Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

I think this is an interesting paper with great potential for future studies that is translational across disciplines. Please see below for my specific comments regarding suggested improvements to the submitted manuscript.

Line 34: Where did fatigue index come from? This was not mentioned earlier in your abstract; Also, please put p-values in for fatigue index and Stroop accuracy

Line 35: I recommend making pHolm as p_Holm to make it more clear

Line 40: Please use p-values for the comparisons between LA+CR and CG, CR, and LA

Introduction: Please provide some further justification of your study; Why should we care about the use of LA and CR?

Lines 103-106: Please revise your start dates in this paper; Your pre-registration states your study occurred from April 1, 2025 and ended on May 15, 2025 but you only submitted the pre-registration on April 14, 2026

Lines 106-107: Please provide time of day

Lines 176-203: Please re-order these three subsections in order of completion to align with your Figure 1

Lines 229-232: Please state how these men were recruited and any incentives for completing the study

Results: To improve clarity and conciseness of the results section, could you remove the figures 3 and 4 and put the pairwise superscripts in the provided tables (specifically, table 2)?  The figures don’t really provide much beyond your tables and being bar charts, don’t actually provide realistic presentation of your results; You could also re-order tables 2, 3, and 4 where you introduce the results of the ANOVA and effect sizes then present the pairwise comparisons within the descriptive statistics; I think this may create a better flow in the paper and improve clarity (I had to keep jumping between tables to follow the results)

Table 7 does not match the style format of your previous tables; Please make sure these all align

While I appreciate the acknowledgement of the study pitfalls, I think this trial should be titled a “exploratory” or “pilot study” in the title and description; I think this would help further caveat the trial to an audience

Author Response

Response to Reviewers

Manuscript metabolites-4527738 — “Acute Responses to Creatine Monohydrate and L-Arginine, Alone and Combined, on Repeated-Sprint Power, Countermovement Jump Height, and Stroop Reaction Time in Recreationally Active Men: An Exploratory, Randomized, Double-Blind Crossover Trial”

We thank the Academic Editor and the three reviewers for their careful and constructive evaluation. All comments are addressed below, and every change is colour-coded in the revised manuscript so that each reviewer can locate the corresponding edits at a glance:

Reviewer 1 = blue   Reviewer 2 = green   Reviewer 3 = red   Academic Editor = purple

As an additional quality-control step, the raw workbook was independently rechecked for condition means/SDs, Bonferroni-adjusted pairwise comparisons, and the 2×2 factorial contrast estimates; these reproduce the values reported in the revised manuscript. The response document and revised manuscript have also been cross-checked for consistency with the reviewer comments and the updated ClinicalTrials.gov record.

Reviewer 1

Line 34 — Where did fatigue index come from? It was not mentioned earlier in the abstract; please add p-values for fatigue index and Stroop accuracy.

Response: The abstract Methods now explicitly lists the secondary outcomes (“Secondary outcomes were RAST minimum power (MP), fatigue index (FI), and Stroop accuracy”), so FI is introduced before it is used. The Results sentence now reports the omnibus p-values for the two non-significant outcomes: fatigue index (p = 0.306) and Stroop accuracy (p = 0.396).

Line 35 — Format pHolm with a subscript for clarity.

Response: Done throughout the manuscript: every instance now reads p with a subscripted “Holm” (p_Holm) in the abstract, Results, Table 7 narrative, and Discussion.

Line 40 — Use p-values for the LA+CR vs CG, CR and LA comparisons.

Response: The abstract now gives explicit p-values for each contrast, e.g. PP: CG (p < 0.001), LA (p = 0.002), CR (p < 0.001); and AP: exceeded CG (p < 0.001) and CR (p = 0.016) but not LA (p = 0.056) after Bonferroni adjustment.

Introduction — Provide further justification: why should we care about LA and CR?

Response: A justification sentence was added to the Introduction explaining the practical relevance (athletes routinely self-select multi-ingredient products assuming additive gains, yet the incremental value and metabolic basis of acute co-supplementation are unestablished). A complementary sentence on the distinct metabolic targets of the two compounds was also added (see Academic Editor response).

Lines 103–106 — The registration timeline is inconsistent (registry lists study April 1–May 15 2025, but the record was submitted 14 April 2026).

Response: Thank you for pointing out this apparent discrepancy. We would like to clarify that the study dates reported in the manuscript are correct. The ClinicalTrials.gov record has been updated to reflect the correct study timeline. However, the updated record has not yet been reflected on the public ClinicalTrials.gov website because it is currently pending PRS review. The updated record was released for PRS review on August 18, 2026, while the last publicly available version was released on April 21, 2026. The study started on 1 April 2025, primary completion occurred on 15 May 2025, and study completion occurred on 16 May 2025. The registration record was first submitted on 14 April 2026; therefore, registration occurred after study completion. The manuscript has been revised to explicitly describe the trial as retrospectively registered, with no implication of prospective registration.

 

Lines 106–107 — Provide time of day.

Response: The retained study records confirm that each participant was tested at the same time of day across visits (±30 min), but they do not preserve an exact absolute clock-time window. We therefore do not report a narrower clock-time range that cannot be verified retrospectively. The revised manuscript states this limitation explicitly.

Lines 176–203 — Re-order the three test subsections to match Figure 1.

Response: The Data-Collection subsections were reordered to follow the Figure 1 sequence: 2.4.3 Stroop Color–Word Test, 2.4.4 Countermovement Jump Test, 2.4.5 Running-Based Anaerobic Sprint Test.

Lines 229–232 — State how participants were recruited and any incentives.

Response: Section 2.2 now states that participants were recruited from the university student and recreational-sport community through in-person announcements and word of mouth. The retained study documentation does not include a participant-incentive record; therefore, the manuscript reports that incentive status could not be reconstructed retrospectively rather than inferring an unsupported answer.

Results — Remove Figures 3 and 4 and put pairwise significance as superscripts in the tables (esp. Table 2); consider re-ordering Tables 2–4.

Response: Figures 3 (RAST bar charts) and 4 (Stroop bar charts) were removed and the former Figure 5 was renumbered to Figure 3. Bonferroni-adjusted pairwise significance is now embedded directly in Table 2 as superscripts (a ≠ CG, b ≠ LA, c ≠ CR, d ≠ LA+CR), with a defining footnote, so readers no longer need to move between tables to read the descriptive means and their contrasts together. Tables 3–6 (omnibus ANOVA and pairwise contrasts) retain their detailed statistics.

Table 7 — Does not match the style of the other tables.

Response: Table 7 was reformatted to the same three-line MDPI style as Tables 1–6: centred cells, matched font size, and bold row labels/header.

Title/description — Title the trial “exploratory” or “pilot” to caveat it.

Response: The title now reads “… An Exploratory, Randomized, Double-Blind Crossover Trial,” and the abstract/conclusions explicitly frame the findings as exploratory and hypothesis-generating.

