Rules of Heliogeomagnetics Diversely Coordinating Biological Rhythms and Promoting Human Health

Round 1

Reviewer 1 Report

My principal concern is the size of the sample (only 16). I understand the troubles to get human participants and also that coincide with major geomagnetic events, but there is a huge dispersion on results, making conclusions not so evident.

The study has many other possible confusors that are not discussed on the paper. It is not clear the inclusion/exclusion criteria employed and it would be important to clarify the physiological health status of all participants:

-do they take medications? It is important to clarify this point because it is well known that many medications alter circadian cycles significantly.

-are they normopressure or with hyper or hypo pressure? Some subjects were eliminated of the study because of this, but it is not clear the inclusion/exclusion criteria.

- do they have any commorbility? Many diseases alter circadian cycles, thus it is important that a medical doctor stablish the health status of all participants.

- women are pre-menopausic? In such a case, all of them were in the same ovulatory phase? It is known that BP and HRV change during the menstrual cycle on women, altering the circadian parameters significantly. I would be careful associating tendencies with women parameters.

In discussion it would be good to include an answer to the question: With respect to the influence of geomagnetic variations, why they are more important that the environmental magnetic changes due to all electromagnetic aparatus on home or office? All participants live under the same exposition (for example with respect to electric transformators, power plants, etc)? 

In discussion I would like to see a physiological explanation of the changes on BP and HRV due to geomagnetic effects. 

 

Author Response

Thank you for your comments and suggestions that helped improve our manuscript.

 

My principal concern is the size of the sample (only 16). I understand the troubles to get human participants and also that coincide with major geomagnetic events, but there is a huge dispersion on results, making conclusions not so evident.

Reply: Thank you for your suggestion that we must pay attention to effects of small sample size. We listed this shortcoming in a new section on Limitations.

The rules of heliogeomagnetics related to human health do not uniquely depend on results from the Alta study, however. Much additional work was carried out, as published previously and cited as references in our manuscript.

The following text was added at L.425: “4.5. Limitations and expectations for future investigations

This investigation has several limitations. First, the sample size is small, being limited to 16 participants. Second, even though 8 women are included, no information was available regarding their menstrual cycle stage at the time of monitoring. Gonadal hormones are known to affect the response of the circadian system to light [143]; whether the menstrual cycle modulates the response to geomagnetic activity deserves further study. Third, several studies reported an interaction of geomagnetic disturbances and their latitude-dependence on the effect of melatonin on BP: apart from the role of melatonin on BP control, it reportedly has therapeutic uses on different pathologies of smooth muscles, including those related to gastrointestinal tract and urinary bladder instability [144]. Any involvement of melatonin in the hormetic response of SBP to geomagnetic activity, or on its circadian phase-dependence, hence deserves further investigation. Finally, it will be important to understand the role human clock genes may play to facilitate hormetic and/or circadian phase-dependent effects of geomagnetic activity on BP, as suggested by an in vitro SCN study [116]. ”

 

The study has many other possible confusors that are not discussed on the paper. It is not clear the inclusion/exclusion criteria employed and it would be important to clarify the physiological health status of all participants:

-do they take medications? It is important to clarify this point because it is well known that many medications alter circadian cycles significantly.

Reply: In accordance with your suggestions, section 2.1. was revised (Lines 84-93) and we added a flowchart showing inclusion/exclusion criteria (Figure 1).

 

-are they normopressure or with hyper or hypo pressure? Some subjects were eliminated of the study because of this, but it is not clear the inclusion/exclusion criteria.

Reply: In this investigation, normotensive subjects were included and both hypertensive and hypotensive participants were excluded. For the definition of “normotension”, we added 4 references in the Subject section.

Lines 112-116: “In records spanning 2 days, the quiet and disturbed days were defined as those 24-hour days with the lowest or highest geomagnetic activity. This definition is the same as that used in our previous studies of HRV in Alta and in space [18, 70-72]. In the two records spanning 5 days or longer, moderate and extreme geomagnetic disturbances correspond to geomagnetic activity 3 or 12 times higher than on quiet days, respectively.”

 

- do they have any commorbility? Many diseases alter circadian cycles, thus it is important that a medical doctor stablish the health status of all participants

Reply: Regarding subjects, they do not have diseases, it was one of exclusion criteria shown in Figure 1and explained in section 2.1.

 

- women are pre-menopausic? In such a case, all of them were in the same ovulatory phase? It is known that BP and HRV change during the menstrual cycle on women, altering the circadian parameters significantly. I would be careful associating tendencies with women parameters.

