, crystallinity index and state of body magnesium in subjects with senile osteoporosis, maturity onset diabetes and women treated with contraceptive preparations. Magnesium 2: 70-75, 1983.

204. Cohen L: Recent data of magnesium and osteoporosis. Magnesium Res 1:85- 87, 1988.

205. Reginster JY, Strause L, Deroisy R, Lecart MP, Saltman P, Franchimont P: Preliminary report of decreased serum magnesium in postmenopausal osteoporosis. Magnesium 8:106-109, 1989.

206. Cohen L, Kitzes R: Infrared spectroscopy and magnesium content of bone mineral in osteoporotic women. Israel J Med Sci 17:1123-1125, 1981.

207. Cohen L, Laor A, Kitzes R: Magnesium malabsorption in postmenopausal osteoporosis. Magnesium 2:139-143, 1983.

208. Cohen L, Laor A, Kitzes R: Lymphocyte and bone magnesium in alcohol-associated osteoporosis. Magnesium 4:148-152, 1985.

209. De Leeuw I, Vertonnen J: The magnesium content of the trabecular bone in diabetic subjects. Biomedicine 29:16-17, 1968.

210. Cohen L, Kitzes R: Relationship of bone and plasma magnesium in magnesium deficient cirrhosis patients. Israel J Med Sci 18:679-682, 1982.

211. Driessens FCM, Verbeeck RMH, vanDijk JWE, Borggreven JMPM: Response of plasma calcium and phosphate to magnesium depletion. A review and its physiological interpretation. Magnesium Bull 9:193-201, 1987.

212. Hanna S, Harrison M, MacIntyre I, Fraser R: The syndrome of magnesium deficiency in man. Lancet 2:172-175, 1960.

213. Booth CC, Babouris MB, Hanna S, Maclntyre I: Incidence of hypomagnesemia in intestinal malabsorption. Brit Med J 2:141-143, 1963.

214. Petersen VP: Metabolic studies in clinical magnesium deficiency. Acta Med Scand 173:285-298, 1963.

215. Fishman RA: Neurological aspects of magnesium metabolism. Arch Neurol 12:562-569, 1965.

216. MacIntyre I, Hanna S, Booth CC, Read AE: Intracellular magnesium deficiency in Man. Clin Sci 20:297-305, 1961.

217. Heaton FW, Fourman P: Magnesium deficiency and hypocalcaemia in intestinal malabsorption. Lancet 2: 50-52, 1965.

218. Nordio S, Donath A, Macagno F, Gatti R: Chronic hypomagnesemia with magnesium-dependent hypocalcemia. Acta Paediat Scand 60:441-455, 1971.

219. Connor TB, Toskes P, Mahaffey J, Martin LG, Williams JB, Walser M: Parathyroid function during chronic magnesium deficiency. Johns Hopkins Med J 131:100-117, 1972.

220. Sann L, Moreau P, Longin B, Sassard J, Francois R: Un syndrom de Bartter associant un hypercortisolisme, un diabete phosphore et magnesium, et une tubulopathie d'origine familiale. Arch Franc Ped 32:349-366, 1975.

221. Seelig MS, Berger AR, Avioli LA: Speculations on renal, hormonal, and metabolic aberrations in a patient with marginal magnesium deficiency. In Magnesium in Health and Disease,eds M Cantin, MS Seelig, Spectrum, NY, NY, 1980, pp 459-468 (2nd Intl Mg Sympos, Quebec, Canada, 1976).

222. Kalbfleisch JM, Lindeman RD, Ginn HE, Smith WO: Effects of ethanol administration on urinary excretion of magnesium and other electrolytes in alcoholic and normal subjects. J Clin Invest 42:1471-1475, 1963.

223. Mendelson JH, Ogata M, Mello N: Effects of alcohol ingestion and withdrawal on magnesium states of alcoholics: clinical and experimental findings. Ann N Y Acad Sci 162:918-933, 1969.

224. Lindeman RD.: Nutritional influences on magnesium homeostasis with emphasis on renal factors. In Magnesium in Health and Disease,eds M Cantin, MS Seelig, Spectrum, NY,NY, 1980, pp 381-399 (2nd Intl Mg Sympos, Quebec, Canada, 1976).

225. Flink EB, Stutzman FL, Anderson AR, Konig T, Fraser R: Magnesium deficiency after prolonged parenteral fluid administration and after chronic alcoholism complicated by delirium tremens. J Lab Clin Med 43:169-183, 1954.

226. Flink EB: Magnesium deficiency in alcoholism. Alcoh: Clin Exp Res 10:590- 594, 1986.

227. Seelig MS: Prenatal and neonatal mineral deficiencies: magnesium, zinc, and chromium. in Clinical Disorders in Pediatric Nutrition, ed F Lifshitz, Publ Marcel Dekker, pp 167-196, 1982.

