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Oxidative stress in critically ill ventilated adults: effects of vitamin D3 and associations with alveolar macrophage function

European Journal of Clinical Nutrition volume 72, pages 744–751 (2018)Cite this article

Subjects

Abstract

Background/objectives

Disruptions in redox balance lead to oxidative stress, a promoter of morbidity in critical illness. This study aimed to: (1) characterize the plasma and alveolar thiol/disulfide redox pools, (2) examine their associations with alveolar macrophage phagocytosis, and (3) determine the effect of high dose vitamin D3 on plasma thiol/disulfide redox.

Subjects/methods

Subjects were 30 critically ill, ventilated adults in a double-blind randomized trial of high-dose (250 000 or 500 000 IU) vitamin D3 or placebo. Baseline bronchoalveolar lavage fluid (BALF) samples were analyzed for determination of alveolar phagocytosis index (PI) and for concentrations of glutathione (GSH), glutathione disulfide (GSSG), cysteine (Cys), cystine (CySS), and their respective redox potentials (EhGSSG and EhCySS). Plasma redox outcomes were assessed at baseline and days 7 and 14.

Results

Baseline plasma Cys was inversely associated with alveolar PI (ρ = −0.69, P = 0.003), and EhCySS was positively associated with PI (ρ = 0.61, P = 0.01). Over time, among all subjects there was an increase in plasma GSH levels and a decrease in EhGSSG (P < 0.01 for both), with no difference by treatment group. Vitamin D3 decreased oxidized plasma GSSG to a more normal state (P for group x time = 0.009).

Conclusions

Oxidative stress indicators were positively associated with alveolar macrophage phagocytic function in acutely ill ventilated adults. High-dose vitamin D3 decreased plasma GSSG concentrations, which suggests that vitamin D can possibly improve the oxidative stress environment.

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Acknowledgements

We would like to acknowledge Mona Brown, Guatam Hebbar, Jennifer Jones, Frank Harris, and Janine Ward for their contribution to the study.

Funding

Funding

This project was supported, in part, by National Institutes of Health grants: NIH R21 HL110044 (GSM, TRZ, LAB, VT, JEH), K24 DK096574 (TRZ), UL1 TR000454 (JEH, GSM, TRZ, VT), K01 DK102851 (JAA), T32 HL076118 (BS), and T32 AA013528 (JEH).

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Author notes

  1. Jenny E. Han and Jessica A. Alvarez are Contributed equally to this work

Authors and Affiliations

  1. Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University, Atlanta, GA, USA

    Jenny E. Han, Bashar Staitieh & Greg S. Martin

  2. Emory Critical Care Center, Emory University, Atlanta, GA, USA

    Jenny E. Han, Bashar Staitieh & Greg S. Martin

  3. Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University, Atlanta, GA, USA

    Jessica A. Alvarez, Vin Tangpricha, Li Hao & Thomas R. Ziegler

  4. Atlanta VA Medical Center, Decatur, GA, USA

    Vin Tangpricha & Thomas R. Ziegler

  5. Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Emory University, Atlanta, GA, USA

    Lou Ann S. Brown

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  1. Jenny E. Han
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Correspondence to Jenny E. Han.

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Han, J.E., Alvarez, J.A., Staitieh, B. et al. Oxidative stress in critically ill ventilated adults: effects of vitamin D3 and associations with alveolar macrophage function. Eur J Clin Nutr 72, 744–751 (2018). https://doi.org/10.1038/s41430-017-0047-0

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