Reviewer 2

Comment 1 — Creatine solubility: 16.2–26.1 g in 250 mL likely formed a suspension, not a solution; discuss dissolution vs suspension and any effect of grittiness on blinding versus the sucrose placebo.

Response: Section 2.4.2 now states that, given creatine’s limited aqueous solubility (≈14 g·L⁻¹), the creatine-containing beverages formed a partial suspension rather than a fully dissolved solution, that participants re-swirled/rinsed the container to consume residual sediment, and that the resulting gritty mouthfeel differed from the clear sucrose placebo and constitutes a potential source of unblinding. The blinding/expectancy implication is expanded in the Limitations.

Comment 2 — Justify the fixed, non-counterbalanced test order in Section 2.3.

Response: Section 2.3 now explains the rationale: the interference (Stroop) and explosive, low-fatigue neuromuscular (CMJ) tasks were deliberately placed before the metabolically exhaustive RAST so that fatigue generated by repeated sprints could not contaminate the reaction-time and jump measures, minimizing within-session carryover between consecutive tasks.

Reviewer 3

Comment 1 — Insufficient creatine washout — quantify the carry-over bias and propose a pharmacokinetically informed washout.

Response: The Limitations now describe both the likely direction and the limits of quantifying carryover bias. Residual creatine in later periods would tend to draw condition means together and bias CR-vs-CG and LA+CR-vs-LA contrasts toward the null, while period-by-treatment structure could inflate variance and distort pairwise contrasts. However, because period/sequence identifiers and direct muscle creatine/phosphocreatine measurements were unavailable, the magnitude of this bias cannot be numerically estimated retrospectively. For future crossover studies we now recommend a washout long enough to document return of muscle creatine/phosphocreatine to baseline; a conservative multi-week interval of approximately 4–6 weeks is noted based on washout after conventional loading, with biochemical confirmation preferable, or alternatively a parallel-group allocation to avoid creatine carryover.

Comment 2 — Missing sequence/period identifiers — refit the model if recoverable, otherwise flag as a major limitation and moderate causal inference.

Response: The randomized sequence and period identifiers were not retained in the analysis dataset and could not be recovered, so a mixed-effects crossover model including period, sequence, and first-order carryover could not be fitted. We have elevated this from a secondary caveat to a primary methodological limitation and correspondingly moderated all causal interpretation of the between-condition contrasts.

Comment 3 — Weak mechanistic basis for an acute single creatine bolus.

Response: The Discussion now states explicitly that a single 0.3 g·kg⁻¹ bolus with a ≈60-min pre-test interval departs from the established loading paradigm and that current evidence does not demonstrate muscle/brain uptake and phosphocreatine conversion within this window; any acute creatine-attributable effect is therefore described as mechanistically unexplained pending direct tissue measurement.

Comment 4 — Language mismatch confounds the Stroop task (English task, Turkish speakers).

Response: This is now emphasized as a key limitation: the reaction-time index reflects foreign-language lexical-processing load in addition to color–word interference and cannot be generalized as a language-independent measure of executive function; interpretation is restricted to incongruent-stimulus response speed under the tested conditions.

Comment 5 — Placebo matching and unvalidated blinding.

Response: The Limitations now discuss how the disparity in solute mass/osmolality and the gritty mouthfeel of the creatine suspension, combined with the absence of a formal blinding check, could have introduced expectancy-driven response bias that cannot be excluded.

Comment 6 — Heterogeneous post-ingestion timing across outcomes — report absolute time windows and PK alignment.

Response: We identified and corrected an internal timing inconsistency in the prior revision. The Stroop test was protocol-timed to begin at approximately 60 min post-ingestion and CMJ followed after a 3-min interval. The RAST protocol included a standardized 10-min warm-up after CMJ before the six sprints; therefore, the earlier ≈66-min RAST label implied a precision that was not supported and has been removed from both Section 2.3 and Figure 1. Because exact RAST timestamps were not retained, the manuscript now reports the sequence accurately without inventing an absolute RAST start time and explains that the registry's nominal 60-min time frame represents the start of the testing session rather than an identical timestamp for every outcome.

Comment 7 — Baseline habitual creatine/arginine intake not quantified.

Response: The Limitations now state that habitual dietary creatine/arginine intake was not captured with a food-frequency questionnaire (not incorporated at study conception) and explain how unmeasured baseline variation — e.g., higher habitual creatine intake producing blunted, ceiling-type responses — may have contributed to inter-individual response variability.

Comment 8 — Near-ceiling Stroop accuracy.

Response: The Discussion now clarifies that near-ceiling accuracy (≈97–98%) limits sensitivity to speed–accuracy trade-offs, may reflect relatively easy stimuli or conservative responding with non-native words, and that the analysis can characterize only incongruent-stimulus response speed rather than global executive function.

Comment 9 — 2×2 factorial interpretation needs more depth.

Response: The Discussion now cautions that a non-significant interaction is not positive evidence of additivity (the test was likely underpowered and unadjusted for period/sequence) and details plausible competitive/antagonistic mechanisms (shared glycine/SAM demand for guanidinoacetate/creatine synthesis, arginine partitioning between NOS and other pathways, and increased osmotic/GI load).

Comment 10 — Counter-intuitive minimum-power pattern needs mechanistic elaboration.

Response: The Discussion now advances testable hypotheses for why adding creatine reduced the LA-only minimum-power advantage: (i) the larger solute mass raises GI osmolality and may slow gastric emptying and arginine absorption, blunting NO-mediated benefit on the most fatigued sprints, and (ii) metabolic competition for arginine flux/methylation capacity; both are proposed as testable with plasma arginine/nitrite kinetics and gastric-emptying/hydration markers.

Academic Editor

Point 1 — The study is performance-focused with limited alignment to the Special Issue’s emphasis on metabolic mechanisms and responses.

Response: The framing has been strengthened toward metabolic mechanism. The Introduction now positions creatine and L-arginine on distinct metabolic nodes (phosphagen/ATP–phosphocreatine buffering; nitric-oxide signalling, guanidinoacetate/creatine biosynthesis, and urea-cycle ammonia handling). The Discussion of the factorial and minimum-power findings is now framed explicitly in terms of metabolic-pathway competition (arginine partitioning, methylation capacity, osmotic/GI load), and a concluding metabolic-interpretation sentence links the outcome-specific pattern to the two supplements engaging different energy-metabolism nodes and to the need for direct measurement of metabolic intermediates. We hope this metabolic reframing better fits the Special Issue scope.

Point 2 — The trial-registration timeline is inconsistent with the current registry record.

Response: Thank you for pointing out this apparent discrepancy. We would like to clarify that the study dates reported in the manuscript are correct. The ClinicalTrials.gov record has been updated to reflect the correct study timeline. However, the updated record has not yet been reflected on the public ClinicalTrials.gov website because it is currently pending PRS review. The updated record was released for PRS review on August 18, 2026, while the last publicly available version was released on April 21, 2026. We have carefully reviewed the relevant dates and ensured that the manuscript is consistent with the updated ClinicalTrials.gov record. The study is now explicitly described as retrospectively registered.

