{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:57:41Z","timestamp":1784613461243,"version":"3.55.0"},"reference-count":32,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of SMEs and Startups of the Republic of Korea","award":["2420030425"],"award-info":[{"award-number":["2420030425"]}]},{"name":"NSTbio Co., Ltd."},{"name":"Atomy Co., Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Fermented polysaccharides derived from Morinda citrifolia (noni) have been suggested to modulate innate immune responses, but clinical evidence remains limited. Objectives: This randomized, double-blind, placebo-controlled trial evaluated the effects of fermented noni polysaccharides on natural killer (NK) cell activity and immune-related biomarkers in adults with recurrent upper respiratory tract infections (URTIs). Methods: A total of 100 adults aged 40 to &lt;75 years with a documented history of \u22652 episodes of upper respiratory tract infection in the prior 12 months were randomly assigned to receive fermented noni polysaccharides (487.5 mg\/tablet, two tablets once daily; 975 mg\/day of FNP extract) or a matched placebo for 8 weeks. The primary endpoint was the change in NK cell activity at effector-to-target (E:T) ratios of 50:1, 25:1, and 12.5:1, assessed using K562 NK-sensitive target cells. Secondary endpoints included circulating cytokines (IFN-\u03b3, TNF-\u03b1, IL-2, IL-6, IL-10, IL-12, IL-1\u03b2) and immunoglobulin G (IgG). Eighty-four participants (43 treatment, 41 placebo) were included in the modified intention-to-treat\/full analysis set (mITT\/FAS); 81 participants (41\/40) constituted the per-protocol set (PPS). Primary efficacy was analyzed in the mITT\/FAS. This trial was retrospectively registered at CRiS (KCT0011316) after trial completion; the IRB-approved protocol was finalised before enrolment and remained unchanged thereafter. Results: NK cell activity in the treatment group increased from baseline at all three E:T ratios, whereas it slightly decreased in the placebo group. Adjusted between-group LS mean differences (95% CI) were +8.94 (\u22120.61, 18.50; p = 0.066) at E:T 50:1, +7.68 (\u22121.14, 16.50; p = 0.087) at 25:1, and +3.29 (\u22122.95, 9.54; p = 0.145) at 12.5:1, all favouring treatment but not reaching the conventional threshold for significance in the mITT\/FAS. Prespecified PPS sensitivity analyses reached significance at E:T 50:1 (+11.03; p = 0.025) and 25:1 (+9.94; p = 0.028). Selected cytokines (IFN-\u03b3, IL-2, IL-6, IL-10, IL-1\u03b2) increased to a greater extent in the treatment group than in the placebo group, whereas TNF-\u03b1, IL-12, and IgG were unchanged. URTI incidence at week 4, week 8, and cumulatively did not differ significantly between groups. The intervention was well tolerated, with no serious adverse events and no treatment-related discontinuations. Conclusions: Compared with placebo, fermented noni polysaccharide supplementation showed numerically greater increases in NK cell activity at all three E:T ratios (50:1, 25:1, and 12.5:1) in the primary mITT\/FAS analysis, although these between-group differences did not reach statistical significance. Prespecified per-protocol set (PPS) sensitivity analyses showed significant between-group differences at E:T ratios of 50:1 and 25:1. The treatment group also showed greater increases in selected cytokines (IFN-\u03b3, IL-2, IL-6, IL-10) relative to placebo. No significant between-group differences were observed in URTI incidence, IgG, GARS, WBC, or leukocyte subset proportions. These exploratory biomarker findings, in the absence of safety signals, suggest a possible immunomodulatory profile but do not establish clinical efficacy. Confirmation in larger, prospectively registered trials with clinically adjudicated infection-related endpoints is warranted.<\/jats:p>","DOI":"10.3390\/nu18111691","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T11:02:51Z","timestamp":1779793371000},"page":"1691","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Fermented Noni Polysaccharides and Immune-Related Biomarkers in Adults with Recurrent URTIs: A Randomized, Double-Blind, Placebo-Controlled Trial"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1660-2973","authenticated-orcid":false,"given":"Seon-Mi","family":"Shin","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, College of Korean Medicine, Semyung University, 65 Semyung-ro, Jecheon-si 27136, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong-Hwan","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Korean Medicine, Semyung University, 65 Semyung-ro, Jecheon-si 27136, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seon-Gyu","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Korean Medicine, Semyung University, 65 Semyung-ro, Jecheon-si 27136, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Young","family":"Park","sequence":"additional","affiliation":[{"name":"R&D Center, NSTbio Co., Ltd., 32 Songdogwahak-ro, Yeonsu-gu, Incheon 21984, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Yeon","family":"Lee","sequence":"additional","affiliation":[{"name":"R&D Center, NSTbio Co., Ltd., 32 Songdogwahak-ro, Yeonsu-gu, Incheon 21984, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Yeon","family":"Kwon","sequence":"additional","affiliation":[{"name":"R&D Center, NSTbio Co., Ltd., 32 Songdogwahak-ro, Yeonsu-gu, Incheon 21984, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5488-5834","authenticated-orcid":false,"given":"Im-Joung","family":"La","sequence":"additional","affiliation":[{"name":"Atomy R&D Center, Atomy Co., Ltd., 3526 Charyeong-ro, Jeongan-myeon, Gongju-si 32511, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2592-7043","authenticated-orcid":false,"given":"Sang-Jun","family":"Youn","sequence":"additional","affiliation":[{"name":"RnBS Corporation, 11 Nonhyeon-ro 155-gil, Gangnam-gu, Seoul 06032, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Choi","sequence":"additional","affiliation":[{"name":"RnBS Corporation, 11 Nonhyeon-ro 155-gil, Gangnam-gu, Seoul 06032, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeong-Eun","family":"Choi","sequence":"additional","affiliation":[{"name":"Redox BioMedicine Laboratory, Wonju College of Medicine, Yonsei University, 1 Yonseidae-gil, Wonju 26493, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Do-Hee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Korean Medicine, Semyung University, 65 Semyung-ro, Jecheon-si 27136, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun-Young","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Korean Medicine, Semyung University, 65 Semyung-ro, Jecheon-si 27136, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheol","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Science, Semyung University, 65 Semyung-ro, Jecheon-si 27136, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Korean Medicine, Semyung University, 65 Semyung-ro, Jecheon-si 27136, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"ref_1","first-page":"11","article-title":"Functional foods for immune regulation focusing on Korean native materials","volume":"25","author":"Hwang","year":"2020","journal-title":"Food Ind. 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