{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:08:36Z","timestamp":1760148516378,"version":"build-2065373602"},"reference-count":43,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T00:00:00Z","timestamp":1683072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>It is widely accepted that extracts of St. John\u2019s wort (Hypericum perforatum) improve depressive symptoms, and tinnitus patients commonly presented with either mild depression or anxiety. We investigated whether co-administration of St. John\u2019s wort and Ginkgo biloba extracts can suppress tinnitus. Participants with subjective tinnitus aged 30\u201370 years were randomly assigned to the experimental (co-administration of St. John\u2019s wort and Ginkgo biloba extract; n = 20) or control (Ginkgo biloba extract only; n = 26) group for 12 weeks. Participants were blinded to the group assignments. After 12 weeks of treatment, no significant change in the minimum masking level on the tinnitogram was observed in either group. In the co-administration group, the Tinnitus Handicap Inventory (THI) score decreased from 34.7 (SD, 15.9) to 29.6 (16.0) (p = 0.102). However, the control group showed a significant decrease in THI score, from 30.5 (16.7) to 25.6 (17.1) (p = 0.046). Regarding the Short Form-36 Health Survey (SF-36), only the \u201cSocial Functioning\u201d domain score changed significantly after extract co-administration, from 74.5 (21.5) to 83.9 (20.5) (p = 0.047). Co-administration of St. John\u2019s wort and Ginkgo biloba extracts did not improve the symptoms of subjective tinnitus compared to administration of Ginkgo biloba extract alone.<\/jats:p>","DOI":"10.3390\/jcm12093261","type":"journal-article","created":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T01:33:36Z","timestamp":1683164016000},"page":"3261","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Efficacy and Safety of Co-Administered St. John\u2019s Wort and Ginkgo biloba Extracts in Patients with Subjective Tinnitus: A Preliminary Prospective Randomized Controlled Trial"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5020-7814","authenticated-orcid":false,"given":"Hantai","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery, Konyang University College of Medicine, Daejeon 35365, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0606-8834","authenticated-orcid":false,"given":"Jungho","family":"Ha","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Ajou University School of Medicine, Suwon 16499, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hun Yi","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Ajou University School of Medicine, Suwon 16499, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun-Hoon","family":"Choung","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Ajou University School of Medicine, Suwon 16499, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeong Hun","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Ajou University School of Medicine, Suwon 16499, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kim, H.J., Lee, H.J., An, S.Y., Sim, S., Park, B., Kim, S.W., Lee, J.S., Hong, S.K., and Choi, H.G. (2015). Analysis of the prevalence and associated risk factors of tinnitus in adults. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0127578"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.amjmed.2010.02.015","article-title":"Prevalence and characteristics of tinnitus among US adults","volume":"123","author":"Shargorodsky","year":"2010","journal-title":"Am. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1001\/jamaoto.2016.1700","article-title":"Prevalence, Severity, Exposures, and Treatment Patterns of Tinnitus in the United States","volume":"142","author":"Bhatt","year":"2016","journal-title":"JAMA Otolaryngol. Head Neck Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"158","DOI":"10.21053\/ceo.2017.01221","article-title":"Relationship Between Diet and Tinnitus: Korea National Health and Nutrition Examination Survey","volume":"11","author":"Lee","year":"2018","journal-title":"Clin. Exp. Otorhinolaryngol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"417","DOI":"10.2188\/jea.JE20140024","article-title":"Prevalence and associated factors of tinnitus: Data from the Korean National Health and Nutrition Examination Survey 2009\u20132011","volume":"24","author":"Park","year":"2014","journal-title":"J. Epidemiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1017\/S1755146300090041","article-title":"Epidemiology of tinnitus: (1) prevalence","volume":"9","author":"Coles","year":"1984","journal-title":"J. Laryngol. Otol. Suppl."