Effect of antioxidant supplementation on the auditory threshold in sensorineural hearing loss: a meta-analysis

Souza, Maria Eduarda Di Cavalcanti Alves de; Costa, Klinger Vagner Teixeira da; Vitorino, Paulo Augusto; Bueno, Nassib Bezerra; Menezes, Pedro de Lemos

doi:10.1016/j.bjorl.2017.07.011

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Brazilian Journal of Otorhinolaryngology

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Review articles • Braz. j. otorhinolaryngol. 84 (3) • May-Jun 2018 • https://doi.org/10.1016/j.bjorl.2017.07.011 copy

Effect of antioxidant supplementation on the auditory threshold in sensorineural hearing loss: a meta-analysis^☆ ☆ Please cite this article as: Souza ME, Costa KV, Vitorino PA, Bueno NB, Menezes PL. Effect of antioxidant supplementation on the auditory threshold in sensorineural hearing loss: a meta-analysis. Braz J Otorhinolaryngol. 2018;84:368-80.

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Introduction:

Hearing loss is conceptualized as any impairment of the ability to hear and/or detect speech or environment sounds, regardless of cause, type, or degree. It may occur at different stages of life; during pregnancy or childbirth, in childhood, adulthood or old age. It should be noted that aging is the most common cause of sensorineural hearing loss followed by noise-induced hearing loss, and both are closely related to the formation of reactive oxygen species. Dietary antioxidant supplementation has been employed as a therapeutic strategy to prevent and/or delay the risks of major human diseases.

Objective:

To assess randomized clinical trials to determine the effect of antioxidant supplementation on the auditory thresholds in patients of different age groups with sensorineural hearing loss.

Methods:

This systematic review consisted of a search in the following databases: MEDLINE, CENTRAL, ScienceDirect, Scopus, Web of Science, LILACS, SciELO and ClinicalTrials.gov. Additionally, the gray literature was also searched. The search strategy included terms related to the intervention (antioxidant supplementation), primary outcome (sensorineural hearing loss), as well as terms related to randomized clinical trials to improve search sensitivity.

Results:

Based on 977 potentially relevant records identified through the search in the databases, ten full-text publications were retrieved for further evaluation. The increase in threshold at the 4 kHz frequency was statistically higher in the control group (1.89 [1.01-2.78], p < 0.0001) when compared to the NAC group and the ginseng group, whereas at 6 kHz, the threshold increase was higher in the control group (1.42 [−1.14-3.97], p = 0.28), but no statistically significant differences were found between groups.

Conclusion:

Ginseng was the antioxidant agent that showed the best effect in preventing auditory threshold worsening at the frequency of 4 kHz, but not at 6 kHz in patients with sensorineural hearing loss caused by exposure to high sound pressure levels. There was no improvement in the thresholds with vitamin E supplementation.

KEYWORDS
Hearing; Reactive oxygen species; Free radicals

Source	City (country)	Sample (gender)	Mean age (years) ± standard deviation
Joachims et al., 2003²⁷27 Joachims HZ, Segal J, Golz A, Netzer A, Goldenberg D. Antioxidants in treatment of idiopathic sudden hearing loss. Otol Neurotol. 2003;24:572-5.	Haifa (Israel)	66 patients	41
		33 in S group	15-70 years (mean age: 41 years)
		33 in C group
Kharkeli et al., 2007²⁸28 Kharkeli E, Kevanishvili Z, Maglakelidze T, Davitashvili O, Schacht J. Does Vitamin E prevent gentamicin-induced ototoxicity?. Georgian Med News. 2007;:14-7.	Georgia (USA)	52 patients (23 males; 29 females)	32.6 (±11.1) - experimental group
		Vitamin E: 23	29.0 (±10.3) - control group
		Placebo: 29
Polanski and Cruz 2013²⁶26 Polanski JF, Cruz OL. Evaluation of antioxidant treatment in presbyacusis: prospective, placebo-controlled, double-blind, randomised trial. J Laryngol Otol. 2013;127:134-41.	São Paulo (Brazil)	120 patients (53 males; 67 females)	74.3 ± 8.5 - ginkgo biloba group
		120 patients (53 males; 67 females)	74.6 ± 5.4 - α-lipoic acid + Vitamin C group
		Placebo: 30
		Ginkgo biloba: 30
		30 α-lipoic acid + Vitamin C group	71.2 ± 6.4 - papaverine hydrochloride + Vitamin E group
		30 papaverine hydrochloride + Vitamin E group	75.4 ± 7.0 - placebo group
Doosti et al., 2014²⁴24 Doosti A, Lofti Y, Moosavi A, Bakhshi E, Talasaz AH. Distortion product otoacoustic emission (DPOAE) as an appropriate tool in assessment of otoprotective effects of antioxidants in noise-induced hearing loss (NIHL). Indian J Otolaryngol Head Neck Surg. 2014;66:325-9.	Teheran (Iran)	48 workers (male)	39.12 (±5)
		NAC - 16	39.38 ± 6.2 - NAC group
		Ginseng - 16	38.38 ± 4.4 - ginseng group
		Control - 16	39.62 ± 4.6 - control group
Doosti et al., 2014²⁵25 Doosti A, Lofti Y, Moosavi A, Bakhshi E, Talasaz AH, Hoozard A. Comparison of the effects of N-acetyl-cysteine and ginseng in prevention of noise induced hearing loss in male textile workers. Noise Health. 2014;16:223-7.	Teheran (Iran)	48 workers (male)	39.12 (± 5)
		NAC - 16	39.38 ± 6 - NAC group
		Ginseng - 16	38.38 ± 4 - ginseng group
		Control - 16	39.62 ± 4 - control group

