Low folate status contributes to elevated homocysteine, a metabolite that has been associated with endothelial dysfunction, arterial stiffness, and a higher risk of stroke and coronary heart disease. Large observational studies consistently show that individuals with higher homocysteine levels have greater rates of cardiovascular events, and folate intake is one of the key nutritional determinants of homocysteine. Clinically, folic acid supplementation (often combined with vitamins B6 and B12) can lower homocysteine and appears to modestly reduce stroke risk in some populations, making the identification and correction of folate deficiency an important part of broader cardiovascular risk reduction. This medication is commonly used for Hypertension.
Yanping Li, et al. Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta‐Analysis of Randomized Controlled Trials. Journal of the American Heart Association. Volume 5, Number 8. August 15 2016.Yi X, Zhou Y, Jiang D, Li X, Guo Y, Jiang X. Efficacy of folic acid supplementation on endothelial function and plasma homocysteine concentration in coronary artery disease: A meta-analysis of randomized controlled trials. Exp Ther Med. 2014 May;7(5):1100-1110. Kaye AD, Jeha GM, Pham AD, Fuller MC, Lerner ZI, Sibley GT, Cornett EM, Urits I, Viswanath O, Kevil CG. Folic Acid Supplementation in Patients with Elevated Homocysteine Levels. Adv Ther. 2020 Oct;37(10):4149-4164. Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, McQueen MJ, Probstfield J, Fodor G, Held C, Genest J Jr; Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006 Apr 13;354(15):1567-77. Wald DS, Bishop L, Wald NJ, et al. Randomized Trial of Folic Acid Supplementation and Serum Homocysteine Levels. Arch Intern Med. 2001;161(5):695–700.
Some side effects may be linked to nutrient depletion caused by this medication.
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.