Ketogenic Diet for Intensive Care Patients: A Scoping Review

COMMENTS

CHANGES MADE

In the introduction, I believe a bibliographical change is appropriate:

Lines 45-46 mention the growing interest in the topic, but only one article from a randomized controlled trial (RCT) is cited;

Thank you for this remark. We agree that the introduction (lines 45–46) refers to the growing interest in the topic, while only one randomised trial is cited in this excerpt. In response, we clarified and completed the context regarding the availability of studies with a higher level of reliability. In the updated version of the manuscript, we explain that the current evidence base on the use of the ketogenic diet in intensive care is limited and randomized trials are scarce. Among them is, m.in, the only RCT for patients with sepsis.

Line 50: It would be helpful to cite some articles on the use of the ketogenic diet in epilepsy;

Thank you for this remark. We agree that where we discuss the historical use of the ketogenic diet, it is worth recalling classic and contemporary publications on its use in the treatment of epilepsy. In the updated version of the manuscript, we have added relevant citations, covering both basic papers describing the effectiveness of KD in drug-resistant epilepsy and more recent systematic reviews.

Lines 51-52: Here too, it would be appropriate to supplement with additional references; the cited article briefly introduces the topic only in the "antioxidant effects" section;

Thank you for this remark. We agree that in this part of the introduction, it is worth referring to the broader literature on the mechanisms of action of the ketogenic diet, not only to the antioxidant aspect. At the same time, we emphasize that the discussed fragment is included in the introduction, the purpose of which is only a synthetic outline of the theoretical background, and not a full mechanistic analysis. However, in response to the reviewer's suggestion, we have expanded this passage with additional sources, including m.in anti-inflammatory, neuroprotective effects and effects on mitochondrial functions, which better reflects multidirectional mechanisms. The whole topic was developed more strongly in the later parts of the publication.

Line 73: Citation error: lines 53 and 54 are missing; lines 3-4 were likely intended;

Of course, we agree with this point. There was an editorial mistake here.

Lines 92-99: The article discusses the possible use of the ketogenic diet for the treatment of various pathologies, but the citation refers only to cardiovascular disease.

Thank you for this remark, we have provided links to other publications.

I believe the article requires further revision; using online programs, a high plagiarism rate of 83-85% was found.

Thank you for this message, which surprised us very much. In connection with the reviewer's allegations, we are sending our report on the plagiarism system used in all universities in Poland. At the same time, we kindly ask you to provide a reviewer's report with information on where plagiarism is located. This is a very hurtful remark for us.

COMMENTS

CHANGES MADE

Describe in the introduction the form of KD diet used in ICU patients- enteral feeding? Are these commercially available or prepared by the hospital formulary/pharmacy?

Thank you for this valuable remark. We agree that briefly clarifying how the ketogenic diet is delivered in intensive care settings increases the clarity of the introduction. At the same time, we emphasize that the Introduction section is synthetic and does not describe detailed nutritional protocols, which are discussed later in the paper.

In response to the reviewer's suggestion, we supplemented the introduction with a brief description of the forms of use of KD in the ICU, including both enteral nutrition and preparation of mixtures by the hospital pharmacy or clinical nutrition department. This information reflects the clinical practice described in the studies included in the review.

Define ketogenic diet (KD) on first use and then use KD.

Thank you for this remark. We agree that fully defining the term on first use improves the clarity of the text and complies with editorial standards. In the updated version of the manuscript, we have added a full definition of the ketogenic diet at the first occurrence and consistently use the abbreviation KD later in the text.

Table 1: Overall, the table needs to provide more detail on the studies including specific data results with p values.  Currently, the results/findings (except Rahmela) are broad and provide inadequate information. Also, include the KD formulas used in each study. List specific adverse effects.

Thank you for this remark. We agree that Table 1 needs to be expanded with more detailed data on the results of individual studies. In the updated version of the manuscript, we supplemented the table with specific numerical results reported in studies (e.g., the percentage of patients achieving ketosis, time to seizure control, changes in metabolic parameters), p-values when available in the original publications, the exact KD formulas used in each study (e.g., classical KD 3:1, 4:1; KD-IF; commercial enteral preparations; mixtures prepared in a hospital pharmacy), a detailed list of adverse reactions, according to the authors' reports (e.g. hypoglycemia, hyperlipidemia, acidosis, electrolyte disorders, food intolerance).

In cases where the studies did not report statistical data (e.g., no p-values in retrospective or descriptive studies), this information was clearly marked in the table to maintain clarity and consistency with the original sources.

Rahmela: include number of participants.

