Does oral prednisolone decrease sodium levels in the blood?

Effect of Oral Prednisolone on Serum Sodium Levels

Oral prednisolone typically increases serum sodium levels rather than decreasing them, due to its mild mineralocorticoid activity that promotes sodium retention. 1

Mechanism of Action

• Prednisolone has slight mineralocorticoid activity that stimulates entry of sodium into cells and loss of intracellular potassium, particularly evident in the kidney where rapid ion exchange leads to sodium retention 1
• The FDA drug label specifically states that prednisolone can cause sodium retention and hypertension through this mineralocorticoid effect 1
• In primary adrenal insufficiency, hyponatremia is a common finding (present in 90% of newly presenting cases), indicating that corticosteroids are necessary for normal sodium homeostasis 2

Clinical Evidence

• A direct study on this question found that prednisolone therapy in stable outpatients results in a small but significant increase in serum sodium concentration of approximately 1.67 mmol/L compared to controls 3
• When prednisolone was initiated in patients, researchers observed an average increase of 2.61 mmol/L in serum sodium levels 3
• The doses and duration of prednisolone therapy did not appear to have a relationship to the magnitude of increase in serum sodium concentration 3

Corticosteroids and Sodium Balance

• Glucocorticoids like prednisolone can actually be used therapeutically to treat hyponatremia in certain conditions, particularly when it is associated with adrenal insufficiency 4
• In patients with symptomatic heart failure, prednisone (a prodrug of prednisolone) has been shown to enhance renal sodium excretion, with high-dose prednisone inducing more potent natriuresis than low-dose prednisone 5
• Despite this natriuretic effect in heart failure patients, the net effect on serum sodium levels remains an increase rather than a decrease 3, 5

Clinical Considerations

• The ESPEN guideline on hospital nutrition recommends that patients on short-term (≤6 weeks) systemic corticosteroid therapy should receive a standard hospital diet without sodium restriction 2
• Salt restriction is not indicated as primary prevention of arterial hypertension in patients on corticosteroid therapy 2
• Only in cases of arterial hypertension during long-term (>10 weeks) corticosteroid therapy might salt reduction be considered 2

Special Situations

• In cases of syndrome of inappropriate antidiuretic hormone secretion (SIADH), glucocorticoids can actually increase sodium levels by reducing the secretion of ADH from the pituitary posterior lobe 6
• Long-term low-dose corticosteroid therapy does not appear to cause significant hyponatremia or biochemical features suggestive of mineralocorticoid excess 7

In conclusion, the evidence consistently shows that oral prednisolone tends to increase rather than decrease serum sodium levels in most clinical scenarios, primarily through its mild mineralocorticoid effects that promote sodium retention.