PDF(Pubmed)
Abstract：
Background: In observational studies, high levels of desphospho-uncarboxylated matrix gla protein (dp-ucMGP) that result from vitamin K deficiency were consistently associated with poor clinical outcomes during COVID-19. Vitamin K-activated matrix gla protein (MGP) is required to protect against elastic fibre degradation, and a deficiency may contribute to pathology. However, intervention trials assessing the effects of vitamin K supplementation in COVID-19 are lacking. Methods: This is a single-centre, phase 2, double-blind, randomised, placebo-controlled trial investigating the effects of vitamin K2 supplementation in 40 hospitalised COVID-19 patients requiring supplemental oxygen. Individuals were randomly assigned in a 1:1 ratio to receive 999 mcg of vitamin K2-menaquinone-7 (MK-7)-or a placebo daily until discharge or for a maximum of 14 days. Dp-ucMGP, the rate of elastic fibre degradation quantified by desmosine, and hepatic vitamin K status quantified by PIVKA-II were measured. Grade 3 and 4 adverse events were collected daily. As an exploratory objective, circulating vitamin K2 levels were measured. Results: Vitamin K2 was well tolerated and did not increase the number of adverse events. A linear mixed model analysis showed that dp-ucMGP and PIVKA-II decreased significantly in subjects that received supplementation compared to the controls (p = 0.008 and p = 0.0017, respectively), reflecting improved vitamin K status. The decrease in dp-ucMGP correlated with higher plasma MK-7 levels (p = 0.015). No significant effect on desmosine was found (p = 0.545). Conclusions: These results demonstrate that vitamin K2 supplementation during COVID-19 is safe and decreases dp-ucMGP. However, the current dose of vitamin K2 failed to show a protective effect against elastic fibre degradation.
摘要：
背景：在观察性研究中，在COVID-19期间，维生素K缺乏导致的高水平去磷酸化未羧化基质gla蛋白（dp-ucMGP）与不良临床结局相关。需要维生素K激活的基质gla蛋白（MGP）来防止弹性纤维降解，缺陷可能会导致病理。然而,缺乏评估补充维生素K对COVID-19影响的干预试验。方法：这是一个单中心，第二阶段，双盲，随机化，安慰剂对照试验研究补充维生素K2对40例需要补充氧气的住院COVID-19患者的影响。个体以1：1的比例随机分配，每天接受999mcg的维生素K2-甲基萘醌-7（MK-7）或安慰剂，直到出院或最多14天。Dp-ucMGP,弹性纤维降解率的量化，和通过PIVKA-II定量的肝脏维生素K状态进行测量。每天收集3级和4级不良事件。作为一个探索目标，测量循环维生素K2水平。结果：维生素K2具有良好的耐受性，并且没有增加不良事件的数量。线性混合模型分析表明，与对照组相比，接受补充的受试者的dp-ucMGP和PIVKA-II显着降低（分别为p=0.008和p=0.0017），反映改善维生素K状态。dp-ucMGP的降低与较高的血浆MK-7水平相关(p=0.015)。未发现对去肌苷的显著影响(p=0.545)。结论：这些结果表明，在COVID-19期间补充维生素K2是安全的，并可降低dp-ucMGP。然而,当前剂量的维生素K2未能显示出对弹性纤维降解的保护作用。
