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Thanks for attending to these remaining minor issues.
[# PeerJ Staff Note - this decision was reviewed and approved by Vladimir Uversky, a PeerJ Section Editor covering this Section #]
Thank you for your efforts, please attend to the remaining minor issues.
Pass
Pass
Pass
I fully acknowledge and appreciate the efforts of the authors to revise and improve this manuscript.
While it is gratifying to see that the authors have decided to report the data as the mean difference in blood pressure, there are still two remaining references to “standardized mean difference” (on lines 43 and 210). These should be corrected.
Although the higher fructose dose does appear to increase systolic blood pressure more, this is not actually supported by the statistical test carried out (it reports no statistical significance). Therefore, the conclusion really needs to be toned down a little, rather than stating “higher doses show a dose-dependent effect”.
As you will see, there are still major concerns highlighted by reviewer-4. These need careful thought and further refinement of your data. In particular, the use if standardized mean difference is recognized as being unsuitable for reporting the changes in blood pressure. As noted by this reviewer, using the mean difference in blood pressure in mmHg would make the difference in systolic blood pressure after treatment with fructose much more readily apparent.
I agree with this point, and would insist that you change your analysis to reflect the actual values which are much more intuitive.
There are other issues raised by both reviewers which must be fully and clearly addressed with appropriate changes.
Now this version of this manuscript is much better. However, still have some concern below.
1. Line 65-66: Is there any difference between fruits contain fructose and table sugar content fructose. If so, please explain.
2. Line 85-86: Why rodent model use as a good model animal for mimic of metabolic syndrome study.
Now this version of this manuscript is much better. However, still have some concern below.
1. Line 65-66: Is there any difference between fruits contain fructose and table sugar content fructose. If so, please explain.
2. Line 85-86: Why rodent model use as a good model animal for mimic of metabolic syndrome study.
Now this version of this manuscript is much better. However, still have some concern below.
1. Line 65-66: Is there any difference between fruits contain fructose and table sugar content fructose. If so, please explain.
2. Line 85-86: Why rodent model use as a good model animal for mimic of metabolic syndrome study.
While the clarity of writing is better in the revised manuscript, there are a number of proofreading issues that do not indicate particularly close attention to detail.
The addition of appropriate references throughout the Introduction is a significant improvement.
As commented upon for the original submission, the description of the actual results is somewhat brief. It is probably not helped by the fact that the data is being reported as the standardized mean difference (see comments to Authors), which does make providing an easy to follow narrative somewhat challenging.
While the Methodology has been improved, there are still some details that are lacking.
The authors do now briefly cover the previously published meta-analysis on this particular topic. However, there could certainly be a little bit more extensive direct comparison provided. In addition, some of the statistical analysis in the current study (when performing sub-group analysis) is still somewhat lacking in detail, to really affirm the validity of the current findings.
Thank you to the Authors for trying to address the issues that were raised in the original review.
Major points
One of the major points raised in the original review was that the manuscript keeps referring to “hypertension”; but in reality, what is being investigated is the issue of whether fructose intake increases blood pressure in rats. It was suggested that either a definition as to what constitutes hypertension in rats needs to be provided, or the results are reported as the increase (change) in blood pressure. Throughout the manuscript the two terms (“hypertension” and “blood pressure”) are used somewhat interchangeably, so for that fact alone consistent and appropriate terminology would be beneficial.
The Authors have replied: “We acknowledge that the manuscript uses 'hypertension' and 'blood pressure' interchangeably, which may lead to ambiguity. To address this, we have:
a) Clearly defined hypertension in rats by specifying the threshold values for elevated systolic blood pressure, as reported in previous studies.
b) Ensured consistency in terminology throughout the manuscript by distinguishing between 'increase in blood pressure' and 'hypertension' where appropriate.
c) Clarified the study's objective to focus on how fructose consumption affects blood pressure levels in rats, rather than making definitive claims about hypertension diagnosis.”
However, where is the clear definition as to what constitutes hypertension in rats provided? Furthermore, these two terms are still being used somewhat interchangeably (e.g. line 96: “This study evaluates the relationship between fructose consumption and hypertension”, line 158: “The key effects of fructose on hypertension are summarized in Table 1”, line 219 “Our findings indicate that fructose-induced hypertension”). There are other mentions of “hypertension” as well.
