Title: Effect of vitamin K2 Administration on Depression Status in Patients with Polycystic
Ovary Syndrome: A Randomized Clinical Trial
Version: 1 Date: 25 Feb 2022
Reviewer's report:
The manuscript provides an interesting finding about the impact of vitamin K2 on depression
status of PCOS women and authors have collected a unique dataset. That said, however, this
data set has not been used to its full extent. The author may consider following suggestion for a
better understanding of things and better representation of their exciting findings. Given these
short comings the manuscript requires a major revision.
1. How vitamin K relates to the etiology of depression among PCOS women is not specified?
The authors have not given insulin resistance indices/body fat composition/hormonal indices
and its correlation with vitamin K/ vitamin K dependent proteins.
2. In methodology section, the authors mention to have computed the intakes of macronutrients
and micronutrients, but the data has not been given in the manuscript. Given data could have
provided insights into the daily dietary intake of vitamin K among  the subjects.
3. In addition to BDII scale, impact of vitamin K supplementation on general health, anxiety,
stress scale, mood disorders and quality of sleep may be included at baseline and 8 weeks to
have a robust methodology to claim the anti-depressive potential of Vitamin K.
4. Kits used for vitamin K estimation should be mentioned properly in the methodology section
along with Cat. No. and company name.
5. Clinically significant vitamin K deficiency in adults is very rare and is usually limited
to people with malabsorption disorders or those taking drugs that interfere with vitamin K
metabolism. The same should be considered and discussed in the light of results.
6. The authors have not defined the appropriate levels of vitamin K among PCOS women and
the change of serum vitamin K concentration with respect to baseline and follow up.
7. The accurate measurement of vitamin K status in humans is still a critical issue. Along with
the direct analysis of blood levels of phylloquinone(vitamin K1) and menaquinones(vitamin
K2) forms, indirect assays, such as the undercarboxylated fractions of vitamin K-dependent
proteins [prothrombin, osteocalcin (OC), and matrix gla protein], might be considered as a more
informative approach for assessing vitamin K status among subjects.
8. Sample size is usually calculated on some key variable, however in current study key variable
used is glucose and authors have not given account of glucose tolerance among subjects under
study. Neither have they put forth association (if any) between the key variable and Vitamin K
supplementation.
9. The authors have given a literature background (in discussion section) about regulation of
inflammation by vitamin K however no such results have been presented in this study.  Following
this authors say lack of vitamin K in brain increases the ceramides with subsequent increase in
cytokines and reactive oxygen species. The authors have no experimental proof to support this
fact for their study.
10. The language of the manuscript needs a major scope for improvement. Grammatical errors
can be found throughout the manuscript.
11. Additionally, better citations will help authors to infer their results better and provide more
accurate information.