May 11, 2004 Feature

Otoprotective Agents Sought for Noise-Induced Hearing Loss

Given the large number of patients with noise-induced hearing loss (NIHL) that audiologists see every day, there is an intense search for agents that could protect or rescue cochlear hair cells from excessive noise exposure. Although no drugs are currently approved by the U.S. Food and Drug Administration (FDA) to prevent or treat NIHL, several hold promise.

A variety of approaches are on the horizon for NIHL. This article focuses on otoprotective agents which are likely to gain FDA approval before cochlear hair cell regeneration ultimately becomes a reality.

Hair Cell Life and Death

An unhealthy lifestyle increases the risk of noise-induced hearing loss. For example, a high fat diet can reduce blood flow. Smoking increases free radicals-molecules with only one electron in the outer shell-which can oxidize and damage other cells. Both have been implicated in increasing the risk of NIHL and have been shown to do so in animal studies. Thus, antioxidants, which detoxify free radicals, or other agents that increase blood flow may also serve to protect or rescue from NIHL.

Some natural otoprotection for NIHL may occur every day. Moderate alcohol consumption inversely correlates with the odds of having NIHL, whereas heavy alcohol consumption increases the risk. Since the 1970s, musicians have been observed to have lower than expected levels of NIHL. Exposure to music that is enjoyable, as opposed to music that is not enjoyable, decreases risk of NIHL. However, the underlying mechanisms are unclear and many musicians still get significant NIHL.

Some otoprotective agents reveal the mechanisms of NIHL in laboratory studies, but pose safety issues for humans. For example, the glutathione pathway is one of our major antioxidant defense systems present throughout the body, but directly administering glutathione systemically may be inadvisable. It is not readily taken up into cells and in some forms and at some high doses, glutathione may have its own toxicities. R-PIA (R-N6-phenylisopropyladenoisine), which increases antioxidant enzyme levels and neurotrophic factors with antioxidant properties, have shown some otoprotection in animal studies but may not be safe for systemic administration in humans because they have multiple actions in the body.

Other agents such as MK801 and carbamathione, which block the neurotransmitter glutamate, can reduce NIHL, but blocking a major neurotransmitter like glutamate has obvious safety issues. Agents that prevent programmed, apoptotic cell death have shown efficacy, but sometimes these cells die for a reason. In many cases, apoptosis (programmed cell death) is a normal and needed process and generally inhibiting it may not be the best clinical approach.

A Look Into the Diet

Interestingly, many of the most promising otoprotective agents are antioxidants that occur naturally in the diet, although not usually in amounts sufficient to provide effective otoprotection against high-level noise. For example, diets rich in vitamins A, C, and E and in selenium have been shown to reduce NIHL in animals.

Several other micronutrients have shown efficacy in preventing NIHL. For example, magnesium, which is found in fish, almonds, spinach, shrimp, bran, chocolate, seeds, whole grains, avocados, bananas, dark green leafy vegetables, and potatoes, is showing some promise. It may act by increasing blood flow or acting on the calcium channels.

Some micronutrients may function primarily as antioxidants. D-methionine (D-Met), which is found in fermented proteins such as cheese and yogurt, may act by increasing glutathione levels within the cell and as a direct antioxidant by scavenging free radicals. N-acetyl cysteine (NAC), present in brussel sprouts, may act in a similar fashion. Recent research has also shown that resveratrol, present in red wine, may also provide some protection against NIHL. Although not a nutritional supplement, there is some evidence that aspirin may also provide some protection, although further research is needed on all of these agents.

The most promising agents approaching clinical trials appear to be D-Met, acetyl L-carnitine (ALCAR), and N-acetyl cysteine (NAC). All three show good protection in animal studies when administered before noise exposure, although D-Met and ALCAR have shown somewhat better hair cell protection than NAC. D-Met and NAC also show some efficacy in preventing permanent NIHL when administered within one hour after noise exposure.

A Note of Caution

Audiologists and their patients shouldn't rush to the Web or health food store to prevent hearing loss. Before audiologists suggest menus for the prevention of NIHL or recommend any dietary pills or supplements beyond recommending a healthy lifestyle and diet, they should wait until a drug is approved by the FDA specifically for prevention or rescue of NIHL. Even then, any medication or dietary supplement should only be recommended by the patient's physician who can consider the patient's other medications and/or medical conditions. Many nutritional and herbal supplements available to the general public over the counter can interact with medications, may have side effects, may not be effective, or may be contraindicated in certain patients.

Prevention will always be the best treatment for NIHL, but for those who experience unavoidable or unexpected noise exposure, the future holds promise of an FDA -approved drug that may one day be available to reduce the incidence of NIHL.

Kathleen C. M. Campbell, is professor and director of audiology research at Southern Illinois University School of Medicine in Springfield. She authored Essential Audiology for Physicians and serves on the AAA Board of Directors. Campbell is also a prolific researcher and lecturer, focusing on ototoxicity and NIHL. She holds two patents for otoprotective agents and is preparing for clinical trials. Contact her by e-mail at

cite as: Campbell, K. C. (2004, May 11). Otoprotective Agents Sought for Noise-Induced Hearing Loss. The ASHA Leader.


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