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Spironolactone

High Homocysteine & Vascular Risk

Folate depletion impairs one-carbon metabolism, leading to elevated homocysteine, endothelial dysfunction and potential promotion of atherothrombotic events. This medication is commonly used for Hypertension.

Research

Meta-analyses of randomized trials show that folic acid supplementation lowers homocysteine and modestly reduces stroke and overall cardiovascular disease risk in some populations, especially where baseline folate status is low, highlighting the adverse vascular profile of folate deficiency.

Sources

Li Y et al. Folic acid supplementation and the risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. J Am Heart Assoc. 2016;5(8):e003768.; Wang Y et al. The effect of folic acid in patients with cardiovascular disease: a meta-analysis. Medicine (Baltimore). 2019;98(38):e17106.; Miller ER et al. Meta-analysis of folic acid supplementation trials on risk of cardiovascular disease. Am J Cardiol. 2010;106(4):517-527.

Nutrients Depleted by Spironolactone

Some side effects may be linked to nutrient depletion caused by this medication.

  • Folic AcidDepletion

    Studies indicate that diuretics including potassium-sparing, can act as folate antagonists, potentially leading to a deficiency. This occurs because some diuretics inhibit the enzyme responsible for utilizing folate (folic acid) in the body. Research suggests a link between long-term diuretic use (over six months) and decreased blood folate levels while also showing a significant increase in damaging homocysteine levels. Folate supplementation during potassium-sparing diuretic therapy should therefore be considered.

Other Health Impacts of Spironolactone

Next Steps
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