Data from Controlled Metabolic Ward Studies Provide Guidance for the Determination of Status Indicators and Dietary Requirements for Magnesium.

Determination of whether magnesium (Mg) is a nutrient of public health concern has been hindered by questionable Dietary Recommended Intakes (DRIs) and problematic status indicators that make Mg deficiency assessment formidable. Balance data obtained since 1997 indicate that the EAR and RDA for 70-kg healthy individuals are about 175 and 250 mg/day, respectively, and these DRIs decrease or increase based on body weight. These DRIs are less than those established for the USA and Canada. Urinary excretion data from tightly controlled metabolic unit balance studies indicate that urinary Mg excretion is 40 to 80 mg (1.65 to 3.29 mmol)/day when Mg intakes are <250 mg (10.28 mmol)/day, and 80 to 160 mg (3.29 to 6.58 mmol)/day when intakes are >250 mg (10.28 mmol)/day. However, changing from low to high urinary excretion with an increase in dietary intake occurs within a few days and vice versa. Thus, urinary Mg as a stand-alone status indicator would be most useful for population studies and not useful for individual status assessment. Tightly controlled metabolic unit depletion/repletion experiments indicate that serum Mg concentrations decrease only after a prolonged depletion if an individual has good Mg reserves. These experiments also found that, although individuals had serum Mg concentrations approaching 0.85 mmol/L (2.06 mg/dL), they had physiological changes that respond to Mg supplementation. Thus, metabolic unit findings suggest that individuals with serum Mg concentrations >0.75 mmol/L (1.82 mg/L), or as high as 0.85 mmol/L (2.06 mg/dL), could have a deficit in Mg such that they respond to Mg supplementation, especially if they have a dietary intake history showing <250 mg (10.28 mmol)/day and a urinary excretion of <80 mg (3.29 mmol)/day.

A case of magnesium deficiency associated with insufficient parathyroid hormone action and severe osteoporosis.

The relationship between osteoporosis and magnesium (Mg) deficiency is still controversial. Here we report a case of an 82-year-old woman with a giant adenomatous goiter and severe osteoporosis with multiple vertebral fractures, whose clinical course indicated that her osteoporosis was probably due to Mg deficiency. She visited our hospital for treatments of tetany. Laboratory data showed the existence of hypomagnesemia, hypocalcemia, hypokalemia, vitamin D deficiency, and slightly elevated intact PTH. Intravenous administration of Mg not only improved these electrolyte abnormalities but also increased serum levels of intact PTH, bone formation markers, 1,25-dihydroxyvitamin D, as well as bone resorption markers in the urine, and lowered urinary phosphate reabsorption. Hypomagnesemia on admission seemed to arise from long-lasting poor food intake and malnutrition, because it improved after the disappearance of dysphagia with a goiter resection. After the operation, BMD values at the lumbar spine and femoral neck obviously increased during 6 months of Mg supplementation without any specific therapies for osteoporosis. Mg deficiency in this case seemed to cause impaired secretion of PTH from the parathyroid and the refractoriness of bone and kidney to the hormone, which led to the suppression of both bone remodeling and renal vitamin D production. These processes were probably linked to her severe osteoporosis, which was reversed by Mg supplementation.

A mild magnesium deprivation affects calcium excretion but not bone strength and shape, including changes induced by nickel deprivation, in the rat.

