{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:53:14Z","timestamp":1791003194643,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Food Science &amp;amp; Nutrition"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Traumatic brain injury (TBI) is the leading cause of death from injury. Many studies have shown that cytokines, chemokines, and oxidative stress play a crucial role in the pathophysiology of TBI. One of the types of interventions that are receiving more and more attention is nutritional support and the use of nutritional supplements to reduce inflammation in these patients. The present study was a double\u2010blind controlled clinical trial, performed on patients with traumatic brain injury. Patients in the intervention group received 600\u2009mg of oral bromelain daily through gavage, while the patients in the control group received a placebo for 14\u2009days. SOFA, APACHE, and NUTRIC scores were evaluated at each time of blood sampling and 28\u2010 and 60\u2010day mortality. Also, clinical and biochemical information (CRP, MDA, IL\u20106, and TAC), anthropometry, and nutritional information of patients were recorded during the study. There was no significant difference between the two groups in terms of gender, weight, BMI, MAC, APACHE SCORE, NUTRIC SCORE, SOFA SCORE, and energy intake at the beginning of the study (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&gt;\u20090.05). Bromelain supplementation significantly reduced IL\u20106 levels (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), APACHE score (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.011), SOFA score (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), and NUTRIC score (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Furthermore, 60\u2010day mortality was significantly lower in the bromelain group compared to the placebo group (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.036). However, there was no significant effect on CRP (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.377), MDA (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.061), TAC levels (\n                    <jats:italic>p<\/jats:italic>\n                    = 0.185). Bromelain supplementation significantly improved IL\u20106 levels, APACHE, SOFA, and NUTRIC scores, and reduced 60\u2010day mortality in patients with traumatic brain injury. However, its effects on CRP, MDA and TAC levels were not statistically significant. These findings suggest that bromelain may serve as a promising adjunctive therapy to reduce inflammation and improve clinical outcomes in critically ill TBI patients. Further studies with larger sample sizes and longer follow\u2010up periods are needed to confirm these results.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.70162","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T05:14:52Z","timestamp":1785388492000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effects of Bromelain Supplementation on Clinical Outcomes, Inflammatory and Oxidative Stress Biomarkers in Patients With Traumatic Brain Injury: A Randomized, Double\u2010Blind Placebo\u2010Controlled Clinical Trial"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2306-9508","authenticated-orcid":false,"given":"Alireza","family":"Gheflati","sequence":"first","affiliation":[{"name":"Nutrition and Food Health Research Center AJA University of Medical Sciences  Tehran Iran"},{"name":"Department of Nutrition Sciences Varastegan Institute for Medical Sciences  Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Rashid Mayvan","sequence":"additional","affiliation":[{"name":"Nutrition and Food Health Research Center AJA University of Medical Sciences  Tehran Iran"},{"name":"Department of Nutrition, Food Sciences and Clinical Biochemistry, School of Medicine, Social Determinants of Health Research Center Gonabad University of Medical Science  Gonabad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mojgan Mehri","family":"Ardestani","sequence":"additional","affiliation":[{"name":"Department of Persian Medicine, Faculty of Medicine AJA University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed Mahdi","family":"Mirghazanfari","sequence":"additional","affiliation":[{"name":"Department of Physiology and Iranian Medicine, Faculty of Medicine AJA University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebrahim","family":"Hazrati","sequence":"additional","affiliation":[{"name":"Departemnt of Anesthesiology and Intensive Care, Medical Faculty AJA University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad Shahab","family":"Kalantar","sequence":"additional","affiliation":[{"name":"Departemnt of Anesthesiology and Intensive Care, Medical Faculty AJA University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vahid","family":"Hadi","sequence":"additional","affiliation":[{"name":"Nutrition and Food Health Research Center AJA University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Jafarzadeh Esfehani","sequence":"additional","affiliation":[{"name":"Metabolic Syndrome Research Center Mashhad University of Medical Sciences  Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeid","family":"Hadi","sequence":"additional","affiliation":[{"name":"Nutrition and Food Health Research Center AJA University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells13070581"},{"issue":"8","key":"e_1_2_11_3_1","article-title":"Bromelain: A Potent Phytomedicine","volume":"14","author":"Agrawal P.","year":"2022","journal-title":"Cureus"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-009-1567-4"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.125.4.1446"},{"issue":"1","key":"e_1_2_11_6_1","first-page":"23","article-title":"Reactive