 

Point 3 — The statistical analysis does not adequately address the factorial crossover design, period/carryover effects, or multiplicity across primary outcomes.

Response: Multiplicity is handled with Holm control across the four co-primary omnibus tests (and separately within each factorial-effect family), with Bonferroni-adjusted within-outcome pairwise tests; this is retained and clarified. The unavailability of period/sequence identifiers, which precludes a full crossover mixed model with period, sequence, and carryover terms, is now stated as a primary limitation. The 2×2 factorial contrasts are presented and interpreted strictly as a secondary sensitivity analysis with moderated causal claims. As an additional QC step, the raw workbook was independently rechecked for condition means/SDs, Bonferroni-adjusted pairwise comparisons, and factorial contrast estimates; these reproduce the manuscript values, and no numerical corrections were required.

 

We believe these revisions substantially strengthen the manuscript’s methodological transparency, metabolic framing, and interpretive caution, and we thank the editor and reviewers for their guidance.

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

This study investigates the acute effects of creatine monohydrate and L-arginine, both alone and co-ingested, on anaerobic sprint performance, jump height, and executive function in recreationally active men. The experimental setup is well-structured, the statistical handling of multiple endpoints and factorial main effects is commendable, and the authors maintain a balanced, non-exaggerated interpretation of their findings.

To strengthen the methodological clarity and rigor of the paper, please address the following points:

1. Participants received a single bolus of creatine at 0.3g/kg resulting in absolute doses ranging from 16.2 g to 26.1 g in 250 mL of water. Because creatine monohydrate exhibits limited solubility at room temperature, especially in quantities exceeding 15–20 g per 250 mL, it likely formed a suspension rather than a fully dissolved solution. Please clarify whether complete dissolution or suspension occurred, and discuss whether the resulting mouthfeel or grittiness compared to the 6 g sucrose placebo might have influenced the effectiveness of participant blinding.
2. All assessments followed a rigid, non-counterbalanced sequence across visits: Stroop test - 3-min rest - CMJ - 3-min rest - RAST. Please add a brief justification for this specific order in Section 2.3 (e.g., explaining that cognitive testing and neuromuscular explosive output had to precede the exhaustive metabolic fatigue induced by repeated anaerobic sprints to prevent acute carryover between consecutive tasks within the session).

Author Response

Response to Reviewers

Manuscript metabolites-4527738 — “Acute Responses to Creatine Monohydrate and L-Arginine, Alone and Combined, on Repeated-Sprint Power, Countermovement Jump Height, and Stroop Reaction Time in Recreationally Active Men: An Exploratory, Randomized, Double-Blind Crossover Trial”

We thank the Academic Editor and the three reviewers for their careful and constructive evaluation. All comments are addressed below, and every change is colour-coded in the revised manuscript so that each reviewer can locate the corresponding edits at a glance:

Reviewer 1 = blue   Reviewer 2 = green   Reviewer 3 = red   Academic Editor = purple

As an additional quality-control step, the raw workbook was independently rechecked for condition means/SDs, Bonferroni-adjusted pairwise comparisons, and the 2×2 factorial contrast estimates; these reproduce the values reported in the revised manuscript. The response document and revised manuscript have also been cross-checked for consistency with the reviewer comments and the updated ClinicalTrials.gov record.

Reviewer 1

Line 34 — Where did fatigue index come from? It was not mentioned earlier in the abstract; please add p-values for fatigue index and Stroop accuracy.

Response: The abstract Methods now explicitly lists the secondary outcomes (“Secondary outcomes were RAST minimum power (MP), fatigue index (FI), and Stroop accuracy”), so FI is introduced before it is used. The Results sentence now reports the omnibus p-values for the two non-significant outcomes: fatigue index (p = 0.306) and Stroop accuracy (p = 0.396).

Line 35 — Format pHolm with a subscript for clarity.

Response: Done throughout the manuscript: every instance now reads p with a subscripted “Holm” (p_Holm) in the abstract, Results, Table 7 narrative, and Discussion.

Line 40 — Use p-values for the LA+CR vs CG, CR and LA comparisons.

Response: The abstract now gives explicit p-values for each contrast, e.g. PP: CG (p < 0.001), LA (p = 0.002), CR (p < 0.001); and AP: exceeded CG (p < 0.001) and CR (p = 0.016) but not LA (p = 0.056) after Bonferroni adjustment.

Introduction — Provide further justification: why should we care about LA and CR?

Response: A justification sentence was added to the Introduction explaining the practical relevance (athletes routinely self-select multi-ingredient products assuming additive gains, yet the incremental value and metabolic basis of acute co-supplementation are unestablished). A complementary sentence on the distinct metabolic targets of the two compounds was also added (see Academic Editor response).

Lines 103–106 — The registration timeline is inconsistent (registry lists study April 1–May 15 2025, but the record was submitted 14 April 2026).

Response: Thank you for pointing out this apparent discrepancy. We would like to clarify that the study dates reported in the manuscript are correct. The ClinicalTrials.gov record has been updated to reflect the correct study timeline. However, the updated record has not yet been reflected on the public ClinicalTrials.gov website because it is currently pending PRS review. The updated record was released for PRS review on August 18, 2026, while the last publicly available version was released on April 21, 2026. The study started on 1 April 2025, primary completion occurred on 15 May 2025, and study completion occurred on 16 May 2025. The registration record was first submitted on 14 April 2026; therefore, registration occurred after study completion. The manuscript has been revised to explicitly describe the trial as retrospectively registered, with no implication of prospective registration.

 

Lines 106–107 — Provide time of day.

Response: The retained study records confirm that each participant was tested at the same time of day across visits (±30 min), but they do not preserve an exact absolute clock-time window. We therefore do not report a narrower clock-time range that cannot be verified retrospectively. The revised manuscript states this limitation explicitly.

Lines 176–203 — Re-order the three test subsections to match Figure 1.

Response: The Data-Collection subsections were reordered to follow the Figure 1 sequence: 2.4.3 Stroop Color–Word Test, 2.4.4 Countermovement Jump Test, 2.4.5 Running-Based Anaerobic Sprint Test.

Lines 229–232 — State how participants were recruited and any incentives.

Response: Section 2.2 now states that participants were recruited from the university student and recreational-sport community through in-person announcements and word of mouth. The retained study documentation does not include a participant-incentive record; therefore, the manuscript reports that incentive status could not be reconstructed retrospectively rather than inferring an unsupported answer.

Results — Remove Figures 3 and 4 and put pairwise significance as superscripts in the tables (esp. Table 2); consider re-ordering Tables 2–4.

