Effects of Varying Caffeine Dosages and Consumption Timings on Cerebral Vascular and Cognitive Functions: A Diagnostic Ultrasound Study

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have presented a study on the influence of caffeine on cardiovascular system (SBP, DBP, PWV, MaxD and MinD of a common cartoid artery), respiratory system (SpO2) and cognitive functions. After consuming 100 mg caffeine, systolic blood pressure (SBP) increased; SpO2 and accuracy rate improved by 30 min but declined by 60 min. HR and response time continuously decreased, while PWV showed no change. After consuming 200 mg caffeine, SBP, diastolic blood pressure, and SpO2 increased significantly, while accuracy rate and response time decreased. PWV remained unchanged. The results revealed distinct dose-dependent patterns on physiological and cognitive changes, with SBP and SpO2 exhibiting greater changes when a higher dose was consumed in a short duration. Although moderate caffeine intake may support vascular health and cognitive function, excessive intake reduces blood flow, alters vascular elasticity, and impairs cognitive activation.

Although the findings of the study are valuable, there are a few minor points the authors should address:

1. Lines 97-100 should be proofread to clarify the inclusion and exclusion criteria.

2. Check the equation (3)

3. Include/expand the limitations of the study.

Author Response

Authors’ Responses to Reviewers’ Comments: 
Thank you very much for your valuable comments and suggestions. We carefully revised the 
manuscript following the reviewer’s recommendations accordingly. Point-by-point responses 
are as follows:  
 
Comments and Suggestions for Authors: ----------------------------------------------------------------------------------------------------- 
Reviewer #1: The authors have presented a study on the influence of caffeine on 
cardiovascular system (SBP, DBP, PWV, MaxD and MinD of a common cartoid artery), 
respiratory system (SpO2) and cognitive functions. After consuming 100 mg caffeine, systolic 
blood pressure (SBP) increased; SpO2 and accuracy rate improved by 30 min but declined by 
60 min. HR and response time continuously decreased, while PWV showed no change. After 
consuming 200 mg caffeine, SBP, diastolic blood pressure, and SpO2 increased significantly, 
while accuracy rate and response time decreased. PWV remained unchanged. The results 
revealed distinct dose-dependent patterns on physiological and cognitive changes, with SBP 
and SpO2 exhibiting greater changes when a higher dose was consumed in a short duration. 
Although moderate caffeine intake may support vascular health and cognitive function, 
excessive intake reduces blood flow, alters vascular elasticity, and impairs cognitive activation. 
 
Although the findings of the study are valuable, there are a few minor points the authors 
should address: 
 
1. Lines 97-100 should be proofread to clarify the inclusion and exclusion criteria. 
R1_1: Thank you for your valuable suggestion. As the reviewer commented, the authors 
added the criteria as follows: 
The criteria for inclusion were healthy adults over the age of 20 without any disease, and the 
exclusion criteria are those who have a history of diseases possibly affecting cardiovascular 
function, take cardiovascular drugs, are physically weak or mentally ill, and are students 
affiliated with the same department as the researchers. 
 
2. Check the equation (3) 
R1_2: we modified the equation (3) as follows: 
Change Rate (CR)= Value at 0,30,or 60 min
 Value at 0 min 
 
3. Include/expand the limitations of the study. 
R1_3: As the reviewer commented, we included the limitations of this study as follows:  
The limitations of this study include that the participants of the experiment were limited to 
their 20s, so it was not possible to compare the results according to age and effect of caffeine 
on the patients with any disease could not be confirmed. In addition, the change after 60 min 
could not be confirmed because the measurement was made within a limited time up to 60 
min after caffeine intake. The number of study participants was still small. Therefore, in future 
study, it is necessary to supplement these limitations and increase the number of samples to 
conduct studies on various age groups and patients with diseases and additional studies on 
changes after 60 min.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The abstract should be structured according to the authors guidelines (introduction, methods, results..) and should include numerical values, especially when presenting the results. Additionally, p-values would add statistical robustness to the findings. Ensure that the abstract specifies the population on which the investigation was conducted.

Please use SI units throughout the text to ensure consistency and clarity.

 

While the introduction provides a solid overview for readers without a background in the topic, consider making it more concise. The aim section is somewhat lengthy; shortening it would enhance readability and focus.

 

Indicate whether all participants underwent assessments at similar times of the day. Furthermore, discuss the potential influence of circadian rhythms on the effects of caffeine in the discussion section.