228. Cushard Jr WG Jr, Creditor M, Canterbury JM, Reiss E: Physiologic hyperparathyroidism in pregnancy. J Clin Endocr Metab 34:767-771, 1972.

229. Martin HE, Mehl J, Wertman M: Clinical studies of magnesium metabolism. Med Clin N.A. 36:1157-1171, 1952.

230. Gordan GS: Recent progress in calcium metabolism: clinical application. Calif Med 114:28-43,1971.

231. Bachem MG, Strobel B, Jastram U, Janssen EG, Paschen K: [Magnesium and Diabetes]. Magnesium Bull 2:35-39, 1980. (in German)

232. Bachem MG, Scheffler K, Jastram U, Pfeiffer EF: [Efficacy of oral magnesium supplementation in type I diabetics with nocturnal leg cramps] Magnesium Bull 8:280-283, 1986. (in German)

233. Lindeman RD, Adler S, Yiengst MJ, Beard ES: Influence of various nutrients on urinary divalent cation excretion. J Lab Clin Med 70:236-245, 1967.

234. Aikawa J: Effect of glucose and insulin on magnesium metabolism in rabbits. Proc Soc Biol Med 103:363-366, 1969.

235. Lostroh AJ, Krahl ME: Magnesium, a second messenger for insulin: ion translocation coupled to transport activity. Adv Enz Regul 12:73-81, 1974.

236. Resnick LM, Gupta RK, Bhargava KK, Gruenspan H, Alderman MH, Laragh JH: Cellular ions in hypertension, diabetes, and obesity. A nuclear magnetic resonance spectroscopic study. Hypertension 17 (6, Part 2):951-957, 1991.

237. Vir SC, Love AHG: Nutritional status of institutionalized and non-institutionalized aged in Belfast. Am J Clin Nutr 32:1934-1947, 1979.

238. Seelig MS: Possible role of magnesium in disorders of the aged. In Intervention in the Aging Process, eds W Regelson & FM Sinex, Publ AR Liss Inc. New York, NY, 1983, pp279-283.

239. Johansson G: Magnesium metabolism. Studies in health, primary hyperparathyroidism and renal stone disease. Scand J Urol Nephrol Suppl 51:1-48, 1979.

240. Mountokalakis Th, Singhellakis PN, Alevizaki CC, Caramanakos E, Ikkos DG: Absorption intestinale du magnesium chez des malades en insuffisante renale chronique. Rev Franc Endocr Clin Nutr Metab 17:229-232, 1976.

241. Schachter D, Rosen SM: Active transport of Ca45 by small intestine and its dependence on vitamin D. Am J Physiol 196:357-362, 1959.

242. Alcock N, MacIntyre I: Interrelation of calcium and magnesium absorption. Clin Sci 22:185-193, 1962.

243. Heaton FW, Hodgkinson A, Rose GA: Observations on the relation between calcium and magnesium metabolism in man. Cin Sci 27:31-40, 1964.

244. Parlier R, Hioco D, LeBlanc R: [Relationship of magnesium metabolism with that of calcium. I. A study of magnesium balance in normal man and in osteopathies and nephropathies.] Rev Franc Endocr Clin 4:93-135, 1963. (in French)

245. DuRuisseau JP, Marineau JM: [Calcium and magnesium treatment of osteoporosis] Proc First Intl Sympos on Mg, 1971. Vittel, France. Ed J Durlach, 2:175-192. (1973)

246. Spencer H, Lesniak M, Kramer L, Coffey J, Osis D: Studies of magnesium metabolism in man. In Magnesium in Health and Disease, eds M Cantin, MS Seelig, Spectrum, NY, NY, 1980, pp 912-919. (2nd Intl Mg Sympos, Quebec, Canada, 1976).

247. Lewis NM, Marcus MSK, Behling AR, Greger JL: Calcium supplements and milk: effects on acid-base balance and on retention of calcium, magnesium, and phosphorus. Am J Clin Nutr 49:527-533, 1989.

248. Clarkson EM, Warren RL, McDonald SJ, de Wardener HE: The effect of a high intake of calcium on magnesium metabolism in normal subjects and patients with chronic renal failure. Clin Sci 32:11-18, 1967.

249. Cunningham IJ: The influence of the level of dietary magnesium and calcium contents of the bone, the bodies and the blood serum of rats. N Zeal J Sci Tech15:191-198, 1933.

