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Daily vitamin D3 in overweight and obese children and adolescents: a randomized controlled trial

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Abstract

Purpose

To assess the efficacy of different doses of vitamin D3 on serum 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone(iPTH), calcium, phosphorus, and alkaline phosphatase concentrations in overweight and obese school-children.

Methods

A total of 378 children and adolescents, 6–13 years of age, with age- and sex-specific body mass index(BMI) Z-score ≥ 1(according to the World Health Organization criteria) were allocated to receive 600, 1000, and 2000 IU vitamin D3/days. 25(OH)D, iPTH, calcium, phosphorus, and alkaline phosphatase concentrations were measured at baseline, 6, and 12 months. In this intention-to-treat analysis, we fitted a linear mixed effect model involving a random effect of participants within treatment groups and fixed effects of dose, time, and their interactions.

Results

Mean(SD) of age and BMI Z-score were 9.3 (1.7) years and 2.55 (0.73), respectively. The median (IQR) for 25(OH)D was 11.5 (8.9), 11.7 (10.5), 12.2 (10.2) ng/mL (28.75, 29.25, and 30.50 nmol/L) at baseline and 23.1 (8.0), 25.6 (8.3), 28.6 (10.4) ng/mL (57.75, 64.00, and 71.50 nmol/L) at the end of 12 months in 600, 1000, and 2000 IU, respectively (p values for dose, time, and the interaction being < 0.0001, < 0.0001,and 0.082, respectively). Prevalence of vitamin D deficiency (< 20 ng/mL) was 80.2, 77.5, and 75.5% in 600, 1000, and 2000 IU groups at baseline, respectively, which decreased to 34, 18.4, and 7.5%, respectively, at 12 months. Patterns of iPTH, calcium, phosphorus, and alkaline phosphatase response over time did not differ significantly among groups (p values = 0.452, 0.670, 0.377, 0.895, respectively).

Conclusions

Increases in 25(OH)D concentration were found with supplementation of 1000 and 2000 IU, compared with 600 IU/days, whereas there was no evidence of iPTH suppression or change in serum calcium, phosphorus, and alkaline phosphatase among children with excess weight.

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References

  1. Kimball S, Fuleihan Gel-H, Vieth R (2008) Vitamin D: a growing perspective. Crit Rev Clin Lab Sci 45(4):339–414

    Article  CAS  Google Scholar 

  2. Wagner CL, Greer FR, American Academy of Pediatrics Section on Breastfeeding; American Academy of Pediatrics Committee on Nutrition (2008) Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics 122(5):1142–1152

    Article  Google Scholar 

  3. Shin YH, Shin HJ, Lee YJ (2013) Vitamin D status and childhood health. Korean J Pediatr 56(10):417–423

    Article  CAS  Google Scholar 

  4. Asghari G, Mirmiran P, Yuzbashian E, Dehghan P, Mahdavi M, Tohidi M, Wagner CL, Neyestani TR, Hosseinpanah F, Azizi F (2019) Association of circulating 25-hydroxyvitamin D and parathyroid hormone with carotid intima media thickness in children and adolescents with excess weight. J Steroid Biochem Mol Biol 188:117–123

    Article  CAS  Google Scholar 

  5. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM, Endocrine Society (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96(7):1911–1930

    Article  CAS  Google Scholar 

  6. Holick MF, Chen TC (2008) Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr 87(4):1080S–1086S

    Article  CAS  Google Scholar 

  7. Palacios C, Gonzalez L (2014) Is vitamin D deficiency a major global public health problem? J Steroid Biochem Mol Biol 144 Pt A:138–145

  8. Abdul-Razzak KK, Ajlony MJ, Khoursheed AM, Obeidat BA (2011) Vitamin D deficiency among healthy infants and toddlers: a prospective study from Irbid, Jordan. Pediatr Int 53(6):839–845

    Article  CAS  Google Scholar 

  9. Al-Othman A, Al-Musharaf S, Al-Daghri NM, Krishnaswamy S, Yusuf DS, Alkharfy KM, Al-Saleh Y, Al-Attas OS, Alokail MS, Moharram O, Sabico S, Chrousos GP (2012) Effect of physical activity and sun exposure on vitamin D status of Saudi children and adolescents. BMC Pediatr 12:92

