Cochlear Homocysteine Metabolism at the Crossroad of Nutrition and Sensorineural Hearing Loss

Abstract

Hearing loss (HL) is one of the most common causes of disability, affecting 360 million people according to the World Health Organization (WHO). HL is most frequently of sensorineural origin, being caused by the irreversible loss of hair cells and/or spiral ganglion neurons. The etiology of sensorineural HL (SNHL) is multifactorial, with genetic and environmental factors such as noise, ototoxic substances and aging playing a role. The nutritional status is central in aging disability, but the interplay between nutrition and SNHL has only recently gained attention. Dietary supplementation could therefore constitute the first step for the prevention and potential repair of hearing damage before it reaches irreversibility. In this context, different epidemiological studies have shown correlations among the nutritional condition, increased total plasma homocysteine (tHcy) and SNHL. Several human genetic rare diseases are also associated with homocysteine (Hcy) metabolism and SNHL confirming this potential link. Accordingly, rodent experimental models have provided the molecular basis to understand the observed effects. Thus, increased tHcy levels and vitamin deficiencies, such as folic acid (FA), have been linked with SNHL, whereas long-term dietary supplementation with omega-3 fatty acids improved Hcy metabolism, cell survival and hearing acuity. Furthermore, pharmacological supplementations with the anti-oxidant fumaric acid that targets Hcy metabolism also improved SNHL. Overall these results strongly suggest that cochlear Hcy metabolism is a key player in the onset and progression of SNHL, opening the way for the design of prospective nutritional therapies.

Avocado Oil Extract Modulates Auditory Hair Cell Function through the Regulation of Amino Acid Biosynthesis Genes

“…As we hypothesized, DKB122 showed protective efficacy on sensory hair cells damaged by neomycin. These results are supported by different studies that showed efficacy of omega-3 fatty acids to attenuate hearing loss [24,31].…”

Vitamin B complex mitigates cardiac dysfunction in high‐methionine diet‐induced hyperhomocysteinemia

“…The methyl group‐rich amino acid methionine is first activated to form S ‐adenosylmethionine (SAM), which serves as a methyl donor in over 115 methyl transfer reactions. The loss of the methyl group results in the residual product S ‐adenosylhomocysteine (SAH), and the hydrolysis of SAH yields Hcy (Figure ) …”

Erythrocyte folate, serum vitamin B12, and hearing loss in the 2003-2004 National Health And Nutrition Examination Survey (NHANES)

“… 14 These results are also consistent with protective effects of folate on hearing and cochlear vascularization that have been observed in animal studies. 15 , 25 , 26 …”

“…Since lower levels of folate or vitamin B12 elevate homocysteine, a metabolite thought to impair blood flow to the cochlea, these nutrients may also affect hearing through their effects on homocysteine. 14 , 15 While most studies have focused on folate and vitamin B12 deficiency or insufficiency as potential risk factors for hearing loss, excess folate from diet or folic acid from supplements and fortified foods could lead to high levels of circulating unmetabolized folic acid that could lead to neurological problems, altered DNA methylation and hearing loss. 16 – 19 …”