Are total omega-3 and omega-6 polyunsaturated fatty acids predictors of fatal stroke in the Adventist Health Study 2 prospective cohort?

Alan Cupino; Gary Fraser; Synnøve Knutsen; Raymond Knutsen; Celine Heskey; Joan Sabaté; David Shavlik

doi:10.1371/journal.pone.0274109

Peer Review History

Original SubmissionApril 13, 2022
20 Jun 2022 Decision Letter - Alvaro Reischak-Oliveira, Editor PONE-D-22-10872Are total omega-3 and omega-6 polyunsaturated fatty acids predictors of fatal stroke in the Adventist Health Study 2 prospective cohort?PLOS ONE Dear Dr. Cupino, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Aug 04 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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We will update your Data Availability statement to reflect the information you provide in your cover letter. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions 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: Yes Reviewer #2: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 3. 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 #1: Yes Reviewer #2: Yes ****** 4. 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 #1: Yes Reviewer #2: No ****** 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: The study "Are total omega-3 and omega-6 polyunsaturated fatty acids predictors of fatal stroke in the Adventist Health Study 2 prospective cohort?" investigated the effects of n-3 PUFA, n-6 PUFA, and the ratio between the two on the risk of stroke mortality in a large prospective cohort (the Adventist Health Study-2 prospective cohort). The authors showed the subjects with greater total n-3 PUFA intakes had lower risk of fatal stroke, and those with a higher n-6 / n-3 PUFA ratio had higher risk. Comments to Author: Abstract: Please include the main objective of the study Methods: Please provide detailed information about supplements intake. Discussion: For discussion the 10th percentile (6.1:1) found in this study (percentile with lower risk of fatal stroke), suggest to the authors add a comment about the n-6/n-3 PUFA ratio found in studies with the Mediterranean Diet (diet known for the protection in cardiovascular and cerebrovascular events) or with the n-6/n-3 PUFA ratio found in longevity studies. Reviewer #2: Dear Authors, The manuscript has an interesting goal. However, the data needs to be reviewed. Methods - What do the authors mean by this sentence, "The AHS-2 has been described in detail elsewhere..."? I suggest indicating proper where all the information has been described. Methods- It is unclear how the authors investigated in the same category participants that had limited or no current consumption of tobacco and alcohol. It seems to me that they should be split into different groups. Methods- I could not find the description appropriate to the acronym BMI. Even if it's a common acronym, it must be defined the first time it is included in the text. Table 1 - What do the authors mean by the smoking ever used? Participants smoked in the past? For how long? How many cigarettes a day? For how long did they stop smoking? Please clarify. -Dietary assessment- The authors chose poor methods of dietary assessment. It is a literature consensus that FFQ associated with 24 dietary recall is not appropriate to analyze food consumption. The more recent recommendation suggests using a 3-day food diary to explore the food consumption in the population. - Dietary pattern- I could not understand if all participants are vegetarian or not. I suggest clarifying participants' dietary patterns. - It is unclear which nutrients were supplemented or not. It made me a bit confused. ****** 6. 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 #1: No Reviewer #2: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. 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Revision 1
2 Aug 2022 Author Response REVIEWER 1: Abstract: Please include the main objective of the study Thank you for your feedback. To highlight the objective of the study, we added the following new line to the abstract introduction: “This study therefore intended to investigate these effects in a cohort for which the vegetarian diet was more prevalent than the general public.” Methods: Please provide detailed information about supplements intake. To clarify the nature of the supplements, we added two new sentences to the Methods section under the Study Variables header: “Approximately 12% of participants supplemented n-3 PUFA, and approximately 15% supplemented n-6 PUFA. However, overall rates of supplementation were low: the 90th percentile of n-3 PUFA supplement contribution was 8.5% of total n-3 PUFA intake, and the corresponding 90th percentile of total n-6 PUFA intake due to n-6 PUFA supplements was 0.1%.” Discussion: For discussion the 10th percentile (6.1:1) found in this study (percentile with lower risk of fatal stroke), suggest to the authors add a comment about the n-6/n-3 PUFA ratio found in studies with the Mediterranean Diet (diet known for the protection in cardiovascular and cerebrovascular events) or with the n-6/n-3 PUFA ratio found in longevity studies. To improve our discussion about the n-6/n-3 PUFA ratio, we added a new sentence in the Discussion section to describe other populations’ n-6/n-3 PUFA ratios: “A previous review has investigated the n-6 / n-3 PUFA ratio of various diets and noted that while the present Western diet has an n-6 / n-3 PUFA ratio of 15-20:1, other populations have much lower ratios. Examples include Japan at 4:1 and rural India at 5-6:1, and specific diets such as Swedish at 4.7:1 or Mediterranean at 2.6:1 (52).” REVIEWER 2: Methods - What do the authors mean by this sentence, "The AHS-2 has been described in detail elsewhere..."