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Antioxidants And Hearing Loss:

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


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.

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.

Role of antioxidants in prevention of age-related hearing loss: a review of literature: *


Age-related hearing loss (ARHL), also known as presbycusis, is one of the most prevalent chronic degenerative conditions. It is characterized by a decline in auditory function. ARHL is caused by the interaction of multiple factors, including cochlear aging, environment, genetic predisposition, and health comorbidities. The primary pathology of ARHL includes the hair cells loss, stria vascularis atrophy, and loss of spiral ganglion neurons as well as the changes in central auditory pathways. The research to date suggests that oxidative stress and mitochondrial DNA deletion (mtDNA) play a major role in pathophysiology of ARHL. Therefore, similar to other otological conditions, several studies have also showed that antioxidants can slow ARHL, but some also indicate that antioxidant therapy is not a magic elixir that will prevent or treat hearing loss associated with aging completely, but why? All available clinical trials, including animal and human studies, in English language that examined the protective effects of antioxidants against ARHL were reviewed. Materials were obtained by searching ELSEVIER, PubMed, Scopus, Web of knowledge, Google Scholar databases, Clinical trials, and Cochrane database of systematic reviews. Although ARHL has been shown to be slowed by supplementation with antioxidants, particularly in laboratory animals, a few studies have investigated the effect of interventions against ARHL in humans. High-quality clinical trials are needed to investigate if ARHL can be delayed or prevented in humans. However, it seems that targeting several cell-death pathways is better than targeting the only oxidative stress pathway.

Folic Acid And Hearing Loss

Folic acid deficiency induces premature hearing loss through mechanisms involving cochlear oxidative stress and impairment of homocysteine metabolism: *


Nutritional imbalance is emerging as a causative factor of hearing loss. Epidemiologic studies have linked hearing loss to elevated plasma total homocysteine (tHcy) and folate deficiency, and have shown that folate supplementation lowers tHcy levels potentially ameliorating age-related hearing loss. The purpose of this study was to address the impact of folate deficiency on hearing loss and to examine the underlying mechanisms. For this purpose, 2-mo-old C57BL/6J mice (Animalia Chordata Mus musculus) were randomly divided into 2 groups (n = 65 each) that were fed folate-deficient (FD) or standard diets for 8 wk. HPLC analysis demonstrated a 7-fold decline in serum folate and a 3-fold increase in tHcy levels. FD mice exhibited severe hearing loss measured by auditory brainstem recordings and TUNEL-positive-apoptotic cochlear cells. RT-quantitative PCR and Western blotting showed reduced levels of enzymes catalyzing homocysteine (Hcy) production and recycling, together with a 30% increase in protein homocysteinylation. Redox stress was demonstrated by decreased expression of catalase, glutathione peroxidase 4, and glutathione synthetase genes, increased levels of manganese superoxide dismutase, and NADPH oxidase-complex adaptor cytochrome b-245, α-polypeptide (p22phox) proteins, and elevated concentrations of glutathione species. Altogether, our findings demonstrate, for the first time, that the relationship between hyperhomocysteinemia induced by folate deficiency and premature hearing loss involves impairment of cochlear Hcy metabolism and associated oxidative stress.

Effects of folic acid supplementation on hearing in older adults: a randomized, controlled trial: *


Background: Age-related hearing loss is a common chronic condition of elderly persons. Low folate status has been associated with poor hearing.

Objective: To determine whether folic acid supplementation slows age-related hearing loss.

Design: Double-blind, randomized, placebo-controlled trial conducted from September 2000 to December 2004.

Setting: The Netherlands.

Participants: 728 older men and women recruited from municipal and blood bank registries with plasma total homocysteine concentrations 13 micromol/L or greater serum and vitamin B12 concentrations 200 pmol/L or greater at screening, and no middle ear dysfunction, unilateral hearing loss, or pathologic ear conditions unrelated to aging.

Intervention: Daily oral folic acid (800 microg) or placebo supplementation for 3 years.

