A Multi-Compound Nutraceutical Formulation for Tinnitus Management: A Retrospective Observational Study
Abstract
Tinnitus is a multifactorial condition with limited effective treatment options. Natural compounds have been proposed to modulate molecular pathways potentially involved in its pathophysiology, although clinical evidence remains preliminary. This retrospective observational study, conducted without a control group, evaluated 92 patients receiving a multi-compound nutraceutical (4 capsules/day) containing Auricularia auricula-judae, Curcuma longa, Hericium erinaceus, Ganoderma lucidum, Berberis aristata, and Rosa canina. Tinnitus severity was assessed using the Tinnitus Handicap Inventory (THI) at baseline (T0), 1.5 months (T1), and 3 months (T2). Concurrently, hearing thresholds were evaluated at T0 and T2. Patients were stratified into secondary (Group A; N = 48) and primary (Group B; N = 44) tinnitus. THI scores decreased significantly in both groups over time (p < 0.001), with more than 90% of patients showing improvement. A shift toward lower severity grades was observed, with a reduction in moderate-to-catastrophic tinnitus. A decline in tinnitus grade occurred in 29% of patients, with no cases of worsening. At T2, approximately 30% of patients achieved a clinically relevant improvement (>7-point THI reduction). Hearing thresholds remained stable in both groups. A modest correlation between THI and dB variation was observed in Group A at T2 (r = 0.346; p < 0.05), although this exploratory finding should be interpreted with caution. These preliminary, hypothesis-generating findings suggest that the nutraceutical may represent a supportive option for tinnitus management, particularly in mild-to-moderate cases, with potential benefits for quality of life. However, given the retrospective, uncontrolled design of this study, randomized controlled trials are warranted to confirm these preliminary findings.
Keywords
References
- 1. Haider, H.F.; Ribeiro, D.; Ribeiro, S.F.; et al. Audiological Biomarkers of Tinnitus in an Older Portuguese Population. Front. Aging Neurosci. 2022, 14, 933117. DOI: https://doi.org/10.3389/fnagi.2022.933117
- 2. Tunkel, D.E.; Bauer, C.A.; Sun, G.H.; et al. Clinical Practice Guideline: Tinnitus. Otolaryngol. Head Neck Surg. 2014, 151, S1–S40. DOI: https://doi.org/10.1177/0194599814545325
- 3. Vijayakumar, K.A.; Cho, G.-W.; Maharajan, N.; et al. A Review on Peripheral Tinnitus, Causes, and Treatments from the Perspective of Autophagy. Exp. Neurobiol. 2022, 31, 232–242. DOI: https://doi.org/10.5607/en22002
- 4. Hofmeister, M. Do Dietary Factors Significantly Influence Tinnitus? Aust. J. Gen. Pract. 2019, 48, 153–157. DOI: https://doi.org/10.31128/AJGP-07-18-4643
- 5. Soni, A.; Dubey, A. Chronic Primary Tinnitus: A Management Dilemma. Audiology Research 2020, 10, 55–66. DOI: https://doi.org/10.3390/audiolres10020010
- 6. Abo-Ollo, E.M.; Assal, S.I.; Abdelmotaleb, H.I. Evaluation of Cochlear Function, Hidden Hearing Loss, and Auditory Temporal Processing in Tinnitus Patients with Normal Audiograms. Acta Otorrinolaringol. Engl. Ed. 2026, 512372. DOI: https://doi.org/10.1016/j.otoeng.2026.512372
- 7. Henshaw, H.; Calvert, S.; Heffernan, E.; et al. New Horizons in Hearing Conditions. Age Ageing 2023, 52, afad150. DOI: https://doi.org/10.1093/ageing/afad150
- 8. Kim, S.H.; Kim, D.; Lee, J.-M.; et al. Review of Pharmacotherapy for Tinnitus. Healthcare 2021, 9, 779. DOI: https://doi.org/10.3390/healthcare9060779
- 9. Abtahi, S.; Hashemi, S.; Mahmoodi, M.; et al. Comparison of Melatonin and Sertraline Therapies on Tinnitus: A Randomized Clinical Trial. Int. J. Prev. Med. 2017, 8, 61. DOI: https://doi.org/10.4103/ijpvm.IJPVM_229_17
- 10. von Boetticher, A. Ginkgo Biloba Extract in the Treatment of Tinnitus: A Systematic Review. Neuropsychiatr. Dis. Treat. 2011, 7, 441–447. DOI: https://doi.org/10.2147/NDT.S22793