? I suggest indicating proper where all the information has been described. Thank you for this suggestion. We used this formal shorthand to denote that a separate journal article exists wherein the study is described in extensive detail. Recent PLOS One articles which have utilized similar statements include DOI=10.1371/journal.pone.0270033 (“Additional details are described elsewhere [18].”), DOI=10.1371/journal.pone.0269042 (“The detailed study design has been previously described [28].”), and DOI=10.1371/journal.pone.0270893 (“The study utilized MHS pregnancy registry, previously described [13].”). For improved clarity, we have updated the text to now read: “The AHS-2 has been described in detail previously by Butler et. al.” Methods- It is unclear how the authors investigated in the same category participants that had limited or no current consumption of tobacco and alcohol. It seems to me that they should be split into different groups. Historic tobacco and alcohol use were low in this cohort, so categories of use were collapsed. For clarity, we have added the following to a sentence in the Methods section describing tobacco and alcohol rates: “so variables controlling for those factors were collapsed” Methods- I could not find the description appropriate to the acronym BMI. Even if it's a common acronym, it must be defined the first time it is included in the text. The definition of BMI was added for the first use of the term, in the Methods section: “or body mass index (BMI).” Table 1 - What do the authors mean by the smoking ever used? Participants smoked in the past? For how long? How many cigarettes a day? For how long did they stop smoking? Please clarify. As previously mentioned, historic tobacco use was very low in this cohort so categories were collapsed. For clarification, the Methods section has now been altered to better define ever use: “current and/or prior use of tobacco; current and/or prior use of alcohol.” -Dietary assessment- The authors chose poor methods of dietary assessment. It is a literature consensus that FFQ associated with 24 dietary recall is not appropriate to analyze food consumption. The more recent recommendation suggests using a 3-day food diary to explore the food consumption in the population. Our review of the literature did not demonstrate a consensus supporting the statement “FFQ associated with 24 dietary recall is not appropriate to analyze food consumption.” However, we were able to find an article from the United States agency National Institutes of Health (DOI=10.1016/j.jand.2015.08.016) which states: “Even though there is bias in 24-hour recalls, because food records potentially have reactivity bias, the 24-hour recall is considered the least biased of the self-report instruments and the best single dietary assessment instrument for many purposes.” To that end, at least two validation papers have been published on the AHS-2 thus far, supporting the use of 24-hour recalls with a food frequency questionnaire: DOI=10.1017/S1368980009992072 and DOI=10.3945/jn.115.225508. Additionally, the AHS-2 has been conducted since 2002 and the authors of the present manuscript are unable to modify the protocols of the prospective cohort described in this manuscript. - Dietary pattern- I could not understand if all participants are vegetarian or not. I suggest clarifying participants' dietary patterns. We clarified by adding a new sentence in the Methods section to describe study participants’ dietary patterns: “Within this final analytical group, 37% were either vegan or lacto-ovo vegetarian, and 16% were either pesco-vegetarian or semi-vegetarian.” - It is unclear which nutrients were supplemented or not. It made me a bit confused. To improve clarity, we added a new sentence in the Methods section to list which nutrients were included from supplements: “Supplemented nutrients included saturated fatty acids, mono-unsaturated fatty acids, poly-unsaturated fatty acids, fiber, sodium, vitamin C, alpha-tocopherol equivalents, and flavonoids.” Attachments Attachment Submitted filename: ResponseToReviewers.docx https://doi.org/10.1371/journal.pone.0274109.r002
23 Aug 2022 Decision Letter - Alvaro Reischak-Oliveira, Editor Are total omega-3 and omega-6 polyunsaturated fatty acids predictors of fatal stroke in the Adventist Health Study 2 prospective cohort? PONE-D-22-10872R1 Dear Dr. Cupino, 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. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Alvaro Reischak-Oliveira, Ph.D. Academic Editor PLOS ONE 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 ******** 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 ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: N/A ****** 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 ****** 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 ****** 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: (No Response) ****** 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: No ******** https://doi.org/10.1371/journal.pone.0274109.r003
Formally Accepted
30 Aug 2022 Acceptance Letter - Alvaro Reischak-Oliveira, Editor PONE-D-22-10872R1 Are total omega-3 and omega-6 polyunsaturated fatty acids predictors of fatal stroke in the Adventist Health Study 2 prospective cohort? Dear Dr. Cupino: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Alvaro Reischak-Oliveira Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0274109.r004

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