{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:03:19Z","timestamp":1790676199231,"version":"4.1.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Periorbital edema and ecchymosis are common and distressing postoperative sequelae after blepharoplasty, often causing patient anxiety and delaying social recovery. Bromelain, a proteolytic enzyme from pineapple, is known for its anti-inflammatory and anti-edematous effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The aim of this study was to investigate the efficacy of oral bromelain in reducing postoperative edema and ecchymosis after upper blepharoplasty.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This randomized, triple-blind, placebo-controlled clinical trial was performed at our tertiary center. Forty-six blepharoplasty candidates were randomly assigned to 2 groups of 23: the intervention group received bromelain capsules (200\u2005mg, equivalent to 500 GDU) every 8\u2005hours, whereas the control group received identical placebo capsules containing starch for 2 weeks. The severity of edema and ecchymosis was evaluated on postoperative Days 1, 3, 7, and 11 using a validated photographic grading scale (Grades 1-4).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Both groups had similar baseline demographic characteristics (P &amp;gt; .05). The bromelain group showed significantly lower edema scores on Days 3, 7, and 11 (P &amp;lt; .001, P = .0002, and P = .001, respectively). Ecchymosis scores were significantly reduced on Day 3 (P = .0002), but there were no significant differences between groups on Days 7 and 11. Similarly, adverse effects did not differ significantly between the 2 groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Oral bromelain markedly reduces swelling after blepharoplasty and has a notable effect on ecchymosis during the early recovery period. It may represent a safe and effective postoperative adjunct following upper blepharoplasty, although larger multicenter trials are required.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Level of Evidence: 2 (Therapeutic)<\/jats:title>\n                    <jats:p\/>\n                  <\/jats:sec>","DOI":"10.1093\/asj\/sjag195","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T11:47:04Z","timestamp":1789127224000},"source":"Crossref","is-referenced-by-count":0,"title":["Oral Bromelain Reduces Postoperative Edema Following Upper Blepharoplasty: A Randomized Triple-Blind Placebo-Controlled Trial"],"prefix":"10.1093","author":[{"given":"Mahshad","family":"Shamloo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Rafiei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atena","family":"Esmaeili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farzad","family":"Zamani Barsari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeed","family":"Golparvaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Aalizade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1487-4385","authenticated-orcid":false,"given":"Benyamin","family":"Rahmaty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,12]]},"reference":[{"key":"2026092905383384100_sjag195-B1","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1001\/jama.2019.1957","article-title":"Upper blepharoplasty","volume":"321","author":"Olds","year":"2019","journal-title":"JAMA"},{"key":"2026092905383384100_sjag195-B2","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1007\/s00266-019-01317-5","article-title":"A flexible suspension technique of blepharoplasty: clinical application and comparison with traditional technique","volume":"43","author":"Pan","year":"2019","journal-title":"Aesthetic Plast Surg"},{"key":"2026092905383384100_sjag195-B3","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1080\/01676830600985841","article-title":"Complications of blepharoplasty","volume":"25","author":"Morax","year":"2006","journal-title":"Orbit"},{"key":"2026092905383384100_sjag195-B4","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1097\/PRS.0b013e3181c830c7","article-title":"Minor complications after blepharoplasty: dry eyes, chemosis, granulomas, ptosis, and scleral show","volume":"125","author":"Pacella","year":"2010","journal-title":"Plast Reconstr Surg"},{"key":"2026092905383384100_sjag195-B5","doi-asserted-by":"publisher","first-page":"252368","DOI":"10.1155\/2012\/252368","article-title":"Complications of blepharoplasty: prevention and management","volume":"2012","author":"Oestreicher","year":"2012","journal-title":"Plast Surg Int"},{"key":"2026092905383384100_sjag195-B6","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1177\/22925503211003836","article-title":"Modalities of post-rhinoplasty edema and ecchymosis measurement: a systematic review","volume":"30","author":"Levin","year":"2022","journal-title":"Plast Surg (Oakv)"},{"key":"2026092905383384100_sjag195-B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjoto.2020.102722","article-title":"Effects of perioperative magnesium sulfate with controlled hypotension on intraoperative bleeding and postoperative ecchymosis and edema in open