Source	Type of hearing loss observed	Intervention for hearing loss	Antioxidant used	Amount administered	Time of supplementation	Hearing loss assessment tool	Effect on auditory threshold	Results found	Observations
Joachims et al., 2003²⁷27 Joachims HZ, Segal J, Golz A, Netzer A, Goldenberg D. Antioxidants in treatment of idiopathic sudden hearing loss. Otol Neurotol. 2003;24:572-5.	Sudden hearing loss (<7 days)	Group C: prednisone (1 mg/kg/day); magnesium sulfate intravenous (4 g/day); carbogen through mask (95% O₂ + 5% CO₂) - 30 min/4 × /day	Vitamin E	Grupo S - 400 mg (2 × /day)	^a a Not specified.	Pure-tone and vocal audiometry.	Group C - 45.45% (n = 15) showed the result	Improvement of 75% or more in the recovery rate	Vitamin E was found as being beneficial in the treatment of sudden hearing loss
							Group C - 45.45% (n = 15) showed the result	Group C - improved N: 15 Total N: 33
		Group S: intervention of group C + Vitamin E (400 mg 2 × /day).					Group S - 78.78% (n = 26) showed the result	Group S - improved N: 26 Total N: 33
Kharkeli et al., 2007²⁸28 Kharkeli E, Kevanishvili Z, Maglakelidze T, Davitashvili O, Schacht J. Does Vitamin E prevent gentamicin-induced ototoxicity?. Georgian Med News. 2007;:14-7.	Induced by ototoxic substances.	Experimental group - 80 mg gentamicin (3×/day) + Vitamin E (2800 mg/day in three doses: 1200 mg, 800 mg, 800 mg)	[1,0]Vitamin E	[1,0]2800 mg/day in three doses: 1200 mg; 800 mg; 800 mg)	[1,0]7 days	[1,0]Pre- and post-pure-tone audiometry	[1,0]Auditory thresholds increased in a similar number of patients from both groups, but with no statistical difference	The analyzed criteria showed no statistical difference	[1,0]Vitamin E is not clinically effective against gentamicin-induced ototoxicity. However, due to the limited number of subjects, the conclusion should be considered delicate
								Control group Improved N: 26 Total N: 29
		Control group - 80 mg gentamicin (3×/day) + placebo (peanut oil, gelatin, glycerin and sorbitol)						Experimental group Improved N: 20 Total N: 23
Polanski and Cruz, 2013²⁶26 Polanski JF, Cruz OL. Evaluation of antioxidant treatment in presbyacusis: prospective, placebo-controlled, double-blind, randomised trial. J Laryngol Otol. 2013;127:134-41.	Presbycusis.	Group 1 - ginkgo biloba (120 mg/day)	Ginkgo biloba; α-lipoic acid + Vitamin C; Vitamin E.	Ginkgo biloba (120 mg/day); α-lipoic acid (60 mg/day) + Vitamin C (600 mg/day); Vitamin E (400 mg/day)	6 months	Pre- and post-pure-tone and vocal audiometry	There were differences in the audiological thresholds: 500 Hz, 1000 Hz and 8000 Hz, being greater for group 4 when compared to group 2	The results before and after treatment were not significantly different in any treatment group	The results did not show a statistically significant difference of the effects of antioxidant substances on the auditory thresholds of this population during the 6-month study period
		Group 2 - α-lipoic acid (60 mg/day) + vitamin C (600 mg/day)
		Group 3 - papaverine hydrochloride (100 mg/day) + vitamin E (400 mg/day)
		Group 4 - placebo.
Doosti et al., 2014²⁴24 Doosti A, Lofti Y, Moosavi A, Bakhshi E, Talasaz AH. Distortion product otoacoustic emission (DPOAE) as an appropriate tool in assessment of otoprotective effects of antioxidants in noise-induced hearing loss (NIHL). Indian J Otolaryngol Head Neck Surg. 2014;66:325-9.	Noise-induced hearing loss.	Control group - no intervention	Ginseng	Ginseng group - 200 mg/day	14 days (2 weeks)	Distortion product otoacoustic emissions - DPOAE (1, 2, 4 and 6 kHz)	NAC and ginseng groups showed the result; additionally, the NAC group showed better amplitude of DPOAE than the ginseng group	Reduced DPOAE amplitude at high frequencies (4 and 6 kHz) in both ears	The generalization of the results found in relation to the protective effects of these interventions requires assays with different doses and in a larger population
		NAC group - NAC 1200 mg/day						Control group N improved: Total N: 16
		Ginseng group- 200 mg/day.						NAC group N improved: Total N: 16
		Ginseng group- 200 mg/day.						Ginseng group N improved: Total N: 16
Doosti et al., 2014²⁵25 Doosti A, Lofti Y, Moosavi A, Bakhshi E, Talasaz AH, Hoozard A. Comparison of the effects of N-acetyl-cysteine and ginseng in prevention of noise induced hearing loss in male textile workers. Noise Health. 2014;16:223-7.	Noise-induced hearing loss	Control group - no intervention;	Ginseng	Group G - ginseng 200 mg/day	14 days (2 weeks)	Pre- and post-pure-tone audiometry and high-frequency audiometry	Groups N and G showed the result	Reduced the temporary change in auditory threshold (4, 6 and 16 kHz)	NAC and ginseng showed to have preventive effects of NIHL. This beneficial effect was most often seen in Group N
		Group N - NAC 1200 mg/day					Group N showed greater reduction	Control group Improved N: Total N: 16
		Group G -ginseng 200 mg/day.						Group NAC Improved N: Total N: 16
		Group G -ginseng 200 mg/day.						Ginseng group Improved N: Total N: 16