Response: Figures 3 (RAST bar charts) and 4 (Stroop bar charts) were removed and the former Figure 5 was renumbered to Figure 3. Bonferroni-adjusted pairwise significance is now embedded directly in Table 2 as superscripts (a ≠ CG, b ≠ LA, c ≠ CR, d ≠ LA+CR), with a defining footnote, so readers no longer need to move between tables to read the descriptive means and their contrasts together. Tables 3–6 (omnibus ANOVA and pairwise contrasts) retain their detailed statistics.

Table 7 — Does not match the style of the other tables.

Response: Table 7 was reformatted to the same three-line MDPI style as Tables 1–6: centred cells, matched font size, and bold row labels/header.

Title/description — Title the trial “exploratory” or “pilot” to caveat it.

Response: The title now reads “… An Exploratory, Randomized, Double-Blind Crossover Trial,” and the abstract/conclusions explicitly frame the findings as exploratory and hypothesis-generating.

Reviewer 2

Comment 1 — Creatine solubility: 16.2–26.1 g in 250 mL likely formed a suspension, not a solution; discuss dissolution vs suspension and any effect of grittiness on blinding versus the sucrose placebo.

Response: Section 2.4.2 now states that, given creatine’s limited aqueous solubility (≈14 g·L⁻¹), the creatine-containing beverages formed a partial suspension rather than a fully dissolved solution, that participants re-swirled/rinsed the container to consume residual sediment, and that the resulting gritty mouthfeel differed from the clear sucrose placebo and constitutes a potential source of unblinding. The blinding/expectancy implication is expanded in the Limitations.

Comment 2 — Justify the fixed, non-counterbalanced test order in Section 2.3.

Response: Section 2.3 now explains the rationale: the interference (Stroop) and explosive, low-fatigue neuromuscular (CMJ) tasks were deliberately placed before the metabolically exhaustive RAST so that fatigue generated by repeated sprints could not contaminate the reaction-time and jump measures, minimizing within-session carryover between consecutive tasks.

Reviewer 3

Comment 1 — Insufficient creatine washout — quantify the carry-over bias and propose a pharmacokinetically informed washout.

Response: The Limitations now describe both the likely direction and the limits of quantifying carryover bias. Residual creatine in later periods would tend to draw condition means together and bias CR-vs-CG and LA+CR-vs-LA contrasts toward the null, while period-by-treatment structure could inflate variance and distort pairwise contrasts. However, because period/sequence identifiers and direct muscle creatine/phosphocreatine measurements were unavailable, the magnitude of this bias cannot be numerically estimated retrospectively. For future crossover studies we now recommend a washout long enough to document return of muscle creatine/phosphocreatine to baseline; a conservative multi-week interval of approximately 4–6 weeks is noted based on washout after conventional loading, with biochemical confirmation preferable, or alternatively a parallel-group allocation to avoid creatine carryover.

Comment 2 — Missing sequence/period identifiers — refit the model if recoverable, otherwise flag as a major limitation and moderate causal inference.

Response: The randomized sequence and period identifiers were not retained in the analysis dataset and could not be recovered, so a mixed-effects crossover model including period, sequence, and first-order carryover could not be fitted. We have elevated this from a secondary caveat to a primary methodological limitation and correspondingly moderated all causal interpretation of the between-condition contrasts.

Comment 3 — Weak mechanistic basis for an acute single creatine bolus.

Response: The Discussion now states explicitly that a single 0.3 g·kg⁻¹ bolus with a ≈60-min pre-test interval departs from the established loading paradigm and that current evidence does not demonstrate muscle/brain uptake and phosphocreatine conversion within this window; any acute creatine-attributable effect is therefore described as mechanistically unexplained pending direct tissue measurement.

Comment 4 — Language mismatch confounds the Stroop task (English task, Turkish speakers).

Response: This is now emphasized as a key limitation: the reaction-time index reflects foreign-language lexical-processing load in addition to color–word interference and cannot be generalized as a language-independent measure of executive function; interpretation is restricted to incongruent-stimulus response speed under the tested conditions.

Comment 5 — Placebo matching and unvalidated blinding.

Response: The Limitations now discuss how the disparity in solute mass/osmolality and the gritty mouthfeel of the creatine suspension, combined with the absence of a formal blinding check, could have introduced expectancy-driven response bias that cannot be excluded.

Comment 6 — Heterogeneous post-ingestion timing across outcomes — report absolute time windows and PK alignment.

Response: We identified and corrected an internal timing inconsistency in the prior revision. The Stroop test was protocol-timed to begin at approximately 60 min post-ingestion and CMJ followed after a 3-min interval. The RAST protocol included a standardized 10-min warm-up after CMJ before the six sprints; therefore, the earlier ≈66-min RAST label implied a precision that was not supported and has been removed from both Section 2.3 and Figure 1. Because exact RAST timestamps were not retained, the manuscript now reports the sequence accurately without inventing an absolute RAST start time and explains that the registry's nominal 60-min time frame represents the start of the testing session rather than an identical timestamp for every outcome.

Comment 7 — Baseline habitual creatine/arginine intake not quantified.

Response: The Limitations now state that habitual dietary creatine/arginine intake was not captured with a food-frequency questionnaire (not incorporated at study conception) and explain how unmeasured baseline variation — e.g., higher habitual creatine intake producing blunted, ceiling-type responses — may have contributed to inter-individual response variability.

Comment 8 — Near-ceiling Stroop accuracy.

Response: The Discussion now clarifies that near-ceiling accuracy (≈97–98%) limits sensitivity to speed–accuracy trade-offs, may reflect relatively easy stimuli or conservative responding with non-native words, and that the analysis can characterize only incongruent-stimulus response speed rather than global executive function.

Comment 9 — 2×2 factorial interpretation needs more depth.

Response: The Discussion now cautions that a non-significant interaction is not positive evidence of additivity (the test was likely underpowered and unadjusted for period/sequence) and details plausible competitive/antagonistic mechanisms (shared glycine/SAM demand for guanidinoacetate/creatine synthesis, arginine partitioning between NOS and other pathways, and increased osmotic/GI load).

Comment 10 — Counter-intuitive minimum-power pattern needs mechanistic elaboration.

Response: The Discussion now advances testable hypotheses for why adding creatine reduced the LA-only minimum-power advantage: (i) the larger solute mass raises GI osmolality and may slow gastric emptying and arginine absorption, blunting NO-mediated benefit on the most fatigued sprints, and (ii) metabolic competition for arginine flux/methylation capacity; both are proposed as testable with plasma arginine/nitrite kinetics and gastric-emptying/hydration markers.

Academic Editor

Point 1 — The study is performance-focused with limited alignment to the Special Issue’s emphasis on metabolic mechanisms and responses.