    Article  Google Scholar 

  10. Bassil D, Rahme M, Hoteit M, Fuleihan Gel-H (2013) Hypovitaminosis D in the Middle East and North Africa: prevalence, risk factors and impact on outcomes. Dermatoendocrinol 5(2):274–298

    Article  Google Scholar 

  11. Lenders CM, Feldman HA, Von Scheven E, Merewood A, Sweeney C, Wilson DM, Lee PD, Abrams SH, Gitelman SE, Wertz MS, Klish WJ, Taylor GA, Chen TC, Holick MF, Elizabeth Glaser Pediatric Research Network Obesity Study Group (2009) Relation of body fat indexes to vitamin D status and deficiency among obese adolescents. Am J Clin Nutr 90(3):459–467

    Article  CAS  Google Scholar 

  12. Alemzadeh R, Kichler J, Babar G, Calhoun M (2008) Hypovitaminosis D in obese children and adolescents: relationship with adiposity, insulin sensitivity, ethnicity, and season. Metabolism 57(2):183–191

    Article  CAS  Google Scholar 

  13. Cediel G, Corvalán C, Aguirre C, de Romaña DL, Uauy R (2016) Serum 25-Hydroxyvitamin D associated with indicators of body fat and insulin resistance in prepubertal chilean children. Int J Obes (Lond) 40(1):147–152

    Article  CAS  Google Scholar 

  14. Abrams SA, Hawthorne KM, Chen Z (2013) Supplementation with 1000 IU vitamin D/d leads to parathyroid hormone suppression, but not increased fractional calcium absorption, in 4-8-y-old children: a double-blind randomized controlled trial. Am J Clin Nutr 97(1):217–223

    Article  CAS  Google Scholar 

  15. Lewis RD, Laing EM, Hill Gallant KM, Hall DB, McCabe GP, Hausman DB, Martin BR, Warden SJ, Peacock M, Weaver CM (2013) A randomized trial of vitamin D3 supplementation in children: dose-response effects on vitamin D metabolites and calcium absorption. J Clin Endocrinol Metab 98(12):4816–4825

    Article  CAS  Google Scholar 

  16. Rajakumar K, Moore CG, Yabes J, Olabopo F, Haralam MA, Comer D, Bogusz J, Nucci A, Sereika S, Dunbar-Jacob J, Holick MF, Greenspan SL (2015) Effect of vitamin D3 supplementation in black and in white children: a randomized, placebo-controlled trial. J Clin Endocrinol Metab 100(8):3183–3192

    Article  CAS  Google Scholar 

  17. Mortensen C, Damsgaard CT, Hauger H, Ritz C, Lanham-New SA, Smith TJ, Hennessy Á, Dowling K, Cashman KD, Kiely M, Mølgaard C (2016) Estimation of the dietary requirement for vitamin D in white children aged 4–8 y: a randomized, controlled, dose-response trial. Am J Clin Nutr 104(5):1310–1317

    Article  CAS  Google Scholar 

  18. Talib HJ, Ponnapakkam T, Gensure R, Cohen HW, Coupey SM (2016) Treatment of vitamin D deficiency in predominantly hispanic and black adolescents: a randomized clinical trial. J Pediatr 170:266.e1–272.e1

    Article  Google Scholar 

  19. Talaat IM, Kamal NM, Alghamdi HA, Alharthi AA, Alshahrani MA (2016) A randomized clinical trial comparing 3 different replacement regimens of vitamin D in clinically asymptomatic pediatrics and adolescents with vitamin D insufficiency. Ital J Pediatr 42(1):106

    Article  Google Scholar 

  20. Sacheck JM, Van Rompay MI, Chomitz VR, Economos CD, Eliasziw M, Goodman E, Gordon CM, Holick MF (2017) Impact of three doses of vitamin D3 on serum 25(OH)D deficiency and insufficiency in at-risk schoolchildren. J Clin Endocrinol Metab 102(12):4496–4505

