N-Acetyl-Cysteine (NAC) in disorders involving hearing or dizziness.

Timothy C. Hain, MD

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N-Acetyl-Cysteine, or NAC, is a cysteine precursor with a strong antioxidant action. Cysteine is an amino acid -- amino acids are building blocks for protein. So when you eat protein, your body usually gets some cysteine too.

NAC provides cysteine to produce glutathione, which acts as a free radical scavenger. NAC has been available for about 3 decades, and has somewhat of a "cult" status. It is used both as an agent to dissolve mucus (mucolytic), as well as a supplement advocated for a large variety of uses, mainly unproven (Mokhtari et al, 2017). Because NAC goes everywhere, and the inner ear is just the size of a dime, one would also think that NAC would affect the whole body, and that practical issues such as side effects and lack of potency would make NAC treatment for inner ear conditions of little value

Logically, one would expect that NAC would be a prevention type medication -- probably best suited to slowly progressive disorders that are somehow involved with toxicity from free radicals. To use farming analogies, NAC is a "lock the barn door" treatment, rather than one that rounds up the cows after they are gone. In other words, don't expect NAC to improve anything after the damage is already done. One would think it might reduce the rate of progression of intrinsically progressive illnesses (perhaps hearing loss), to a very small extent. One would not think that it would be very useful for viral illnesses such as vestibular neuritis or, but perhaps NAC might be slightly useful for anticipated ear damage such as Meniere's. There is a bias towards positive trials in the scientific literature, and we think that it is unlikely that a strong effect of NAC oral supplementation (by itself) is plausible from any human study, past or future. Methods of increasing concentration in the inner ear might make this treatment more plausible (we are not sure how to do this). We would be very dubious about trials involving small numbers, or magical combinations of different drugs.

While "hope springs eternal", there is usually greater predictive value in evidence and common sense. With NAC, we have very little evidence or common sense. Nothing wrong with hope.

Availability

NAC is available as a food supplement, and is available from Amazon, etc. It is inexpensive.

Rationale for use of NAC:

Antioxidents slow down disorders that produce free radicals. Burning is an example of oxidation. When iron oxidises, it rusts. So this chemical slows down oxidation. Sort of the opposite idea to using oxygen as a treatment for sudden hearing loss (such as hyperbaric chambers).

Reports of the effect of NAC on hearing disorders

By way of a general comment, from the animal literature and just common sense, one would predict that NAC would have a tiny positive effect on hearing preservation after an injury, such as noise.

Ada et al (2017) reported that NAC was protective (in rats) for noise injury. Of course, rats are not people and one can dose rats at much higher doses.

Bielefeld et al (2011) combined two anti-oxidants, SRC-PTK and NAC in "animals". They stated "Treatment in the rescue paradigm did not produce any reductions in threshold shift from the 2-hour exposure. " Bielefield et al (2007) suggested there was protection in Chinchillas to "high-kurtosis" noise.

Clifford et al (2011) reported protection from noise in Chinchillas from a mixture of two similar amino-acids, methionine and NAC. It is unlikely that there is anything magical about mixing together two nutritional supplements.

Davis et al (2010) reported that NAC did not protect mice exposed to noise, even in doses that were much higher (300-600 mg/kg) per weight, than those used in humans. This was a small study and we suspect a larger # of mice (i.e more than 5) might show a small effect.

Ding et al (2016) reported that "N-acetyl-cysteine prevents age-related hearing loss and the progressive loss of inner hair cells in gamma-glutamyl transferase 1 deficient mice."

Doosti et al (2014) reported in 48 participants randomized into 3 groups, "Our results show that NAC and ginseng can reduce noise induced TTS in workers exposed to occupational noise. " We think that the number of subjects is low.

Feghali et al (2001) reported that NAC protected against cisplatin (chemo) damage to cultured auditory hair cells. This is somewhat of a "test of concept" paper.

Habybabady et al (2018) reported better results in ear pathology in rats exposed to noise, while getting intravenous NAC.

Hamernik et al (2008) reported in a small study of chinchillas, that "There was no statistically significant difference among the three groups in all measures of noise-induced trauma. " We suspect that a larger study may have documented a small effect.

Hoffer (2013) reported on 81 persons exposed to blast injuries, involving 7 days of treatment. They reported "Logistic regression on the outcome of 'no day 7 symptoms' indicated that NAC treatment was significantly better than placebo (OR = 3.6, p = 0.006). Secondary analysis revealed subjects receiving NAC within 24 hours of blast had an 86% chance of symptom resolution with no reported side effects versus 42% for those seen early who received placebo. " We find this strong effect surprising and would like to have more studies.

Lin et al (2010) reported that in a study of 53 workers "NAC may prevent noise-induced TTS among occupationally noise-exposed men. The protective effect of NAC was more prominent in subjects with both GSTM1-null and GSTT1-null genotypes." GST is a glutathione transferase gene, with two polymorphisms. This study is small and should be repeated.

Lorito et al (2006) reported that huge doses of NAC in rats (1500 mg/kg) was protective for noise induced hearing loss. "These data suggest that while L-Nacetyl-cysteine can partially protect the cochlea from continuous noise, the protection effect is strongly dose-dependent: lower dosages do not fully protect the cochlea and higher dosages can damage the rat systemically (e.g. pulmonary toxicity)." The doses in humans are roughly 100 times smaller than this.

Lu et al (2011) reported that L-cysteine protected rat hearing neurons in culture from oxidative toxicity. This is a rather obvious conclusion showing that an anti-oxidant reduces oxidation.

Rosenhall et al (2019) reported reduction in temporary threshold shifts in swedish military who underwent "acoustic accidents", and in whom were given NAC immediately after. This paper, published in the "Int J Audiol", stated that "The risk reduction to get a temporary hearing loss (TTS), affecting one or both ears was 39% (significant) in the NAC group. "

Yang et al (2009) reported that NAC injected into rats at relatively high doses compared to humans, protected the rats from hearing loss due to styrene.

Side Effects

The literature on NAC rarely mentions any side effects in humans. This would be the expected situation for a nearly inert substance. It is probably safer than potato chips, for example, which have salt and oil. Mokhtari et al (2017) states that studies have shown no maternal or fetal harmful effects of NAC treatment.

Summary:

NAC, basically an amino acid (i.e. a building block of protein), is a nutritional supplement with a mechanism of action involving antioxidation. It probably is slightly helpful for hearing disorders. In the usual doses, it appears to be harmless. It would seem well suited for situations where there is a benefit of providing hope for ear disorders that have no conventional treatment, or in whom conventional treatment has failed.

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