PONE-D-23-11590Self-Reported Menses Physiology is Positively Modulated by A Well-Formulated, Energy-Controlled Ketogenic Diet in Women of Reproductive Age with Overweight/ObesityPLOS ONE

Dear Dr. Volek,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Oct 26 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

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We look forward to receiving your revised manuscript.

Kind regards,

Licy Yanes Cardozo

Academic Editor

PLOS ONE

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7. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: 1. Introduction: Paragraph 2. I recommend that the authors rephrase the second sentence to say "is rapidly inducible (~3-5 days) when carbohydrates are limited and primarily derived from non-starchy vegetables (20-50 g/day)." because one key component and nutrition recommendation for the Keto diet is low carbohydrate intake.

2. Methods: Is the last sentence of the first paragraph needed- “Consent to participate was obtained from each participant as written signatures.” It is common practice that enrolled participants in a clinical trial sign a consent form that he/she agrees to participate in the research study.

3. Methods. First sentence under the participants section- Please correct the spelling of enrollment.

4. Methods: Last paragraph. The authors should remove the last paragraph. The paragraph discusses common practices to deidentify participants. This information should be encompassed in the IRB approval, and the information is not important for the overall methodology of the research study.

5. Methods: The following sentences under Blood Chemistry should be removed. This information is not needed, and removing the sentences will decrease the wordiness of the manuscript. 1. The 3rd and 4th sentences regarding the number of times the tubes were inverted. 4. The sentence regarding aliquoting plasma. 5. The last sentence about lancing and collecting a second blood droplet.

6. Results: Please report height in meters in Table 1 and Supplemental Tables 1-2.

7. Results: The authors termed women who reported change in menses as “responders” and those who reported no change as “non-responders.” I suggest changing the terms responder and non-responder to something else. This terminology makes it seem that women who had no change in menses did not respond to the survey, and those who had change in menses responded to the survey. I suggest changing the term non-responders and responders to something else and re-titling Supplemental Table 1 to “Predictive Baseline Characteristics Between Reported Change in Menses vs. No Change in Menses.”

8. Results: Please edit the sentence “The women who were randomized to the KD+PL diet attained clinically significant weight-loss at day 14, whereas by day 28 on the KD+KS and the LFD.” To “The women who were randomized to the KD+PL diet attained clinically significant weight-loss at day 14, whereas by day 28 weight loss was clinically significant for women on the KD+KS and the LFD.”

9. Results: Please define what clinically significant weight loss means.

10. Abstract: The women in this study are defined as overweight, yet your average BMI is >30. Please change this to overweight and obese.

11. The full data set is not attached with this manuscript submission. I only see the attached tables with means and SDs.

Reviewer #2: Dear authors

It is a very good and valuable work, but if the following points are included in, it will be a very good paper.

-The title doesn't match with the text. Because in your title, there is no mention of ketone supplementation and compared with a low fat diet (LFD).

- The necessity and objectives of the research are not well stated at the end of the introduction, so there should be more discussion about supplementation and why it is used during menstruation.

- In the methods section, the method of prescribing and controlling diets must be described in more detail. How is ketosis status controlled?

-The composition of macronutrients and total energy in each diet plan better to be mentioned and compared in a table.

-Which reference was used for the Menses Survey? Is it valid? Please give a reference.

-It is better to be mentioned the Menses stages by the participants at the time of evaluation

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Reviewer #1: No

Reviewer #2: No

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Attachments

Attachment

Submitted filename: rev. one plose.docx

PONE-D-23-11590R1Self-Reported Menses Physiology is Positively Modulated by A Well-Formulated, Energy-Controlled Ketogenic Diet vs. Low Fat Diet in Women of Reproductive Age with Overweight/ObesityPLOS ONE

Dear Dr. Volek,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Nov 23 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Licy Yanes Cardozo

Academic Editor

PLOS ONE

Journal Requirements:

1. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

Please address the minor comments that we were brought by the reviewers

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: No

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The author addressed all my suggested revisions. I believe that this manuscript is ready for acceptance. My only reason to suggest minor revisions is because the link to the dataset did not work in my browser. It is the journal policy that the reviewers receive access to the dataset, and without this, I cannot suggest acceptance.

Reviewer #2: Dear author

Thanks for complete correction of comments. But, need to two minor edit in the results section.

1. Is the table st3 for baseline measurements? If the answer is yes, it should be mentioned in the title of the table.

2. I did not see your addressed Table st4 for the blood parameters section in the main text. Please give the address of all tables and figures in its own section in the main text.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-23-11590R2Self-Reported Menses Physiology is Positively Modulated by A Well-Formulated, Energy-Controlled Ketogenic Diet vs. Low Fat Diet in Women of Reproductive Age with Overweight/Obesity.PLOS ONE

Dear Dr. Volek,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Jan 14 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Licy Yanes Cardozo

Academic Editor

PLOS ONE

Additional Editor Comments:

Please address concerns risen by reviewer about statistical analysis. Thanks

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

Reviewer #3: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors addressed all of my recommendations and suggestions. I think that this manuscript is ready for publication. This manuscript made good use of a previously collected dataset. The study made some interesting findings that warrant further analysis of the underlying mechanisms.

