Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus, Denmark.
Department of Clinical Medicine, Aarhus University, Palle Juul-Jensens Boulevard 82, 8200 Aarhus, Denmark.
Int J Mol Sci. 2022 Aug 28;23(17):9748. doi: 10.3390/ijms23179748.
A way to maintain an adequate vitamin D status is through supplementation. Demonstration of blood-metabolome rhythmicity of vitamin D3 post-dosing effects is lacking in the pharmaco-metabonomics area. Thus, the overall aim of this study was to investigate the diurnal changes in the blood metabolome and how these are affected by vitamin D3 supplementation. The study was conducted as a crossover study, and the treatment included 200 µg (8000 IU) of vitamin D3 as compared with placebo with a washout period of at least 10 days. The participants were postmenopausal women aged 60−80 years (N = 29) with vitamin D insufficiency (serum 25-hydroxyvitamin D < 50 nmol/L) but otherwise healthy. During the intervention day, blood samples were taken at 0 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, and 24 h, and plasma was analysed by proton nuclear magnetic resonance (NMR) spectroscopy as a metabolomics approach. In general, diurnal effects were identified for the majority of the 20 quantified metabolites, and hierarchical cluster analysis revealed a change in the overall plasma metabolome around 12 AM (6 h after intervention), suggesting that the diurnal rhythm is reflected in two diurnal plasma metabolomes; a morning metabolome (8−12 AM) and an afternoon/evening metabolome (2−8 PM). Overall, the effect of vitamin D supplementation on the blood metabolome was minor, with no effect on the diurnal rhythm. However, a significant effect of the vitamin D supplementation on plasma acetone levels was identified. Collectively, our findings reveal an influence of diurnal rhythm on the plasma metabolome, while vitamin D supplementation appears to have minor influence on fluctuations in the plasma metabolome.
一种维持足够维生素 D 状态的方法是通过补充。在药物代谢组学领域，缺乏维生素 D3 给药后血液代谢组节律性的证明。因此，本研究的总体目标是研究血液代谢组的昼夜变化，以及这些变化如何受到维生素 D3 补充的影响。该研究采用交叉设计进行，治疗包括 200 µg（8000 IU）维生素 D3 与安慰剂相比，洗脱期至少 10 天。参与者为绝经后年龄 60-80 岁的女性（N=29），维生素 D 不足（血清 25-羟维生素 D<50 nmol/L）但其他健康。在干预日，在 0 h、2 h、4 h、6 h、8 h、10 h、12 h 和 24 h 时采集血样，并用质子磁共振（NMR）光谱法分析血浆作为代谢组学方法。一般来说，大多数 20 种定量代谢物都存在昼夜效应，层次聚类分析显示，在 12 点左右（干预后 6 小时）整体血浆代谢组发生变化，这表明昼夜节律反映在两种昼夜血浆代谢组中；上午代谢组（8-12 AM）和下午/晚上代谢组（2-8 PM）。总的来说，维生素 D 补充对血液代谢组的影响较小，对昼夜节律没有影响。然而，维生素 D 补充对血浆丙酮水平有显著影响。总之，我们的发现揭示了昼夜节律对血浆代谢组的影响，而维生素 D 补充对血浆代谢组的波动似乎影响较小。