Response: The framing has been strengthened toward metabolic mechanism. The Introduction now positions creatine and L-arginine on distinct metabolic nodes (phosphagen/ATP–phosphocreatine buffering; nitric-oxide signalling, guanidinoacetate/creatine biosynthesis, and urea-cycle ammonia handling). The Discussion of the factorial and minimum-power findings is now framed explicitly in terms of metabolic-pathway competition (arginine partitioning, methylation capacity, osmotic/GI load), and a concluding metabolic-interpretation sentence links the outcome-specific pattern to the two supplements engaging different energy-metabolism nodes and to the need for direct measurement of metabolic intermediates. We hope this metabolic reframing better fits the Special Issue scope.

Point 2 — The trial-registration timeline is inconsistent with the current registry record.

Response: Thank you for pointing out this apparent discrepancy. We would like to clarify that the study dates reported in the manuscript are correct. The ClinicalTrials.gov record has been updated to reflect the correct study timeline. However, the updated record has not yet been reflected on the public ClinicalTrials.gov website because it is currently pending PRS review. The updated record was released for PRS review on August 18, 2026, while the last publicly available version was released on April 21, 2026. We have carefully reviewed the relevant dates and ensured that the manuscript is consistent with the updated ClinicalTrials.gov record. The study is now explicitly described as retrospectively registered.

 

Point 3 — The statistical analysis does not adequately address the factorial crossover design, period/carryover effects, or multiplicity across primary outcomes.

Response: Multiplicity is handled with Holm control across the four co-primary omnibus tests (and separately within each factorial-effect family), with Bonferroni-adjusted within-outcome pairwise tests; this is retained and clarified. The unavailability of period/sequence identifiers, which precludes a full crossover mixed model with period, sequence, and carryover terms, is now stated as a primary limitation. The 2×2 factorial contrasts are presented and interpreted strictly as a secondary sensitivity analysis with moderated causal claims. As an additional QC step, the raw workbook was independently rechecked for condition means/SDs, Bonferroni-adjusted pairwise comparisons, and factorial contrast estimates; these reproduce the manuscript values, and no numerical corrections were required.

 

We believe these revisions substantially strengthen the manuscript’s methodological transparency, metabolic framing, and interpretive caution, and we thank the editor and reviewers for their guidance.

Author Response File: Author Response.docx

Reviewer 3 Report

Comments and Suggestions for Authors

Thank you very much for the invitation to review this manuscript. I appreciate the opportunity to evaluate the work by Eken, Uçar, Kurtoğlu, Ozan, Buzdağlı, Söyler, and Aldhahi. This randomized, double‑blind crossover trial investigates the acute physiological effects of creatine monohydrate, L‑arginine, and their combined supplementation on repeated‑sprint performance, countermovement jump height, and Stroop reaction time in recreationally active men. The manuscript addresses a pertinent, timely research question within sports nutrition. The adoption of a crossover design reflects considerable methodological effort to unpack the effects of multi‑ingredient supplements. This work possesses clear exploratory value and fills a notable gap in the literature regarding acute co‑supplementation strategies.

 

Overall Evaluation

 

In summary, the study reports outcome‑specific performance improvements in peak anaerobic power and jump height following combined LA+CR supplementation, alongside selective reductions in Stroop reaction time. Nevertheless, as a randomized crossover trial, the manuscript exhibits several notable methodological limitations that compromise internal validity, statistical rigor, and result interpretability. Major concerns include an insufficient washout interval for creatine, missing sequence‑ and period‑related identifiers within the analytical dataset, suboptimal placebo matching, and language‑driven confounds affecting the cognitive task. Detailed comments are provided below to support the authors in strengthening the manuscript and refining their conclusions.

 

1. Regarding the insufficient washout period for creatine. The protocol implements a minimum 72‑hour interval between experimental sessions (Lines 107‑109). For creatine monohydrate, however, a 72‑hour washout period is inadequate to restore muscle creatine to baseline concentrations. Skeletal muscle stores of total creatine and phosphocreatine remain elevated for days to weeks after supplementation ceases. Although the authors acknowledge that complete elimination of carry‑over effects cannot be guaranteed (Lines 224‑226, 473‑475), this issue substantially undermines the internal validity of the crossover design, given that residual creatine may contaminate observations from subsequent treatment periods. The authors should elaborate quantitatively on how creatine carry‑over might bias effect sizes and distort pairwise between‑condition comparisons, and propose pharmacokinetically informed washout durations for future experimental designs.

 

2. Missing sequence and period identifiers impair the statistical strengths of the crossover design. As documented in Lines 221‑223 and 363‑366, the analytical dataset excludes randomized sequence and period identifiers, precluding modelling of period effects, sequence effects, and first‑order carry‑over. This forfeits one core statistical advantage inherent to crossover trial designs. If original sequence‑period records are retrievable, the statistical model ought to be refit incorporating these critical terms. If such records cannot be recovered, this shortcoming must be explicitly highlighted as a major methodological limitation, and causal inferences concerning treatment effects should be appropriately moderated.

 

3. The physiological mechanistic foundation supporting acute single‑bolus creatine administration remains weak. A single bolus of 0.3 g/kg body‑mass creatine was administered, with testing initiated approximately 60 min post‑ingestion (Lines 152‑156). As discussed by the authors (Lines 398‑402), well‑established ergogenic benefits of creatine stem primarily from multi‑day loading regimens that elevate intramuscular phosphocreatine reserves. Existing literature offers limited evidence that circulating creatine can be rapidly taken up and converted into intramuscular phosphocreatine within a 60‑minute window. The authors should either strengthen this mechanistic justification by citing relevant evidence on short‑term skeletal‑muscle or cerebral creatine uptake and metabolic conversion, or explicitly state that this acute bolus protocol deviates from conventional creatine‑loading paradigms.

 

4. Language mismatch introduces measurement confounds for the Stroop Color‑Word Test. The Stroop task was delivered in English to a cohort of Turkish‑speaking participants (Lines 201‑203, 442‑444). For lexical‑interference paradigms, semantic automaticity is heavily dependent on language proficiency. Accordingly, measured reaction time and accuracy reflect foreign‑language processing load in addition to canonical color‑word incongruence. This confound prevents unambiguous attribution of behavioural differences to executive‑function alterations. This language‑related bias should be emphasised as a key limitation within the Discussion section, with explicit clarification that Stroop‑derived observations are context‑specific and cannot be generalised as broad evidence for cognitive enhancement.

 

5. Concerns persist regarding placebo matching and unvalidated blinding integrity. The placebo beverage consisted of 6 g sucrose dissolved in 250 mL water, whereas active interventions contained 0.3 g/kg creatine, with or without 6 g L‑arginine (Lines 159‑161, 481‑483). Substantial disparities in total solute mass, osmolality, and potential sensory properties (taste, texture) raise the risk of unblinding and consequent expectancy‑driven response bias. Moreover, the effectiveness of blinding was not formally assessed (Lines 168‑169). The authors should discuss potential expectancy effects stemming from poorly matched formulations, and reflect on how compromised blinding could have modulated study outcomes.

