{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T08:06:47Z","timestamp":1784102807334,"version":"3.55.0"},"reference-count":17,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Objective: This multicenter retrospective real-world data study aimed to evaluate whether the use of a preparation containing polyphenol, vitamin D3, vitamin C, and zinc in addition to antiviral therapy was associated with symptom duration and severity, time to fever resolution, and functional recovery in children diagnosed with influenza. Materials and Methods: This was a five-center, multicenter, retrospective, comparative real-world data analysis. A total of 128 patients aged 4\u201310 years with a clinical diagnosis of influenza were classified into a control group receiving antiviral therapy alone (n = 64) and a combined polyphenol group receiving, in addition to antiviral therapy, a preparation containing polyphenol, vitamin D3, vitamin C, and zinc (n = 64). Clinical data were obtained from electronic patient records and parent-reported information. Symptom severity (0\u20133 ordinal score), recovery time, and functional outcomes were assessed on Days 0, 3, 5, and 7. Continuous variables were compared using the independent-samples t test, categorical variables using the chi-square or Fisher exact test, and changes over time using a repeated-measures general linear model. Statistical significance was accepted as a two-sided p value of &lt;0.05. Results: In this study including 128 pediatric patients, there were no significant differences between the combined polyphenol and control groups in demographic or baseline clinical characteristics (p &gt; 0.05). During follow-up, all symptom scores improved more rapidly and markedly in the combined polyphenol group than in the control group. By Day 3, significant differences were observed between groups in fever, cough, rhinorrhea, sore throat, fatigue, general condition, and physical activity scores (p &lt; 0.001 for all parameters). By Day 5, almost complete resolution of symptoms (score 0) was observed in the combined polyphenol group, whereas symptoms persisted to a substantial extent in the control group (p &lt; 0.001). The time to fever resolution was significantly shorter in the combined polyphenol group (1.84 \u00b1 0.72 days vs. 4.5 \u00b1 1.36 days; p &lt; 0.001). Similarly, time to return to school (3.21 \u00b1 0.9 days vs. 5.8 \u00b1 1.91 days; p &lt; 0.001) and time for parents to return to work were significantly shorter in the combined polyphenol group (p &lt; 0.001). The need for additional healthcare visits and antipyretic use was markedly lower in the combined polyphenol group (Day 3: 20.3% vs. 53.1%; Day 5: 0% vs. 15.6%; p &lt; 0.001 for both comparisons). Repeated-measures analyses showed a significant time-by-group interaction, indicating that the reduction in symptom scores occurred more rapidly and prominently in the combined polyphenol group (p &lt; 0.001). Treatment was generally well tolerated in the combined polyphenol group; no serious adverse events were reported, and parent-reported tolerability was high (9.39 \u00b1 0.7). Conclusions: This multicenter retrospective real-world data study suggests that the use of a preparation containing polyphenol, vitamin D3, vitamin C, and zinc in addition to antiviral therapy was associated with shorter symptom duration, lower symptom severity scores, and faster functional recovery in children diagnosed with influenza. These findings suggest that this combination may represent a promising and well-tolerated adjunctive approach in the management of pediatric influenza.<\/jats:p>","DOI":"10.3390\/pharmaceutics18070858","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T03:06:52Z","timestamp":1784084812000},"page":"858","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of Combined Polyphenol on the Disease Course in Children Diagnosed with Influenza"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4316-2491","authenticated-orcid":false,"given":"Eren","family":"G\u00fczelo\u011flu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Prof. Dr. Cemil Ta\u015fc\u0131o\u011flu City Hospital, University of Health Sciences, Istanbul 34384, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2080-4677","authenticated-orcid":false,"given":"Vefik","family":"Arica","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Prof. Dr. Cemil Ta\u015fc\u0131o\u011flu City Hospital, University of Health Sciences, Istanbul 34384, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4525-8764","authenticated-orcid":false,"given":"Belen","family":"Ate\u015f","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Prof. Dr. Cemil Ta\u015fc\u0131o\u011flu City Hospital, University of Health Sciences, Istanbul 34384, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taner","family":"Adig\u00fczel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Yalova Training and Research Hospital, Faculty of Medicine, Yalova University, Yalova 77200, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9574-9529","authenticated-orcid":false,"given":"Aysun","family":"Bo\u011fa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Sancaktepe Prof. Dr. \u0130lhan Varank Training and Research Hospital, University of Health Sciences, Istanbul 34785, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali R\u0131za","family":"Akg\u00fcn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Esenyurt Necmi Kad\u0131o\u011flu State Hospital, Istanbul 34517, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6055-7746","authenticated-orcid":false,"given":"Mehmet Tolga","family":"K\u00f6le","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ankara Etlik City Hospital, University of Health Sciences, Ankara 06170, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ay\u015fe","family":"Ademo\u011flu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Prof. Dr. Cemil Ta\u015fc\u0131o\u011flu City Hospital, University of Health Sciences, Istanbul 