TY - BOOK

T1 - Vitamin D, Immune Defence, and Cardiometabolic Health in Children

AU - Hauger, Hanne

N1 - CURIS 2018 NEXS 392

PY - 2018

Y1 - 2018

N2 - Background: Vitamin D is important for skeletal health, but in recent years there has been a growing interest in the potential non-skeletal effects of vitamin D. Up to 76% of children aged 0-18 years worldwide are estimated to have inadequate vitamin D status. Furthermore, the vitamin D status of children living in Denmark and other countries in moderate-higher northern latitudes inevitably declines during winter as the solar UVB radiation, which induces cutaneous vitamin Dproduction, diminishes in this season. Maintaining adequate vitamin D status through supplementation in children with vitamin D has been suggested as a strategy to prevent acute respiratory infections and to aid early prevention of cardiovascular disease - two areas of major importance for public health. Based on studies ex vivo in adults and in vitro, potential effects of vitamin D on respiratory infections are suggested to occur via effects on the innate immune system. The effects of vitamin D on markers of the innate immune defence, however, are yet to be investigated in young healthy children in a randomized controlled trial. In addition, the cardiometabolic effects of vitamin D are yet to be explored in a randomized controlled trial in this population. Moreover, an overview of current trials investigating effects of vitamin D supplementation on cardiometabolic health in children aged 0-18 years is lacking.Objective: The main objective of this PhD thesis was to investigate effects of winter vitamin D supplementation on markers of the innate immune defence and on cardiometabolic health in a randomized controlled trial in healthy, 4-8 year-old Danish children living in northern latitudes. Additionally, the aim was to provide an overview of the effects of vitamin D supplementation on cardiometabolic health across randomized controlled trials conducted in overweight as well as normal weight children aged 0-18 years.Methods: Paper I-II report the effects of daily supplementation with 0 (placebo), 10 and 20 µg of vitamin D during 5 winter months on markers of the innate immune defence and cardiometabolic health, respectively, in healthy 4-8 year-old children living in Denmark (55ºN). The markers investigated were secondary outcomes from the randomized controlled vitamin D trial, ODIN Junior, including 119 children. In these papers, we explore whether prevention of the decline invitamin D status over winter favourably affects immune and cardiometabolic markers. Immune outcomes included a range of host defence peptides with antibacterial, antiviral, pro-inflammatory, and chemotactic functions. They were measured as gene expression in the oral mucosa, and as peptide concentrations in plasma and ex vivo stimulated whole-blood. Cardiometabolic outcomes included markers of glucose metabolism, blood lipids, blood pressure, body mass index, and waist circumference. Paper III reports results of a systematic literature search on randomized controlled trials examining cardiometabolic effects of vitamin D supplementation in children aged 0-18 years. Results: In ODIN Junior, the children’s mean vitamin D status (serum 25-hydroxyvitamin D) was 56.8 ± 12.5 nmol/L at baseline, and decreased considerably to 31.1 ± 7.5 nmol/L with placebo, while it increased to 61.8 ± 10.6 and 75.8 ± 11.5 nmol/L in the groups receiving 10 and 20 μg/d of vitamin D, respectively. Overall, the winter vitamin D supplementation had no effects on a range of markers of the innate immune system and cardiometabolic risk in healthy, 4-8 year-old children living in northern latitudes. However, there was a tendency towards having a greater production of a few host defence peptides in the group receiving 20 µg/d, whereas the production decreased in the placebo group, although this was not significant. The review showed that most (12 out of 14) randomized controlled trials including ODIN Junior found no cardiometabolic effects of vitamin D, regardless of body mass index and baseline serum 25(OH)D. One study showed positive effects of vitamin D on insulin resistance in obese adolescents, while another found mixed effects on blood lipids in Iranian school children. The ability to draw conclusions were limited by the small sample sizes in most studies combined with a considerable heterogeneity in the dose of vitamin D given, body mass index and baseline vitamin D status. Conclusion: Vitamin D intakes at one and two times the recommended daily intake during winter, had no effects on a range of markers of the innate immune defence and cardiometabolic health in young, healthy children living in moderate-higher northern latitudes. Consequently, the pronounced seasonal variation in serum 25(OH)D commonly observed in these latitudes does not seem to have any considerable short-term adverse effects on immune- or cardiometabolic function. Similarly, the review of studies investigating the cardiometabolic effects of vitamin D in children provided little support for the suggestion that vitamin D plays a role in early prevention of cardiovascular disease. Due to limited available evidence for the role of vitamin D in modulation of immunological and cardiometabolic markers in children, there is a clear need for more high-quality randomized controlled trials before more certain conclusions can be made. 

