{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T02:21:18Z","timestamp":1780366878159,"version":"3.54.1"},"reference-count":65,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Patients with type 2 diabetes (T2D) develop vascular complications due to arginine deficiency-induced microvascular endothelial dysfunction, which is related to the loss of muscle strength (MS) associated with aging. Thus, increased nitric oxide (NO)-mediated vasodilation may improve MS. We investigated the impact of the NO precursor citrulline on microvascular function (endothelial and muscle reactivity) and MS in T2D patients. Methods: Sixteen participants with T2D (53\u201372 years, nine females) were randomized to citrulline supplementation (CITS, 6 g\/day) or placebo for 4 weeks prior to an 8-week washout period, followed by the opposite supplement for 4 weeks in a crossover trial. Endothelial function (log-transformed reactive hyperemia index, LnRHI), forearm muscle reactivity (near-infrared spectroscopy-derived tissue oxygen index (TOI) reperfusion indices), plasma arginine levels (ARG), and handgrip strength (HGSrel) and calf MS (CMSrel) adjusted for body weight were measured at baseline and 4 weeks for each condition. Results: CITS increased the LnRHI (\u22060.11 \u00b1 0.16 vs. \u2206\u22120.08 \u00b1 0.24, p &lt; 0.05), TOI range (\u22062.6 \u00b1 3.3 vs. \u2206\u22121.5 \u00b1 4.8%, p &lt; 0.01), TOI hyperemic response (\u22061.2 \u00b1 1.4 vs. \u2206\u22120.6 \u00b1 2.8%, p &lt; 0.05), TOI 2 min area under the curve (\u2206154 \u00b1 187 vs. \u2206\u221241 \u00b1 194%\/s, p &lt; 0.01), ARG (\u220643 \u00b1 28 vs. \u22061 \u00b1 16\u03bcM\/L, p &lt; 0.001), CMS (\u22061.5 \u00b1 2.8 vs. \u2206\u22120.3 \u00b1 1.2 kg, p &lt; 0.05), and CMSrel (\u22060.02 \u00b1 0.03 vs. \u2206\u22120.01 \u00b1 0.02 kg\/kg, p &lt; 0.01) compared to placebo. The improvements in LnRHI and CMSrel were correlated (r = 0.37, p &lt; 0.05). Conclusions: This study showed that CITS improves microvascular endothelial function, muscle microvascular reactivity, and calf muscle strength in middle-aged and older patients with T2D.<\/jats:p>","DOI":"10.3390\/nu17172790","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T07:43:16Z","timestamp":1756366996000},"page":"2790","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Citrulline Supplementation Improves Microvascular Function and Muscle Strength in Middle-Aged and Older Adults with Type 2 Diabetes"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9710-038X","authenticated-orcid":false,"given":"Arturo","family":"Figueroa","sequence":"first","affiliation":[{"name":"Department of Kinesiology and Sport Management, Texas Tech University, Lubbock, TX 79409, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine N.","family":"Dillon","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Sport Management, Texas Tech University, Lubbock, TX 79409, USA"},{"name":"Department of Kinesiology, Albion College, Albion, MI 49224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1865-1971","authenticated-orcid":false,"given":"Danielle E.","family":"Levitt","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Sport Management, Texas Tech University, Lubbock, TX 79409, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3436-1846","authenticated-orcid":false,"given":"Yejin","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Sport Management, Texas Tech University, Lubbock, TX 79409, USA"},{"name":"Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia (UBC), Vancouver, BC V6T 1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1161\/01.ATV.0000215951.36219.a4","article-title":"Endothelial dysfunction and low-grade inflammation explain much of the excess cardiovascular mortality in individuals with type 2 diabetes: The Hoorn Study","volume":"26","author":"Dekker","year":"2006","journal-title":"Arterioscler. 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