250. Orent ER, Kruse HD, McCollum EV: Studies on magnesium deficiency in animals. VI. Chemical changes in the bone, with associated blood changes resulting from magnesium deprivation. J Biol Chem 106:573-592, 1934.

251. Watchorn E, McCane RA: Subacute magnesium deficiency in rats. Biochem J 31: 1379-1390, 1937.

252. U.S. Dept Agric Nationwide Consumption Survey, 1977-1978 U.S.D.A. Sci & Educ Administration, 1980.

253. Lakshmanan FL, Rao RB, Kim WW, Kelsay JL: Magnesium intakes, balances, and blood levels of adults consuming self-selected diets. Am J Clin Nutr 40:1380-1389, 1984.

254. Morgan KJ, Stampley GL, Zabik ME, Fischer DR: Magnesium and calcium dietary intakes of the U.S. population. J Am Coll Nutr 4:195-206, 1985.

255. Spillman, DM: Calcium, magnesium and calorie intake and activity levels of healthy adult women. J Am Coll Nutr 6:454, 1987.

256. Morgan KJ, Stampley GL: Dietary intake levels and food sources of magnesium and calcium for selected segments of the US population. Magnesium 7:225-233, 1988

257. Abdulla M, Behbehani A, Dashti H: Marginal deficiency of magnesium and the suggested treatment. In Magnesium in Health and Disease. eds Y Itokawa, J Durlach, Publ J. Libbey, London, 1989 (5th Intl Mg Sympos, Kyoto, 1988), pp 111-117.

258. Pennington JA, Young BE, Wilson DB: Nutritional elements in U.S. diets; results from the Total DietStudy, 1982 to 1986. J Am Diet Assoc 89:659-664, 1989.

259. Tsang RC: Neonatal magnesium disturbances. Am J Dis Child 124:282-293, 1972.

260. Paunier L, Radde IC, Kooh SW, Conen PEE, Fraser D: Primary hypomagnesemia with secondary hypocalcemia in an infant. Pediatrics 41:385-402, 1968.

261. Paunier L: Magnesium malabsorption. Adv in Intern Med & Pediatr 42:113- 131, 1979.

262. Mimouni F, Loughead J, Miodovnik M, Khoury J, Tsang RC: Early neonatal predictors of neonatal hypocalcemia in infants of diabetic mothers: an epidemiologic study. Am J Perinatol 7:203-206, 1990.

263. Turner TL, Cockburn F, Forfar JO: Magnesium therapt in neonatal tetany. Lancet 1:282-284, 1977.

264. Heaton FW, Parsons FM: Metabolic effect of high magnesium intake. Clin Sci 21:273-284,1961.

265. Estep H, Shaw WA, Watlington C, Hobe R, Holland W, Tucker SG: Hypocalcemia due to hypomagnesemia and reversible parathyroid hormone responsiveness. J Clin Endocrinol Metab 29:842-848, 1969.

266. Anast CS, Winnacker JL, Forte LR, Burns TW: Impaired release of parathyroid hormone in magnesium deficiency. J Clin Endocr Metab 42:707- 720, 1976.

267. Suh SM, Tashjian Jr AH, Matsuo N, Parkinson DK, Fraser D: Pathogenesis of hypocalcemia in primary hypomagnesemia: normal end-organ responsiveness to parathyroid hormone, impaired parathyroid gland function. J Clin Invest 52:153-160, 1973.

268. Rude RK, Oldham SB, Singer FR: Functional hypoparathyroidism and parathyroid hormone end-organ resistance in human magnesium deficiency. Clin Endocr 5:209-224, 1976.

269. Rude RK, Oldham SB, Sharp CF, Singer F: Parathyroid hormone secretion in magnesium deficiency. J Clin Endocr Metab 47:800-806, 1978.

270. Rude RK, Oldham SB: Hypocalcemia of Mg deficiency: altered modulation of adenylate cyclase by Mg++ and Ca++ may result in impaired PTH secretion and PTH end-organ resistance. In Magnesium in Cellular Processes and Medicine, Eds BM Altura, JDurlach, MS Seelig, Publ Karger, Basel, Switzerland, pp 183-195, 1987.

271. Norman AW, Henry H: 1,25-dihydroxycholecalciferol - A hormonally active form of vitamin D3. Rec Progr Hormone Res 30:431-480, 1974.

272. DeLuca HF: Vitamin D endocrinology. Ann Intern Med 85:367-377, 1976.

273. McGeown M: Sex, age, and hyperparathyroidism. Lancet 1:887-888, 1969.

274. Muller H: Sex, age and hyperparathyroidism. Lancet 1:449-450, 1969.

275. Hossain M, Smith DA, Nordin BEC: Parathyroid activity and menopausal osteoporosis. Lancet 1:809-811, 1970.

276. Ranney R: Antagonism between estrone and parathyroid extract in their effects upon bone structure. Endocrinology 64:594-601, 1959.

