The effect of varying molar ratios of potassium-magnesium citrate on thiazide-induced hypokalemia and magnesium loss

This study was conducted to compare the value of an older formulation of potassium-magnesium citrate (K₄MgCit₂) with newer formulations (K₃MgHCit₂ and K₅MgCit₂Cl) with respect to the correction of thiazide-induced hypokalemia and magnesium loss, alkalinizing effect, and citraturic action. Sixty-two healthy volunteers first took hydrochlorothiazide 50 mg/day. After 3 weeks of thiazide treatment (or earlier if hypokalemia developed), they were randomized to take one of three drugs for 3 weeks while continuing thiazide: K₄MgCit₂ (49 mEq K, 25 mEq Mg, and 74 mEq citrate/day), K₃MgHCit₂ (49 mEq K, 33 mEq Mg, and 98 mEq citrate/day), and K₅MgCit₂Cl (49 mEq K, 20 mEq Mg, 10 mEq Cl and 59 mEq citrate/day). Outcome measures were changes in serum potassium and magnesium, and urinary potassium, magnesium, pH, and citrate. The three drugs were equally effective in correcting thiazide-induced hypokalemia. K₃MgHCit₂ and K₄MgCit₂ produced a small but significant increase in serum magnesium concentration, whereas K₅MgCit₂Cl did not. Although all three supplements significantly increased urinary pH and citrate, these effects were more marked with K₃MgHCit₂ and K₄MgCit₂ than with K₅MgCit₂Cl. All three supplements were generally well tolerated, with the lowest side effect profile obtained with K₄MgCit₂. The new formulation of K₃MgHCit₂ exerts similar correction of thiazide-induced hypokalemia and magnesium loss, and enhancement of urinary pH and citrate, compared with the older K₄MgCit₂. However, it is less well tolerated. The new formulation of K₅MgCit₂Cl does not avert magnesium loss, and has less prominent alkalinizing and citraturic effects than the older preparation.