PONE-D-24-03107Dietary Supplementations to Mitigate the Cardiopulmonary Effects of Air Pollution Toxicity: A Systematic Review of Clinical TrialsPLOS ONE

Dear Dr. Zangiabadian,

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PLOS ONE

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Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: N/A

Reviewer #2: N/A

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3. Have the authors made all data underlying the findings in their manuscript fully available?

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This paper attempts to inform the literature of the beneficial effects of certain dietary supplements in populations and settings of poor air quality/air pollutant exposure. Authors utilized a systematic review approach to assess the impacts of particulate matter and ozone exposure on cardiovascular and pulmonary functioning and the potential for dietary supplements to mitigate these effects. Results of this systemic review were inconclusive in regard to the overall benefit of dietary supplementation in these exposure scenarios. The inconclusive results may be due to the wide array of studies included in this review, as discussed in the comments below. In addition to stylistic and organizational shortfalls of the paper, there are deficiencies in the background and rationale provided as well as fundamental flaws in the review.

Comments:

1. This review is focused on the cardiopulmonary effects of air pollution. However, the introduction only discusses the basic mechanisms through which particulates and other pollutants contribute to pulmonary detriments with no mention of the cardiovascular effects. Discussion of how pollutant exposure contributes to cardiovascular disease and alterations in cardiovascular functioning (specifically those discussed in the review) should be included.

2. Authors do not provide context as to why these outcome measures were chosen for evaluation and how they are illustrative cardiopulmonary dysfunction as mentioned above.

3. Authors should also elaborate further as to how dietary supplements, drawing on epidemiological and mechanistic research, may mitigate the deleterious effects of pollutants.

4. Check for proper use of defined abbreviations throughout.

5. There are multiple B vitamins, authors should be more specific about which B vitamin or combination of them is being evaluated in each study.

6. Authors should mention dosages and duration of both supplementation and pollutant exposure within the text.

7. The discussion provides description of metabolic and cellular changes resulting from dietary supplementation and pollution but there is very little of the results into this discussion.

8. The inconclusiveness of these findings does not inform the literature. Inconclusiveness is likely related to the wide array of outcomes measures and the number of dietary supplement interventions assessed in the review. Due to the variety in the studies included, in the review, it is difficult to make comparisons or conclusions on specific dietary supplements or parameters of interest.

Reviewer #2: This systematic review on the potential for dietary supplements to prevent the cardiorespiratory effects of air pollution is very timely. The concerning health effects of air pollution are more prominent than ever, yet efforts to improve air pollution progress remains slow and consequently the health burden very large. There have been suggestions in the field that dietary supplements or medicines could ameliorate the health effects of air pollution, but a clear picture in missing.

The systematic review follows PRISMA guidelines. The manuscript is clearly written.

I have a few suggestions that the authors should address:

1. In addition to subclinical cardiorespiratory outcomes the review could have included hospitalisation for cardiorespiratory conditions and cardiorespiratory mortality. If this is not done, the authors should justify why not. Some other subclinical parameters could have been included such as carotid-intimal media thickness or coronary artery calcium score.

2. The authors could go further in their scrutiny of the results to look for emerging patterns. For example, could some of the inconsistency be explained by the differences in doses of the supplements or the duration of use, or the type and concentrations of pollutant? The authors raise these possibilities very briefly, but do not indicate whether the studies they have assessed provide insight on these.

3. Although animal studies are not within the scope of the review, the authors could mention some key animal studies with use of natural antioxidant/anti-inflammatory agents on air pollution to bolster their Discussion on where effects may or may not be present in the human studies.

4. In the Discussion it should be noted that in several studies the air pollution itself did not affect the cardiorespiratory parameters, therefore, the ability of the supplement to modify the effect of air pollution could not be appropriately assessed.

5. There are a few reviews on the ability of medicinal agents to ameliorate the effects of air pollution on the respiratory and cardiovascular systems (e.g. Romieu et al. Eur Respir J 2008; Tong. Biochim Biophys Acta 2016; Barthelemy et al. Int J Environ Res Public Health 2020; Miller, Pharmacol Ther 2022; please also check for others). These also encompass dietary supplements and there is an opportunity to describe whether the conclusions of these reviews align with the present study, and how the literature has developed since the most recent review.

6. In Table 4, please add a column to state the key findings of each study (ideally with risk estimate/change and a confidence interval/error estimate).

Minor points:

7. Third paragraph of intro – please mention other non-combustion sources of PM2.5 such as secondary aerosols. Noe that particle size also affects toxicity.

8. Second line of page 16 – Did the olive oil decrease the FMD or the effect of the pollution on FMD?

9. Page 17. Given the role of oxidative stress on NO, the authors may wish to speculate on why vitamin C did not reverse the cardiovascular effects of air pollution.

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Reviewer #1: No

Reviewer #2: Yes: Mark R Miller

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Attachments

Attachment

Submitted filename: PLOS ONE_020824.docx

Dietary Supplementations to Mitigate the Cardiopulmonary Effects of Air Pollution Toxicity: A Systematic Review of Clinical Trials

PONE-D-24-03107R1

Dear Dr. Zangiabadian,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Rami Salim Najjar, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: N/A

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: The authors have given good thought to all my comments and made appropriate changes to address them. Thank you.

As very minor points:

on page 3, the authors may wish to add construction work, secondary formation of PM (e.g. from reactions with ammonia and nitrate/sulphate) and non-exhaust emissions from traffic (brake, tyre and road wear) as major sources of non-combustion PM.

On page 4, other prominent mechanisms of the cardiovascular effects of air pollution include imbalance between vasodilation/vasoconstriction, and promotion of blood clotting.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: Yes: Mark R Miller

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