Winter vitamin D3 supplementation does not increase muscle strength, but modulates the IGF-axis in young children
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To explore whether muscle strength, the insulin-like growth factor axis (IGF-axis), height, and body composition were associated with serum 25-hydroxyvitamin D [25(OH)D] and affected by winter vitamin D supplementation in healthy children, and furthermore to explore potential sex differences.
We performed a double-blind, placebo-controlled, dose–response winter trial at 55ºN. A total of 117 children aged 4–8 years were randomly assigned to either placebo, 10, or 20 µg/day of vitamin D3 for 20 weeks. At baseline and endpoint, we measured muscle strength with handgrip dynamometer, fat mass index (FMI), fat free mass index (FFMI), height, plasma IGF-1, IGF-binding protein 3 (IGFBP-3), and serum 25(OH)D.
At baseline, serum 25(OH)D was positively associated with muscle strength, FFMI, and IGFBP-3 in girls only (all p < 0.01). At endpoint, baseline-adjusted muscle strength, FMI and FFMI did not differ between intervention groups. However, baseline-adjusted IGF-1 and IGFBP-3 were higher after 20 µg/day compared to placebo (p = 0.043 and p = 0.006, respectively) and IGFBP-3 was also higher after 20 µg/day compared to 10 µg/day (p = 0.011). Children tended to be taller after 20 µg/day compared to placebo (p = 0.064). No sex interactions were seen at endpoint.
Avoiding the winter-related decline in serum 25(OH)D may influence IGF-1 and IGFBP-3 in children. Larger trials are required to confirm these effects, and the long-term implication for linear growth.
KeywordsChildren IGF-1 IGFBP-3 Muscle strength Randomized controlled trial Vitamin D
Bioelectrical impedance analysis
Body mass index
Coefficient of variation
Fat free mass
Fat free mass index
Fat mass index
Intraclass correlation coefficient
Insulin-like growth factor 1
Liquid chromatography tandem mass spectrometry
Food-based solutions for optimal vitamin D nutrition and health through the life cycle
Vitamin D receptor
We thank all the participating children and their parents.
CTD and CMø: Designed the study; CMo, CTD, HH, and CMø: Conducted the research; CMo: Performed the statistical analyses and drafted the manuscript; CTD, CMø, HH, and MK: Assisted in the manuscript preparation. All authors read and approved the final manuscript.
This project was funded by the European Commission (FP7/2007–2013) under Grant Agreement 613977 for the ODIN Integrated Project [Food-based solutions for optimal vitamin D nutrition and health through the life cycle http://www.odin-vitd.eu/].
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This study involving humans was approved by the Committees on Biomedical Research Ethics for the Capital Region of Denmark (H-3-2014-022), and has, therefore, been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. We obtained informed written consent from all parents. Any details that may have disclosed the identity of the participants were omitted. The study was registered at http://www.clinicaltrials.gov as NCT02145195.
- 1.Webb AR, Kline L, Holick MF (1988) Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in boston and edmonton will not promote vitamin D3 synthesis in human skin. J Clin Endocrinol Metab 67:373–378. https://doi.org/10.1210/jcem-67-2-373 CrossRefGoogle Scholar
- 3.Institute of Medicine Food and Nutrition Board (2011) Dietary reference intakes for calcium and vitamin D. National Academies Press, Washington, DCGoogle Scholar
- 4.Nordisk Ministerråd (2014) Nordic Nutrition Recommendations 2012, integrating nutrition and physical activity, 5th edn, 1. oplag. Nordic Council of MinistersGoogle Scholar
- 9.Valtueña J, Gracia-Marco L, Huybrechts I et al (2013) Cardiorespiratory fitness in males, and upper limbs muscular strength in females, are positively related with 25-hydroxyvitamin D plasma concentrations in European adolescents: the HELENA study. QJM 106:809–821. https://doi.org/10.1093/qjmed/hct089 CrossRefGoogle Scholar
- 17.Soliman AT, Al Khalaf F, AlHemaidi N et al (2008) Linear growth in relation to the circulating concentrations of insulin-like growth factor I, parathyroid hormone, and 25-hydroxy vitamin D in children with nutritional rickets before and after treatment: endocrine adaptation to vitamin D deficiency. Metabolism 57:95–102. https://doi.org/10.1016/j.metabol.2007.08.011 CrossRefGoogle Scholar
- 26.Molenaar HM (Ties), Selles RW, Zuidam JM et al (2009) Growth diagrams for grip strength in children. Clin Orthop Relat Res 468:217. https://doi.org/10.1007/s11999-009-0881-z
- 28.World Health Organization Application tools WHO AnthroPlus software. In: WHO. http://www.who.int/growthref/tools/en/. Accessed 4 Jan 2016
- 29.Talma H, Chinapaw MJM, Bakker B et al (2013) Bioelectrical impedance analysis to estimate body composition in children and adolescents: a systematic review and evidence appraisal of validity, responsiveness, reliability and measurement error. Obes Rev 14:895–905. https://doi.org/10.1111/obr.12061 CrossRefGoogle Scholar
- 31.Kiely M, Collins A, Lucey AJ et al (2016) Development, validation and implementation of a quantitative food frequency questionnaire to assess habitual vitamin D intake. J Hum Nutr Diet 1–10. https://doi.org/10.1111/jhn.12348
- 36.Juul A, Dalgaard P, Blum WF et al (1995) Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants, children, and adolescents: the relation to IGF-I, IGF-II, IGFBP-1, IGFBP-2, age, sex, body mass index, and pubertal maturation. J Clin Endocrinol Metab 80:2534–2542. https://doi.org/10.1210/jcem.80.8.7543116 Google Scholar