Effects of Plant Extract and Dietary Supplements on Tinnitus Perception in Adults: A Systematic Review and Meta-Analysis
DOI:
https://doi.org/10.14306/renhyd.28.1.2308Keywords:
Tinnitus, Dietary Supplements, Melatonin, Plant Extract, Randomized Controlled TrialsAbstract
Introduction. Tinnitus, the perception of sound without an external source, affects millions worldwide and significantly impacts the health-related quality of life (HRQoL). Despite various management strategies, no universally effective treatment exists. While tinnitus sufferers frequently use dietary supplements, their efficacy remains unclear. This systematic review and meta-analysis evaluated the effectiveness of plant extracts and dietary supplements in treating tinnitus symptoms.
Methods. We conducted a systematic search in PubMed for randomized controlled trials (RCTs) and crossover trials comparing plant extracts and dietary supplements with placebo or control groups in adults with tinnitus. Selection criteria included patients with subjective tinnitus and studies examining plant extracts or dietary supplements. Using a random-effects model, we estimated standardized mean differences and odds ratios with 95% confidence intervals (95% CIs). Study quality was assessed using the Revised Cochrane risk-of-bias tool for randomized trials. Protocol registered on PROSPERO (CRD42023446824).
Results. Twenty-one studies involving 1,759 participants evaluated four plant extracts and six dietary supplements. Five trials investigated plant extracts (Euterpe oleracea, traditional herbal medicine Hangekobokuto, Neurotec, and caffeine), while sixteen studies examined dietary supplements (melatonin, zinc, alpha-lipoic acid, manganese, vitamin B complex, and nicotinamide). Meta-analysis revealed no significant efficacy for caffeine in reducing tinnitus impact on HRQoL (SMD=0.07; 95% CI: -0.73 to 0.86; I²=0.0%). However, melatonin showed a modest reduction in tinnitus loudness compared to placebo (OR=2.52; 95% CI: 1.33-4.80; k=2, 168 participants).
Conclusions. Among the studied interventions, only melatonin showed modest efficacy in reducing tinnitus loudness, though evidence remains uncertain due to methodological limitations. Further high-quality RCTs with larger samples, standardized outcome measures, and long-term follow-up are necessary to confirm these findings and explore melatonin’s potential role in tinnitus management.
References
(1) Langguth B, De Ridder D, Schlee W, Kleinjung T. Tinnitus: Clinical Insights in Its Pathophysiology-A Perspective. J Assoc Res Otolaryngol. 2024;25(3):249-58, doi: 10.1007/s10162-024-00939-0.
(2) Jarach CM, Lugo A, Scala M, van den Brandt PA, Cederroth CR, Odone A, et al. Global Prevalence and Incidence of Tinnitus: A Systematic Review and Meta-analysis. JAMA Neurol. 2022;79(9):888-900, doi: 10.1001/jamaneurol.2022.2189.
(3) Cima RFF, Mazurek B, Haider H, Kikidis D, Lapira A, Noreña A, et al. A multidisciplinary European guideline for tinnitus: diagnostics, assessment, and treatment. Hno. 2019;67(1):10-42.
(4) Cederroth CR, Gallus S, Hall DA, Kleinjung T, Langguth B, Maruotti A, et al. Editorial: Towards an Understanding of Tinnitus Heterogeneity. Front Aging Neurosci. 2019;11.
(5) Bhatt JM, Lin HW, Bhattacharyya N. Prevalence, Severity, Exposures, and Treatment Patterns of Tinnitus in the United States. JAMA Otolaryngol Neck Surg. 2016;142(10):959-65, doi: 10.1001/jamaoto.2016.1700.
(6) Hall DA, Haider H, Szczepek AJ, Lau P, Rabau S, Jones-Diette J, et al. Systematic review of outcome domains and instruments used in clinical trials of tinnitus treatments in adults. Trials. 2016;17(1):270, doi: 10.1186/s13063-016-1399-9.
