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  1. Evaluation Summary:

    Pan et al investigated associations of self-reported egg consumption with plasma metabolic markers and these plasma metabolic markers with the risk of cardiovascular diseases. In general there was some impact on metabolic markers which could protect against CVD. The paper will interest scientists in the field of nutritional epidemiology.

    (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

  2. Reviewer #1 (Public Review):

    The study simultaneously explored the associations of self-reported egg consumption with plasma metabolic markers, and of these markers with the risk of CVD in a nested case-control study in the China Kadoorie Biobank (CKB). In general the authors achieved their aims, and the results support their conclusions. The authors found that egg consumption was associated with several metabolic markers, and these associations were directionally opposite to associations between these metabolites and risk of CVD. The major strengths of the study include relatively large sample size, accurately identified CVD and its subtype events, collection of as many covariates as possible, and the quantification of a wide range of metabolites based on NMR platform. These results not only potentially reveal at the small molecule level that lipid metabolism metabolites may play a role in the beneficial effects of egg consumption on CVD, but also provide Chinese population-based evidence for the formulation of strategies and policies to encourage egg consumption. The causal roles of lipid metabolites in the association between egg consumption and CVD risk can be not verified because of the cross-sectional nature of the study.

  3. Reviewer #2 (Public Review):

    The submitted manuscript by Pan et al discusses the associations of self-reported egg consumption with plasma metabolic markers and these plasma metabolic markers with the risk of cardiovascular diseases.

    1. The current study did not consider the difference between hypercholesterolemia patients and participants without hypercholesterolemia. Diagnosed hypercholesterolemia patients preferred to eat less egg, which is the richest source of dietary cholesterol as the authors mentioned. Hypercholesterolemia patients also had a higher risk of cardiovascular diseases. The potential bias should be considered.

    2. Whether all the dietary assessments of participants in this study had reliable quality? The authors do not address the information about the exclusion of any unreliable dietary questionnaires.

    3. Based on the results of this study, eggs could be a component in a healthy diet. However, the current evidence of egg consumption based on observational studies was not consistent. It is not appropriate to appeal for more health education and health promotion strategies and policies to encourage egg consumption.