{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:15:51Z","timestamp":1785417351601,"version":"3.56.0"},"reference-count":35,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports and Technology of Japan","doi-asserted-by":"publisher","award":["#21K08427"],"award-info":[{"award-number":["#21K08427"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports and Technology of Japan","doi-asserted-by":"publisher","award":["#24K11527"],"award-info":[{"award-number":["#24K11527"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports and Technology of Japan","doi-asserted-by":"publisher","award":["#23K0783"],"award-info":[{"award-number":["#23K0783"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hayashikane Sangyo Co., Ltd."},{"id":[{"id":"https:\/\/ror.org\/01x1rgw45","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Background: Ascophyllan, a sulfated polysaccharide extracted from brown seaweed, has shown immunomodulatory and antioxidant effects in preclinical studies, yet human clinical evidence remains scarce. This randomized, double-blind, placebo-controlled pilot trial evaluated the safety and exploratory biological effects of daily ascophyllan supplementation in healthy adults. Methods: Twelve participants were randomized to receive either ascophyllan (n = 6) or placebo (n = 6) for 28 days. Safety was monitored through adverse event reporting and repeated laboratory assessments, including hematology, biochemistry, and inflammatory markers. Immune cell populations were analyzed via serial flow cytometry, serum total antioxidant capacity was measured at multiple time points, and gut microbiome composition was profiled using 16S rRNA gene sequencing. All analyses were exploratory in nature. Results: Ascophyllan supplementation proved well tolerated, with no adverse events observed and stable hematologic, renal, and biochemical parameters throughout the study. Exploratory longitudinal analyses suggested directional modulation of NK-cell-associated phenotypes during ascophyllan supplementation, including directional changes in CD57+, NKp46+, and NKG2D+ NK-cell phenotypes; however, group \u00d7 time interaction analyses did not remain statistically significant after correction for multiple comparisons. Serum antioxidant capacity showed inter-individual variability with a directional but non-significant increase in the ascophyllan group at intermediate time points. Exploratory microbiome analyses suggested modest directional compositional differences involving members of the Bacteroidaceae and Bifidobacteriaceae families; however, no taxon remained statistically significant after correction for multiple comparisons. Conclusions: These preliminary findings indicate that ascophyllan is safe and well tolerated in healthy adults and may be associated with modulation of innate immune phenotypes, subtle microbiome compositional differences, and directional changes in antioxidant capacity. Larger, adequately powered clinical trials are warranted to confirm these observations and further investigate potential biological and clinical effects.<\/jats:p>","DOI":"10.3390\/md24060213","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T05:59:47Z","timestamp":1781503187000},"page":"213","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ascophyllan Supplementation Is Safe and Associated with Exploratory Modulation of Innate Immune Phenotypes, Biochemical Parameters, and the Gut Microbiome in a Randomized Pilot Trial"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4405-8808","authenticated-orcid":false,"given":"Shohei","family":"Mizuno","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Aichi Medical University, Nagakute 480-1195, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1794-6666","authenticated-orcid":false,"given":"Jorge Luis","family":"Espinoza","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Kanazawa University, Kodatsuno 5-11-18, Kanazawa 920-0942, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5440-1120","authenticated-orcid":false,"given":"Lam Quang","family":"Vu","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Aichi Medical University, Nagakute 480-1195, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirona","family":"Banno","sequence":"additional","affiliation":[{"name":"Department of Central Clinical Laboratory, Aichi Medical University Hospital, Nagakute 480-1195, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Iida","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Aichi Medical University, Nagakute 480-1195, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saki","family":"Shinohara","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Aichi Medical University, Nagakute 480-1195, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3007-2596","authenticated-orcid":false,"given":"Do Tung","family":"Dac","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Kanazawa University, Kodatsuno 5-11-18, Kanazawa 920-0942, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"Nakagami","sequence":"additional","affiliation":[{"name":"Department of Central Clinical Laboratory, Aichi Medical University Hospital, Nagakute 480-1195, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2983-2129","authenticated-orcid":false,"given":"Kaori","family":"Uchino","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Aichi Medical University, Nagakute 480-1195, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3485-6857","authenticated-orcid":false,"given":"Tomohiro","family":"Horio","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Aichi Medical University, Nagakute 480-1195, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6681-8927","authenticated-orcid":false,"given":"Ichiro","family":"Hanamura","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Aichi Medical University, Nagakute 480-1195, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiro","family":"Asai","sequence":"additional","affiliation":[{"name":"Department of Clinical Infectious Diseases, Aichi Medical University, Nagakute 480-1195, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumi","family":"Enomoto","sequence":"additional","affiliation":[{"name":"Department of Central Clinical Laboratory, Aichi Medical University Hospital, Nagakute 480-1195, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroya","family":"Tani","sequence":"additional","affiliation":[{"name":"Department of Central Clinical Laboratory, Aichi Medical University Hospital, Nagakute 480-1195, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2389-2542","authenticated-orcid":false,"given":"Takayuki","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion and Clinical Laboratory, Aichi Medical University, Nagakute 480-1195, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1466-8824","authenticated-orcid":false,"given":"Susumu","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Research Creation Support Center, Aichi Medical University, Nagakute 480-1195, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1822-9976","authenticated-orcid":false,"given":"Akiyoshi","family":"Takami","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Aichi Medical University, Nagakute 480-1195, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Li, Y., Zheng, Y., Zhang, Y., Yang, Y., Wang, P., Imre, B., Wong, A.C.Y., Hsieh, Y.S.Y., and Wang, D. 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