Ecdysterone: A Component of Dietary Supplements with Ergogenic Potential?

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Authors have written a good article entitled as Ecdysterone. A Component of Dietary Supplements with Ergogenic Potential?. Here are some important suggestions and comments that should must be addressed to improve the quality and readability of the article.

Authors have not provided all the aspects of article in the abstract, abstract should represent the summary of complete article.

Please add a conclusive line in the end of abstract section.

In table 1 Classification of the main nutritional and non-nutritional ergogenic aids. Please provide reference in each row for better presentation and for verification.

Last paragraph of the introduction should must provide a detailed rationale, reasoning and importance of the study.

In materials and methods section, The manuscript states it is a “narrative review” using a “standardized protocol,” but does not report key items needed for reproducibility: search dates, time window covered, number of records retrieved per database, deduplication method, screening flow, reasons for exclusion, and the final number of included studies.​ It would be better to expand the Materials and methods, include proper date last searched and years that you have covered. Similarly, Exact search strings for Web of Science, Google Scholar, and Punto Q (not only PubMed), plus any filters/limits used.

It would be better to provide A PRISMA flow diagram for selection  especially inclusion and exclusion criteria.

 Authors should provide a table of studies including design, population, dose formulation, duration, outcomes and mainly key limitations.

The manuscript mixes in vitro, animal and human evidence without a formal appraisal of study quality or risk of biasness, it would be better to present mechanistic data are sometimes used to imply clinical performance benefits.​

The abstract and conclusions assert “comparable ergogenic potential” to AAS and a more favorable safety profile the conclusion states ecdysterone has “similar ergogenic potential to anabolic androgenic steroids without their side effects.”​

Authors should provide a dedicated section “Human evidence for performance and hypertrophy” along with table of comparison and short narrative explanation because the text cites a double blind placebo controlled trial reporting no significant effects in resistance trained males and also cites a controlled human study reporting increased muscle mass/power, but does not reconcile differences in design, population, dose, product verification, or endpoints.​

Safety is very important aspect in any study involving human or animal trials based data it would be better to recheck the safety section emphasizes rodent LD50 and concludes there are “no known short and/or long-term side effects” while acknowledging high supplemental doses and widespread supplement mislabeling this is internally inconsistent and too definitive for the available human data.​ Please provide a separate toxicology for animals from human safety data and also focus on their limitations including duration, endpoints, dose relevance.

Authors should focus on manuscript notes frequent discrepancies between labeled and actual ecdysterone content and generic labeling but does not clearly translate this into how readers should interpret efficacy and safety claims for commercial products.​

It would be better to provide a clear and separate section  of ant-doping for the analytical and policy claims or at least restructure the anti-doping content in different subsections including pharmacokinetics or excretion, prevelance and regulatory status.

It would be better to check the whole article thoroughly or perform a full technical language edit and standardize all the compound names/synonyms, metabolite nomenclature, units (fresh vs dry weight) and tone (avoid broad safety generalizations).

Please reduce the iThenticate rate, which is 45;% it should not be more than 19 percent.

Author Response

Thank you very much for your review and comments. We have responded to your suggestions in the attached Word file.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

This article aims to systematically evaluate whether ecdysterone, as a dietary supplement, has the potential to enhance athletic performance, particularly as a possible alternative to anabolic steroids, with a focus on its natural sources and intake pathways, mechanisms for promoting protein synthesis and muscle hypertrophy, actual content and quality control in sports supplements, and the detection of ecdysterone and its metabolites in urine for anti-doping purposes.

This study, for the first time, systematically integrates the mechanisms of action, metabolic pathways, and anti-doping detection methods of ecdysterone within the framework of sports nutrition, incorporating the latest experimental and regulatory developments. It directly addresses athletes' demand for natural supplements and the urgency of anti-doping monitoring, demonstrating clear scientific and policy significance. By synthesizing basic research, market conditions, human metabolic data, and policy analysis, it fills a gap in the field where systematic, interdisciplinary reviews have been lacking.

It not only discusses the biological effects of ecdysterone but also addresses supplement quality control, urinary metabolic kinetics, and anti-doping policy recommendations, offering a comprehensive perspective from laboratory research to practical application. It explicitly suggests the inclusion of ecdysterone in the World Anti-Doping Agency's monitoring program, demonstrating strong practical relevance. The study also provides data on the excretion time and concentration ranges of ecdysterone and its metabolites in human urine, offering experimental evidence for anti-doping detection.

Currently, the study primarily relies on a narrative review. It is suggested that future research could incorporate systematic reviews and meta-analyses to enhance the level of evidence. Some of the cited studies have small sample sizes (e.g., only four positive samples), and caution is advised when extrapolating their conclusions; it is recommended to emphasize these limitations in the discussion. While the article notes significant variations in ecdysterone content across supplements, it lacks a systematic comparison of physiological effects at different doses. Adding charts or summaries of dose-response analyses is recommended.

Based on the available evidence, the article draws the following reasonable conclusions: ecdysterone exhibits anabolic potential and acts through the ER-β mechanism, potentially avoiding the side effects associated with traditional steroids; the supplement market suffers from serious quality issues; urine testing can differentiate between dietary intake and supplement abuse; and it is recommended to include ecdysterone in anti-doping monitoring programs. These conclusions are supported by in vitro, animal, and preliminary human studies cited in the text.

The references are generally appropriate, encompassing both classical research and recent publications up to 2023, with sources spanning multiple fields such as sports medicine, pharmacology, analytical chemistry, and anti-doping policy. However, it is recommended to include more literature on ecdysterone concerning female athletes or long-term safety studies.

The article lacks a metabolic pathway diagram. It is recommended to add a schematic illustrating the metabolic pathways and detection markers of ecdysterone in the human body to enhance the readability and scientific rigor of the paper. Furthermore, it is advised to explicitly outline future research directions in the conclusion section, emphasizing the need for large-scale randomized controlled trials, long-term safety assessments, and the development of standardized detection methods.

Author Response

Thank you very much for your review and comments. We have responded to your suggestions in the attached Word file.

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

This paper has a thorough review of ecdysterone and its use as a dietary supplement. In general, it has a nice summary of previous literature. It would be nice to include some critical analysis and discussion. It would also be better to provide more details about the methods. For example, how many articles were screened, how many were excluded, and how many were included in the manuscript. This can also be shown on a flow chart. In addition, Line 363. The title seems weird. All abbreviations should be written out when they first appear.

Author Response

Thank you very much for your review and comments. We have responded to your suggestions in the attached Word file.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Authors have addressed my concerns and it could be accepted after language improvement.

This similarity must be less than 18 percent according to the recommended guidelines.
In addition, I would suggest the authors to reduce its similarity index and submit the final version again.

 

Author Response

Dear reviewer, we have once again reviewed the manuscript and attempted to reduce the similarity score that was indicated. We are sending you the article with track changes and the final version.
Thank you very much.