Measurements: 3-year change in hearing thresholds, assessed as the average of the pure-tone air conduction thresholds of both ears of the low (0.5-kHz, 1-kHz, and 2-kHz) and high (4-kHz, 6-kHz, and 8-kHz) frequencies.

Results: Initial median hearing thresholds were 11.7 dB (interquartile range, 7.5 to 17.5 dB) for low frequencies and 34.2 dB (interquartile range, 22.5 to 50.0 dB) for high frequencies. Sixteen participants (2%) were lost to follow-up. After 3 years, thresholds of the low frequencies increased by 1.0 dB (95% CI, 0.6 to 1.4 dB) in the folic acid group and by 1.7 dB (CI, 1.3 to 2.1 dB) in the placebo group (difference, -0.7 dB [CI, -1.2 to -0.1 dB]; P = 0.020). Folic acid supplementation did not affect the decline in hearing high frequencies.

Ginkgo Biloba And Hearing Loss

An efficacy comparison of betahistin, trimetazidine and ginkgo biloba extract in patients with tinnitus *


Objectives: This study aims to investigate the efficacy of trimetazidine, betahistine and ginkgo biloba extract in the treatment of tinnitus.

Patients and methods: Complete clinical data of 90 patients (48 males, 42 females; mean age 52.3±15.1 years; range 20 to 61 years) who received betahistine, trimetazidine and ginkgo biloba extract for three months were retrospectively analyzed. The patients were divided into three groups including 30 in each group according to treatments received. Pre-treatment and post-treatment scores of tinnitus disability questionnaire were compared statistically.

Results: There was no statistically significant difference between pre-treatment scores of tinnitus disability questionnaire among all three groups (p>0.05), while there was a statistically significant difference among the groups following treatment (p=0.019, p<0.05). After a-three-month treatment, a decrease of 19.7±15.5 units in trimetazidine group, 12.2±12.7 units in betahistine group, and 3.80±5.9 units in ginkgo biloba extract group were found to be statistically significant, compared to the mean pretreatment tinnitus disability questionnaire scores (p=0.002, p<0.01).

Conclusion: Our study results suggest that trimetazidine, betahistin and ginkgo biloba extract reduce tinnitus symptoms. However, symptomatic relief can be mostly achieved with trimetazidine treatment.

Green Tea Extract And Hearing Loss

Role of green tea polyphenols in noise-induced hearing loss.*


Objective: To investigate the role and mechanism of action of green tea polyphenols in noise-induced hearing loss. Methods: Male specific pathogen-free guinea pigs were randomly divided into normal control group with 9 guinea pigs, noise exposure group with 36 guinea pigs, and green tea polyphenol intervention group with 36 guinea pigs. Auditory brainstem response (ABR) threshold shift was examined before noise exposure and at 1, 3, 7, and 14 days of noise exposure. The surface preparation of cochlear basilar membrane was used for hair cell count and the morphology of hair cells was also observed. Western blot was used to observe the expression of cysteinyl aspartate-specific protease-9 (caspase-9) and cysteinyl aspartate-specific protease-3 (caspase-3) in cochlear tissue. Results: Both the noise exposure group and the green tea polyphenol intervention group had an increase in ABR threshold after noise exposure, and the green tea polyphenol intervention group had a significantly lower ABR threshold shift than the noise exposure group at all time points (P<0.05). Both groups had enlargement, atrophy, or loss of hair cells after noise exposure, and at 7 and 14 days of noise exposure, the noise exposure group had a significantly higher rate of abnormal hair cells than the green tea polyphenol intervention group (P<0.05). Both groups had an increase in the expression of caspase-9 and caspase-3 after noise exposure, and the noise exposure group had a significantly greater increase than the green tea polyphenol intervention group (P<0.05). Conclusion: Green tea polyphenols can reduce noise-induced hearing loss and hair cell injury, possibly by regulating the expression of caspase-9 and caspase-3.

