To the Editor:
The authors thank the readers for their letter and comments regarding “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.” Those comments are valuable, and we try our best to figure out probable issues. We have answered carefully the letter, based on the comments from readers.
Response to reader’s comments one by one
In the selection of studies for children, authors have omitted six studies, two from Middle East and North Africa region [1, 2], one from Finland , one from Australia , and two from the United States [5, 6], with over 800 participants, which examined the safety and efficacy of various doses of VitD supplementation for improving the serum 25(OH)D. The exclusion criteria did not justify excluding these studies. The exclusion of four large studies may skew the estimates and make them unreliable.
Sorry for the mistake. We did omit eligible two studies [1, 6] of the six. One study  from Lebanon was the same with the study by El-Hajj Fuleihan et al. . The other two did not meet the inclusion criteria for no complete data [3, 5] and another one did not meet the inclusion criteria for intervals of VitD intake of >1 month . Totally, two studies with 212 children were omitted. The basic characteristics of two studies were shown in the following Table 1. After comparing the results of these two studies with our result, it is shown that our final results will not be much influenced by either study.
Furthermore, the authors declared that RCTs were included if the study participants were apparently healthy or patients with mild diseases with no known effects on VitD metabolism. The exact definition of being healthy or having only a mild illness is not clear. Authors had included study by Saad et al. , which was performed on children with autism spectrum disorder (ASD), a complex neurodevelopmental syndrome. The association between the risk of ASD and VitD insufficiency has been reported. In the other hand, some mild diseases with less effect on VitD metabolism such as obesity, atopic dermatitis, attention-deficit hyperactivity disorder, allergic rhinitis, asthma may have been excluded.
Thanks for your comment. It is true that accumulated data over these past years has confirmed that vitamin D deficiency is a risk factor for ASD. However, whether ASD will influence VitD metabolism and the effect of ASD on VitD metabolism has not been demonstrated . So, the study by Saad et al.  was not excluded.
Furthermore, conditions or drug therapy might affect VitD metabolism including malabsorption, anticonvulsants, steroids, and antifungal medications. Mild diseases with less effect on VitD metabolism such as obesity, atopic dermatitis, attention-deficit hyperactivity disorder, allergic rhinitis, asthma were not excluded.
In addition, study by Saad et al.  was retracted and this may cause flaw and bias, other studies were included in the MENA region since only two.
Thanks for your reminding. However, our literature search was conducted up to October 2018, the retraction date of that study was June 2019 .
Lastly, inception time of electronic literature searches has not been specified in this study. Considering that the inception date for various included databases i.e., MEDLINE/PubMed, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) is different, to homogenize the literature search of all online databases, it is better that a unique inception time be determined for the systematic review and applied for all databases.
The inception time of electronic literature searches has been specified in the part of search strategy in the article, which was accurate to up to October, 2018.
El-Hajj Fuleihan G, Nabulsi M, Tamim H, Maalouf J, Salamoun M, Khalife H, et al. Effect of vitamin D replacement on musculoskeletal parameters in school children: a randomized controlled trial. J Clin Endocrinol Metab. 2006;91:405–12.
Maalouf J, Nabulsi M, Vieth R, Kimball S, El-Rassi R, Mahfoud Z, et al. Short- and long-term safety of weekly high-dose vitamin D3 supplementation in school children. J Clin Endocrinol Metab. 2008;93:2693–701.
Viljakainen HT, Natri AM, Karkkainen M, Huttunen MM, Palssa A, Jakobsen J, et al. A positive dose-response effect of vitamin D supplementation on site-specific bone mineral augmentation in adolescent girls: A double-blinded randomized placebo-controlled 1-year intervention. J Bone Miner Res. 2006;21:836–44.
Wu FT, Xiao C, Aitken D, Jones G, Winzenberg T. The optimal dosage regimen of vitamin D supplementation for correcting deficiency in adolescents: a pilot randomized controlled trial. Eur J Clin Nutr. 2018;72:534–40.
Lewis RD, Laing EM, Gallant KMH, Hall DB, McCabe GP, Hausman DB, et al. A randomized trial of vitamin D-3 supplementation in children: dose-response effects on vitamin D metabolites and calcium absorption. J Clin Endocrinol Metab. 2013;98:4816–25.
Dong Y, Stallmann-Jorgensen IS, Pollock NK, Harris RA, Keeton D, Huang Y, et al. 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. 2010;95:4584–91.
Saad K, Abdel-Rahman AA, Elserogy YM, Al-Atram AA, El-Houfey AA, Othman HAK, et al. Randomized controlled trial of vitamin D supplementation in children with autism spectrum disorder. J Child Psychol Psychiatry. 2018;59:20–9.
Alzghoul L. Role of vitamin D in autism spectrum disorder. Curr Pharm Des. 2019;25:4357–67.
Saad K, Abdel-Rahman A, Elserogy Y, Al-Atram A, El-Houfey A, Othman H. et al. Randomized controlled trial of vitamin D supplementation in children with autism spectrum disorder (Retraction of Vol 59, Pg 20, 2017). J Child Psychol Psychiatry. 2019;60:711.
Conflict of interest
The authors declare that they have no conflict of interest.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Mo, M., Yu, Y. 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”. Eur J Clin Nutr 74, 1615–1617 (2020). https://doi.org/10.1038/s41430-020-00769-2