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.
Thiazide diuretics can cause potassium to leave your cells. These medications work by making your kidneys flush out water and sodium, but unfortunately, potassium gets swept along too. This raises the risk of a moderate or severe potassium deficiency, called hypokalemia and potassium supplementation should be considered.
Studies indicate thiazide diuretics may act like folate antagonists, potentially leading to folate deficiency. Research suggests long-term use (over six months) can significantly decrease blood folate levels while increasing homocysteine, a potentially harmful amino acid linked to vascular disease. Folate supplementation should be considered while on thiazide diuretics.
Taking thiazide diuretics long-term can increase magnesium loss. Monitoring magnesium levels and considering supplementation might be necessary when taking thiazide diuretics for an extended period of time.