The study by Toop and Gentili (2016) ((Nutrients 2016, 8, 577; doi:10.3390/nu8090577) did actually look at the duration of fructose consumption on blood pressure changes. While they used slightly different time periods (less than 16 weeks or over 16 weeks) it is slightly disingenuous to imply in the rebuttal that the current study extends from the published study by examining this particular aspect. It is also somewhat questionable as to whether the current study “specifically evaluates the dose-response relationship between fructose intake and systolic blood pressure in rats”. The data is split into two groups (10-30% w/v as solution and 60-70% w/v as diet), so how can that really be described as determining the dose-response relationship?
It is somewhat unclear why the standardised mean difference is being used in this study, when the data is all being reported in mmHg (according to Table 1). The standardised mean difference is dimensionless and not a particularly intuitive measure, as it relates to units of standard deviation. Using the mean difference would make the difference in systolic blood pressure after treatment with fructose much more readily apparent. Why can the authors not present the data in this format?
Minor points
Line 39: The abstract is better than the original version. However, there is too much unnecessary detail in the Methods part (e.g. number of articles identified). Although it is stated in the rebuttal that the abstract has been “modified”, there is still no indication as to how large the effect of fructose on blood pressure is. The findings are simply described as fructose caused “a significant increase in SBP compared to controls”. As such, it gives no indication as to the magnitude of the observed effect.
Line 42: The “relative risk of hypertension” is a term that was highlighted in the original version of the manuscript as meaning something quite specific with regard to statistics. The relative risk is the ratio of the probability of an outcome in the treatment group to the probability of an outcome in the control group. In this study it is simply the difference (standardised mean difference) in blood pressure that is being measured, so the text should really reflect that more accurately.
Line 44: Why has the duration of treatment been changed in the revised version of the manuscript “(<8 weeks, 8 weeks, and >8 weeks)”, without any explanation? The original version identified the time periods as “(<12 weeks, 12 weeks and >12 weeks)”.
Line 68: It should be “Marriott et al., 2009”, rather than “Marriott, Cole & Lee, 2009”.
Figure 2: The PRISMA flow chart lacks a bit of detail in places. For instance, 108 records were removed as they were “not relevant”; but there are no examples of some of the main reasons as to why they were considered as “not relevant”.
Line 115: There is some detail added regarding the search terms used; but it would not really be described as a “detailed description”. In the revised text, it also mentions articles being “chosen” or “selected”. This is not the correct approach, or certainly it is not the proper terminology. The inclusion/exclusion criteria allow articles to be identified for inclusion into a systematic review and meta-analysis. They are not “chosen” or “selected” they are “included”. The inclusion/exclusion criteria should not be provided as a numbered list.
Line 130: It is s.e.m. “standard error of the mean” not “standard error”.
Line 165: What P value was considered as being significant?
Line 167: “The effect size of persistence and continuous outcomes was assessed using the random effects model (REM), incorporating a 95% confidence interval (CI) and odds ratio, respectively.” What data is reported in the current study as an odds ratio?
Line 171: It is “heterogeneity” rather than “heterogenicity”. There are other instances of this term being used.
Line 186: It is somewhat unclear what is meant by “substantial heterogeneity was observed in both the normal and fructose-fed groups”. Heterogeneity refers to variation across studies.
Line 192: What statistical analysis was used to determine whether there was any significant difference between the two types of fructose treatment? It is stated that “no significant difference in SBP was observed between the different fructose concentrations, as both the 10-30% and 60-75% groups exhibited similar heterogeneity (86%) and Z values of 6.23 and 6.09, respectively”. However, that alone is not a test of statistical significance.
Line 195: Additionally, it has to be reported what statistical test was used to determine the significant difference between the <8 week and >8 week fructose treatment. Presumably it was the same test as used in relation to the previous comment.
Line 214: It should be “Perret-Guillaume et al., 2009” rather than “Perret-Guillaume, Joly & Benetos, 2009”.
Line 222: It is stated that “our subgroup analysis revealed that fructose consumption for more than 8 weeks leads to a two-fold increase in SBP”. This point was raised in the previous review, as fructose was not literally causing a two-fold increase in SBP. The rebuttal states “We have revised the sentence to accurately reflect the results in terms of the standardized mean difference, ensuring clarity and correctness”. There is still an issue with this sentence as it makes no mention of the “standardized mean difference”.
