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

Hanne Hauger, Christian Ritz, Charlotte Mortensen, Christian Mølgaard, Stine Broeng Metzdorff, Hanne Frøkiær, Camilla Trab Damsgaard
Author Information
  1. Hanne Hauger: Department of Nutrition, Exercise and Sports, University of Copenhagen, Rolighedsvej 26, 1958, Frederiksberg C, Denmark. hha@nexs.ku.dk. ORCID
  2. Christian Ritz: Department of Nutrition, Exercise and Sports, University of Copenhagen, Rolighedsvej 26, 1958, Frederiksberg C, Denmark. ORCID
  3. Charlotte Mortensen: Department of Nutrition, Exercise and Sports, University of Copenhagen, Rolighedsvej 26, 1958, Frederiksberg C, Denmark. ORCID
  4. Christian Mølgaard: Department of Nutrition, Exercise and Sports, University of Copenhagen, Rolighedsvej 26, 1958, Frederiksberg C, Denmark. ORCID
  5. Stine Broeng Metzdorff: Department of Veterinary and Animal Sciences, University of Copenhagen, Ridebanevej 9, 1870, Frederiksberg C, Denmark.
  6. Hanne Frøkiær: Department of Veterinary and Animal Sciences, University of Copenhagen, Ridebanevej 9, 1870, Frederiksberg C, Denmark. ORCID
  7. Camilla Trab Damsgaard: Department of Nutrition, Exercise and Sports, University of Copenhagen, Rolighedsvej 26, 1958, Frederiksberg C, Denmark. ORCID

Abstract

PURPOSE: We explored the effect of winter cholecalciferol (vitamin D) supplementation on innate immune markers in healthy Danish children (55°N).
METHODS: In the double-blind, placebo-controlled trial, ODIN Junior, 119 healthy, white, 4-8 year-olds were randomized to 0 (placebo), 10 or 20 µg/day of vitamin D for 20 weeks (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].
RESULTS: Serum 25(OH)D was 56.7 ± 12.3 nmol/L at baseline and 31.1 ± 7.5, 61.8 ± 10.6, and 75.8 ± 11.5 nmol/L at endpoint after placebo, 10 and 20 µg/day of vitamin D (P < 0.0001), respectively. A decreased oral mucosal S100A9 expression with placebo [- 18 (95% CI - 1; - 32)%] was marginally avoided with 20 µg/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 µg/day [- 109 (- 374; 157) ng/L] (P = 0.07). All other immune markers and respiratory infection episodes were unaffected by vitamin D supplementation (all P > 0.11).
CONCLUSIONS: Winter vitamin D supplementation of 10 µg/day did not affect innate immune markers, whereas 20 µg/day tended to maintain the capacity to produce a few markers in healthy children.

Keywords

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Grants

  1. R180-2014-3481/Lundbeckfonden
  2. A26842/Brødrene Hartmanns Fond
  3. 613877/Seventh Framework Programme

MeSH Term

Biomarkers
Child
Child, Preschool
Cholecalciferol
Dietary Supplements
Double-Blind Method
Female
Humans
Immunity, Innate
Male
Seasons
Vitamin D

Chemicals

Biomarkers
Vitamin D
Cholecalciferol
25-hydroxyvitamin D

Word Cloud

Created with Highcharts 10.0.0Dimmunemarkersvitamin20 µg/daysupplementationhealthyplaceboinnatechildrentrialmucosalIL-8effectcholecalciferol55°Nrandomized10respiratorybaselineendpointInnatesecondaryvivooralexpressionS100A9cathelicidinOHdecreased95%CI%]marginallyavoidedP = 0ng/L]WintercontrolledPURPOSE:exploredwinterDanishMETHODS:double-blindplacebo-controlledODINJunior119white4-8 year-olds020 weeksOctober-MarchCheekswabsbloodsamplesquestionnairesacuteinfectionspreviousmonthcollectedmeasuredoutcomesincludinggenecalprotectinlipocalin-2LCN2beta-defensin-4DEFB4interleukin-8viperinRSAD2cathelicidin-antimicrobial-peptideCAMPexwhole-bloodlipopolysaccharideLPS-inducedIL-6plasmatogetherserum25-hydroxyvitamin[25D]RESULTS:Serum25567 ± 123 nmol/L311 ± 75618 ± 106758 ± 115 nmol/LP < 00001respectively[- 18- 1- 32[6- 132806LikewiseLPS-induced[- 438- 693- 184[- 109- 37415707infectionepisodesunaffectedP > 011CONCLUSIONS:10 µg/dayaffectwhereastendedmaintaincapacityproducelittledefenseaged4-8 years:analysisAntimicrobialpeptidesChildrenCytokinesfunctionRandomizedVitamin

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