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In this patient population, hypertension is a prevalent modifiable cardiovascular risk factor that is associated with poor prognosis. Resistant hypertension in dialysis patients is challenging to manage since some individuals do not respond to antihypertensive medications or volume control. Hyperhomocysteinemia is common among ESRD patients. \u201cH-type hypertension\u201d or hyperhomocysteinemia-associated hypertension refers to resistant hypertension with elevated cardiovascular risk. The current study examined the efficacy of methylfolate and methylcobalamin supplementation in reducing serum homocysteine levels and improving blood pressure (BP) control in ESRD patients with resistant hypertension on regular hemodialysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Throughout the study, 51 ESRD patients with resistant hypertension were randomly allocated to receive either daily doses of L-methylfolate 800 mcg and methylcobalamin 1000 mcg capsule (intervention group) or no medication (control group). Serum homocysteine levels were measured twice: at baseline and three months later. In addition, average pre- and post-dialysis blood pressure readings were obtained at baseline, one month, two months, and three months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      After three months, mean serum homocysteine levels were significantly lower than at the commencement of therapy (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.035), nonetheless, control patients showed no significant difference. Between-group analysis found a statistically significant difference in the change in homocysteine levels among the two groups (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.006). Furthermore, the treatment group had statistically significant lower pre- and post-dialysis blood pressure readings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A three-month supplementation with a combination of 800 mcg methylfolate and 1000 mcg methylcobalamin showed promise in lowering blood pressure and serum homocysteine levels in ESRD patients with resistant hypertension. These findings require additional exploration in larger studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov Identifier NCT05807711 registered on 20,230,329.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12882-025-04726-8","type":"journal-article","created":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T14:15:08Z","timestamp":1769264108000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy of L-methylfolate and methylcobalamin in treating resistant hypertension associated with elevated serum homocysteine in hemodialysis patients"],"prefix":"10.1186","volume":"27","author":[{"given":"Mohamed Sherif","family":"Salem","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noha Alaa","family":"Hamdy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9591-7297","authenticated-orcid":false,"given":"Hesham Abdallah","family":"Elghoneimy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanan MS","family":"El Gowelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,24]]},"reference":[{"issue":"5","key":"4726_CR1","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1016\/S0272-6386(98)70146-5","volume":"32","author":"LU Mailloux","year":"1998","unstructured":"Mailloux LU, Haley WE. 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