Line 234: While it is stated “Due to limited strain-specific data, we were unable to perform a subgroup analysis based on strain, which remains a limitation of this meta-analysis”, Table 1 nevertheless indicates a reasonable number of studies used Sprague Dawley (9 studies) or Wistar rats (12 studies). While there may not be sufficient data to carry out the sub-group analysis (based on dose and time of fructose administration), there is surely adequate data to assess whether there is any difference between these two strains.
Line 254: “Our study emphasizes that chronic consumption of high fructose concentrations (60-75%) significantly increases the risk of developing hypertension by elevating SBP”. Where exactly is this data reported? It was stated in the results that there was no significant difference in the increase in SBP that was observed with the different fructose concentrations, so why is it now being implied that the higher concentration has this effect?
Line 269: How can it be realistic to suggest “Future research should minimize this bias by incorporating unpublished data”. If the data is unpublished, how exactly is it going to be accessible to other investigators?
Abbreviations only need to be defined once, when first introduced.
Table 1 provides valuable and informative data. However, it would be more precise to include the actual n numbers alongside the associated blood pressure measurements. It is currently unclear whether the reported n values represent the total sample size or the number per treatment group. Additionally, for transparency, please indicate which data in the table were extracted digitally from figures in the original studies, as this context is important for accurate interpretation.
I will be honest that I have debated between a rejection and major revision decision on this manuscript. Three of the reviewers have all raised substantive issues with your interpretation of the analyses, the means of selection and the quality of writing which make it clear that a major and extensive revision of this work is needed. This is nearing the stage of requiring a complete re-write - hence my debate about the decision.
What has swayed it for me is the importance and interest of the area. I am therefore giving you a chance to revise the article, based upon the issues raised in the reviews. Note however, that you must attend to all issues raised, without exception. Your responses should also be outlined in a cover letter so each reviewer can inspect changes you make in response to their comments.
I look forward to seeing your revisions, and if you require longer than the 30 days suggested (and I expect you might), please liaise with the editorial office.
[# PeerJ Staff Note: The review process has identified that the English language MUST be improved. PeerJ can provide language editing services if you wish - please contact us at [email protected] for pricing (be sure to provide your manuscript number and title). Your revision deadline is always extended while you undergo language editing. #]
It is clear enough
The study is properly done, but if possible publication bias can be added
It is quite impactful as it can give better understanding about the fructose effect on blood pressure
The manuscript entitled “Fructose consumption and metabolic hypertension in rats: a systematic review and meta-analysis” is very crucial tropic in this era, because people are taking processed food which affect metabolic disorder. However, this manuscript has some major concerns. Please check the below-
Major concerns
1.
I am requesting ton the author for rewrite the introduction because of lack of coherence and reference. Please organize the introduction and more specific with this study.
2.
It is very difficult mention the exact number of all the variable with the eye view. How did you extract data and standard deviation from the figure.
3.
The authors did not analyze the publication biasness, it may affect this study.
4.
I would like to suggest to the authors for analysis of effect size analysis.
5.
Please re-organize the table 1-
i.
Mention where the fructose mixed for study. For example, fructose was mixed with food or water.
ii.
Please mention the species of animal.
iii.
The reference style is not match with this journal.
6.
I would like to recommend to the authors to re-write the discussion part and try to support your results in discussion section.
7.
Overall, most of the reference are missing in reference section. It is very difficult to recheck the results.
Minor concerns
8.
Line 66: This sentence is confusing. Please explain how body created fructose.
9.
Line 68: Does sorbitol induce hypertension? If not, please rewrite the sentence.
10.
Line 75-77: Please add the reference
11.
Line 77-79: Please add reference
12.
Line 96-101: Please add reference
13.
Line 187: Mention the figure number
14.
Line 215: What does mean central player
15.
Line 225-230: You already mention this results in your result section. I will suggest you do not repeat in results and discussion.
16.
Figure 1: Increase the font size.
17.
Please explain the figure 6.
The manuscript entitled “Fructose consumption and metabolic hypertension in rats: a systematic review and meta-analysis” is very crucial tropic in this era, because people are taking processed food which affect metabolic disorder. However, this manuscript has some major concerns. Please check the below-
Major concerns
1.
I am requesting ton the author for rewrite the introduction because of lack of coherence and reference. Please organize the introduction and more specific with this study.
2.
It is very difficult mention the exact number of all the variable with the eye view. How did you extract data and standard deviation from the figure.
3.