 

6. Heterogeneous post‑ingestion timing across outcome measures complicates pharmacokinetic interpretation. Tests were completed in a fixed sequential order: the Stroop test commenced at 60 min post‑supplementation, immediately followed by the countermovement‑jump test and then the repeated‑sprint test (Lines 132‑134, 452‑454). Each outcome metric was therefore assessed at distinct time points relative to ingestion. Given the time‑dependent pharmacokinetic profile of L‑arginine, temporal misalignment between measurement windows and expected biological peak activity may distort observed effect magnitudes. The authors should report precise absolute time windows for each test and discuss their alignment with anticipated absorption and activity peaks for both supplements.

 

7. Baseline habitual dietary intakes of creatine and arginine were not quantified. While the study controlled for macronutrient composition and caffeine consumption (Lines 170‑174), habitual pre‑study dietary exposure to creatine and arginine was not characterised (Lines 484‑486). Unmeasured inter‑individual baseline variation can produce ceiling effects that attenuate supplement‑driven responses, as participants with higher habitual creatine intake tend to exhibit blunted supplementation effects. The authors should explain why a food‑frequency questionnaire was not implemented at study conception, and elaborate how unmeasured dietary heterogeneity may contribute to inter‑participant response variability.

 

8. Near‑ceiling accuracy on the Stroop test constrains interpretations of executive function. Across all experimental conditions, Stroop accuracy reached approximately 97‑98 % (Lines 205‑206, 260‑261). As acknowledged (Lines 314‑316), such uniformly high accuracy imposes a ceiling effect, substantially reducing analytical sensitivity for detecting speed‑accuracy trade‑offs. The authors should explore whether this pattern originates from overly simple task stimuli or conservative response strategies adopted by participants processing non‑native vocabulary. It should be clarified that the present analysis can only characterise incongruent‑stimulus reaction speed, rather than global executive‑function performance.

 

9. Interpretation of the 2 × 2 factorial decomposition requires greater depth. After Holm correction, no statistically significant interaction effect emerged for any co‑primary endpoint from the secondary factorial analysis (Lines 216‑221, 349‑362). A non‑significant interaction term neither confirms additive effects nor rules out metabolic antagonism; the null finding may simply result from the absence of sequence and period statistical controls. The Discussion section ought to expand upon potential competitive or antagonistic metabolic interactions between creatine and L‑arginine, and caution readers against assuming purely additive performance benefits under combined supplementation.

 

10. The counter‑intuitive pattern observed for minimum sprint power demands mechanistic elaboration. L‑arginine‑only supplementation yielded the highest minimum power values, significantly exceeding both placebo and combined‑supplement conditions (Lines 279‑281, 403‑406). This outcome dissociation demonstrates that combined supplementation does not confer uniform advantages across the full power‑duration spectrum of repeated‑sprint exercise. The authors should advance testable physiological hypotheses explaining why co‑administering creatine diminishes the minimum‑power advantage observed under L‑arginine alone. Plausible mechanisms include metabolic‑pathway competition or elevated gastrointestinal hyperosmolar burden that delays nutrient absorption.

 

Overall, this work yields valuable preliminary observations but calls for substantial revisions concerning methodological framing, statistical interpretation, and limitation disclosure. Findings should be framed as exploratory and hypothesis‑generating rather than definitive proof of ergogenic supplementation effects. Following adequate revisions addressing the points raised above, this manuscript could make a meaningful contribution to sports‑nutrition research. I look forward to evaluating the revised manuscript.

Author Response

Response to Reviewers

Manuscript metabolites-4527738 — “Acute Responses to Creatine Monohydrate and L-Arginine, Alone and Combined, on Repeated-Sprint Power, Countermovement Jump Height, and Stroop Reaction Time in Recreationally Active Men: An Exploratory, Randomized, Double-Blind Crossover Trial”

We thank the Academic Editor and the three reviewers for their careful and constructive evaluation. All comments are addressed below, and every change is colour-coded in the revised manuscript so that each reviewer can locate the corresponding edits at a glance:

Reviewer 1 = blue   Reviewer 2 = green   Reviewer 3 = red   Academic Editor = purple

As an additional quality-control step, the raw workbook was independently rechecked for condition means/SDs, Bonferroni-adjusted pairwise comparisons, and the 2×2 factorial contrast estimates; these reproduce the values reported in the revised manuscript. The response document and revised manuscript have also been cross-checked for consistency with the reviewer comments and the updated ClinicalTrials.gov record.

Reviewer 1

Line 34 — Where did fatigue index come from? It was not mentioned earlier in the abstract; please add p-values for fatigue index and Stroop accuracy.

Response: The abstract Methods now explicitly lists the secondary outcomes (“Secondary outcomes were RAST minimum power (MP), fatigue index (FI), and Stroop accuracy”), so FI is introduced before it is used. The Results sentence now reports the omnibus p-values for the two non-significant outcomes: fatigue index (p = 0.306) and Stroop accuracy (p = 0.396).

Line 35 — Format pHolm with a subscript for clarity.

Response: Done throughout the manuscript: every instance now reads p with a subscripted “Holm” (p_Holm) in the abstract, Results, Table 7 narrative, and Discussion.

Line 40 — Use p-values for the LA+CR vs CG, CR and LA comparisons.

Response: The abstract now gives explicit p-values for each contrast, e.g. PP: CG (p < 0.001), LA (p = 0.002), CR (p < 0.001); and AP: exceeded CG (p < 0.001) and CR (p = 0.016) but not LA (p = 0.056) after Bonferroni adjustment.

Introduction — Provide further justification: why should we care about LA and CR?

Response: A justification sentence was added to the Introduction explaining the practical relevance (athletes routinely self-select multi-ingredient products assuming additive gains, yet the incremental value and metabolic basis of acute co-supplementation are unestablished). A complementary sentence on the distinct metabolic targets of the two compounds was also added (see Academic Editor response).

Lines 103–106 — The registration timeline is inconsistent (registry lists study April 1–May 15 2025, but the record was submitted 14 April 2026).

Response: Thank you for pointing out this apparent discrepancy. We would like to clarify that the study dates reported in the manuscript are correct. The ClinicalTrials.gov record has been updated to reflect the correct study timeline. However, the updated record has not yet been reflected on the public ClinicalTrials.gov website because it is currently pending PRS review. The updated record was released for PRS review on August 18, 2026, while the last publicly available version was released on April 21, 2026. The study started on 1 April 2025, primary completion occurred on 15 May 2025, and study completion occurred on 16 May 2025. The registration record was first submitted on 14 April 2026; therefore, registration occurred after study completion. The manuscript has been revised to explicitly describe the trial as retrospectively registered, with no implication of prospective registration.

 

Lines 106–107 — Provide time of day.

Response: The retained study records confirm that each participant was tested at the same time of day across visits (±30 min), but they do not preserve an exact absolute clock-time window. We therefore do not report a narrower clock-time range that cannot be verified retrospectively. The revised manuscript states this limitation explicitly.

