trimethyllysine and Stroke

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.

Topics: Carnitine; Case-Control Studies; Fabaceae; Glycine; Humans; Ischemic Stroke; Lysine; Stroke; Tandem Mass Spectrometry

γ-butyrobetaine (γBB) is a metabolite from dietary Carnitine, involved in the gut microbiota-dependent conversion from Carnitine to the pro-atherogenic metabolite trimethylamine-N-oxide (TMAO). Orally ingested γBB has a pro-atherogenic effect in experimental studies, but γBB has not been studied in relation to atherosclerosis in humans. The aim of this study was to evaluate associations between serum levels of γBB, TMAO and their common precursors Carnitine and trimethyllysine (TML) and carotid atherosclerosis and adverse outcome.. Serum γBB, Carnitine, TML and TMAO were quantified by high performance liquid chromatography in patients with carotid artery atherosclerosis (n = 264) and healthy controls (n = 62).. Serum γBB (p = 0.024) and Carnitine (p = 0.001), but not TMAO or TML, were increased in patients with carotid atherosclerosis. Higher levels of γBB and TML, but not TMAO or Carnitine were independently associated with cardiovascular death also after adjustment for age and eGFR (adjusted HR [95%] 3.3 [1.9-9.1], p = 0.047 and 6.0 [1.8-20.34], p = 0.026, respectively).. Patients with carotid atherosclerosis had increased serum levels of γBB, and elevated levels of γBB and its precursor TML were associated with cardiovascular mortality. Long-term clinical studies of γBB, as a cardiovascular risk marker, and safety studies regarding dietary supplementation of γBB, are warranted.

Topics: Aged; Betaine; Biomarkers; Carnitine; Carotid Stenosis; Case-Control Studies; Cause of Death; Chromatography, High Pressure Liquid; Female; Humans; Kaplan-Meier Estimate; Lysine; Male; Methylamines; Middle Aged; Myocardial Infarction; Prognosis; Proportional Hazards Models; Risk Assessment; Risk Factors; Severity of Illness Index; Stroke; Ultrasonography, Doppler, Color