The authors did not analyze the publication biasness, it may affect this study.
4.
I would like to suggest to the authors for analysis of effect size analysis.
5.
Please re-organize the table 1-
i.
Mention where the fructose mixed for study. For example, fructose was mixed with food or water.
ii.
Please mention the species of animal.
iii.
The reference style is not match with this journal.
6.
I would like to recommend to the authors to re-write the discussion part and try to support your results in discussion section.
7.
Overall, most of the reference are missing in reference section. It is very difficult to recheck the results.
Minor concerns
8.
Line 66: This sentence is confusing. Please explain how body created fructose.
9.
Line 68: Does sorbitol induce hypertension? If not, please rewrite the sentence.
10.
Line 75-77: Please add the reference
11.
Line 77-79: Please add reference
12.
Line 96-101: Please add reference
13.
Line 187: Mention the figure number
14.
Line 215: What does mean central player
15.
Line 225-230: You already mention this results in your result section. I will suggest you do not repeat in results and discussion.
16.
Figure 1: Increase the font size.
17.
Please explain the figure 6.
The manuscript entitled “Fructose consumption and metabolic hypertension in rats: a systematic review and meta-analysis” is very crucial tropic in this era, because people are taking processed food which affect metabolic disorder. However, this manuscript has some major concerns. Please check the below-
Major concerns
1.
I am requesting ton the author for rewrite the introduction because of lack of coherence and reference. Please organize the introduction and more specific with this study.
2.
It is very difficult mention the exact number of all the variable with the eye view. How did you extract data and standard deviation from the figure.
3.
The authors did not analyze the publication biasness, it may affect this study.
4.
I would like to suggest to the authors for analysis of effect size analysis.
5.
Please re-organize the table 1-
i.
Mention where the fructose mixed for study. For example, fructose was mixed with food or water.
ii.
Please mention the species of animal.
iii.
The reference style is not match with this journal.
6.
I would like to recommend to the authors to re-write the discussion part and try to support your results in discussion section.
7.
Overall, most of the reference are missing in reference section. It is very difficult to recheck the results.
Minor concerns
8.
Line 66: This sentence is confusing. Please explain how body created fructose.
9.
Line 68: Does sorbitol induce hypertension? If not, please rewrite the sentence.
10.
Line 75-77: Please add the reference
11.
Line 77-79: Please add reference
12.
Line 96-101: Please add reference
13.
Line 187: Mention the figure number
14.
Line 215: What does mean central player
15.
Line 225-230: You already mention this results in your result section. I will suggest you do not repeat in results and discussion.
16.
Figure 1: Increase the font size.
17.
Please explain the figure 6.
Abstract:
The abstract does not comply with Prima guidelines and lacks essential information, such as (1) inclusion/exclusion criteria for study selection; (2) methods for assessing the risk of bias; (3) the total number of studies and animals with key characteristics; (4) a summary of the limitations of the evidence.
The lack of information on study selection criteria and risk of bias assessment hinders the reader's ability to judge the validity and reliability of the review's findings.
Introduction:
The introduction is long and could be trimmed. The historical overview of fructose research could be condensed to focus more directly on the knowledge gaps addressed by this meta-analysis. A good beginning is from line 84. The sentences in lines 99-105 are redundant and out of the scope of this study. The paragraph on lines 106-116 can be condensed.
Sentences in lines 124-129 can be eliminated as the analysis objective is “to evaluate the effect of fructose intake and the relative risk of hypertension based on the dose (10-30% w/v and 60-70% w/v) and duration of administration” This analysis does not respond to the mechanisms by which fructose induce hypertension in rodent models.
While Toop and Gentili (2016) examined the effects of fructose on various metabolic parameters, this meta-analysis focuses explicitly on the dose-response relationship between fructose and blood pressure in rat models. Please include what this new analysis adds to the Toop and Gentili one.
Discussion:
The authors mention the influence of rat strain but fail to provide any analysis of this factor. A subgroup analysis or discussion of strain-specific effects would be valuable for researchers designing future studies."
Given the variability in fructose-induced hypertension across rat models, the authors should recommend models that best mimic human physiological responses to fructose consumption, considering factors like dose, duration, and route of administration.
A dedicated section comparing the findings of this meta-analysis with those from human studies is crucial. This would help explain the consistent hypertensive effect of fructose in rats contrasted with the more nuanced findings in humans. Potential explanations, such as differences in fructose metabolism or study designs, should be explored.