rhinoplasty","volume":"41","author":"Kosucu","year":"2020","journal-title":"Am J Otolaryngol"},{"key":"2026092905383384100_sjag195-B8","first-page":"45","article-title":"Use of steroids in rhinoplasty with lateral osteotomies for reducing post operative oedema","volume":"30","author":"Sanober","year":"2018","journal-title":"J Ayub Med Coll Abbottabad"},{"key":"2026092905383384100_sjag195-B9","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.bjps.2023.04.053","article-title":"The efficacy of cryotherapy in reducing edema and ecchymosis in patients who underwent rhinoplasty: a narrative review","volume":"84","author":"Jardak","year":"2023","journal-title":"J Plast Reconstr Aesthet Surg"},{"key":"2026092905383384100_sjag195-B10","doi-asserted-by":"publisher","first-page":"2638","DOI":"10.1016\/j.joms.2017.06.014","article-title":"Perioperative systemic corticosteroids in orthognathic surgery: a systematic review and meta-analysis","volume":"75","author":"Jean","year":"2017","journal-title":"J Oral Maxillofac Surg"},{"key":"2026092905383384100_sjag195-B11","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1111\/j.1472-8206.2011.00991.x","article-title":"Adverse drug reactions associated with the use of NSAIDs: a case\/noncase analysis of spontaneous reports from the French pharmacovigilance database 2002-2006","volume":"27","author":"Lapeyre-Mestre","year":"2013","journal-title":"Fundam Clin Pharmacol"},{"key":"2026092905383384100_sjag195-B12","doi-asserted-by":"publisher","first-page":"e157","DOI":"10.4317\/medoral.19105","article-title":"Prospective double-blind clinical trial evaluating the effectiveness of bromelain in the third molar extraction postoperative period","volume":"19","author":"de la Barrera-N\u00fa\u00f1ez","year":"2014","journal-title":"Med Oral Patol Oral Cir Bucal"},{"key":"2026092905383384100_sjag195-B13","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1097\/DSS.0000000000000701","article-title":"Is there a role for arnica and bromelain in prevention of post-procedure ecchymosis or edema? A systematic review of the literature","volume":"42","author":"Ho","year":"2016","journal-title":"Dermatol Surg"},{"key":"2026092905383384100_sjag195-B14","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1016\/0049-3848(79)90121-x","article-title":"Bromelian, a thiolprotease from pineapple stem, depletes high molecular weight kininogen by activation of Hageman factor (Factor XIII)","volume":"14","author":"Oh-ishi","year":"1979","journal-title":"Thromb Res"},{"key":"2026092905383384100_sjag195-B15","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1016\/0306-9877(80)90134-6","article-title":"Fibrinolytic and antithrombotic action of bromelain may eliminate thrombosis in heart patients","volume":"6","author":"Felton","year":"1980","journal-title":"Med Hypotheses"},{"key":"2026092905383384100_sjag195-B16","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1007\/PL00000936","article-title":"Bromelain: biochemistry, pharmacology and medical use","volume":"58","author":"Maurer","year":"2001","journal-title":"Cell Mol Life Sci"},{"key":"2026092905383384100_sjag195-B17","first-page":"110","article-title":"Possible involvement of eicosanoids in the pharmacological action of bromelain","volume":"36","author":"Vellini","year":"1986","journal-title":"Arzneimittelforschung"},{"key":"2026092905383384100_sjag195-B18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0078988","article-title":"Bromelain decreases neutrophil interactions with p-selectin, but not E-selectin, in vitro by proteolytic cleavage of P-selectin glycoprotein ligand-1","volume":"8","author":"Banks","year":"2013","journal-title":"PLoS One"},{"key":"2026092905383384100_sjag195-B19","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1006\/clim.2002.5254","article-title":"Bromelain treatment alters leukocyte expression of cell surface molecules involved in cellular adhesion and activation","volume":"104","author":"Hale","year":"2002","journal-title":"Clin Immunol"},{"key":"2026092905383384100_sjag195-B20","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1002\/ptr.4678","article-title":"Placebo-controlled randomized clinical trial on the immunomodulating activities of low- and high-dose bromelain after oral administration\u2014new evidence on the antiinflammatory mode of action of bromelain","volume":"27","author":"M\u00fcller","year":"2013","journal-title":"Phytother Res"},{"key":"2026092905383384100_sjag195-B21","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1007\/BF01923166","article-title":"Effect of bromelain (Ananase) on human platelet aggregation","volume":"28","author":"Heinicke","year":"1972","journal-title":"Experientia"},{"key":"2026092905383384100_sjag195-B22","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1007\/s00210-013-0890-z","article-title":"Bromelain down-regulates myofibroblast differentiation in an in vitro wound healing assay","volume":"386","author":"Aichele","year":"2013","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"2026092905383384100_sjag195-B23","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.burns.2011.06.002","article-title":"Efficacy