Low-Intensity Whole-Body Vibration: A Useful Adjuvant in Managing Obesity? A Pilot Study

Round 1

Reviewer 1 Report

This study has merit even though the findings were mostly statistically insignificant.  It was found that static WBV exercise was not sufficient to enhance weight change or improve muscular function or strength. However, I believe that closer adherence to the overload principle of exercise adaptation should have been attempted.  This study did not really structure the WB Vibration exercise program to produce the type of overload known to be needed to enhance strength, to enhance weight loss or make metabolic changes.  It was clear that this intervention was at too low an intensity and was too short in duration to produce changes.  Also static, non specific, exercise was done.  The SAID principle must be followed to enhance sig training effects.  Based on this research it is impossible to know if obese clients would benefit from a more intense and specific exercise program.  

See comments above.  Authors should consider adding more discussion about the OVERLOAD and SAID principles of exercise training with regard to the WBV protocol used.  

Author Response

During the training period we did not modulate variables such as: intensity, volume, exercise selected, rest intervals between sets and frequency, as usually performed in a  progressive resistance training program. We opted for a steady low intensity WBV because our aim was to observe whether low intensity vibration certainly falling within the safety recommended limits could affected the musculoskeletal responses of neuromuscular spindles, tendon organs of Golgi and mechanoreceptors or elicit metabolic responses. However, a program duration of 3 weeks may represent a short lapse of time to observe muscular adaptation. Furthermore, the strength tests carried out were not specific enough for the proposed exercise with. The patients being tested for lower limbs’ strength in a sitting and not in a standing position,  as during training.

Author Response File: Author Response.docx

Reviewer 2 Report

Review of the article "Low-intensity whole-body vibration: a useful adjuvant in managing obesity? A pilot study". The article is devoted to an undoubtedly interesting and topical problem, however, in my opinion, the article has a number of problems.
- The introduction does not reveal the objectives of the study, it seems to me that the authors should formulate the premises of this study much more accurately. Also, the introduction contains information that is essentially incorrect. Let's take the first sentence. "Obesity (BMI ≥30 kg / m2) is the most common form of malnutrition in industrialized countries". Obesity is a medical condition in which excess body fat has accumulated to an extent that it may have a negative effect on health. That's what obesity is!
- Tables 2 and 3. The presentation of the two tables is redundant, in Table 2 it is possible to mark with asterisks the groups that differ from each other statistically.
- Why show tables 4 and 5? No significant results are presented in these tables. You can write - no difference!
- The article contains a large number of abbreviations for which there is no decoding (FC [bpm], FFM [kg], FFM [%], CHO [mg / dl], HDL [mg / dl], LDL [mg / dl], HB1Ac [% ]).
- Table 6, GH [μg / L], Group 3 - mean 0.08, SEM 1.42. How, mathematically, can the mean be significantly less than the standard deviation? Did the authors measure the concentration of the substance in negative values?
- Conclusion. WBV is not effective. Perhaps the authors will be able to write a more intelligible conclusion. A large number of parameters have been measured, a lot of work has been done.

Minor points
- m2, cm2, etc. - you need to use a superscript
- It is necessary to decipher what SD is in the tables, there is no decryption anywhere. Why not represent the results as mean + -SD?
- Whole numbers and decimal fractions are separated by a full stop, not a comma 

Author Response

Review of the article "Low-intensity whole-body vibration: a useful adjuvant in managing obesity? A pilot study". The article is devoted to an undoubtedly interesting and topical problem, however, in my opinion, the article has a number of problems.

- The introduction does not reveal the objectives of the study, it seems to me that the authors should formulate the premises of this study much more accurately. Also, the introduction contains information that is essentially incorrect. Let's take the first sentence. "Obesity (BMI ≥30 kg / m2) is the most common form of malnutrition in industrialized countries". Obesity is a medical condition in which excess body fat has accumulated to an extent that it may have a negative effect on health. That's what obesity is!

As suggested, we have modified the introduction to focus on the purpose of the study:

Excessive body weight increases mechanical stress to the joints and tissues and induces physical limitations and pain[1], leading to a reduction of physical activity that contributes to the loss of muscle mass and strength. Weight loss is conventionally achieved through dietary modifications[2] behavioral correction, and/or exercise prescription [3]. In individuals with obesity, a modest weight loss (5 to –10% of body weight) helps to alleviate cardiovascular risk [2].  However, the success rate of therapy for obesity is very low: dieting may work in the short term, but severe dietary restriction alone reduces muscle mass and leads to a decline in physical fitness [4]; traditional exercise, such as aerobic and resistance training, improves heart rate variability, physical strength, and body composition. Pain is one of the major determinants of ceasing physical activity [1,5]. Aerobic or resistance exercise can be associated with increased risk of musculoskeletal injuries, thus reducing adherence to exercise prescription[5].