Figure 6, which depicts the putative effects for why fructose induces hypertension, pops out from nothing specific in the manuscript and should be eliminated.
No comment
No comment
No comment
While the manuscript is understandable, there are certainly a number of areas where the English could be improved, and it has been recommended that the authors seek some assistance with this aspect.
In the Introduction, there a number of quite specific statements being made, which aren’t supported by any reference to the appropriate literature.
The figures themselves are of a good standard, but the description of the actual results is somewhat scant and certainly need to be addressed.
There was no specific hypothesis provided.
While the objectives of the study are clearly defined, some aspects of the Methodology are incomplete and there are quite a number of important details that need to be addressed. These have been outlined in the comments to the Authors.
While the topic is an interesting one, there has already been a meta-analysis investigating the effect of fructose intake on blood pressure in rats. The relevance and need for this study has to be addressed a bit more directly by the Authors. Given the questions relating to how the data is being presented, it is difficult to really say whether or not the conclusions are valid at this particular time.
This study is a systematic review and meta-analysis that aims to determine whether an increased dietary intake of fructose has an effect on blood pressure. The original data that is utilised comes from studies on the rat. While the question being considered relates to an interesting and important topic, there are a number of issues (both major and minor) that will need to be addressed by the Authors.
Major Points
The manuscript keeps referring to “hypertension”; but in reality, what is being investigated here is the issue of whether fructose intake increases blood pressure in rats. Either a definition as to what constitutes hypertension in rats needs to be provided, or the results are reported as the increase (change) in blood pressure. Throughout the manuscript the two terms (“hypertension” and “blood pressure”) are used somewhat interchangeably, so for that fact alone consistent and appropriate terminology would be beneficial.
There has already been a published article on this specific topic: Fructose beverage consumption induces a metabolic syndrome phenotype in the rat: A systematic review and meta-analysis (Nutrients 2016, 8, 577; doi:10.3390/nu8090577). Therefore, it has to be more fully explained in the Introduction why the current study is necessary, and the differences/similarities between the two studies should be more comprehensively discussed in the Discussion.
The narrative describing the results is very brief and simply focuses more on the statistical elements (heterogeneity) than providing details of the magnitude of any effect observed. As the details of the articles included in this meta-analysis are not shown in the bibliography (they appear in Table 1 as numbered items), this makes cross checking of the original data almost impossible. However, assuming Kho et al. 2016 is the article: Fermented Red Ginseng Potentiates Improvement of Metabolic Dysfunction in Metabolic Syndrome Rat Models, the “control” data reported for this study appears to be from animals that were treated with fermented red ginseng (FRG). As indicated below, it is very difficult to understand what was considered a “control” treatment in the included studies; but such comparators, if they vary from study to study, surely brings into question the specific approach being taken here.
In some of the included studies, the standardised mean difference for the effect of fructose on blood pressure is shown as being several hundred. This is obviously due to the standard deviation in such studies being so small. Are the standard deviations shown in the forest plot values that have been reported in the original articles, or have they been estimated in some way by the authors?
Minor points
Abstract
Line 48: How can it really be stated that “…with the final aim of promoting a healthy diet among the general population”, when the focus of this investigation is on animals? The study aims have to be achievable.
There is no actual data being presented in the abstract. It simply indicates how the data has been analysed and reports on the heterogeneity observed between the different studies. Similarly, the conclusion is somewhat meaningless in the sense it reports a P value without indicating the magnitude of the effect observed.
It isn’t necessary to include the PROSPERO registration number in the abstract body.
Is “public health” really an appropriate keyword for a basic science study?
Introduction
There are a number of quite specific statements throughout the Introduction that are not supported by any reference to the relevant literature. This needs to be addressed.
Line 111: Not sure why there is such a specific focus on India, when the issue of sugar consumption is initially described as being worldwide.
Line 135: “relative risk of hypertension”. The relative risk means something else in a meta-analysis. In this study it is simply the difference (standardised mean difference) that is being measured, so the text should really reflect that more accurately. It is not determining the relative risk of hypertension. This also relates to one of the major criticisms of the manuscript where it becomes somewhat muddled if the animals have “hypertension”, or fructose is causing “hypertension”, or whatever. On review of the data presented it would seem more accurate to simply refer to the effect of fructose on blood pressure.