(7) Okayasu T, Mitani K, Kitahara T. Reviewing Kampo medicine (Traditional Japanese Herbal Medicine) for otology/neurotology diseases. Auris Nasus Larynx. 2024;51(1):25-30, doi: 10.1016/j.anl.2023.04.009.
(8) Lee HY, Jung DJ. Recent Updates on Tinnitus Management. J Audiol Otol. 2023;27(4):181-92, doi: 10.7874/jao.2023.00416.
(9) Coelho C, Tyler R, Ji H, Rojas-Roncancio E, Witt S, Tao P, et al. Survey on the Effectiveness of Dietary Supplements to Treat Tinnitus. Am J Audiol. 2016;25(3):184-205, doi: 10.1044/2016_AJA-16-0021.
(10) Alonso Street EM, Grutzmacher S, Branscum A, Smit E. Self-Perceived Health and Chronic Conditions Among Users of Supplements With and Without Botanical Ingredients: Findings from the 2009–2014 National Health and Nutrition Examination Survey. J Diet Suppl. 2022;19(6):689-703.
(11) Sereda M, Xia J, Scutt P, Hilton MP, El Refaie A, Hoare DJ. Ginkgo biloba for tinnitus. Cochrane Database Syst Rev. 2022;2023(1), doi: 10.1002/14651858.CD013514.pub2.
(12) Miroddi M, Bruno R, Galletti F, Calapai F, Navarra M, Gangemi S, et al. Clinical pharmacology of melatonin in the treatment of tinnitus: a review. Eur J Clin Pharmacol. 2015;71(3):263-70, doi: 10.1007/s00228-015-1805-3.
(13) Person OC, Puga ME, da Silva EM, Torloni MR. Zinc supplementation for tinnitus. Cochrane Database Syst Rev. 2016;2016(11), doi: 10.1002/14651858.CD009832.pub2.
(14) Hulshof JH, Vermeij P. The effect of nicotinamide on tinnitus: a double-blind controlled study. Clin Otolaryngol. 1987;12(3):211-4, doi: 10.1111/j.1365-2273.1987.tb00189.x.
(15) Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015;349(jan02 1):g7647-g7647, doi: 10.1136/bmj.g7647.
(16) Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019:l4898, doi: 10.1136/bmj.l4898.
(17) Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. Bmj. 2003;327(7414):557-60.
(18) Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629-34, doi: 10.1136/bmj.315.7109.629.
(19) Guyatt GH, Oxman AD, Kunz R, Brozek J, Alonso-Coello P, Rind D, et al. GRADE guidelines 6. Rating the quality of evidence—imprecision. J Clin Epidemiol. 2011;64(12):1283-93.
(20) Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. Cochrane Handbook for Systematic Reviews of Interventions. 2nd ed. Newark: John Wiley & Sons, Incorporated; 2019.
(21) Coelho C, Witt SA, Ji H, Hansen MR, Gantz B, Tyler R. Zinc to Treat Tinnitus in the Elderly: A Randomized Placebo Controlled Crossover Trial. 2013;34(6).
(22) Hurtuk A, Dome C, Holloman CH, Wolfe K, Welling DB, Dodson EE, et al. Melatonin: Can it Stop the Ringing? Ann Otol Rhinol Laryngol. 2011;120(7):433-40, doi: 10.1177/000348941112000703.
(23) Rojas-Roncancio E, Tyler R, Jun H-J, Wang T-C, Ji H, Coelho C, et al. Manganese and Lipoflavonoid Plus® to Treat Tinnitus: A Randomized Controlled Trial. J Am Acad Audiol. 2016;27(08):661-8, doi: 10.3766/jaaa.15106.
(24) Rosenberg SI, Silverstein H, Rowan PT, Olds MJ. Effect of Melatonin on Tinnitus. The Laryngoscope. 1998;108(3):305-10, doi: 10.1097/00005537-199803000-00001.
(25) Oppitz SJ, Garcia MV, Bruno RS, Zemolin CM, Baptista BO, Turra BO, et al. Supplementation with açaí (Euterpe Oleracea Martius) for the treatment of chronic tinnitus: effects on perception, anxiety levels and oxidative metabolism biomarkers. CoDAS. 2022;34(4):e20210076, doi: 10.1590/2317-1782/20212021076.
