Mildly Elevated Serum Bilirubin is Associated with a Lower Risk of Hearing Loss in Chinese Adults
Hearing loss is the most common sensory deficit in humans, significantly impacting daily communication and overall quality of life. Oxidative stress is a critical factor in the development and progression of age-related hearing loss. Studies have shown that deficiencies in endogenous antioxidants or insufficient dietary antioxidant intake can increase the risk of hearing loss, while antioxidant supplementation may help prevent its development. Bilirubin, a catabolic product of heme in mammals, has traditionally been viewed as a cytotoxic waste product. However, recent evidence suggests that unconjugated bilirubin (UCB) can act as an endogenous antioxidant by scavenging oxidative radicals or inhibiting their production. This has led to the hypothesis that mildly elevated serum bilirubin levels may be associated with a lower risk of oxidative stress-related chronic diseases, including hearing loss.
This cross-sectional study aimed to explore the association between physiologically elevated serum bilirubin levels and the risk of hearing loss in Chinese adults. The study was conducted under the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of Hangzhou Normal University. A total of 3,684 participants aged 19 to 98 years were recruited from the general population undergoing routine health examinations in five regional hospitals in Zhejiang Province, China, between September 2016 and June 2018. All participants provided written informed consent. Among the participants, 1,702 (46.2%) were defined as having high-frequency hearing loss, and 1,103 (29.9%) were defined as having speech-frequency hearing loss. The median levels of serum total bilirubin (TB) and UCB were 14.0 mmol/L and 10.2 mmol/L, respectively.
Participants with hearing loss were, on average, 17 years older than those without hearing loss. Hearing loss was also associated with male gender, cigarette smoking, alcohol drinking, noise exposure, and a history of hypertension, diabetes, and dyslipidemia. Additionally, higher serum aspartate aminotransferase activity was observed in individuals with hearing loss. While TB serum levels were significantly higher in individuals with hearing loss, no significant difference in UCB serum concentrations was found between those with and without hearing loss.
Logistic regression analysis was used to examine the association between serum bilirubin concentrations and the risk of hearing loss, stratified by age. For participants aged 60 years and younger, the highest TB quartile was associated with a lower risk of high-frequency hearing loss (odds ratio [OR] = 0.74, 95% confidence interval [CI]: 0.56 to 0.97) but not speech-frequency hearing loss after adjusting for confounders. In contrast, serum UCB levels were inversely associated with risks of both high-frequency (OR = 0.57, 95% CI: 0.43 to 0.76) and speech-frequency hearing loss (OR = 0.70, 95% CI: 0.50 to 1.00) in the fully adjusted model. For participants aged 60 years and older, no significant associations were found between serum TB or UCB levels and either type of hearing loss. These results suggest that physiologically elevated serum bilirubin might be protective against hearing loss in younger individuals, with UCB being a more sensitive indicator of hearing loss risk.
The findings of this study contrast with those of two other studies, one of which retrospectively examined adult subjects over 40 years of age from a Korean population, and the other analyzed adolescents from the NHANES 2007 to 2010 data. Both studies suggested that elevated serum bilirubin increased the risk of hearing loss. The disparity in findings may be attributed to differences in the age of study participants. The current study included participants aged 19 to 98 years, while the other studies focused on adolescents or middle-aged and older adults. Hearing loss risk factors vary at different stages of life, and bilirubin may contribute differently to the risk. Additionally, age is an important factor affecting serum bilirubin levels, which might subsequently influence its association with hearing loss. Furthermore, this study excluded individuals with pathologically high serum bilirubin levels, which might eliminate the deleterious effects of bilirubin.
Several limitations of the study should be considered. First, the cross-sectional design precludes the establishment of a causal relationship. It is possible that the oxidative condition of hearing loss might consume antioxidant bilirubin, thereby lowering serum bilirubin levels. Second, the confounding effects of unmeasured factors, such as ear infections or family hearing loss histories, cannot be excluded. Information regarding some potential confounders, such as medical history and medication use, was based on self-reporting, and occupational and recreational noise exposures could not be quantified. These factors might obscure the true relationship between serum bilirubin and hearing loss risk. Therefore, the conclusions of this study should be further validated in well-designed prospective studies.
In summary, despite its limitations, this study suggests that serum bilirubin, particularly in its unconjugated form, might be a protective factor against hearing loss in adults. The findings provide additional evidence supporting the beneficial effects of elevated serum bilirubin on oxidative stress-related chronic diseases. Further research is warranted to explore the mechanisms underlying this association and to confirm these findings in diverse populations.
doi.org/10.1097/CM9.0000000000001268
Was this helpful?
0 / 0