School of Public Health, Suzhou Medical College of Soochow University, Suzhou, China.
Department of Chronic Disease Control and Prevention, Changshu Center for Disease Control and Prevention, Changshu, China.
Clin Nutr. 2022 Sep;41(9):1889-1895. doi: 10.1016/j.clnu.2022.07.004. Epub 2022 Jul 10.
BACKGROUND & AIMS: Carnitine biosynthesis has been related to fatty acid oxidation, a process probably exerting neuroprotective effects. However, the role of carnitine biosynthesis in the development of ischemic stroke (IS) remains unclear. We aimed to examine the associations between plasma markers of carnitine biosynthesis and the IS risk.
We performed a case-control study nested in a community-based cohort (2013-2018, n = 16457). The study included 321 incident cases of IS and 321 controls matched by age and gender. Carnitine, lysine, trimethyllysine (TML), glycine, and their ratios were measured/calculated in the baseline plasma samples using ultra-high performance liquid chromatography-tandem mass-spectrometry (UHPLC-MS/MS). Conditional logistic regression analyses were used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs).
Plasma carnitine, lysine, TML, and glycine were not significantly associated with the IS risk, although a gradually reduced risk was observed across the increasing tertiles of glycine. Notably, the ratios of glycine/carnitine, glycine/lysine, and glycine/TML were all inversely associated with the IS risk. Compared to the lowest tertiles, the corresponding odds ratios for the highest tertiles were 0.60 (95% CI: 0.40-0.91), 0.63 (95% CI: 0.42-0.94), and 0.63 (95% CI: 0.42-0.95), respectively, after adjustment for body mass index, smoking, hypertension, family history of stroke, estimated glomerular filtration rate and total cholesterol. Repeating the analyses by excluding the first two years of follow-up did not materially alter the risk associations for the ratios of glycine/lysine and glycine/carnitine.
Increased ratios of plasma glycine to carnitine, lysine, and TML were associated with a lower risk of incident IS. Our observational findings suggest that the homeostasis of circulating carnitine, lysine, TML, and glycine may involve in the pathogenesis of IS.
肉碱生物合成与脂肪酸氧化有关，后者可能具有神经保护作用。然而，肉碱生物合成在缺血性中风（IS）发展中的作用尚不清楚。我们旨在研究血浆肉碱生物合成标志物与 IS 风险之间的关联。
我们进行了一项病例对照研究，该研究嵌套在基于社区的队列中（2013-2018 年，n=16457）。该研究包括 321 例缺血性中风病例和 321 名年龄和性别匹配的对照。使用超高效液相色谱-串联质谱（UHPLC-MS/MS）在基线血浆样本中测量/计算肉碱、赖氨酸、三甲赖氨酸（TML）、甘氨酸及其比值。使用条件逻辑回归分析计算比值比（OR）及其 95%置信区间（CI）。
血浆肉碱、赖氨酸、TML 和甘氨酸与 IS 风险无显著相关性，尽管甘氨酸随着 tertiles 的增加呈逐渐降低的趋势。值得注意的是，甘氨酸/肉碱、甘氨酸/赖氨酸和甘氨酸/TML 的比值均与 IS 风险呈负相关。与最低 tertiles 相比，最高 tertiles 的相应比值比分别为 0.60（95%CI：0.40-0.91）、0.63（95%CI：0.42-0.94）和 0.63（95%CI：0.42-0.95），调整体重指数、吸烟、高血压、中风家族史、估计肾小球滤过率和总胆固醇后。在排除前两年的随访后重复分析，对甘氨酸/赖氨酸和甘氨酸/肉碱比值的风险关联没有明显改变。
血浆甘氨酸与肉碱、赖氨酸和 TML 的比值增加与缺血性中风的发生风险降低相关。我们的观察性发现表明，循环肉碱、赖氨酸、TML 和甘氨酸的内环境平衡可能与缺血性中风的发病机制有关。