- 11. Enrico, P.; Sirca, D.; Mereu, M. Antioxidants, Minerals, Vitamins, and Herbal Remedies in Tinnitus Therapy. Prog. Brain Res. 2007, 166, 323–330. DOI: https://doi.org/10.1016/s0079-6123(07)66029-4
- 12. Li, N.; Yan, X.; Huang, W.; et al. Curcumin Protects against the Age-Related Hearing Loss by Attenuating Apoptosis and Senescence via Activating Nrf2 Signaling in Cochlear Hair Cells. Biochem. Pharmacol. 2023, 212, 115575. DOI: https://doi.org/10.1016/j.bcp.2023.115575
- 13. Kim, Y.-R.; Baek, J.-I.; Lee, K.-Y.; et al. Berberine Chloride Protects Cochlear Hair Cells from Aminoglycoside-Induced Ototoxicity by Reducing the Accumulation of Mitochondrial Reactive Oxygen Species. Free Radic. Biol. Med. 2023, 204, 177–183. DOI: https://doi.org/10.1016/j.freeradbiomed.2023.04.017
- 14. Haryuna, T.S.H.; Riawan, W.; Nasution, A.; et al. Curcumin Reduces the Noise-Exposed Cochlear Fibroblasts Apoptosis. Int. Arch. Otorhinolaryngol. 2016, 20, 370–376. DOI: https://doi.org/10.1055/s-0036-1579742
- 15. Kim, J.-H.; Baek, J.-I.; Lee, I.-K.; et al. Protective Effect of Berberine Chloride against Cisplatin-Induced Ototoxicity. Genes Genom. 2022, 44, 1–7. DOI: https://doi.org/10.1007/s13258-021-01157-1
- 16. Shevelev, O.B.; Seryapina, A.A.; Zavjalov, E.L.; et al. Hypotensive and Neurometabolic Effects of Intragastric Reishi (Ganoderma Lucidum) Administration in Hypertensive ISIAH Rat Strain. Phytomedicine 2018, 41, 1–6. DOI: https://doi.org/10.1016/j.phymed.2018.01.013
- 17. Bell, V.; Fernandes, T.H. Mushrooms as Functional Foods for Ménière’s Disease. Appl. Sci. 2023, 13, 12348. DOI: https://doi.org/10.3390/app132212348
- 18. Shevchuk, Y.; Kuypers, K.; Janssens, G.E. Fungi as a Source of Bioactive Molecules for the Development of Longevity Medicines. Ageing Res. Rev. 2023, 87, 101929. DOI: https://doi.org/10.1016/j.arr.2023.101929
- 19. Bian, C.; Ji, L.; Qu, H.; et al. A Novel Polysaccharide from Auricularia Auricula Alleviates Thrombosis Induced by Carrageenan in Mice. Molecules 2022, 27, 4831. DOI: https://doi.org/10.3390/molecules27154831
- 20. Brandalise, F.; Roda, E.; Ratto, D.; et al. Hericium Erinaceus in Neurodegenerative Diseases: From Bench to Bedside and Beyond, How Far from the Shoreline? J. Fungi 2023, 9, 551. DOI: https://doi.org/10.3390/jof9050551
- 21. Monzani, D.; Genovese, E.; Marrara, A.; et al. Validity of the Italian Adaptation of the Tinnitus Handicap Inventory; Focus on Quality of Life and Psychological Distress in Tinnitus-Sufferers. Acta Otorhinolaryngol. Ital. 2008, 28, 126–134.
- 22. Newman, C.W.; Jacobson, G.P.; Spitzer, J.B. Development of the Tinnitus Handicap Inventory. Arch. Otolaryngol. Head Neck Surg. 1996, 122, 143–148. DOI: https://doi.org/10.1001/archotol.1996.01890140029007
- 23. Steinmetz, L.G.; Zeigelboim, B.S.; Lacerda, A.B.; et al. The Characteristics of Tinnitus in Workers Exposed to Noise. Braz. J. Otorhinolaryngol. 2009, 75, 7–14. DOI: https://doi.org/10.1016/S1808-8694(15)30825-9
- 24. Van Den Borne, S.; Snik, A.F.M.; Hoekstra, C.C.; et al. Assessment of Basal Sound Identification Skills and Communication Abilities in Profoundly Deaf Children Fitted with Hearing Aids or a Cochlear Implant. Clin. Otolaryngol. 1998, 23, 455–461. DOI: https://doi.org/10.1046/j.1365-2273.1998.00180.x
- 25. De Ridder, D.; Kleinjung, T.; Song, J.-J.; et al. Tinnitus and Tinnitus Disorder: Genetic, Neurobiological, and Clinical Differentiation. iScience 2026, 29, 116080. DOI: https://doi.org/10.1016/j.isci.2026.116080
- 26. Salvi, R.; Lobarinas, E.; Sun, W. Pharmacological Treatments for Tinnitus: New and Old. Drugs Fut. 2009, 34, 381. DOI: https://doi.org/10.1358/dof.2009.34.5.1362442