The initial paragraph of discussion should emphasize the study’s main findings without commenting on or comparing them with other studies. Revise this section to focus solely on the primary results and defer comparisons and commentary to later sections.

 

Address the limitations of the study, such as the relatively small sample size.

Author Response

Authors’ Responses to Reviewers’ Comments: 
Thank you very much for your valuable comments and suggestions. We carefully revised the 
manuscript following the reviewer’s recommendations accordingly. Point-by-point responses 
are as follows:  
 
Comments and Suggestions for Authors: ----------------------------------------------------------------------------------------------------- 
Reviewer #2: The abstract should be structured according to the authors guidelines 
(introduction, methods, results..) and should include numerical values, especially when 
presenting the results. Additionally, p-values would add statistical robustness to the findings. 
Ensure that the abstract specifies the population on which the investigation was conducted. 
R2_1: Thank you for your valuable suggestion. We corrected the abstract according to the 
guidelines.  
 
Please use SI units throughout the text to ensure consistency and clarity. 
R2_2: Thank you for your comments. We corrected the units using SI units. For example, ‘h’ 
to ‘hr’ and ‘s’ to ‘sec’. 
 
While the introduction provides a solid overview for readers without a background in the 
topic, consider making it more concise. The aim section is somewhat lengthy; shortening it 
would enhance readability and focus. 
R2_3: We modified the introduction as the reviewer commented. The aim section was 
shortened as follows:   
To address the above knowledge gaps, the present study aimed to analyze the physiological 
and cognitive responses to varying doses of caffeine intake in a short duration using 
diagnostic ultrasonography and cognitive function task. 
 
Indicate whether all participants underwent assessments at similar times of the day. 
Furthermore, discuss the potential influence of circadian rhythms on the effects of caffeine in 
the discussion section. 
R2_4: As the reviewer recommended, we included the experimental time of each participant. 
as follows: 
The participants completed two experimental sessions held at the same time, one week apart. 
 
The initial paragraph of discussion should emphasize the study’s main findings without 
commenting on or comparing them with other studies. Revise this section to focus solely on 
the primary results and defer comparisons and commentary to later sections. 
R2_5: We added an overall summary of the results to the discussion as follows:  
In this study, the effects of caffeine intake on BP, HR, SpO₂, blood vessel diameter, and 
cognitive function were analyzed. The BP change was not significant when 100 mg was 
ingested in a short duration, but BP increased significantly after 200 mg intake. HR tended to 
decrease at both doses, and SpO₂ increased further when 200 mg was ingested. In the cognitive 
function evaluation, the accuracy improved until 30 min after 100 mg intake, but decreased 
thereafter, and the accuracy continuously decreased when 200 mg was ingested. On the other 
hand, the reaction time was shortened under all conditions, suggesting the possibility that 
caffeine may have a positive effect on rapid cognitive response. 
Address the limitations of the study, such as the relatively small sample size. 
R2_6: We included the limitations of this study as follows:  
The limitations of this study include that the participants of the experiment were limited to 
their 20s, so it was not possible to compare the results according to age and effect of caffeine 
on the patients with any disease could not be confirmed. In addition, the change after 60 min 
could not be confirmed because the measurement was made within a limited time up to 60 
min after caffeine intake. The number of study participants was still small. Therefore, in future 
study, it is necessary to supplement these limitations and increase the number of samples to 
conduct studies on various age groups and patients with diseases and additional studies on 
changes after 60 min.

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

The manuscript entitled "Effects of varying caffeine dosages and consumption timings on cerebral vascular and cognitive functions: A diagnostic ultrasound study" reports a study of changes in physiological cerebrovascular and cognitive functions following caffeine intake (100 and 200 mg) in healthy adults after 0/30/60 min.  The authors concluded that "though moderate caffeine intake may support vascular health and cognitive function, excessive intake reduces blood flow, alters vascular elasticity, and impairs cognitive activation."

The manuscript shows results that can be used in further studies. Some points need to be clarified to increase the visibility of the manuscript.

1 - The manuscript could use colored plots to increase the visibility of the results. In their current form, the plots do not increase the visibility of the results.

2 - Critical point: Table 1, discussion and conclusion

Please, add in the discussion and conclusion the study's limitations regarding the number of participants and age range.  Please, compare with similar studies.

