Hydrochlorothiazide can affect this through 2 different nutrient pathways: Folic Acid, Zinc. This medication is commonly used for Hypertension.
Each nutrient below contributes to this impact through a different mechanism.
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.
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.
Zinc deficiency has been associated with a range of neurological and behavioral changes, including increased irritability, poor attention, and slowed cognitive processing. In children, low zinc status has been linked to poorer performance on tests of attention, memory, and school achievement, and some trials have found that zinc supplementation can modestly improve certain cognitive scores, especially in previously deficient populations. Clinically, even mild zinc deficiency may present with subtle symptoms such as mood changes, reduced stress tolerance, and “brain fog,” which can easily be overlooked but may improve when zinc status is corrected.
de Moura JE, de Moura EN, Alves CX, Vale SH, Dantas MM, Silva Ade A, Almeida Md, Leite LD, Brandão-Neto J. Oral zinc supplementation may improve cognitive function in schoolchildren. Biol Trace Elem Res. 2013 Oct;155(1):23-8. Colombo J, Zavaleta N, Kannass KN, Lazarte F, Albornoz C, Kapa LL, Caulfield LE. Zinc supplementation sustained normative neurodevelopment in a randomized, controlled trial of Peruvian infants aged 6-18 months. J Nutr. 2014 Aug;144(8):1298-305. Lee J, Park S and Jang W (2023) Serum zinc deficiency could be associated with dementia conversion in Parkinson’s disease. Front. Aging Neurosci. 15:1132907. Jung A, Spira D, Steinhagen-Thiessen E, Demuth I, Norman K. Zinc Deficiency Is associated With Depressive Symptoms-Results From the Berlin Aging Study II. J Gerontol A Biol Sci Med Sci. 2017 Aug 1;72(8):1149-1154.
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.
Thiazide diuretics may decrease the effectiveness of enzymes in your heart that rely on CoQ10 for function. This nutrient is essential for cellular energy production. Patients taking these medications might consider CoQ10 supplementation to address potential deficiencies.
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.
Thiazide diuretics, a common medication for high blood pressure, can increase how much zinc your body gets rid of through urine. It's advisable to monitor your blood zinc levels while taking these medications and consider zinc supplementation.
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.