- 27. Curhan, S.G.; Zeleznik, O.A.; Curhan, G.C. Longitudinal Study of Seafood and Fish Oil Supplement Intake and Risk of Persistent Tinnitus. Am. J. Clin. Nutr. 2024, 120, 1409–1418. DOI: https://doi.org/10.1016/j.ajcnut.2024.09.028
- 28. Klimas, M.; Jucha, D.; Krupa-Nurcek, S. Nutritional Strategies and Dietary Patterns in Ménière’s Disease and Tinnitus: A Scoping Review of the Available Evidence. Nutrients 2026, 18, 2102. DOI: https://doi.org/10.3390/nu18132102
- 29. Shen, X.; Yang, M.; Tian, J.; et al. Clinical Efficacy of Vitamin D Combined with Conventional Therapy for Sudden Sensorineural Hearing Loss in Patients with Vitamin D Deficiency: A Randomized Controlled Trial. Head Face Med. 2025, 21, 68. DOI: https://doi.org/10.1186/s13005-025-00545-2
- 30. Kalentakis, Z.; Feretzakis, G.; Baxevani, G.; et al. The Efficacy of a Food Supplement in the Treatment of Tinnitus with Comorbid Headache: A Statistical and Machine Learning Analysis with a Literature Review. Audiol. Neurotol. 2024, 1–12. DOI: https://doi.org/10.1159/000541842
- 31. Zeman, F.; Koller, M.; Figueiredo, R.; et al. Tinnitus Handicap Inventory for Evaluating Treatment Effects: Which Changes Are Clinically Relevant? Otolaryngol. Head Neck Surg. 2011, 145, 282–287. DOI: https://doi.org/10.1177/0194599811403882
- 32. Knäpper, J.; Girauta, M.V.; Coromina, J. Effectiveness of Tinnitan Duo® in Subjective Tinnitus with Emotional Affectation: A Prospective, Interventional Study. J. Diet. Suppl. 2023, 20, 1–14. DOI: https://doi.org/10.1080/19390211.2021.1944947
- 33. König, O.; Schaette, R.; Kempter, R.; et al. Course of Hearing Loss and Occurrence of Tinnitus. Hear. Res. 2006, 221, 59–64. DOI: https://doi.org/10.1016/j.heares.2006.07.007
- 34. Moore, B.C.J.; Vinay; Sandhya. The Relationship between Tinnitus Pitch and the Edge Frequency of the Audiogram in Individuals with Hearing Impairment and Tonal Tinnitus. Hear. Res. 2010, 261, 51–56. DOI: https://doi.org/10.1016/j.heares.2010.01.003
- 35. Shekhawat, G.S.; Searchfield, G.D.; Stinear, C.M. The Relationship between Tinnitus Pitch and Hearing Sensitivity. Eur. Arch. Otorhinolaryngol. 2014, 271, 41–48. DOI: https://doi.org/10.1007/s00405-013-2375-6
- 36. Pan, T.; Tyler, R.S.; Ji, H.; et al. The Relationship between Tinnitus Pitch and the Audiogram. Int. J. Audiol. 2009, 48, 277–294. DOI: https://doi.org/10.1080/14992020802581974
- 37. Lazzeri, G.; Biagioni, F.; Ferrucci, M.; et al. The Relevance of Autophagy within Inner Ear in Baseline Conditions and Tinnitus-Related Syndromes. Int. J. Mol. Sci. 2023, 24, 16664. DOI: https://doi.org/10.3390/ijms242316664
- 38. Haider, H.F.; Bojić, T.; Ribeiro, S.F.; et al. Pathophysiology of Subjective Tinnitus: Triggers and Maintenance. Front. Neurosci. 2018, 12, 866. DOI: https://doi.org/10.3389/fnins.2018.00866
- 39. Salvi, R.; Sun, W.; Ding, D.; et al. Inner Hair Cell Loss Disrupts Hearing and Cochlear Function Leading to Sensory Deprivation and Enhanced Central Auditory Gain. Front. Neurosci. 2017, 10, 621. DOI: https://doi.org/10.3389/fnins.2016.00621
- 40. Yamaguchi, T.; Yoneyama, M.; Onaka, Y.; et al. Preventive Effect of Curcumin and Its Highly Bioavailable Preparation on Hearing Loss Induced by Single or Repeated Exposure to Noise: A Comparative and Mechanistic Study. J. Pharmacol. Sci. 2017, 134, 225–233. DOI: https://doi.org/10.1016/j.jphs.2017.07.003
- 41. Fan, C.; Pacier, C.; Martirosyan, D.M. Rose Hip (Rosa Canina L.): A Functional Food Perspective. Funct. Foods Health Dis. 2014, 4, 493. DOI: https://doi.org/10.31989/ffhd.v4i12.159
- 42. Khosravi, M.H.; Atefi, A.; Mehri, 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, 151–157. DOI: https://doi.org/10.1111/coa.13989
- 43. Mori, K.; Kikuchi, H.; Obara, Y.; et al. Inhibitory Effect of Hericenone B from Hericium Erinaceus on Collagen-Induced Platelet Aggregation. Phytomedicine 2010, 17, 1082–1085. DOI: https://doi.org/10.1016/j.phymed.2010.05.004