School of Pharmacy, Unit of Molecular Biology, University of Camerino, 62032 Camerino, Italy.
Doctoral School for Physical Culture Sciences, 80-336 Gdansk, Poland.
Int J Mol Sci. 2020 Feb 5;21(3):1047. doi: 10.3390/ijms21031047.
l-carnitine supplementation has been used for cardiovascular health protection for a long time. Recently, trimethylamine-N-oxide (TMAO), which is an end product of l-carnitine metabolism via the activity of microbiota, has been identified as a cardiovascular disease (CVD) biomarker. The aim of this study was to assess the effect of 6 months of l-carnitine supplementation in a group of aged women engaged in a regular physical training. Platelet mitochondrial DNA methylation, an emerging and innovative biomarker, lipid profile and TMAO levels have been measured. TMAO increased after l-carnitine supplementation (before 344.3 ± 129.8 ng/mL vs. after 2216.8 ± 1869.0 ng/mL; = 9; paired t-test, = 0.02). No significant effects on TMAO were exerted by training alone ( = 9) or by l-leucine supplementation ( = 12). TMAO levels after 6 months of l-carnitine supplementation were associated with higher low-density lipoprotein-cholesterol (LDL-c) (Spearman Rho = 0.518, = 0.003) and total cholesterol (TC) (Spearman Rho = 0.407, = 0.026) levels. l-carnitine supplementation increased D-loop methylation in platelets (+6.63%; paired t-test, = 0.005). D-loop methylation was not directly correlated to the TMAO augmentation observed in the supplemented group, but its increase inversely correlated with TC (Pearson coefficient = -0.529, = 0.029) and LDL-c (Pearson coefficient = -0.439, = 0.048). This evidence supports the hypothesis that the correlation between l-carnitine, TMAO and atherosclerosis might be more complex than already postulated, and the alteration of mitochondrial DNA (mtDNA) methylation in platelets could be involved in the pathogenesis of this multifactorial disease.
左旋肉碱补充剂长期以来一直被用于保护心血管健康。最近，三甲胺 N-氧化物（TMAO）被确定为心血管疾病（CVD）的生物标志物，它是左旋肉碱代谢的终产物，通过微生物的活性产生。本研究旨在评估 6 个月左旋肉碱补充剂对一组进行常规体育锻炼的老年女性的影响。血小板线粒体 DNA 甲基化，一种新兴的创新生物标志物，脂质谱和 TMAO 水平已经被测量。TMAO 在左旋肉碱补充后增加（补充前 344.3±129.8ng/mL 与补充后 2216.8±1869.0ng/mL；n=9；配对 t 检验，=0.02）。单独训练（n=9）或补充 L-亮氨酸（n=12）对 TMAO 没有显著影响。6 个月左旋肉碱补充后 TMAO 水平与低密度脂蛋白胆固醇（LDL-c）（Spearman Rho=0.518，=0.003）和总胆固醇（TC）（Spearman Rho=0.407，=0.026）水平呈正相关。左旋肉碱补充增加血小板 D-环甲基化（+6.63%；配对 t 检验，=0.005）。D-环甲基化与补充组观察到的 TMAO 增加没有直接相关性，但与 TC（Pearson 系数=-0.529，=0.029）和 LDL-c（Pearson 系数=-0.439，=0.048）呈负相关。这一证据支持这样一种假设，即左旋肉碱、TMAO 和动脉粥样硬化之间的相关性可能比已经假设的更为复杂，血小板中线粒体 DNA（mtDNA）甲基化的改变可能与这种多因素疾病的发病机制有关。