Reply: Information on the menstrual cycle was not available in this study; we added some sentences in the Limitations section and cited one more reference [143].

 

In discussion it would be good to include an answer to the question: With respect to the influence of geomagnetic variations, why they are more important that the environmental magnetic changes due to all electromagnetic aparatus on home or office? All participants live under the same exposition (for example with respect to electric transformators, power plants, etc)?

 

In discussion I would like to see a physiological explanation of the changes on BP and HRV due to geomagnetic effects.

Reply: Thank you for suggestion. Yes, we added several considerations on it in the Discussion section: “Lastly, a link between geomagnetic activity and human physiology and behavior has been suggested [45,46], including cardiovascular outcomes [138-142]. Our study on BP variability in a subarctic area ,where the influence of geomagnetic disturbances is felt more strongly, adds to the already available body of evidence.”

and added 5 more references [138-142].

Author Response File: Author Response.pdf

Reviewer 2 Report

In the study titled “Rules of Heliogeomagnetics Diversely Coordinating Biological 2

Rhythms and promoting Human Health” Denis Gubinand co-authors evaluate if and in what way geomagnetic activity impacts the circadian variation in blood pressure (BP) and heart rate (HR) and their variabilities of clinically healthy volunteers in the Alta study (Norway). They found interesting correlations and geomagnetic stimulation was found to be circadian-phase dependent, with stimulation in the evening inducing an approximately 50% upsurge in the circadian amplitude of Systolic BP.

 The paper contains new information. The study design is clear and sound. All potential biases have been appropriately addressed. The methods are appropriate and well described, and sufficient details are provided. There are no apparent errors of fact or logic. The discussion and conclusions are well balanced and adequately supported by the data.

Author Response

Thank you very much for your warm comments and suggestions that helped improve our manuscript.

 

Author Response File: Author Response.pdf

Reviewer 3 Report

This is a very interesting study by Otsuka et al., providing experimental evidence of the complexity of heliogiomagnetic effects on human physiology carried out with a small population of 16 Citizens from specific magneto-biotrophic region-Alta, Norway from 30 April 2002 and 5 January 2005. The authors have meticulously prepared this article, even though the data obtained is from nearly two decades back. This study might add to their track record of several publications in this area. Overall, the paper is well-prepared and written. However, the author should address the following issues, which could help improve the significance of the study:

General comments:

The main concerns with this manuscript are listed below:

a)     It would be clearer if the authors mentioned the inclusion criteria in the methodology section.

b)     Why haven’t the authors considered using melatonin or clock genes as the physiology marker but blood pressure and heart rate?

c)     How do the authors categorize quieter and disturbed days?

d)     The authors must provide demographic data and a Consort flow chart.

 

e)     It is strange to find Group A and Group B suddenly introduced only in the results section. Kindly provide a consort flow chart which will make the reader understand the manuscript better.

Author Response

Thank you for your comments and suggestions that helped improve our manuscript.

This is a very interesting study by Otsuka et al., providing experimental evidence of the complexity of heliogiomagnetic effects on human physiology carried out with a small population of 16 Citizens from specific magneto-biotrophic region-Alta, Norway from 30 April 2002 and 5 January 2005. The authors have meticulously prepared this article, even though the data obtained is from nearly two decades back. This study might add to their track record of several publications in this area. Overall, the paper is well-prepared and written. However, the author should address the following issues, which could help improve the significance of the study:

 

1. It would be clearer if the authors mentioned the inclusion criteria in the methodology section.

Reply: Subject section was revised and we added a flowchart showing inclusion/exclusion criteria (Figure 1).

 

 

2. Why haven’t the authors considered using melatonin or clock genes as the physiology marker but blood pressure and heart rate?

Reply: Thank you for your suggestions. Yes, it is a very important issue and we discussed it in the Limitations section, and added one reference [116].

 

3. How do the authors categorize quieter and disturbed days?

Reply: Regarding the definition of “disturbed” days, we added an explanation in the Geomagnetic monitoring section and quoted previous papers [18, 70, 71, 72]. Thank you for your important question.

 

4. The authors must provide demographic data and a Consort flow chart.

Reply: In accordance with your suggestions, section 2.1. was revised and we added a flowchart showing inclusion/exclusion criteria (Figure 1).

 

5. It is strange to find Group A and Group B suddenly introduced only in the results section. Kindly provide a consort flow chart which will make the reader understand the manuscript better.

Reply: Groups A and B are now defined in Figure 1.

Author Response File: Author Response.pdf