PDF(Pubmed)
Abstract：
Vitamin D3\'s role in mineral homeostasis through its endocrine function, associated with the main circulating metabolite 25-hydroxyvitamin D3, is well characterized. However, the increasing recognition of vitamin D3\'s paracrine and autocrine functions-such as cell growth, immune function, and hormone regulation-necessitates examining vitamin D3 levels across different tissues post-supplementation. Hence, this review explores the biodistribution of vitamin D3 in blood and key tissues following oral supplementation in humans and animal models, highlighting the biologically active metabolite, 1,25-dihydroxyvitamin D3, and the primary clearance metabolite, 24,25-dihydroxyvitamin D3. While our findings indicate significant progress in understanding how circulating metabolite levels respond to supplementation, comprehensive insight into their tissue concentrations remains limited. The gap is particularly significant during pregnancy, a period of drastically increased vitamin D3 needs and metabolic alterations, where data remains sparse. Within the examined dosage ranges, both human and animal studies indicate that vitamin D3 and its metabolites are retained in tissues selectively. Notably, vitamin D3 concentrations in tissues show greater variability in response to administered doses. In contrast, its metabolites maintain a more consistent concentration range, albeit different among tissues, reflecting their tighter regulatory mechanisms following supplementation. These observations suggest that serum 25-hydroxyvitamin D3 levels may not adequately reflect vitamin D3 and its metabolite concentrations in different tissues. Therefore, future research should aim to generate robust human data on the tissue distribution of vitamin D3 and its principal metabolites post-supplementation. Relating this data to clinically appropriate exposure metrics will enhance our understanding of vitamin D3\'s cellular effects and guide refinement of clinical trial methodologies.
摘要：
维生素D3通过其内分泌功能在矿物质稳态中的作用，与主要循环代谢物25-羟基维生素D3相关的特征很好。然而,越来越认识到维生素D3的旁分泌和自分泌功能，如细胞生长，免疫功能，和激素调节-需要检查补充后不同组织的维生素D3水平。因此，这篇综述探讨了维生素D3在人类和动物模型中口服补充剂后血液和关键组织中的生物分布，突出生物活性代谢物，1,25-二羟基维生素D3和主要清除代谢物，24,25-二羟基维生素D3。虽然我们的研究结果表明，在理解循环代谢物水平如何对补充剂做出反应方面取得了重大进展，对其组织浓度的全面了解仍然有限。这种差距在怀孕期间尤其显著，一个急剧增加的维生素D3需求和代谢改变的时期，其中数据保持稀疏。在检查的剂量范围内，人类和动物研究均表明维生素D3及其代谢物选择性地保留在组织中。值得注意的是,组织中的维生素D3浓度在响应给药剂量时显示出更大的变异性.相比之下,它的代谢物保持更一致的浓度范围，尽管组织不同，反映了他们在补充后更严格的监管机制。这些观察结果表明，血清25-羟基维生素D3水平可能无法充分反映不同组织中的维生素D3及其代谢物浓度。因此,未来的研究应旨在获得关于补充维生素D3及其主要代谢物组织分布的可靠人类数据.将这些数据与临床适当的暴露指标联系起来，将增强我们对维生素D3细胞效应的理解，并指导临床试验方法的改进。
