Prescription ·Strong evidence ·Reviewed May 2026
Spironolactone is a non-selective mineralocorticoid receptor antagonist with landmark evidence from the RALES trial demonstrating a 30% mortality reduction in severe heart failure. It is also used for resistant hypertension, primary hyperaldosteronism, and ascites due to cirrhosis.
The bottom line
Evidence rating strong. Most-documented uses: 30% mortality reduction in severe heart failure (rales trial), effective for resistant hypertension, potassium-sparing diuresis. 10 sources indexed (2016–2025), with 2 interaction records on file.
Core mechanism
Competitively binds to aldosterone receptors (mineralocorticoid receptors) in the distal tubule and collecting duct. Blocks aldosterone-mediated sodium reabsorption and potassium excretion, resulting in mild diuresis and potassium retention. In heart failure, it blocks the harmful effects of aldosterone on cardiac fibrosis, hypertrophy, and vascular inflammation. Also has anti-androgenic and progesterone receptor activity.8
Food increases bioavailability by ~100%; take with meals for optimal absorption
Both ACE inhibitors and spironolactone increase serum potassium through different mechanisms. Combined use significantly increases the risk of life-threatening hyperkalemia, especially in patients with renal impairment.
Recommendation: While used intentionally in heart failure (RALES trial protocol), requires close potassium and renal function monitoring. Check potassium within 3-7 days of initiation. Avoid in patients with eGFR <30.
Spironolactone is a potassium-sparing diuretic that blocks aldosterone. Adding potassium supplements creates very high hyperkalemia risk, which can cause fatal cardiac arrest.
Recommendation: Do NOT take potassium supplements with spironolactone unless specifically prescribed with close monitoring. Avoid potassium-containing salt substitutes. This combination can be lethal.
Numbered references. Citations throughout the page link here.
Rossignol P, Zannad F, Massy Z et al.. Spironolactone in patients on chronic haemodialysis at high risk of adverse cardiovascular outcomes (ALCHEMIST): a multicentre, double-blind, randomised, placebo-controlled trial and updated meta-analysis. Lancet (London, England). 2025
Elshahat A, Mansour A, Ellabban M et al.. Comparative effectiveness and safety of eplerenone and spironolactone in patients with heart failure: a systematic review and meta-analysis. BMC cardiovascular disorders. 2024
Wang C, Du Y, Bi L et al.. The Efficacy and Safety of Oral and Topical Spironolactone in Androgenetic Alopecia Treatment: A Systematic Review. Clinical, cosmetic and investigational dermatology. 2023
Liu J, Jia W, Yu C. Safety and Efficacy of Spironolactone in Dialysis-Dependent Patients: Meta-Analysis of Randomized Controlled Trials. Frontiers in medicine. 2022
Zhao JV, Xu L, Lin SL et al.. Spironolactone and glucose metabolism, a systematic review and meta-analysis of randomized controlled trials. Journal of the American Society of Hypertension : JASH. 2016
This page is educational. Do not start, stop, or change a supplement or medication based on it without checking with a qualified healthcare professional.
Use this with your stack
Add it to your stack, see how it interacts with everything else you take, and get a Stack Score that updates the moment it does.
NutriStack is an informational and organizational tool, not a medical service, and not a substitute for professional advice. Always consult a qualified healthcare professional before starting, stopping, or changing any supplement or medication.
NutriStack