Lines 176–203 — Re-order the three test subsections to match Figure 1.

Response: The Data-Collection subsections were reordered to follow the Figure 1 sequence: 2.4.3 Stroop Color–Word Test, 2.4.4 Countermovement Jump Test, 2.4.5 Running-Based Anaerobic Sprint Test.

Lines 229–232 — State how participants were recruited and any incentives.

Response: Section 2.2 now states that participants were recruited from the university student and recreational-sport community through in-person announcements and word of mouth. The retained study documentation does not include a participant-incentive record; therefore, the manuscript reports that incentive status could not be reconstructed retrospectively rather than inferring an unsupported answer.

Results — Remove Figures 3 and 4 and put pairwise significance as superscripts in the tables (esp. Table 2); consider re-ordering Tables 2–4.

Response: Figures 3 (RAST bar charts) and 4 (Stroop bar charts) were removed and the former Figure 5 was renumbered to Figure 3. Bonferroni-adjusted pairwise significance is now embedded directly in Table 2 as superscripts (a ≠ CG, b ≠ LA, c ≠ CR, d ≠ LA+CR), with a defining footnote, so readers no longer need to move between tables to read the descriptive means and their contrasts together. Tables 3–6 (omnibus ANOVA and pairwise contrasts) retain their detailed statistics.

Table 7 — Does not match the style of the other tables.

Response: Table 7 was reformatted to the same three-line MDPI style as Tables 1–6: centred cells, matched font size, and bold row labels/header.

Title/description — Title the trial “exploratory” or “pilot” to caveat it.

Response: The title now reads “… An Exploratory, Randomized, Double-Blind Crossover Trial,” and the abstract/conclusions explicitly frame the findings as exploratory and hypothesis-generating.

Reviewer 2

Comment 1 — Creatine solubility: 16.2–26.1 g in 250 mL likely formed a suspension, not a solution; discuss dissolution vs suspension and any effect of grittiness on blinding versus the sucrose placebo.

Response: Section 2.4.2 now states that, given creatine’s limited aqueous solubility (≈14 g·L⁻¹), the creatine-containing beverages formed a partial suspension rather than a fully dissolved solution, that participants re-swirled/rinsed the container to consume residual sediment, and that the resulting gritty mouthfeel differed from the clear sucrose placebo and constitutes a potential source of unblinding. The blinding/expectancy implication is expanded in the Limitations.

Comment 2 — Justify the fixed, non-counterbalanced test order in Section 2.3.

Response: Section 2.3 now explains the rationale: the interference (Stroop) and explosive, low-fatigue neuromuscular (CMJ) tasks were deliberately placed before the metabolically exhaustive RAST so that fatigue generated by repeated sprints could not contaminate the reaction-time and jump measures, minimizing within-session carryover between consecutive tasks.

Reviewer 3

Comment 1 — Insufficient creatine washout — quantify the carry-over bias and propose a pharmacokinetically informed washout.

Response: The Limitations now describe both the likely direction and the limits of quantifying carryover bias. Residual creatine in later periods would tend to draw condition means together and bias CR-vs-CG and LA+CR-vs-LA contrasts toward the null, while period-by-treatment structure could inflate variance and distort pairwise contrasts. However, because period/sequence identifiers and direct muscle creatine/phosphocreatine measurements were unavailable, the magnitude of this bias cannot be numerically estimated retrospectively. For future crossover studies we now recommend a washout long enough to document return of muscle creatine/phosphocreatine to baseline; a conservative multi-week interval of approximately 4–6 weeks is noted based on washout after conventional loading, with biochemical confirmation preferable, or alternatively a parallel-group allocation to avoid creatine carryover.

Comment 2 — Missing sequence/period identifiers — refit the model if recoverable, otherwise flag as a major limitation and moderate causal inference.

Response: The randomized sequence and period identifiers were not retained in the analysis dataset and could not be recovered, so a mixed-effects crossover model including period, sequence, and first-order carryover could not be fitted. We have elevated this from a secondary caveat to a primary methodological limitation and correspondingly moderated all causal interpretation of the between-condition contrasts.

Comment 3 — Weak mechanistic basis for an acute single creatine bolus.

Response: The Discussion now states explicitly that a single 0.3 g·kg⁻¹ bolus with a ≈60-min pre-test interval departs from the established loading paradigm and that current evidence does not demonstrate muscle/brain uptake and phosphocreatine conversion within this window; any acute creatine-attributable effect is therefore described as mechanistically unexplained pending direct tissue measurement.

Comment 4 — Language mismatch confounds the Stroop task (English task, Turkish speakers).

Response: This is now emphasized as a key limitation: the reaction-time index reflects foreign-language lexical-processing load in addition to color–word interference and cannot be generalized as a language-independent measure of executive function; interpretation is restricted to incongruent-stimulus response speed under the tested conditions.

Comment 5 — Placebo matching and unvalidated blinding.

Response: The Limitations now discuss how the disparity in solute mass/osmolality and the gritty mouthfeel of the creatine suspension, combined with the absence of a formal blinding check, could have introduced expectancy-driven response bias that cannot be excluded.

Comment 6 — Heterogeneous post-ingestion timing across outcomes — report absolute time windows and PK alignment.

Response: We identified and corrected an internal timing inconsistency in the prior revision. The Stroop test was protocol-timed to begin at approximately 60 min post-ingestion and CMJ followed after a 3-min interval. The RAST protocol included a standardized 10-min warm-up after CMJ before the six sprints; therefore, the earlier ≈66-min RAST label implied a precision that was not supported and has been removed from both Section 2.3 and Figure 1. Because exact RAST timestamps were not retained, the manuscript now reports the sequence accurately without inventing an absolute RAST start time and explains that the registry's nominal 60-min time frame represents the start of the testing session rather than an identical timestamp for every outcome.

Comment 7 — Baseline habitual creatine/arginine intake not quantified.

Response: The Limitations now state that habitual dietary creatine/arginine intake was not captured with a food-frequency questionnaire (not incorporated at study conception) and explain how unmeasured baseline variation — e.g., higher habitual creatine intake producing blunted, ceiling-type responses — may have contributed to inter-individual response variability.

Comment 8 — Near-ceiling Stroop accuracy.

Response: The Discussion now clarifies that near-ceiling accuracy (≈97–98%) limits sensitivity to speed–accuracy trade-offs, may reflect relatively easy stimuli or conservative responding with non-native words, and that the analysis can characterize only incongruent-stimulus response speed rather than global executive function.

Comment 9 — 2×2 factorial interpretation needs more depth.

Response: The Discussion now cautions that a non-significant interaction is not positive evidence of additivity (the test was likely underpowered and unadjusted for period/sequence) and details plausible competitive/antagonistic mechanisms (shared glycine/SAM demand for guanidinoacetate/creatine synthesis, arginine partitioning between NOS and other pathways, and increased osmotic/GI load).

