Vitamin D is more bio-available when children are critically ill (less Binding Protein) – Sept 2015

Critically Ill Children Have Low Vitamin D Binding Protein, Influencing Bioavailability of Vitamin D

Annals ATS.(Annals of the American Thoracic Society) First published online 10 Sep 2015 as DOI: 10.1513/AnnalsATS.201503-160OC
Kate Madden kate.madden at childrens.harvard.edu , Henry A. Feldman, Rene F. Chun, Ellen M Smith, Ryan M Sullivan, Anna A Agan, Shannon M Keisling, Angela Panoskaltsis-Mortari, and Adrienne G Randolph

Rationale: Vitamin D deficiency, often defined by total serum 25-hydroxyvitamin D (25(OH)D) <20 ng/mL, is common in critically ill patients, with associations to increased mortality and morbidity in the intensive care unit. Correction of vitamin D deficiency in critical illness has been recommended, and ongoing clinical trials are investigating the effect of repletion on patient outcome. The biologically active amount of 25(OH)D depends on the concentration and protein isoform of vitamin D binding protein, also an acute phase reactant affected by inflammation and injury.

Objectives: We performed a secondary analysis of a cohort of critically ill children in which we reported a high rate of vitamin D deficiency, to examine how vitamin D binding protein level and genotype would impact vitamin D status. Methods: We prospectively enrolled 511 children admitted to the pediatric intensive care unit over a 12-month period.

Measurements and Main Results: We measured serum vitamin D binding protein in 479 children. We genotyped single nucleotide polymorphisms rs7041 and rs4588 in the vitamin D binding protein gene (GC) to determine haplotypes GC1F, GC1S, and GC2 in 178 subjects that consented, then calculated bioavailable 25-hydroxyvitamin D from serum 25(OH)D, vitamin D binding protein, albumin and GC haplotype. The median serum vitamin D binding protein level was 159 µg/mL (IQR 108, 221), lower than has been reported in healthy children. Factors predicting lower levels in multivariate analysis included age <1 year, non-white race, being previously healthy, 25(OH)D <20 ng/mL and higher illness severity.
In the subgroup that were genotyped, GC haplotype had the strongest association with vitamin D binding protein level; carriage of one additional copy of GC1S was associated with 37.5% higher level (95%CI 31.9, 44.8; p<0.001).
Bioavailable 25OHD was also inversely associated with illness severity (r= -0.24, p<0.001), ratio to measured total 25(OH)D was variable and related to haplotype.

Conclusions: Physiologic deficiency of 25(OH)D in critical illness may be more difficult to diagnose, given that lower vitamin D binding protein levels increase bioavailability. Treatment studies based on total 25(OH)D level, without consideration of vitamin D binding protein concentration and genotype, may increase the risk of falsely negative results.

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Summary of very interesting graphs in the PDF

• Bioavailable Vitamin D varies from 10% to 50% of total Vitamin D, depending on haplotype
• Vitamin D binding protein decreases with severity of illness – from 195 ug/mL down to 150 at most severe
• Vitamin D binding protein varied with haplotype from 195 ug/ml down to 30 ug/m?

A haplotype is a set of DNA variations, or polymorphisms, that tend to be inherited together.
the highest levels

Binding protein vs race from the PDF)

White non-Hispanic	166 µg/mL
White Hispanic	152 µg/mL
AfricanAmerican	141 µg/mL

See also VitaminDWiki

• Vitamin D Binding Protein category listing has 178 items along with related searches
• Bioavailable Vitamin D is the same blacks and whites, but measured vit D is not – Oct 2014
• Benefits of Vitamin D often limited by genes