An experiment was performed to determine the effect of a mild magnesium deprivation on calcium metabolism and bone composition, shape, and strength in rats, and whether nickel deprivation exacerbated or alleviated any changes caused by the magnesium deprivation. Weanling male rats were assigned to groups of 10 in a factorial arrangement, with variables being supplemental nickel at 0 and 1 mg/kg and magnesium at 250 and 500 mg/kg of diet. The basal diet contained about 30 ng Ni/g. Urine was collected for 24 h during wk 8 and 12, and rats were euthanized 13 wk after dietary treatments began. Mild magnesium deprivation decreased the urinary excretion of calcium and increased the tibia concentration of calcium but did not affect femur shape or strength (measured by a three-point bending test). Dietary nickel did not alter these effects of magnesium deficiency. Nickel deprivation increased the urinary excretion of phosphorus and the femur strength variables maximum force and moment of inertia. Strength differences might have been the result of changes in bone shape. Magnesium deprivation did not alter the effects of nickel deprivation on bone. The findings indicate that a mild magnesium deficiency affects calcium metabolism but that this does not markedly affect bone strength or shape, and these effects are not modified by dietary nickel. Also, nickel deprivation affects phosphorus metabolism and bone strength and shape; these effects apparently are not caused by changes in magnesium metabolism or utilization.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive tubular disorder that is frequently associated with progressive renal failure. The primary defect is related to impaired tubular reabsorption of magnesium (Mg) and calcium (Ca) in the thick ascending limb of Henle's loop. We have studied seven Arab patients with this syndrome who belong to four different families. The mean age at first presentation was 1.5+/-1.3 years (range 0.1-3 years) and at diagnosis 5.9+/-4.3 years (range 0.5-12 years). The presenting features were convulsions and carpopedal spasms (5 patients), polydipsia and polyuria (2 patients), rickets (2 patients), and recurrent urinary tract infections (1 patient). Bilateral nephrocalcinosis was observed in all patients. All patients had hypomagnesemia with a mean serum Mg of 0.45+/-0.09 mmol/l, an inappropriately high urine Mg of 2.07+/-0.73 mmol/24 h or fractional excretion of 15.3+/-7.1%, high urine Ca excretion of 4.1+/-1.2 mmol/24 h or urine Ca to creatinine ratio of 2.6+/-1.6, and normal serum potassium level of 4.4+/-0.34 mmol/l. All patients received Mg supplements and thiazide but exhibited slow worsening of their kidney function. After a mean follow-up of 4.4+/-3.9 years, one patient progressed to end-stage renal failure (ESRF). In conclusion, we report seven Arab patients with FHHNC syndrome. The clinical and biochemical data were similar to previous reports. However, they tend to show a slower rate of progression to ESRF.

Magnesium loading effect on magnesium deficiency in endurance-trained subjects during prolonged restriction of muscular activity.

The aim of this study was to evaluate the effect of magnesium (Mg) loading (10.0 mg Mg/kg body wt) and daily Mg supplements (5.0 mg Mg/kg body wt) on Mg deficiency shown by increased and not by decreased serum Mg concentration during hypokinesia (decreased km number/d). The studies were done during 30 d of prehypokinesia and 364 d of hypokinesia (HK) periods. Forty endurance-trained volunteers aged 22-26 yr with a peak VO2 max of 66.3 mL.kg-1 min-1 and with an average 15.0 km/d running distance were chosen as subjects. They were equally divided into four groups: 1. Unsupplemented ambulatory control subjects (UACS). 2. Unsupplemented hypokinetic subjects (UHKS). 3. Supplemented hypokinetic subjects (SHKS). 4. Supplemented ambulatory control subjects (SACS). The SHKS and SACS groups took daily 5.0 mg elemental Mg/kg body wt and subjected to Mg loading (10.0 mg Mg/kg body wt). Both the SHKS and UHKS groups were maintained under an average running distance of 4.7 km/d, whereas the SACS and UACS groups did not experience any modifications to their normal training routines and diets. During the prehypokinetic and hypokinetic periods, excretion of Mg in feces and urine, concentration of Mg in serum, and Mg balance were measured. Urinary and serum sodium (Na), potassium (K), and calcium (Ca) were also determined. In both SHKS and UHKS groups, fecal Mg loss, urinary excretion of electrolytes, and serum concentrations of electrolytes increased significantly (p < or = 0.05) when compared with the SACS and UACS groups. During Mg loading tests, urinary and fecal Mg excretion was also greater in the SHKS and UHKS groups than in the SACS and UACS groups. Throughout the study, Mg balance was negative in the SHKS and UHKS groups, whereas in the SACS and UACS groups, Mg balance was positive. It was concluded that significant losses of Mg occurred in the presence of negative Mg balance and Mg deficiency in endurance-trained subjects during prolonged exposure to HK, daily mg supplements, and Mg loading tests. This suggests that Mg is not entering or being retaining by the bones and cells of many tissues where most Mg is deposited normally, resulting in Mg deficiency as was shown by the increased serum Mg concentration.

Bone histomorphometry of ovariectomized or orchiectomized rats fed a moderately magnesium-deficient fructose diet and treated with exogenous oestrogen or testosterone.

