Potassium-depleting diuretics, including thiazide diuretics, cause the body to lose potassium; they may also cause cellular magnesium depletion,¹ although this deficiency may not be reflected by a low blood level of magnesium.² Magnesium loss induced by potassium-depleting diuretics can cause additional potassium loss. Until more is known, it has been suggested that people taking potassium-depleting diuretics, including thiazide diuretics, should supplement both potassium and magnesium.³

People taking thiazide diuretics should be monitored by their prescribing doctor, who will prescribe potassium supplements if needed. Such supplementation is particularly critical before surgery in patients with a history of heart disease. In a preliminary study, people with low blood levels of potassium (in part related to diuretic use) had a higher incidence of serious problems resulting from surgery (including death) compared with those having normal potassium levels.⁴ A double-blind trial showed that thiazide diuretic use led to a reduction in blood levels of potassium in some participants. Those experiencing decreased potassium levels were also more likely to experience cardiovascular events, such as heart attacks, stroke, heart failure, aneurysm, and sudden cardiac death.⁵ Fruit is high in potassium, and increasing fruit intake (especially bananas) is another way of supplementing potassium.

Magnesium supplementation for people taking thiazide diuretics is typically 300–600 mg per day, though higher amounts (over 800 mg per day) have been reported in a controlled study to reduce side effects of thiazides.⁶ Combining supplementation of both potassium and magnesium has been reported to correct abnormally low blood levels of potassium and also to protect against excessive loss of magnesium.⁷

Thiazide diuretics can increase urinary zinc loss.⁸

Diuretics, including thiazide diuretics, 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.

Digitalis (Digitalis purpurea) refers to a family of plants commonly called foxglove, which contains digitalis glycosides, chemicals with actions and toxicities similar to the prescription drug digoxin. Thiazide diuretics can increase the risk of digitalis-induced heart disturbances.⁹ Thiazide diuretics and digitalis-containing products should be used only under the direct supervision of a doctor trained in their use.

Herbs that have a diuretic effect should be avoided when taking diuretic medications, as they may enhance the effect of these drugs and lead to possible cardiovascular side effects. These herbs include dandelion , uva ursi , juniper , buchu , cleavers , horsetail , and gravel root.¹⁰

Use buckthorn (Rhamnus catartica, Rhamnus frangula, Frangula alnus) or alder buckthorn for more than ten days consecutively may cause a loss of electrolytes (especially the mineral potassium). Medications that also cause potassium loss, such as some diuretics, should be used with caution when taking buckthorn or alder buckthorn.¹¹

Licorice (Glycyrrhiza glabra) may increase the side effects of potassium-depleting diuretics, including thiazide diuretics.¹² Thiazide diuretics and licorice should be used together only under careful medical supervision. At the time of this writing, no evidence was found of interactions between deglycyrrhizinated licorice (DGL) and any diuretic was found in the medical literature.

One case was reported in which ginkgo use was associated with high blood pressure in a person treated with a thiazide diuretic.¹³ Ginkgo was not proven to be the cause of this reaction.

Thiazide diuretics decrease calcium loss in the urine due to actions on the kidneys.¹⁴ As a result, it may be less important for some people taking thiazide diuretics to supplement calcium than it is for other people.

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.¹⁵ Homocysteine, a toxic amino acid byproduct, has been associated with atherosclerosis. Until further information is available, people taking diuretics for longer than six months should probably supplement with folic acid.

The reduction in urinary calcium loss resulting from treatment with thiazide diuretics is due primarily to changes in kidney function and may also be due, in part, to changes in vitamin D metabolism.¹⁶ However, there is no evidence to suggest that people taking diuretics have different requirements for vitamin D.