    Article  Google Scholar 

  21. Rajakumar K, Fernstrom JD, Holick MF, Janosky JE, Greenspan SL (2008) Vitamin D status and response to Vitamin D(3) in obese vs. non-obese African American children. Obesity (Silver Spring) 16(1):90–95

    Article  CAS  Google Scholar 

  22. Aguirre Castaneda R, Nader N, Weaver A, Singh R, Kumar S (2012) Response to vitamin D3 supplementation in obese and non-obese Caucasian adolescents. Horm Res Paediatr 78(4):226–231

    Article  CAS  Google Scholar 

  23. Harel Z, Flanagan P, Forcier M, Harel D (2011) Low vitamin D status among obese adolescents: prevalence and response to treatment. J Adolesc Health 48(5):448–452

    Article  Google Scholar 

  24. Ghazi AA, Hosseinpanah F, Ardakani ME, Ghazi S, Hedayati M, Azizi F (2010) Effects of different doses of oral cholecalciferol on serum 25(OH)D, PTH, calcium and bone markers during fall and winter in schoolchildren. Eur J Clin Nutr 64(12):1415–1422

    Article  CAS  Google Scholar 

  25. El-Hajj Fuleihan G, Nabulsi M, Tamim H, Maalouf J, Salamoun M, Khalife H, Choucair M, Arabi A, Vieth R (2006) Effect of vitamin D replacement on musculoskeletal parameters in school children: a randomized controlled trial. J Clin Endocrinol Metab 91(2):405–412

    Article  Google Scholar 

  26. Marwaha RK, Garg MK, Sethuraman G, Gupta N, Mithal A, Dang N, Kalaivani M, Ashraf Ganie M, Narang A, Arora P, Singh A, Chadha A, Manchanda RK (2019) Impact of three different daily doses of vitamin D3 supplementation in healthy schoolchildren and adolescents from North India: a single-blind prospective randomised clinical trial. Br J Nutr 121(5):538–548

    Article  CAS  Google Scholar 

  27. World Health Organization (2007) Growth reference 5–19 years. Retrieved July 26, 2018, from https://www.who.int/growthref/who2007_bmi_for_age/en/

  28. Rosen CJ, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS (2012) IOM committee members respond to endocrine society vitamin D guideline. J Clin Endocrinol Metab 97(4):1146–1152

    Article  CAS  Google Scholar 

  29. Holick M (2010) Vitamin D: physiology, molecular biology, and clinical applications. Humana Press

  30. Heaney RP, Armas LA, Shary JR, Bell NH, Binkley N, Hollis BW (2008) 25-Hydroxylation of vitamin D3: relation to circulating vitamin D3 under various input conditions. Am J Clin Nutr 87(6):1738–1742

    Article  CAS  Google Scholar 

  31. Shab-Bidar S, Bours S, Geusens PP, Kessels AG, van den Bergh JP (2014) Serum 25(OH)D response to vitamin D3 supplementation: a meta-regression analysis. Nutrition 30(9):975–985

    Article  CAS  Google Scholar 

  32. Al-Shaar L, Mneimneh R, Nabulsi Maalouf J, Fuleihan Gel-H (2014) Vitamin D3 dose requirement to raise 25-hydroxyvitamin D to desirable levels in adolescents: results from a randomized controlled trial. J Bone Miner Res 29(4):944–951

    Article  CAS  Google Scholar 

  33. Dong Y, Stallmann-Jorgensen IS, Pollock NK, Harris RA, Keeton D, Huang Y, Li K, Bassali R, Guo DH, Thomas J, Pierce GL, White J, Holick MF, Zhu H (2010) A 16-week randomized clinical trial of 2000 international units daily vitamin D3 supplementation in black youth: 25-hydroxyvitamin D, adiposity, and arterial stiffness. J Clin Endocrinol Metab 95(10):4584–4591

    Article  CAS  Google Scholar 

  34. Newton DA, Baatz JE, Kindy MS, Gattoni-Celli S, Shary JR, Hollis BW, Wagner CL (2019) Vitamin D binding protein polymorphisms significantly impact vitamin D status in children. Pediatr Res 86(5):662–669

