{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:58:01Z","timestamp":1792789081703,"version":"4.5.0"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T00:00:00Z","timestamp":1744934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ARMATURA, Greece (Spermotrend\u00ae, CATALYSIS, S.L.)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>A randomized, placebo-controlled, quadruple-blind trial was performed to evaluate the effect of oral administration of the antioxidant combination Spermotrend\u00ae for three months on semen quality in infertile men with at least one abnormal variable in semen analysis. Eighty men were randomized between 2019 and 2022, receiving either the antioxidant combination Spermotrend\u00ae\u00a0(n = 40, spermotrend-group) or placebo (n = 40, placebo-group). Although a total of 80 patients were enrolled in the study, the final data is only from 70 patients. The primary outcome measure was sperm motility (rapid progressive, progressive, and total motility). The values of primary and secondary outcomes between treatment initiation and treatment completion were compared within groups. Moreover, their changes between treatment initiation and treatment completion were compared between the placebo- and the spermotrend-groups. Sperm rapid progressive motility significantly increased in infertile men treated for three months with antioxidant combination Spermotrend\u00ae (+1.0%, 95% CI: 0.0 to +2.0, p = 0.04), while this increase was not observed in the placebo-group. Sperm progressive motility significantly increased in infertile men treated for three months with antioxidant combination Spermotrend\u00ae (+3.0%, 95% CI: 0.0 to +15.1, p = 0.02), while this increase was not observed in the placebo-group. Similarly, DFI was significantly decreased in infertile men treated for three months by antioxidant combination Spermotrend\u00ae (\u22123.2%, 95% CI: \u22125.8 to \u22120.5, p = 0.02). However, no statistically significant differences were observed in the changes of pre- and post-treatment values between the spermotrend- and the placebo-group regarding sperm progressive motility, concentration, normal morphology, DFI, and formation of 8-OH-dG. The antioxidant combination Spermotrend\u00ae appears to exert limited benefit on sperm motility and DFI in infertile men with at least one abnormal variable in semen analysis.<\/jats:p>","DOI":"10.3390\/antiox14040488","type":"journal-article","created":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T05:11:16Z","timestamp":1744953076000},"page":"488","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Effect of Antioxidant Administration on Semen Quality in Men with Infertility: A Randomized Placebo-Controlled Clinical Trial"],"prefix":"10.3390","volume":"14","author":[{"given":"Pinelopi","family":"Ioannidou","sequence":"first","affiliation":[{"name":"Unit for Human Reproduction, 1st Department of Obstetrics-Gynecology, School of Medicine, Aristotle University of Thessaloniki, Papageorgiou General Hospital, 56403 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodosia","family":"Zeginiadou","sequence":"additional","affiliation":[{"name":"Andrologylab, Andrology Diagnostic Center, 54624 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos","family":"Venetis","sequence":"additional","affiliation":[{"name":"Unit for Human Reproduction, 1st Department of Obstetrics-Gynecology, School of Medicine, Aristotle University of Thessaloniki, Papageorgiou General Hospital, 56403 Thessaloniki, Greece"},{"name":"Centre for Big Data Research in Health, Faculty of Medicine & Health, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Papanikolaou","sequence":"additional","affiliation":[{"name":"2nd Department of Urology, School of Medicine, Aristotle University of Thessaloniki, Papageorgiou General Hospital, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonidas","family":"Zepiridis","sequence":"additional","affiliation":[{"name":"Unit for Human Reproduction, 1st Department of Obstetrics-Gynecology, School of Medicine, Aristotle University of Thessaloniki, Papageorgiou General Hospital, 56403 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Despoina","family":"Savvaidou","sequence":"additional","affiliation":[{"name":"Unit for Human Reproduction, 1st Department of Obstetrics-Gynecology, School of Medicine, Aristotle University of Thessaloniki, Papageorgiou General Hospital, 56403 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Chatzimeletiou","sequence":"additional","affiliation":[{"name":"Unit for Human Reproduction, 1st Department of Obstetrics-Gynecology, School of Medicine, Aristotle University of Thessaloniki, Papageorgiou General Hospital, 56403 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8887-222X","authenticated-orcid":false,"given":"Alexandros","family":"Lambropoulos","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Biology\u2014Genetics, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5005-1995","authenticated-orcid":false,"given":"Dimitrios G.","family":"Goulis","sequence":"additional","affiliation":[{"name":"Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, 56429 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grigoris","family":"Grimbizis","sequence":"additional","affiliation":[{"name":"Unit for Human Reproduction, 1st Department of Obstetrics-Gynecology, School of Medicine, Aristotle University of Thessaloniki, Papageorgiou General Hospital, 56403 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0031-9460","authenticated-orcid":false,"given":"Efstratios M.","family":"Kolibianakis","sequence":"additional","affiliation":[{"name":"Unit for Human Reproduction, 1st Department of Obstetrics-Gynecology, School of Medicine, Aristotle University of Thessaloniki, Papageorgiou General Hospital, 56403 Thessaloniki, Greece"},{"name":"Centre for Big Data Research in Health, Faculty of Medicine & Health, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"385","DOI":"10.4111\/icu.2017.58.6.385","article-title":"Oxidation-reduction potential as a new marker for oxidative stress: Correlation to male infertility","volume":"58","author":"Agarwal","year":"2017","journal-title":"Investig. Clin. Urol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"217","DOI":"10.3109\/14647273.2010.532279","article-title":"The role of antioxidant therapy in the treatment of male infertility","volume":"13","author":"Agarwa","year":"2010","journal-title":"Hum. Fertil."