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"313","DOI":"10.3766\/jaaa.16154","article-title":"Expectations for Tinnitus Treatment and Outcomes: A Survey Study of Audiologists and Patients","volume":"29","author":"Husain","year":"2018","journal-title":"J. Am. Acad. Audiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/S0079-6123(07)66040-3","article-title":"Tinnitus retraining therapy","volume":"166","author":"Jastreboff","year":"2007","journal-title":"Prog. Brain Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3109\/03005369309077884","article-title":"A neurophysiological approach to tinnitus: Clinical implications","volume":"27","author":"Jastreboff","year":"1993","journal-title":"Br. J. Audiol."},{"key":"ref_10","first-page":"S1","article-title":"Clinical practice guideline: Tinnitus","volume":"151","author":"Tunkel","year":"2014","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.anl.2019.09.007","article-title":"Clinical practice guidelines for diagnosis and treatment of chronic tinnitus in Japan","volume":"47","author":"Ogawa","year":"2020","journal-title":"Auris Nasus Larynx"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1001\/archinternmed.2011.1408","article-title":"Prevalence of hearing aid use among older adults in the United States","volume":"172","author":"Chien","year":"2012","journal-title":"Arch. Intern. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e1580","DOI":"10.1097\/MD.0000000000001580","article-title":"Hearing Aid Use and Associated Factors in South Korea","volume":"94","author":"Moon","year":"2015","journal-title":"Medicine"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kim, S.H., Kim, D., Lee, J.M., Lee, S.K., Kang, H.J., and Yeo, S.G. (2021). Review of Pharmacotherapy for Tinnitus. Healthcare, 9.","DOI":"10.3390\/healthcare9060779"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1002\/lary.26107","article-title":"Relationships between tinnitus and the prevalence of anxiety and depression","volume":"127","author":"Bhatt","year":"2017","journal-title":"Laryngoscope"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"489","DOI":"10.3109\/15622975.2011.575178","article-title":"Tinnitus and depression","volume":"12","author":"Langguth","year":"2011","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Choi, J., Lee, C.H., and Kim, S.Y. (2021). Association of Tinnitus with Depression in a Normal Hearing Population. Medicina, 57.","DOI":"10.3390\/medicina57020114"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1001\/archinte.1993.00410190091011","article-title":"A randomized trial of nortriptyline for severe chronic tinnitus. Effects on depression, disability, and tinnitus symptoms","volume":"153","author":"Sullivan","year":"1993","journal-title":"Arch. Intern. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1177\/000348948809700204","article-title":"The tricyclic trimipramine in the treatment of subjective tinnitus","volume":"97","author":"Mihail","year":"1988","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1097\/01.jcp.0000195111.86650.19","article-title":"The effects of sertraline on severe tinnitus suffering--a randomized, double-blind, placebo-controlled study","volume":"26","author":"Svedlund","year":"2006","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/S1808-8694(15)30084-7","article-title":"Tinnitus treatment with Trazodone","volume":"73","author":"Dib","year":"2007","journal-title":"Braz. J. Otorhinolaryngol."},{"key":"ref_22","first-page":"CD003853","article-title":"Antidepressants for patients with tinnitus","volume":"2012","author":"Baldo","year":"2012","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_23","first-page":"157","article-title":"Ginkgo special extract EGb 761 in tinnitus therapy. An overview of results of completed clinical trials","volume":"118","author":"Holstein","year":"2001","journal-title":"Fortschr. Med. Orig."},{"key":"ref_24","first-page":"441","article-title":"Ginkgo biloba extract in the treatment of tinnitus: A systematic review","volume":"7","year":"2011","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1111\/j.1365-2273.2004.00814.x","article-title":"Ginkgo biloba does not benefit patients with tinnitus: A randomized placebo-controlled double-blind trial and meta-analysis of randomized trials","volume":"29","author":"Rejali","year":"2004","journal-title":"Clin. Otolaryngol. Allied Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1186\/s13643-016-0325-2","article-title":"A systematic review of St. John\u2019s wort for major depressive disorder","volume":"5","author":"Apaydin","year":"2016","journal-title":"Syst. Rev."