Folate (folic acid) deficiency impairs DNA synthesis in rapidly dividing cells, which leads to megaloblastic anemia characterized by enlarged red blood cells, fatigue, pallor, and sometimes shortness of breath. Population studies have shown that folate deficiency and macrocytosis can be present for months before overt symptoms appear, and in some cohorts, up to roughly one quarter of anemic adults had an underlying folate or B12 deficiency rather than iron deficiency alone. The encouraging clinical point is that, once identified, folate‑responsive megaloblastic anemia often improves within weeks of adequate folic acid repletion, with reticulocyte counts rising in about 5–7 days and hemoglobin recovering more gradually over several weeks. This medication is commonly used for Hypertension.
Koury MJ, Price JO, Hicks GG. Apoptosis in megaloblastic anemia occurs during DNA synthesis by a p53-independent, nucleoside-reversible mechanism. Blood. 2000 Nov 1;96(9):3249-55. Daniel S. Socha, MD, Sherwin I. DeSouza, MD, Aron Flagg, MD, Mikkael Sekeres, MD, MS and Heesun J. Rogers, MD, PhD. Severe megaloblastic anemia: Vitamin deficiency and other causes. Cleveland Clinic Journal of Medicine March 2020, 87 (3) 153-164. H.B. Castellanos-Sinco, et al. Megaloblastic anaemia: Folic acid and vitamin B12 metabolism. Revista Médica del Hospital General de México. Vol. 78. Issue 3. Pages 105-150 (July - September 2015). Anis Hariz, et al. Megaloblastic Anemia. StatPearls April 3, 2023.
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.