(26) Ledesma ALL, Leite Rodrigues D, Monteiro De Castro Silva I, Oliveira CA, Bahmad F. The effect of caffeine on tinnitus: Randomized triple-blind placebo-controlled clinical trial. PLOS ONE. 2021;16(9):e0256275, doi: 10.1371/journal.pone.0256275.
(27) Claire LSt, Stothart G, McKenna L, Rogers PJ. Caffeine abstinence: an ineffective and potentially distressing tinnitus therapy. Int J Audiol. 2010;49(1):24-9, doi: 10.3109/14992020903160884.
(28) Markou K, Nikolaou A, Petridis DG, Vlachtsis KC, Kouloulas A, Daniilidis IC. Evaluation of various therapeutic schemes in the treatment of tinnitus due to acute acoustic trauma. Kulak Burun Bogaz Ihtis Derg KBB J Ear Nose Throat. 2004;12(5-6):107-14.
(29) Petridou AI, Zagora ET, Petridis P, Korres GS, Gazouli M, Xenelis I, et al. The Effect of Antioxidant Supplementation in Patients with Tinnitus and Normal Hearing or Hearing Loss: A Randomized, Double-Blind, Placebo Controlled Trial. Nutrients. 2019;11(12):3037, doi: 10.3390/nu11123037.
(30) Balatsouras DG, Papitsi I, Koukoutsis G, Katotomichelakis M. The effect of MemoVigor 2 on recent-onset idiopathic tinnitus: a randomized double-blind placebo-controlled clinical trial. Front Pharmacol. 2024;15:1252343, doi: 10.3389/fphar.2024.1252343.
(31) Lopez-Gonzalez MA, Santiago AM, Esteban-Ortega F. Sulpiride and Melatonin Decrease Tinnitus Perception Modulating the Auditolimbic Dopaminergic Pathway. J Otolaryngol. 2007;36(04):213, doi: 10.2310/7070.2007.0018.
(32) Paaske PB, Kjems G, Pedersen CB, Sam ILK. Zinc in the Management of Tinnitus: Placebo-Controlled Trial. Ann Otol Rhinol Laryngol. 1991;100(8):647-9, doi: 10.1177/000348949110000809.
(33) Neri G, De Stefano A, Baffa C, Kulamarva G, Di Giovanni P, Petrucci G, et al. Treatment of central and sensorineural tinnitus with orally administered Melatonin and Sulodexide: personal experience from a randomized controlled study. Acta Otorhinolaryngol Ital Organo Uff Della Soc Ital Otorinolaringol E Chir Cerv-Facc. 2009;29(2):86-91.
(34) Albu S, Chirtes F. Intratympanic dexamethasone plus melatonin versus melatonin only in the treatment of unilateral acute idiopathic tinnitus. Am J Otolaryngol. 2014;35(5):617-22, doi: 10.1016/j.amjoto.2014.06.009.
(35) Arda HN, Tuncel U, Akdogan O, Ozluoglu LN. The Role of Zinc in the Treatment of Tinnitus: Otol Neurotol. 2003;24(1):86-9, doi: 10.1097/00129492-200301000-00018.
(36) Abtahi S, Hashemi S, Mahmoodi M, Nilforoush M. Comparison of melatonin and sertraline therapies on tinnitus: A randomized clinical trial. Int J Prev Med. 2017;8(1):61, doi: 10.4103/ijpvm.IJPVM_229_17.
(37) Khosravi MH, Atefi A, Mehri A, Sodeifian F, Yousefi J, Bagheri Hagh A, et al. Therapeutic effects of Rosa canina, Urtica dioica and Tanacetum vulgare herbal combination in treatment of tinnitus symptoms: A double‐blind randomised clinical trial. Clin Otolaryngol. 2023;48(2):151-7, doi: 10.1111/coa.13989.
