By Marcello Cherchi, MD PhD
For patients
Medications and foods with anti-oxidant properties are supposed to help with a chemical process called “oxidative stress” that may have to do with some diseases, including diseases that cause disequilibrium and ear symptoms. Anti-oxidants to not seem to be risky, but we do not yet know whether they really help with these diseases.
For clinicians
Overview
Reactive oxygen species (ROS) are the most commonly occurring type of free radical in biological systems. Abnormal accumulation of ROS leads to “oxidative stress” which can result in cellular damage, leading to various disease states. There is modest evidence that oxidative stress may contribute to several otoneurological conditions (such as sudden sensorineural hearing loss, idiopathic tinnitus, benign paroxysmal positional vertigo, Ménière’s disease). While it seems logical to attempt treatment of these conditions with anti-oxidants, convincing evidence of any efficacy is lacking.
Introduction
In chemistry the term “free radical” refers to an atom or compound with unpaired valence electrons, which makes them unstable, imparting a tendency to interact with other molecules. In biological systems the most common free radicals are reactive oxygen species (ROS); these are natural byproducts of various cellular metabolic processes, and can be naturally disposed of in healthy biological states. However, if reactive oxygen species are produced in unusually high quantities, or inadequately disposed of, then their abnormal accumulation (referred to as “oxidative stress”) can result in damage to proteins, cellular DNA and other compounds, resulting in cellular structural and functional deterioration which may predispose to various disease states.
Pharmacology
Some endogenous substances (chemicals naturally produced by the body) and exogenous substances (drugs, vitamins, etc.) function as free radical scavengers and thus are sometimes referred to as “anti-oxidants.”
Adverse effects, cautions and contraindications
Anti-oxidants appear to be low risk.
Relevance in otoneurology
Various anti-oxidants have been studied in the management of several otoneurological conditions.
Vitamin E, which has anti-oxidant properties, has been studied in the treatment of idiopathic sudden sensorineural hearing loss (Joachims et al. 2003).
Lipoflavonoids (another class of anti-oxidant compounds) have been studied in the treatment of tinnitus (Rojas-Roncancio et al. 2016), though most investigators have concluded that there is insufficient evidence for its efficacy (Coelho et al. 2016; Vendra et al. 2019).
Superoxide dismutases (SODs) are a family of endogenous anti-oxidant enzymes. Techniques for boosting SOD activity have been studied as a method for reducing the oxidative stress that results from administration of aminoglycoside antibiotics (Kawamoto et al. 2004), because such oxidative stress is thought to be partly responsible for the ototoxic effects of aminoglycosides.
Some investigators have observed that low levels of superoxide dismutase (Li et al. 2020) and other anti-oxidants (Xie et al. 2020) — presumably resulting in reduced anti-oxidant activity — correlate with an increased risk of benign paroxysmal positional vertigo (Li et al. 2020). Such observations have led to studies in which anti-oxidants were used with the intention of reducing the recurrence of benign paroxysmal positional vertigo (Libonati et al. 2022).
Some investigators reported that patients with Ménière’s disease exhibit both higher serum concentrations of free radicals, and lower levels of anti-oxidants (Raponi et al. 2003), leading to speculation that oxidative stress may be a contributory mechanism of this disease. Such observations motivated studies of free radical scavengers in the treatment of Ménière’s disease (Takumida et al. 2003).
Since anti-oxidants are low risk and easily available, many patients with otoneurological conditions elect to try them, though in our view evidence of their efficacy for any particular condition is lacking.
References
Coelho C, Tyler R, Ji H, Rojas-Roncancio E, Witt S, Tao P, Jun HJ, Wang TC, Hansen MR, Gantz BJ (2016) Survey on the Effectiveness of Dietary Supplements to Treat Tinnitus. Am J Audiol 25: 184-205. doi: 10.1044/2016_AJA-16-0021
Joachims HZ, Segal J, Golz A, Netzer A, Goldenberg D (2003) Antioxidants in treatment of idiopathic sudden hearing loss. Otol Neurotol 24: 572-5. doi: 10.1097/00129492-200307000-00007
Kawamoto K, Sha SH, Minoda R, Izumikawa M, Kuriyama H, Schacht J, Raphael Y (2004) Antioxidant gene therapy can protect hearing and hair cells from ototoxicity. Mol Ther 9: 173-81. doi: 10.1016/j.ymthe.2003.11.020
Li J, Wu R, Xia B, Wang X, Xue M (2020) Serum levels of superoxide dismutases in patients with benign paroxysmal positional vertigo. Biosci Rep 40. doi: 10.1042/BSR20193917
Libonati GA, Leone A, Martellucci S, Gallo A, Albera R, Lucisano S, Bavazzano M, Chiarella G, Viola P, Galletti F, Freni F, Ciodaro F, Marcelli V, Tortoriello G, di Santillo LS, Picciotti PM, Galli J, Vitale S, Quaranta N, Cavallaro G, Gamba P, Teggi R, Cangiano I, Faralli M, Barboni A, Messina A, Graziano G (2022) Prevention of Recurrent Benign Paroxysmal Positional Vertigo: The Role of Combined Supplementation with Vitamin D and Antioxidants. Audiol Res 12: 445-456. doi: 10.3390/audiolres12040045
Raponi G, Alpini D, Volonte S, Capobianco S, Cesarani A (2003) The role of free radicals and plasmatic antioxidant in Meniere’s syndrome. Int Tinnitus J 9: 104-8.
Rojas-Roncancio E, Tyler R, Jun HJ, Wang TC, Ji H, Coelho C, Witt S, Hansen MR, Gantz BJ (2016) Manganese and Lipoflavonoid Plus((R)) to Treat Tinnitus: A Randomized Controlled Trial. J Am Acad Audiol 27: 661-8. doi: 10.3766/jaaa.15106
Takumida M, Anniko M, Ohtani M (2003) Radical scavengers for Meniere’s disease after failure of conventional therapy: a pilot study. Acta Otolaryngol 123: 697-703. doi: 10.1080/00016480310000728a
Vendra V, Vaisbuch Y, Mudry AC, Jackler RK (2019) Over-the-Counter Tinnitus “Cures”: Marketers’ Promises Do Not Ring True. Laryngoscope 129: 1898-1906. doi: 10.1002/lary.27677
Xie KH, Liu LL, Su CY, Huang XF, Wu BX, Liu RN, Li H, Chen QQ, He JS, Ruan YK (2020) Low Antioxidant Status of Serum Uric Acid, Bilirubin, Albumin, and Creatinine in Patients With Benign Paroxysmal Positional Vertigo. Front Neurol 11: 601695. doi: 10.3389/fneur.2020.601695