In the last two decades, whole-body vibration (WBV) emerged as an alternative exercise modality for strength training[6]. WBV involves exercising on a vibrating platform. Vibrations mechanically generate rapid variations in length of the muscle-tendon complex[7], stimulating repetitive eccentric-concentric muscular work and reflexive muscle contractions[8]. WBV was first recognized as an alternative to resistance exercise for its ability in enhancing force and power in skeletal muscle[6,9]. A major problem in the field is that the different stimulus intensities and safety of WBV devices are often poorly de-scribed [10]. Only earlier this year, the empirical foundation for reporting guidelines for human WBV studies has been published. It has established a final 40-item panel of aspects of WBV studies[11] expanding previous recommendations on the use of WBV[12]. However, vibration can have adverse effects on a number of physiologic systems and concern about potential risks for musculoskeletal[13,14] circulatory and neurological disorders[15], Raynaud’s phenomenon[16] after exposure to WBV is still present in the literature. Vibration thresholds for human exposure during a work shift have been explicited in the International Standards Organization ISO-2631 recommendations and are in use only in the field of occupational medicine[15]. Despite the growth of WBV as a surrogate or supplement to exercise, no similar limits have been set so far for its use in rehabilitation[15]. It is true, however, that exposure to vibration during a rehabilitation session is constrained within some minutes of exercise repeated daily for different training durations, whereas occupational exposure is spread throughout the daily work shift and therefore, comparison between the levels of exposure is difficult.

WBV training modality is characterized by several variables: frequency (Hz), type of vibration (rotating or vertical), amplitude in terms of displacement (mm) or, acceleration (g), exposure time and knee flexion grade, series, number of repetitions, rest period, frequency and duration[17]. In some WBV studies, the acceleration delivered by whole body vibration devices at the plantar surfaces of standing subjects and transmitted through the axial and appendicular skeleton exceeded the safety threshold limit values established by the International Standards Organization ISO-2631[8,15]. The use of WBV for therapeutic purposes appears therefore far from being standardized and caution should be used when using WBV devices providing high vibration levels on patients[15]. In light of those gaps in knowledge, we decided to investigate whether the use of low vibration intensities that certainly fall within the existing recommended safety limits would induce any benefit in subjects with obesity where weight loss or gain in muscle strength represent clinically meaningful goals.

In fact, some evidence exists that WBV improves body composition [18], muscle strength[6] and cardiovascular function in various populations, including individuals with obesity[19,20]. WBV seems to yield the potential to induce both mechanical and metabolic adaptive responses. From the mechanical point of view, exposure to 20-30 Hz WBV has shown neuromuscular adaptations [7,8]. Evidence that body vibrations slow down fat accumulation and reduce adipogenesis in rats[21] suggests a possible clinical use of WBV in the treatment of obesity. Changes in neuromuscular response, testosterone, and growth hormone concentrations have been observed after WBV [22]. An increase in circulating levels of irisin, favoring the browning of the adipose tissue, testosterone and IGF-1 has also been observed [23]. Scanty evidence on the effects of WBV in weight loss and reduction in visceral fat exists [24]. It may cause an increase in lipolysis and energy expenditure through enhancement of the afore-mentioned anabolic hormones[8,22,23]. A recent systematic review[17] attempted to define the outcomes of WBV on individuals with obesity, the optimal combination of vibration and exercise, and to identify gaps of knowledge that may lead to improper use of WBV with consequent harmful effects. It was shown that when combined with dietary intervention, 10 or more weeks of WBV produced significant body weight reduction [24,25] and improvements in lower limb strength [9,25]. WBV may also appeal to subjects that are not so much prone to engage in regular active exercise as it represents a quick and “passive” training modality.

The present study aimed at investigating whether WBV performed at lower intensi-ties falling within the safety limits recommended by the ISO-2631 would be able to induce any metabolic or mechanical effect in subjects with obesity . The primary endpoints were: changes in body composition, metabolic syndrome, performance and muscle strength. The secondary endpoints were: modification of irisin, testosterone, GH and IGF1 levels.

- Tables 2 and 3. The presentation of the two tables is redundant, in Table 2 it is possible to mark with asterisks the groups that differ from each other statistically.

Thank you for the suggestion. We believe it is important to keep both tabs as it allows us to show whether the statistically significant difference is between groups or temporal (pre vs post)

- Why show tables 4 and 5? No significant results are presented in these tables. You can write - no difference!

Thank you. The tables have been removed.

- The article contains a large number of abbreviations for which there is no decoding (FC [bpm], FFM [kg], FFM [%], CHO [mg / dl], HDL [mg / dl], LDL [mg / dl], HB1Ac [% ]).