Comment 10 — Counter-intuitive minimum-power pattern needs mechanistic elaboration.

Response: The Discussion now advances testable hypotheses for why adding creatine reduced the LA-only minimum-power advantage: (i) the larger solute mass raises GI osmolality and may slow gastric emptying and arginine absorption, blunting NO-mediated benefit on the most fatigued sprints, and (ii) metabolic competition for arginine flux/methylation capacity; both are proposed as testable with plasma arginine/nitrite kinetics and gastric-emptying/hydration markers.

Academic Editor

Point 1 — The study is performance-focused with limited alignment to the Special Issue’s emphasis on metabolic mechanisms and responses.

Response: The framing has been strengthened toward metabolic mechanism. The Introduction now positions creatine and L-arginine on distinct metabolic nodes (phosphagen/ATP–phosphocreatine buffering; nitric-oxide signalling, guanidinoacetate/creatine biosynthesis, and urea-cycle ammonia handling). The Discussion of the factorial and minimum-power findings is now framed explicitly in terms of metabolic-pathway competition (arginine partitioning, methylation capacity, osmotic/GI load), and a concluding metabolic-interpretation sentence links the outcome-specific pattern to the two supplements engaging different energy-metabolism nodes and to the need for direct measurement of metabolic intermediates. We hope this metabolic reframing better fits the Special Issue scope.

Point 2 — The trial-registration timeline is inconsistent with the current registry record.

Response: Thank you for pointing out this apparent discrepancy. We would like to clarify that the study dates reported in the manuscript are correct. The ClinicalTrials.gov record has been updated to reflect the correct study timeline. However, the updated record has not yet been reflected on the public ClinicalTrials.gov website because it is currently pending PRS review. The updated record was released for PRS review on August 18, 2026, while the last publicly available version was released on April 21, 2026. We have carefully reviewed the relevant dates and ensured that the manuscript is consistent with the updated ClinicalTrials.gov record. The study is now explicitly described as retrospectively registered.

 

Point 3 — The statistical analysis does not adequately address the factorial crossover design, period/carryover effects, or multiplicity across primary outcomes.

Response: Multiplicity is handled with Holm control across the four co-primary omnibus tests (and separately within each factorial-effect family), with Bonferroni-adjusted within-outcome pairwise tests; this is retained and clarified. The unavailability of period/sequence identifiers, which precludes a full crossover mixed model with period, sequence, and carryover terms, is now stated as a primary limitation. The 2×2 factorial contrasts are presented and interpreted strictly as a secondary sensitivity analysis with moderated causal claims. As an additional QC step, the raw workbook was independently rechecked for condition means/SDs, Bonferroni-adjusted pairwise comparisons, and factorial contrast estimates; these reproduce the manuscript values, and no numerical corrections were required.

 

We believe these revisions substantially strengthen the manuscript’s methodological transparency, metabolic framing, and interpretive caution, and we thank the editor and reviewers for their guidance.

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Table 7 still does not match the formatting of the other tables in the manuscript; Please make sure this matches

Author Response

Response to Reviewers

Manuscript ID: metabolites-4527738

Acute Responses to Creatine Monohydrate and L-Arginine, Alone and Combined, on Repeated-Sprint Power, Countermovement Jump Height, and Stroop Reaction Time in Recreationally Active Men: An Exploratory, Randomized, Double-Blind Crossover Trial

Dear Editor and Reviewers,

Thank you for the careful evaluation of our revised manuscript. We have addressed the remaining formatting comment from Reviewer 1 and appreciate Reviewer 3’s positive assessment and recommendation for acceptance. For ease of verification, the Reviewer 1-related revision is highlighted in yellow in the revised manuscript.

Reviewer 1

Comment: “Table 7 still does not match the formatting of the other tables in the manuscript; Please make sure this matches.”

Response: Thank you for identifying this remaining formatting inconsistency. We have reformatted Table 7 so that its table-body typography and paragraph formatting now match the formatting used consistently in Tables 1–6. The table content, numerical values, and statistical results were not changed. The revised Table 7 and its caption are highlighted in yellow in the manuscript to make this correction easy to identify.

Reviewer 3

Comment: “The authors have adequately addressed all my concerns raised in the previous round of review. I appreciate the authors’ considerable efforts and valuable contributions to this manuscript. I am very satisfied with this revised version and recommend its acceptance for publication. I look forward to seeing further great achievements from the authors in their future-related research.”

Response: We sincerely thank Reviewer 3 for the positive evaluation of the revised manuscript, the encouraging comments, and the recommendation for acceptance. We greatly appreciate the reviewer’s time and constructive input throughout the review process. As no additional revisions were requested in this round, no further change to the manuscript was required in response to this comment.

Sincerely,

Özgür Eken, on behalf of all authors

Author Response File: Author Response.docx

Reviewer 3 Report

Comments and Suggestions for Authors

The authors have adequately addressed all my concerns raised in the previous round of review. I appreciate the authors’ considerable efforts and valuable contributions to this manuscript. I am very satisfied with this revised version and recommend its acceptance for publication. I look forward to seeing further great achievements from the authors in their future‑related research.

Author Response

Response to Reviewers

Manuscript ID: metabolites-4527738

Acute Responses to Creatine Monohydrate and L-Arginine, Alone and Combined, on Repeated-Sprint Power, Countermovement Jump Height, and Stroop Reaction Time in Recreationally Active Men: An Exploratory, Randomized, Double-Blind Crossover Trial

Dear Editor and Reviewers,

Thank you for the careful evaluation of our revised manuscript. We have addressed the remaining formatting comment from Reviewer 1 and appreciate Reviewer 3’s positive assessment and recommendation for acceptance. For ease of verification, the Reviewer 1-related revision is highlighted in yellow in the revised manuscript.

Reviewer 1

Comment: “Table 7 still does not match the formatting of the other tables in the manuscript; Please make sure this matches.”

Response: Thank you for identifying this remaining formatting inconsistency. We have reformatted Table 7 so that its table-body typography and paragraph formatting now match the formatting used consistently in Tables 1–6. The table content, numerical values, and statistical results were not changed. The revised Table 7 and its caption are highlighted in yellow in the manuscript to make this correction easy to identify.

Reviewer 3

Comment: “The authors have adequately addressed all my concerns raised in the previous round of review. I appreciate the authors’ considerable efforts and valuable contributions to this manuscript. I am very satisfied with this revised version and recommend its acceptance for publication. I look forward to seeing further great achievements from the authors in their future-related research.”

Response: We sincerely thank Reviewer 3 for the positive evaluation of the revised manuscript, the encouraging comments, and the recommendation for acceptance. We greatly appreciate the reviewer’s time and constructive input throughout the review process. As no additional revisions were requested in this round, no further change to the manuscript was required in response to this comment.

Sincerely,

Özgür Eken, on behalf of all authors

Author Response File: Author Response.docx