Reviewer #2: (No Response)

Reviewer #3: A research study was conducted which aimed to compare the self-reported menses fluctuations between a controlled, hypocaloric well-formulated ketogenic diet (KD) and an isocaloric/isonitrogenous low-fat diet (LFD). Women randomized to the KD+KS (30%) and KD+PL (43%) reported subjective increases in menses frequency and intensity after 14 days, whereas another third reported a regain of menses (>1 year since the last period) after 28 days. No LFD participants reported menses changes.

Major revisions:

In general, since the sample sizes are small and the distribution of the data cannot be shown to be normal, non-parametric tests should be used for comparisons among/between the groups. An underlying assumption of the t-test and ANOVA is normally distributed data.

1- Statistics section: Clarify how the within-diets were quantified using Kruskal-Wallis tests since this test is for independent samples.

2- Table 1: The sample sizes in the three groups are small; therefore, the Kruskal-Wallis test, a nonparametric test, would be more powerful when comparing the central tendencies of these baseline characteristics in the three groups.

3- If the interaction effect is significant, provide an interpretation of the results, but do not test main effects because the tests for main effects are uninteresting in light of significant interactions. If interaction effects are non-significant, drop the interaction effects from the model and test the main effects. Determining which results to present when testing interactions is often a multi-step process.

4- Table 2: An underlying assumption of the Kruskal-Wallis test is independent samples; therefore, it is not valid for comparing the data in Table 2.

Minor revisions:

1- Abstract: Identify the statistical testing methods from which p-values were estimated.

2- Menses section: A) In addition to the frequencies provide the corresponding percentages.

B) Due to small sample sizes, compare BMI and serum MCP-1 in the two groups using non-parametric tests such as Wilcoxon rank sum tests.

3- Indicate the date range subjects participated in the study.

4- State and justify the study’s target sample size with a pre-study statistical power calculation. The power calculation should include: (1) the estimated outcomes in each group; (2) the α (type I) error level; (3) the statistical power (or the β (type II) error level); (4) the target sample size, (5) the statistical testing method and (6) for continuous outcomes, the standard deviation of the measurements.

5- To assist in the review process, add line numbering to the document and double space the lines.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Laura E. Coats, PhD, RDN

Reviewer #2: No

Reviewer #3: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-23-11590R3Self-Reported Menses Physiology is Positively Modulated by A Well-Formulated, Energy-Controlled Ketogenic Diet vs. Low Fat Diet in Women of Reproductive Age with Overweight/Obesity.PLOS ONE

Dear Dr. Volek,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================

Please addresses comments that were made by statistical reviewer.

==============================

Please submit your revised manuscript by Apr 01 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Licy Yanes Cardozo

Academic Editor

PLOS ONE

Additional Editor Comments:

Please addresses statistical review comments.

thanks

Associate Editor

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

Reviewer #3: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: Yes

Reviewer #3: No

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Line 113- Remove the typo "In Brief"

The authors met all of my requested changes and answered all my questions. Reviewer #3 had many technical and statistical suggestions and revisions for this manuscript. Statistical methodology is not my area of expertise, thus I will defer to reviewer 3 as to the correctness and soundness of the revised statistical analysis within this manuscript.

Reviewer #2: I agree with the opinion of the authors and the small sample size is not a good reason to use the non-parametric test. It is true that the sample size is small, but if the hypothesis of normality has been met, parametric tests are more suitable.

Reviewer #3: Major revision:

The statistics section states, "Changes within- and between-diets were quantified using a series of Kruskal-Wallis tests for non-parametric independent samples." An underlying assumption of the Kruskal-Wallis test is independent samples. Thus, it may be appropriate for comparing between samples data. However, it is inappropriate for comparing within diets at different time points (days 14, 28, and 42). Testing the group by time interaction effect in a repeated measures ANOVA or linear mixed model would be superior to the statistical methods currently employed for testing the primary aims of the study. Both of these methods are appropriate for analyzing repeated measures data and the choice depends on the distribution of the data. If the interaction effect is significant, provide an interpretation of the results, but do not test main effects because the tests for main effects are uninteresting in light of significant interactions. If interaction effects are non-significant, drop the interaction effects from the model and test the main effects. Determining which results to present when testing interactions is often a multi-step process.

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Reviewer #1: No

Reviewer #2: Yes: Kazem Khodaei

Reviewer #3: No

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Self-Reported Menses Physiology is Positively Modulated by A Well-Formulated, Energy-Controlled Ketogenic Diet vs. Low Fat Diet in Women of Reproductive Age with Overweight/Obesity.

PONE-D-23-11590R4

Dear Dr. Volek,

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Reviewer #3: All comments have been addressed

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Reviewer #3: (No Response)

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Reviewer #3: (No Response)

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Reviewer #3: (No Response)

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Reviewer #3: No

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