We have rechecked and fixed any missing abbreviations. Those noted can be found in the caption of the tables.

- Table 6, GH [μg / L], Group 3 - mean 0.08, SEM 1.42. How, mathematically, can the mean be significantly less than the standard deviation? Did the authors measure the concentration of the substance in negative values?

Thank you for reporting the error. The correct values have been entered into the text.

- Conclusion. WBV is not effective. Perhaps the authors will be able to write a more intelligible conclusion. A large number of parameters have been measured, a lot of work has been done.

Isometric low-intensity WBV for 3 weeks does not appear effective in improving strength or function in subjects with obesity due to an insufficient training stimulus from the vibration platform. Further studies will need to investigate longer training duration and/or relatively higher intensities falling within the safety limits proposed in the litera-ture. As for the metabolic effects, an acute change in salivary irisin levels after WBV but not in irisin plasma levels suggest a potential role for this analyte to work as a readily measurable indicator revealing potential dynamic changes in muscle energy Larger studies are also needed to deeper investigate the relationship of irisin, exercise capacity and body mass and the potential role of low-intensity WBV in managing weight

Minor points
- m2, cm2, etc. - you need to use a superscript

Thank you, the text has been updated as indicated.

- It is necessary to decipher what SD is in the tables, there is no decryption anywhere. Why not represent the results as mean + -SD?

Thank you, SD is shown in brackets as indicated in the columns of each table.

- Whole numbers and decimal fractions are separated by a full stop, not a comma 

Thank you, the text has been updated as indicated.

 

 

Author Response File: Author Response.docx

Reviewer 3 Report

The Low-intensity whole-body vibration: a useful adjuvant in managing
obesity? A pilot study, is a manuscript geared towards understanding if whole body frequencies resulted in significant changes in obesogenic profiles. The authors showed that there was no significant association with WBV use and obesity, although there were data to show that there was a significant improvement in cardiometabolic although this was seen amongst all participants. This study does a good job identifying opposition to a controversial technique used for addressing obesity. Below are my critiques:

• Representation of the data is extremely confusing. I'd expect a graph to represent the data in a more concise way. Although not mandatory, please consider this change.
• The authors used HgB1ac, instead HgbA1c or HbA1c, please change.
• Were blood samples used at any point to assess other factors obesogenic parameters such as inflammatory markers.
• Would you expect there to be a significant change if the patients were set on a eu-caloric diet? Please discuss.
• Could you speak on how your relatively relaxed exclusion criteria resulted in a significantly low amount of selected participants. This inquiry is posed due to your stating of the limited study sample size.    

Author Response

Review of the article "The Low-intensity whole-body vibration: a useful adjuvant in managing

obesity? A pilot study, is a manuscript geared towards understanding if whole body frequencies resulted in significant changes in obesogenic profiles. The authors showed that there was no significant association with WBV use and obesity, although there were data to show that there was a significant improvement in cardiometabolic although this was seen amongst all participants. This study does a good job identifying opposition to a controversial technique used for addressing obesity. Below are my critiques:

Representation of the data is extremely confusing. I'd expect a graph to represent the data in a more concise way. Although not mandatory, please consider this change.

Thank you for the suggestion. We believe it is important to represent the data in the tabs

The authors used HgB1ac, instead HgbA1c or HbA1c, please change.

Thank you for the suggestion. We changed it.

Were blood samples used at any point to assess other factors obesogenic parameters such as inflammatory markers.

we did not evaluate other non-routinaries inflammatory markers for budget choices

Would you expect there to be a significant change if the patients were set on a eu-caloric diet? Please discuss.

Thank you for your punctualization. During weight loss the level of protein intake is essential to preserve fat free mass and muscle strength. It is possible that the low-calorie diet with a protein intake of 1-1.3g protein / kg ideal body weight may have compromised the fat free mass of patients. When combined with exercise program an hypo-energetic diet with an elevated daily intake of protein (2-3 x RDA) can promote overall improvements in body composition[29]. So it is possible to obtained a different result with a eu-caloric diet.

Could you speak on how your relatively relaxed exclusion criteria resulted in a significantly low amount of selected participants. This inquiry is posed due to your stating of the limited study sample size.”ù

One of the inclusion criteria was normal HbA1c values. We excluded all the patients with HbA1c > 6,4%. Most of the patients were above this value.

Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

The manuscript has been improved by the efforts of the authors, but the Introduction section of the manuscript is still in need of improvement. The authors write: "Vibrations mechanically generate rapid variations in length of the muscle-tendon complex[7], stimulating repetitive eccentric-concentric muscular work and reflexive muscle contractions[8]". This is true, but what are the molecular mechanisms underlying vibration therapy? Readers far from the topic of the study will be confident that vibration therapy is akin to alternative medicine. It seems to me that this should not be allowed. In a recent article on vibration therapy (10.3390/app11072969), it was suggested that reactive oxygen species, namely hydrogen peroxide, could be the main active principle. Hydrogen peroxide plays an important signaling role in the human body. It has recently been found that hydrogen peroxide is generated by vibration (10.3390/ijms21218033). 