To investigate the effects of sex hormones on bone histomorphometry, and bone density (BMD), 10 week old ovariectomized (OVX), orchiectomized (ORX), and sham-operated (SHAM) rats fed a moderately magnesium-deficient fructose diet were studied. One third of the OVX and ORX rats were injected with beta-oestradiol-3-benzoate; another third, testosterone cypionate; and the remaining SHAM rats, vehicle only. After 14 weeks, a 24 h urine sample was collected for measurements of calcium, phosphorus and cyclic AMP (cAMP). Blood was collected for determination of calcium, phosphorus, and parathyroid hormone (PTH). Femurs and tibias were removed and weighed. Femurs were used to measure bone areas, mineral contents (BMC), and BMD. Tibias were used for bone histomorphometry (that is, trabecular numbers, thicknesses, % areas and separations). Oestrogen treatment increased serum and urine calcium significantly in both OVX and ORX rats, whereas testosterone decreased serum and urine calcium significantly. Oestrogen decreased urinary cAMP and PTH in both OVX and ORX rats, whereas testosterone treatment increased them significantly. Oestrogen treatment increased BMD, trabecular numbers, thicknesses, and % areas, and decreased bone separations in both OVX and ORX rats. In contrast, testosterone did not increase these bone indices in either OVX or ORX rats; rather, it increased bone separations by decreasing bone strength. Testosterone treatment improved trabecular histomorphometry slightly in OVX rats. The results of the present study are concordant with our previous findings that exogenous oestrogen treatment can prevent osteoporosis in either OVX or ORX rats, whereas exogenous testosterone cannot.

The importance of urinary magnesium values in patients with gut failure.

OBJECTIVE: To determine whether urinary magnesium (Mg) values in patients with gut failure would be more helpful than serum Mg measurements in assessment of Mg deficiency. DESIGN: We compared serum and urinary Mg values in 16 patients with gut failure and 16 age- and sex-matched control subjects. MATERIAL AND METHODS: Sixteen patients with gut failure (nine women and seven men; mean age, 59 years) had serum and 24-hour urinary mg measured before Mg replacement therapy. Short bowel syndrome was present in 75%, and diffuse small bowel disease was present in 25%. RESULTS: The median value for serum Mg was 1.7 mg/dL for patients and 2.0 mg/dL for healthy control subjects (P < 0.001). The median values for urinary Mg were 19 mg and 127 mg per 24-hour specimen in patient and control groups, respectively (P < 0.001). A strong correlation was noted between serum Mg and urinary Mg levels. All patients had low urinary Mg values even though 9 of 16 (56%) had normal serum Mg values. Two patients with normal serum Mg concentrations had urinary Mg values of 20 mg/24 h (25% of normal). Serum, but not urinary, Mg correlated significantly with the length of remaining small bowel (P = 0.03). CONCLUSIONS: Urinary Mg declines before serum Mg and is an earlier and more reliable indicator of evolving Mg deficiency. On the basis of these observations and those showing beneficial effects of parenterally administered Mg supplements on urinary citrate excretion (and, presumably, formation of calcium oxalate stones), replacement of Mg in patients with gut failure should be targeted at normalizing urinary Mg.

Oxalate metabolism in magnesium-deficient rats.

Male weanling rats were maintained on magnesium-deficient diet for 30 d and compared with pair-fed control rats fed magnesium-supplemented diet. Magnesium deficiency led to slow growth and finally to a significant decrease in body weight (P < 0.001) accompanied by a significant hypomagnesaemia, hypomagnesuria and hyperoxaluria (P < 0.001 in each case) in experimental rats as compared to the control rats. Magnesium deficiency altered the glyoxylate metabolism in the liver and kidney mitochondria by significantly decreasing glyoxylate oxidation (by 26 per cent in liver and 17 per cent in kidney) and activity of alpha-ketoglutarate:glyoxylate carboligase enzyme (by 35 per cent in liver and 27 per cent in kidney) in the experimental animals. A significant increase in the specific activities of glycolic acid oxidase (P < 0.001) and glycolic acid dehydrogenase (P < 0.01) and a significant decrease in alanine transaminase (P < 0.01) was also observed in magnesium-deficient rats. No change in liver and kidney lactate dehydrogenase was observed. Thus magnesium deficiency in rats leads to accumulation of glyoxylate in the tissues, a part of which is converted into oxalate, thereby promoting hyperoxaluria.

[Asymptomatic hypokalemia and hypomagnesemia with renal cation loss (Gitelman syndrome)]. / Asymptomatische Hypokaliämie und Hypomagnesiämie mit renalem Kationenverlust (Gitelman-Syndrom).

Hypokalemia with hyperkaliuresis was diagnosed in a 10 1/4-year-old boy, who presented with spontaneously disappearing abdominal pain. The diagnosis of Gitelman-Syndrome (asymptomatic chronic hypokalemia and -magnesemia) was established after detection of hypomagnesemia, renal magnesium losing but normal renin-angiotensin-aldosterone system and glomerular filtration rate. After oral supplementation of potassium hypokalemia persisted and hyperkaliuresis increased. The substitution was discontinued, the hyperkaliuresis diminished and the child remained asymptomatic during a 24 months follow-up. The substitution of potassium and magnesium can be avoided in children with Gitelman-Syndrome as long as they remain asymptomatic.