AB - Background: Vitamin D is important for skeletal health, but in recent years there has been a growing interest in the potential non-skeletal effects of vitamin D. Up to 76% of children aged 0-18 years worldwide are estimated to have inadequate vitamin D status. Furthermore, the vitamin D status of children living in Denmark and other countries in moderate-higher northern latitudes inevitably declines during winter as the solar UVB radiation, which induces cutaneous vitamin Dproduction, diminishes in this season. Maintaining adequate vitamin D status through supplementation in children with vitamin D has been suggested as a strategy to prevent acute respiratory infections and to aid early prevention of cardiovascular disease - two areas of major importance for public health. Based on studies ex vivo in adults and in vitro, potential effects of vitamin D on respiratory infections are suggested to occur via effects on the innate immune system. The effects of vitamin D on markers of the innate immune defence, however, are yet to be investigated in young healthy children in a randomized controlled trial. In addition, the cardiometabolic effects of vitamin D are yet to be explored in a randomized controlled trial in this population. Moreover, an overview of current trials investigating effects of vitamin D supplementation on cardiometabolic health in children aged 0-18 years is lacking.Objective: The main objective of this PhD thesis was to investigate effects of winter vitamin D supplementation on markers of the innate immune defence and on cardiometabolic health in a randomized controlled trial in healthy, 4-8 year-old Danish children living in northern latitudes. Additionally, the aim was to provide an overview of the effects of vitamin D supplementation on cardiometabolic health across randomized controlled trials conducted in overweight as well as normal weight children aged 0-18 years.Methods: Paper I-II report the effects of daily supplementation with 0 (placebo), 10 and 20 µg of vitamin D during 5 winter months on markers of the innate immune defence and cardiometabolic health, respectively, in healthy 4-8 year-old children living in Denmark (55ºN). The markers investigated were secondary outcomes from the randomized controlled vitamin D trial, ODIN Junior, including 119 children. In these papers, we explore whether prevention of the decline invitamin D status over winter favourably affects immune and cardiometabolic markers. Immune outcomes included a range of host defence peptides with antibacterial, antiviral, pro-inflammatory, and chemotactic functions. They were measured as gene expression in the oral mucosa, and as peptide concentrations in plasma and ex vivo stimulated whole-blood. Cardiometabolic outcomes included markers of glucose metabolism, blood lipids, blood pressure, body mass index, and waist circumference. Paper III reports results of a systematic literature search on randomized controlled trials examining cardiometabolic effects of vitamin D supplementation in children aged 0-18 years. Results: In ODIN Junior, the children’s mean vitamin D status (serum 25-hydroxyvitamin D) was 56.8 ± 12.5 nmol/L at baseline, and decreased considerably to 31.1 ± 7.5 nmol/L with placebo, while it increased to 61.8 ± 10.6 and 75.8 ± 11.5 nmol/L in the groups receiving 10 and 20 μg/d of vitamin D, respectively. Overall, the winter vitamin D supplementation had no effects on a range of markers of the innate immune system and cardiometabolic risk in healthy, 4-8 year-old children living in northern latitudes. However, there was a tendency towards having a greater production of a few host defence peptides in the group receiving 20 µg/d, whereas the production decreased in the placebo group, although this was not significant. The review showed that most (12 out of 14) randomized controlled trials including ODIN Junior found no cardiometabolic effects of vitamin D, regardless of body mass index and baseline serum 25(OH)D. One study showed positive effects of vitamin D on insulin resistance in obese adolescents, while another found mixed effects on blood lipids in Iranian school children. The ability to draw conclusions were limited by the small sample sizes in most studies combined with a considerable heterogeneity in the dose of vitamin D given, body mass index and baseline vitamin D status. Conclusion: Vitamin D intakes at one and two times the recommended daily intake during winter, had no effects on a range of markers of the innate immune defence and cardiometabolic health in young, healthy children living in moderate-higher northern latitudes. Consequently, the pronounced seasonal variation in serum 25(OH)D commonly observed in these latitudes does not seem to have any considerable short-term adverse effects on immune- or cardiometabolic function. Similarly, the review of studies investigating the cardiometabolic effects of vitamin D in children provided little support for the suggestion that vitamin D plays a role in early prevention of cardiovascular disease. Due to limited available evidence for the role of vitamin D in modulation of immunological and cardiometabolic markers in children, there is a clear need for more high-quality randomized controlled trials before more certain conclusions can be made. 

UR - https://soeg.kb.dk/permalink/45KBDK_KGL/1pioq0f/alma99122417839305763

M3 - Ph.D. thesis

SN - 978-87-7209-201-0

BT - Vitamin D, Immune Defence, and Cardiometabolic Health in Children

PB - Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen

CY - Copenhagen

ER -