(38) Dadgarnia M, Mandegari M, Zand V, Vaziribozorg S, Zare-Zardini H, Mousaviyazdi K, et al. The effect of vitamin B12 on idiopathic tinnitus. Am J Otolaryngol. 2024;45(1):104028, doi: 10.1016/j.amjoto.2023.104028.
(39) Singh C, Kawatra R, Gupta J, Awasthi V, Dungana H. Therapeutic role of Vitamin B12 in patients of chronic tinnitus: A pilot study. Noise Health. 2016;18(81):93-7, doi: 10.4103/1463-1741.178485.
(40) Ino T, Odaguchi H, Wakasugi A, Oikawa T, Sano H, Okamoto M, et al. A randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy of hangekobokuto in adult patients with chronic tinnitus. J Tradit Med. 2013;30(2):72-81, doi: 10.11339/jtm.30.72.
(41) Minich DM, Henning M, Darley C, Fahoum M, Schuler CB, Frame J. Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements. Nutrients. 2022;14(19):3934, doi: 10.3390/nu14193934.
(42) Chen J-J, Chen Y-W, Zeng B-Y, Hung C-M, Zeng B-S, Stubbs B, et al. Efficacy of pharmacologic treatment in tinnitus patients without specific or treatable origin: A network meta-analysis of randomised controlled trials. EClinicalMedicine. 2021;39:101080, doi: 10.1016/j.eclinm.2021.101080.
(43) Hofmeister M. Do dietary factors significantly influence tinnitus? Aust J Gen Pract. 2019;48(3):153-7, doi: 10.31128/AJGP-07-18-4643.
(44) DiSogra RM, O’Brien-Russo CA, Deshpande AK. Dietary Supplements, Essential Oils, and Cannabinoids for Tinnitus Relief. Tinnitus: Advances in Prevention, Assessment, and Management. San Diego, CA: Plural Publishing; 2022. p. 247-60.
(45) Meijers S, Stegeman I, Van Der Leun JA, Assegaf SA, Smit AL. Analysis and comparison of clinical practice guidelines regarding treatment recommendations for chronic tinnitus in adults: a systematic review. BMJ Open. 2023;13(9):e072754, doi: 10.1136/bmjopen-2023-072754.
(46) Ashan SF, Tyler RS. Use of Supplements for Management of Bothersome Subjective Tinnitus. 2019.
(47) Genitsaridi E, Hoare DJ, Kypraios T, Hall DA. A Review and a Framework of Variables for Defining and Characterizing Tinnitus Subphenotypes. Brain Sci. 2020;10(12):938, doi: 10.3390/brainsci10120938.
(48) Simoes JP, Schoisswohl S, Schlee W, Basso L, Bernal-Robledano A, Boecking B, et al. The statistical analysis plan for the unification of treatments and interventions for tinnitus patients randomized clinical trial (UNITI-RCT). Trials. 2023;24(1):472, doi: 10.1186/s13063-023-07303-2.
(49) Biswas R, Genitsaridi E, Trpchevska N, Lugo A, Schlee W, Cederroth CR, et al. Low Evidence for Tinnitus Risk Factors: A Systematic Review and Meta-analysis. J Assoc Res Otolaryngol. 2022;24(1):81-94, doi: 10.1007/s10162-022-00874-y.
(50) Bromis K, Sarafidis M, Manta O, Kouris I, Vellidou E, Schlee W, et al. Predicting the optimal therapeutic intervention for tinnitus patients using random forest regression: A preliminary study of UNITI’s decision support system model. 2022 44th Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC). IEEE; 2022. p. 2655-8.
(51) De Gruy JA, Laurenzo WW, Vu T-H, Paul O, Lee C, Spankovich C. Prevalence and predictors of problematic tinnitus. Int J Audiol. 2024:1-7, doi: 10.1080/14992027.2024.2378804.
Downloads
Additional Files
Published
How to Cite
Issue
Section
License
Copyright (c) 2020 Yordanis Enriquez Canto, Giovani Díaz Gervasi, Luis Menacho Alvirio, Rafael Pizarro Mena
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
This journal 