The Diurnal Blood Metabolome and Effects of Vitamin D Supplementation: A Randomised Crossover Trial in Postmenopausal Women

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A way to maintain an adequate vitamin D status is through supplementation. Demonstration of blood-metabolome rhythmicity of vitamin D 3 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 D 3 supplementation. The study was conducted as a crossover study, and the treatment included 200 µg (8000 IU) of vitamin D 3 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.

Original languageEnglish
Article number9748
JournalInternational Journal of Molecular Sciences
Number of pages13
Publication statusPublished - Aug 2022


  • NMR metabolomics
  • blood metabolites
  • diurnal rhythm
  • rhythmicity
  • vitamin D metabolism


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