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This pilot randomized clinical trial (RCT) tested the efficacy of combining aerobic exercise with the NAD booster nicotinamide riboside (NR) to enhance BP control. In this double-blinded RCT, 54 sedentary adults (\u2265\u200955\u00a0years) with mean daytime systolic BP (SBP)\u2009\u2265\u2009130\u00a0mmHg were randomized to 6\u00a0weeks of 1000\u00a0mg\/day of NR combined with 3\u00a0days\/week of supervised 30-min walking exercise (NR\u2009+\u2009Ex), Placebo combined with the same exercise regimen (PL\u2009+\u2009Ex), or NR alone (NR). The primary outcome was daytime SBP. Other outcomes included pulse wave velocity (PWV), NAD catabolites, and nighttime BP. The primary comparison was between NR\u2009+\u2009Ex and PL\u2009+\u2009Ex. Of 54 participants (mean age 67\u00a0years, 61% female), 49 (NR\u2009+\u2009Ex:\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200915, PL\u2009+\u2009Ex:\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200916, NR:\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200918) completed all study visits (93% adherence to exercise and 90% to supplementation). NR\u2009+\u2009Ex (mean change\u2009=\u20095.19\u2009\u00b1\u200913.2\u00a0mmHg) did not reduce SBP more than PL\u2009+\u2009Ex (\u2212\u20092.71\u2009\u00b1\u200910.5\u00a0mmHg). NR\u2009+\u2009Ex (\u2212\u20090.31\u2009\u00b1\u20090.77\u00a0m\/s) showed a trend toward a greater reduction in PWV. Levels of NAD catabolites were higher in NR groups. In a post hoc analysis, NR\u2009+\u2009Ex showed a trend toward greater nighttime BP reductions (systolic:\u2009\u2212\u20099.6\u2009\u00b1\u20099.22; diastolic:\u2009\u2212\u20094.51\u2009\u00b1\u20097.12\u00a0mmHg) in participants without antihypertensive medications. NR\u2009+\u2009Ex was not superior to PL\u2009+\u2009Ex in reducing BP in hypertensive middle-aged and older. However, trends toward greater nighttime BP reduction in NR\u2009+\u2009Ex in participants without antihypertensive medication warrant further investigation in a Phase IIb RCT.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s11357-025-01815-2","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T23:27:50Z","timestamp":1754522870000},"page":"6895-6908","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Nicotinamide riboside combined with exercise to treat hypertension in middle-aged and older adults: a pilot randomized clinical trial"],"prefix":"10.1007","volume":"47","author":[{"given":"Yi","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rola S.","family":"Zeidan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Lapierre-Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah M.","family":"Costello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen D.","family":"Anton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas W.","family":"Buford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demetra D.","family":"Christou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle L.","family":"Gumz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiaan","family":"Leeuwenburgh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher R.","family":"Martens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M.","family":"McDermott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie E.","family":"Migaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhanuprasad","family":"Sandesara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas R.","family":"Seals","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peihua","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yipeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert T.","family":"Mankowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,7]]},"reference":[{"issue":"4","key":"1815_CR1","doi-asserted-by":"publisher","first-page":"e65","DOI":"10.1161\/CIR.0000000000001256","volume":"150","author":"KE Joynt Maddox","year":"2024","unstructured":"Joynt Maddox KE, et al. 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