An Oral Combination of Vitamins A, C, E, and Mg++ Improves Auditory Thresholds in Age-Related Hearing Loss

Abstract

The increasing rate of age-related hearing loss (ARHL), with its subsequent reduction in quality of life and increase in health care costs, requires new therapeutic strategies to reduce and delay its impact. The goal of this study was to determine if ARHL could be reduced in a rat model by administering a combination of antioxidant vitamins A, C, and E acting as free radical scavengers along with Mg++, a known powerful cochlear vasodilator (ACEMg). Toward this goal, young adult, 3 month-old Wistar rats were divided into two groups: one was fed with a diet composed of regular chow (“normal diet,” ND); the other received a diet based on chow enriched in ACEMg (“enhanced diet,” ED). The ED feeding began 10 days before the noise stimulation. Auditory brainstem recordings (ABR) were performed at 0.5, 1, 2, 4, 8, 16, and 32 kHz at 3, 6–8, and 12–14 months of age. No differences were observed at 3 months of age, in both ND and ED animals. At 6–8 and 12–14 months of age there were significant increases in auditory thresholds and a reduction in the wave amplitudes at all frequencies tested, compatible with progressive development of ARHL. However, at 6–8 months threshold shifts in ED rats were significantly lower in low and medium frequencies, and wave amplitudes were significantly larger at all frequencies when compared to ND rats. In the oldest animals, differences in the threshold shift persisted, as well as in the amplitude of the wave II, suggesting a protective effect of ACEMg on auditory function during aging. These findings indicate that oral ACEMg may provide an effective adjuvant therapeutic intervention for the treatment of ARHL, delaying the progression of hearing impairment associated with age.

Oral Antioxidant Vitamins and Magnesium Limit Noise-induced Hearing Loss by Promoting Sensory Hair Cell Survival: Role of Antioxidant Enzymes and Apoptosis Genes

“…As illustrated in Figure 1, and consistent with previous studies [24,25,34], ABR recordings from both ND-CTR and ED-CTR rats ( Figures 1A and 1E), not exposed to noise, showed the usual pattern of 4 to 5 evoked waveforms following the stimulus onset, where wave II was the largest, followed by waves I, IV, V and III. Similar to what has been described elsewhere in rats [24,31], ABR recordings carried out at 1 day ( Figure 1B), 10 days ( Figure 1C), and 30 days ( Figure 1D) after noise exposure in the ND rats, showed lack of evoked responses at any time point and frequency evaluated.…”

Antioxidants and Vasodilators for the Treatment of Noise-Induced Hearing Loss: Are They Really Effective?

“…The antioxidant mechanisms of vitamins are diverse. For instance, vitamin A (an in vivo product derived mainly from β-carotene) is an excellent scavenger of singlet oxygen, blocking and/or reverting lipid peroxidation in the plasma membrane (Sies and Stahl, 1995 ; Le Prell et al, 2007a ; Alvarado et al, 2015 , 2018 ). Experimentally, when retinoic acid, the most active metabolite of vitamin A, is administered in noise-exposed mice, it protects the cochlea by reducing significantly the apoptosis of hair cells and consequently, inducing a faster recovery of the auditory thresholds when compared to untreated animals (Ahn et al, 2005 , 2013 ; Prasad and Bondy, 2020 ).…”

“…Experimentally, when retinoic acid, the most active metabolite of vitamin A, is administered in noise-exposed mice, it protects the cochlea by reducing significantly the apoptosis of hair cells and consequently, inducing a faster recovery of the auditory thresholds when compared to untreated animals (Ahn et al, 2005 , 2013 ; Prasad and Bondy, 2020 ). Vitamin E is one of the main radical scavengers of the cell membrane as it blocks and/or reverts lipid peroxidation, by reacting with, and reducing peroxyl radicals (Sies and Stahl, 1995 ; Le Prell et al, 2007a ; Alvarado et al, 2015 , 2018 ). Vitamin E also has a protective effect in the cochlea by reducing cell death and cellular damage in guinea pigs (Hou et al, 2003 ; Fetoni et al, 2008 ), and by diminishing the auditory threshold shifts following noise over-exposure in guinea pigs (Hou et al, 2003 ; Fetoni et al, 2008 ) and humans (Kapoor et al, 2011 ).…”

“…Vitamin E also has a protective effect in the cochlea by reducing cell death and cellular damage in guinea pigs (Hou et al, 2003 ; Fetoni et al, 2008 ), and by diminishing the auditory threshold shifts following noise over-exposure in guinea pigs (Hou et al, 2003 ; Fetoni et al, 2008 ) and humans (Kapoor et al, 2011 ). Vitamin C, a water-soluble molecule, is considered a primary extracellular antioxidant and it is extremely effective in blocking and/or reverting lipid peroxidation in the plasma membrane (Sies and Stahl, 1995 ; Le Prell et al, 2007a ; Alvarado et al, 2015 , 2018 ). Additionally, this vitamin also protects the cell membrane by regenerating vitamin E from its oxidized form.…”

“…There is overwhelming evidence that demonstrates that elevated calcium concentration, inflammation, increased oxidative stress, as well as a reduction in blood flow, are some of the pathophysiological mechanisms underlying NIHL ( Figure 1 ; Lamm and Arnold, 1998 ; Henderson et al, 2006 ; Le Prell et al, 2007b ; Shen et al, 2007 ; Bao et al, 2013 ; Fetoni et al, 2013 ; Altschuler and Dolan, 2015 ; Tan et al, 2016 ; Fuentes-Santamaría et al, 2017 ; Śliwińska-Kowalska and Zaborowski, 2017 ). It is worth noting, that at least the latter two cellular mechanisms seem to be part of a common pathogenic pathway that involves other sensorineural hearing loss conditions such as age-related hearing loss (ARHL) and drug-induced hearing loss (DIHL; Alvarado et al, 2015 , 2018 , 2019 ; Tavanai and Mohammadkhani, 2017 ). Therefore, therapies based on antioxidants and/or vasodilators have been postulated as strategies to prevent and/or reduce the progression of NIHL in several animal models and humans.…”