Thank you for this remark. We agree that providing the number of participants increases the clarity of the table and makes it easier to interpret the results. In the updated version of Table 1, we have supplemented the entry on the Rahmel et al. study with the number of patients included in the analysis.

Park: "description the experience" is not correct English.

We have corrected a fragment of the text.

Worden: pacjentów is not in English.

We have corrected a fragment of the text.

Feil: As an SOP, this paper does not seem appropriate to include in the study table. It is more appropriate to address in the discussion.

Thank you for this remark. We agree that an SOP document differs from classic clinical trials in terms of methodology. However, as part of the scoping review, the aim is to map the entire range of available literature, including not only empirical research, but also procedural studies, which play an important role in the practical implementation of clinical interventions. Therefore, we have expanded the inclusion criteria to include SOP documents

Table 2: Citations are needed to support the statements.

We have added references to literature.

Figure 2 is not positioned properly and obstructs the text. The images of whole foods to represent the KD does not fit the ICU setting. Perhaps use images of ingredients used in KD liquid formulas (unless whole foods are liquified in certain hospitals).

The authors have decided to remove Figure 2.

COMMENTS

CHANGES MADE

This study is positioned as a "scoping review," but in reality, the discussion section presents fairly strong conclusions regarding the efficacy and safety of KD, raising concerns about consistency with the review methodology. In particular, while the Results section only includes seven studies, the Discussion and subsequent sections contain many definitive statements across a wide range of areas, including SRSE, sepsis, immunomodulation, and neurological outcomes. Some of the cited references are not actually included in the review. The primary purpose of a scoping review is to organize "what research currently exists," and strong conclusions about efficacy require systematic review methods and quality assessment. Therefore, we recommend revising the wording in the Discussion and Conclusion to reflect the scope of "evidence mapping" and to more clearly indicate the limitations of the evidence. Furthermore, please clarify which descriptions are actually based on the seven selected studies.

(Revisions: Discussion (entire book, pp. 7–12), Conclusion (p. 13, lines 410–434))

Thank you for this valuable remark. We agree that the original version of the Discussions and Conclusions contained wording that could be read as too strong in the context of a scoping review. The aim of our study was to "present a synthetic picture of the current state of knowledge" and "map the available research", but some fragments may have suggested conclusions of an efficiency nature, beyond the scope of the scoping review methodology.

We have made corrections in such a way that they exactly correspond to the Reviewer's comments in the text, not only in the Discussion section.

The explanation of the study design in the Methods section is ambiguous. The use of multiple terms such as "comprehensive review" and "broad review" is inconsistent, making the reason for ultimately conducting a scoping review unclear. Furthermore, the section explaining the "difference from a systematic review" is redundant; a more concise statement of the study's unique objectives would be preferable.

(Correction: Methods 2.1 Study Design p.3 lines 101–111)

Thank you for this remark. We agree that the original description of the study design in the Study Design section may have been ambiguous due to the use of several terms ("comprehensive review", "broad review") that inaccurately reflected the reason for choosing scoping review. We also agree that the passage on "differences from systematic review" was redundant and could be perceived as a repetition of obvious methodological information.

In response to the reviewer's comment, we made the following changes: the terms "comprehensive review" and "broad review" were removed, replacing them with an unambiguous statement that the purpose was to conduct a scoping review;

shortened and simplified the study design description to clearly indicate the unique purpose of the review — mapping the available studies on the use of KD in intensive care; removed the passage about the differences between Scoping Review and Systematic Review, replacing it with a brief explanation of why Scoping Review was the right approach.

Regarding the search strategy, the search formula is not sufficiently detailed. Currently, only keyword examples are provided; however, if adhering to PRISMA-ScR standards, it is recommended to provide a complete search formula for at least one database (e.g., PubMed) as supplementary material. Additionally, unnatural search terms such as "benefits of ICU patients" are included, raising concerns about their impact on search sensitivity and specificity.

(Correction: Methods 2.3 Search Strategy, p.4, lines 145–151)

Thank you for this valuable remark. We agree that the original description of the search strategy was too general and did not fully meet the PRISMA-ScR standards. In response to the Reviewer's comments, we made corrections to the text. We have also added in the text Table 1.

While Figure 2 is visually interesting, its resolution and composition are insufficient, and its correspondence with the text is somewhat unclear. Furthermore, although it states, "Figure 2 shows the mechanism…", much of the content shown in the figure appears to be hypothetical or conceptual, and not directly derived from the reviewed research. It is recommended to clearly indicate the source of the figure's information and simplify it where necessary.

(Correction: Conclusion, p.13, lines 434–437, Figure 2)

Thank you for your valuable attention. Due to major problems with Figure 2, the authors decided to remove Figure 2 so that it does not create unnecessary misunderstandings.