34384, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatice Demet","family":"Kemalbay","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Prof. Dr. Cemil Ta\u015fc\u0131o\u011flu City Hospital, University of Health Sciences, Istanbul 34384, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feyza Ayd\u0131n","family":"\u00d6zg\u00fcr","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Prof. Dr. Cemil Ta\u015fc\u0131o\u011flu City Hospital, University of Health Sciences, Istanbul 34384, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1904-6606","authenticated-orcid":false,"given":"Hatice Y\u0131ld\u0131z","family":"\u00d6zkan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Prof. Dr. Cemil Ta\u015fc\u0131o\u011flu City Hospital, University of Health Sciences, Istanbul 34384, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3254-5534","authenticated-orcid":false,"given":"Eda","family":"\u00c7ift\u00e7i","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Prof. Dr. Cemil Ta\u015fc\u0131o\u011flu City Hospital, University of Health Sciences, Istanbul 34384, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00fcseyin","family":"Da\u011f","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Prof. Dr. Cemil Ta\u015fc\u0131o\u011flu City Hospital, University of Health Sciences, Istanbul 34384, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S2213-2600(18)30496-X","article-title":"Mortality, morbidity, and hospitalisations due to influenza lower respiratory tract infections, 2017: An analysis for the Global Burden of Disease Study 2017","volume":"7","author":"Troeger","year":"2019","journal-title":"Lancet Respir. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lafond, K.E., Porter, R.M., Whaley, M.J., Suizan, Z., Ran, Z., Aleem, M.A., Thapa, B., Sar, B., Proschle, V.S., and Peng, Z. (2021). Global burden of influenza-associated lower respiratory tract infections and hospitalizations among adults: A systematic review and meta-analysis. PLoS Med., 18.","DOI":"10.1371\/journal.pmed.1003550"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1093\/cid\/cix1040","article-title":"Efficacy and safety of oseltamivir in children: Systematic review and individual patient data meta-analysis of randomized controlled trials","volume":"66","author":"Malosh","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/S2213-2600(14)70041-4","article-title":"Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: A meta-analysis of individual participant data","volume":"2","author":"Muthuri","year":"2014","journal-title":"Lancet Respir. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Calder, P.C., Carr, A.C., Gombart, A.F., and Eggersdorfer, M. (2020). Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections. Nutrients, 12.","DOI":"10.3390\/nu12041181"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Yahfoufi, N., Alsadi, N., Jambi, M., and Matar, C. (2018). The Immunomodulatory and Anti-Inflammatory Role of Polyphenols. Nutrients, 10.","DOI":"10.3390\/nu10111618"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1264074","DOI":"10.1155\/2018\/1264074","article-title":"Regulation of Immune Function by Polyphenols","volume":"2018","author":"Ding","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Chojnacka, K., Skrzypczak, D., Mikula, K., Witek-Krowiak, A., and Izydorczyk, G. (2021). Antiviral Properties of Polyphenols from Plants. Foods, 10.","DOI":"10.3390\/foods10102277"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ninfali, P., Antonelli, A., Magnani, M., and Scarpa, E.S. (2020). Antiviral Properties of Flavonoids and Delivery Strategies. Nutrients, 12.","DOI":"10.3390\/nu12092534"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1111\/j.1541-4337.2010.00131.x","article-title":"Pomegranate and its many functional components as related to human health: A review","volume":"9","year":"2010","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Tito, A., Colantuono, A., Pirone, L., Pedone, E., Intartaglia, D., Giamundo, G., Conte, I., Vitaglione, P., and Apone, F. (2021). Pomegranate Peel Extract as an Inhibitor of SARS-CoV-2 Spike Binding to Human ACE2 Receptor in vitro: A Promising Source of Novel Antiviral Drugs. Front. Chem., 9.","DOI":"10.3389\/fchem.2021.638187"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.jep.2012.07.004","article-title":"Pomegranate peel and fruit extracts: A review of potential anti-inflammatory and anti-infective effects","volume":"143","author":"Ismail","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_13","first-page":"227","article-title":"Serum Zinc levels in children of 0-24 months diagnosed with pneumonia admitted to our clinic","volume":"4","author":"Dag","year":"2011","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_14","first-page":"488","article-title":"Risk factors for lower respiratory tract infections in children","volume":"28","author":"Silfeler","year":"2012","journal-title":"Pak. J. Med. Sci. Q."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Hemil\u00e4, H. (2017). Vitamin C and infections. Nutrients, 9.","DOI":"10.3390\/nu9040339"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"i6583","DOI":"10.1136\/bmj.i6583","article-title":"Vitamin D supplementation to prevent acute respiratory infections","volume":"356","author":"Martineau","year":"2017","journal-title":"BMJ"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1093\/advances\/nmz013","article-title":"The Role of Zinc in Antiviral Immunity","volume":"10","author":"Read","year":"2019","journal-title":"Adv. Nutr."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/7\/858\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T07:32:14Z","timestamp":1784100734000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/7\/858"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,14]]},"references-count":17,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["pharmaceutics18070858"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics18070858","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,14]]}}}