The manuscript by Pérez-Castrillón et al describes a simple study in which the authors have investigated the impact of supplementation with conventional vitamin D3 (cholecalciferol) relative to 25-hydroxyvitamin D3 (calcifediol). There is currently much interest in the potential advantages of calcifediol as form of vitamin D that more effectively and rapidly elevates serum 25-hydroxyvitamin D3 concentrations. Likewise there is ongoing debate concerning the effectiveness of monthly bolus dosing with vitamin D, and this is also a feature of the current study. The major criticism of the study is that it does not significantly advance our understanding of calcifediol vs cholecalciferol beyond existing publications – the authors list some of these studies but appear to have some of the references mixed up. Thus, it is unclear what the major advance of the current manuscript is over these previous reports– what is new?
Specific comments
1) The data and stats presented in this study are very difficult to, partly because the legends to figures and tables are almost non-existent. In many cases it is simply unclear what p values are referring to.
2) In Table 2, there appear to be significant differences in response to calcifediol vs cholecalciferol depending on what the baseline 25-hydroxyvitamin D level is. For example at month 4 there appears to be no difference in the serum 25-hydroxyvitamin D for calcifediol vs cholecalciferol for women <10. The number of these patients is not large but the data as presented suggest that there is no difference between calcifediol vs cholecalciferol if your starting 25-hydroxyvitamin D levels is very low (i.e. < 10). This is a crucial point and needs discussion.
3) The PTH values shown in Table 3 suggest a slight elevation in both calcifediol vs cholecalciferol at baseline. However, there is a huge variation in these values (+/- >20). This means that some women had very PTH levels, while some had very low. The authors should sub-divide the women based on their PTH values – are the high PTH values also the women with the lowest serum 25-hydroxyvitamin D?
4) It is unclear why the free serum 25-hydroxyvitamin D values were included. Why are free 25-hydroxyvitamin D values not included in the subsequent (post-supplementation) analyses? It would be interesting to know if free 25-hydroxyvitamin D is significantly different between calcifediol vs cholecalciferol. Does one particular form of supplementation favour free 25-hydroxyvitamin D?
5) The authors should also clear that there is still come debate over the reproducibility of the free 25-hydroxyvitamin D ELISA kit. This is not a validated or accredited assay – unlike the serum total 25-hydroxyvitamin D.
6) The study overall shows that calcifediol is better than cholecalciferol in raising serum 25-hydroxyvitamin D levels. However, as nothing else changes in response to this (no suppression of PTH etc) it is unclear what benefit this supplementation has for these women. What is the advantage of using calcifediol?

The manuscript has been improved.