Enzyme and or hormone actions have not been shown to be consistently changed by consuming a low-magnesium diet similar to one that may occur in the general population. Thus, a human metabolic study was performed to determine whether deficient intakes of magnesium similar to those that occur naturally have pathophysiological effects through altering calcium retention and the metabolism of other minerals (sodium, potassium, phosphorus) involved in cellular ionic balance. Fifteen postmenopausal Caucasian women were recruited by advertisement throughout the United States. Eleven women (ages 49 to 71 years) completed the study as designed. The women resided in a metabolic research unit and consumed a basal Western-type diet that resulted in a mean intake of 4.40 mmol (107 mg) magnesium/d. The women were fed the basal diet supplemented with 9.05 mmol (220 mg) magnesium/d for 18 d (equilibration) before being assigned to one of two groups in an experiment with a double blind, crossover design. One group was fed the basal diet and supplemented with a lactose placebo while the other group continued consuming the basal diet supplemented with 9.05 mmol magnesium/d for 72 d, then each group switched to the other's diet, which they consumed for 72 d. Magnesium was supplemented as magnesium gluconate. Magnesium deprivation resulted in a non-positive magnesium balance (-0.21 mmol or -5 mg/d) that was highly positive during magnesium supplementation (+2.22 mmol or +54 mg/d). Magnesium deprivation decreased red blood cell membrane magnesium (2.5 versus 2.7 nmol or 0.061 versus 0.065 microg/mg protein; p < or = 0.05). Magnesium deprivation increased calcium balance (+0.82 mmol or +35 mg/d versus -0.02 or -1 mg/d; p < or = 0.009); decreased the fecal excretion of phosphorus (28.9% versus 32.3% of intake; p < or =0.0001); increased the urinary excretion of phosphorus (73.4% versus 71.0%; p < 0.003); and decreased the urinary excretion of potassium (40.4 mmol or 1.58 g/d versus 41.9 mmol or 1.64 g/d; p < 0.04). Non-positive magnesium balance and decreased red blood cell membrane magnesium concentration apparently are indicators of magnesium deprivation. Moderate magnesium deprivation achieved through diet alone results in increased calcium retention. Magnesium deprivation also alters phosphorus and potassium excretion. The changes indicate that an intake of 4.40 mmol (107 mg) magnesium/d is inadequate for postmenopausal women because of changes in cellular ionic balance that may lead to pathophysiological conditions.