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zhao, J., Huang, X., Xu, B., Yan, Y., Zhang, Q., and Li, Y. (2018). Whether vitamin D was associated with clinical outcome after IVF\/ICSI: A systematic review and meta-analysis. Reprod. Biol. Endocrinol., 16.","DOI":"10.1186\/s12958-018-0324-3"},{"key":"ref_4","first-page":"867","article-title":"[WHO Laboratory Manual for the Examination and Processing of Human Semen: Its applicability to andrology laboratories in China]","volume":"16","author":"Lu","year":"2010","journal-title":"Zhonghua Nan Ke Xue"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/S0015-0282(16)57861-3","article-title":"A double-blind randomized placebo cross-over controlled trial using the antioxidant vitamin E to treat reactive oxygen species associated male infertility","volume":"64","author":"Kessopoulou","year":"1995","journal-title":"Fertil. Steril."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1007\/s10815-013-9961-9","article-title":"Effects of supplement therapy on sperm parameters, protamine content and acrosomal integrity of varicocelectomized subjects","volume":"30","author":"Azizollahi","year":"2013","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1007\/BF03346521","article-title":"Coenzyme Q10 and male infertility","volume":"32","author":"Balercia","year":"2009","journal-title":"J. Endocrinol. Invest."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.fertnstert.2005.03.064","article-title":"Placebo-controlled double-blind randomized trial on the use of L-carnitine, L-acetylcarnitine, or combined L-carnitine and L-acetylcarnitine in men with idiopathic asthenozoospermia","volume":"84","author":"Balercia","year":"2005","journal-title":"Fertil. Steril."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e12927","DOI":"10.1111\/and.12927","article-title":"Effect of metabolic and antioxidant supplementation on sperm parameters in oligo-astheno-teratozoospermia, with and without varicocele: A double-blind placebo-controlled study","volume":"50","author":"Busetto","year":"2018","journal-title":"Andrologia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1111\/j.1479-828X.2007.00723.x","article-title":"A randomised control trial examining the effect of an antioxidant (Menevit) on pregnancy outcome during IVF-ICSI treatment","volume":"47","author":"Tremellen","year":"2007","journal-title":"Aust. N. Z. J. Obstet. Gynaecol."},{"key":"ref_11","first-page":"CD007411","article-title":"Antioxidants for male subfertility","volume":"5","author":"Smits","year":"2022","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"hoad020","DOI":"10.1093\/hropen\/hoad020","article-title":"The lack of evidence behind over-the-counter antioxidant supplements for male fertility patients: A scoping review","volume":"2023","author":"Fleischer","year":"2023","journal-title":"Hum. Reprod. Open"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1093\/humupd\/dmp048","article-title":"World Health Organization reference values for human semen characteristics","volume":"16","author":"Cooper","year":"2010","journal-title":"Hum. Reprod. Update"},{"key":"ref_14","first-page":"227","article-title":"Artificial intelligence-based fluorescence method versus traditional flow cytometry in detection of sperm DNA fragmentation index","volume":"28","author":"Kai","year":"2022","journal-title":"Zhonghua Nan Ke Xue"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1530\/REP-12-0404","article-title":"Development of a specific method to evaluate 8-hydroxy, 2-deoxyguanosine in sperm nuclei: Relationship with semen quality in a cohort of 94 subjects","volume":"145","author":"Cambi","year":"2013","journal-title":"Reproduction"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e13874","DOI":"10.1111\/and.13874","article-title":"Sperm DNA fragmentation testing: Summary evidence and clinical practice recommendations","volume":"53","author":"Esteves","year":"2021","journal-title":"Andrologia"},{"key":"ref_17","unstructured":"Hintze (2011). PASS 11, NCSS, LLC."},{"key":"ref_18","first-page":"CD007411","article-title":"Antioxidants for male subfertility","volume":"3","author":"Smits","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1177\/1536867X1201200202","article-title":"What hypotheses do \u201cnonparametric\u201d two-group tests actually test?","volume":"12","author":"Conroy","year":"2012","journal-title":"Stata J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1023\/A:1022585000740","article-title":"Sperm motility is a major determinant of pregnancy outcome following intrauterine insemination","volume":"15","author":"Shulman","year":"1998","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Vahedi Raad, M., Firouzabadi, A.M., Tofighi Niaki, M., Henkel, R., and Fesahat, F. (2024). The impact of mitochondrial impairments on sperm function and male fertility: A systematic review. Reprod. Biol. Endocrinol., 22.","DOI":"10.1186\/s12958-024-01252-4"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5732","DOI":"10.1073\/pnas.1800779115","article-title":"Placebo treatment facilitates social trust and approach behavior","volume":"115","author":"Yan","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","first-page":"301","article-title":"Influence of Male Obesity on Fertility","volume":"55","author":"Kasum","year":"2016","journal-title":"Acta Clin. Croat."