Oxygen Species: Physiological and Physiopathological Effects on Synaptic Plasticity","volume":"10","author":"Beckhauser T. F.","year":"2016","journal-title":"Journal of Experimental Neuroscience"},{"issue":"1","key":"e_1_2_11_7_1","first-page":"1","article-title":"Niosome Encapsulated Bromelain Reduced IL\u20106 and TNF\u2010\u03b1 in LPS Induced Human Skin Fibroblast Cell Line","volume":"2","author":"Chermahini S. H.","year":"2021","journal-title":"OSP Journal of Health Care and Medicine"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/5342559"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1024\/0300-9831\/a000058"},{"issue":"6","key":"e_1_2_11_10_1","article-title":"The Effect of Diosmin, Escin, and Bromelain on Human Endothelial Cells Derived From the Umbilical Vein and the Varicose Vein\u2014A Preliminary Study","volume":"11","author":"Gwozdzinski L.","year":"2023","journal-title":"Biomedicine"},{"issue":"1","key":"e_1_2_11_11_1","first-page":"33","article-title":"Modulation of Lipopolysaccharide Stimulated Nuclear Factor Kappa B Mediated iNOS\/NO Production by Bromelain in Rat Primary Microglial Cells","volume":"20","author":"Habashi S. A.","year":"2016","journal-title":"Iranian Biomedical Journal"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf052390k"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-016-3363-1"},{"issue":"1","key":"e_1_2_11_14_1","first-page":"299","article-title":"Anti\u2010Inflammatory Effects of Bromelain in Lps\u2010Induced Human U937 Macrophages","volume":"45","author":"Kasemsuk T.","year":"2018","journal-title":"Chiang Mai Journal of Science"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.5812\/atr.22594"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871527317666180627120501"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3FO01060K"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001199-200609000-00001"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.12691\/jfnr-6-12-8"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00000936"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-022-04290-9"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2007.11.002"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114520002548"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnesp.2023.02.028"},{"issue":"11","key":"e_1_2_11_25_1","article-title":"Bromelain Extract Exerts Antiarthritic Effects via Chondroprotection and the Suppression of TNF\u2010\u03b1\u2010Induced NF\u2010\u03baB and MAPK Signaling","volume":"10","author":"Pothacharoen P.","year":"2021","journal-title":"Plants (Basel, Switzerland)"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.19070\/2377-8075-21000493"},{"key":"e_1_2_11_27_1","first-page":"303","article-title":"Injury and Traumatic Brain Injury\u2010Related Death Rates by Age\u2014United States, 2006","volume":"59","author":"QuickStats C","year":"2010","journal-title":"MMWR. Morbidity and Mortality Weekly Report"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2022.2042250"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3892\/br.2016.720"},{"issue":"7","key":"e_1_2_11_30_1","first-page":"1640","article-title":"Safety & Efficacy Report Bromelain","volume":"118","author":"Roger A.","year":"2006","journal-title":"Plastic and Reconstructive Surgery"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eujim.2020.101271"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00754"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1208708"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(02)00626-2"},{"issue":"3","key":"e_1_2_11_35_1","first-page":"41","article-title":"Evaluation of TRAP and FRAP Methods for Assessing Total Antioxidant Capacity of Rat Serum","volume":"9","author":"Tayefi\u2010Nasrabadi h.","year":"2007","journal-title":"Scientific Magazine Yafte"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.3923\/pjn.2008.513.520"},{"key":"e_1_2_11_37_1","first-page":"1","article-title":"Role of Bromelain as Herbal Anti\u2010Inflammatory Compound Using In\u00a0Vitro and In\u00a0Vivo Model of Colitis","volume":"3","author":"Verma N.","year":"2017","journal-title":"Journal of Autoimmune Diseases"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2015.10.010"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005373-200202000-00021"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2013.00018"},{"issue":"272","key":"e_1_2_11_41_1","first-page":"1","article-title":"Dietary Bromelain Supplementation for Improving Laying Performance, Egg Quality and Antioxidant Status","volume":"83","author":"Yenice G.","year":"2019","journal-title":"European Poultry Science\/Archiv f\u00fcr Gefl\u00fcgelkunde"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nurt.2009.10.016"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000215112.84523.F0"}],"container-title":["Food Science &amp; Nutrition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/fsn3.70162","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/fsn3.70162","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/fsn3.70162","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:13:57Z","timestamp":1791000837000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/fsn3.70162"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,29]]},"references-count":42,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/fsn3.70162"],"URL":"https:\/\/doi.org\/10.1002\/fsn3.70162","archive":["Portico"],"relation":{},"ISSN":["2048-7177","2048-7177"],"issn-type":[{"value":"2048-7177","type":"print"},{"value":"2048-7177","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,29]]},"assertion":[{"value":"2024-07-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70162"}}