277. Atkins D, Zanelli JM, Peacock M, Nordin BEC: The effect of oestrogens on the response of bone to parathyroid hormone in vitro. J Endocr 54:107- 117, 1972.

278. Orimo H, Fujita T, Yoshikawa M: Increased sensitivity of bone to parathyroid hormone in ovariectomized rats. Endocrinology 90: 760-763, 1972.

279. Heaney RP: Prevention of osteoporotic fracture in women. In The Osteoporotic Syndrome. LV Avioli, publ Grune & Stratton Inc. Orlando, FL, 1987, 67-90.

280. Riggs BL, Jowsey J, Kelly PJ, Jones JD, Maher FT: Effect of sex hormones on bone in primary osteoporosis. Clin Invest 48:1065-1072, 1969.

281. Larvor P, Girard A, Brochart M, Parodi A, Sevestre J: [Study of experimental Mg deficiency in the calf..I Clinical, biochemical, and pathologic observations.] Ann Biol Anim Bioch Biophys 4:345-369, 1964. (in French)

282. Care AD, Sherwood LM, Potts Jr JT, Aurbach GD: Perfusion of the isolated parathyroid gland of the goat and sheep. Nature 209:55-57. 1967.

283. Buckle RM, Care AD, Cooper CW, Gitelman HJ: The influence of plasma magnesium concentration on parathyroid Hormone secretion. J Endocr 42:529-534, 1968.

284. Targovnik JH, Rodman JS, Sherwood LM: Regulation of parathyroid hormone secretion in vitro; quantitative aspects of calcium and magnesium ion control. Endocrinol 88:1477-1482, 1971.

285. Gallagher JC, Riggs BL, Eisman J, Hamstra A, Arnaud SB, DeLuca HF: Intestinal calcium absorption and serum vitamin metabolites in normal subjects and osteoporotic patients. J Clin Invest 64:729-736, 1979.

286. Slovik DM, Adams SJ, Neer RM, Holick MF, Potts Jr JT: Deficient production of 1,25-dihydroxyvitamin D in elderly osteoporotic patients. N Engl J Med 305:372-374, 1981.

287. Tsai K-S, Heath III H, Kumar R, Riggs BL: Impaired vitamin D metabolism with aging in women. Possible role in pathogenesis of senile osteoporosis. J Clin Invest 73:1668-1672, 1984.

288. Riggs BL, Melton III LJ: Involutional osteoporosis. N Engl J Med 314: 1676-1686, 1986.

289. Reichel H, Koeffler HP, Norman AN: The role of the vitamin D endocrine system in health and disease. N Engl J Med 320:980-991, 1989.

290. Silverberg SJ, Shane E, de la Cruz L, Segre GV, Clemens TL, Bilezikian JP: Abnormalities in parathyroid hormone secretion and 1,25-dihydroxyvitamin D3 formation in women with osteoporosis. N Engl J Med 320:277-281, 1989.

291. Franz KB: Abnormalities in parathyroid hormone secretion and 1,25-dihydroxyvitamin D3 formation in women with osteoporosis. N Engl J Med 320:1697-1698, 1989.

292. Kumar R, Cohen WR, Silva P, Epstein FH: Elevated 1,25-dihydroxyvitamin D plasma levels in normal human pregnancy and lactation. J Clin Invest 63: 342-344, 1979.

293. Gallagher JC, Riggs BL, DeLuca HF: Effect of estrogen on calcium absorption and serum vitamin D metabolites in postmenopausal osteoporosis. J Clin Endocrinol Metabol 51:1359-1364, 1980.

294. Cheema C, Grant BF, Marcus R: Effects of estrogen on circulating "free" and total 1,25-dihydroxyvitamin D and on the parathyroid-vitamin D axis in postmenopausal women. J Clin Invest 83:537-542, 1989.

295. Rude RK, Adams JS, Ryzen E, Endres DB, Nimni H, Horst RL, Haddad Jr JG, Singer FR: Low serum concentrations of 1,25-dihydroxyvitamin D in human magnesium deficiency. J Clin Endocr Metab 61:933-940, 1985.

296. Fuss M, Cogan E, Gillet C: Magnesium administration reverses the hypocalcemia secondary to hypomagnesemia despite low circulating levels of 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D. Clin Endocrinol 22:807-815, 1985.

(This article has been placed on this web site with the permission of the Journal of the American College of Nutrition. We thank Dr. Mildred S. Seelig for providing us the information on a diskette.)

This page was first uploaded to The Magnesium Web Site on October 16, 1995