Abstract
Critically ill patients have low circulating 25-hydroxyvitamin D (25OHD),
vitamin D binding protein (DBP), and 1,25-dihydroxyvitamin D
[1,25(OH)2D]. Low 25OHD is associated with poor outcomes,
possibly explained by its effect on bone and immunity. In this prospective,
randomized double-blind, placebo-controlled study, we investigated the
feasibility of normalizing 25OHD in prolonged (>10 days) critically
ill patients and the effects thereof on 1,25(OH)2D, bone
metabolism, and innate immunity. Twenty-four patients were included and
compared with 24 matched healthy subjects. Patients were randomized to
either intravenous bolus of 200 μg 25OHD followed by daily
infusion of 15 μg 25OHD for 10 days, or to placebo.
Parameters of vitamin D, bone and mineral metabolism, and innate immune
function were measured. As safety endpoints, ICU length of stay and
mortality were registered. Infusion of 25OHD resulted in a sustained
increase of serum 25OHD (from median baseline
9.2 –16.1 ng/ml at day 10), which,
however, remained below normal levels. There was no increase in serum
1,25(OH)2D but a slight increase in serum
24,25(OH)2D. Mineral homeostasis, innate immunity and
clinical safety endpoints were unaffected. Thus, intravenous 25OHD
administration during critical illness increased serum 25OHD concentrations,
though less than expected from data in healthy subjects, which suggests
illness-induced alterations in 25OHD metabolism and/or increased
25OHD distribution volume. The increased serum 25OHD concentrations were not
followed by a rise in 1,25(OH)2D nor were bone metabolism or
innate immunity affected, which suggests that low 25OHD and 1,25OHD levels
are part of the adaptive response to critical illness.
Key words
vitamin D - critical illness - innate immunity - bone metabolism