Author Response

Review of the article "The manuscript has been improved by the efforts of the authors, but the Introduction section of the manuscript is still in need of improvement. The authors write: "Vibrations mechanically generate rapid variations in length of the muscle-tendon complex[7], stimulating repetitive eccentric-concentric muscular work and reflexive muscle contractions[8]". This is true, but what are the molecular mechanisms underlying vibration therapy? Readers far from the topic of the study will be confident that vibration therapy is akin to alternative medicine. It seems to me that this should not be allowed. In a recent article on vibration therapy (10.3390/app11072969), it was suggested that reactive oxygen species, namely hydrogen peroxide, could be the main active principle. Hydrogen peroxide plays an important signaling role in the human body. It has recently been found that hydrogen peroxide is generated by vibration (10.3390/ijms21218033).”

 Thank you for the suggestion, we add a section in the introduction:

“ On the other hand at molecular level, vibrations lead to the formation of ROS (reactive oxygen species) including hydrogen peroxide in water and biological fluids[10]. A moderate level of ROS induces the body’s to a positive adaptive responses. At the same time have been known that high dosage of ROS leading to a decrease in muscle protein synthesis[11]”.

 

10. Ghazi, M.; Rippetoe, J.; Chandrashekhar, R.; Wang, H. Focal vibration therapy: Vibration parameters of effective wearable devices. Appl. Sci. 2021, 11, doi:10.3390/app11072969.

11.          Le Moal, E.; Pialoux, V.; Juban, G.; Groussard, C.; Zouhal, H.; Chazaud, B.; Mounier, R. Redox Control of Skeletal Muscle Regeneration. Antioxidants Redox Signal. 2017, 27, 276–310, 

Author Response File: Author Response.docx

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

What an interesting paper. First because the subject is actual and controversial. Second, because the authors were able to stay humble and cautious with their interpretation. It is clearly stated that it is a pilot study, so the major flaws are the ones that are common in pilot studies.

However, I need to make some suggestions before making deeper considerations.

1) it is hard to me to accept that “The majority of people with obesity are reluctant to enrol in conventional exercise programs”. I really can’t understand what’s the point on passing this negative idea (based on a single reference), when so much work has been done on the last years to overcome this challenge.

2) the quality of the writing should be improved. There are some paragraphs that we have to read it twice (or more) to understand the meaning.

3) I really need to see the results. I’m talking about the values (mean±sd) obtained for each variable. As it is, readers don’t get an idea of the type of subjects. With data, results would get more robust and being able to fill the purpose of a pilot study. Easy question for further studies: how much did their subjects walk on the 6min? we don’t know…

And just some small comments:

- weight is measured in Newton.

- oxycon pro I know is not from carefusion.

- why mentioning the dominant hand, if that wasn’t used (both hands were tested)?

- should be better explained what’s the Sit To Stand vs. Stand To Sit.

- deeper explanation should be given on the hypocaloric diet calculation.

Author Response

Point-by-point reply to the reviewer’s 1 comments

Below, we report all the changes to the text including punctual references. Changes have been reported in the paper, except for five sentences with references (in bold) that have been reported only in this point-by-point reply in quotation marks. The paper has been further revised for the English language.

1) it is hard to me to accept that “The majority of people with obesity are reluctant to enrol in conventional exercise programs”. I really can’t understand what’s the point on passing this negative idea (based on a single reference), when so much work has been done on the last years to overcome this challenge.

“To achieve significant weight loss, it is recommended to carry out 250 to 300 minutes of moderate physical activity per week(1). Roughly 3/4 of adults in the United States do not meet current Physical Activity Guidelines in order to achieve significant weight loss (2), and adherence to long-term exercise prescription can be low(3,4). Whole-body vibration exercise has recently been compared to resistance training(5,6) and could be a more feasible and time-efficient physical exercise for overweight/obese people”.

2) the quality of the writing should be improved. There are some paragraphs that we have to read it twice (or more) to understand the meaning.

The manuscript underwent further english editing

3) I really need to see the results. I’m talking about the values (mean±sd) obtained for each variable. As it is, readers don’t get an idea of the type of subjects. With data, results would get more robust and being able to fill the purpose of a pilot study. Easy question for further studies: how much did their subjects walk on the 6min? we don’t know…

It’s possible to understand the type of patients from table 1.

For the success of the study it was not important how many meters the subjects completed during the 6-minute test, but if there were differences between the groups so as to verify if the vibrating platform could induce a training adaptation. It is not important for us in an absolute sense the meters covered but the difference over time and above all between the groups.