Methods
Should really be providing details of the actual search strategy (the keywords and how they were used in combination), otherwise it cannot be replicated, and it doesn’t show how systematic it was either.
Line 155: The PICO model described is somewhat ambiguous and not clearly enough defined. In Population it indicates the rats were “with or without hypertension”. If they had hypertension, what would be the rationale for providing them with fructose? The Intervention was surely the administration of fructose. The Comparator does not really follow the conventional format. Typically, it would be placebo or control. Therefore, it’s unclear why it is stated as “variables aimed for hypertension including concentration of fructose, duration of fructose administration and methods of feeding (solution or diet)”. The Outcome is stated as “estimation of the association between the development of metabolic hypertension after fructose administration”; but that would typically be a binary outcome (i.e. the rats either did or didn’t develop hypertension). That is not really what is reported in the study.
Line 168: “as well as those received from alternative sources”. It should really be defined what the “alternative sources” were.
Line 169: “The objective is to find research that has the potential to meet the specified inclusion criteria”. This is just stating the obvious and so it is unnecessary.
Line 174: The statement “The mean and standard deviation data for hypertension” doesn’t really make sense. Presumably it is simply blood pressure that is being referred to, and if so, that should be stated. Also, is it both systolic and diastolic, or mean arterial pressure data that is used? This has to be clarified. Similarly, is it the post treatment values that are being reported, or the change in blood pressure? Is the specified data always provided in the text, or has it been extracted from graphs? Overall, there has to be a bit more detail as to what and how the data was obtained from the included studies.
There is no detail as to how the control animals were treated.
Results
Figure 1: The PRISMA flow chart could provide a bit more detail as to why articles were excluded (rather than just reporting a single number).
Line 206: It seems somewhat odd to be commenting on differences in the heterogeneity between high and low doses of fructose as they are both very high and statistically significant to begin with.
Line 212: It is very unclear whether statistical comparisons were made between the different treatment durations. Is it really being stated that fructose treatment for 12 weeks or longer had a significantly different effect on blood pressure (“hypertension”), compared to animals that were treated for less than 12 weeks? If so, details need to be provided to indicate how this statistical comparison was made.
Discussion
A lot of the Discussion is simply repeating the results (including the reporting of data that should really be in the Results section, and reference to the Figures). In this section, there needs to be greater consideration towards explaining the findings.
Line 217: “…fructose feeding and hypertension are independently associated with the animal strain”. There are no details provided about the strain of rat used in these studies, so this statement cannot be verified.
Line 243: Has it really been established that there are varying degrees of change in blood pressure depending on the duration of treatment? How was this conclusion arrived at?
Line 245: There wasn’t literally a “two fold increase in blood pressure”. That would mean something equivalent to an increase from 100 mmHg to 200 mmHg. What the forest plots are reporting is the standardized mean difference.
Line 249: Fructose is described as being involved in myriad reactions, which have a negative impact on blood pressure. Whilst this perhaps strays beyond the current investigation, there is still very little specific detail provided. Figure 6 is nice, but in order for it to be an appropriate part of the study, there perhaps needs to be more detail provided regarding the deleterious effects of fructose.
Line 252: There is no evidence provided here to support the statement: “The studies included in the meta-analysis process data that supports the potential of fructose to induce endothelial dysfunction by altering several different pathways”.
Line 266: Too much of the Conclusion is simply a repeat of what has been stated previously.
Table 1
The studies included in the meta-analysis are presented as numbered items in the table; but these are not included in the bibliography.
Some of the table formatting could be better.
Figures 3 – 5
The authors initials are not typically included in a forest plot.
The legend for Figure 6 is not particularly comprehensive and there are abbreviations shown in the figure that aren’t defined.
The English language needs to be improved, in places, to ensure that the manuscript is clear and easily understood. Sometimes it is just the odd word that is somewhat inappropriate (e.g. line 42 “exterminating”, line 53 “procured”; but at other times it is a complete or partial sentence of text (e.g. line 72 “those appended while the commercial or household culinary art excludes intrinsic sugars found in foods”; line 223 “utilization of fructose in the human system aggrandizes the burgeoning of hypertension, a sweeping peril for cardiovascular diseases”). In some sections the writing is rather unnatural (notably in parts of the Discussion), and I would suggest that you have a colleague who is proficient in English, and familiar with the subject matter, review your manuscript. Certainly, the adage about keeping the language plain and simple should be followed.
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