    Article  Google Scholar 

  35. Drincic A, Fuller E, Heaney RP, Armas LA (2013) 25-Hydroxyvitamin D response to graded vitamin D3 supplementation among obese adults. J Clin Endocrinol Metab 98(12):4845–4851

    Article  CAS  Google Scholar 

  36. Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF (2000) Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 72(3):690–693

    Article  CAS  Google Scholar 

  37. Öhlund I, Lind T, Hernell O, Silfverdal SA, Karlsland Åkeson P (2017) Increased vitamin D intake differentiated according to skin color is needed to meet requirements in young Swedish children during winter: a double-blind randomized clinical trial. Am J Clin Nutr 106(1):105–112

    Article  Google Scholar 

  38. Smith TJ, Tripkovic L, Damsgaard CT, Mølgaard C, Ritz C, Wilson-Barnes SL, Dowling KG, Hennessy Á, Cashman KD, Kiely M, Lanham-New SA, Hart KH (2016) Estimation of the dietary requirement for vitamin D in adolescents aged 14–18 y: a dose-response, double-blind, randomized placebo-controlled trial. Am J Clin Nutr 104(5):1301–1309

    Article  CAS  Google Scholar 

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Acknowledgements

The authors would like to acknowledge Ms. Niloofar Shiva for critical editing of English grammar and syntax of the manuscript. We express our appreciation to the participants for their enthusiastic support, and the staff of the Research Institute for Endocrine Sciences, for their valuable help.

Funding

No external funding for this manuscript.

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Authors and Affiliations

  1. Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, P.O. Box: 19395-4763, Tehran, Iran

    Golaleh Asghari, Emad Yuzbashian & Parvin Mirmiran

  2. Department of Pediatrics, Division of Neonatology, Shawn Jenkins Children’s Hospital, Charleston, SC, USA

    Carol L. Wagner

  3. Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, USA

    Yeonhee Park

  4. Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, P.O. Box: 19395-4763, Tehran, Iran

    Farhad Hosseinpanah

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  1. Golaleh Asghari
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Contributions

GA, PM and FH conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript. EY collected data, carried out the initial analyses, and reviewed and revised the manuscript. CLW interpreted the results and drafted the initial manuscript. YP carried out the analyses and critically reviewed the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding authors

Correspondence to Parvin Mirmiran or Farhad Hosseinpanah.

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The authors have no conflicts of interest relevant to this article to disclose.

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Supplementary Figure 1

Main effects of supplementation with vitamin D on serum 25(OH)D, PTH, 25(OH)D: PTH ratio, calcium, phosphorus, and alkaline phosphatase in the per-protocol analysis. Supplementary Figure 2 Main effects of supplementation with vitamin D on serum 25(OH)D across subgroups of sex, obesity status, and puberty maturation in the intention-to-treat analysis. Supplementary Figure 3 Main effects of supplementation with vitamin D on serum PTH across subgroups of sex, obesity status, and puberty maturation in the intention-to-treat analysis. Supplementary Figure 4 Main effects of supplementation with vitamin D on serum 25(OH)D: PTH ratio across subgroups of sex, obesity status, and puberty maturation in the intention-to-treat analysis. Supplementary Figure 5 Main effects of supplementation with vitamin D on serum calcium across subgroups of sex, obesity status, and puberty maturation in the intention-to-treat analysis. Supplementary Figure 6 Main effects of supplementation with vitamin D on serum phosphorus across subgroups of sex, obesity status, and puberty maturation in the intention-to-treat analysis. Supplementary Figure 7 Main effects of supplementation with vitamin D on serum alkaline phosphatase across subgroups of sex, obesity status, and puberty maturation in the intention-to-treat analysis. (DOCX 1508 kb)

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Asghari, G., Yuzbashian, E., Wagner, C.L. et al. Daily vitamin D3 in overweight and obese children and adolescents: a randomized controlled trial. Eur J Nutr 60, 2831–2840 (2021). https://doi.org/10.1007/s00394-020-02406-x

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  • DOI: https://doi.org/10.1007/s00394-020-02406-x

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