NAC And Hearing Loss

The Antioxidant Role of Glutathione and N-Acetyl-Cysteine Supplements and Exercise-Induced Oxidative Stress*


An increase in exercise intensity is one of the many ways in which oxidative stress and free radical production has been shown to increase inside our cells. Effective regulation of the cellular balance between oxidation and antioxidation is important when considering cellular function and DNA integrity as well as the signal transduction of gene expression. Many pathological states, such as cancer, Parkinson’s disease, and Alzheimer’s disease have been shown to be related to the redox state of cells. In an attempt to minimize the onset of oxidative stress, supplementation with various known antioxidants has been suggested. Glutathione and N-acetyl-cysteine (NAC) are antioxidants which are quite popular for their ability to minimize oxidative stress and the downstream negative effects thought to be associated with oxidative stress. Glutathione is largely known to minimize the lipid peroxidation of cellular membranes and other such targets that is known to occur with oxidative stress. N-acetyl-cysteine is a by-product of glutathione and is popular due to its cysteine residues and the role it has on glutathione maintenance and metabolism. The process of oxidative stress is a complicated, inter-twined series of events which quite possibly is related to many other cellular processes. Exercise enthusiasts and researchers have become interested in recent years to identify any means to help minimize the detrimental effects of oxidative stress that are commonly associated with intense and unaccustomed exercise. It is possible that a decrease in the amount of oxidative stress a cell is exposed to could increase health and performance.

Treatment of military acoustic accidents with N-Acetyl-L-cysteine (NAC)*


Objective: To study if the antioxidant (AO) N-Acetyl-L-cysteine (NAC) reduces the risk of hearing loss after acoustic accidents in humans.

Design: A retrospective, observational study.

Study sample: Personnel of the Swedish Armed Forces (SAF) exposed to military acoustic accidents during a 5 year period. Included in the study were 221 cases (mean age: 22.9 years). Most of the exposures, 84%, were weapon related. NAC (400 mg) was given directly after the accident in 146 cases; 75 had not received NAC.

Results: The prevalence of hearing thresholds ≥25 dB HL, and the incidence of threshold shifts ≥10 dB, was lower in the NAC group than in the non-NAC group directly after the noise exposure. The deterioration was temporary and not discernable a long time after the accident. The difference was most pronounced in the right ear. The risk reduction to get a temporary hearing loss (TTS), affecting one or both ears was 39% (significant) in the NAC group.

Efficacy and safety of N-acetylcysteine in prevention of noise induced hearing loss: A randomized clinical trial*


Despite a robust hearing conservation program, military personnel continue to be at high risk for noise induced hearing loss (NIHL). For more than a decade, a number of laboratories have investigated the use of antioxidants as a safe and effective adjunct to hearing conservation programs. Of the antioxidants that have been investigated, N-acetylcysteine (NAC) has consistently reduced permanent NIHL in the laboratory, but its clinical efficacy is still controversial. This study provides a prospective, randomized, double-blinded, placebo-controlled clinical trial investigating the safety profile and the efficacy of NAC to prevent hearing loss in a military population after weapons training.
Of the 566 total study subjects, 277 received NAC while 289 were given placebo. The null hypothesis for the rate of STS was not rejected based on the measured results. While no significant differences were found for the primary outcome, rate of threshold shifts, the right ear threshold shift rate difference did approach significance (p = 0.0562). No significant difference was found in the second primary outcome, percentage of subjects experiencing an adverse event between placebo and NAC groups (26.7% and 27.4%, respectively, p = 0.4465). Results for the secondary outcome, STS rate in the trigger hand ear, did show a significant difference (34.98% for placebo-treated, 27.14% for NAC-treated, p-value = 0.0288). Additionally, post-hoc analysis showed significant differences in threshold shift rates when handedness was taken into account.
While the secondary outcomes and post-hoc analysis suggest that NAC treatment is superior to the placebo, the present study design failed to confirm this. The lack of significant differences in overall hearing loss between the treatment and placebo groups may be due to a number of factors, including suboptimal dosing, premature post-exposure audiograms, or differences in risk between ears or subjects. Based on secondary outcomes and post hoc analyses however, further studies seem warranted and are needed to clarify dose response and the factors that may have played a role in the observed results.


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