Does Spironolactone Increase LDL Cholesterol?
No, spironolactone does not increase LDL cholesterol; in fact, it either has no effect or may modestly reduce LDL-C levels based on available evidence.
Evidence from Clinical Studies
The most direct evidence comes from a 1983 study examining spironolactone 100 mg daily over 12 months in hypertensive patients, which found that total cholesterol and LDL cholesterol remained unchanged throughout the treatment period 1. This demonstrates that spironolactone does not adversely affect LDL-C levels even with prolonged use at standard doses.
More recent evidence from 2011 in non-obese women with polycystic ovary syndrome showed that spironolactone 100 mg daily for 6 months actually decreased both total cholesterol (from 4.8 to 4.4 mmol/L) and LDL cholesterol (from 2.5 to 2.2 mmol/L), both statistically significant reductions 2. This suggests spironolactone may have beneficial effects on lipid profiles in certain populations.
Comparative Context with Other Diuretics
A 1988 review clarified that spironolactone has a lesser effect on lipids than thiazide diuretics, which are known to increase total cholesterol by 6-7% on average through raised LDL or VLDL cholesterol 3. This positions spironolactone as a more lipid-neutral diuretic option.
Systematic Review Findings
A 2021 systematic review and meta-analysis of 11 randomized placebo-controlled trials (640 participants) in patients with both hypertension and diabetes found no significant difference in lipid metabolism parameters between spironolactone and placebo groups 4. This high-quality evidence confirms the lipid-neutral profile of spironolactone across diverse patient populations.
Clinical Implications
- Spironolactone can be safely used without concern for LDL elevation in patients requiring aldosterone antagonism for heart failure, resistant hypertension, or cirrhotic ascites 5, 6
- The drug's cardiovascular benefits (30% mortality reduction in severe heart failure) far outweigh any theoretical lipid concerns 5, 6
- HDL cholesterol may decrease modestly (from 1.5 to 1.0 mmol/L after 12 months), which is the primary lipid change observed with spironolactone 1
Important Caveats
The primary metabolic concern with spironolactone is a mild, transient increase in glycosylated hemoglobin (HbA1c) by approximately 0.3% in diabetic patients, not lipid abnormalities 4. Monitor glucose control rather than lipid panels when initiating spironolactone in patients with diabetes.