Winter cholecalciferol supplementation at 55°N has little effect on markers of innate immune defense in healthy children aged 4-8years: a secondary analysis from a randomized controlled trial

PurposeWe explored the effect of winter cholecalciferol (vitamin D-3) supplementation on innate immune markers in healthy Danish children (55 degrees N).MethodsIn the double-blind, placebo-controlled trial, ODIN Junior, 119 healthy, white, 4-8year-olds were randomized to 0 (placebo), 10 or 20 mu g/day of vitamin D-3 for 20weeks (October-March). Cheek mucosal swabs, blood samples, and questionnaires on acute respiratory infections the previous month were collected at baseline and endpoint. Innate immune markers were measured as secondary outcomes including in vivo oral mucosal gene expression of calprotectin (S100A9), lipocalin-2 (LCN2), beta-defensin-4 (DEFB4), interleukin-8 (IL-8), viperin (RSAD2), and the cathelicidin-antimicrobial-peptide (CAMP); ex vivo whole-blood lipopolysaccharide (LPS)-induced cathelicidin, IL-8, and IL-6; and plasma cathelicidin, together with serum 25-hydroxyvitamin D [25(OH)D].ResultsSerum 25(OH)D was 56.712.3nmol/L at baseline and 31.1 +/- 7.5, 61.8 +/- 10.6, and 75.8 +/- 11.5nmol/L at endpoint after placebo, 10 and 20 mu g/day of vitamin D-3 (P<0.0001), respectively. A decreased oral mucosal S100A9 expression with placebo [-18 (95% CI -1; -32)%] was marginally avoided with 20 mu g/day [6 (-13; 28)%] (P=0.06). Likewise, a decreased LPS-induced IL-8 with placebo [-438 (95% CI -693; -184) ng/L] was marginally avoided with 20 mu g/day [-109 (-374; 157) ng/L] (P=0.07). All other immune markers and respiratory infection episodes were unaffected by vitamin D-3 supplementation (all P>0.11).ConclusionsWinter vitamin D-3 supplementation of 10 mu g/day did not affect innate immune markers, whereas 20 mu g/day tended to maintain the capacity to produce a few markers in healthy children.