In some adults, chronic folate deficiency has been linked to neurological manifestations such as peripheral neuropathy, gait disturbance, and subtle to more overt cognitive impairment, especially in older age. Cohort studies have reported that low serum or red cell folate, and elevated homocysteine, correlate with worse performance on memory and executive‑function tests, and may be associated with increased risk of vascular dementia. The encouraging aspect is that, when folate deficiency is identified early and corrected alongside vitamin B12 when needed, some patients experience improvement in neuropathic symptoms and stabilization or modest gains in cognitive performance, particularly when other vascular risk factors are also addressed. This medication is commonly used for Hypertension.
Boumenna T, Scott TM, Lee JS, Palacios N, Tucker KL. Folate, vitamin B-12, and cognitive function in the Boston Puerto Rican Health Study. Am J Clin Nutr. 2021 Jan 4;113(1):179-186. Alves Maues AC, Moren Abat MG, Benlloch M, Mariscal G. Folate Supplementation for Peripheral Neuropathy: A Systematic Review. Nutrients. 2025 Oct 20;17(20):3299. Mottaghi T, Khorvash F, Maracy M, Bellissimo N, Askari G. Effect of folic acid supplementation on nerve conduction velocity in diabetic polyneuropathy patients. Neurol Res. 2019 Apr;41(4):364-368. Manzoor M, Runcie J. Folate-responsive neuropathy: report of 10 cases. Br Med J. 1976 May 15;1(6019):1176-8. Kang WB, Chen YJ, Lu DY, Yan JZ. Folic acid contributes to peripheral nerve injury repair by promoting Schwann cell proliferation, migration, and secretion of nerve growth factor. Neural Regen Res. 2019 Jan;14(1):132-139.
Some side effects may be linked to nutrient depletion caused by this medication.
Thiamine (vitamin B1) deficiency in patients with cardiovascular disease might be linked to two factors associated with loop diuretics: increased urine output, and cellular uptake inhibition. Loop diuretics can significantly increase urine volume and urinary flow rate, potentially leading to increased thiamine excretion through urine. Emerging evidence suggests loop diuretics may directly inhibit the cellular uptake of thiamine, further contributing to deficiency. Thiamine supplementation during loop diuretic therapy should therefore be considered.
Long-term use with Loop diuretics can come with potential side effects related to nutrient depletion. One such essential nutrient that these medications can impact is potassium. Potassium plays a critical role in various bodily functions including regulating blood pressure, ensuring proper balance of fluids and electrolytes within cells, and may contribute to a lower risk of developing kidney stones and bone loss. Potassium supplementation during loop diuretic therapy should therefore be considered.
Studies indicate that Loop diuretics 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 loop diuretic therapy should therefore be considered.
Loop diuretics can disrupt the kidneys' ability to reabsorb magnesium, leading to increased excretion of this essential mineral through urine. This potential depletion necessitates monitoring magnesium levels, especially in individuals undergoing long-term loop diuretic therapy. Supplementing with magnesium may be beneficial in such cases to help protect against a deficiency.
Calcium, crucial for strong bones and teeth, can be depleted by loop diuretics. These medications can unfortunately decrease calcium levels in the body. To protect against a deficiency and maintain optimal bone health, individuals taking loop diuretics may benefit from calcium supplementation.