Vitamin D deficiency is common in adolescents but the optimal dosage regimen for correcting deficiency is unknown. To test the safety and efficacy of two different vitamin D dosage regimens to correct vitamin D deficiency in adolescents.
In this 12-month, double-blind, randomized placebo-controlled trial, 28 adolescents (serum 25 hydroxyvitamin D (25(OH)D) of 21 to 50 nmol/L) were randomly assigned to one of three groups: monthly (n = 9; vitamin D3 50,000 IU orally monthly plus three placebo tablets 3-monthly), 3-monthly (n = 9; 150,000 IU (3 × 50,000 IU tablets) 3-monthly and placebo orally monthly), or placebo (n = 10; placebo monthly and three placebo tablets 3-monthly). Serum 25(OH)D was measured at baseline, 3, 6 and 12 months.
Two participants withdrew after their baseline measurement from the 3-monthly group. At 12 months, one participant was deficient (≤50 nmol/L) in both the monthly and 3-monthly groups, whereas six out of ten in the placebo remained deficient (P = 0.055). At 12 months, the average serum 25(OH)D levels for the monthly, 3-monthly and placebo groups were 76.4, 64.7 and 49.7 nmol/L, respectively (P < 0.001 and P = 0.04 for differences between monthly and placebo groups and 3-monthly and placebo groups respectively, after adjustment for age, sex and seasonal variation). Adherence was 100% and adverse events were minor.
Both 50,000 IU monthly and 150,000 IU 3-monthly of vitamin D3 safely and effectively corrects vitamin D deficiency in adolescents. These data provide treatment options which can be used by health practitioners to tailor vitamin D dosage regiments according to patient preference and context.
This is a preview of subscription content, access via your institution
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Get just this article for as long as you need it
Prices may be subject to local taxes which are calculated during checkout
Cauley JA. Public health impact of osteoporosis. J Gerontol A Biol Sci Med Sci. 2013;68:1243–51. https://doi.org/10.1093/gerona/glt093
Jones G, Cooley HM. Symptomatic fracture incidence in those under 50 years of age in southern Tasmania. J Paediatr Child Health. 2002;38:278–83.
Lofthus CM, Osnes EK, Meyer HE, Kristiansen IS, Nordsletten L, Falch JA. Young patients with hip fracture: a population-based study of bone mass and risk factors for osteoporosis. Osteoporos Int. 2006;17:1666–72. https://doi.org/10.1007/s00198-006-0176-0
Goulding A, Jones IE, Taylor RW, Williams SM, Manning PJ. Bone mineral density and body composition in boys with distal forearm fractures: a dual-energy x-ray absorptiometry study. J Pediatr. 2001;139:509–15. https://doi.org/10.1067/mpd.2001.116297
Clark EM, Ness AR, Bishop NJ, Tobias JH. Association between bone mass and fractures in children: a prospective cohort study. J Bone Miner Res. 2006;21:1489–95.
Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ. 1996;312:1254–9.
Hansen MA, Overgaard K, Riis BJ, Christiansen C. Role of peak bone mass and bone loss in postmenopausal osteoporosis: 12 year study. BMJ (Clin Res Ed.) 1991;303:961–4.
Hernandez CJ, Beaupre GS, Carter DR. A theoretical analysis of the relative influences of peak BMD, age-related bone loss and menopause on the development of osteoporosis. Osteoporos Int. 2003;14:843–7. https://doi.org/10.1007/s00198-003-1454-8
Cummings SR, Black DM, Nevitt MC, Browner W, Cauley J, Ensrud K, et al. Bone density at various sites for prediction of hip fractures. The Study of Osteoporotic Fractures Research Group. Lancet. 1993;341:72–5.
Bailey DA, McKay HA, Mirwald RL, Crocker PR, Faulkner RA. A six-year longitudinal study of the relationship of physical activity to bone mineral accrual in growing children: the university of Saskatchewan bone mineral accrual study. J Bone Miner Res. 1999;14:1672–9. https://doi.org/10.1359/jbmr.19220.127.116.112
Munns C, Zacharin MR, Rodda CP, Batch JA, Morley R, Cranswick NE, et al. Prevention and treatment of infant and childhood vitamin D deficiency in Australia and New Zealand: a consensus statement. Med J Aust. 2006;185:268–72.
