One study showed that people taking diuretics for more than six months had dramatically lower blood levels of folic acid and higher levels of homocysteine compared with individuals not taking diuretics.¹ Homocysteine, a toxic amino acid byproduct, has been associated with atherosclerosis . Folic acid is also an important cause of elevated homocysteine levels. Until further information is available, people taking diuretics for longer than six months should probably supplement with folic acid.

Preliminary research in animals suggests that amiloride , a drug similar to spironolactone, may inhibit the urinary excretion of magnesium.⁹ It is unknown if this same effect would occur in humans or with spironolactone. Persons taking more than 300 mg of magnesium per day and spironolactone should consult with a doctor as this combination may lead to potentially dangerous increases in the level of magnesium in the body. The combination of spironolactone and hydrochlorothiazide would likely eliminate this problem, as hydrochlorothiazide may deplete magnesium.

As a potassium-sparing diuretic, spironolactone reduces urinary loss of potassium, which can lead to elevated potassium levels.¹⁰ People taking spironolactone should avoid potassium supplements, potassium-containing salt substitutes (Morton Salt Substitute, No Salt, Lite Salt, and others), and even high-potassium foods (primarily fruit). Doctors should monitor potassium blood levels in patients taking spironolactone to prevent problems associated with elevated potassium levels.

However, one medication (Aldactazide) contains the combination of the potassium-sparing drug spironolactone and the potassium-depleting drug hydrochlorothiazide. With the use of Aldactazide, potassium excess and potassium depletion are both possible. People taking this combination drug should have their potassium levels monitored by a doctor to determine whether their potassium intake should be increased, reduced, or kept the same.

Diuretics, including spironolactone, cause increased loss of sodium in the urine. By removing sodium from the body, diuretics also cause water to leave the body. This reduction of body water is the purpose of taking diuretics. Therefore, there is usually no reason to replace lost sodium, although strict limitation of salt intake in combination with the actions of diuretics can sometimes cause excessive sodium depletion. On the other hand, people who restrict sodium intake and in the process reduce blood pressure may need to have their dose of diuretics lowered. People taking spironolactone should talk with their prescribing doctor before severely restricting salt.