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 for this work

Lifecourse Nutrition & Health

4 Citations (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.

Original language	English
Journal	European Journal of Nutrition
Volume	58
Issue number	4
Pages (from-to)	1453-1462
Number of pages	10
ISSN	1436-6207
DOIs	https://doi.org/10.1007/s00394-018-1671-8
Publication status	Published - 1 Jun 2019

Keywords

Faculty of Science
Randomized controlled trial
Vitamin D
Children
Innate immune function
Antimicrobial peptides
Cytokines

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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.

In: European Journal of Nutrition, Vol. 58, No. 4, 01.06.2019, p. 1453-1462.

Research output: Contribution to journal › Journal article › Research › 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, vol. 58, no. 4, pp. 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}",

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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

Abstract

Keywords

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