In the conclusion section, the authors confirm that "..should explore the effects of caffeine in diverse age groups, health conditions, and the long-term effects of caffeine consumption to establish comprehensive guidelines" 

Please, it is important to mention it in the discussion (the limitations and consequences of the reported results)  and it is possible in the abstract too.

It is common for the profile of participants to be crucial and significantly influence the results in similar studies.

3 - Tables

Please improve the tables highlighting statistically significant results.

4 - Conclusion

Please, in the conclusion section, the acronyms could be avoided.

 

 

 

 

 

 

 

 

 

 

Author Response

Authors’ Responses to Reviewers’ Comments: 
Thank you very much for your valuable comments and suggestions. We carefully revised the 
manuscript following the reviewer’s recommendations accordingly. Point-by-point responses 
are as follows:  
 
Comments and Suggestions for Authors: ----------------------------------------------------------------------------------------------------- 
Reviewer #3: The manuscript entitled "Effects of varying caffeine dosages and consumption 
timings on cerebral vascular and cognitive functions: A diagnostic ultrasound study" reports 
a study of changes in physiological cerebrovascular and cognitive functions following caffeine 
intake (100 and 200 mg) in healthy adults after 0/30/60 min.  The authors concluded that 
"though moderate caffeine intake may support vascular health and cognitive function, 
excessive intake reduces blood flow, alters vascular elasticity, and impairs cognitive 
activation." 
The manuscript shows results that can be used in further studies. Some points need to be 
clarified to increase the visibility of the manuscript. 
1 - The manuscript could use colored plots to increase the visibility of the results. In their 
current form, the plots do not increase the visibility of the results. 
R3_1: Thank you for your valuable comments. We changed the figures with colors as the 
reviewer suggested. 
 
2 - Critical point: Table 1, discussion and conclusion 
Please, add in the discussion and conclusion the study's limitations regarding the number of 
participants and age range.  Please, compare with similar studies. 
R3_2: We included the limitations of this study as follows:  
The limitations of this study include that the participants of the experiment were limited to 
their 20s, so it was not possible to compare the results according to age and effect of caffeine 
on the patients with any disease could not be confirmed. In addition, the change after 60 min 
could not be confirmed because the measurement was made within a limited time up to 60 
min after caffeine intake. The number of study participants was still small. Therefore, in future 
study, it is necessary to supplement these limitations and increase the number of samples to 
conduct studies on various age groups and patients with diseases and additional studies on 
changes after 60 min. 
Furthermore, we discussed similar studies in the discussion as follows: 
Unlike some previous studies that were conducted at the lying down position and/or a single 
dose [32,51], this study was conducted in a sitting position and two different doses. In addition, 
this study examined vascular physiology of caffeine, cognitive function and subjective 
changes in comparison to the previous study [51]. 
 
In the conclusion section, the authors confirm that "..should explore the effects of caffeine in 
diverse age groups, health conditions, and the long-term effects of caffeine consumption to 
establish comprehensive guidelines"  
Please, it is important to mention it in the discussion (the limitations and consequences of the 
reported results) and it is possible in the abstract too. 
It is common for the profile of participants to be crucial and significantly influence the results 
in similar studies. 
R3_3: We included the limitations of this study and added inclusion and exclusion criteria of 
the participants as the reviewer commented. 
3 - Tables 
Please improve the tables highlighting statistically significant results. 
R3_4: Significant difference was clearly indicated with the bold text and * in the tables. 
4 - Conclusion 
Please, in the conclusion section, the acronyms could be avoided. 
R3_5: As the reviewer recommended, we corrected the conclusion section. 

Author Response File: Author Response.pdf

Reviewer 4 Report

Comments and Suggestions for Authors

 

The study aims to analyze the effects of varying caffeine dosages and consumption timings on cerebrovascular and cognitive functions.

ABSTRACT

The abstract describes the study aim clearly 

Try to reformulate repetitions ("after consuming 100 mg caffeine", "after consuming 200 mg caffeine" )

""significant" should be followed by the p value

Include main statistical results with p value

 

INTRO

The introduction is comprehensive, providing a lot of relevant information, from caffeine consumption habits, recommended limits to its mechanisms of action and potential side effects.

The information is well-presented in a logical order and help the reader understand the background of the topic

It states clearly the novelty of the study  in relation to the gap in existing

Materials

"public announcements," add information about the recruitment modality

"those with" replace with subjects

Define "healthy" more specifically.

how the head was stabilized?