},{"key":"ref_27","first-page":"CD000448","article-title":"St John\u2019s wort for major depression","volume":"2008","author":"Linde","year":"2008","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ctim.2019.05.028","article-title":"The effect of Hypericum perforatum on postmenopausal symptoms and depression: A randomized controlled trial","volume":"45","author":"Eatemadnia","year":"2019","journal-title":"Complement Ther. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1097\/gme.0b013e3181b8e02d","article-title":"Effect of St John\u2019s wort on severity, frequency, and duration of hot flashes in premenopausal, perimenopausal and postmenopausal women: A randomized, double-blind, placebo-controlled study","volume":"17","author":"Abdali","year":"2010","journal-title":"Menopause"},{"key":"ref_30","first-page":"e29468","article-title":"Advantages and Disadvantages of Using St. John\u2019s Wort as a Treatment for Depression","volume":"14","author":"Hernandez","year":"2022","journal-title":"Cureus"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"117","DOI":"10.5935\/0946-5448.20120022","article-title":"Development and standardization of tinnitus handicap inventory in Kannada","volume":"17","author":"Zacharia","year":"2012","journal-title":"Int. Tinnitus J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.jpsychores.2012.04.015","article-title":"Screening for anxiety and depression in dialysis patients: Comparison of the Hospital Anxiety and Depression Scale and the Beck Depression Inventory","volume":"73","author":"Preljevic","year":"2012","journal-title":"J. Psychosom. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1007\/s00405-021-07092-x","article-title":"Prevalence of sleep impairment in patients with tinnitus: A systematic review and single-arm meta-analysis","volume":"279","author":"Gu","year":"2022","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1136\/bmj.305.6846.160","article-title":"Validating the SF-36 health survey questionnaire: New outcome measure for primary care","volume":"305","author":"Brazier","year":"1992","journal-title":"BMJ"},{"key":"ref_35","first-page":"24","article-title":"Pharmacology of benzodiazepine receptors: An update","volume":"19","author":"Sieghart","year":"1994","journal-title":"J. Psychiatry Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1001\/archotol.1993.01880200042006","article-title":"Use of alprazolam for relief of tinnitus. A double-blind study","volume":"119","author":"Johnson","year":"1993","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_37","first-page":"PI55","article-title":"The effects of alprazolam on tinnitus: A cross-over randomized clinical trial","volume":"15","author":"Jalali","year":"2009","journal-title":"Med. Sci. Monit."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1017\/S0022215115000808","article-title":"The use of benzodiazepines for tinnitus: Systematic review","volume":"129","author":"Jufas","year":"2015","journal-title":"J. Laryngol. Otol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.anl.2020.01.005","article-title":"Typewriter tinnitus: An investigative comparison with middle ear myoclonic tinnitus and its long-term therapeutic response to carbamazepine","volume":"47","author":"Han","year":"2020","journal-title":"Auris Nasus Larynx"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1001\/archotol.133.4.390","article-title":"Relief of idiopathic subjective tinnitus: Is gabapentin effective?","volume":"133","author":"Piccirillo","year":"2007","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1097\/01.MLG.0000216812.65206.CD","article-title":"Effect of gabapentin on the sensation and impact of tinnitus","volume":"116","author":"Bauer","year":"2006","journal-title":"Laryngoscope"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1177\/0003489420930773","article-title":"Impact of Acamprosate on Chronic Tinnitus: A Randomized-Controlled Trial","volume":"129","author":"Farhadi","year":"2020","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"48","DOI":"10.5213\/jkcs.2008.12.1.48","article-title":"Recognitional study about patients and caregivers\u2019 understanding of clinical trial","volume":"12","author":"Kim","year":"2008","journal-title":"J. Korean Cont. Soc."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/9\/3261\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:28:40Z","timestamp":1760124520000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/9\/3261"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,3]]},"references-count":43,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["jcm12093261"],"URL":"https:\/\/doi.org\/10.3390\/jcm12093261","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2023,5,3]]}}}