健康老年男性血液中烟酸水平与听力能力呈负相关。
Blood levels of nicotinic acid negatively correlate with hearing ability in healthy older men.
机构信息
Department of Diabetes & Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Data Science Office, Clinical Research Promotion Center, The University of Tokyo Hospital, Tokyo, Japan.
出版信息
BMC Geriatr. 2023 Feb 15;23(1):97. doi: 10.1186/s12877-023-03796-3.
BACKGROUND
Age-related hearing loss (ARHL) is a common phenomenon observed during aging. On the other hand, the decrease in Nicotinamide adenine dinucleotide (NAD +) levels is reported to be closely related to the age-related declines in physiological functions such as ARHL in animal studies. Moreover, preclinical studies confirmed NAD + replenishment effectively prevents the onset of age-related diseases. However, there is a paucity of studies on the relationship between NAD metabolism and ARHL in humans.
METHODS
This study was analyzed the baseline results of our previous clinical trial, in which nicotinamide mononucleotide or placebo was administered to 42 older men (Igarashi et al., NPJ Aging 8:5, 2022). The correlations between blood levels of NAD-related metabolites at baseline and pure-tone hearing thresholds at different frequencies (125, 250, 500, 1000, 2000, 4000, and 8000 Hz) in 42 healthy Japanese men aged > 65 years were analyzed using Spearman's rank correlation. Multiple linear regression analysis was performed with hearing thresholds as the dependent variable and age and NAD-related metabolite levels as independent variables.
RESULTS
Positive associations were observed between levels of nicotinic acid (NA, a NAD precursor in the Preiss-Handler pathway) and right- or left-ear hearing thresholds at frequencies of 1000 Hz (right: r = 0.480, p = 0.001; left: r = 0.422, p = 0.003), 2000 Hz (right: r = 0.507, p < 0.001, left: r = 0.629, p < 0.001), and 4000 Hz (left: r = 0.366, p = 0.029). Age-adjusted multiple linear regression analysis revealed that NA was an independent predictor of elevated hearing thresholds (1000 Hz (right): p = 0.050, regression coefficient (β) = 1610; 1000 Hz (left): p = 0.026, β = 2179; 2000 Hz (right): p = 0.022, β = 2317; 2000 Hz (left): p = 0.002, β = 3257). Weak associations of nicotinic acid riboside (NAR) and nicotinamide (NAM) with hearing ability were observed.
CONCLUSIONS
We identified negative correlations between blood concentrations of NA and hearing ability at 1000 and 2000 Hz. NAD metabolic pathway might be associated with ARHL onset or progression. Further studies are warranted.
TRIAL REGISTRATION
The study was registered at UMIN-CTR (UMIN000036321) on 1st June 2019.
背景
年龄相关性听力损失（ARHL）是衰老过程中观察到的一种常见现象。另一方面，据报道，烟酰胺腺嘌呤二核苷酸（NAD）水平的下降与动物研究中与年龄相关的生理功能下降密切相关，如 ARHL。此外，临床前研究证实 NAD 的补充可以有效预防与年龄相关疾病的发生。然而，关于 NAD 代谢与人类 ARHL 之间的关系的研究很少。
方法
本研究分析了我们之前临床试验的基线结果，在该试验中，给 42 名年龄在 65 岁以上的日本男性服用烟酰胺单核苷酸或安慰剂（Igarashi 等人，NPJ 衰老 8:5, 2022）。使用 Spearman 秩相关分析，分析 42 名健康日本男性基线时 NAD 相关代谢物的血液水平与不同频率（125、250、500、1000、2000、4000 和 8000 Hz）的纯音听力阈值之间的相关性。使用听力阈值作为因变量，年龄和 NAD 相关代谢物水平作为自变量进行多元线性回归分析。
结果
在右耳或左耳 1000 Hz（右耳：r = 0.480，p = 0.001；左耳：r = 0.422，p = 0.003）、2000 Hz（右耳：r = 0.507，p < 0.001，左耳：r = 0.629，p < 0.001）和 4000 Hz（左耳：r = 0.366，p = 0.029）频率下，观察到烟碱（NAD 前体在 Preiss-Handler 途径中的一种）水平与右耳或左耳听力阈值之间存在正相关。年龄调整后的多元线性回归分析表明，NA 是听力阈值升高的独立预测因子（1000 Hz（右耳）：p = 0.050，回归系数（β）= 1610；1000 Hz（左耳）：p = 0.026，β = 2179；2000 Hz（右耳）：p = 0.022，β = 2317；2000 Hz（左耳）：p = 0.002，β = 3257）。烟碱酸核糖苷（NAR）和烟酰胺（NAM）与听力能力的弱相关性也被观察到。
结论
我们发现烟碱酸的血液浓度与 1000 和 2000 Hz 的听力能力之间存在负相关。NAD 代谢途径可能与 ARHL 的发生或进展有关。需要进一步的研究。
试验注册
该研究于 2019 年 6 月 1 日在 UMIN-CTR（UMIN000036321）注册。
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