In any case, we can report in the table the descriptive data requested divided by groups.

Variable	Time	Results for Group = 1		Results for Group = 3
		Mean	StDev	Mean	StDev
Mass [kg]	post	118,45	18,29	125,22	16,29
BMI [kg/m2]	pre	124,47	19,28	132,5	18,32
Abdomen circumference [cm]	post	41,82	5,28	44,28	4,96
PAS [mm/hg]	pre	44,23	7,05	46,8	5,21
PAD [mm/hg]	post	115,3	11,37	132,4	10,18
FC [bpm]	pre	120,6	11,63	135,2	10,4
FFM [kg]	post	123,64	10,98	130	12,25
FFM [%]	pre	137,73	19,15	144	16,47
CHO [mg/dl]	post	78,64	6,74	85	5
HDL [mg/dl]	pre	80	8,94	92,5	17,2
LDL [mg/dl]	post	72,55	8,38	76,11	7,94
HB1Ac [%]	pre	85,82	14,07	88,6	15,99
Insulin [mU/L]	post	66,33	16,05	68,42	14,37
Glucose [mg/dl]	pre	67,98	17,73	70,96	16,46

 

Variable	Time	Results for Group = 2		Results for Group = 4
		Mean	StDev	Mean	StDev
Mass [kg]	post	111,28	14,26	117,92	23,89
BMI [kg/m2]	pre	118,27	16,05	123,61	26,96
Abdomen circumference [cm]	post	53,9	42,1	41,95	6,48
PAS [mm/hg]	pre	43,21	6,4	43,89	7,18
PAD [mm/hg]	post	124,5	8,82	130,8	17,92
FC [bpm]	pre	126,7	9,51	134,05	17,89
FFM [kg]	post	120,5	6,85	119,44	12,86
FFM [%]	pre	137,5	19,61	142	15,49
CHO [mg/dl]	post	76	5,16	75,56	8,82
HDL [mg/dl]	pre	84,5	10,66	87	8,23
LDL [mg/dl]	post	76,7	9,37	77,78	9,01
HB1Ac [%]	pre	83,2	9,91	82,9	6,54
Insulin [mU/L]	post	62,11	13,01	66,24	14,29
Glucose [mg/dl]	pre	64,7	12,65	66,48	16,75

 

Statistics for all groups togheter
Variable	Tempo	Mean	StDev
HG DX	post	40,27	10,3
	pre	38,98	11,16
HG XS	post	38,04	9,57
	pre	37,04	10,24
ISO EX	post	176,6	70,5
	pre	154,6	66,2
ISO DIN.EX	post	160,98	54,9
	pre	151,73	51,43
6MWT	post	536,3	75,7
	pre	737	1505
MAXFLEX_SIT2STAND_T0	post	38,47	7,99
	pre	42,53	8,95
MAXFLEX_STAND2SIT_T0	post	45,96	9,49
	pre	49,92	12,21
GH	post	0,5	0,802
	pre	0,616	1,23
TESTO	post	7,82	8,3
	pre	7,22	7,8

 

And just some small comments:

 

- weight is measured in Newton.

We reported body mass in Kg

- oxycon pro I know is not from CareFusion.

JAEGER

- why mentioning the dominant hand, if that wasn’t used (both hands were tested)?

Both hands have been tested and results reported accordingly

- should be better explained what’s the Sit To Stand vs. Stand To Sit.

We used both the instrumented sit-to-stand and stand-to-sit tests; they have been explained in the manuscript and results reported accordingly

- deeper explanation should be given on the hypocaloric diet calculation.

We added these sentences at line 550

Patients followed a low-calorie diet. Caloric intake was calculated based on the basal metabolic rate calculated by indirect calorimeters (oxycon pro). Patients were assigned a low-calorie diet equal to their basal metabolic rate with a caloric deficit estimated according to SIOADI(7) guidelines between 500-1000 kcal/day. If the dietician assessed that the assigned diet was too low they adapted it during the following days, to keep it in a range between 500 and 1000 kcal of caloric deficit/day.

Meals were administered with a daily frequency of 3 meals.

The % of kcal were divided among the macronutrients as follows: 55-60% derived from carbohydrates (< 15% sugar), 1-1.3 g of protein/kg of ideal weight (weight calculated at BMI 22.5)(7), 25-20%  and deriving from fats (<10% saturated fats).

All patients ate 5 portions of fruit and vegetables daily. All macronutrients: carbohydrates, proteins and fats were present in every meal.

