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

doi:10.1007/s00394-018-1671-8

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

^*Corresponding author af dette arbejde

Ernæring og Sundhed hos børn og voksne

4 Citationer (Scopus)

Abstract

Purpose: We explored the effect of winter cholecalciferol (vitamin D₃) 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 D₃ 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 D₃ (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 D₃ supplementation (all P > 0.11). Conclusions: Winter vitamin D₃ 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.

Originalsprog	Engelsk
Tidsskrift	European Journal of Nutrition
Vol/bind	58
Udgave nummer	4
Sider (fra-til)	1453-1462
Antal sider	10
ISSN	1436-6207
DOI	https://doi.org/10.1007/s00394-018-1671-8
Status	Udgivet - 1 jun. 2019

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Det Natur- og Biovidenskabelige Fakultet

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10.1007/s00394-018-1671-8

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Hauger, H., Ritz, C., Mortensen, C., Mølgaard, C., Metzdorff, S. B., Frøkiær, H., & Damsgaard, C. T. (2019). 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. European Journal of Nutrition, 58(4), 1453-1462. https://doi.org/10.1007/s00394-018-1671-8

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. / Hauger, Hanne; Ritz, Christian; Mortensen, Charlotte et al.
I: European Journal of Nutrition, Bind 58, Nr. 4, 01.06.2019, s. 1453-1462.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Hauger, H, Ritz, C, Mortensen, C, Mølgaard, C, Metzdorff, SB, Frøkiær, H & Damsgaard, CT 2019, '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', European Journal of Nutrition, bind 58, nr. 4, s. 1453-1462. https://doi.org/10.1007/s00394-018-1671-8

@article{4da02b9a78a6458bab806d67824bf4d7,

title = "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",

abstract = "Purpose: We explored the effect of winter cholecalciferol (vitamin D3) 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 D3 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 D3 (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 D3 supplementation (all P > 0.11). Conclusions: Winter vitamin D3 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 = "Faculty of Science, Randomized controlled trial, Vitamin D, Children, Innate immune function, Antimicrobial peptides, Cytokines",

author = "Hanne Hauger and Christian Ritz and Charlotte Mortensen and Christian M{\o}lgaard and Metzdorff, {Stine Broeng} and Hanne Fr{\o}ki{\ae}r and Damsgaard, {Camilla Trab}",

note = "CURIS 2019 NEXS 207",

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doi = "10.1007/s00394-018-1671-8",

language = "English",

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pages = "1453--1462",

journal = "European Journal of Nutrition",

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TY - JOUR

T1 - Winter cholecalciferol supplementation at 55°N has little effect on markers of innate immune defense in healthy children aged 4-8 years

T2 - A secondary analysis from a randomized controlled trial

AU - Hauger, Hanne

AU - Ritz, Christian

AU - Mortensen, Charlotte

AU - Mølgaard, Christian

AU - Metzdorff, Stine Broeng

AU - Frøkiær, Hanne

AU - Damsgaard, Camilla Trab

N1 - CURIS 2019 NEXS 207

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Purpose: We explored the effect of winter cholecalciferol (vitamin D3) 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 D3 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 D3 (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 D3 supplementation (all P > 0.11). Conclusions: Winter vitamin D3 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.

AB - Purpose: We explored the effect of winter cholecalciferol (vitamin D3) 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 D3 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 D3 (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 D3 supplementation (all P > 0.11). Conclusions: Winter vitamin D3 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.

KW - Faculty of Science

KW - Randomized controlled trial

KW - Vitamin D

KW - Children

KW - Innate immune function

KW - Antimicrobial peptides

KW - Cytokines

U2 - 10.1007/s00394-018-1671-8

DO - 10.1007/s00394-018-1671-8

M3 - Journal article

C2 - 29572676

SN - 1436-6207

VL - 58

SP - 1453

EP - 1462

JO - European Journal of Nutrition

JF - European Journal of Nutrition

IS - 4

ER -

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

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