Thiazide can cause
magnesium depletion, which may exaggerate renal
potassium wasting and
hypokalemia. The purpose of this double-blind, randomized trial was to compare the metabolic effects of
potassium-magnesium-citrate (K-
Mg-citrate) and
potassium chloride (KCl) during long-term treatment with
thiazide. Twenty-two normal volunteers received
hydrochlorothiazide 50 mg/d. Ten subjects concurrently took K-
Mg-citrate (42 mEq K/d and 21 mEq Mg/d), and 12 subjects were given KCl 42 mEq/d. Serum
potassium concentration remained unchanged during K-
Mg-citrate supplementation, with a change from baseline of 21.7% over 6 months, compared with 26.4% with KCl supplementation. Serum
electrolytes were normal and not significantly different between K-
Mg-citrate and KCl. During K-
Mg-citrate treatment, serum
magnesium increased significantly by about 10%, associated with an adequate increase in urinary
magnesium and a nonsignificant increase in monocyte and free muscle
magnesium. Serum
magnesium was unchanged, and monocyte and free muscle
magnesium showed a nonsignificant decline during KCl supplementation. K-
Mg-citrate provided an
alkali load, increasing urinary pH, and reducing urinary undissociated
uric acid. It also increased urinary
citrate and tended to lower the saturation of
calcium oxalate. KCl supplementation lacked these actions. K-
Mg-citrate prevents
thiazide-induced
hypokalemia without provoking metabolic
alkalosis. It seems to prevent
magnesium depletion. By providing an
alkali load, it retards the propensity for the crystallization of
uric acid and probably of
calcium oxalate. Though not conclusive, KCl supplementation may be less effective than K-
Mg-citrate in maintaining normokalemia because of a subtle
magnesium wasting. Moreover, KCl is devoid of protective action toward crystallization of stone-forming
salts.