Pharmacological Prevention of Noise-Induced Tinnitus and Hearing Loss

By Barry Keate
Barry Keate, has lived with tinnitus over 40 years and has published 150+ research articles on numerous aspects of tinnitus. He is an expert on the condition and a well-known advocate for those with tinnitus.

A new scientific study examines the use of various “agents” for the prevention of noise-induced hearing loss (NIHL) and, by extension, tinnitus. (1) Most of these agents are over-the-counter dietary supplements while two, are prescription medications.

The supplements used consisted of Magnesium aspartate, alpha-lipoic acid (ALA), N-acetylcysteine (NAC), beta-carotene (vitamin A), vitamins C, E and B12; and the prescription medications were carbogen and ebselen.

Carbogen is a gas, generally consisting of 5% CO2 and 95% oxygen. It is used to stimulate breathing in the treatment of respiratory disease. Ebselen is a synthetic organoselenium molecule with anti-inflammatory and antioxidant activity. Interestingly, both of these agents are currently being studied for COVID-19 treatment

Published in the January 2021 issue of Otology and Neurotology, the study is termed a systematic review, meaning there were several different studies involved and researchers tried to systematize the results into a coherent picture. One of the major drawbacks was there were no standardized guidelines in the individual studies for what kind of noise exposure was employed, the duration of exposure, the measurement of hearing loss or what timeline to measure the response.

Hearing Loss Study Methods

Noise exposure in the studies varied widely. Some used white noise, some loud music or pure tone sound at 4 KHz. One study relied on rifle fire on a military firing range. All were designed to observe reduced hearing levels and follow whether hearing returned and to what level. The agents involved were given to people before they were exposed to the noise.

The measurement of hearing loss used was the threshold shift in hearing. The Standard Threshold Shift (STS) indicating hearing loss, according the US Office of Occupational Safety and Health Administration (OSHA), is a 10 decibel (dB) loss, or more, at 2,000, 3,000 and 4,000 Hz in one or both ears. However, many of the studies used different criteria, from 5 dB to 25 dB.

 

Graph of results of temporary threshold shift after exposure to broadband noise

 

Most studies centered on the 4KHz to 6KHz frequency, since that is the most common audiological notch that indicates noise-induced hearing loss. As a person is exposed to longer episodes of noise exposure, they often demonstrate patterns of more profound hearing loss above and below this frequency range.

The authors of the review state, “Inherently, it is not possible to compare the effect of hearing recovery among different individuals who were exposed to various types, intensities and durations of noise exposures after varying regimens and doses of different pharmaceutical agents.” And, “These results should be interpreted with caution, as there were variable study designs, pharmacologic agents, and reporting of outcome data, suggesting that research concerning the effects of various pharmacological agents is at an early stage.”

Having said all this, and taking into account the limitations of the review, there were several positive trials, showing that using some of these agents were effective in preventing noise-induced hearing loss.

All the studies were randomized, placebo-controlled trials.

Hearing Loss Study Results

Carbogen

Subjects receiving carbogen inhalation had a significantly lower threshold shift 2 minutes after a 20-minute 100 dB white noise exposure when compared with atmospheric air inhalation. However, the results were short-lived without any significant difference in hearing outcomes after 60 minutes.

Ebselen

Fifteen minutes after exposure to 100 dB music for 4 hours, there was a significant difference in threshold shift after a course of 400 mg of ebselen compared with placebo. It is important to note here that the difference was only 2.4 dB. The clinical efficacy of this treatment should be interpreted with caution.

Magnesium Aspartate

Two studies using dosages of 167 mg per day for 8 weeks and 122 mg for 10 days showed significant improvement in threshold shifts. We have written previously about the protective effects of Magnesium in preventing noise-induced hearing loss.

Alpha-Lipoic Acid

One study, 2 minutes after a 10-minute 90 dB pure-tone exposure showed nonsignificant differences when comparing two different ALA regimens vs. a control group. Another study using 600 mg ALA showed significant improvement.

Vitamin B12

A study using intramuscular injection of 7 doses of 1 mg and 1 dose of 5 mg over 8 days showed significant improvement in threshold shift. B12 is also clinically helpful for tinnitus. Arches Tinnitus B12 Formula uses methylcobalamin the highest quality and most absorbable form of B12.

N-Acetylcysteine (NAC)

NAC is one of my favorites. However, a study on NAC in a military population after weapons training did not meet the primary objective of threshold shift in both ears. But the results for the secondary objective of shift in the trigger-hand ear did show a significant difference in the shift. Further analysis suggests that NAC is superior to placebo but the present study design failed to prove this.

This shows the difficulty in designing randomized, placebo-controlled studies. If the secondary objective were to have been the primary objective, the study would have clearly shown its superiority over placebo. It’s very important to observe the total of scientific evidence in these studies and not to rely on one that stands out from the body of work on the subject.

Pharmacological agents that did not produce significant results, aside from the NAC trial, included administration of a combination regimen of beta-carotene, vitamins C and E, and magnesium.

Ginkgo biloba and zinc were not included in this review. They should have been and hopefully will be in the future. Ginkgo and zinc have demonstrated in numerous trials to be effective in treating hearing loss and tinnitus and are also effective in preventing it. Arches Tinnitus Formula contains Ginkgo Max 26/7®, our proprietary ginkgo extract, and zinc picolinate, the most absorbable form of zinc.

Ginkgo has the pharmacological properties sought of agents in this review. That is, antioxidant activity and an increase in oxygen to the cochlea through increased circulation in the microcapillaries. Additionally, Ginkgo biloba contains high amounts of Bilobalide, which is a glutamate antagonist, reducing the excitatory properties of glutamate. Glutamate excitotoxicity is the largest contributor to tinnitus and glutamate is released when the cochlea is exposed to loud noise levels.

Zinc is a powerful antioxidant. The highest concentration of zinc is in the cochlea and is depleted when exposed to loud noise.

This is the first systematic review of agents that may be able to prevent hearing loss and tinnitus. Much more study is called for and hopefully can lead to preventive measures that reduce the amount of hearing loss in our society.

References:

1 – Gupta A, Koochakzadeh S, Nguyen S, et. Al. Pharmacological Prevention of Noise-induced Hearing Loss: A Systematic Review. Otol Neurotol 42:2-9, 2021. https://journals.lww.com/otology-neurotology/Abstract/2021/01000/Pharmacological_Prevention_of_Noise_induced.2.aspx