{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:11:41Z","timestamp":1792181501999,"version":"4.4.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":19,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"ISCIII","doi-asserted-by":"publisher","award":["CM23\/00216"],"award-info":[{"award-number":["CM23\/00216"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Instituto de Salud Carlos III","award":["RD24\/0009\/0007"],"award-info":[{"award-number":["RD24\/0009\/0007"]}]},{"name":"National Instituto de Salud Carlos III","award":["PI21\/01158"],"award-info":[{"award-number":["PI21\/01158"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Cerebral small vessel disease is a major cause of lacunar stroke and vascular cognitive impairment, for which effective disease-modifying treatments are lacking. Polyphenols have shown neurovascular and neuroprotective effects in experimental models. We conducted a randomised pilot trial primarily to evaluate the safety and tolerability of a polyphenol-rich Salicornia extract in patients with lacunar stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>In this randomised, double-blind, placebo-controlled, parallel-group pilot trial, patients with recent lacunar stroke received either 1\u00a0g\/day of a polyphenol-rich Salicornia extract or placebo for 12\u00a0months (ClinicalTrials.gov NCT06076122). The primary endpoint was safety and tolerability. Secondary exploratory outcomes included cognitive performance (Montreal Cognitive Assessment), physical function (6-min walk test and gait speed), biochemical parameters, ambulatory blood pressure and neuroimaging markers, assessed at baseline, 6\u00a0months and study completion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Seventy-one participants were randomised (40 to placebo and 31 to Salicornia extract). No treatment-related serious adverse events were observed. Exploratory analyses of secondary outcomes suggested possible between-group differences in some cognitive and physical measures. At 12\u00a0months, adjusted MoCA scores were higher in the Salicornia group than in the placebo group (adjusted mean difference 2.22 points; 95% CI, 0.08\u20134.36; P\u00a0=\u00a0.042), although cognitive data were available for only 22\/40 placebo-treated and 19\/31 Salicornia-treated participants. Apparent differences were also observed in some physical function measures during follow-up. In biochemical parameters, a reduction in homocysteine levels was observed in both groups. No relevant between-group differences were detected in neuroimaging markers during follow-up. These secondary findings should be interpreted as exploratory only and not as evidence of efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Any apparent differences in secondary exploratory cognitive, functional and biochemical outcomes should be interpreted cautiously because of baseline imbalances, small sample size and substantial missing follow-up data. These findings should be considered hypothesis-generating only and not as evidence of efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Long-term supplementation with a polyphenol-rich S ramosissima extract showed an acceptable safety profile in patients with lacunar stroke, although tolerability should be interpreted cautiously given the withdrawal rate. Larger, adequately powered trials are needed to determine whether these preliminary findings represent true treatment effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/esj\/aakag049","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T19:19:56Z","timestamp":1779304796000},"source":"Crossref","is-referenced-by-count":1,"title":["Polyphenol-rich\n                    <i>Salicornia<\/i>\n                    extract in lacunar stroke: a pilot randomised trial of safety and exploratory clinical outcomes"],"prefix":"10.1093","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8940-9763","authenticated-orcid":false,"given":"Soledad","family":"P\u00e9rez-S\u00e1nchez","sequence":"first","affiliation":[{"name":"Department of Neurology, Hospital Universitario Virgen Macarena , Sevilla ,","place":["Spain"]},{"name":"Neurovascular Research Group, Instituto de Biomedicina de Sevilla, IBiS\/Hospital Universitario Virgen Macarena\/CSIC\/Universidad de Sevilla , Sevilla ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"del R\u00edo","sequence":"additional","affiliation":[{"name":"Neurovascular Research Group, Instituto de Biomedicina de Sevilla, IBiS\/Hospital Universitario Virgen Macarena\/CSIC\/Universidad de Sevilla , Sevilla ,","place":["Spain"]},{"name":"Department of Biochemistry, Hospital Universitario Virgen Macarena , Sevilla ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"N\u00fa\u00f1ez-Jurado","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Universitario Virgen Macarena , Sevilla ,","place":["Spain"]},{"name":"Neurovascular Research Group, Instituto de Biomedicina de Sevilla, IBiS\/Hospital Universitario Virgen Macarena\/CSIC\/Universidad de Sevilla , Sevilla ,","place":["Spain"]},{"name":"Department of Biochemistry, Hospital Universitario Virgen 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