of enzymatic debridement of deeply burned hands","volume":"38","author":"Krieger","year":"2012","journal-title":"Burns"},{"key":"2026092905383384100_sjag195-B24","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1097\/BCR.0b013e31822dc467","article-title":"Reepithelialization of mid-dermal porcine burns after rapid enzymatic debridement with Debrase\u00ae","volume":"32","author":"Singer","year":"2011","journal-title":"J Burn Care Res"},{"key":"2026092905383384100_sjag195-B25","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1016\/j.burns.2012.02.011","article-title":"Selectivity of a bromelain based enzymatic debridement agent: a porcine study","volume":"38","author":"Rosenberg","year":"2012","journal-title":"Burns"},{"key":"2026092905383384100_sjag195-B26","first-page":"84","article-title":"Evaluating the effect of oral bromelain (pineapple) on episiotomy wound healing in primiparus women","volume":"15","author":"Golozar","year":"2011","journal-title":"Feyz Med Sci J"},{"key":"2026092905383384100_sjag195-B27","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1177\/02601060231173732","article-title":"Efficacy and safety of bromelain: a systematic review and meta-analysis","volume":"29","author":"Leelakanok","year":"2023","journal-title":"Nutr Health"},{"key":"2026092905383384100_sjag195-B28","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/j.jss.2011.11.1027","article-title":"Bromelain ameliorates the wound microenvironment and improves the healing of firearm wounds","volume":"176","author":"Wu","year":"2012","journal-title":"J Surg Res"},{"key":"2026092905383384100_sjag195-B29","doi-asserted-by":"publisher","DOI":"10.5812\/ircmj.21019","article-title":"Ananas comosus effect on perineal pain and wound healing after episiotomy: a randomized double-blind placebo-controlled clinical trial","volume":"18","author":"Golezar","year":"2016","journal-title":"Iran Red Crescent Med J"},{"key":"2026092905383384100_sjag195-B30","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1097\/SCS.0000000000004862","article-title":"In vitro effect of bromelain on the regenerative properties of mesenchymal stem cells","volume":"30","author":"Ghensi","year":"2019","journal-title":"J Craniofac Surg"},{"key":"2026092905383384100_sjag195-B31","doi-asserted-by":"publisher","first-page":"3648","DOI":"10.1007\/s00266-024-04646-2","article-title":"The effectiveness of bromelain on oedema, subconjunctival haemorrhage, and ecchymosis after rhinoplasty: a randomised, double-blind, placebo-controlled trial","volume":"49","author":"Rahmaty","year":"2025","journal-title":"Aesthetic Plast Surg"},{"key":"2026092905383384100_sjag195-B32","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1001\/jamafacial.2018.1730","article-title":"Association of periosteal sweeping vs periosteal preservation with early periorbital sequelae among patients undergoing external perforating osteotomy during rhinoplasty","volume":"21","author":"El-Sisi","year":"2019","journal-title":"JAMA Facial Plast Surg"},{"key":"2026092905383384100_sjag195-B33","doi-asserted-by":"publisher","first-page":"33","DOI":"10.26355\/eurrev_202303_31699","article-title":"Bromelain: a candidate to enhance wound healing after endonasal surgeries","volume":"27","author":"Esen","year":"2023","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"2026092905383384100_sjag195-B34","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1002\/ptr.6244","article-title":"Is bromelain effective in controlling the inflammatory parameters of pain, edema, and trismus after lower third molar surgery? A systematic review and meta-analysis","volume":"33","author":"de Souza","year":"2019","journal-title":"Phytother Res"},{"key":"2026092905383384100_sjag195-B35","author":"Lent-Schochet"},{"key":"2026092905383384100_sjag195-B36","first-page":"61","article-title":"A review of clinical signs related to ecchymosis","volume":"114","author":"Epperla","year":"2015","journal-title":"WMJ"},{"key":"2026092905383384100_sjag195-B37","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1016\/j.burns.2018.01.012","article-title":"Time to start putting down the knife: a systematic review of burns excision tools of randomised and non-randomised trials","volume":"44","author":"Edmondson","year":"2018","journal-title":"Burns"}],"container-title":["Aesthetic Surgery Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/asj\/advance-article-pdf\/doi\/10.1093\/asj\/sjag195\/71036046\/sjag195.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/asj\/advance-article-pdf\/doi\/10.1093\/asj\/sjag195\/71036046\/sjag195.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:38:42Z","timestamp":1790674722000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/asj\/advance-article\/doi\/10.1093\/asj\/sjag195\/8791258"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,12]]},"references-count":37,"URL":"https:\/\/doi.org\/10.1093\/asj\/sjag195","relation":{},"ISSN":["1090-820X","1527-330X"],"issn-type":[{"value":"1090-820X","type":"print"},{"value":"1527-330X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,12]]},"article-number":"sjag195"}}