 

 

1. Donnelly JE, Blair SN, Jakicic JM, Manore MM, Rankin JW, Smith BK. Appropriate physical activity intervention strategies for weight loss and prevention of weight regain for adults. Med Sci Sports Exerc. 2009;41(2):459–71.
2. Hollingsworth JC, Young KC, Abdullah SF, Wadsworth DD, Abukhader A, Elfenbein B, et al. Protocol for Minute Calisthenics: a randomized controlled study of a daily, habit-based, bodyweight resistance training program. BMC Public Health [Internet]. 2020;20(1):1242. Available from: https://doi.org/10.1186/s12889-020-09355-4
3. Colley RC, Hills AP, O’Moore-Sullivan TM, Hickman IJ, Prins JB, Byrne NM. Variability in adherence to an unsupervised exercise prescription in obese women. Int J Obes [Internet]. 2008;32(5):837–44. Available from: https://doi.org/10.1038/sj.ijo.0803799
4. Alberga AS, Sigal RJ, Sweet SN, Doucette S, Russell-Mayhew S, Tulloch H, et al. Understanding low adherence to an exercise program for adolescents with obesity: the HEARTY trial. Obes Sci Pract. 2019;5(5):437–48.
5. Milanese C, Piscitelli F, Zenti MG, Moghetti P, Sandri M, Zancanaro C. Ten-week whole-body vibration training improves body composition and muscle strength in obese women. Int J Med Sci. 2013;10(3):307–11.
6. Machado A, García-López D, González-Gallego J, Garatachea N. Whole-body vibration training increases muscle strength and mass in older women: A randomized-controlled trial. Scand J Med Sci Sport. 2010;20(2):200–7.
7. Italian Standards for Treatment of Obesity, released by the Italian Society for the Study of Obesity (SIO) and the Italian Association of Dietetics and Clinical Nutrition (ADI) [Internet]. SIO-ADI; Available from: https://www.sio-obesita.org/wp-content/uploads/2017/09/STANDARD-OBESITA-SIO-ADI.pdf

 

Reviewer 2 Report

In the introduction, the authors present the problem of the obesity.  Obesity is a vast public health problem, it is  generally associated with premature mortality.
They also describe the role of the whole-body vibration with low intensity. However, this is not standard procedure.
The study is novel. However, I have a few questions and comments
2.4 Laboratory Analyses – and salivary irisin test - please justify the test in terms of reliability of the results
2.7 Fitness Training –This part needs supplementing, it is only briefly described
for example 
line 210 „65–70% of maximal measured heart rate”-  whether it was maintained for the full duration of these activities
line 211 “muscle strengthening exercises for the large muscle groups of the body”-  what kind of exercises they were
Did participants exercise in teams? If so, how many in each team?
I’m not satisfied with the description of training intervention – it’s impossible to reproduce it without doubts.
Results: 
The authors showed only population descriptive data. The metabolic (Table 2), hormonal (Table 3), and functional components (Table 4) are presented only in relation to significance levels. 
In case of  irisin the authors do not show the result at all. They declare only the significance of the differences.
The results should be identified clearly.
In addition the authors report contradictory data:
Line 301: in our program, the patients did not perform any dynamic exercise and in the Limitation: All of the patients were involved in multidisciplinary rehabilitation program and in the abstract: recruited to participate in a 3-week multidisciplinary inpatient rehabilitation program including  fitness training and WBV training.
In my opinion this manuscript requires a  revision before it could be considered for publication

Author Response

Point-by-point reply (A) to reviewer’s 2 (R2) comments

Below, we report all the changes to the text including punctual references. Changes have been reported in the paper, except for two sentences with references (in bold) that have been reported only in this point-by-point reply in quotation marks. The paper has been further revised for the English language.

R2: Laboratory Analyses – and salivary irisin test - please justify the test in terms of reliability of the results

A: Serum and saliva irisin levels were assessed using a commercially available human ELISA kit EK-067–29 (Phoenix Pharmaceutics, Inc, Burlingame, CA, USA) in accordance with the manufacturer’s instructions. This ELISA is specific for human irisin, and quality controls were included in all ELISA measurements with the results falling within the expected range. All samples were analyzed in duplicate. Intra-assay and inter-assay coefficients of variation (CV) of irisin immunoassays were less than 10% and 15% respectively, and minimum detectable concentration was 1.5 ng/mL.

Results obtained with this commercial kit have been previously validated and published in other papers on the detection of irisin in saliva  ( Ref  34. Aydin S, Aydin S, Kuloglu T, Yilmaz M, Kalayci M, Sahin I, et al. Alterations of irisin concentrations in saliva and serum of obese and normal-weight subjects, before and after 45 min of a Turkish bath or running. Peptides 2013;50:13–8; Aydin S, Aydin S, Kobat MA, Kalayci M, Eren MN, Yilmaz M, Kuloglu T, Gul E, Secen O, Alatas OD, Baydas A. Decreased saliva/serum irisin concentrations in the acute myocardial infarction promising for being a new candidate biomarker for diagnosis of this pathology. Peptides. 2014 Jun;56:141-5.  Hirsch HJ, Gross I, Pollak Y, Eldar-Geva T, Gross-Tsur V Irisin and the Metabolic Phenotype of Adults with Prader-Willi Syndrome.. PLoS One. 2015 Sep 3;10(9)).  In a previous internal study in our laboratory, results were obtained in a larger number of human saliva from normal subjects according to the methods described in published papers.