Winzenberg T, Jones G. Vitamin D and bone health in childhood and adolescence. Calcif Tissue Int. 2013;92:140–50. https://doi.org/10.1007/s00223-012-9615-4
Winzenberg T, Powell S, Shaw KA, Jones G. Effects of vitamin D supplementation on bone density in healthy children: systematic review and meta-analysis. BMJ. 2011;342:c7254 https://doi.org/10.1136/bmj.c7254
Carnes J, Quinn S, Nelson M, Jones G, Winzenberg T. Intermittent high-dose vitamin D corrects vitamin D deficiency in adolescents: a pilot study. Eur J Clin Nutr. 2012;66:530–2. https://doi.org/10.1038/ejcn.2011.204
Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. Jama. 2010;303:1815–22.
Dwyer T, Blizzard L, Gies PH, Ashbolt R, Roy C. Assessment of habitual sun exposure in adolescents via questionnaire--a comparison with objective measurement using polysulphone badges. Melanoma Res. 1996;6:231–9.
Morris N, Urdy J. Validation of a self-administered instrument to assess stage of adolescent development. J Youth Adolesc. 1980;9:271–80.
Vieth R. How to optimize vitamin D supplementation to prevent cancer, based on cellular adaptation and hydroxylase enzymology. Anticancer Res. 2009;29:3675–84.
Hammonds T, Rickert K, Goldstein C, Gathright E, Gilmore S, Derflinger B. et al. Adherence to antidepressant medications: a randomized controlled trial of medication reminding in college students. J Am Coll Health: J ACH. 2015;63:204–8. https://doi.org/10.1080/07448481.2014.975716
Ilahi M, Armas LA, Heaney RP. Pharmacokinetics of a single, large dose of cholecalciferol. Am J Clin Nutr. 2008;87:688–91.
Dalle Carbonare L, Valenti MT, Del Forno F, Caneva E, Pietrobelli A. Vitamin D: daily vs. monthly use in children and elderly-what is going on? Nutrients 2017; 9. https://doi.org/10.3390/nu9070652
Tripkovic L, Lambert H, Hart K, Smith CP, Bucca G, Penson S. et al. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. Am J Clin Nutr. 2012;95:1357–64. https://doi.org/10.3945/ajcn.111.031070.
Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911–30. https://doi.org/10.1210/jc.2011-0385
Paxton GA, Teale GR, Nowson CA, Mason RS, McGrath JJ, Thompson MJ, et al. Vitamin D and health in pregnancy, infants, children and adolescents in Australia and New Zealand: a position statement. Med J Aust. 2013;198:142–3.
Ghazi AA, Hosseinpanah F, M Ardakani E, Ghazi S, Hedayati M, Azizi F. 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. 2010;64:1415–22.
Kuchay MS, Jevalikar GS, Mithal A, Mishra SK, Dang N. Efficacy and safety of a single monthly dose of cholecalciferol in healthy school children. J Pediatr Endocrinol Metab. 2016;29:413–6. https://doi.org/10.1515/jpem-2015-0187
Batchelor AJ, Watson G, Compston JE. Changes in plasma half-life and clearance of 3H-25-hydroxyvitamin D3 in patients with intestinal malabsorption. Gut. 1982;23:1068–71.
Jones KS, Assar S, Vanderschueren D, Bouillon R, Prentice A, Schoenmakers I. Predictors of 25(OH)D half-life and plasma 25(OH)D concentration in The Gambia and the UK. Osteoporos Int. 2015;26:1137–46. https://doi.org/10.1007/s00198-014-2905-0
The researchers gratefully acknowledge the RACGP Foundation for their support of this project, which was funded jointly by the RACGP Foundation and Osteoporosis Australia.
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Wu, F., Xiao, C., Aitken, D. et al. The optimal dosage regimen of vitamin D supplementation for correcting deficiency in adolescents: a pilot randomized controlled trial. Eur J Clin Nutr 72, 534–540 (2018). https://doi.org/10.1038/s41430-018-0098-x
This article is cited by
Response to editor “A systematic review and meta-analysis of the response of serum 25-hydroxyvitamin D concentration to vitamin D supplementation from RCTs from around the globe”
European Journal of Clinical Nutrition (2020)
A systematic review and meta-analysis of the response of serum 25-hydroxyvitamin D concentration to vitamin D supplementation from RCTs from around the globe
European Journal of Clinical Nutrition (2020)