Melatonin: Both a Messenger of Darkness and a Participant in the Cellular Actions of Non-Visible Solar Radiation of Near Infrared Light
Round 1
Reviewer 1 Report
The manuscript “Melatonin: Both a messenger of darkness and a participant in the cellular actions of non-visible solar radiation of near infra-red (NIR)” by Tan et al. details extra-pineal sources and actions of melatonin. The purpose of this review was to investigate at melatonin regulating mechanisms from a relatively less well studied peripheral synthesis outside the pineal gland, including the effects of near infrared light, and how these might contribute to global melatonin-related health concerns. The authors look at the possibilities of microbial synthesis as well as the effects of infrared light in regard to melatonin production, which shows great promise.
Specific comments:
Page 2; Melatonin's amphiphilic nature: please clarify the wording to emphasize the meaning in the statement.
Page 3 - “Indeed, Zhao et. al…” : please clarify the wording. Also, this statement could be placed further below to sum up the notion of melatonin synthesis occurring in locations other than the pineal gland.
Extrapineal sources of melatonin include: a) statement needs reference(s), b) I would suggest including these sources of melatonin like mitochondrial, microbial, and gastrointestinal source information into a table format or figure with a brief description for improved audience understanding. A figure showing the different sources and their relative contributions would be very helpful.
“Due to its size, the gastrointestinal tract…”: please include a quantitative comparison of melatonin sources as well.
Last paragraph of introduction: 2nd sentence - Please explain the rationale and importance of your focus on near-infrared radiation and melatonin synthesis. Especially when no relevant information about this issue was previously presented in the introduction.
Page 6; the authors note that melatonin syntheses in mitochondria is protective against ROS, and also note that melatonin levels in cancers can be substantially reduced. It would be helpful to give examples of melatonin levels in different cancers, and discuss how cancer cells avoid excess ROS mitochondrial damage in the absence of normal melatonin levels.
Page 8; the term scotophase is used once, without definition. It would be helpful for readers to define the term.
Page 8; it may be confusing to readers to refer to a “troglodytic phase” of mammalian evolution as a driver of the loss of direct photo stimulation of the pineal gland.
Page 11; “Sunlight provides up to 30 MJ/day to the body and represents the single largest energy input.” Please provide a reference for this statement.
The authors mention diet as a source of melatonin, but do not go into much detail on this topic. For example, high protein western diets would be expected to generate more melatonin that plant-based diets and this may affect health. As another source of dietary melatonin, many people take melatonin supplements, and this may be worth discussing as well.
Author Response
The manuscript “Melatonin: Both a messenger of darkness and a participant in the cellular actions of non-visible solar radiation of near infra-red (NIR)” by Tan et al. details extra-pineal sources and actions of melatonin. The purpose of this review was to investigate at melatonin regulating mechanisms from a relatively less well studied peripheral synthesis outside the pineal gland, including the effects of near infrared light, and how these might contribute to global melatonin-related health concerns. The authors look at the possibilities of microbial synthesis as well as the effects of infrared light in regard to melatonin production, which shows great promise.
Response: Thanks for your positive evaluation!
Specific comments:
Page 2; Melatonin's amphiphilic nature: please clarify the wording to emphasize the meaning in the statement.
Response: We have clarified this word.
Page 3 - “Indeed, Zhao et. al…” : please clarify the wording. Also, this statement could be placed further below to sum up the notion of melatonin synthesis occurring in locations other than the pineal gland.
Response: Yes, we have modified this sentence as your suggestion.
Extrapineal sources of melatonin include: a) statement needs reference(s), b) I would suggest including these sources of melatonin like mitochondrial, microbial, and gastrointestinal source information into a table format or figure with a brief description for improved audience understanding. A figure showing the different sources and their relative contributions would be very helpful.
Response: We have added an additional figure (figure 4) as you suggested.
“Due to its size, the gastrointestinal tract…”: please include a quantitative comparison of melatonin sources as well.
Response: We have added the number and reference.
Last paragraph of introduction: 2nd sentence - Please explain the rationale and importance of your focus on near-infrared radiation and melatonin synthesis. Especially when no relevant information about this issue was previously presented in the introduction.
Response: Yes, we have explained the rational on this issue.
Page 6; the authors note that melatonin syntheses in mitochondria is protective against ROS, and also note that melatonin levels in cancers can be substantially reduced. It would be helpful to give examples of melatonin levels in different cancers, and discuss how cancer cells avoid excess ROS mitochondrial damage in the absence of normal melatonin levels.
Response: Yes, we have addressed this with references.
Page 8; the term scotophase is used once, without definition. It would be helpful for readers to define the term.
Response: Yes, we have explained this expression.
Page 8; it may be confusing to readers to refer to a “troglodytic phase” of mammalian evolution as a driver of the loss of direct photo stimulation of the pineal gland.
Response: Yes, we have modified this terminology.
Page 11; “Sunlight provides up to 30 MJ/day to the body and represents the single largest energy input.” Please provide a reference for this statement.
Response: Yes, the reference has been provided.ssue
The authors mention diet as a source of melatonin, but do not go into much detail on this topic. For example, high protein western diets would be expected to generate more melatonin that plant-based diets and this may affect health. As another source of dietary melatonin, many people take melatonin supplements, and this may be worth discussing as well.
Response: We keep this issue open since we have no solid evidence to back up this claim.
Reviewer 2 Report
Dear authors,
I have found this review very interesting, original and novel. I think it contains important information and new insights and it is my pleasure to recommend it for publication with just minor revisions. Please use the annotated pdf supplied with this letter, to perform small revisions in the text.
Best regards
Comments for author File: 
Comments.pdf
Author Response
Dear authors,
I have found this review very interesting, original and novel. I think it contains important information and new insights and it is my pleasure to recommend it for publication with just minor revisions. Please use the annotated pdf supplied with this letter, to perform small revisions in the text.
Best regards
Response:
Thanks for your positive evaluation. We have accepted all corrections that you made in the PDF file.