R2:  Fitness Training –This part needs supplementing, it is only briefly described

for example

line 210 „65–70% of maximal measured heart rate”-  whether it was maintained for the full duration of these activitie

line 211 “muscle strengthening exercises for the large muscle groups of the body”-  what kind of exercises they were

Did participants exercise in teams? If so, how many in each team?

I’m not satisfied with the description of training intervention – it’s impossible to reproduce it without doubts.

We added these sentences at line 560

A: Before starting the training course, each patient was educated to maintain 65-70% of the maximum heart rate and the intensity level to be maintained was evaluated during the first training session on the cyclergometer. Heart rate was kept at 65-70% throughout the cycle ergometer activity. Patients were trained in groups of 8-10 and were monitored by 2 physiotherapists. During the walking activity the patients were asked to maintain a continuous and sustained pace, but they were not monitored. The path and distance were the same for all patients.

The exercise program consisted of 6 bodyweight exercises or with small equipment choosen from 3 exercise category by the physiotherapist: lower limb ( squat, split squat, Contralateral forward lunge, deadlift) upper limb (push up, wall push up, wall tricep push-up, dumbbell curl, overhead tricep extension) core (knee plank or plank, back extension, brid dog exercise, knee to chest, crunch) with 3 sets for each exercise and 1-2 minute of recovery between sets. No repetitions are mentioned because the physiotherapist instructs patients to cease exercise when a score of 5-6 of fatigue perception on the omni scale is reached(1).

patients worked in groups of 12-18 people; sessions were scheduled weekly and physiotherapists may have changed according to their workshifts.

R2 Results:

The authors showed only population descriptive data. The metabolic (Table 2), hormonal (Table 3), and functional components (Table 4) are presented only in relation to significance levels.

In case of irisin, the authors did not show the results. Instead, only the significance of the differences is reported.

A: As many variables measured did not change significantly (i.e. the hormonal parameters), for the sake of clarity we decided to report in the Tables only the significance in the differences between groups

Irisin, first identified in 2012 as a muscle-derived factor capable of inducing the browning of white adipose tissue (WAT) (Boström, P. et al. Nature (2012), acts as a myokine and increases energy expenditure and glucose (Hofmann, T., et al. Peptides  (2014).Mice and humans studies investigating irisin-mediated pathways in have demonstrated that exercise increases the expression of peroxisome proliferator-activated receptor (PPAR)-γ coactivator, (PGC)-1α, which results in the expression of fibronectin type III domain containing (FNDC)5, a transmembrane protein acting as the precursor of irisin, as confirmed by evidence that irisin is produced by proteolytic cleavage of FNCD5 at the level of cell membrane  (Boström, P. et al. Nature (2012). Once it is released into the circulation, irisin is able to stimulate the expression of the uncoupling protein-1(UCP1) and the browning of WAT, which prompts an increase in total body energy expenditure by increasing UCP1-mediated thermogenesis (Zhang, Y. et al. 2014). On the other hand, there is accumulating evidence that FNDC5/irisin also acts as an adipokine, as it is both expressed and secreted by WAT in rats and humans (Roca-Rivada, A. et al. PLoS One (2013). Regarding exercise, several studies shown that circulating irisin levels increased level after acute exercise  whereas chronic exercise did not affect irisin levels. (J. Y. Huh et al., Metabolism 2014; Norheim F.et al.  FEBS, 2014;  Löffler, D. J Clin Endocrinol Metab 2015; C. Winn et al. Plos One 2017).

We added these table at line 684

1) Salivary irisin levels PRE and POST at Time T1 and T9

	T1			T9
	Salivary irisin (ng/ml)			Salivary irisin (ng/ml)
	PRE	POST	∆% Pre	PRE	POST	∆% Post
Group  2	4,26  ± 3,31	10,80 ± 5,70	839,14  ±  1984,41	2,99 ± 2,10	8,79 ± 3,80	478,01 ± 823,44
Group 4	25,15 ± 0,68	43,09 ± 40,67	578,72 ± 2630,94	22,06 ± 29,46	71,48 ± 246,77	509,58 ± 351,21

 

The analysis show increase salivary irisin levels in both group PRE and POST at T1 and T9. In particular at

time 1, group 2 showed percent delta value (∆%) greater as compared to group

 

The analysis show increased salivary irisin levels after WVB exercise (group 2) and without WVB (group 4), while serum irisin levels are similar at T0 and T10. These data seem agree with other studies, in particular with J. Y. Huh et al. which showed that acute bouts of whole-body vibration exercise are effective in increasing circulating irisin levels but chronic training does not change levels of baseline irisin levels in humans. (J. Y. Huh et al., Metabolism 2014).