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1111\/andr.12805","article-title":"Dietary supplementation with a novel l-carnitine multi-micronutrient in idiopathic male subfertility involving oligo-, astheno-, teratozoospermia: A randomized clinical study","volume":"8","author":"Kopets","year":"2020","journal-title":"Andrology"},{"key":"ref_25","first-page":"213","article-title":"[Treatment with carnitine, acetyl carnitine, L-arginine and ginseng improves sperm motility and sexual health in men with asthenopermia]","volume":"62","author":"Morgante","year":"2010","journal-title":"Minerva Urol. Nefrol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Popova, A.Y., Ovchinnikov, R.I., and Gamidov, S.I. (2019). Antioxidant therapy improves the results of -test in infertile men during a preparation for assisted reproductive technology (IVF\/ICSI). Urologiia, 90\u201396.","DOI":"10.18565\/urology.2019.16.90-96"},{"key":"ref_27","first-page":"8","article-title":"The Effect of Daily Intake of Selenium, Vitamin E and Folic Acid on Sperm Parameters in Males with Idiopathic Infertility: A Single-Blind Randomized Controlled Clinical Trial","volume":"15","author":"Bahmyari","year":"2021","journal-title":"Int. J. Fertil. Steril."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"64","DOI":"10.18565\/urol.2017.2-supplement.64-72","article-title":"Adjuvant antioxidant therapy in varicocele infertility","volume":"2","author":"Gamidov","year":"2017","journal-title":"Urologiia"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Gamidov, S.I., Ovchinnikov, R.I., and Popova, A.Y. (2019). Double-blind, randomized placebo-controlled study of efficiency and safety of complex acetyl-L-carnitine, L-carnitine fumarate and alpha-lipoic acid (Spermactin Forte) for treatment of male infertility. Urologiia, 62\u201368.","DOI":"10.18565\/urology.2019.4.61-68"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"hoaa050","DOI":"10.1093\/hropen\/hoaa050","article-title":"Antioxidant pretreatment for male partner before ART for male factor subfertility: A randomized controlled trial","volume":"2020","author":"Joseph","year":"2020","journal-title":"Hum. Reprod. Open"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e13267","DOI":"10.1111\/and.13267","article-title":"Double-blind, randomised, placebo-controlled trial on the effect of L-carnitine and L-acetylcarnitine on sperm parameters in men with idiopathic oligoasthenozoospermia","volume":"51","author":"Micic","year":"2019","journal-title":"Andrologia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1111\/andr.12547","article-title":"Impact of antioxidant treatment on DNA fragmentation index: A double-blind placebo-controlled randomized trial","volume":"6","author":"Stenqvist","year":"2018","journal-title":"Andrology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.fertnstert.2019.11.008","article-title":"The effect of antioxidants on male factor infertility: The Males, Antioxidants, and Infertility (MOXI) randomized clinical trial","volume":"113","author":"Steiner","year":"2020","journal-title":"Fertil. Steril."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"28","DOI":"10.12793\/tcp.2023.31.e6","article-title":"Impact of antioxidants in improving semen parameters like count, motility and DNA fragmentation in sub-fertile males: A randomized, double-blind, placebo-controlled clinical trial","volume":"31","author":"Patki","year":"2023","journal-title":"Transl. Clin. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1002\/j.1939-4640.1996.tb01830.x","article-title":"Lipid peroxidation and human sperm motility: Protective role of vitamin E","volume":"17","author":"Suleiman","year":"1996","journal-title":"J. Androl."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1159\/000112963","article-title":"Indications of the mechanisms involved in improved sperm parameters by zinc therapy","volume":"17","author":"Omu","year":"2008","journal-title":"Med. Princ. Pract."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1111\/and.12494","article-title":"Association between seminal plasma zinc level and asthenozoospermia: A meta-analysis study","volume":"48","author":"Taravati","year":"2016","journal-title":"Andrologia"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5534\/wjmh.2014.32.1.1","article-title":"Effect of oxidative stress on male reproduction","volume":"32","author":"Agarwal","year":"2014","journal-title":"World J. Mens. Health"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e14062","DOI":"10.1111\/acel.14062","article-title":"Trioxidized cysteine in the aging proteome mimics the structural dynamics and interactome of phosphorylated serine","volume":"23","author":"Guo","year":"2024","journal-title":"Aging Cell"},{"key":"ref_40","first-page":"11484","article-title":"Trioxidized cysteine and aging: A molecular binomial that extends far beyond classical proteinopathic paradigms","volume":"16","author":"Mulet","year":"2024","journal-title":"Aging"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/4\/488\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:17:03Z","timestamp":1760030223000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/4\/488"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,18]]},"references-count":40,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["antiox14040488"],"URL":"https:\/\/doi.org\/10.3390\/antiox14040488","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,18]]}}}