While participants were blinded to the caffeine dose, was the person administering it also blinded? This would further reduce bias.

Information on US acquisition are missing: operator's experience, equipment, equipment adjustments... Add images to clearly show the measurements acquisition

Results

Use the past tense

Conclusions

"The practical implications of this study are as follows: 362

1.

Moderation in caffeine intake can promote vascular health and cognitive function. 363

2.

Individualized guidelines should account for varying physiological responses to caffeine. 364

3.

The strategic use of the positive effects of caffeine, coupled with measures to prevent 365 overconsumption, is crucial." avoid a list

Author Response

Authors’ Responses to Reviewers’ Comments: 
Thank you very much for your valuable comments and suggestions. We carefully revised the 
manuscript following the reviewer’s recommendations accordingly. Point-by-point responses 
are as follows:  
Comments and Suggestions for Authors: ----------------------------------------------------------------------------------------------------- 
Reviewer #4: The study aims to analyze the effects of varying caffeine dosages and 
consumption timings on cerebrovascular and cognitive functions. 
ABSTRACT 
The abstract describes the study aim clearly try to reformulate repetitions ("after consuming 
100 mg caffeine", "after consuming 200 mg caffeine" ) 
R4_1: Thank you for your valuable suggestions. To improve the readability, we corrected the 
abstract.   
""significant" should be followed by the p value 
Include main statistical results with p value 
R4_2: We discussed and added p-values for each result.  
INTRO 
The introduction is comprehensive, providing a lot of relevant information, from caffeine 
consumption habits, recommended limits to its mechanisms of action and potential side 
effects. 
The information is well-presented in a logical order and help the reader understand the 
background of the topic 
It states clearly the novelty of the study  in relation to the gap in existing 
R4_3: Thank you for your positive evaluation. 
Materials 
"public announcements," add information about the recruitment modality 
R4_4: We corrected the phrase as follows:  
Participants in this study were recruited through bulletin boards of recruiting target 
institutions or public announcements posted on social networks, and 30 participants (male: 
15; female: 15) voluntarily participated. 
"those with" replace with subjects 
R4_5: Thank you for your comment. 
Define "healthy" more specifically. 
R4_6: We discussed and added as follows:  
The criteria for inclusion were healthy adults over the age of 20 without any disease, and the 
exclusion criteria are those who have a history of diseases possibly affecting cardiovascular 
function, take cardiovascular drugs, are physically weak or mentally ill, and are students 
affiliated with the same department as the researchers. 
 
 
how the head was stabilized? 
R4_7: We explained the word in detail as follows:  
All participants were seated on a fixed chair in the same position, with the back of their heads 
touching the wall. Velcro tape and polyester band were placed around their foreheads to 
secure their heads in place and prevent any movement away from the wall. 
 
While participants were blinded to the caffeine dose, was the person administering it also 
blinded? This would further reduce bias. 
R4_8: Thank you for your valuable comment. In the first experiment, participants were 
randomly assigned to consume either 100 mg or 200 mg of caffeine, and the alternate dose 
was consumed in the second experiment. Therefore, a single-blind method was used, in which 
the participants were unaware of the intake amount. This procedure was included in the 
method section. 
 
Information on US acquisition are missing: operator's experience, equipment, equipment 
adjustments... Add images to clearly show the measurements acquisition 
R4_9: The ultrasound measurements were performed by a radiologic technologist with 
experience in multiple ultrasound-related studies. We included an image showing the 
measurements acquisition as the reviewer suggested. 
 
Results 
Use the past tense 
R4_10: We corrected the sentences as the reviewer recommended. 
 
Conclusions 
"The practical implications of this study are as follows: 362 
1. Moderation in caffeine intake can promote vascular health and cognitive function. 363 
2. Individualized guidelines should account for varying physiological responses to caffeine. 
364 
3. The strategic use of the positive effects of caffeine, coupled with measures to prevent 365 
overconsumption, is crucial." avoid a list 
R4_11: Thank you for your comment and we corrected the list as follows.  
The practical implications of this study are as follows. Consuming a moderate amount of 
caffeine can promote vascular health and cognitive function. In addition, individualized 
guidelines should account for varying physiological responses to caffeine. Lastly, strategic use 
of the positive effects of caffeine, coupled with measures to prevent excessive consumption, 
is crucial.

Author Response File: Author Response.pdf