The results should be identified clearly.

In addition the authors report contradictory data:

Line 301: in our program, the patients did not perform any dynamic exercise and in the Limitation: All of the patients were involved in multidisciplinary rehabilitation program and in the abstract: recruited to participate in a 3-week multidisciplinary inpatient rehabilitation program including  fitness training and WBV training.

CORRECTION: in our program, the patients did not perform any dynamic exercise during WBV training, they kept an isometric position on the vibrating platform.

Round 2

Reviewer 1 Report

Dear authors, thank you for your effort trying to improve the quality of the manuscript.

However,

1^st, what was written in the fist previous comment was that “I really can’t understand what’s the point on passing this negative idea”. Your answer demonstrates that you have that idea;

2^nd, “it is not important for us in an absolute sense the meters covered but the difference over time and above all between the groups”, demonstrates that authors are more worried with their intentions than contribution to knowledge. How is it possible to state “this study can serve as a basis for sample size estimation in future studies” not demonstrating the obtained results, to which further studies can compare? And with the presented table things get worst (abdomen circumference of 40 com???).

Author Response

Dear authors, thank you for your effort trying to improve the quality of the manuscript.

However,

1^st, what was written in the fist previous comment was that “I really can’t understand what’s the point on passing this negative idea”. Your answer demonstrates that you have that idea;

A: The sentence you commented has been erased. What you called "negative idea" was not intended as a matter of stigma or bias, which would be in absolut contrast with our work and mission, instead it was meant as a consideration based on statistics from the literature about poor engagement in physical activity of patients with obesity for different reasons and decades-long experience of our institution and group in the treatment of patients with obesity, where we do, in fact, frequently observe a poor attitude towards physical exercise. However, we do understand your comment and we amended the text accordingly

 

2^nd, “it is not important for us in an absolute sense the meters covered but the difference over time and above all between the groups”, demonstrates that authors are more worried with their intentions than contribution to knowledge. How is it possible to state “this study can serve as a basis for sample size estimation in future studies” not demonstrating the obtained results, to which further studies can compare? And with the presented table things get worst (abdomen circumference of 40 com???).

A: We added an annex at the end of the paper with all of raw datas

A2: we apologize because we have reported the data in the tables incorrectly as you have noticed, as the abdominal circumference cannot be 40 centimeters.

Reviewer 2 Report

The resubmitted paper is  improved, but still has some flaws:

Authors  justify the test in terms of reliability of the results only in the  review response: "Results obtained with this commercial kit have been previously validated and published in other papers on the detection of irisin in saliva"  
 - The information should be included in the paper, not just in the review response

The new description of the results is not very clear, still missing results for pre-and post-intervention. For all results reports, one would be interested to know the exact numbers of increase/decrease.

line 300: .... time, group and group x time?? after 3 weeks of intervention - what the question marks mean

Author Response

The resubmitted paper is  improved, but still has some flaws:

Authors  justify the test in terms of reliability of the results only in the  review response: "Results obtained with this commercial kit have been previously validated and published in other papers on the detection of irisin in saliva"  
 - The information should be included in the paper, not just in the review response

A: As requested from the reviewer we include the new information in the paper.

The new description of the results is not very clear, still missing results for pre-and post-intervention. For all results reports, one would be interested to know the exact numbers of increase/decrease.

A: We added an annex at the end of the paper with all of raw datas.

line 300: .... time, group and group x time?? after 3 weeks of intervention - what the question marks mean

A: typographical error

Round 3

Reviewer 1 Report

It is not a very good paper, like others already revised for applied Sciences, but it is ok. Best Regards,

Author Response

thank you for your work as a reviewer 

Reviewer 2 Report

I think we don't understand each other.
All results - should be presented either in a table or in figures, not as an annexe. For all results reports, one would be interested to know the exact numbers of increase/decrease. Please bear in mind the clinical interpretation of your results, so the reader knows in which direction and the magnitude of the results in relation to an available range or norm.

Author Response

 Due to the large amount of data and variables investigated, we decided to report in Table 2 the mean and the standard deviation values only for the variables for which statistical significance was reached (Table 2). The whole picture of the parameters measured in this study is reported in Annex 1, as means and standard deviations. The following tables for metabolic (Table 3), hormonal (Table 4), and functional components (Table 5) report the statistics between groups.