Department of Pediatrics, Louisiana State University Health Sciences Center , Shreveport, Louisiana.
Antioxid Redox Signal. 2018 Dec 10;29(17):1792-1807. doi: 10.1089/ars.2017.7462. Epub 2018 Oct 9.
25-Hydroxyvitamin D [25(OH)VD] deficiency/inadequacy is a major public health issue affecting more than 1 billion people worldwide. A convincing association exists between low levels of circulating 25(OH)VD and the poor health outcomes associated with chronic diseases. However, high supraphysiological doses of VD are needed to achieve the required 25(OH)VD levels in the blood, because many subjects respond poorly to supplementation.
This study reports a link between 25(OH)VD deficiency and a reduction in glutathione (GSH) in obese adolescents. The improvement in GSH status that results from cosupplementation with VD and l-cysteine (LC; a GSH precursor) significantly reduced oxidative stress in a mouse model of 25(OH)VD deficiency. It also positively upregulated VD regulatory genes (VDBP/VD-25-hydroxylase/VDR) in the liver and glucose metabolism genes (PGC-1α/VDR/GLUT-4) in muscle, boosted 25(OH)VD, and reduced inflammation and insulin resistance (IR) levels in the blood compared with supplementation with VD alone. In vitro GSH deficiency caused increased oxidative stress and downregulation of VDBP/VD-25-hydroxylase/VDR and upregulation of CYP24a1 in hepatocytes and downregulation of PGC-1α/VDR/GLUT-4 in myotubes. This study demonstrates that improvement in the GSH status exerts beneficial effects on the blood levels of 25(OH)VD, as well as on the inflammation and IR in a VD-deficient mouse model. Thus, the VD supplements widely consumed by the public are unlikely to be successful unless the GSH status is also corrected.
These studies demonstrate a previously undiscovered mechanism by which GSH status positively upregulates the bioavailability of 25(OH)VD.
Supplementation with a combination of VD and LC or GSH precursor, rather than supplementation with VD alone, is beneficial and helps achieve more successful VD supplementation. Antioxid. Redox Signal. 00, 000-000.
25-羟维生素 D [25(OH)VD] 缺乏/不足是一个主要的公共卫生问题，影响着全球超过 10 亿人。循环 25(OH)VD 水平低与慢性疾病相关的健康不良结局之间存在令人信服的关联。然而，需要高生理剂量的 VD 才能在血液中达到所需的 25(OH)VD 水平，因为许多受试者对补充剂的反应不佳。
本研究报告了肥胖青少年中 25(OH)VD 缺乏与谷胱甘肽 (GSH) 减少之间的联系。VD 和 L-半胱氨酸 (LC；GSH 前体) 联合补充显著改善 GSH 状态，可显著减轻 25(OH)VD 缺乏症小鼠模型中的氧化应激。它还在肝脏中正向上调 VD 调节基因 (VDBP/VD-25-羟化酶/VDR) 和肌肉中的葡萄糖代谢基因 (PGC-1α/VDR/GLUT-4)，增加 25(OH)VD，并降低血液中的炎症和胰岛素抵抗 (IR) 水平，与单独补充 VD 相比。体外 GSH 缺乏导致肝细胞中氧化应激增加、VDBP/VD-25-羟化酶/VDR 下调和 CYP24a1 上调，以及肌管中 PGC-1α/VDR/GLUT-4 下调。本研究表明，改善 GSH 状态对 VD 缺乏症小鼠模型中的 25(OH)VD 血液水平以及炎症和 IR 具有有益作用。因此，除非同时纠正 GSH 状态，否则公众广泛服用的 VD 补充剂不太可能成功。
这些研究表明，GSH 状态正向调节 25(OH)VD 生物利用度的一种以前未被发现的机制。
补充 VD 和 LC 或 GSH 前体的组合，而不是单独补充 VD，是有益的，并有助于实现更成功的 VD 补充。抗氧化剂。氧化还原信号。00，000-000。