Source	Sequence generation	Allocation concealment	Participant and researcher blinding	Blinding of evaluators	Handling of missing data
Joachims et al., 2003²⁷27 Joachims HZ, Segal J, Golz A, Netzer A, Goldenberg D. Antioxidants in treatment of idiopathic sudden hearing loss. Otol Neurotol. 2003;24:572-5.	Uncertain	Uncertain	Low	Low	Low
Kharkeli et al., 2007²⁸28 Kharkeli E, Kevanishvili Z, Maglakelidze T, Davitashvili O, Schacht J. Does Vitamin E prevent gentamicin-induced ototoxicity?. Georgian Med News. 2007;:14-7.	Uncertain	Uncertain	Low	Uncertain	Low
Polanski & Cruz, 2013²⁶26 Polanski JF, Cruz OL. Evaluation of antioxidant treatment in presbyacusis: prospective, placebo-controlled, double-blind, randomised trial. J Laryngol Otol. 2013;127:134-41.	Low	Low	Low	Low	Low
Doosti et al., 2014²⁴24 Doosti A, Lofti Y, Moosavi A, Bakhshi E, Talasaz AH. Distortion product otoacoustic emission (DPOAE) as an appropriate tool in assessment of otoprotective effects of antioxidants in noise-induced hearing loss (NIHL). Indian J Otolaryngol Head Neck Surg. 2014;66:325-9.	Low	Low	Low	Low	Low
Doosti et al., 2014²⁵25 Doosti A, Lofti Y, Moosavi A, Bakhshi E, Talasaz AH, Hoozard A. Comparison of the effects of N-acetyl-cysteine and ginseng in prevention of noise induced hearing loss in male textile workers. Noise Health. 2014;16:223-7.	Low	Low	Low	Low	Low

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[1] * Corresponding author. E-mail:grupodepesquisalatec@gmail.com (M.E. Souza).